Rate-Based Model Predictive Control of Turbofan Engine Clearance

NASA Technical Reports Server (NTRS)

DeCastro, Jonathan A.

2006-01-01

An innovative model predictive control strategy is developed for control of nonlinear aircraft propulsion systems and sub-systems. At the heart of the controller is a rate-based linear parameter-varying model that propagates the state derivatives across the prediction horizon, extending prediction fidelity to transient regimes where conventional models begin to lose validity. The new control law is applied to a demanding active clearance control application, where the objectives are to tightly regulate blade tip clearances and also anticipate and avoid detrimental blade-shroud rub occurrences by optimally maintaining a predefined minimum clearance. Simulation results verify that the rate-based controller is capable of satisfying the objectives during realistic flight scenarios where both a conventional Jacobian-based model predictive control law and an unconstrained linear-quadratic optimal controller are incapable of doing so. The controller is evaluated using a variety of different actuators, illustrating the efficacy and versatility of the control approach. It is concluded that the new strategy has promise for this and other nonlinear aerospace applications that place high importance on the attainment of control objectives during transient regimes.

Noncontact Capacitive Clearance Control System For Laser Cutting Machines

NASA Astrophysics Data System (ADS)

Topkaya, Ahmet; Schmall, Karl-Heinz; Majoli, Ralf

1989-03-01

For a continuous high quality laser cut, it is necessary among other things to position the focal point of the laser beam correctly. This means that a constant clearance between the cutting head and the workpiece with a tolerance of +/- 0.Imm must he ensured. When cutting corrugated automobile bodysheet for example, a good quality cut can only be achieved with automatic clearance control. In the following, a method of automatic clearance control is described using the assistance of a noncontact capacitive sensor system. The copper nozzle of the laser cutting head acts as the electrode of the clearance sensor. The nozzle electrode and the workpiece build a small variable capacitance depending on the clearance. A change of clearance also changes the capacitance, which in turn influences a high frequency oscillator circuit. This shift in frequency is then converted into an analogue DC signal, which can be used to operate a servo motor control for the positioning of the laser cutting head in a closed loop servo system. Laser cutting heads with clearance sensor nozzles of different shapes, suited fur most applications in the industry, with focal lengths from 2.5" to 5" have been developed. They are capable to cut metal sheet from 0.2 to 12 mm of thickness, using CO2-lasers with output power up to 2.5 kW. For special applications involving difficult workpiece topographies in automobile production applications special "trunk" nozzles have been developed. For 5-axis cutting machines and robots, new laser cutting heads with integrated nozzle sensors in combination with a high dynamic Z-axis motor drive are in a stage of development.

48 CFR 952.204-73 - Facility clearance.

Code of Federal Regulations, 2014 CFR

2014-10-01

....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign ownership...

48 CFR 952.204-73 - Facility clearance.

Code of Federal Regulations, 2011 CFR

2011-10-01

....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign ownership...

48 CFR 952.204-73 - Facility clearance.

Code of Federal Regulations, 2012 CFR

2012-10-01

....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign ownership...

48 CFR 952.204-73 - Facility clearance.

Code of Federal Regulations, 2013 CFR

2013-10-01

....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign ownership...

48 CFR 952.204-73 - Facility clearance.

Code of Federal Regulations, 2010 CFR

2010-10-01

....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign ownership...

Turbine blade tip clearance measurements using skewed dual optical beams of tip timing

NASA Astrophysics Data System (ADS)

Ye, De-chao; Duan, Fa-jie; Guo, Hao-tian; Li, Yangzong; Wang, Kai

2011-12-01

Optimization and active control of the clearance between turbine blades and case of the engine is identified, especially in aerospace community, as a key technology to increase engine efficiency, reduce fuel consumption and emissions and increase service life .However, the tip clearance varies during different operating conditions. Thus a reliable non-contact and online detection system is essential and ultimately used to close the tip clearance control loop. This paper described a fiber optical clearance measuring system applying skewed dual optical beams to detect the traverse time of passing blades. Two beams were specially designed with an outward angle of 18 degree and the beam spot diameters are less than 100μm within 0-4mm working range to achieve high signal-to-noise and high sensitivity. It could be theoretically analyzed that the measuring accuracy is not compromised by degradation of signal intensity caused by any number of environmental conditions such as light source instability, contamination and blade tip imperfection. Experimental tests were undertaken to achieve a high resolution of 10µm in the rotational speed range 2000-18000RPM and a measurement accuracy of 15μm, indicating that the system is capable of providing accurate and reliable data for active clearance control (ACC).

CF6 Jet Engine Performance Improvement: High Pressure Turbine Active Clearance Control

NASA Technical Reports Server (NTRS)

Rich, S. E.; Fasching, W. A.

1982-01-01

An active clearance control system was developed which reduces fuel consumption and performance degradation. This system utilizes compressor discharge air during takeoff and fan discharge air during cruise to impinge on the shroud structure to improve the thermal response. The system was evaluated in component and engine tests. The test results demonstrated a performance improvement of 0.7 percent in cruise SFC.

Toward a Fast-Response Active Turbine Tip Clearance Control

NASA Technical Reports Server (NTRS)

Melcher, Kevin J.; Kypuros, Javier A.

2003-01-01

This paper describes active tip clearance control research being conducted by NASA to improve turbine engine systems. The target application for this effort is commercial aircraft engines. However, technologies developed for clearance control can benefit a broad spectrum of current and future turbomachinery. The first portion of the paper addresses the research from a programmatic viewpoint. Recent studies that provide motivation for the work, identification of key technologies, and NASA's plan for addressing deficiencies in the technologies are discussed. The later portion of the paper drills down into one of the key technologies by presenting equations and results for a preliminary dynamic model of the tip clearance phenomena.

Planar rigid-flexible coupling spacecraft modeling and control considering solar array deployment and joint clearance

NASA Astrophysics Data System (ADS)

Li, Yuanyuan; Wang, Zilu; Wang, Cong; Huang, Wenhu

2018-01-01

Based on Nodal Coordinate Formulation (NCF) and Absolute Nodal Coordinate Formulation (ANCF), this paper establishes rigid-flexible coupling dynamic model of the spacecraft with large deployable solar arrays and multiple clearance joints to analyze and control the satellite attitude under deployment disturbance. Considering torque spring, close cable loop (CCL) configuration and latch mechanisms, a typical spacecraft composed of a rigid main-body described by NCF and two flexible panels described by ANCF is used as a demonstration case. Nonlinear contact force model and modified Coulomb friction model are selected to establish normal contact force and tangential friction model, respectively. Generalized elastic force are derived and all generalized forces are defined in the NCF-ANCF frame. The Newmark-β method is used to solve system equations of motion. The availability and superiority of the proposed model is verified through comparing with numerical co-simulations of Patran and ADAMS software. The numerical results reveal the effects of panel flexibility, joint clearance and their coupling on satellite attitude. The effects of clearance number, clearance size and clearance stiffness on satellite attitude are investigated. Furthermore, a proportional-differential (PD) attitude controller of spacecraft is designed to discuss the effect of attitude control on the dynamic responses of the whole system.

Inhaled nano- and microparticles for drug delivery

PubMed Central

El-Sherbiny, Ibrahim M.; El-Baz, Nancy M.; Yacoub, Magdi H.

2015-01-01

The 21st century has seen a paradigm shift to inhaled therapy, for both systemic and local drug delivery, due to the lung's favourable properties of a large surface area and high permeability. Pulmonary drug delivery possesses many advantages, including non-invasive route of administration, low metabolic activity, control environment for systemic absorption and avoids first bypass metabolism. However, because the lung is one of the major ports of entry, it has multiple clearance mechanisms, which prevent foreign particles from entering the body. Although these clearance mechanisms maintain the sterility of the lung, clearance mechanisms can also act as barriers to the therapeutic effectiveness of inhaled drugs. This effectiveness is also influenced by the deposition site and delivered dose. Particulate-based drug delivery systems have emerged as an innovative and promising alternative to conventional inhaled drugs to circumvent pulmonary clearance mechanisms and provide enhanced therapeutic efficiency and controlled drug release. The principle of multiple pulmonary clearance mechanisms is reviewed, including mucociliary, alveolar macrophages, absorptive, and metabolic degradation. This review also discusses the current approaches and formulations developed to achieve optimal pulmonary drug delivery systems. PMID:26779496

Effect of Short-Term Fasting on Systemic Cytochrome P450-Mediated Drug Metabolism in Healthy Subjects: A Randomized, Controlled, Crossover Study Using a Cocktail Approach.

PubMed

Lammers, Laureen A; Achterbergh, Roos; van Schaik, Ron H N; Romijn, Johannes A; Mathôt, Ron A A

2017-10-01

Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance. Therefore, the aim of our study was to assess the effect of short-term fasting on oral bioavailability and systemic clearance of different drugs. In a randomized, controlled, crossover trial, 12 healthy subjects received a single administration of a cytochrome P450 (CYP) probe cocktail, consisting of caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A4), omeprazole (CYP2C19) and warfarin (CYP2C9), on four occasions: an oral (1) and intravenous (2) administration after an overnight fast (control) and an oral (3) and intravenous (4) administration after 36 h of fasting. Pharmacokinetic parameters of the probe drugs were analyzed using the nonlinear mixed-effects modeling software NONMEM. Short-term fasting increased systemic caffeine clearance by 17% (p = 0.04) and metoprolol clearance by 13% (p < 0.01), whereas S-warfarin clearance decreased by 19% (p < 0.01). Fasting did not affect bioavailability. The study demonstrates that short-term fasting alters CYP-mediated drug metabolism in a non-uniform pattern without affecting oral bioavailability.

System-Level Design of a Shape Memory Alloy Actuator for Active Clearance Control in the High-Pressure Turbine

NASA Technical Reports Server (NTRS)

DeCastro, Jonathan A.; Melcher, Kevin J.; Noebe, Ronald D.

2005-01-01

This paper describes results of a numerical analysis evaluating the feasibility of high-temperature shape memory alloys (HTSMA) for active clearance control actuation in the high-pressure turbine section of a modern turbofan engine. The prototype actuator concept considered here consists of parallel HTSMA wires attached to the shroud that is located on the exterior of the turbine case. A transient model of an HTSMA actuator was used to evaluate active clearance control at various operating points in a test bed aircraft engine simulation. For the engine under consideration, each actuator must be designed to counteract loads from 380 to 2000 lbf and displace at least 0.033 inches. Design results show that an actuator comprised of 10 wires 2 inches in length is adequate for control at critical engine operating points and still exhibits acceptable failsafe operability and cycle life. A proportional-integral-derivative (PID) controller with integrator windup protection was implemented to control clearance amidst engine transients during a normal mission. Simulation results show that the control system exhibits minimal variability in clearance control performance across the operating envelope. The final actuator design is sufficiently small to fit within the limited space outside the high-pressure turbine case and is shown to consume only small amounts of bleed air to adequately regulate temperature.

Integrated Turbine Tip Clearance and Gas Turbine Engine Simulation

NASA Technical Reports Server (NTRS)

Chapman, Jeffryes W.; Kratz, Jonathan; Guo, Ten-Huei; Litt, Jonathan

2016-01-01

Gas turbine compressor and turbine blade tip clearance (i.e., the radial distance between the blade tip of an axial compressor or turbine and the containment structure) is a major contributing factor to gas path sealing, and can significantly affect engine efficiency and operational temperature. This paper details the creation of a generic but realistic high pressure turbine tip clearance model that may be used to facilitate active tip clearance control system research. This model uses a first principles approach to approximate thermal and mechanical deformations of the turbine system, taking into account the rotor, shroud, and blade tip components. Validation of the tip clearance model shows that the results are realistic and reflect values found in literature. In addition, this model has been integrated with a gas turbine engine simulation, creating a platform to explore engine performance as tip clearance is adjusted. Results from the integrated model explore the effects of tip clearance on engine operation and highlight advantages of tip clearance management.

Thermal Response Turbine Shroud.

DTIC Science & Technology

1979-11-01

AD-AO82 754. GENERAL ELECTRIC CO CINCINNATI OH AIRCRAFT ENGINE GROUP F/G 21/5 THERMAL RESPONSE TURBINE SHROUO.(UI NOV 79 C N GAY F33615-7B-C-2071...SUPPLEMENTARY NOTES IS. IEV WORDS (C..tIam. ON guinea 80410 Itf08M 8". 1~0 &VU~ b lma n-M-) Clearance Shroud Clearance Control Turbine Shroud engine / aircrafte ...compressor Active Clearance Control Systems (ACC) de-signed for aircraft gas turbine engine applications. The study vas conducted by personnel of the

The CF6 Jet Engine Performance Improvement - Low Pressure Turbine Active Clearance Control

NASA Technical Reports Server (NTRS)

Beck, B. D.; Fasching, W. A.

1982-01-01

A low pressure turbine (LPT) active clearance control (ACC) cooling system was developed to reduce the fuel consumption of current CF6-50 turbofan engines for wide bodied commercial aircraft. The program performance improvement goal of 0.3% delta sfc was determined to be achievable with an improved impingement cooling system. The technology enables the design of an optimized manifold and piping system which is capable of a performance gain of 0.45% delta sfc.

Improved Temperature Dynamic Model of Turbine Subcomponents for Facilitation of Generalized Tip Clearance Control

NASA Technical Reports Server (NTRS)

Kypuros, Javier A.; Colson, Rodrigo; Munoz, Afredo

2004-01-01

This paper describes efforts conducted to improve dynamic temperature estimations of a turbine tip clearance system to facilitate design of a generalized tip clearance controller. This work builds upon research previously conducted and presented in and focuses primarily on improving dynamic temperature estimations of the primary components affecting tip clearance (i.e. the rotor, blades, and casing/shroud). The temperature profiles estimated by the previous model iteration, specifically for the rotor and blades, were found to be inaccurate and, more importantly, insufficient to facilitate controller design. Some assumptions made to facilitate the previous results were not valid, and thus improvements are presented here to better match the physical reality. As will be shown, the improved temperature sub- models, match a commercially validated model and are sufficiently simplified to aid in controller design.

High Temperature Investigations into an Active Turbine Blade Tip Clearance Control Concept

NASA Technical Reports Server (NTRS)

Taylor, Shawn; Steinetz, Bruce M.; Oswald, Jay J.

2007-01-01

System studies have shown the benefits of reducing blade tip clearances in modern turbine engines. Minimizing blade tip clearances throughout the engine will contribute materially to meeting NASA s Ultra-Efficient Engine Technology (UEET) turbine engine project goals. NASA GRC is examining two candidate approaches including rub-avoidance and regeneration which are explained in subsequent slides.

High Temperature Investigations into an Active Turbine Blade Tip Clearance Control Concept

NASA Technical Reports Server (NTRS)

Taylor, Shawn C.; Steinetz, Bruce; Oswald, Jay J.

2008-01-01

System studies have shown the benefits of reducing blade tip clearances in modern turbine engines. Minimizing blade tip clearances throughout the engine will contribute materially to meeting NASA s Ultra-Efficient Engine Technology (UEET) turbine engine project goals. NASA GRC is examining two candidate approaches including rub-avoidance and regeneration which are explained in subsequent slides.

Energy efficient engine high pressure turbine test hardware detailed design report

NASA Technical Reports Server (NTRS)

Halila, E. E.; Lenahan, D. T.; Thomas, T. T.

1982-01-01

The high pressure turbine configuration for the Energy Efficient Engine is built around a two-stage design system. Moderate aerodynamic loading for both stages is used to achieve the high level of turbine efficiency. Flowpath components are designed for 18,000 hours of life, while the static and rotating structures are designed for 36,000 hours of engine operation. Both stages of turbine blades and vanes are air-cooled incorporating advanced state of the art in cooling technology. Direct solidification (DS) alloys are used for blades and one stage of vanes, and an oxide dispersion system (ODS) alloy is used for the Stage 1 nozzle airfoils. Ceramic shrouds are used as the material composition for the Stage 1 shroud. An active clearance control (ACC) system is used to control the blade tip to shroud clearances for both stages. Fan air is used to impinge on the shroud casing support rings, thereby controlling the growth rate of the shroud. This procedure allows close clearance control while minimizing blade tip to shroud rubs.

Development of a Novel System to Measure a Clearance of a Passenger Platform

NASA Astrophysics Data System (ADS)

Shimizu, M.; Oizumi, J.; Matsuoka, R.; Takeda, H.; Okukura, H.; Ooya, A.; Koike, A.

2016-06-01

Clearances of a passenger platform at a railway station should be appropriately maintained for safety of both trains and passengers. In most Japanese railways clearances between a platform and a train car is measured precisely once or twice a year. Because current measurement systems operate on a track, the closure of the track is unavoidable. Since the procedure of the closure of a track is time-consuming and bothersome, we decided to develop a new system to measure clearances without the closure of a track. A new system is required to work on a platform and the required measurement accuracy is less than several millimetres. We have adopted a 3D laser scanner and stop-and-go operation for a new system. The current systems on a track measure clearances continuously at walking speed, while our system on a platform measures clearances at approximately ten metres intervals. The scanner controlled by a PC acquires a set of point data at each measuring station. Edge points of the platform, top and side points of two rails are detected from the acquired point data. Finally clearances of the platform are calculated by using the detected feature points of the platform and the rails. The results of an experiment using a prototype of our system show that the measurement accuracy by our system would be satisfactory, but our system would take more time than the current systems. Since our system requires no closure of a track, we conclude that our system would be convenient and effective.

A high-fidelity airbus benchmark for system fault detection and isolation and flight control law clearance

NASA Astrophysics Data System (ADS)

Goupil, Ph.; Puyou, G.

2013-12-01

This paper presents a high-fidelity generic twin engine civil aircraft model developed by Airbus for advanced flight control system research. The main features of this benchmark are described to make the reader aware of the model complexity and representativeness. It is a complete representation including the nonlinear rigid-body aircraft model with a full set of control surfaces, actuator models, sensor models, flight control laws (FCL), and pilot inputs. Two applications of this benchmark in the framework of European projects are presented: FCL clearance using optimization and advanced fault detection and diagnosis (FDD).

Progress on Shape Memory Alloy Actuator Development for Active Clearance Control

NASA Technical Reports Server (NTRS)

DeCastro, Jonathan; Melcher, Kevin; Noebe, Ronald

2006-01-01

Results of a numerical analysis evaluating the feasibility of high-temperature shape memory alloys (HTSMA) for active clearance control actuation in the high-pressure turbine section of a modern turbofan engine has been conducted. The prototype actuator concept considered here consists of parallel HTSMA wires attached to the shroud that is located on the exterior of the turbine case. A transient model of an HTSMA actuator was used to evaluate active clearance control at various operating points in a test bed aircraft engine simulation. For the engine under consideration, each actuator must be designed to counteract loads from 380 to 2000 lbf and displace at least 0.033 in. Design results show that an actuator comprised of 10 wires 2 in. in length is adequate for control at critical engine operating points and still exhibit acceptable failsafe operability and cycle life. A proportional-integral-derivative (PID) controller with integrator windup protection was implemented to control clearance amidst engine transients during a normal mission. Simulation results show that the control system exhibits minimal variability in clearance control performance across the operating envelope. The final actuator design is sufficiently small to fit within the limited space outside the high-pressure turbine case and is shown to consume only small amounts of bleed air to adequately regulate temperature.

Effect of increased surface hydrophobicity via drug conjugation on the clearance of inhaled PEGylated polylysine dendrimers.

PubMed

Haque, Shadabul; McLeod, Victoria M; Jones, Seth; Fung, Sandy; Whittaker, Michael; McIntosh, Michelle; Pouton, Colin; Owen, David J; Porter, Christopher J H; Kaminskas, Lisa M

2017-10-01

PEGylated polylysine dendrimers are attractive and well tolerated inhalable drug delivery platforms that have the potential to control the release, absorption kinetics and lung retention time of conjugated drugs. The clinical application of these systems though, would likely require partial substitution of surface PEG groups with drug molecules that are anticipated to alter their lung clearance kinetics and clearance pathways. In the current study, we therefore evaluated the impact of increased surface hydrophobicity via substitution of 50% surface PEG groups with a model hydrophobic drug (α-carboxyl OtButylated methotrexate) on the lung clearance of a Generation 5 PEGylated polylysine dendrimer in rats. PEG substitution with OtBu-methotrexate accelerated lung clearance of the dendrimer by increasing polylysine scaffold catabolism, improving systemic absorption of the intact dendrimer and low molecular weight products of scaffold catabolism, and enhancing mucociliary clearance. These results suggest that the conjugation of hydrophobic drug on the surface of a PEGylated dendrimer is likely to accelerate lung clearance when compared to a fully PEGylated dendrimer. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Turbine Engine Clearance Control Systems: Current Practices and Future Directions

NASA Astrophysics Data System (ADS)

Lattime, Scott B.; Steinetz, Bruce M.

2002-09-01

Improved blade tip sealing in the high pressure compressor (HPC) and high pressure turbine (HPT) can provide dramatic reductions in specific fuel consumption (SFC), time-on-wing, compressor stall margin, and engine efficiency as well as increased payload and mission range capabilities. Maintenance costs to overhaul large commercial gas turbine engines can easily exceed 1M. Engine removal from service is primarily due to spent exhaust gas temperature (EGT) margin caused mainly by the deterioration of HPT components. Increased blade tip clearance is a major factor in hot section component degradation. As engine designs continue to push the performance envelope with fewer parts and the market drives manufacturers to increase service life, the need for advanced sealing continues to grow. A review of aero gas turbine engine HPT performance degradation and the mechanisms that promote these losses are discussed. Benefits to the HPT due to improved clearance management are identified. Past and present sealing technologies are presented along with specifications for next generation engine clearance control systems.

Turbine Engine Clearance Control Systems: Current Practices and Future Directions

NASA Technical Reports Server (NTRS)

Lattime, Scott B.; Steinetz, Bruce M.

2002-01-01

Improved blade tip sealing in the high pressure compressor (HPC) and high pressure turbine (HPT) can provide dramatic reductions in specific fuel consumption (SFC), time-on-wing, compressor stall margin, and engine efficiency as well as increased payload and mission range capabilities. Maintenance costs to overhaul large commercial gas turbine engines can easily exceed $1M. Engine removal from service is primarily due to spent exhaust gas temperature (EGT) margin caused mainly by the deterioration of HPT components. Increased blade tip clearance is a major factor in hot section component degradation. As engine designs continue to push the performance envelope with fewer parts and the market drives manufacturers to increase service life, the need for advanced sealing continues to grow. A review of aero gas turbine engine HPT performance degradation and the mechanisms that promote these losses are discussed. Benefits to the HPT due to improved clearance management are identified. Past and present sealing technologies are presented along with specifications for next generation engine clearance control systems.

Turbine blade tip clearance measurement using a skewed dual-beam fiber optic sensor

NASA Astrophysics Data System (ADS)

Ye, De-chao; Duan, Fa-jie; Guo, Hao-tian; Li, Yangzong; Wang, Kai

2012-08-01

Optimization and active control of the tip clearance of turbine blades has been identified as a key to improve fuel efficiency, reduce emission, and increase service life of the engine. However, reliable and real-time tip clearance measurement is difficult due to the adverse environmental conditions that are typically found in a turbine. We describe a dual-beam fiber optic measurement system that can measure the tip timing and tip clearance simultaneously. Because the tip timing information is used to calculate the tip clearance, the method is insensitive to the signal intensity variation caused by fluctuations in environmental conditions such as light source instability, contamination, and blade tip imperfection. The system was calibrated and tested using experimental rotors. The test results indicated a high resolution of 4.5 μm and measurement accuracy of ±20 μm over the rotation speed range of 2000 to 10,000 rpm.

Turbo machine tip clearance and vibration measurements using a fibre optic laser Doppler position sensor

NASA Astrophysics Data System (ADS)

Pfister, T.; Büttner, L.; Czarske, J.; Krain, H.; Schodl, R.

2006-07-01

This paper presents a novel fibre optic laser Doppler position sensor for single blade tip clearance and vibration measurements at turbo machines, which offers high temporal resolution and high position resolution simultaneously. The sensor principle is based on the generation of a measurement volume consisting of two superposed fan-like interference fringe systems with contrary fringe spacing gradients using wavelength division multiplexing. A flexible and robust measurement system with an all-passive fibre coupled measurement head has been realized employing diffractive and refractive optics. Measurements of tip clearance and rotor vibrations at a transonic centrifugal compressor performed during operation at up to 50 000 rpm (833 Hz) corresponding to 21.7 kHz blade frequency and 586 m s-1 blade tip velocity are presented. The results are in excellent agreement with those of capacitive probes. The mean uncertainty of the position measurement was around 20 µm and, thus, considerably better than for conventional tip clearance probes. Consequently, this sensor is capable of fulfilling the requirements for future active clearance control systems and has great potential for in situ and online tip clearance and vibration measurements at metallic and non-metallic turbine blades with high precision.

Mucus clearance from the pulmonary system by mechanical means: a dual-excitation approach.

PubMed

Ignagni, Mario; O'Dea, Thomas

2013-01-01

A dual-excitation approach to mechanical clearance of mucus from the pulmonary system is described. The approach employs independently controlled vibratory and constrictive pressure stimulations to the thorax. Patient cooperative efforts are integrated into the therapy regimen as a means of enhancing the efficacy of the treatment. An engineering model that demonstrates the capability to generate vibratory and constrictive pressure variations at specified levels is described.

Advanced turbine blade tip seal system

NASA Technical Reports Server (NTRS)

Zelahy, J. W.

1981-01-01

An advanced blade/shroud system designed to maintain close clearance between blade tips and turbine shrouds and at the same time, be resistant to environmental effects including high temperature oxidation, hot corrosion, and thermal cycling is described. Increased efficiency and increased blade life are attained by using the advanced blade tip seal system. Features of the system include improved clearance control when blade tips preferentially wear the shrouds and a superior single crystal superalloy tip. The tip design, joint location, characterization of the single crystal tip alloy, the abrasive tip treatment, and the component and engine test are among the factors addressed. Results of wear testing, quality control plans, and the total manufacturing cycle required to fully process the blades are also discussed.

75 FR 2457 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-15

... INFORMATION: A. Background Contractor business systems and internal controls are the first line of defense against waste, fraud, and abuse. Weak control systems increase the risk of unallowable and unreasonable... Office of Management and Budget (OMB) as follows: (1) Accounting Systems--OMB Clearance 9000-0011; (2...

Fuel conservation through active control of rotor clearances

NASA Technical Reports Server (NTRS)

Beitler, R. S.; Saunders, A. A.; Wanger, R. P.

1980-01-01

Under the NASA-sponsored Energy Efficient Engine (EEE) Project, technology is being developed which will significantly reduce the fuel consumption of turbofan engines for subsonic transport aircraft. One technology concept being pursued is active control of rotor tip clearances. Attention is given to rotor tip clearance considerations and an overview of preliminary study results as well as the General Electric EEE clearance control approach is presented. Finally, potential fuel savings with active control of rotor clearances for a typical EEE mission are predicted.

Turbomachine Interface Sealing

NASA Technical Reports Server (NTRS)

Hendricks, Robert C.; Chupp, Raymond E.; Lattime, Scott B.; Steinetz, Bruce M.

2005-01-01

Sealing interfaces and coatings, like lubricants, are sacrificial, giving up their integrity for the benefit of the component. Clearance control is a major issue in power systems turbomachine design and operational life. Sealing becomes the most cost-effective way to enhance system performance. Coatings, films, and combined use of both metals and ceramics play a major role in maintaining interface clearances in turbomachine sealing and component life. This paper focuses on conventional and innovative materials and design practices for sealing interfaces.

Antibody to endotoxin core glycolipid reverses reticuloendothelial system depression in an animal model of severe sepsis and surgical injury

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

Aldridge, M.C.; Chadwick, S.J.; Cheslyn-Curtis, S.

To study the effect of severe sepsis on the function of the reticuloendothelial system (RES) we have measured the clearance kinetics and organ distribution of both low-dose technetium tin colloid (TTC) and /sup 75/selenomethionine-labelled E. coli in rabbits 24 hours after either sham laparotomy or appendix devascularization. Sepsis resulted in similar delayed blood clearance and reduced liver (Kupffer cell) uptake of both TTC and E. coli. To investigate the ability of polyclonal antibody to E. coli-J-5 (core glycolipid) to improve RES function in the same model of sepsis, further animals were pretreated with either core glycolipid antibody or control serummore » (10 ml IV) 2 hours before induction of sepsis. TTC clearance kinetics were determined 24 hours later. Antibody pretreated animals showed: a reduced incidence of bacteremia; normalization of the rate of blood clearance and liver uptake of TTC; and a 'rebound' increase in splenic uptake of TTC. We conclude that antibody to E. coli-J-5 enhances bacterial clearance by the RES.« less

Active control of surge in centrifugal compressors using magnetic thrust bearing actuation

NASA Astrophysics Data System (ADS)

Sanadgol, Dorsa

This research presents a new method for active surge control in centrifugal compressors with unshrouded impellers using a magnetic thrust bearing to modulate the impeller tip clearance. Magnetic bearings offer the potential for active control of flow instabilities. This capability is highly dependent on the sensitivity of the compressor characteristics to blade tip clearance. If the position of the shaft can be actuated with sufficient authority and speed, the induced pressure modulation makes control of surge promising. The active nature of the magnetic bearing system makes the real-time static and dynamic positioning of the rotor and therefore modulation of the impeller tip clearance possible. A theoretical model is first established that describes the sensitivity of the centrifugal compressor characteristic curve to tip clearance variations induced by axial motion of the rotor. Results from simulation of the nonlinear model for a single stage high-speed centrifugal compressor show that using the proposed control method, mass flow and pressure oscillations associated with compressor surge are quickly suppressed with acceptable tip clearance excursions, typically less than 20% of the available clearance. It is shown that it is possible to produce adequate axial excursions in the clearance between the impeller blades and the adjacent stationary shroud using a magnetic thrust bearing with practical levels of drive voltage. This surge control method would allow centrifugal compressors to reliably and safely operate with a wider range than is currently done in the field. The principal advantage of the proposed approach over conventional surge control methods lies in that, in machines already equipped with magnetic bearing, the method can potentially be implemented by simply modifying controller software. This dispenses with the need to introduce additional hardware, permitting adaptation of existing machinery at virtually no cost. In addition, since the controller is designed with the objective of keeping the trajectories on the compressor characteristic curve, the compressor performance and efficiency are no longer sacrificed by excessive recycling to achieve stability. In order to explore these conjectures experimentally, a high speed centrifugal compressor test facility with active magnetic bearings is developed. The test facility can be used for implementing the proposed surge control method and also for assessing the impeller and bearing loads at off-design conditions. This data can then be used to verify and refine analytical models used in compressor design. (Abstract shortened by UMI.)

2003 NASA Seal/Secondary Air System Workshop. Volume 1

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M. (Editor); Hendricks, Robert C. (Editor)

2004-01-01

The following reports were included in the 2003 NASA Seal/Secondary Air System Workshop:Low Emissions Alternative Power (LEAP); Overview of NASA Glenn Seal Developments; NASA Ultra Efficient Engine Technology Project Overview; Development of Higher Temperature Abradable Seals for Industrial Gas Turbines; High Misalignment Carbon Seals for the Fan Drive Gear System Technologies; Compliant Foil Seal Investigations; Test Rig for Evaluating Active Turbine Blade Tip Clearance Control Concepts; Controls Considerations for Turbine Active Clearance Control; Non-Contacting Finger Seal Developments and Design Considerations; Effect of Flow-Induced Radial Load on Brush Seal/Rotor Contact Mechanics; Seal Developments at Flowserve Corporation; Investigations of High Pressure Acoustic Waves in Resonators With Seal-Like Features; Numerical Investigations of High Pressure Acoustic Waves in Resonators; Feltmetal Seal Material Through-Flow; "Bimodal" Nuclear Thermal Rocket (BNTR) Propulsion for Future Human Mars Exploration Missions; High Temperature Propulsion System Structural Seals for Future Space Launch Vehicles; Advanced Control Surface Seal Development for Future Space Vehicles; High Temperature Metallic Seal Development for Aero Propulsion and Gas Turbine Applications; and BrazeFoil Honeycomb.

Therapeutic intervention at cellular quality control systems in Alzheimer's and Parkinson's diseases.

PubMed

Arduino, Daniela M; Esteves, A Raquel; Silva, Diana F F; Martins-Branco, Diogo; Santos, Daniel; Pimentel, Diana F Gomes; Cardoso, Sandra M

2011-01-01

Cellular homeostasis relies on quality control systems so that damaged biologic structures are either repaired or degraded and entirely replaced by newly formed proteins or even organelles. The clearance of dysfunctional cellular structures in long-lived postmitotic cells, like neurons, is essential to eliminate, per example, defective mitochondria, lipofuscin-loaded lysosomes and oxidized proteins. Short-lived proteins are degraded mainly by proteases and proteasomes whether most long-lived proteins and all organelles are digested by autophagy in the lysosomes. Recently, it an interplay was established between the ubiquitin-proteasome system and macroautophagy, so that both degradative mechanisms compensate for each other. In this article we describe each of these clearance systems and their contribution to neuronal quality control. We will highlight some of the findings that provide evidence for the dysfunction of these systems in Alzheimer's and Parkinson's diseases. Ultimately, we provide an outline on potential therapeutic interventions based on the modulation of cellular degradative systems.

Analysis, design, fabrication and testing of an optical tip clearance sensor. [turbocompressor blade tips

NASA Technical Reports Server (NTRS)

Poppel, G. L.; Marple, D. T. F.; Kingsley, J. D.

1981-01-01

Analyses and the design, fabrication, and testing of an optical tip clearance sensor with intended application in aircraft propulsion control systems are reported. The design of a sensor test rig, evaluation of optical sensor components at elevated temperatures, sensor design principles, sensor test results at room temperature, and estimations of sensor accuracy at temperatures of an aircraft engine environment are discussed. Room temperature testing indicated possible measurement accuracies of less than 12.7 microns (0.5 mils). Ways to improve performance at engine operating temperatures are recommended. The potential of this tip clearance sensor is assessed.

Compressor blade clearance measurement using capacitance and phase lock techniques

NASA Astrophysics Data System (ADS)

Demers, Rosario N.

1986-11-01

The clearance measurement system has several unique features which mimimize problems plaguing earlier systems. These include tuning stability and sensitivity drift. Both these problems are intensified by the environmental factors present in compressors i.e., wide temperature fluctuations, vibrations, and conductive contamination of probe tips. The circuitry in this new system provides phase lock feedback to control tuning and shut calibration to measure sensitivity. The use of high frequency excitation lowers the probe tip impedance, thus miminizing the effects of contamination. A prototype has been built and tested. The ability to calibrate has been demonstrated. An eight channel system is now being constructed for use in the Compressor Research Facility at Wright-Patterson AFB. The efficiency of a turbine engine is to a large extent dependent upon the mechanical tolerances maintained between its moving parts. On critical tolerance is the blade span. Although this tolerance may not appear severe, the impact on compressor efficiency is dramatic. The penalty in percent efficiency has been shown to be three times the percent clearance to blade span ratio. In addition, each percent loss in compressor efficiency represents one half percent loss in specific fuel consumption. Factors which affect blade tip clearance are identified.

Impact of impaired renal function on the pharmacokinetics of the antiepileptic drug lacosamide.

PubMed

Cawello, Willi; Fuhr, Uwe; Hering, Ursula; Maatouk, Haidar; Halabi, Atef

2013-10-01

The antiepileptic drug lacosamide is eliminated predominantly via the kidneys. Therefore, an evaluation of the impact of renal impairment on its pharmacokinetic profile is an important component of its safety assessment. The objective of this study was to evaluate the pharmacokinetic profile of lacosamide among individuals with renal impairment (mild, moderate, or severe) and among patients with end-stage renal disease (ESRD), including those on hemodialysis. This was an open-label, Phase I trial. The pharmacokinetics of a single oral 100-mg lacosamide dose were evaluated in five groups of participants: healthy controls, patients with mild, moderate, or severe renal impairment, and patients with ESRD (with and without hemodialysis). Forty participants completed the trial, eight in each group. In healthy volunteers, renal clearance accounted for approximately 30 % of total body clearance [geometric mean 0.5897 l/h (coefficient of variation 37.9 %) vs 2.13 l/h (20.8 %)]. With severe renal impairment, renal clearance was approximately 11 % of total body clearance [0.1428 l/h (31.8 %) vs 1.34 l/h (26.9 %)]. Terminal half-life and systemic exposure were increased with renal impairment, while total body clearance, renal clearance, and urinary excretion were decreased. Strong positive correlations between creatinine clearance, renal clearance, and urinary excretion were observed. Among patients with ESRD, approximately 50 % of lacosamide was cleared from systemic circulation by 4-h hemodialysis. In patients with essentially no renal clearance, nonrenal clearance was still present (1.1 l/h). Lacosamide was well tolerated by healthy volunteers and patients. In patients with mild-to-moderate renal impairment, lacosamide dose adjustment is not necessary, because total body clearance decreased by only approximately 20 %. Dose adjustment, however, is required for patients with severe renal impairment. Hemodialysis removes approximately 50 % of lacosamide from plasma; therefore, dose supplementation following hemodialysis should be considered.

49 CFR 236.73 - Open-wire transmission line; clearance to other circuits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and Instructions: All Systems Wires and Cables § 236.73 Open-wire transmission...

49 CFR 236.73 - Open-wire transmission line; clearance to other circuits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and Instructions: All Systems Wires and Cables § 236.73 Open-wire transmission...

49 CFR 236.73 - Open-wire transmission line; clearance to other circuits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and Instructions: All Systems Wires and Cables § 236.73 Open-wire transmission...

Nutritional Status Differentially Alters Cytochrome P450 3A4 (CYP3A4) and Uridine 5'-Diphospho-Glucuronosyltransferase (UGT) Mediated Drug Metabolism: Effect of Short-Term Fasting and High Fat Diet on Midazolam Metabolism.

PubMed

Lammers, Laureen A; Achterbergh, Roos; Romijn, Johannes A; Mathôt, Ron A A

2018-06-06

Previous studies have shown that nutritional status can alter drug metabolism which may result in treatment failure or untoward side effects. This study assesses the effect of two nutritional conditions, short-term fasting, and a short-term high fat diet (HFD) on cytochrome P450 3A4 (CYP3A4) and uridine 5'-diphospho-glucuronosyltransferase (UGT) mediated drug metabolism by studying the pharmacokinetics of midazolam and its main metabolites. In a randomized-controlled cross-over trial, nine healthy subjects received a single intravenous administration of 0.015 mg/kg midazolam after: (1) an overnight fast (control); (2) 36 h of fasting; and (3) an overnight fast after 3 days of a HFD consisting of 500 ml of cream supplemented to their regular diet. Pharmacokinetic parameters were analyzed simultaneously using non-linear mixed-effects modeling. Short-term fasting increased CYP3A4-mediated midazolam clearance by 12% (p < 0.01) and decreased UGT-mediated metabolism apparent 1-OH-midazolam clearance by 13% (p < 0.01) by decreasing the ratio of clearance and the fraction metabolite formed (ΔCL 1-OH-MDZ /f 1-OH-MDZ ). Furthermore, short-term fasting decreased apparent clearance of 1-OH-midazolam-O-glucuronide (CL 1-OH-MDZ-glucuronide /(f 1-OH-MDZ-glucuronide  × f 1-OH-MDZ )) by 20% (p < 0.01). The HFD did not affect systemic clearance of midazolam or metabolites. Short-term fasting differentially alters midazolam metabolism by increasing CYP3A4-mediated metabolism but by decreasing UGT-mediated metabolism. In contrast, a short-term HFD did not affect systemic clearance of midazolam.

14 CFR 23.623 - Bearing factors.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Bearing factors. (a) Each part that has clearance (free fit), and that is subject to pounding or vibration... control surface hinges and control system joints, compliance with the factors prescribed in §§ 23.657 and...

14 CFR 23.623 - Bearing factors.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Bearing factors. (a) Each part that has clearance (free fit), and that is subject to pounding or vibration... control surface hinges and control system joints, compliance with the factors prescribed in §§ 23.657 and...

14 CFR 23.623 - Bearing factors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Bearing factors. (a) Each part that has clearance (free fit), and that is subject to pounding or vibration... control surface hinges and control system joints, compliance with the factors prescribed in §§ 23.657 and...

14 CFR 23.623 - Bearing factors.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Bearing factors. (a) Each part that has clearance (free fit), and that is subject to pounding or vibration... control surface hinges and control system joints, compliance with the factors prescribed in §§ 23.657 and...

Test Rig for Evaluating Active Turbine Blade Tip Clearance Control Concepts

NASA Technical Reports Server (NTRS)

Lattime, Scott B.; Steinetz, Bruce M.; Robbie, Malcolm G.; Erker, Arthur H.

2004-01-01

The objectives of the research presented in this viewgraph presentation are to 1) Design a mechanical ACC system for HPT tip seal clearance management; 2) Design a test rig to evaluate ACC system concepts. We have focused our efforts on designing mechanical ACC systems that articulate the seal shroud via mechanical linkages connected to actuators that reside outside the extreme environment of the HPT. We opted for this style of design due to a lack of high temperature/low profile actuators that are presently available. We have also selected multiple hydraulic actuators for this first generation ACC system. Fuel-draulic actuators are already a well established technology.

Esophageal Acid Clearance During Random Swallowing Is Faster in Patients with Barrett’s Esophagus Than in Healthy Controls

PubMed Central

Lottrup, Christian; Krarup, Anne L; Gregersen, Hans; Ejstrud, Per; Drewes, Asbjørn M

2016-01-01

Background/Aims Impaired esophageal acid clearance may be a contributing factor in the pathogenesis of Barrett’s esophagus. However, few studies have measured acid clearance as such in these patients. In this explorative, cross-sectional study, we aimed to compare esophageal acid clearance and swallowing rate in patients with Barrett’s esophagus to that in healthy controls. Methods A total of 26 patients with histology-confirmed Barrett’s esophagus and 12 healthy controls underwent (1) upper endoscopy, (2) an acid clearance test using a pH-impedance probe under controlled conditions including controlled and random swallowing, and (3) an ambulatory pH-impedance measurement. Results Compared with controls and when swallowing randomly, patients cleared acid 46% faster (P = 0.008). Furthermore, patients swallowed 60% more frequently (mean swallows/minute: 1.90 ± 0.74 vs 1.19 ± 0.58; P = 0.005), and acid clearance time decreased with greater random swallowing rate (P < 0.001). Swallowing rate increased with lower distal esophageal baseline impedance (P = 0.014). Ambulatory acid exposure was greater in patients (P = 0.033), but clearance times assessed from the ambulatory pH-measurement and acid clearance test were not correlated (all P > 0.3). Conclusions More frequent swallowing and thus faster acid clearance in Barrett’s esophagus may constitute a protective reflex due to impaired mucosal integrity and possibly acid hypersensitivity. Despite these reinforced mechanisms, acid clearance ability seems to be overthrown by repeated, retrograde acid reflux, thus resulting in increased esophageal acid exposure and consequently mucosal changes. PMID:27557545

Novel sensors to enable closed-loop active clearance control in gas turbine engines

NASA Astrophysics Data System (ADS)

Geisheimer, Jonathan; Holst, Tom

2014-06-01

Active clearance control within the turbine section of gas turbine engines presents and opportunity within aerospace and industrial applications to improve operating efficiencies and the life of downstream components. Open loop clearance control is currently employed during the development of all new large core aerospace engines; however, the ability to measure the gap between the blades and the case and close down the clearance further presents as opportunity to gain even greater efficiencies. The turbine area is one of the harshest environments for long term placement of a sensor in addition to the extreme accuracy requirements required to enable closed loop clearance control. This paper gives an overview of the challenges of clearance measurements within the turbine as well as discusses the latest developments of a microwave sensor designed for this application.

Active clearance control system for a turbomachine

NASA Technical Reports Server (NTRS)

Johnston, R. P.; Knapp, M. H.; Coulson, C. E. (Inventor)

1982-01-01

An axial compressor is provided with a cooling air manifold surrounding a portion of the shroud, and means for bleeding air from the compressor to the manifold for selectively flowing it in a modulating manner axially along the outer side of the stator/shroud to cool and shrink it during steady state operating conditions so as to obtain minimum shroud/rotor clearance conditions. Provision is also made to selectively divert the flow of cooling air from the manifold during transient periods of operation so as to alter the thermal growth or shrink rate of the stator/shroud and result in adequate clearance with the compressor rotor.

Simulation of Controller Pilot Data Link Communications over VHF Digital Link Mode 3

NASA Technical Reports Server (NTRS)

Bretmersky, Steven C.; Murawski, Robert; Nguyen, Thanh C.; Raghavan, Rajesh S.

2004-01-01

The Federal Aviation Administration (FAA) has established an operational plan for the future Air Traffic Management (ATM) system, in which the Controller Pilot Data Link Communications (CPDLC) is envisioned to evolve into digital messaging that will take on an ever increasing role in controller to pilot communications, significantly changing the way the National Airspace System (NAS) is operating. According to FAA, CPDLC represents the first phase of the transition from the current analog voice system to an International Civil Aviation Organization (ICAO) compliant system in which digital communication becomes the alternate and perhaps primary method of routine communication. The CPDLC application is an Air Traffic Service (ATS) application in which pilots and controllers exchange messages via an addressed data link. CPDLC includes a set of clearance, information, and request message elements that correspond to existing phraseology employed by current Air Traffic Control (ATC) procedures. These message elements encompass altitude assignments, crossing constraints, lateral deviations, route changes and clearances, speed assignments, radio frequency assignments, and various requests for information. The pilot is provided with the capability to respond to messages, to request clearances and information, to report information, and to declare/rescind an emergency. A 'free text' capability is also provided to exchange information not conforming to defined formats. This paper presents simulated results of the aeronautical telecommunication application Controller Pilot Data Link Communications over VHF Digital Link Mode 3 (VDL Mode 3). The objective of this simulation study was to determine the impact of CPDLC traffic loads, in terms of timely message delivery and capacity of the VDL Mode 3 subnetwork. The traffic model is based on and is used for generating air/ground messages with different priorities. Communication is modeled for the en route domain of the Cleveland Center air traffic (ZOB ARTCC).

Flight deck human factors issues for National Airspace System (NAS) en route controller pilot data link communications (CPDLC)

DOT National Transportation Integrated Search

2017-05-01

Fundamental differences exist between transmissions of Air Traffic Control clearances over voice and those transmitted via Controller Pilot Data Link Communications (CPDLC). This paper provides flight deck human factors issues that apply to processin...

An Investigation of Flight Deck Data Link in the Terminal Area

NASA Technical Reports Server (NTRS)

Martin, Lynne; Lozito, Sandra; Kaneshige, John; Dulchinos, Vicki; Sharma, Shivanjli

2013-01-01

The Next Generation Air Transportation System (NextGen) and Europe's Single European Sky ATM Research (SESAR) concepts require an increased use of trajectory-based operations, including extensive strategic air traffic control clearances. The clearances are lengthy and complex, which necessitate data link communications to allow for message permanence and integration into the autoflight systems (i.e., autoload capability). This paper examines the use of flight deck data link communications for strategic and tactical clearance usage in the terminal area. A human-in-the-loop simulation was conducted using a high-fidelity flight deck simulator, with ten commercial flight crews as participants. Data were collected from six flight scenarios in the San Francisco terminal airspace. The variables of interest were ATC message modality (voice v. data link), temporal quality of the message (tactical v. strategic) and message length. Dependent variables were message response times, communication clarifications, communication-related errors, and pilot workload. Response time results were longer in data link compared to voice, a finding that has been consistently revealed in a number of other simulations [1]. In addition, strategic clearances and longer messages resulted in a greater number of clarifications and errors, suggesting an increase in uncertainty of message interpretation for the flight crews when compared to tactical clearances. The implications for strategic and compound clearance usage in NextGen and SESAR are discussed

Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET.

PubMed

de Leon, Mony J; Li, Yi; Okamura, Nobuyuki; Tsui, Wai H; Saint-Louis, Les A; Glodzik, Lidia; Osorio, Ricardo S; Fortea, Juan; Butler, Tracy; Pirraglia, Elizabeth; Fossati, Silvia; Kim, Hee-Jin; Carare, Roxana O; Nedergaard, Maiken; Benveniste, Helene; Rusinek, Henry

2017-09-01

Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing the cribriform plate, human CSF clearance pathways are not well characterized. Dynamic PET with 18 F-THK5117, a tracer for tau pathology, was used to estimate the ventricular CSF time-activity as a biomarker for CSF clearance. We tested 3 hypotheses: extracranial CSF is detected at the superior turbinates; CSF clearance is reduced in AD; and CSF clearance is inversely associated with amyloid deposition. Methods: Fifteen subjects, 8 with AD and 7 normal control volunteers, were examined with 18 F-THK5117. Ten subjects additionally underwent 11 C-Pittsburgh compound B ( 11 C-PiB) PET scanning, and 8 were 11 C-PiB-positive. Ventricular time-activity curves of 18 F-THK5117 were used to identify highly correlated time-activity curves from extracranial voxels. Results: For all subjects, the greatest density of CSF-positive extracranial voxels was in the nasal turbinates. Tracer concentration analyses validated the superior nasal turbinate CSF signal intensity. AD patients showed ventricular tracer clearance reduced by 23% and 66% fewer superior turbinate CSF egress sites. Ventricular CSF clearance was inversely associated with amyloid deposition. Conclusion: The human nasal turbinate is part of the CSF clearance system. Lateral ventricle and superior nasal turbinate CSF clearance abnormalities are found in AD. Ventricular CSF clearance reductions are associated with increased brain amyloid depositions. These data suggest that PET-measured CSF clearance is a biomarker of potential interest in AD and other neurodegenerative diseases. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Flight control optimization from design to assessment application on the Cessna Citation X business aircraft =

NASA Astrophysics Data System (ADS)

Boughari, Yamina

New methodologies have been developed to optimize the integration, testing and certification of flight control systems, an expensive process in the aerospace industry. This thesis investigates the stability of the Cessna Citation X aircraft without control, and then optimizes two different flight controllers from design to validation. The aircraft's model was obtained from the data provided by the Research Aircraft Flight Simulator (RAFS) of the Cessna Citation business aircraft. To increase the stability and control of aircraft systems, optimizations of two different flight control designs were performed: 1) the Linear Quadratic Regulation and the Proportional Integral controllers were optimized using the Differential Evolution algorithm and the level 1 handling qualities as the objective function. The results were validated for the linear and nonlinear aircraft models, and some of the clearance criteria were investigated; and 2) the Hinfinity control method was applied on the stability and control augmentation systems. To minimize the time required for flight control design and its validation, an optimization of the controllers design was performed using the Differential Evolution (DE), and the Genetic algorithms (GA). The DE algorithm proved to be more efficient than the GA. New tools for visualization of the linear validation process were also developed to reduce the time required for the flight controller assessment. Matlab software was used to validate the different optimization algorithms' results. Research platforms of the aircraft's linear and nonlinear models were developed, and compared with the results of flight tests performed on the Research Aircraft Flight Simulator. Some of the clearance criteria of the optimized H-infinity flight controller were evaluated, including its linear stability, eigenvalues, and handling qualities criteria. Nonlinear simulations of the maneuvers criteria were also investigated during this research to assess the Cessna Citation X's flight controller clearance, and therefore, for its anticipated certification.

Recovery of hepatic clearance and extraction following a release of common bile duct obstruction in the rat.

PubMed

Melzer, E; Krepel, Z; Ronen, I; Bar-Meir, S

1992-01-01

The rate of recovery for hepatic clearance and extraction following release of common-duct obstruction was investigated in the rat. Male Wistar rats underwent ligation of a cannulated common bile duct. Two weeks later, the cannula was opened and implanted into the duodenum, thus re-establishing enterohepatic circulation. Hepatic extraction and indocyanine green clearance were determined in three groups of six rats each, which differed by the time elapsed from the re-establishment of communication between the common bile duct and duodenum, i.e., 1, 48 and 168 h, respectively. A fourth group, in which a sham operation was performed, served as a control. Clearance was reduced from 16.9 +/- 2.5 ml/min per kg in the control group to 2.9 +/- 0.8, 5.4 +/- 2.4, and 8.5 +/- 3.3 ml/min per kg 1, 48, and 168 h, respectively, after release of common-bile-duct obstruction. Extraction rate was reduced from 37.3 +/- 5.9% to 17.5 +/- 2.7% in the 1st hour and recovered completely at 1 week. Thus, in the rat, release of a 2-week common-bile-duct obstruction is associated with complete recovery of the extraction capacity of the liver within a week, but only incomplete recovery of clearance. This decrease in clearance seems to be due to a decrease in effective hepatic blood flow, mostly probably due to the development of porto-systemic shunts.

Management by consent in human-machine systems: when and why it breaks down.

PubMed

Olson, W A; Sarter, N B

2001-01-01

This study examined the effects of conflict type, time pressure, and display design on operators' ability to make informed decisions about proposed machine goals and actions in a management-by-consent context. A group of 30 B757 pilots were asked to fly eight descent scenarios while responding to a series of air traffic control clearances. Each scenario presented pilots with a different conflict that arose from either incompatible goals contained in the clearance or inappropriate implementation of the clearance by automated flight deck systems. Pilots were often unable to detect these conflicts, especially under time pressure, and thus failed to disallow or intervene with proposed machine actions. Detection performance was particularly poor for conflicts related to clearance implementation. These conflicts were most likely to be missed when automated systems did more than the pilot expected of them. Performance and verbal protocol data indicate that the observed difficulties can be explained by a combination of poor system feedback and pilots' difficulties with generating expectations of future system behavior. Our results are discussed in terms of their implications for the choice and implementation of automation management strategies in general and, more specifically, with respect to risks involved in envisioned forms of digital air-ground communication in the future aviation system. Actual or potential applications of this research include the design of future data link systems and procedures, as well as the design of future automated systems in any domain that rely on operator consent as a mechanism for human-machine coordination.

Railway Tunnel Clearance Inspection Method Based on 3D Point Cloud from Mobile Laser Scanning

PubMed Central

Zhou, Yuhui; Wang, Shaohua; Mei, Xi; Yin, Wangling; Lin, Chunfeng; Mao, Qingzhou

2017-01-01

Railway tunnel clearance is directly related to the safe operation of trains and upgrading of freight capacity. As more and more railway are put into operation and the operation is continuously becoming faster, the railway tunnel clearance inspection should be more precise and efficient. In view of the problems existing in traditional tunnel clearance inspection methods, such as low density, slow speed and a lot of manual operations, this paper proposes a tunnel clearance inspection approach based on 3D point clouds obtained by a mobile laser scanning system (MLS). First, a dynamic coordinate system for railway tunnel clearance inspection has been proposed. A rail line extraction algorithm based on 3D linear fitting is implemented from the segmented point cloud to establish a dynamic clearance coordinate system. Second, a method to seamlessly connect all rail segments based on the railway clearance restrictions, and a seamless rail alignment is formed sequentially from the middle tunnel section to both ends. Finally, based on the rail alignment and the track clearance coordinate system, different types of clearance frames are introduced for intrusion operation with the tunnel section to realize the tunnel clearance inspection. By taking the Shuanghekou Tunnel of the Chengdu–Kunming Railway as an example, when the clearance inspection is carried out by the method mentioned herein, its precision can reach 0.03 m, and difference types of clearances can be effectively calculated. This method has a wide application prospects. PMID:28880232

Facile synthesis, pharmacokinetic and systemic clearance evaluation, and positron emission tomography cancer imaging of 64Cu-Au alloy nanoclusters

NASA Astrophysics Data System (ADS)

Zhao, Yongfeng; Sultan, Deborah; Detering, Lisa; Luehmann, Hannah; Liu, Yongjian

2014-10-01

Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of 64Cu alloyed gold nanoclusters (64CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled 64Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the 64CuAuNCs-PEG350 afforded optimal biodistribution and significant renal and hepatobiliary excretion. PET imaging showed low non-specific tumor uptake, indicating its potential for active targeting of clinically relevant biomarkers in tumor and metastatic organs.Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of 64Cu alloyed gold nanoclusters (64CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled 64Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the 64CuAuNCs-PEG350 afforded optimal biodistribution and significant renal and hepatobiliary excretion. PET imaging showed low non-specific tumor uptake, indicating its potential for active targeting of clinically relevant biomarkers in tumor and metastatic organs. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr04569f

Step responses of a torsional system with multiple clearances: Study of vibro-impact phenomenon using experimental and computational methods

NASA Astrophysics Data System (ADS)

Oruganti, Pradeep Sharma; Krak, Michael D.; Singh, Rajendra

2018-01-01

Recently Krak and Singh (2017) proposed a scientific experiment that examined vibro-impacts in a torsional system under a step down excitation and provided preliminary measurements and limited non-linear model studies. A major goal of this article is to extend the prior work with a focus on the examination of vibro-impact phenomena observed under step responses in a torsional system with one, two or three controlled clearances. First, new measurements are made at several locations with a higher sampling frequency. Measured angular accelerations are examined in both time and time-frequency domains. Minimal order non-linear models of the experiment are successfully constructed, using piecewise linear stiffness and Coulomb friction elements; eight cases of the generic system are examined though only three are experimentally studied. Measured and predicted responses for single and dual clearance configurations exhibit double sided impacts and time varying periods suggest softening trends under the step down torque. Non-linear models are experimentally validated by comparing results with new measurements and with those previously reported. Several metrics are utilized to quantify and compare the measured and predicted responses (including peak to peak accelerations). Eigensolutions and step responses of the corresponding linearized models are utilized to better understand the nature of the non-linear dynamic system. Finally, the effect of step amplitude on the non-linear responses is examined for several configurations, and hardening trends are observed in the torsional system with three clearances.

2005 NASA Seal/Secondary Air System Workshop, Volume 1

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M. (Editor); Hendricks, Robert C. (Editor)

2006-01-01

The 2005 NASA Seal/Secondary Air System workshop covered the following topics: (i) Overview of NASA s new Exploration Initiative program aimed at exploring the Moon, Mars, and beyond; (ii) Overview of the NASA-sponsored Propulsion 21 Project; (iii) Overview of NASA Glenn s seal project aimed at developing advanced seals for NASA s turbomachinery, space, and reentry vehicle needs; (iv) Reviews of NASA prime contractor, vendor, and university advanced sealing concepts including tip clearance control, test results, experimental facilities, and numerical predictions; and (v) Reviews of material development programs relevant to advanced seals development. Turbine engine studies have shown that reducing high-pressure turbine (HPT) blade tip clearances will reduce fuel burn, lower emissions, retain exhaust gas temperature margin, and increase range. Several organizations presented development efforts aimed at developing faster clearance control systems and associated technology to meet future engine needs. The workshop also covered several programs NASA is funding to develop technologies for the Exploration Initiative and advanced reusable space vehicle technologies. NASA plans on developing an advanced docking and berthing system that would permit any vehicle to dock to any on-orbit station or vehicle. Seal technical challenges (including space environments, temperature variation, and seal-on-seal operation) as well as plans to develop the necessary "androgynous" seal technologies were reviewed. Researchers also reviewed tests completed for the shuttle main landing gear door seals.

An Experimental Study of the Effects of Automation on Pilot Situational Awareness in the Datalink ATC Environment

NASA Technical Reports Server (NTRS)

Hahn, Edward C.; Hansman, R. John, Jr.

1992-01-01

An experiment to study how automation, when used in conjunction with datalink for the delivery of air traffic control (ATC) clearance amendments, affects the situational awareness of aircrews was conducted. The study was focused on the relationship of situational awareness to automated Flight Management System (FMS) programming and the readback of ATC clearances. Situational awareness was tested by issuing nominally unacceptable ATC clearances and measuring whether the error was detected by the subject pilots. The experiment also varied the mode of clearance delivery: Verbal, Textual, and Graphical. The error detection performance and pilot preference results indicate that the automated programming of the FMS may be superior to manual programming. It is believed that automated FMS programming may relieve some of the cognitive load, allowing pilots to concentrate on the strategic implications of a clearance amendment. Also, readback appears to have value, but the small sample size precludes a definite conclusion. Furthermore, because textual and graphical modes of delivery offer different but complementary advantages for cognitive processing, a combination of these modes of delivery may be advantageous in a datalink presentation.

Adaptive Hierarchical Voltage Control of a DFIG-Based Wind Power Plant for a Grid Fault

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

Kim, Jinho; Muljadi, Eduard; Park, Jung-Wook

This paper proposes an adaptive hierarchical voltage control scheme of a doubly-fed induction generator (DFIG)-based wind power plant (WPP) that can secure more reserve of reactive power (Q) in the WPP against a grid fault. To achieve this, each DFIG controller employs an adaptive reactive power to voltage (Q-V) characteristic. The proposed adaptive Q-V characteristic is temporally modified depending on the available Q capability of a DFIG; it is dependent on the distance from a DFIG to the point of common coupling (PCC). The proposed characteristic secures more Q reserve in the WPP than the fixed one. Furthermore, it allowsmore » DFIGs to promptly inject up to the Q limit, thereby improving the PCC voltage support. To avert an overvoltage after the fault clearance, washout filters are implemented in the WPP and DFIG controllers; they can prevent a surplus Q injection after the fault clearance by eliminating the accumulated values in the proportional-integral controllers of both controllers during the fault. Test results demonstrate that the scheme can improve the voltage support capability during the fault and suppress transient overvoltage after the fault clearance under scenarios of various system and fault conditions; therefore, it helps ensure grid resilience by supporting the voltage stability.« less

Clearance systems in the brain-implications for Alzheimer disease.

PubMed

Tarasoff-Conway, Jenna M; Carare, Roxana O; Osorio, Ricardo S; Glodzik, Lidia; Butler, Tracy; Fieremans, Els; Axel, Leon; Rusinek, Henry; Nicholson, Charles; Zlokovic, Berislav V; Frangione, Blas; Blennow, Kaj; Ménard, Joël; Zetterberg, Henrik; Wisniewski, Thomas; de Leon, Mony J

2015-08-01

Accumulation of toxic protein aggregates-amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles-is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood-brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ.

Clearance systems in the brain—implications for Alzheimer disease

PubMed Central

Tarasoff-Conway, Jenna M.; Carare, Roxana O.; Osorio, Ricardo S.; Glodzik, Lidia; Butler, Tracy; Fieremans, Els; Axel, Leon; Rusinek, Henry; Nicholson, Charles; Zlokovic, Berislav V.; Frangione, Blas; Blennow, Kaj; Ménard, Joël; Zetterberg, Henrik; Wisniewski, Thomas; de Leon, Mony J.

2015-01-01

Accumulation of toxic protein aggregates—amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles—is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood–brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ. PMID:26195256

Online monitoring of dynamic tip clearance of turbine blades in high temperature environments

NASA Astrophysics Data System (ADS)

Han, Yu; Zhong, Chong; Zhu, Xiaoliang; Zhe, Jiang

2018-04-01

Minimized tip clearance reduces the gas leakage over turbine blade tips and improves the thrust and efficiency of turbomachinery. An accurate tip clearance sensor, measuring the dynamic clearances between blade tips and the turbine case, is a critical component for tip clearance control. This paper presents a robust inductive tip clearance sensor capable of monitoring dynamic tip clearances of turbine machines in high-temperature environments and at high rotational speeds. The sensor can also self-sense the temperature at a blade tip in situ such that temperature effect on tip clearance measurement can be estimated and compensated. To evaluate the sensor’s performance, the sensor was tested for measuring the tip clearances of turbine blades under various working temperatures ranging from 700 K to 1300 K and at turbine rotational speeds ranging from 3000 to 10 000 rpm. The blade tip clearance was varied from 50 to 2000 µm. The experiment results proved that the sensor can accurately measure the blade tip clearances with a temporal resolution of 10 µm. The capability of accurately measuring the tip clearances at high temperatures (~1300 K) and high turbine rotation speeds (~30 000 rpm), along with its compact size, makes it promising for online monitoring and active control of blade tip clearances of high-temperature turbomachinery.

Servo-control of water and sodium homeostasis during renal clearance measurements in conscious rats.

PubMed

Thomsen, Klaus; Shirley, David G

2007-01-01

Servo-controlled fluid and sodium replacement during clearance studies is used in order to prevent loss of body fluid and sodium following diuretic/natriuretic procedures. However, even under control conditions, the use of this technique is sometimes associated with increases in proximal tubular fluid output (assessed by lithium clearance) and excretion rates. The present study examined the reason for these increases. The first series of experiments showed that one cause is volume overloading. This can occur if the servo system is activated from the start, i.e., during the establishment of a suitably high urine flow rate by constant infusion of hypotonic glucose solution. The second series of experiments showed that replacement of blood samples with donor blood can also lead to increases in fractional lithium excretion and accompanying increases in water and sodium excretion, a problem not seen when blood samples are replaced with the animal's own red blood cells resuspended in isotonic saline. When these pitfalls are avoided, servo-controlled sodium and fluid replacement is a reliable technique that makes it possible to study the effects of natriuretic and/or diuretic stimuli without interference from unwanted changes in extracellular volume. 2007 S. Karger AG, Basel

48 CFR 245.7101-4 - DD Form 1640, Request for Plant Clearance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false DD Form 1640, Request for Plant Clearance. 245.7101-4 Section 245.7101-4 Federal Acquisition Regulations System DEFENSE... Forms 245.7101-4 DD Form 1640, Request for Plant Clearance. Use to request plant clearance assistance or...

A Glossary of Terms, Definitions, Acronyms, and Abbreviations Related to the National Airspace System (NAS)

DTIC Science & Technology

1990-06-01

System ACAS Airborne Collision Avoidance System ACB Adjacent Center Backup ACC ACCumulator ACC Area Control Center ACCAS Alto Cumulus CAtellanuS ACCC...subsystem) FFC For Further Clearance FFF Form, Fit, and Function FFF Form, Fix, and Function FFLT Familiarize FLighT FFM Far Field Monitor (associated with

On the development of a magnetoresistive sensor for blade tip timing and blade tip clearance measurement systems

NASA Astrophysics Data System (ADS)

Tomassini, R.; Rossi, G.; Brouckaert, J.-F.

2014-05-01

The accurate control of the gap between static and rotating components is vital to preserve the mechanical integrity and ensure a correct functioning of any rotating machinery. Moreover, tip leakage above the airfoil tip results in relevant aerodynamic losses. One way to measure and to monitor blade tip gaps is by the so-called Blade Tip Clearance (BTC) technique. Another fundamental phenomenon to control in the turbomachines is the vibration of the blades. For more than half a century, this has been performed by installing strain gauges on the blades and using telemetry to transmit the signals. The Blade Tip Timing (BTT) technique, (i.e. measuring the blade time of arrival from the casing at different angular locations with proximity sensors) is currently being adopted by all manufacturers as a replacement for the classical strain gauge technique because of its non-intrusive character. This paper presents a novel magnetoresistive sensor for blade tip timing and blade tip clearance systems, which offers high temporal and high spatial resolution simultaneously. The sensing element adopted is a Wheatstone bridge of Permalloy elements. The principle of the sensor is based on the variation of magnetic field at the passage of ferromagnetic objects. Two different configurations have been realized, a digital and an analogue sensor. Measurements of tip clearance have been performed in an high speed compressor and the calibration curve is reported. Measurements of blade vibration have been carried out in a dedicated calibration bench; results are presented and discussed. The magnetoresistive sensor is characterized by high repeatability, low manufacturing costs and measurement accuracy in line with the main probes used in turbomachinery testing. The novel sensor has great potential and is capable of fulfilling the requirements for a simultaneous BTC and BTT measurement system.

Effect of isolated hepatic ischemia on organic anion clearance and oxidative metabolism.

PubMed

Minard, G; Bynoe, R; Wood, G C; Fabian, T C; Croce, M; Kudsk, K A

1992-04-01

Hepatic failure is frequently seen following severe hemorrhagic shock, sepsis, and trauma. Clearance of various drugs has been used to evaluate hepatocellular dysfunction, including indocyanine green (ICG), an organic anionic dye that is transported similarly to bilirubin, and antipyrine (AP), a marker of oxidative phosphorylation. Previous investigators have noted a decrease in ICG excretion following systemic hemorrhage. The effect of isolated hepatic ischemia on the clearances of ICG and AP was studied in 16 pigs after 90 minutes of vascular occlusion to the liver. Antipyrine clearance decreased almost 50% from baseline values at 24 and 72 hours after the ischemia procedure, indicating a significant depression in the cytochrome P-450 system. On the other hand, ICG clearance did not change significantly. In conclusion, ICG clearance is not depressed after isolated hepatic ischemia in pigs. Changes in organic anion clearance after systemic hemorrhage may be because of release of toxic products from ischemic peripheral tissue.

Thyrotoxic atrial fibrillation.

PubMed

Parmar, Malvinder S

2005-01-04

Atrial fibrillation is the most common cardiac complication of hyperthyroidism and occurs in 15% of patients with hyperthyroidism. It is associated with a higher risk of thromboembolism that often involves the central nervous system. Oral anticoagulation is important in the majority of these patients to prevent thromboembolic complications. These patients require adjustment in the dose of various rate-controlling agents because of increased clearance associated with hyperthyroidism and a decrease in warfarin dosage because of increased clearance of vitamin K-dependent clotting factors. The management of thyrotoxic atrial fibrillation is summarized in this clinical review.

Advanced optical blade tip clearance measurement system

NASA Technical Reports Server (NTRS)

Ford, M. J.; Honeycutt, R. E.; Nordlund, R. E.; Robinson, W. W.

1978-01-01

An advanced electro-optical system was developed to measure single blade tip clearances and average blade tip clearances between a rotor and its gas path seal in an operating gas turbine engine. This system is applicable to fan, compressor, and turbine blade tip clearance measurement requirements, and the system probe is particularly suitable for operation in the extreme turbine environment. A study of optical properties of blade tips was conducted to establish measurement system application limitations. A series of laboratory tests was conducted to determine the measurement system's operational performance characteristics and to demonstrate system capability under simulated operating gas turbine environmental conditions. Operational and environmental performance test data are presented.

CTAS: Computer intelligence for air traffic control in the terminal area

NASA Technical Reports Server (NTRS)

Erzberger, Heinz

1992-01-01

A system for the automated management and control of arrival traffic, referred to as the Center-TRACON Automation System (CTAS), has been designed by the ATC research group at NASA Ames research center. In a cooperative program, NASA and the FAA have efforts underway to install and evaluate the system at the Denver and Dallas/Ft. Worth airports. CTAS consists of three types of integrated tools that provide computer-generated intelligence for both Center and TRACON controllers to guide them in managing and controlling arrival traffic efficiently. One tool, the Traffic Management Advisor (TMA), establishes optimized landing sequences and landing times for aircraft arriving in the center airspace several hundred miles from the airport. In TRACON, TMA frequencies missed approach aircraft and unanticipated arrivals. Another tool, the Descent Advisor (DA), generates clearances for the center controllers handling at crossing times provided by TMA. In the TRACON, the final approach spacing tool (FAST) provides heading and speed clearances that produce and accurately spaced flow of aircraft on the final approach course. A data base consisting of aircraft performance models, airline preferred operational procedures and real time wind measurements contribute to the effective operation of CTAS. Extensive simulator evaluations of CTAS have demonstrated controller acceptance, delay reductions, and fuel savings.

48 CFR 945.603-70 - Plant clearance function.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Plant clearance function... Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the contracting officer shall assume all responsibilities of the plant clearance officer...

48 CFR 945.603-70 - Plant clearance function.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Plant clearance function... Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the contracting officer shall assume all responsibilities of the plant clearance officer...

Mitochondria drive autophagy pathology via microtubule disassembly

PubMed Central

Arduíno, Daniela M.; Esteves, A. Raquel; Cardoso, Sandra Morais

2013-01-01

Neurons are exquisitely dependent on quality control systems to maintain a healthy intracellular environment. A permanent assessment of protein and organelle “quality” allows a coordinated action between repair and clearance of damage proteins and dysfunctional organelles. Impairments in the intracellular clearance mechanisms in long-lived postmitotic cells, like neurons, result in the progressive accumulation of damaged organelles and aggregates of aberrant proteins. Using cells bearing Parkinson disease (PD) patients’ mitochondria, we demonstrated that aberrant accumulation of autophagosomes in PD, commonly interpreted as an abnormal induction of autophagy, is instead due to defective autophagic clearance. This defect is a consequence of alterations in the microtubule network driven by mitochondrial dysfunction that hinder mitochondria and autophagosome trafficking. We uncover mitochondria and microtubule-directed traffic as main players in the regulation of autophagy in PD. PMID:23075854

10 CFR 95.49 - Security of automatic data processing (ADP) systems.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Security of automatic data processing (ADP) systems. 95.49 Section 95.49 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Control of Information § 95.49 Security of...

Mobile Laser Scanning Systems for Measuring the Clearance Gauge of Railways: State of Play, Testing and Outlook

PubMed Central

Mikrut, Sławomir; Kohut, Piotr; Pyka, Krystian; Tokarczyk, Regina; Barszcz, Tomasz; Uhl, Tadeusz

2016-01-01

The paper contains a survey of mobile scanning systems for measuring the railway clearance gauge. The research was completed as part of the project carried out for the PKP (PKP Polish Railway Lines S.A., Warsaw, Poland) in 2011–2013. The authors conducted experiments, including a search for the latest solutions relating to mobile measurement systems that meet the basic requirement. At the very least, these solutions needed to be accurate and have the ability for quick retrieval of data. In the paper, specifications and the characteristics of the component devices of the scanning systems are described. Based on experiments, the authors did some examination of the selected mobile systems to be applied for measuring the clearance gauge. The Riegl (VMX-250) and Z+F (Zoller + Fröhlich) Solution were tested. Additional test measurements were carried out within a 30-kilometer section of the Warsaw-Kraków route. These measurements were designed so as to provide various elements of the railway infrastructure, the track geometry and the installed geodetic control network. This ultimately made it possible to reduce the time for the preparation of geodetic reference measurements for the testing of the accuracy of the selected systems. Reference measurements included the use of the polar method to select profiles perpendicular to the axis of the track. In addition, the coordinates selected were well defined as measuring points of the objects of the infrastructure of the clearance gauge. All of the tested systems meet the accuracy requirements initially established (within the range of 2 cm as required by the PKP). The tested systems have shown their advantages and disadvantages. PMID:27187400

2006 NASA Seal/Secondary Air System Workshop; Volume 1

NASA Technical Reports Server (NTRS)

Steinetz, Bruce, M. (Editor); Hendricks, Robert C. (Editor); Delgado, Irebert (Editor)

2007-01-01

The 2006 NASA Seal/Secondary Air System workshop covered the following topics: (i) Overview of NASA s new Exploration Initiative program aimed at exploring the Moon, Mars, and beyond; (ii) Overview of NASA s new fundamental aeronautics technology project; (iii) Overview of NASA Glenn Research Center s seal project aimed at developing advanced seals for NASA s turbomachinery, space, and reentry vehicle needs; (iv) Reviews of NASA prime contractor, vendor, and university advanced sealing concepts including tip clearance control, test results, experimental facilities, and numerical predictions; and (v) Reviews of material development programs relevant to advanced seals development. Turbine engine studies have shown that reducing seal leakages as well as high-pressure turbine (HPT) blade tip clearances will reduce fuel burn, lower emissions, retain exhaust gas temperature margin, and increase range. Several organizations presented development efforts aimed at developing faster clearance control systems and associated technology to meet future engine needs. The workshop also covered several programs NASA is funding to develop technologies for the Exploration Initiative and advanced reusable space vehicle technologies. NASA plans on developing an advanced docking and berthing system that would permit any vehicle to dock to any on-orbit station or vehicle. Seal technical challenges (including space environments, temperature variation, and seal-on-seal operation) as well as plans to develop the necessary "androgynous" seal technologies were reviewed. Researchers also reviewed seal technologies employed by the Apollo command module that serve as an excellent basis for seals for NASA s new Crew Exploration Vehicle (CEV).

48 CFR 801.602-76 - Business clearance review.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or blanket...

48 CFR 801.602-76 - Business clearance review.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or blanket...

78 FR 23626 - Agency Information Collection Activities; Requests for Comments; Clearance of Renewed Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-19

... Dependent Surveillance--Broadcast (ADS-B) Out Performance Requirements To Support Air Traffic Control (ATC.... The final rule titled ``Automatic Dependent Surveillance-- Broadcast (ADS-B) Equipage Mandate To... System. The rule facilitates the use of ADS-B for aircraft surveillance by FAA air traffic controllers to...

Effects of semi-floating ring bearing outer clearance on the subsynchronous oscillation of turbocharger rotor

NASA Astrophysics Data System (ADS)

Liang, Feng; Zhou, Ming; Xu, Quanyong

2016-09-01

Semi-floating ring bearing(SFRB) is developed to control the vibration of turbocharger rotor. The outer clearance of SFRB affects the magnitude and frequency of nonlinear whirl motion, which is significant for the design of turbocharger. In order to explore the effects of outer clearance, a transient finite element analysis program for rotor and oil film bearing is built and validated by a published experimental case. The nonlinear dynamic behaviors of rotor-SFRB system are simulated. According to the simulation results, two representative subsynchronous oscillations excited by the two bearings respectively are discovered. As the outer clearance of SFRB increases from 24 μm to 60 μm, the low-frequency subsynchronous oscillation experiences three steps, including a strong start, a gradual recession and a combination with the other one. At the same time, the high-frequency subsynchronous oscillation starts to appear gradually, then strengthens, and finally combines. If gravity and unbalance are neglected, the combination will start starts from high rotor speed and extents to low rotor speed, just like a "zipper". It is found from the quantitative analysis that when the outer clearance increases, the vibration amplitude experiences large value firstly, then reduction, and suddenly increasing after combination. A useful design principle of SFRB outer clearance for minimum vibration amplitude is proposed: the outer clearance value should be chosen to keep the frequency of two subsynchronous oscillations clearly separated and their amplitudes close.

Abnormal norepinephrine clearance and adrenergic receptor sensitivity in idiopathic orthostatic intolerance

NASA Technical Reports Server (NTRS)

Jacob, G.; Shannon, J. R.; Costa, F.; Furlan, R.; Biaggioni, I.; Mosqueda-Garcia, R.; Robertson, R. M.; Robertson, D.

1999-01-01

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of >/=30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses. METHODS AND RESULTS: Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55+/-5% versus 30+/-7%, P<0.02). After tyramine, NE spillover did not change significantly in patients but increased 50+/-10% in control subjects (P<0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5+/-0.05 versus 1.0+/-0.1 microg, P<0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105+/-11 versus 210+/-12 microg, P<0.001). Baroreflex sensitivity was lower in patients (12+/-1 versus 18+/-2 ms/mm Hg, P<0.02), but the intrinsic heart rate was similar in both groups. CONCLUSIONS: The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.

ANSYS-MATLAB co-simulation of mucus flow distribution and clearance effectiveness of a new simulated cough device.

PubMed

Ren, Shuai; Shi, Yan; Cai, Maolin; Zhao, Hongmei; Zhang, Zhaozhi; Zhang, Xiaohua Douglas

2018-06-01

Coughing is an irritable reaction that protects the respiratory system from infection and improves mucus clearance. However, for the patients who cannot cough autonomously, an assisted cough device is essential for mucus clearance. Considering the low efficiency of current assisted cough devices, a new simulated cough device based on the pneumatic system is proposed in this paper. Given the uncertainty of airflow rates necessary to clear mucus from airways, the computational fluid dynamics Eulerian wall film model and cough efficiency (CE) were used in this study to simulate the cough process and evaluate cough effectiveness. The Ansys-Matlab co-simulation model was set up and verified through experimental studies using Newtonian fluids. Next, model simulations were performed using non-Newtonian fluids, and peak cough flow (PCF) and PCF duration time were analyzed to determine their influence on mucus clearance. CE growth rate (λ) was calculated to reflect the CE variation trend. From the numerical simulation results, we find that CE rises as PCF increases while the growth rate trends to slow as PCF increases; when PCF changes from 60 to 360 L/min, CE changes from 3.2% to 51.5% which is approximately 16 times the initial value. Meanwhile, keeping a long PCF duration time could greatly improve CE under the same cough expired volume and PCF. The results indicated that increasing the PCF and PCF duration time can improve the efficiency of mucus clearance. This paper provides a new approach and a research direction for control strategy in simulated cough devices for airway mucus clearance. Copyright © 2018 John Wiley & Sons, Ltd.

48 CFR 245.602-70 - Plant clearance procedures.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case. ...

48 CFR 245.602-70 - Plant clearance procedures.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case. ...

48 CFR 245.602-70 - Plant clearance procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case. ...

48 CFR 245.602-70 - Plant clearance procedures.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case. ...

Elimination of soluble sup 123 I-labeled aggregates of IgG in patients with systemic lupus erythematosus. Effect of serum IgG and numbers of erythrocyte complement receptor type 1

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

Halma, C.; Breedveld, F.C.; Daha, M.R.

1991-04-01

Using soluble {sup 123}I-labeled aggregates of human IgG ({sup 123}I-AHIgG) as a probe, we examined the function of the mononuclear phagocyte system in 22 patients with systemic lupus erythematosus (SLE) and 12 healthy controls. In SLE patients, a decreased number of erythrocyte complement receptor type 1 was associated with less binding of {sup 123}I-AHIgG to erythrocytes and a faster initial rate of elimination of {sup 123}I-AHIgG (mean +/- SEM half-maximal clearance time 5.23 +/- 0.2 minutes, versus 6.58 +/- 0.2 minutes in the controls), with possible spillover of the material outside the mononuclear phagocyte system of the liver and spleen.more » However, multiple regression analysis showed that serum concentrations of IgG were the most important factor predicting the rate of {sup 123}I-AHIgG elimination. IgG concentration may thus reflect immune complex clearance, which in turn, would influence the inflammatory reaction, in SLE.« less

An evaluation of flight path management automation in transport category aircraft

NASA Technical Reports Server (NTRS)

Chandra, D.; Bussolari, S. R.

1991-01-01

A desk-top simulation of a Boeing 757/767 Electronic Flight Instrumentation System (EFIS) and Control Display Unit (CDU) was used in an experiment to compare three modes of communication for the clearance amendment process: standard voice procedures, a textual delivery method, and a graphical delivery method. Eight qualified Boeing 757/767 pilots served as subjects. Each flew nine landing scenarios with three amendments given in each scenario. Both acceptable and unacceptable clearance amendments were presented in order to assess situational awareness. Times for comprehension and execution of the amendment were recorded along with workload ratings, responses to unacceptable amendments, and subjective impressions. The graphical mode was found to be superior in terms of the time measures and subjective ratings. No difference was found between the modes in the ability to detect unacceptable clearances.

Mitochondria drive autophagy pathology via microtubule disassembly: a new hypothesis for Parkinson disease.

PubMed

Arduíno, Daniela M; Esteves, A Raquel; Cardoso, Sandra Morais

2013-01-01

Neurons are exquisitely dependent on quality control systems to maintain a healthy intracellular environment. A permanent assessment of protein and organelle "quality" allows a coordinated action between repair and clearance of damage proteins and dysfunctional organelles. Impairments in the intracellular clearance mechanisms in long-lived postmitotic cells, like neurons, result in the progressive accumulation of damaged organelles and aggregates of aberrant proteins. Using cells bearing Parkinson disease (PD) patients' mitochondria, we demonstrated that aberrant accumulation of autophagosomes in PD, commonly interpreted as an abnormal induction of autophagy, is instead due to defective autophagic clearance. This defect is a consequence of alterations in the microtubule network driven by mitochondrial dysfunction that hinder mitochondria and autophagosome trafficking. We uncover mitochondria and microtubule-directed traffic as main players in the regulation of autophagy in PD.

Modifying and Testing ATC Controller Interface (CI) for Data Link Clearances

NASA Technical Reports Server (NTRS)

2001-01-01

The Controller-Pilot Data Link Communications (CPDLC) and Air Traffic Control workstation research was conducted as part of the 1997 NASA Low Visibility Landing and Surface Operations (LVLASO) demonstration program at Atlanta Hartsfield airport. Research activity under this grant increased the sophistication of the Controllers' Communication and Situational Awareness Terminal (C-CAST) and developed a VHF Data Link -Mode 2 communications platform. The research culminated with participation in the 2000 NASA Aviation Safety Program's Synthetic Vision System (SVS) / Runway Incursion Prevention System (RIPS) flight demonstration at Dallas-Fort Worth Airport.

Measurement of Rotating Blade Tip Clearance with Fibre-Optic Probe

NASA Astrophysics Data System (ADS)

Cao, S. Z.; Duan, F. J.; Zhang, Y. G.

2006-10-01

This paper described a tip clearance measuring system with fibre-optic probe. The system is based on a novel tip clearance sensor of optical fibre-bundle mounted on the casing, rotating speed synchronization sensor mounted on the rotating shaft, the tip clearance preamplification processing circuit followed by high speed data-acquisition unit. A novel tip clearance sensor of trifurcated optical fibre bundle was proposed and demonstrated. It is independent of material of measured surface but capacitive probe demands target conductive. Measurements can be taken under severe conditions such as ionization. Sensor circuitry and data acquisition circuit were successfully designed. With the help of Rotation synchronized sensor, all the blades can be detected in real-time. Because of fibre-optic sensor, the measuring system has commendably frequency response, which can work well in high rotating speed from 0-15000rpm.The measurement range of tip clearance is 0-3mm with 25um precision.

48 CFR 832.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking the...

48 CFR 32.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance office...

48 CFR 32.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance office...

48 CFR 832.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking the...

48 CFR 32.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance office...

48 CFR 832.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking the...

48 CFR 832.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking the...

48 CFR 32.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance office...

Compressor airfoil tip clearance optimization system

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

Little, David A.; Pu, Zhengxiang

2015-08-18

A compressor airfoil tip clearance optimization system for reducing a gap between a tip of a compressor airfoil and a radially adjacent component of a turbine engine is disclosed. The turbine engine may include ID and OD flowpath boundaries configured to minimize compressor airfoil tip clearances during turbine engine operation in cooperation with one or more clearance reduction systems that are configured to move the rotor assembly axially to reduce tip clearance. The configurations of the ID and OD flowpath boundaries enhance the effectiveness of the axial movement of the rotor assembly, which includes movement of the ID flowpath boundary.more » During operation of the turbine engine, the rotor assembly may be moved axially to increase the efficiency of the turbine engine.« less

Initial, Cockpit Anthropometric Assessment of U.S. Navy T-6 Life Support Equipment

DTIC Science & Technology

2007-11-05

DEP was not specified. Zone 1, 2, and 3 reach conditions to controls and pedals and clearances were in accordance with military standard...functional leg reach as operation of pedals ; cockpit volume clearances, including ejection clearances not striking objects unintention-ally; and overhead...was measured from knee to any obstruction. Reach to pedals was measured from a position where full control was achieved. Arm reach was measured for

48 CFR 1432.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to taking...

48 CFR 1432.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to taking...

48 CFR 1432.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to taking...

48 CFR 1432.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to taking...

48 CFR 832.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Progress Payments Based on Costs 832.502-2 Contract finance office clearance. Contracting...

48 CFR 32.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Progress Payments Based on Costs 32.502-2 Contract finance office clearance. The contracting...

[The respiratory system--its self-cleaning system. General mechanisms of clearance].

PubMed

Mustajbegović, J; Zuskin, E

1998-01-01

The behaviour of particles and deposition in different parts of respiratory system are described. Listed are factors which contribute to the deposition of particles in the lungs and upper areas of the respiratory system. The general mechanisms of lung clearance and their action such as cough, mucociliary transport, alveolar clearance and immunological system are reported. Particularly is stressed the necessity of coordination of all defense mechanisms in order to maintain normal respiratory function.

[Home Daily Hemodialysis with NxStage System One: monocentric italian casistic results].

PubMed

Brunati, Chiara; Cassaro, Franca; Cretti, Laura; Izzo, Michela; Pegoraro, Marisa; Negri, Daniela; Gervasi, Francesca; Colussi, Giacomo

2017-09-28

NxStage System One is a new dialytic technology based on easy setup, simplicity of use and reduced dimensions, which is increasingly in use worldwide for home hemodialysis treatments. The system utilizes a low amount of dialysate, usually 15-30 liters according to anthropometric patients' values. The dialysate is supplied at very low flux, generally about 1/3 of blood flow, in order to obtain an elevated saturation of dialysate for solutes. In these conditions the clearance of urea will be almost equal to dialysate flow rate. In order to achieve an obptimal weekly clearance evaluated by Std Kt/V the dialysis sessions are repeated six times a week. In this way a good control of blood voleme can be reached. In this paper we report our experience of treatment with NxStage System One in 12 patients from May 2011 to Dicember 2016. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Design of Launch Vehicle Flight Control Systems Using Ascent Vehicle Stability Analysis Tool

NASA Technical Reports Server (NTRS)

Jang, Jiann-Woei; Alaniz, Abran; Hall, Robert; Bedossian, Nazareth; Hall, Charles; Jackson, Mark

2011-01-01

A launch vehicle represents a complicated flex-body structural environment for flight control system design. The Ascent-vehicle Stability Analysis Tool (ASAT) is developed to address the complicity in design and analysis of a launch vehicle. The design objective for the flight control system of a launch vehicle is to best follow guidance commands while robustly maintaining system stability. A constrained optimization approach takes the advantage of modern computational control techniques to simultaneously design multiple control systems in compliance with required design specs. "Tower Clearance" and "Load Relief" designs have been achieved for liftoff and max dynamic pressure flight regions, respectively, in the presence of large wind disturbances. The robustness of the flight control system designs has been verified in the frequency domain Monte Carlo analysis using ASAT.

48 CFR 945.670-1 - Plant clearance function.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Plant clearance function... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal 945.670-1 Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the...

48 CFR 945.670-1 - Plant clearance function.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Plant clearance function... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal 945.670-1 Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the...

Impact of mechanism vibration characteristics by joint clearance and optimization design of its multi-objective robustness

NASA Astrophysics Data System (ADS)

Zeng, Baoping; Wang, Chao; Zhang, Yu; Gong, Yajun; Hu, Sanbao

2017-12-01

Joint clearances and friction characteristics significantly influence the mechanism vibration characteristics; for example: as for joint clearances, the shaft and bearing of its clearance joint collide to bring about the dynamic normal contact force and tangential coulomb friction force while the mechanism works; thus, the whole system may vibrate; moreover, the mechanism is under contact-impact with impact force constraint from free movement under action of the above dynamic forces; in addition, the mechanism topology structure also changes. The constraint relationship between joints may be established by a repeated complex nonlinear dynamic process (idle stroke - contact-impact - elastic compression - rebound - impact relief - idle stroke movement - contact-impact). Analysis of vibration characteristics of joint parts is still a challenging open task by far. The dynamic equations for any mechanism with clearance is often a set of strong coupling, high-dimensional and complex time-varying nonlinear differential equations which are solved very difficultly. Moreover, complicated chaotic motions very sensitive to initial values in impact and vibration due to clearance let high-precision simulation and prediction of their dynamic behaviors be more difficult; on the other hand, their subsequent wearing necessarily leads to some certain fluctuation of structure clearance parameters, which acts as one primary factor for vibration of the mechanical system. A dynamic model was established to the device for opening the deepwater robot cabin door with joint clearance by utilizing the finite element method and analysis was carried out to its vibration characteristics in this study. Moreover, its response model was carried out by utilizing the DOE method and then the robust optimization design was performed to sizes of the joint clearance and the friction coefficient change range so that the optimization design results may be regarded as reference data for selecting bearings and controlling manufacturing process parameters for the opening mechanism. Several optimization objectives such as x/y/z accelerations for various measuring points and dynamic reaction forces of mounting brackets, and a few constraints including manufacturing process were taken into account in the optimization models, which were solved by utilizing the multi-objective genetic algorithm (NSGA-II). The vibration characteristics of the optimized opening mechanism are superior to those of the original design. In addition, the numerical forecast results are in good agreement with the test results of the prototype.

Delayed clearance of triglyceride‐rich lipoproteins in young, healthy obese subjects†

PubMed Central

Goll, R.; Lekahl, S.; Moen, O. S.; Florholmen, J.

2015-01-01

Summary Obesity is associated with the metabolic syndrome. The aims were, first, to study the postprandial triglyceride clearance in young, healthy obese subjects and, second, to investigate if fasting triglycerides can predict delayed postprandial triglyceride clearance. Eighteen apparently healthy, obese subjects with no clinical signs of metabolic disturbances participated. Controls were age‐ and sex‐matched, healthy, normal weight subjects. Subclinical markers of metabolic disturbances were assessed by measuring postprandial triglycerides in serum and in chylomicrons by oral fat tolerance test. Postprandial triglyceride clearance for 8 h was assessed indirectly as removal of the lipid from serum during the oral fat tolerance test. Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA‐IR). Twelve (66%) of the apparently healthy obese individuals had insulin resistance measured by HOMA‐IR. There was a delayed clearance of serum triglycerides and chylomicron triglycerides at 6 h when compared with the control group, while, at 8 h, the differences were only detected for the chylomicron triglyceride clearance. Triglyceride response was significantly greater in the obese subjects. Fasting triglycerides in upper normal level predicted a delayed postprandial triglyceride clearance and insulin resistance. In young, apparently healthy obese subjects early metabolic disturbances including insulin resistance and delayed postprandial triglyceride clearance can be detected. Fasting serum triglyceride in upper normal level predicted delayed postprandial triglyceride clearance and insulin resistance. PMID:26469529

A prototype wireless inertial-sensing device for measuring toe clearance.

PubMed

Lai, Daniel T H; Charry, E; Begg, R; Palaniswami, M

2008-01-01

Tripping and slipping are serious health concerns for the elderly because they result in life threatening injuries i.e., fractures and high medical costs. Our recent work in detection of tripping gait patterns has demonstrated that minimum toe clearance (MTC) is a sensitive falls risk predictor. MTC measurement has previously been done in gait laboratories and on treadmills which potentially imposes controlled walking conditions. In this paper, we describe a prototype design of a wireless device for monitoring vertical toe clearance. The sensors consists of a tri-axis accelerometer and dual-axis gyroscope connected to Crossbow sensor motes for wireless data transmission. Sensor data are transmitted to a laptop and displayed on a Matlab graphic user interface (GUI). We have performed zero base and treadmill experiments to investigate sensor performance to environmental variations and compared the calculated toe clearance against measurements made by an Optotrak motion system. It was found that device outputs were approximately independent of small ambient temperature variations, had a reliable range of 20m indoors and 50m outdoors and a maximum transmission rate of 20 packets/s. Toe clearance measurements were found to follow the Optotrak measurement trend but could be improved further by dealing with double integration errors and improving data transmission rates.

Heparin induced alterations in clearance and distribution of blood-borne microparticles following operative trauma.

PubMed

Saba, T M; Antikatzides, T G

1979-04-01

The influence of systemic heparin administration on the vascular clearance and tissue distribution of blood-borne microparticles was evaluated in normal rats and rats after operation (laparotomy plus intestinal manipulation) utilizing an (131)I- colloid which is phagocytized by the reticuloendothelial system (RES). Intravenous heparin administration (100 USP/100g body weight) into normal animals three minutes prior to colloid injection (50 mg/lOOg) induced a significant increase in pulmonary localization of the microparticles as compared to nonheparinized control rats, while hepatic and splenic uptake were decreased. Surgical trauma decreased hepatic RE uptake and increased pulmonary localization of the microparticles when injected systemically at 60 minutes postsurgery. Heparin administration 60 minutes after surgery and three minutes prior to colloid injection, magnified the increased pulmonary localization response with an associated further depression of the RES. The ability of heparin to alter both RE clearance function and lung localization of microparticles was dose dependent and a function of the interval between heparin administration and systemic particulate infusion. Thus, low dose heparin administration was capable of stimulating RE activity while heparin in doses of excess of 50 USP units/lOOg body weight decreased RE function. These findings suggest that the functional state of the hepatic RE system can be greatly affected in a dose-dependent manner by systemic heparin administration which may influence distribution of blood-borne microparticles.

Signals for glucagon secretion.

PubMed

Bloom, S R

1977-01-01

The normal physiological role of glucagon is in controlling hepatic glucose output. Glucagon subserves the role of homeostasis by maintaining plasma glucose and of a stress hormone by producing hyperglycaemia. While control of glucagon release by circulating metabolites and also other hormones is clearly important, it seems likely that the nervous system exerts an over-riding influence. The parasympathetic nervous system maintains homeostasis and the sympathetic acts in stress. Glucagon levels are found to be high in cirrhosis and also after acute hepatic failure. It is likely that these changes in glucagon concentration are secondary to metabolic abnormalities. While some glucagon is cleared by the liver, a similar clearance is seen by many other tissues and it is not likely that the elevation of glucagon seen in liver failure is due solely to a gross deficiency of glucagon clearance. No liver abnormality is seen in the glucagonoma syndrome, where glucagon concentration are chronically high, or in patients who have had a total pancreatectomy, where plasma glucagon is undetectably low. It thus seems unlikely that liver mass is importantly controlled by glucagon.

Glymphatic fluid transport controls paravascular clearance of AAV vectors from the brain

PubMed Central

Murlidharan, Giridhar; Crowther, Andrew; Reardon, Rebecca A.; Song, Juan

2016-01-01

Adeno-associated viruses (AAV) are currently being evaluated in clinical trials for gene therapy of CNS disorders. However, host factors that influence the spread, clearance, and transduction efficiency of AAV vectors in the brain are not well understood. Recent studies have demonstrated that fluid flow mediated by aquaporin-4 (AQP4) channels located on astroglial end feet is essential for exchange of solutes between interstitial and cerebrospinal fluid. This phenomenon, which is essential for interstitial clearance of solutes from the CNS, has been termed glial-associated lymphatic transport or glymphatic transport. In the current study, we demonstrate that glymphatic transport profoundly affects various aspects of AAV gene transfer in the CNS. Altered localization of AQP4 in aged mouse brains correlated with significantly increased retention of AAV vectors in the parenchyma and reduced systemic leakage following ventricular administration. We observed a similar increase in AAV retention and transgene expression upon i.c.v. administration in AQP4–/– mice. Consistent with this observation, fluorophore-labeled AAV vectors showed markedly reduced flux from the ventricles of AQP4–/– mice compared with WT mice. These results were further corroborated by reduced AAV clearance from the AQP4-null brain, as demonstrated by reduced transgene expression and vector genome accumulation in systemic organs. We postulate that deregulation of glymphatic transport in aged and diseased brains could markedly affect the parenchymal spread, clearance, and gene transfer efficiency of AAV vectors. Assessment of biomarkers that report the kinetics of CSF flux in prospective gene therapy patients might inform variable treatment outcomes and guide future clinical trial design. PMID:27699236

Dynamic Performance of High Bypass Ratio Turbine Engines With Water Ingestion

NASA Technical Reports Server (NTRS)

Murthy, S. N. B.

1996-01-01

The research on dynamic performance of high bypass turbofan engines includes studies on inlets, turbomachinery and the total engine system operating with air-water mixture; the water may be in vapor, droplet, or film form, and their combinations. Prediction codes (WISGS, WINCOF, WINCOF-1, WINCLR, and Transient Engine Performance Code) for performance changes, as well as changes in blade-casing clearance, have been established and demonstrated in application to actual, generic engines. In view of the continuous changes in water distribution in turbomachinery, the performance of both components and the total engine system must be determined in a time-dependent mode; hence, the determination of clearance changes also requires a time-dependent approach. In general, the performance and clearances changes cannot be scaled either with respect to operating or ingestion conditions. Removal of water prior to phase change is the most effective means of avoiding ingestion effects. Sufficient background has been established to perform definitive, full scale tests on a set of components and a complete engine to establish engine control and operability with various air-water vapor-water mixtures.

20 CFR 653.501 - Requirements for accepting and processing clearance orders.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., DEPARTMENT OF LABOR SERVICES OF THE EMPLOYMENT SERVICE SYSTEM Agricultural Clearance Order Activity § 653.501... function of the job service as a no-fee labor exchange, that is, as a forum for bringing together employers... referred through the clearance system shall be notified to contact a local job service office, preferably...

20 CFR 653.501 - Requirements for accepting and processing clearance orders.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., DEPARTMENT OF LABOR SERVICES OF THE EMPLOYMENT SERVICE SYSTEM Agricultural Clearance Order Activity § 653.501... function of the job service as a no-fee labor exchange, that is, as a forum for bringing together employers... referred through the clearance system shall be notified to contact a local job service office, preferably...

48 CFR 1432.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Progress Payments Based on Costs 1432.502-2 Contract finance office clearance. The CO shall...

NASA Aviation Safety Reporting System

NASA Technical Reports Server (NTRS)

1980-01-01

Problems in briefing of relief by air traffic controllers are discussed, including problems that arise when duty positions are changed by controllers. Altimeter reading and setting errors as factors in aviation safety are discussed, including problems associated with altitude-including instruments. A sample of reports from pilots and controllers is included, covering the topics of ATIS broadcasts an clearance readback problems. A selection of Alert Bulletins, with their responses, is included.

22 CFR 16.6 - Security clearances.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a fair...

22 CFR 16.6 - Security clearances.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a fair...

22 CFR 16.6 - Security clearances.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a fair...

48 CFR 2452.237-75 - Clearance of contractor personnel.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Clearance of contractor... Clauses 2452.237-75 Clearance of contractor personnel. As prescribed in 2437.110(e), insert the following clause in solicitations and contracts. Clearance of Contractor Personnel (OCT 1999) (a) General. This...

46 CFR 56.75-10 - Joint clearance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be no...

Pre-Departure Clearance (PDC): An Analysis of Aviation Safety Reporting System Reports Concerning PDC Related Errors

NASA Technical Reports Server (NTRS)

Montalyo, Michael L.; Lebacqz, J. Victor (Technical Monitor)

1994-01-01

Airlines operating in the United States are required to operate under instrument flight rules (EFR). Typically, a clearance is issued via voice transmission from clearance delivery at the departing airport. In 1990, the Federal Aviation Administration (FAA) began deployment of the Pre-Departure Clearance (PDC) system at 30 U.S. airports. The PDC system utilizes aeronautical datalink and Aircraft Communication and Reporting System (ACARS) to transmit departure clearances directly to the pilot. An objective of the PDC system is to provide an immediate reduction in voice congestion over the clearance delivery frequency. Participating airports report that this objective has been met. However, preliminary analysis of 42 Aviation Safety Reporting System (ASRS) reports has revealed problems in PDC procedures and formatting which have caused errors in the proper execution of the clearance. It must be acknowledged that this technology, along with other advancements on the flightdeck, is adding more responsibility to the crew and increasing the opportunity for error. The present study uses these findings as a basis for further coding and analysis of an additional 82 reports obtained from an ASRS database search. These reports indicate that clearances are often amended or exceptions are added in order to accommodate local ATC facilities. However, the onboard ACARS is limited in its ability to emphasize or highlight these changes which has resulted in altitude and heading deviations along with increases in ATC workload. Furthermore, few participating airports require any type of PDC receipt confirmation. In fact, 35% of all ASRS reports dealing with PDC's include failure to acquire the PDC at all. Consequently, this study examines pilots' suggestions contained in ASRS reports in order to develop recommendations to airlines and ATC facilities to help reduce the amount of incidents that occur.

Timing of intermittent torque control with wire-driven gait training robot lifting toe trajectory for trip avoidance.

PubMed

Miyake, Tamon; Kobayashi, Yo; Fujie, Masakatsu G; Sugano, Shigeki

2017-07-01

Gait training robots are useful for changing gait patterns and decreasing risk of trip. Previous research has reported that decreasing duration of the assistance or guidance of the robot is beneficial for efficient gait training. Although robotic intermittent control method for assisting joint motion has been established, the effect of the robot intervention timing on change of toe clearance is unclear. In this paper, we tested different timings of applying torque to the knee, employing the intermittent control of a gait training robot to increase toe clearance throughout the swing phase. We focused on knee flexion motion and designed a gait training robot that can apply flexion torque to the knee with a wire-driven system. We used a method of timing detecting for the robot conducting torque control based on information from the hip, knee, and ankle angles to establish a non-time dependent parameter that can be used to adapt to gait change, such as gait speed. We carried out an experiment in which the conditions were four time points: starting the swing phase, lifting the foot, maintaining knee flexion, and finishing knee flexion. The results show that applying flexion torque to the knee at the time point when people start lifting their toe is effective for increasing toe clearance in the whole swing phase.

78 FR 22020 - Agency Information Collection Activities: Requests for Comments; Clearance of New Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-12

... Control Number: 2120-XXXX. Title: Safety Awareness, Feedback, and Evaluation (SAFE) Program. Form Numbers: No FAA forms are associated with this collection. Type of Review: Clearance of a new information... Activities: Requests for Comments; Clearance of New Approval of Information Collection: Safety Awareness...

5 CFR 1320.11 - Clearance of collections of information in proposed rules.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Clearance of collections of information in proposed rules. 1320.11 Section 1320.11 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET OMB DIRECTIVES CONTROLLING PAPERWORK BURDENS ON THE PUBLIC § 1320.11 Clearance of collections of...

5 CFR 1320.12 - Clearance of collections of information in current rules.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Clearance of collections of information in current rules. 1320.12 Section 1320.12 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET OMB DIRECTIVES CONTROLLING PAPERWORK BURDENS ON THE PUBLIC § 1320.12 Clearance of collections of...

76 FR 77244 - Renewal of Information Collection; OMB Control Number 1040-0001, DOI Programmatic Clearance for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-12

... Number 1040-0001, DOI Programmatic Clearance for Customer Satisfaction Surveys AGENCY: Department of [email protected] . Reference ``DOI Programmatic Clearance for Customer Satisfaction Surveys'' in your email... public accountability by promoting a new focus on results, service quality, and customer satisfaction...

Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury.

PubMed

Brosius Lutz, Amanda; Chung, Won-Suk; Sloan, Steven A; Carson, Glenn A; Zhou, Lu; Lovelett, Emilie; Posada, Sean; Zuchero, J Bradley; Barres, Ben A

2017-09-19

Ineffective myelin debris clearance is a major factor contributing to the poor regenerative ability of the central nervous system. In stark contrast, rapid clearance of myelin debris from the injured peripheral nervous system (PNS) is one of the keys to this system's remarkable regenerative capacity, but the molecular mechanisms driving PNS myelin clearance are incompletely understood. We set out to discover new pathways of PNS myelin clearance to identify novel strategies for activating myelin clearance in the injured central nervous system, where myelin debris is not cleared efficiently. Here we show that Schwann cells, the myelinating glia of the PNS, collaborate with hematogenous macrophages to clear myelin debris using TAM (Tyro3, Axl, Mer) receptor-mediated phagocytosis as well as autophagy. In a mouse model of PNS nerve crush injury, Schwann cells up-regulate TAM phagocytic receptors Axl and Mertk following PNS injury, and Schwann cells lacking both of these phagocytic receptors exhibit significantly impaired myelin phagocytosis both in vitro and in vivo. Autophagy-deficient Schwann cells also display reductions in myelin clearance after mouse nerve crush injury, as has been recently shown following nerve transection. These findings add a mechanism, Axl/Mertk-mediated myelin clearance, to the repertoire of cellular machinery used to clear myelin in the injured PNS. Given recent evidence that astrocytes express Axl and Mertk and have previously unrecognized phagocytic potential, this pathway may be a promising avenue for activating myelin clearance after CNS injury.

Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials.

PubMed

Lebwohl, Mark; Dinehart, Scott; Whiting, David; Lee, Peter K; Tawfik, Naji; Jorizzo, Joseph; Lee, James H; Fox, Terry L

2004-05-01

The immune system plays a critical role in the development and pathogenesis of actinic keratosis (AK). Imiquimod has been shown to stimulate the cutaneous immune response and be effective for the treatment of nonmelanoma skin cancers. Two phase III, randomized, double-blind, vehicle-controlled studies evaluated the efficacy of imiquimod 5% cream compared with vehicle in the treatment of AK lesions on the face and balding scalp. A total of 436 participants at 24 centers in the United States and Canada were randomized to either imiquimod 5% or vehicle cream. Study cream was applied one time per day, 2 days per week for 16 weeks. Clearance of AK lesions was clinically assessed at an 8-week posttreatment visit. The complete clearance rate was 45.1% for the imiquimod group and 3.2% for the vehicle group. The difference in complete clearance rates (imiquimod minus vehicle) was 41.9% with a 95% confidence interval of 34.9% to 49%. The partial (> or =75%) clearance rate was 59.1% for the imiquimod group and 11.8% for the vehicle group. The difference in partial clearance rates (imiquimod minus vehicle) was 47.3% with a 95% confidence interval of 39.5% to 55.1%. The median percent reduction in AK lesions was 83.3% for the imiquimod group and 0% for the vehicle group. Local skin reactions were common. Severe erythema was reported by 17.7% of participants who received imiquimod and 2.3% of participants who received vehicle. Overall, imiquimod was very well tolerated. Imiquimod 5% cream used 2 times per week for 16 weeks is an effective and well-tolerated treatment for AK.

49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis.

PubMed

Tracy, T S; Krohn, K; Jones, D R; Bradley, J D; Hall, S D; Brater, D C

1992-01-01

We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.

CF6 High Pressure Compressor and Turbine Clearance Evaluations

NASA Technical Reports Server (NTRS)

Radomski, M. A.; Cline, L. D.

1981-01-01

In the CF6 Jet Engine Diagnostics Program the causes of performance degradation were determined for each component of revenue service engines. It was found that a significant contribution to performance degradation was caused by increased airfoil tip radial clearances in the high pressure compressor and turbine areas. Since the influence of these clearances on engine performance and fuel consumption is significant, it is important to accurately establish these relatonships. It is equally important to understand the causes of clearance deterioration so that they can be reduced or eliminated. The results of factory engine tests run to enhance the understanding of the high pressure compressor and turbine clearance effects on performance are described. The causes of clearance deterioration are indicated and potential improvements in clearance control are discussed.

Simulations of Continuous Descent Operations with Arrival-management Automation and Mixed Flight-deck Interval Management Equipage

NASA Technical Reports Server (NTRS)

Callantine, Todd J.; Kupfer, Michael; Martin, Lynne Hazel; Prevot, Thomas

2013-01-01

Air traffic management simulations conducted in the Airspace Operations Laboratory at NASA Ames Research Center have addressed the integration of trajectory-based arrival-management automation, controller tools, and Flight-Deck Interval Management avionics to enable Continuous Descent Operations (CDOs) during periods of sustained high traffic demand. The simulations are devoted to maturing the integrated system for field demonstration, and refining the controller tools, clearance phraseology, and procedures specified in the associated concept of operations. The results indicate a variety of factors impact the concept's safety and viability from a controller's perspective, including en-route preconditioning of arrival flows, useable clearance phraseology, and the characteristics of airspace, routes, and traffic-management methods in use at a particular site. Clear understanding of automation behavior and required shifts in roles and responsibilities is important for controller acceptance and realizing potential benefits. This paper discusses the simulations, drawing parallels with results from related European efforts. The most recent study found en-route controllers can effectively precondition arrival flows, which significantly improved route conformance during CDOs. Controllers found the tools acceptable, in line with previous studies.

Nuclear core positioning system

DOEpatents

Garkisch, Hans D.; Yant, Howard W.; Patterson, John F.

1979-01-01

A structural support system for the core of a nuclear reactor which achieves relatively restricted clearances at operating conditions and yet allows sufficient clearance between fuel assemblies at refueling temperatures. Axially displaced spacer pads having variable between pad spacing and a temperature compensated radial restraint system are utilized to maintain clearances between the fuel elements. The core support plates are constructed of metals specially chosen such that differential thermal expansion produces positive restraint at operating temperatures.

DOE DISS/ET pilot system

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

Strait, R.S.; Wagner, E.E.

1994-07-01

The US Department of Energy (DOE) Office of Safeguards and Security initiated the DOE Integrated Security System / Electronic Transfer (DISS/ET) for the purpose of reducing the time required to process security clearance requests. DISS/ET will be an integrated system using electronic commerce technologies for the collection and processing of personnel security clearance data, and its transfer between DOE local security clearance offices, DOE Operations Offices, and the Office of Personnel Management. The system will use electronic forms to collect clearance applicant data. The forms data will be combined with electronic fingerprint images and packaged in a secure encrypted electronicmore » mail envelope for transmission across the Internet. Information provided by the applicant will be authenticated using digital signatures. All processing will be done electronically.« less

49 CFR 802.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... control of the NTSB pursuant to Federal law or in connection with the transaction of public business... purposes ordered by a court referral to potential employers, and for security clearance; Statistical record means a record in a system of records maintained for statistical research or reporting purposes only and...

Long-term clearance from small airways in subjects with ciliary dysfunction.

PubMed

Lindström, Maria; Falk, Rolf; Hjelte, Lena; Philipson, Klas; Svartengren, Magnus

2006-05-20

The objective of this study was to investigate if long-term clearance from small airways is dependent on normal ciliary function. Six young adults with primary ciliary dyskinesia (PCD) inhaled 111 Indium labelled Teflon particles of 4.2 microm geometric and 6.2 microm aerodynamic diameter with an extremely slow inhalation flow, 0.05 L/s. The inhalation method deposits particles mainly in the small conducting airways. Lung retention was measured immediately after inhalation and at four occasions up to 21 days after inhalation. Results were compared with data from ten healthy controls. For additional comparison three of the PCD subjects also inhaled the test particles with normal inhalation flow, 0.5 L/s, providing a more central deposition. The lung retention at 24 h in % of lung deposition (Ret24) was higher (p < 0.001) in the PCD subjects, 79 % (95% Confidence Interval, 67.6;90.6), compared to 49% (42.3;55.5) in the healthy controls. There was a significant clearance after 24 h both in the PCD subjects and in the healthy controls with equivalent clearance. The mean Ret24 with slow inhalation flow was 73.9 +/- 1.9% compared to 68.9 +/- 7.5% with normal inhalation flow in the three PCD subjects exposed twice. During day 7-21 the three PCD subjects exposed twice cleared 9% with normal flow, probably representing predominantly alveolar clearance, compared to 19% with slow inhalation flow, probably representing mainly small airway clearance. This study shows that despite ciliary dysfunction, clearance continues in the small airways beyond 24 h. There are apparently additional clearance mechanisms present in the small airways.

Treatment of the control mechanisms of light airplanes in the flutter clearance process

NASA Technical Reports Server (NTRS)

Breitbach, E. J.

1979-01-01

It has become more and more evident that many difficulties encountered in the course of aircraft flutter analyses can be traced to strong localized nonlinearities in the control mechanisms. To cope with these problems, more reliable mathematical models paying special attention to control system nonlinearities were established by means of modified ground vibration test procedures in combination with suitably adapted modal synthesis approaches. Three different concepts are presented.

75 FR 75189 - 30-Day Notice of Proposed Information Collection: Form DS-3057, Medical Clearance Update, OMB...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-02

... on whether a federal employee and family members will have sufficient medical resources at a...-3057, Medical Clearance Update, OMB 1405-0131 ACTION: Notice of request for public comments. SUMMARY... Reduction Act of 1995. Title of Information Collection: Medical Clearance Update. OMB Control Number: 1405...

78 FR 5855 - Agency Information Collection Activities: Requests for Comments; Clearance of a New Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-28

... generic clearance for the purpose of gathering customer satisfaction data directly from customers for a... Activities: Requests for Comments; Clearance of a New Approval of Information Collection: FAA Customer... INFORMATION: OMB Control Number: 2120-XXXX Title: FAA Customer Service Surveys Form Numbers: There are no FAA...

Dynamic alteration in splenic function during acute falciparum malaria

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

Looareesuwan, S.; Ho, M.; Wattanagoon, Y.

Plasmodium-infected erythrocytes lose their normal deformability and become susceptible to splenic filtration. In animal models, this is one mechanism of antimalarial defense. To assess the effect of acute falciparum malaria on splenic filtration, we measured the clearance of heated /sup 51/Cr-labeled autologous erythrocytes in 25 patients with acute falciparum malaria and in 10 uninfected controls. Two groups of patients could be distinguished. Sixteen patients had splenomegaly, markedly accelerated clearance of the labeled erythrocytes (clearance half-time, 8.4 +/- 4.4 minutes (mean +/- SD) vs. 62.5 +/- 36.5 minutes in controls; P less than 0.001), and a lower mean hematocrit than didmore » the patients without splenomegaly (P less than 0.001). In the nine patients without splenomegaly, clearance was normal. After institution of antimalarial chemotherapy, however, the clearance in this group accelerated to supernormal rates similar to those in the patients with splenomegaly, but without the development of detectable splenomegaly. Clearance was not significantly altered by treatment in the group with splenomegaly. Six weeks later, normal clearance rates were reestablished in most patients in both groups. We conclude that splenic clearance of labeled erythrocytes is enhanced in patients with malaria if splenomegaly is present and is enhanced only after treatment if splenomegaly is absent. Whether this enhanced splenic function applies to parasite-infected erythrocytes in patients with malaria and has any clinical benefit will require further studies.« less

Shape memory alloy adaptive control of gas turbine engine compressor blade tip clearance

NASA Astrophysics Data System (ADS)

Schetky, Lawrence M.; Steinetz, Bruce M.

1998-06-01

The ambient air ingested through the inlet of a gas turbine is first compressed by an axial compressor followed by further compression in a centrifugal compressor and then fed into the combustion chamber where ignition and expansion take place to produce the engine thrust. The axial compressor typically has five or more stages which consist of revolving blades and stators and the overall performance of the turbine is strongly affected by the compressor efficiency. When the turbine is turned on, to accommodate the rapid initial increase in the compressor blade length due to centrifugal force, the cold turbine has a built in clearance between the turbine blade tip and the casing. As the turbine reached its operating temperature there is a further increase in the blade length due to thermal expansion and, at the same time, the diameter of the casing increases. The net result is that when these various components have reached their equilibrium temperatures, the initial cold build clearance is reduced, but there remains a residual clearance. The magnitude of this clearance has a direct effect on the compressor efficiency and can be stated as: Δη/Δ CLR equals 0.5 where η is efficiency and CLR is the tip clearance. The concept of adaptive tip clearance control is based on the ability of a shape memory alloy ring to shrink to a predetermined diameter when heated to the temperature of a particular stage, and thus reducing the tip clearance. The ring is fabricated from a CuAlNi shape memory alloy and is mounted in the casing so as to be coaxial with the rotating blades of the particular stage. When cold, the ring dimensions are such as to provide the required cold build clearance, but when at operating temperature the reduced diameter creates a very small tip clearance. The clearance provided by this concept is much smaller than the clearance normally obtained for a turbine of the size being studied.

Turbomachinery Clearance Control

NASA Technical Reports Server (NTRS)

Chupp, Raymond E.; Hendricks, Robert C.; Lattime, Scott B.; Steinetz, Bruce M.; Aksit, Mahmut F.

2007-01-01

Controlling interface clearances is the most cost effective method of enhancing turbomachinery performance. Seals control turbomachinery leakages, coolant flows and contribute to overall system rotordynamic stability. In many instances, sealing interfaces and coatings are sacrificial, like lubricants, giving up their integrity for the benefit of the component. They are subjected to abrasion, erosion, oxidation, incursive rubs, foreign object damage (FOD) and deposits as well as extremes in thermal, mechanical, aerodynamic and impact loadings. Tribological pairing of materials control how well and how long these interfaces will be effective in controlling flow. A variety of seal types and materials are required to satisfy turbomachinery sealing demands. These seals must be properly designed to maintain the interface clearances. In some cases, this will mean machining adjacent surfaces, yet in many other applications, coatings are employed for optimum performance. Many seals are coating composites fabricated on superstructures or substrates that are coated with sacrificial materials which can be refurbished either in situ or by removal, stripping, recoating and replacing until substrate life is exceeded. For blade and knife tip sealing an important class of materials known as abradables permit blade or knife rubbing without significant damage or wear to the rotating element while maintaining an effective sealing interface. Most such tip interfaces are passive, yet some, as for the high-pressure turbine (HPT) case or shroud, are actively controlled. This work presents an overview of turbomachinery sealing. Areas covered include: characteristics of gas and steam turbine sealing applications and environments, benefits of sealing, types of standard static and dynamics seals, advanced seal designs, as well as life and limitations issues.

Abnormal oral glucose tolerance and glucose malabsorption after vagotomy and pyloroplasty. A tracer method for measuring glucose absorption rates

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

Radziuk, J.; Bondy, D.C.

1982-11-01

The mechanisms underlying the abnormal glucose tolerance in patients who had undergone vagotomy and pyloroplasty were investigated by measuring the rates of absorption of ingested glucose and the clearance rate of glucose using tracer methods. These methods are based on labeling a 100-g oral glucose load with (1-/sup 14/C)glucose and measuring glucose clearance using plasma levels of infused (3-/sup 3/H)glucose. The rate of appearance of both ingested and total glucose is then calculated continuously using a two-compartment model of glucose kinetics. It was found that about 30% of the ingested glucose (100 g) failed to appear in the systemic circulation.more » That this was due to malabsorption was confirmed using breath-hydrogen analysis. The absorption period is short (101 +/- 11 min) compared with normal values but the clearance of glucose is identical to that in control subjects, and it peaks 132 +/- 7 min after glucose loading. The peak plasma insulin values were more than four times higher in patients than in normal subjects, and this may afford an explanation of rates of glucose clearance that are inappropriate for the short absorption period. The combination of glucose malabsorption and this clearance pattern could yield the hypoglycemia that may be observed in patients after gastric surgery.« less

76 FR 65777 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-24

... the regulations governing freight power brakes and equipment in October 2008 by adding a new Subpart... being submitted for clearance by OMB as required by the PRA. Title: Inspection Brake System Safety Standards for Freight and Other Non-Passenger Trains and Equipment (Power Brakes and Drawbars). OMB Control...

Nanoparticle-macrophage interactions: A balance between clearance and cell-specific targeting

PubMed Central

Rattan, Rahul; Bhattacharjee, Somnath; Zong, Hong; Swain, Corban; Siddiqui, Muneeb A.; Visovatti, Scott H.; Kanthi, Yogendra; Desai, Sajani; Pinsky, David J.; Goonewardena, Sascha N.

2017-01-01

The surface properties of nanoparticles (NPs) are a major factor that influences how these nanomaterials interact with biological systems. Interactions between NPs and macrophages of the reticuloendothelial system (RES) can reduce the efficacy of NP diagnostics and therapeutics. Traditionally, to limit NP clearance by the RES system, the NP surface is neutralized with molecules like poly(ethylene glycol) (PEG) which are known to resist protein adsorption and RES clearance. Unfortunately, PEG modification is not without drawbacks including difficulties with the synthesis and associations with immune reactions. To overcome some of these obstacles, we neutralized the NP surface by acetylation and compared this modification to PEGylation for RES clearance and tumor-specific targeting. We found that acetylation was comparable to PEGylation in reducing RES clearance. Additionally, we found that dendrimer acetylation did not impact folic acid (FA)-mediated targeting of tumor cells whereas PEG surface modification reduced the targeting ability of the NP. These results clarify the impact of different NP surface modifications on RES clearance and cell-specific targeting and provide insights into the design of more effective NPs. PMID:28705434

Development and gamma-scintigraphy study of Hibiscus rosasinensis polysaccharide-based microspheres for nasal drug delivery.

PubMed

Sharma, Nitin; Tyagi, Shanu; Gupta, Satish Kumar; Kulkarni, Giriraj Thirupathirao; Bhatnagar, Aseem; Kumar, Neeraj

2016-11-01

This work describes the application of natural plant polysaccharide as pharmaceutical mucoadhesive excipients in delivery systems to reduce the clearance rate through nasal cavity. Novel natural polysaccharide (Hibiscus rosasinensis)-based mucoadhesive microspheres were prepared by using emulsion crosslinking method for the delivery of rizatriptan benzoate (RB) through nasal route. Mucoadhesive microspheres were characterized for different parameters and nasal clearance of technetium-99m ((99m)Tc)-radiolabeled microspheres was determined by using gamma-scintigraphy. Their Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) studies showed that the drug was stable during preparation of microspheres. Aerodynamic diameter of microspheres was in the range 13.23 ± 1.83-33.57 ± 3.69 µm. Change in drug and polysaccharide ratio influenced the mucoadhesion, encapsulation efficiency and in-vitro release property. Scintigraphs taken at regular interval indicate that control solution was cleared rapidly from nasal cavity, whereas microspheres showed slower clearance (p < 0.005) with half-life of 160 min. Natural polysaccharide-based microspheres achieved extended residence by minimizing effect of mucociliary clearance with opportunity of sustained delivery for longer duration.

Measles virus, immune control and persistence

PubMed Central

Griffin, Diane E.; Lin, Wen-Hsuan; Pan, Chien-Hsiung

2012-01-01

Measles remains one of the most important causes of child morbidity and mortality worldwide with the greatest burden in the youngest children. Most acute measles deaths are due to secondary infections that result from a poorly understood measles-induced suppression of immune responses. Young children are also vulnerable to late development of subacute sclerosing panencephalitis, a progressive, uniformly fatal neurologic disease caused by persistent measles virus (MeV) infection. During acute infection, the rash marks the appearance of the adaptive immune response and CD8+ T cell-mediated clearance of infectious virus. However, after clearance of infectious virus, MeV RNA persists and can be detected in blood, respiratory secretions, urine and lymphoid tissue for many weeks to months. This prolonged period of virus clearance may help to explain measles immunosuppression and the development of lifelong immunity to re-infection, as well as occasional infection of the nervous system. Once MeV infects neurons, the virus can spread transynaptically and the envelope proteins needed to form infectious virus are unnecessary, accumulate mutations and can establish persistent infection. Identification of the immune mechanisms required for clearance of MeV RNA from multiple sites will enlighten our understanding of the development of disease due to persistent infection. PMID:22316382

Dynamic modelling and experimental study of cantilever beam with clearance

NASA Astrophysics Data System (ADS)

Li, B.; Jin, W.; Han, L.; He, Z.

2012-05-01

Clearances occur in almost all mechanical systems, typically such as the clearance between slide plate of gun barrel and guide. Therefore, to study the clearances of mechanisms can be very important to increase the working performance and lifetime of mechanisms. In this paper, rigid dynamic modelling of cantilever with clearance was done according to the subject investigated. In the rigid dynamic modelling, clearance is equivalent to the spring-dashpot model, the impact of beam and boundary face was also taken into consideration. In ADAMS software, the dynamic simulation was carried out according to the model above. The software simulated the movement of cantilever with clearance under external excitation. Research found: When the clearance is larger, the force of impact will become larger. In order to study how the stiffness of the cantilever's supporting part influences natural frequency of the system, A Euler beam which is restricted by a draught spring and a torsion spring at its end was raised. Through numerical calculation, the relationship between natural frequency and stiffness was found. When the value of the stiffness is close to the limit value, the corresponding boundary condition is illustrated. An ADAMS experiment was carried out to check the theory and the simulation.

Confusion in Using Pre-Departure Clearances

DOT National Transportation Integrated Search

1996-12-20

In 1990, the FAA implemented the Pre-Departure Clearance (PDC) program at a : number of U.S. airports. This system allows pilots to obtain IFR clearances : through aircraft ACARS units prior to taxi-out, thus eliminating the need for : verbal communi...

Piloted simulation of an air-ground profile negotiation process in a time-based Air Traffic Control environment

NASA Technical Reports Server (NTRS)

Williams, David H.; Green, Steven M.

1993-01-01

Historically, development of airborne flight management systems (FMS) and ground-based air traffic control (ATC) systems has tended to focus on different objectives with little consideration for operational integration. A joint program, between NASA's Ames Research Center (Ames) and Langley Research Center (Langley), is underway to investigate the issues of, and develop systems for, the integration of ATC and airborne automation systems. A simulation study was conducted to evaluate a profile negotiation process (PNP) between the Center/TRACON Automation System (CTAS) and an aircraft equipped with a four-dimensional flight management system (4D FMS). Prototype procedures were developed to support the functional implementation of this process. The PNP was designed to provide an arrival trajectory solution which satisfies the separation requirements of ATC while remaining as close as possible to the aircraft's preferred trajectory. Results from the experiment indicate the potential for successful incorporation of aircraft-preferred arrival trajectories in the CTAS automation environment. Fuel savings on the order of 2 percent to 8 percent, compared to fuel required for the baseline CTAS arrival speed strategy, were achieved in the test scenarios. The data link procedures and clearances developed for this experiment, while providing the necessary functionality, were found to be operationally unacceptable to the pilots. In particular, additional pilot control and understanding of the proposed aircraft-preferred trajectory, and a simplified clearance procedure were cited as necessary for operational implementation of the concept.

Testing of a Microwave Blade Tip Clearance Sensor at the NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Woike, Mark R.; Roeder, James W.; Hughes, Christopher E.; Bencic, Timothy J.

2009-01-01

The development of new active tip clearance control and structural health monitoring schemes in turbine engines and other types of rotating machinery requires sensors that are highly accurate and can operate in a high-temperature environment. The use of a microwave sensor to acquire blade tip clearance and tip timing measurements is being explored at the NASA Glenn Research Center. The microwave blade tip clearance sensor works on principles that are very similar to a short-range radar system. The sensor sends a continuous microwave signal towards a target and measures the reflected signal. The phase difference of the reflected signal is directly proportional to the distance between the sensor and the target being measured. This type of sensor is beneficial in that it has the ability to operate at extremely high temperatures and is unaffected by contaminants that may be present in turbine engines. The use of microwave sensors for this application is a new concept. Techniques on calibrating the sensors along with installation effects are not well quantified as they are for other sensor technologies. Developing calibration techniques and evaluating installation effects are essential in using these sensors to make tip clearance and tip timing measurements. As a means of better understanding these issues, the microwave sensors were used on a benchtop calibration rig, a large axial vane fan, and a turbofan. Background on the microwave tip clearance sensor, an overview of their calibration, and the results from their use on the axial vane fan and the turbofan will be presented in this paper.

Testing of a Microwave Blade Tip Clearance Sensor at the NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Woike, Mark R.; Roeder, James W.; Hughes, Christopher E.; Bencic, Timothy J.

2009-01-01

The development of new active tip clearance control and structural health monitoring schemes in turbine engines and other types of rotating machinery requires sensors that are highly accurate and can operate in a high temperature environment. The use of a microwave sensor to acquire blade tip clearance and tip timing measurements is being explored at the NASA Glenn Research Center. The microwave blade tip clearance sensor works on principles that are very similar to a short range radar system. The sensor sends a continuous microwave signal towards a target and measures the reflected signal. The phase difference of the reflected signal is directly proportional to the distance between the sensor and the target being measured. This type of sensor is beneficial in that it has the ability to operate at extremely high temperatures and is unaffected by contaminants that may be present in turbine engines. The use of microwave sensors for this application is a new concept. Techniques on calibrating the sensors along with installation effects are not well quantified as they are for other sensor technologies. Developing calibration techniques and evaluating installation effects are essential in using these sensors to make tip clearance and tip timing measurements. As a means of better understanding these issues, the microwave sensors were used on a bench top calibration rig, a large axial vane fan, and a turbofan. Background on the microwave tip clearance sensor, an overview of their calibration, and the results from their use on the axial vane fan and the turbofan will be presented in this paper.

A Matter of Millimeters: Defining the Processes for Critical Clearances on Curiosity

NASA Technical Reports Server (NTRS)

Florow, Brandon

2013-01-01

The Mars Science Laboratory (MSL) mission presents an immense packaging problem in that it takes a rover the size of a car with a sky crane landing system and packs it tightly into a spacecraft. This creates many areas of close and critical clearances. Critical Clearances are defined as hardware-to-hardware or hardware-to-envelope clearances which fall below a pre-established location dependent threshold and pose a risk of hardware to hardware contact during events such as launch, entry, landing, and operations. Close Clearances, on the other hand, are defined as any clearance value that is chosen to be tracked but is larger than the critical clearance threshold for its region. Close clearances may be tracked for various reasons including uncertainty in design, large expected dynamic motion, etc.

Pairwise Trajectory Management (PTM): Concept Overview

NASA Technical Reports Server (NTRS)

Jones, Kenneth M.; Graff, Thomas J.; Chartrand, Ryan C.; Carreno, Victor; Kibler, Jennifer L.

2017-01-01

Pairwise Trajectory Management (PTM) is an Interval Management (IM) concept that utilizes airborne and ground-based capabilities to enable the implementation of airborne pairwise spacing capabilities in oceanic regions. The goal of PTM is to use airborne surveillance and tools to manage an "at or greater than" inter-aircraft spacing. Due to the precision of Automatic Dependent Surveillance-Broadcast (ADS-B) information and the use of airborne spacing guidance, the PTM minimum spacing distance will be less than distances a controller can support with current automation systems that support oceanic operations. Ground tools assist the controller in evaluating the traffic picture and determining appropriate PTM clearances to be issued. Avionics systems provide guidance information that allows the flight crew to conform to the PTM clearance issued by the controller. The combination of a reduced minimum distance and airborne spacing management will increase the capacity and efficiency of aircraft operations at a given altitude or volume of airspace. This paper provides an overview of the proposed application, description of a few key scenarios, high level discussion of expected air and ground equipment and procedure changes, overview of a potential flight crew human-machine interface that would support PTM operations and some initial PTM benefits results.

P-glycoprotein, but not Multidrug Resistance Protein 4, Plays a Role in the Systemic Clearance of Irinotecan and SN-38 in Mice

PubMed Central

Tagen, Michael; Zhuang, Yanli; Zhang, Fan; Harstead, K. Elaine; Shen, Jun; Schaiquevich, Paula; Fraga, Charles H.; Panetta, John C.; Waters, Christopher M.; Stewart, Clinton F.

2015-01-01

The ATP-binding cassette transporters P-glycoprotein (ABCB1, MDR1) and multidrug resistance protein 4 (MRP4) efflux irinotecan and its active metabolite SN-38 in vitro, and thus may contribute to system clearance of these compounds. Mdr1a/b−/−, Mrp4−/−, and wild-type mice were administered 20 or 40 mg/kg irinotecan, and plasma samples were collected for 6 hours. Irinotecan and SN-38 lactone and carboxylate were quantitated and data were analyzed with nonlinear mixed-effects modeling. Mdr1a/b genotype was a significant covariate for the clearance of both irinotecan lactone and SN-38 lactone. Exposures to irinotecan lactone and SN-38 lactone after a 40 mg/kg dose were 1.6-fold higher in Mdr1a/b−/− mice compared to wild-type mice. Plasma concentrations of irinotecan lactone, irinotecan carboxylate, and SN-38 lactone in Mrp4−/− mice were similar to the wild-type controls. These results suggest that P-gp plays a role in irinotecan and SN-38 elimination, but Mrp4 does not affect irinotecan or SN-38 plasma pharmacokinetics. PMID:20583968

Zinc supplementation leads to immune modulation and improved survival in a juvenile model of murine sepsis.

PubMed

Ganatra, Hammad A; Varisco, Brian M; Harmon, Kelli; Lahni, Patrick; Opoka, Amy; Wong, Hector R

2017-01-01

Children with severe sepsis are known to have altered zinc homeostasis and decreased circulating zinc levels, suggesting a role for zinc supplementation to improve outcomes. We tested the hypothesis that zinc supplementation would improve survival in a juvenile model of polymicrobial sepsis. Juvenile (13-14-d-old) C57BL/6 mice were treated with 10 mg/kg of zinc via i.p. injections (or vehicle) for 3 d prior to induction of polymicrobial sepsis via i.p. cecal slurry injections. Survival after sepsis was followed for 3 d, and bacterial clearance, ex vivo phagocytosis, systemic inflammatory markers and neutrophil extracellular trap (NET) formation were quantified. We found a significant survival benefit and decreased bacterial burden among zinc supplemented mice when compared with the control group. Zinc supplementation also resulted in enhanced phagocytic activity, greater neutrophil recruitment in the peritoneal cavity and NET formation, suggesting a possible mechanism for improved bacterial clearance and survival. We also noted decreased serum cytokine levels and decreased myeloperoxidase activity in lung tissue following zinc supplementation, suggesting attenuation of the systemic inflammatory response. In conclusion, zinc supplementation improves bacterial clearance, and hence survival, in juvenile mice with polymicrobial sepsis.

The Immune Response in Measles: Virus Control, Clearance and Protective Immunity.

PubMed

Griffin, Diane E

2016-10-12

Measles is an acute systemic viral infection with immune system interactions that play essential roles in multiple stages of infection and disease. Measles virus (MeV) infection does not induce type 1 interferons, but leads to production of cytokines and chemokines associated with nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling and activation of the NACHT, LRR and PYD domains-containing protein (NLRP3) inflammasome. This restricted response allows extensive virus replication and spread during a clinically silent latent period of 10-14 days. The first appearance of the disease is a 2-3 day prodrome of fever, runny nose, cough, and conjunctivitis that is followed by a characteristic maculopapular rash that spreads from the face and trunk to the extremities. The rash is a manifestation of the MeV-specific type 1 CD4⁺ and CD8⁺ T cell adaptive immune response with lymphocyte infiltration into tissue sites of MeV replication and coincides with clearance of infectious virus. However, clearance of viral RNA from blood and tissues occurs over weeks to months after resolution of the rash and is associated with a period of immunosuppression. However, during viral RNA clearance, MeV-specific antibody also matures in type and avidity and T cell functions evolve from type 1 to type 2 and 17 responses that promote B cell development. Recovery is associated with sustained levels of neutralizing antibody and life-long protective immunity.

Modeling Relationships Between Flight Crew Demographics and Perceptions of Interval Management

NASA Technical Reports Server (NTRS)

Remy, Benjamin; Wilson, Sara R.

2016-01-01

The Interval Management Alternative Clearances (IMAC) human-in-the-loop simulation experiment was conducted to assess interval management system performance and participants' acceptability and workload while performing three interval management clearance types. Twenty-four subject pilots and eight subject controllers flew ten high-density arrival scenarios into Denver International Airport during two weeks of data collection. This analysis examined the possible relationships between subject pilot demographics on reported perceptions of interval management in IMAC. Multiple linear regression models were created with a new software tool to predict subject pilot questionnaire item responses from demographic information. General patterns were noted across models that may indicate flight crew demographics influence perceptions of interval management.

Communication and Control for Fleets of Autonomous Underwater Vehicles

DTIC Science & Technology

2006-10-30

Washington State University (WSU) on fuzzy logic control systems [2-4] and autonomous vehicles [5-10]. The ALWSE-MC program developed at NAVSEA CSS was...rotating head sonar on crawlers as an additional sensor for navigation. We have previously investigated the use of video cameras on autonomous vehicles for...simulates autonomous vehicles performing mine reconnaissance/mapping, clearance, and surveillance in a littoral region. Three simulations were preformed

Clearance Analysis of CTC2 (on ELC4) to S-TRRJ HRS Radiator Rotation Envelope

NASA Technical Reports Server (NTRS)

Liddle, Donn

2014-01-01

In response to the planned retirement of the Space Shuttle Program, International Space Station (ISS) management began stockpiling spare parts on the ISS. Many of the larger orbital replacement units were stored on the Expedite the Processing of Experiments to Space Station (EXPRESS) Logistics Carriers (ELCs) mounted on the end of the S3 and P3 truss segments, immediately outboard of the Thermal Radiator Rotary Joints (TRRJs) and their attached radiators. In an August 2009 computer-aided design (CAD) assessment, it was determined that mounting the Cargo Transport Container (CTC) 2 on the inboard face of ELC4 as planned would create insufficient clearance between the CTC2 and the rotational envelope of the radiators when the TRRJs were rotated to a gamma angle of 35.0 degrees. The true clearance would depend on how the Unpressurized Cargo Carrier Attachment System (UCCAS) was mounted to the S3 truss and how the ELC4 was attached to it. If the plane of the UCCAS attachment points were tilted even slightly inboard, it would significantly change the clearance between CTC2 and the Starboard TRRJ (S-TRRJ) radiators. Additionally, since CTC2 would be covered in multilayer insulation (MLI), the true outer profile of CTC2 was not captured in the CAD models used for the clearance assessment. It was possible that, even if the S-TRRJ radiators cleared CTC2, they could snag the MLI covering. In the fall of 2010, the Image Science and Analysis Group (ISAG) was asked to perform an on-orbit clearance analysis to determine the location of CTC2 on ELC4 and the S-TRRJ radiators at the angle of closest approach so that a positive clearance could be assured. To provide the measurements as quickly as possible to aid in the assessment, it was decided that the clearance analysis would be broken into two phases. Phase I: The location and orientation of the UCCAS fittings, which support and hold the ELC4 in place, would be measured relative to the ISS Analytical Coordinate System (ISSACS) as defined by nine preexisting Space Vision System (SVS) targets affixed to the forward/zenith side of the S1 and S3 truss segments. The location of the outboard edge of the S-TRRJ radiator would also be measured when positioned at the angle of closest approach to CTC2 (gamma = 35.0 degrees). This data would allow the Digital Pre-Assembly Group to predict how the ELC4 would sit on the UCCAS and how that would translate into the clearance between CTC2 and the S-TRRJ radiators. Phase II: After the ELC4 was delivered and installed into the UCCAS, the position of the CTC2 mounting plate on the inboard face of ELC4, would be measured in the ISSACS coordinate system relative to the SVS control points used in Phase I. Although CTC2 would not yet be mounted on ELC4, the working envelope of CTC2 could be mathematically added to the measured position of ELC4 to produce a best estimate for CTC2's mounted location. Comparing CTC2's best estimated location to the S-TRRJ radiator (measured in Phase I); relative to the ISSACS coordinate system, would provide a direct measurement of the expected clearance. Due to the impending delivery of ELC4 (scheduled for January 2011), planning for the Phase I clearance analysis began immediately. Using the Dynamic Onboard Ubiquitous Graphics (DOUG) program, ISAG designed a way to acquire images of the SVS control points on truss segments S1 and S3, the aft facing edge of the S-TRRJ Heat Rejection Subsystem (HRS) radiator, and the three UCCAS latch mechanisms mounted on the zenith face of the S3 truss using the Space Station Remote Manipulator System (SSRMS). To minimize the number of SSRMS movements, the Special Purpose Dexterous Manipulator (SPDM) would be attached to the SSRMS. This would make it possible to park the SPDM in one position and acquire multiple images by changing the viewing orientation of the SPDM body cameras using the pan/tilt units on which they are mounted. Using this implementation concept, ISAG identified four SSRMS/SPDM positions from which the majority of the needed imagery could be acquired. Five additional images would be acquired using the CP-3 external ISS camera mounted on the S1 truss immediately inboard of ELC4. Based on a photogrammetric simulation, it was estimated that the measured location of the HRS radiator and UCCAS latch points would be accurate to about 0.3 in. in each of the three axes relative to ISSACS. Working with ROBO, ISAG collected 78 images of the ISS December 29, 2010. From this imagery, the best 40 were selected for use in the analysis process. The images were radiometrically enhanced to improve color and contrast and loaded into the FotoG analysis software along with the camera parameters and control data, which consisted of the coordinates for the nine SVS targets on the S1 and S3 trusses in the ISSACS coordinate system.

Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load.

PubMed

Iredahl, Fredrik; Högstedt, Alexandra; Henricson, Joakim; Sjöberg, Folke; Tesselaar, Erik; Farnebo, Simon

2016-10-01

Insulin causes capillary recruitment in muscle and adipose tissue, but the metabolic and microvascular effects of insulin in the skin have not been studied in detail. The aim of this study was to measure glucose metabolism and microvascular blood flow in the skin during local insulin delivery and after an oral glucose load. Microdialysis catheters were inserted intracutanously in human subjects. In eight subjects two microdialysis catheters were inserted, one perfused with insulin and one with control solution. First the local effects of insulin was studied, followed by a systemic provocation by an oral glucose load. Additionally, as control experiment, six subjects did not recieve local delivery of insulin or the oral glucose load. During microdialysis the local blood flow was measured by urea clearance and by laser speckle contrast imaging (LSCI). Within 15 minutes of local insulin delivery, microvascular blood flow in the skin increased (urea clearance: P=.047, LSCI: P=.002) paralleled by increases in pyruvate (P=.01) and lactate (P=.04), indicating an increase in glucose uptake. An oral glucose load increased urea clearance from the catheters, indicating an increase in skin perfusion, although no perfusion changes were detected with LSCI. The concentration of glucose, pyruvate and lactate increased in the skin after the oral glucose load. Insulin has metabolic and vasodilatory effects in the skin both when given locally and after systemic delivery through an oral glucose load. © 2016 John Wiley & Sons Ltd.

Impairment of nasal mucociliary clearance in woodworkers in the furniture industry

PubMed Central

Black, A.; Evans, J. C.; Hadfield, Esme H.; Macbeth, R. G.; Morgan, A.; Walsh, M.

1974-01-01

Black, A., Evans, J. C., Hadfield, Esme H., Macbeth, R. G., Morgan, A., and Walsh, M. (1974).British Journal of Industrial Medicine,31, 10-17. Impairment of nasal mucociliary clearance in woodworkers in the furniture industry. Measurements of mucociliary clearance from the anterior end of the middle turbinate were made using technetium-99m-labelled particles in nine woodworkers from the furniture industry and in 12 controls, none of whom had been occupationally exposed to wood dust. Clearance rates in the controls ranged from 1·9 to 18·5 mm min-1 with a mean of 6·8. These values are in good agreement with measurements reported elsewhere for normal subjects. Only one of the woodworkers had a clearance rate which fell within the normal range and he had been occupationally exposed for the shortest period (6 years). In four woodworkers clearance was very slow (< 1 mm min-1) and in three there was almost complete stasis. The results of this preliminary investigation suggest that nasal mucociliary function is significantly impaired in workers who have been exposed to wood dust in the furniture industry for more than 10 years. PMID:4821406

Adaptive Engine Technologies for Aviation CO2 Emissions Reduction

NASA Technical Reports Server (NTRS)

Mercer, Carolyn R.; Haller, William J.; Tong, Michael T.

2006-01-01

Adaptive turbine engine technologies are assessed for their potential to reduce carbon dioxide emissions from commercial air transports.Technologies including inlet, fan, and compressor flow control, compressor stall control, blade clearance control, combustion control, active bearings and enabling technologies such as active materials and wireless sensors are discussed. The method of systems assessment is described, including strengths and weaknesses of the approach. Performance benefit estimates are presented for each technology, with a summary of potential emissions reduction possible from the development of new, adaptively controlled engine components.

Human factors in aviation operations: The hearback problem

NASA Technical Reports Server (NTRS)

Monan, William P.

1988-01-01

This report covers a study of ASRS reports wherein ATC controllers failed to monitor adequately (hearback) incorrect readbacks of ATC clearances. A total of 417 reports received over a period of 29 months from April 1981 through July 1983 comprised the study data set. Factors examined were: the reasons for a flight crew's getting clearances incorrectly, the operating factors that caused controllers to mishear or not hear the correct readbacks, and consequences of the various types of hearback misses. The principle conclusion of the study takes the form of a precaution to flight crews that a controller's not challenging a readback does not necessariliy mean the readback is correct and that flight crews must explicitly question any doubtful or unusual aspects of clearances rather than depending on controllers to detect readback errors.

Thermal injury decreases hepatic blood flow and the intrinsic clearance of indocyanine green in the rat.

PubMed

Pollack, G M; Brouwer, K L

1991-01-01

The influence of severe thermal injury (full-thickness burns involving 50% of the body surface area) on hepatic blood flow in the rat was assessed using the tricarbocyanine dye indocyanine green (ICG). In a randomized crossover fashion, rats received sequential infusions of ICG through both the femoral vein and the portal vein, allowing the estimation of total hepatic plasma clearance and transhepatic extraction of the dye. These two parameters, along with the hematocrit, were used to calculate intrinsic hepatic clearance of ICG and hepatic blood flow. Animals were examined at 0 (control), 0.5, 12, or 24 hr following infliction of scald burns. Hepatic blood flow was decreased significantly by 0.5 hr postburn and remained approximately 20% below normal throughout the remainder of the study. The intrinsic efficiency of the liver in removing ICG from the systemic circulation was also decreased by thermal injury. The potential mechanisms involved in these two physiologic perturbations are discussed.

Physiological and histological alterations in the bronchial mucociliary clearance system of rabbits following intermittent oral or nasal inhalation of sulfuric acid mist

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

Schlesinger, R.B.; Naumann, B.D.; Chen, L.C.

Rabbits were exposed to submicrometer sulfuric acid mist (H/sub 2/SO/sub 4/) for 1 h/d, 5 d/w for 4 wk, during which time mucociliary clearance was monitored by external in vivo measurements of tagged tracer aerosol retention. One group was exposed orally to 250 ..mu..g/m/sup 3/, another to the same concentration via the nose, and a third to 500 ..mu..g/m/sup 3/ also via nasal breathing. Clearance was accelerated on specific individual days during the course of the acid exposures, especially at 500 ..mu..g/m/sup 3/. In all series, clearance was significantly faster, compared to preexposure controls, during a 2-wk follow-up period aftermore » acid exposures had ceased. At the end of this period, the rabbits were sacrificed, and histological sections were obtained from the tracheobronchial tree. Significantly increased epithelial thickness of small conducting airways, compared to sham exposure controls, occurred in rabbits exposed orally at 250 ..mu..g/m/sup 3/ or nasally at 500 ..mu.., and additionally the lumen of the smallest airways of the former group was narrower than control. The number of airways containing epithelial secretory cells was also significantly greater in these acid exposure groups compared to sham controls. The only change in the rabbits exposed nasally at 250 ..mu..g/m/sup 3/ was a significant increase in the number of airways with epithelial secretory cells in the smallest airway classfication. Differences in site and degree of histological response and degree of physiological change between the two groups exposed to identical acid concentrations appear to have been due to differences in exposure mode, with resultant effects on breathing pattern, aerosol size distribution, and concentration penetrating beyond the upper respiratory tract to specific lung sites.« less

78 FR 27402 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-10

... Request; Medicated Feed Mill License Application; Extension AGENCY: Food and Drug Administration, HHS... review and clearance. Medicated Feed Mill Licensing Application--21 CFR Part 515 (OMB Control Number 0910... medicated feed with a general licensing system for feed mills. Before passage of the ADAA, medicated feed...

Methodological uncertainty in quantitative prediction of human hepatic clearance from in vitro experimental systems.

PubMed

Hallifax, D; Houston, J B

2009-03-01

Mechanistic prediction of unbound drug clearance from human hepatic microsomes and hepatocytes correlates with in vivo clearance but is both systematically low (10 - 20 % of in vivo clearance) and highly variable, based on detailed assessments of published studies. Metabolic capacity (Vmax) of commercially available human hepatic microsomes and cryopreserved hepatocytes is log-normally distributed within wide (30 - 150-fold) ranges; Km is also log-normally distributed and effectively independent of Vmax, implying considerable variability in intrinsic clearance. Despite wide overlap, average capacity is 2 - 20-fold (dependent on P450 enzyme) greater in microsomes than hepatocytes, when both are normalised (scaled to whole liver). The in vitro ranges contrast with relatively narrow ranges of clearance among clinical studies. The high in vitro variation probably reflects unresolved phenotypical variability among liver donors and practicalities in processing of human liver into in vitro systems. A significant contribution from the latter is supported by evidence of low reproducibility (several fold) of activity in cryopreserved hepatocytes and microsomes prepared from the same cells, between separate occasions of thawing of cells from the same liver. The large uncertainty which exists in human hepatic in vitro systems appears to dominate the overall uncertainty of in vitro-in vivo extrapolation, including uncertainties within scaling, modelling and drug dependent effects. As such, any notion of quantitative prediction of clearance appears severely challenged.

Acute Mucociliary Clearance Response to Aerobic Exercise in Smokers.

PubMed

Ramos, Ercy M C; Vanderlei, Luiz Carlos M; Ito, Juliana T; Lima, Fabiano F; Rodrigues, Fernanda M M; Manzano, Beatriz M; Fernandes, Rômulo A; Cecílio, Michel J; Toledo-Arruda, Alessandra C; Ramos, Dionei

2015-11-01

Mucociliary clearance is the main defense mechanism of the respiratory system, and it is influenced by several stimuli, including aerobic exercise and cigarette smoking. We evaluated the acute response of mucociliary clearance to aerobic exercise in smokers and nonsmokers compared with that found after acute smoking and smoking combined with exercise. Also, we investigated whether there was a correlation between mucociliary clearance and the autonomic nervous system under these conditions. Twenty-one smokers were evaluated for mucociliary clearance by saccharin transit time (STT), and the response of the autonomic nervous system was evaluated by heart rate variability after aerobic exercise, after exercise followed by smoking, after acute smoking, and after rest. For comparison, 17 nonsmokers were also assessed during exercise. Repeated-measures analysis of variance with the Tukey test or the Friedman test followed by the Dunn test was used to evaluate the STT, autonomic response, and other variables to exercise and/or smoking in smokers. A paired t test or Wilcoxon test was used to analyze responses to exercise in nonsmokers. Correlations were evaluated using Pearson or Spearman coefficients. The STT was reduced after exercise in both groups, with similar responses between them. Other stimuli also reduced the STT. The STT showed a negative correlation with sympathetic activity in smokers and a positive correlation with the parasympathetic system in nonsmokers. Although impaired in smokers, mucociliary clearance responded to the stimulus of exercise, as demonstrated by similar STTs compared with nonsmokers. This response was correlated with the autonomic nervous system in both groups. In smokers, mucociliary clearance also responded to the stimuli of smoking and exercise followed by smoking. Copyright © 2015 by Daedalus Enterprises.

Nonlinear Dynamics of a Multistage Gear Transmission System with Multi-Clearance

NASA Astrophysics Data System (ADS)

Xiang, Ling; Zhang, Yue; Gao, Nan; Hu, Aijun; Xing, Jingtang

The nonlinear torsional model of a multistage gear transmission system which consists of a planetary gear and two parallel gear stages is established with time-varying meshing stiffness, comprehensive gear error and multi-clearance. The nonlinear dynamic responses are analyzed by applying the reference of backlash bifurcation parameters. The motions of the system on the change of backlash are identified through global bifurcation diagram, largest Lyapunov exponent (LLE), FFT spectra, Poincaré maps, the phase diagrams and time series. The numerical results demonstrate that the system exhibits rich features of nonlinear dynamics such as the periodic motion, nonperiodic states and chaotic states. It is found that the sun-planet backlash has more complex effect on the system than the ring-planet backlash. The motions of the system with backlash of parallel gear are diverse including some different multi-periodic motions. Furthermore, the state of the system can change from chaos into quasi-periodic behavior, which means that the dynamic behavior of the system is composed of more stable components with the increase of the backlash. Correspondingly, the parameters of the system should be designed properly and controlled timely for better operation and enhancing the life of the system.

[Conservative calibration of a clearance monitor system for waste material from nuclear medicine].

PubMed

Wanke, Carsten; Geworski, Lilli

2014-09-01

Clearance monitor systems are used for gross gamma measurements of waste potentially contaminated with radioactivity. These measurements are to make sure that legal requirements, e.g. clearance criteria according to the german radiation protection ordinance, are met. This means that measurement results may overestimate, but must not underestimate the true values. This paper describes a pragmatic way using a calibrated Cs-137 point source to generate a conservative calibration for the clearance monitor system used in the Medizinische Hochschule Hannover (MHH). The most important nuclides used in nuclear medicine are considered. The measurement result reliably overestimates the true value of the activity present in the waste. The calibration is compliant with the demands for conservativity and traceability to national standards. Copyright © 2014. Published by Elsevier GmbH.

Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

PubMed

Shukla, Sanjay K; Cook, Dane; Meyer, Jacob; Vernon, Suzanne D; Le, Thao; Clevidence, Derek; Robertson, Charles E; Schrodi, Steven J; Yale, Steven; Frank, Daniel N

2015-01-01

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease characterized by intense and debilitating fatigue not due to physical activity that has persisted for at least 6 months, post-exertional malaise, unrefreshing sleep, and accompanied by a number of secondary symptoms, including sore throat, memory and concentration impairment, headache, and muscle/joint pain. In patients with post-exertional malaise, significant worsening of symptoms occurs following physical exertion and exercise challenge serves as a useful method for identifying biomarkers for exertion intolerance. Evidence suggests that intestinal dysbiosis and systemic responses to gut microorganisms may play a role in the symptomology of ME/CFS. As such, we hypothesized that post-exertion worsening of ME/CFS symptoms could be due to increased bacterial translocation from the intestine into the systemic circulation. To test this hypothesis, we collected symptom reports and blood and stool samples from ten clinically characterized ME/CFS patients and ten matched healthy controls before and 15 minutes, 48 hours, and 72 hours after a maximal exercise challenge. Microbiomes of blood and stool samples were examined. Stool sample microbiomes differed between ME/CFS patients and healthy controls in the abundance of several major bacterial phyla. Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005). There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls. These results provide evidence for a systemic effect of an altered gut microbiome in ME/CFS patients compared to controls. Upon exercise challenge, there were significant changes in the abundance of major bacterial phyla in the gut in ME/CFS patients not observed in healthy controls. In addition, compared to controls clearance of bacteria from the blood was delayed in ME/CFS patients following exercise. These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients that may account for the profound post-exertional malaise experienced by ME/CFS patients.

Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

PubMed Central

Shukla, Sanjay K.; Cook, Dane; Meyer, Jacob; Vernon, Suzanne D.; Le, Thao; Clevidence, Derek; Robertson, Charles E.; Schrodi, Steven J.; Yale, Steven; Frank, Daniel N.

2015-01-01

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease characterized by intense and debilitating fatigue not due to physical activity that has persisted for at least 6 months, post-exertional malaise, unrefreshing sleep, and accompanied by a number of secondary symptoms, including sore throat, memory and concentration impairment, headache, and muscle/joint pain. In patients with post-exertional malaise, significant worsening of symptoms occurs following physical exertion and exercise challenge serves as a useful method for identifying biomarkers for exertion intolerance. Evidence suggests that intestinal dysbiosis and systemic responses to gut microorganisms may play a role in the symptomology of ME/CFS. As such, we hypothesized that post-exertion worsening of ME/CFS symptoms could be due to increased bacterial translocation from the intestine into the systemic circulation. To test this hypothesis, we collected symptom reports and blood and stool samples from ten clinically characterized ME/CFS patients and ten matched healthy controls before and 15 minutes, 48 hours, and 72 hours after a maximal exercise challenge. Microbiomes of blood and stool samples were examined. Stool sample microbiomes differed between ME/CFS patients and healthy controls in the abundance of several major bacterial phyla. Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005). There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls. These results provide evidence for a systemic effect of an altered gut microbiome in ME/CFS patients compared to controls. Upon exercise challenge, there were significant changes in the abundance of major bacterial phyla in the gut in ME/CFS patients not observed in healthy controls. In addition, compared to controls clearance of bacteria from the blood was delayed in ME/CFS patients following exercise. These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients that may account for the profound post-exertional malaise experienced by ME/CFS patients. PMID:26683192

49 CFR 230.110 - Pilots.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Pilots. 230.110 Section 230.110 Transportation... and Equalizing System § 230.110 Pilots. (a) General provisions. Pilots shall be securely attached... clearance. The minimum clearance of pilot above the rail shall be 3 inches and the maximum clearance shall...

Design of Center-TRACON Automation System

NASA Technical Reports Server (NTRS)

Erzberger, Heinz; Davis, Thomas J.; Green, Steven

1993-01-01

A system for the automated management and control of terminal area traffic, referred to as the Center-TRACON Automation System (CTAS), is being developed at NASA Ames Research Center. In a cooperative program, NASA and FAA have efforts underway to install and evaluate the system at the Denver area and Dallas/Ft. Worth area air traffic control facilities. This paper will review CTAS architecture, and automation functions as well as the integration of CTAS into the existing operational system. CTAS consists of three types of integrated tools that provide computer-generated advisories for both en-route and terminal area controllers to guide them in managing and controlling arrival traffic efficiently. One tool, the Traffic Management Advisor (TMA), generates runway assignments, landing sequences and landing times for all arriving aircraft, including those originating from nearby feeder airports. TMA also assists in runway configuration control and flow management. Another tool, the Descent Advisor (DA), generates clearances for the en-route controllers handling arrival flows to metering gates. The DA's clearances ensure fuel-efficient and conflict free descents to the metering gates at specified crossing times. In the terminal area, the Final Approach Spacing Tool (FAST) provides heading and speed advisories that help controllers produce an accurately spaced flow of aircraft on the final approach course. Data bases consisting of several hundred aircraft performance models, airline preferred operational procedures, and a three dimensional wind model support the operation of CTAS. The first component of CTAS, the Traffic Management Advisor, is being evaluated at the Denver TRACON and the Denver Air Route Traffic Control Center. The second component, the Final Approach Spacing Tool, will be evaluated in several stages at the Dallas/Fort Worth Airport beginning in October 1993. An initial stage of the Descent Advisor tool is being prepared for testing at the Denver Center in late 1994. Operational evaluations of all three integrated CTAS tools are expected to begin at the two field sites in 1995.

Chaos vibration of pinion and rack steering trapezoidal mechanism containing two clearances

NASA Astrophysics Data System (ADS)

Wei, Daogao; Wang, Yu; Jiang, Tong; Zheng, Sifa; Zhao, Wenjing; Pan, Zhijie

2017-08-01

The multi-clearances of breaking type steering trapezoidal mechanism joints influences vehicle steering stability. Hence, to ascertain the influence of clearance value on steering stability, this paper takes the steering mechanism of a certain vehicle type as a prototype that can be simplified into a planar six-bar linkage, then establishes the system dynamic differential equations after considering the two clearances of tie rods and the steering knuckle arms. The influence of the clearance parameters on the movement stability of the steering mechanism is studied using a numerical computation method. Results show that when the two clearances are equal, the planar movement of the tie rods changes from period-doubling to chaos as the clearances increase. When the two clearances are 0.25 mm and 1.5 mm respectively, the planar movements of the two side tie rods come into chaos, causing the steering stability to deteriorate. Moreover, with the increase of clearances, turning moment fluctuates more intensively and the peak value increases.

75 FR 52798 - State-07, Cryptographic Clearance Records

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-27

... of records, Authority for maintenance of the system, Purpose, Safeguards and Retrievability as well... INDIVIDUALS COVERED BY THE SYSTEM: All current Civil Service and Foreign Service direct hire employees of the... well as those who have already received cryptographic clearance. CATEGORIES OF RECORDS IN THE SYSTEM...

Synergistic Roles of Antibody and Interferon in Noncytolytic Clearance of Sindbis Virus from Different Regions of the Central Nervous System▿

PubMed Central

Burdeinick-Kerr, Rebeca; Wind, Jennifer; Griffin, Diane E.

2007-01-01

Sindbis virus (SINV) is an alphavirus that causes infection of neurons and encephalomyelitis in adult immunocompetent mice. Recovery can occur without apparent neurological damage. To better define the factors facilitating noncytolytic clearance of SINV in different regions of the central nervous system (CNS) and the roles of innate and adaptive immune responses at different times during infection, we have characterized SINV infection and clearance in the brain, brain stem, and spinal cords of severe combined immunodeficiency (SCID) and C57BL/6 (wild-type [WT]) mice and mice deficient in beta interferon (IFN-β) (BKO), antibody (μMT), IFN-γ (GKO), IFN-γ receptor (GRKO), and both antibody and IFN-γ (μMT/GKO). WT mice cleared infectious virus by day 8, while SCID mice had persistent virus replication at all sites. For 3 days after infection, BKO mice had higher titers at all sites than WT mice, despite similar IFN-α production, but cleared virus similarly. GKO and GRKO mice cleared infectious virus from all sites by days 8 to 10 and, like WT mice, displayed transient reactivation at 12 to 22 days. μMT mice did not clear virus from the brain, and clearance from the brain stem and lumbar spinal cord was delayed, followed by reactivation. Eighty-one days after infection, μMT/GKO mice had not cleared virus from any site, but titers were lower than for SCID mice. These studies show that IFN-β is independently important for early control of CNS virus replication, that antiviral antibody is critical for clearance from the brain, and that both antibody and IFN-γ contribute to prevention of reactivation after initial clearance. PMID:17376910

The Glymphatic Pathway.

PubMed

Benveniste, Helene; Lee, Hedok; Volkow, Nora D

2017-01-01

The overall premise of this review is that cerebrospinal fluid (CSF) is transported within a dedicated peri-vascular network facilitating metabolic waste clearance from the central nervous system while we sleep. The anatomical profile of the network is complex and has been defined as a peri-arterial CSF influx pathway and peri-venous clearance routes, which are functionally coupled by interstitial bulk flow supported by astrocytic aquaporin 4 water channels. The role of the newly discovered system in the brain is equivalent to the lymphatic system present in other body organs and has been termed the "glymphatic pathway" or "(g)lymphatics" because of its dependence on glial cells. We will discuss and review the general anatomy and physiology of CSF from the perspective of the glymphatic pathway, a discovery which has greatly improved our understanding of key factors that control removal of metabolic waste products from the central nervous system in health and disease and identifies an additional purpose for sleep. A brief historical and factual description of CSF production and transport will precede the ensuing discussion of the glymphatic system along with a discussion of its clinical implications.

Monitoring the synthesis of biomolecules using mass spectrometry.

PubMed

Miyagi, Masaru; Kasumov, Takhar

2016-10-28

The controlled and selective synthesis/clearance of biomolecules is critical for most cellular processes. In most high-throughput 'omics' studies, we measure the static quantities of only one class of biomolecules (e.g. DNA, mRNA, proteins or metabolites). It is, however, important to recognize that biological systems are highly dynamic in which biomolecules are continuously renewed and different classes of biomolecules interact and affect each other's production/clearance. Therefore, it is necessary to measure the turnover of diverse classes of biomolecules to understand the dynamic nature of biological systems. Herein, we explain why the kinetic analysis of a diverse range of biomolecules is important and how such an analysis can be done. We argue that heavy water ((2)H2O) could be a universal tracer for monitoring the synthesis of biomolecules on a global scale.This article is part of the themed issue 'Quantitative mass spectrometry'. © 2016 The Author(s).

Monitoring the synthesis of biomolecules using mass spectrometry

PubMed Central

2016-01-01

The controlled and selective synthesis/clearance of biomolecules is critical for most cellular processes. In most high-throughput ‘omics’ studies, we measure the static quantities of only one class of biomolecules (e.g. DNA, mRNA, proteins or metabolites). It is, however, important to recognize that biological systems are highly dynamic in which biomolecules are continuously renewed and different classes of biomolecules interact and affect each other's production/clearance. Therefore, it is necessary to measure the turnover of diverse classes of biomolecules to understand the dynamic nature of biological systems. Herein, we explain why the kinetic analysis of a diverse range of biomolecules is important and how such an analysis can be done. We argue that heavy water (2H2O) could be a universal tracer for monitoring the synthesis of biomolecules on a global scale. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644976

Radioaerosol lung clearance in patients with active pulmonary sarcoidosis

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

Jacobs, M.P.; Baughman, R.P.; Hughes, J.

1985-05-01

Pulmonary radioaerosol clearance rate of /sup 99m/Tc diethylenetriamine pentacetate (DTPA) in 14 patients with untreated sarcoidosis was compared with /sup 67/Ga lung scan and increased lymphocytes in the bronchoalveolar lavage (BAL) fluid. Nine healthy nonsmoking subjects had a mean DTPA clearance rate of 1.18%/min (range, 0.54 to 1.60%/min). Eight of 14 patients with sarcoidosis had clearance rates greater than 1.60%/min. Of those 8 patients with abnormal DTPA clearance, 4 had positive gallium scans, 4 had more than 17% lymphocytes in the BAL fluid, and 3 had both tests positive. To study the cause of abnormal DTPA clearance, 23 subjects (includingmore » 3 normal controls, all 14 patients with sarcoidosis, and 6 patients with localized disease on chest roentgenogram) underwent both DTPA clearance studies and BAL for quantitation of the amount of albumin in lung fluid. There was a positive correlation between the rate of DTPA clearance and the albumin concentration in lung fluid (r = 0.87, p less than 0.01).« less

Participation of the hypophyseal-adrenal cortex system in thrombin clearance during immobilization stress

NASA Technical Reports Server (NTRS)

Kudryashov, B. A.; Uljanov, A. M.; Shapiro, F. B.; Bazazyan, G. G.

1981-01-01

Thrombin marked with I-131 resulted in a considerable increase of the thrombined clearance rate in healthy male rats during stress caused by an immobilization lasting 30 minutes, and in an increase of thrombin clearance occurred by a combination of immobilization and administration of adrenocorticotropin (ACTH). Contrary to ACTH, the thrombin clearance is not stimulated in healthy animals by hydrocortisone. The results of the examination are presented.

Effect of the presence of dental plaque on oral sugar clearance and salivary pH: an in vivo study.

PubMed

Pradhan, Debapriya; Jain, Deepak; Gulati, Amit; Kolhe, Swapnil J; Baad, Rajendra; Rao, B Sunil

2012-11-01

Fermentable carbohydrates and microorganisms in the plaque play a significant role in the pathogenesis of dental caries. Oral clearance of sugars and salivary pH is affected by the presence of plaque. This study was conducted to study the effect of the presence of plaque on the salivary clearance of sucrose and on salivary pH. The study design was of a randomized controlled parallel group clinical trial and included two groups: The control group and plaque group, as follows: Control group--subjects without plaque and plaque group--subjects with plaque. Salivary sucrose determination was done by using the anthrone technique. A digital pH meter estimated the salivary pH. The Student's t test and Mann-Whitney test was employed to compare the intergroup differences. Pearson's correlation coefficient was used for analysis. The salivary sucrose clearance time was increased by presence of plaque. The presence of plaque led to increased salivary sucrose concentrations and increased the salivary sucrose clearance time. The dental caries is the dynamic relationship among the dental plaque microbiota, dietary carbohydrates, saliva and cariogenic potential of the dental plaque. Caries occur preferentially in the dentition sites characterized by high exposure to carbohydrate and diminished salivary effect.

High-Speed, capacitance-based tip clearance sensing

NASA Astrophysics Data System (ADS)

Haase, W. C.; Haase, Z. S.

This paper discusses recent advances in tip clearance measurement systems for turbine engines using capacitive probes. Real time measurements of individual blade pulses are generated using wideband signal processing providing 3 dB bandwidths of typically 5 MHz. Subsequent mixed-signal processing circuitry provide real-time measurements of maximum, minimum, and average clearance with latencies of one blade-to-blade time interval. Both guarded and unguarded probe configurations are possible with the system. Calibration techniques provide high accuracy measurements.

Omega-3 polyunsaturated fatty acids promote amyloid-β clearance from the brain through mediating the function of the glymphatic system.

PubMed

Ren, Huixia; Luo, Chuanming; Feng, Yanqing; Yao, Xiaoli; Shi, Zhe; Liang, Fengyin; Kang, Jing X; Wan, Jian-Bo; Pei, Zhong; Su, Huanxing

2017-01-01

Impairment of amyloid-β (Aβ) clearance leads to Aβ accumulation in the brain during the development of Alzheimer's disease (AD). Strategies that can restore or improve the clearance function hold great promise in delaying or preventing the onset of AD. Here, we show that n-3 polyunsaturated fatty acids (PUFAs), by use of fat-1 transgenic mice and oral administration of fish oil, significantly promote interstitial Aβ clearance from the brain and resist Aβ injury. Such beneficial effects were abolished in Aqp4-knockout mice, suggesting that the AQP4-dependent glymphatic system is actively involved in the promoting the effects of n-3 PUFAs on the clearance of extracellular Aβ. Imaging on clarified brain tissues clearly displayed that n-3 PUFAs markedly inhibit the activation of astrocytes and protect the AQP4 polarization in the affected brain region after Aβ injection. The results of the present study prove a novel mechanism by which n-3 PUFAs exert protective roles in reducing Aβ accumulation via mediating the glymphatic system function.-Ren, H., Luo, C., Feng, Y., Yao, X., Shi, Z., Liang, F., Kang, J. X., Wan, J.-B., Pei, Z., Su, H. Omega-3 polyunsaturated fatty acids promote amyloid-β clearance from the brain through mediating the function of the glymphatic system. © FASEB.

SIGN-R1 and complement factors are involved in the systemic clearance of radiation-induced apoptotic cells in whole-body irradiated mice

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

Park, Jin-Yeon; Loh, SoHee; Cho, Eun-hee

Although SIGN-R1-mediated complement activation pathway has been shown to enhance the systemic clearance of apoptotic cells, the role of SIGN-R1 in the clearance of radiation-induced apoptotic cells has not been characterized and was investigated in this study. Our data indicated that whole-body γ-irradiation of mice increased caspase-3{sup +} apoptotic lymphocyte numbers in secondary lymphoid organs. Following γ-irradiation, SIGN-R1 and complements (C4 and C3) were simultaneously increased only in the mice spleen tissue among the assessed tissues. In particular, C3 was exclusively activated in the spleen. The delayed clearance of apoptotic cells was markedly prevalent in the spleen and liver ofmore » SIGN-R1 KO mice, followed by a significant increase of CD11b{sup +} cells. These results indicate that SIGN-R1 and complement factors play an important role in the systemic clearance of radiation-induced apoptotic innate immune cells to maintain tissue homeostasis after γ-irradiation. - Highlights: • Splenic SIGN-R1{sup +} macrophages are activated after γ-irradiation. • C3 and C4 levels increased and C3 was activated in the spleen after γ-irradiation. • SIGN-R1 mediated the systemic clearance of radiation-induced apoptotic cells in spleen and liver.« less

Visual Confirmation (VICON) of Takeoff Clearance Signal System Impact Study

DOT National Transportation Integrated Search

1980-11-01

A study was performed to evaluate the impact on airport capacity and voice communications of the Visual Confirmation of Takeoff Clearance (VICON) Signal System. Befoe-and-after test data collection and analysis were conducted at Bradley International...

Active Piezoelectric Structures for Tip Clearance Management Assessed

NASA Technical Reports Server (NTRS)

1995-01-01

Managing blade tip clearance in turbomachinery stages is critical to developing advanced subsonic propulsion systems. Active casing structures with embedded piezoelectric actuators appear to be a promising solution. They can control static and dynamic tip clearance, compensate for uneven deflections, and accomplish electromechanical coupling at the material level. In addition, they have a compact design. To assess the feasibility of this concept and assist the development of these novel structures, the NASA Lewis Research Center developed in-house computational capabilities for composite structures with piezoelectric actuators and sensors, and subsequently used them to simulate candidate active casing structures. The simulations indicated the potential of active casings to modify the blade tip clearance enough to improve stage efficiency. They also provided valuable design information, such as preliminary actuator configurations (number and location) and the corresponding voltage patterns required to compensate for uneven casing deformations. An active ovalization of a casing with four discrete piezoceramic actuators attached on the outer surface is shown. The center figure shows the predicted radial displacements along the hoop direction that are induced when electrostatic voltage is applied at the piezoceramic actuators. This work, which has demonstrated the capabilities of in-house computational models to analyze and design active casing structures, is expected to contribute toward the development of advanced subsonic engines.

The unexploded ordnance (UXO) contamination problem and the state of the art of UXO remediation technologies

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

Thomsen, K.O.; Richardson, C.B.; Valder, K.M.

1996-12-31

Millions of acres of US government property are contaminated with unexploded ordnance (UXO) as a result of weapons system testing and troop training activities conducted over the past century at Department of Defense (DoD) sites. Recent DoD downsizing has resulted in the closing of many military bases, many of which are contaminated with UXO. One unexpected result of DoD`s downsizing is the attention focused on the unique problems associated with UXO remediation at these closed military bases. The U.S. Army Environmental Center (U SAEC) is the lead DoD agency for UXO clearance technology demonstrations, evaluation, and technology transfer. USAEC directedmore » the Naval Explosive Ordnance Disposal Technology Division (NAVEODTECHDIV) to serve as the technical lead for the advanced technology demonstration (ATD) program. In 1994, USAEC and NAVEODTECHDIV created controlled test facilities at the U.S. Army Jefferson Proving Ground in Madison, Indiana, to demonstrate and evaluate commercial UXO clearance systems and technologies. Phase I controlled site demonstrations were conducted during the summer of 1994. These demonstrations were followed by the Phase II controlled site demonstrations at JPG. This paper presents the results of the Phase II controlled site demonstrations. The overall performance of the demonstrators is presented along with the operational characteristics and limitations of the various systems and technologies evaluated. Individual demonstrator performance statistics are evaluated by sensor type and sensor transport method.« less

Carbon Nanotubes in the Human Respiratory Tract-Clearance Modeling.

PubMed

Sturm, Robert

2017-03-01

Clearance of single-wall carbon nanotubes (SWCNT, diameter: 5 nm) and multi-wall carbon nanotubes (MWCNT, diameter: 50 nm) in the respiratory tract was predicted for various age groups (infants, children, adolescents, and adults). The model was founded on the assumption that lung clearance takes place in three distinct phases: (i) fast mucociliary clearance, (ii) slow bronchial clearance, and (iii) alveolar clearance. To each of these phases a specific fraction of deposited particles was attributed, the amount of which depended on particles' geometry and particles' deposition sites in the respiratory system. Clearance velocities were expressed by respective clearance half-times ranging from several hours in the case of fast clearance to tens of days in the case of slow clearance. Results of the simulations clearly demonstrate that for the specific deposition scenario (sitting, nasal breathing) considered here fast clearance fraction exhibits a slight decrease with increasing age, but total clearance times (i.e. time spans, within which 100% of the deposited particulate mass are removed) are rather constant among the age groups. Nanotubes deposited in the respiratory bronchioles and alveoli are usually subject to a long-term storage in these structures and, thus, may trigger malignant transformations in adjacent cells and tissues. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

The effects of topical agents of fluticasone propionate, oxymetazoline, and 3% and 0.9% sodium chloride solutions on mucociliary clearance in the therapy of acute bacterial rhinosinusitis in vivo.

PubMed

Inanli, Selçuk; Oztürk, Ozmen; Korkmaz, Mukadder; Tutkun, Alper; Batman, Cağlar

2002-02-01

The aims of the study were to determine: 1) how mucociliary activity in acute bacterial rhinosinusitis is affected; 2) how this activity is changed by therapy; 3) the effects of topical agents on mucociliary clearance, and 4) the most appropriate topical agent(s) to be used in the therapy of sinusitis. Five groups of patients with acute bacterial rhinosinusitis were studied prospectively. All patients had 500 mg oral amoxicillin and 125 mg oral clavulanic acid preparations given three times daily for 3 weeks. According to the topical agent applications, these groups included: group I (n = 12), no topical treatment was given; group II (n = 14), two puffs for each nostril once daily of 50 microg/100 mL fluticasone propionate was given; group III (n = 9), one puff for each nostril three times daily of 0.05% oxymetazoline was given; group IV (n =12), 3% sodium chloride (NaCl) (buffered to pH 6.5-7 at room temperature) was given; and group V (n =13), 10-mL solutions of 0.9% NaCl (buffered to pH 6.5--7 at room temperature) were given for nasal irrigations three times daily. All patients had medication for 3 weeks and were controlled each week. The saccharin method was used to measure nasal mucociliary clearance. To investigate the early effects of the topical agents for groups II to V, an additional test was repeated 20 minutes after the basal mucociliary clearance recordings. The test was repeated in the first, second, and third weeks of the treatment. The mucociliary clearance was significantly slower in the acute bacterial rhinosinusitis group than in the control group. There was no significant difference between the basal mucociliary clearance and the 20th minute mucociliary clearance of the fluticasone propionate and 0.9% NaCl solution groups. The mean values of the basal and the 20 minute's mucociliary clearance of the oxymetazoline group were 24.72 +/- 6.16 and 15.5 +/- 7.45 minutes, respectively, which were statistically significant. The mean values of the basal and the 20th minute mucociliary clearance of the 3% NaCl solution groups were 19.45 +/- 9.35 and 15.45 +/- 8.20 minutes, respectively, which were also statistically significant. In the first group (without topical treatment), the basal mucociliary clearance became significantly shorter after the second week of treatment. In the first and second weeks of the treatment of the oxymetazoline group, the mucociliary clearance did not change significantly, but after the third week the mucociliary clearance was significantly shorter. In the 3% NaCl solution group, significant improvement began from the first week and continued through the third week. Comparing the basal and the third weeks' mucociliary clearance values among the groups, the oxymetazoline and 3% NaCl solution groups revealed more significant improvement than the other groups, but this improvement was not different from the improvement of group I. There was still a statistically significant difference in the mucociliary clearance of the post-treatment sinusitis groups from the control group. The oxymetazoline and 3% NaCl solution groups seemed to be more effective in mucociliary clearance, but there was no significant difference in improvement among the groups. The improvement of acute bacterial rhinosinusitis takes more than 3 weeks, according to the mucociliary clearance values of the groups.

An investigation of TNAV equipped aircraft in a simulated en route metering environment

NASA Technical Reports Server (NTRS)

Groce, J. L.; Izumi, K. H.; Markham, C. H.; Schwab, R. W.; Taylor, J. A.

1986-01-01

This document presents the results of an effort to estimate how often a TNAV (Time Navigation) equipped aircraft could be given a TNAV clearance in the En Route Metering (ERM) system as a function of the percentage of arriving traffic which is TNAV equipped. A fast-time simulation of Denver Stapleton international arrival traffic in the Denver Air Route Traffic Control Center route structure, including en route metering operations, was used to develop data on estimated conflicts, clearance communications and fuel usage for traffic mixes of 25, 50, 75 and 100% TNAV equipped. This study supports an overall effort by NASA to assess the benefits and required technology for using TNAV-equipped aircraft in the ERM environment.

Flow Instability and Flow Control Scaling Laws

NASA Astrophysics Data System (ADS)

van Ness, Daniel; Corke, Thomas; Morris, Scott

2006-11-01

A flow instability that is receptive to perturbations is present in the tip clearance leakage flow over the tip of a turbine blade. This instability was investigated through the introduction of active flow control in the viscous flow field. Control was implemented in the form of a dielectric barrier discharge created by a weakly-ionized plasma actuation arrangement. The experimental setup consisted of a low-speed linear turbine cascade made up of an array of nine Pratt & Whitney ``PakB'' turbine blades. This idealized cascade configuration was used to examine the tip clearance leakage flow that exists within the low pressure turbine stage of a gas-turbine engine. The center blade of the cascade array had a variable tip clearance up to five percent chord. Reynolds numbers based on axial blade chord varied from 10^4 to 10^5. Multi-port pressure probe measurements, as well as Stereo Particle Image Velocimetry were used to document the dependence of the instability on the frequency and amplitude of flow control perturbations. Scaling laws based on the variation of blade tip clearance height and inflow conditions were investigated. These results permitted an improved understanding of the mechanism of flow instability.

The effects of selected air pollutants on clearance of titanic oxide particles from the lungs of rats.

PubMed

Ferin, J; Leach, L J

1975-09-01

A procedure utilizing the lung clearance kinetics of titanic oxide (TiO2) particles was used to determine the effects of inhaled sulphur dioxide (SO2) and nitrogen oxides (NO x) on particle clearance. The procedure is reproducible and mainly tests clearance mechanisms involving alveolar macrophages and the mucociliary transport system at the alveolobronchial clearance pathway. At low SO2 or NOx exposures enhanced particle clearance was observed. Lung clearance was depressed at 15 and 24 ppm of NO2 after 22 exposures as well as at 20 ppm of SO2 after 11 exposures, and also at 1 ppm of SO2 after 25 exposures. Dose-response curves for the SO2 and NOx exposures showed differences explainable by the routes by which these gases reach the alveolar macrophages.

Impaired lipid clearance in patients with previous acute pancreatitis.

PubMed Central

Guzmán, S; Nervi, F; Llanos, O; León, P; Valdivieso, V

1985-01-01

Fasting serum triglycerides were measured in 52 patients who had sustained an attack of pancreatitis (gall stone related 33, alcoholism six) at least six months earlier. Several patients (23%) had raised fasting serum triglycerides, with a type IV phenotype in all but one patient. The 40 patients with normal fasting serum triglycerides received an oral load of 100 g sunflower oil to compare their clearance of dietary triglycerides with that of a control group of 54 subjects. The clearance of ingested triglycerides was significantly impaired in the patients - irrespective of the presumed aetiological factor, or clinical condition associated with pancreatitis - compared with the clearance in controls. A triglyceride tolerance test is the only way to detect those patients in whom a future attack of pancreatitis may be precipitated by a diet rich in fat, or endogenous over production of triglycerides as after an alcoholic debauch. PMID:4029716

Advantage I-75 mainline automated clearance system : final evaluation report

DOT National Transportation Integrated Search

1998-08-01

The focus of this evaluation was to determine if the Advantage I-75 Mainline Automated Clearance Systems (MACS) produced significant fuel savings for motor carriers. The fundamental hypothesis tested was that the reduction or elimination of stops at ...

Profile negotiation: An air/ground automation integration concept for managing arrival traffic

NASA Technical Reports Server (NTRS)

Williams, David H.; Arbuckle, P. Douglas; Green, Steven M.; Denbraven, Wim

1993-01-01

NASA Ames Research Center and NASA Langley Research Center conducted a joint simulation study to evaluate a profile negotiation process (PNP) between a time-based air traffic control ATC system and an airplane equipped with a four dimensional flight management system (4D FMS). Prototype procedures were developed to support the functional implementation of this process. The PNP was designed to provide an arrival trajectory solution that satisfies the separation requirements of ATC while remaining as close as possible to the airplane's preferred trajectory. The Transport Systems Research Vehicle cockpit simulator was linked in real-time to the Center/TRACON Automation System (CTAS) for the experiment. Approximately 30 hours of simulation testing were conducted over a three week period. Active airline pilot crews and active Center controller teams participated as test subjects. Results from the experiment indicate the potential for successful incorporation of airplane preferred arrival trajectories in the CTAS automation environment. Controllers were able to consistently and effectively negotiate nominally conflict-free trajectories with pilots flying a 4D-FMS-equipped airplane. The negotiated trajectories were substantially closer to the airplane's preference than would have otherwise been possible without the PNP. Airplane fuel savings relative to baseline CTAS were achieved in the test scenarios. The datalink procedures and clearances developed for this experiment, while providing the necessary functionality, were found to be operationally unacceptable to the pilots. Additional pilot control and understanding of the proposed airplane-preferred trajectory and a simplified clearance procedure were cited as necessary for operational implementation of the concept. From the controllers' perspective, the main concerns were the ability of the 4D airplane to accurately track the negotiated trajectory and the workload required to support the PNP as implemented in this study.

Vehicle Characteristics

DTIC Science & Technology

2008-02-14

g. Material. 5.1.7 Wheel Geometry. a. Camber angle. b. Caster angle. c. Pivot angle. d. Static toe-in. e. Turning angles...the vehicle characteristics to be obtained during testing of wheeled and tracked vehicles and their components. Physical characterization of test...frontal area Characteristic data sheet Power train Suspention Wheel geometry Vehicle clearance angles Armament Gun control systems 16. SECURITY

Comparison of Bite Registration Material Accuracy on in office Laser Scanned Digital Model Occlusion

DTIC Science & Technology

2014-05-20

School/Department/Center: Two Year Advanced Education in General Dentistry . Fort Bragg,NC 4. Phone:910-429-6626 5. Type of clearance: _X_Paper...Date: 11.~ l~ 4. Higher approval clearance required (for University-, DoD- or US Gov’t-level policy, communication systems or weapons issues review...or US Gov’t-level policy, communications systems or weapons issues review). *Note: It is DoD policy that clearance of information or material

The measurement of skin lymph flow by isotope clearance--reliability, reproducibility, injection dynamics, and the effect of massage

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

Mortimer, P.S.; Simmonds, R.; Rezvani, M.

1990-12-01

The measurement of skin lymph flow was investigated using an isotope clearance technique (ICT). Multiple lymph flow determinations were undertaken in the skin of anaesthetized large white pigs to test for reproducibility, ascertain the most suitable tracer, study the influence of injection dynamics, and observe the effect of massage as a stimulus to lymph flow. Blood clearance of tracer was also investigated. Results demonstrated that lymphatic clearance is a monoexponential function with good reproducibility under controlled laboratory conditions. 99mTc-colloid (TCK17 Cis) compared favorably with 131I-human serum albumin as a tracer and both performed better than colloid gold (198Au). Lymph flowmore » was significantly faster in one pig than in the other. No difference existed between left and right sides or between caudal and rostral sites on each flank, but clearance was significantly slower in thigh than flank skin. Sub-epidermal injections cleared faster and more consistently than either deep or subcutaneous injections. Neither injection volume nor needle tract backflow of tracer influenced results, but local massage significantly enhanced clearance. Escape of 99mTc-colloid by the blood was negligible. These results indicate that skin lymph flow can be reliably measured when conditions are controlled. Extrinsic factors such as massage strongly influence lymph flow. Greater sensitivity in detecting degrees of lymphatic insufficiency may be achieved if a standardized stimulus to lymph flow is administered during isotope clearance measurement.« less

Comparison of lung vascular and epithelial permeability indices in the adult respiratory distress syndrome

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

Braude, S.; Nolop, K.B.; Hughes, J.M.

1986-06-01

Measurements of pulmonary clearance of inhaled /sup 99m/Tc-DTPA and transvascular 113mIn-transferrin flux were made in 12 patients with established ARDS and 14 volunteer control subjects (7 smokers and 7 nonsmokers). Smokers had significantly increased /sup 99m/Tc-DTPA clearance (clearance rate constant, 3.6 +/- 0.8; mean +/- SEM) compared with nonsmokers (1.2 +/- 0.1). All patients with ARDS had increased clearance of /sup 99m/Tc-DTPA (5.2 +/- 0.9), but the finding was nonspecific in that increased clearance overlapped with the findings in normal smokers. Protein flux in smokers (protein flux units, 0.0 +/- 0.2) was similar to that in nonsmokers (0.3 +/- 0.2).more » In 9 of the 12 patients with ARDS, protein flux was increased, and as a group (3.2 +/- 1.0) they differed significantly (p less than 0.01) from the combined smoking and nonsmoking control subjects (0.2 +/- 0.1, n = 14). The parameters of DTPA clearance and transvascular protein flux correlated well in the patients with ARDS (Spearman's rank correlation = 0.71, p less than 0.01). Although /sup 99m/Tc-DTPA clearance is a sensitive technique in ARDS, a single study in this context does not allow a diagnostic conclusion because of its non-specificity. Abnormal protein flux appears to be more specific for ARDS but was not a universal finding in the patients studied.« less

Adjustable Bracket For Entry Of Welding Wire

NASA Technical Reports Server (NTRS)

Gilbert, Jeffrey L.; Gutow, David A.

1993-01-01

Wire-entry bracket on welding torch in robotic welding system provides for adjustment of angle of entry of welding wire over range of plus or minus 30 degrees from nominal entry angle. Wire positioned so it does not hide weld joint in view of through-the-torch computer-vision system part of robot-controlling and -monitoring system. Swiveling bracket also used on nonvision torch on which wire-feed-through tube interferes with workpiece. Angle simply changed to one giving sufficient clearance.

Gas turbine engine active clearance control

NASA Technical Reports Server (NTRS)

Deveau, Paul J. (Inventor); Greenberg, Paul B. (Inventor); Paolillo, Roger E. (Inventor)

1985-01-01

Method for controlling the clearance between rotating and stationary components of a gas turbine engine are disclosed. Techniques for achieving close correspondence between the radial position of rotor blade tips and the circumscribing outer air seals are disclosed. In one embodiment turbine case temperature modifying air is provided in flow rate, pressure and temperature varied as a function of engine operating condition. The modifying air is scheduled from a modulating and mixing valve supplied with dual source compressor air. One source supplies relatively low pressure, low temperature air and the other source supplies relatively high pressure, high temperature air. After the air has been used for the active clearance control (cooling the high pressure turbine case) it is then used for cooling the structure that supports the outer air seal and other high pressure turbine component parts.

49 CFR 236.73 - Open-wire transmission line; clearance to other circuits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Open-wire transmission line; clearance to other..., AND APPLIANCES Rules and Instructions: All Systems Wires and Cables § 236.73 Open-wire transmission line; clearance to other circuits. Open-wire transmission line operating at voltage of 750 volts or...

49 CFR 236.73 - Open-wire transmission line; clearance to other circuits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Open-wire transmission line; clearance to other..., AND APPLIANCES Rules and Instructions: All Systems Wires and Cables § 236.73 Open-wire transmission line; clearance to other circuits. Open-wire transmission line operating at voltage of 750 volts or...

14 CFR 29.411 - Ground clearance: tail rotor guard.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Ground clearance: tail rotor guard. 29.411 Section 29.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 29.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to...

14 CFR 27.411 - Ground clearance: tail rotor guard.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Ground clearance: tail rotor guard. 27.411 Section 27.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to...

14 CFR 27.411 - Ground clearance: tail rotor guard.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Ground clearance: tail rotor guard. 27.411 Section 27.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to...

14 CFR 29.411 - Ground clearance: tail rotor guard.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Ground clearance: tail rotor guard. 29.411 Section 29.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 29.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to...

Microparticles in the blood of patients with systemic lupus erythematosus (SLE): phenotypic characterization and clinical associations

PubMed Central

Mobarrez, Fariborz; Vikerfors, Anna; Gustafsson, Johanna T.; Gunnarsson, Iva; Zickert, Agneta; Larsson, Anders; Pisetsky, David S.; Wallén, Håkan; Svenungsson, Elisabet

2016-01-01

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by circulating autoantibodies and the formation of immune complexes. In these responses, the selecting self-antigens likely derive from the remains of dead and dying cells, as well as from disturbances in clearance. During cell death/activation, microparticles (MPs) can be released to the circulation. Previous MP studies in SLE have been limited in size and differ regarding numbers and phenotypes. Therefore, to characterize MPs more completely, we investigated 280 SLE patients and 280 individually matched controls. MPs were measured with flow cytometry and phenotyped according to phosphatidylserine expression (PS+/PS−), cellular origin and inflammatory markers. MPs, regardless of phenotype, are 2–10 times more abundant in SLE blood compared to controls. PS− MPs predominated in SLE, but not in controls (66% vs. 42%). Selectively in SLE, PS− MPs were more numerous in females and smokers. MP numbers decreased with declining renal function, but no clear association with disease activity was observed. The striking abundance of MPs, especially PS− MPs, suggests a generalized disturbance in SLE. MPs may be regarded as “liquid biopsies” to assess the production and clearance of dead, dying and activated cells, i.e. pivotal events for SLE pathogenesis. PMID:27777414

Investigation on the electromagnetic centring technique in compressor with labyrinth seal structure

NASA Astrophysics Data System (ADS)

Zhang, W.; Feng, C.; Cheng, J.; Feng, Q.; Wu, W.

2017-08-01

At present, the piston of compressors with labyrinth seal structure generally runs eccentrically, which causes uneven radial clearance, serious leakages and lower volumetric efficiency. This has become an urgent problem in the development of labyrinth compressors. In this study, electromagnetic levitation technology was introduced to achieve concentric centering between the piston and cylinder, and the conventional cantilever structure for the piston centering was replaced by a simple support structure using the through-piston rod. Furthermore, the simulation model of the electromagnetic centering system was established and the experimental prototype was built. The mathematical simulation model was verified by comparing simulated and tested results. Then, the centering effect of the system was assessed and the variation of the leakage in the compressor was studied by models using dynamic mesh technology. The results showed that the radial clearance between piston and cylinder can be maintained in the range of -0.3 mm to 0.3 mm through the electromagnetic centering control. In addition, the inner leakage of the compressor was quite appreciable without the electromagnetic control. However, it was reduced by 1.8 times with the introduction of the electromagnetic control. Thus, it can be concluded that the precise centering between the piston and the cylinder can be achieved by the introduction of the electromagnetic centering technique.

76 FR 12394 - Form Submitted to the Office of Management and Budget for Extension of Clearance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-07

... SELECTIVE SERVICE SYSTEM Form Submitted to the Office of Management and Budget for Extension of Clearance AGENCY: Selective Service System. ACTION: Notice. The following form has been submitted to the... boards in the Selective Service System. Respondents: Potential board members. Burden: A burden of 15...

75 FR 53012 - Form Submitted to the Office of Management and Budget for Extension of Clearance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-30

... Regulatory Affairs, Attention: Desk Officer, Selective Service System, Office of Management and Budget, New... SELECTIVE SERVICE SYSTEM Form Submitted to the Office of Management and Budget for Extension of Clearance AGENCY: Selective Service System. ACTION: Notice. The following form has been submitted to the...

76 FR 41855 - Forms Submitted to the Office of Management and Budget for Extension of Clearance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-15

... Regulatory Affairs, Attention: Desk Officer, Selective Service System, Office of Management and Budget, New... SELECTIVE SERVICE SYSTEM Forms Submitted to the Office of Management and Budget for Extension of Clearance AGENCY: Selective Service System. ACTION: Notice. The following form has been submitted to the...

Cryotherapy versus salicylic acid for the treatment of plantar warts (verrucae): a randomised controlled trial

PubMed Central

Hewitt, Catherine; Hicks, Kate; Jayakody, Shalmini; Kang’ombe, Arthur Ricky; Stamuli, Eugena; Turner, Gwen; Thomas, Kim; Curran, Mike; Denby, Gary; Hashmi, Farina; McIntosh, Caroline; McLarnon, Nichola; Torgerson, David; Watt, Ian

2011-01-01

Objective To compare the clinical effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts. Design A multicentre, open, two arm randomised controlled trial. Setting University podiatry school clinics, NHS podiatry clinics, and primary care in England, Scotland, and Ireland. Participants 240 patients aged 12 years and over, with a plantar wart that in the opinion of the healthcare professional was suitable for treatment with both cryotherapy and salicylic acid. Interventions Cryotherapy with liquid nitrogen delivered by a healthcare professional, up to four treatments two to three weeks apart. Patient self treatment with 50% salicylic acid (Verrugon) daily up to a maximum of eight weeks. Main outcome measures Complete clearance of all plantar warts at 12 weeks. Secondary outcomes were (a) complete clearance of all plantar warts at 12 weeks controlling for age, whether the wart had been treated previously, and type of wart, (b) patient self reported clearance of plantar warts at six months, (c) time to clearance of plantar wart, (d) number of plantar warts at 12 weeks, and (e) patient satisfaction with the treatment. Results There was no evidence of a difference between the salicylic acid and cryotherapy groups in the proportions of participants with complete clearance of all plantar warts at 12 weeks (17/119 (14%) v 15/110 (14%), difference 0.65% (95% CI –8.33 to 9.63), P=0.89). The results did not change when the analysis was repeated but with adjustment for age, whether the wart had been treated previously, and type of plantar wart or for patients’ preferences at baseline. There was no evidence of a difference between the salicylic acid and cryotherapy groups in self reported clearance of plantar warts at six months (29/95 (31%) v 33/98 (34%), difference –3.15% (–16.31 to 10.02), P=0.64) or in time to clearance (hazard ratio 0.80 (95% CI 0.51 to 1.25), P=0.33). There was also no evidence of a difference in the number of plantar warts at 12 weeks (incident rate ratio 1.08 (0.81 to 1.43), P=0.62). Conclusions Salicylic acid and the cryotherapy were equally effective for clearance of plantar warts. Trial registration Current Controlled Trials ISRCTN18994246, National Research Register N0484189151. PMID:21652750

Dual clearance squeeze film damper

NASA Technical Reports Server (NTRS)

Fleming, D. P. (Inventor)

1985-01-01

A dual clearance hydrodynamic liquid squeeze film damper for a gas turbine engine is described. Under normal operating conditions, the device functions as a conventional squeeze film damper, using only one of its oil films. When an unbalance reaches abusive levels, as may occur with a blade loss or foreign object damage, a second, larger clearance film becomes active, controlling vibration amplitudes in a near optimum manner until the engine can be safely shut down and repaired.

Mucosal and systemic immune modulation by Trichuris trichiura in a self-infected individual.

PubMed

Dige, A; Rasmussen, T K; Nejsum, P; Hagemann-Madsen, R; Williams, A R; Agnholt, J; Dahlerup, J F; Hvas, C L

2017-01-01

Helminthic therapy of immune-mediated diseases has gained attention in recent years, but we know little of how helminths modulate human immunity. In this study, we investigated how self-infection with Trichuris (T.) trichiura in an adult man without intestinal disease affected mucosal and systemic immunity. Colonic mucosal biopsies were obtained at baseline, during T. trichiura infection, and after its clearance following mebendazole treatment. Unexpectedly, the volunteer experienced a Campylobacter colitis following T. trichiura clearance, and this served as a positive infectious control. Trichuris trichiura colonization induced equally increased expressions of T-helper (h)1-, Th2-, Th17- and Treg-associated cytokines and transcription factors, measured by quantitative polymerase chain reaction. We observed several indicators of modulation of systemic immunity during the T. trichiura infection. Plasma eosinophils and anti-Trichuris antibodies rose markedly during the inoculation phase, and a shift towards a Th2-dominated T cell response at the expense of the Th1-response was observed in circulating T cells. Taken together, our findings corroborate that helminths modulate regional and systemic human immunity. © 2016 John Wiley & Sons Ltd.

Collaboration of Antibody and Inflammation in Clearance of Rabies Virus from the Central Nervous System

PubMed Central

Hooper, D. Craig; Morimoto, Kinjiro; Bette, Michael; Weihe, Eberhard; Koprowski, Hilary; Dietzschold, Bernhard

1998-01-01

To investigate the involvement of various cellular and humoral aspects of immunity in the clearance of rabies virus from the central nervous system, (CNS), we studied the development of clinical signs and virus clearance from the CNS in knockout mice lacking either B and T cells, CD8+ cytotoxic T cells, B cells, alpha/beta interferon (IFN-α/β) receptors, IFN-γ receptors, or complement components C3 and C4. Following intranasal infection with the attenuated rabies virus CVS-F3, normal adult mice of different genetic backgrounds developed a transient disease characterized by loss of body weight and appetite depression which peaked at 13 days postinfection (p.i.). While these animals had completely recovered by day 21 p.i., mice lacking either B and T cells or B cells alone developed a progressive disease and succumbed to infection. Mice lacking either CD8+ T cells, IFN receptors, or complement components C3 and C4 showed no significant differences in the development of clinical signs by comparison with intact counterparts having the same genetic background. However, while infectious virus and viral RNA could be detected in normal control mice only until day 8 p.i., in all of the gene knockout mice studied except those lacking C3 and C4, virus infection persisted through day 21 p.i. Analysis of rabies virus-specific antibody production together with histological assessment of brain inflammation in infected animals revealed that clearance of CVS-F3 by 21 days p.i. correlated with both a strong inflammatory response in the CNS early in the infection (day 8 p.i.), and the rapid (day 10 p.i.) production of significant levels of virus-neutralizing antibody (VNA). These studies confirm that rabies VNA is an absolute requirement for clearance of an established rabies virus infection. However, for the latter to occur in a timely fashion, collaboration between VNA and inflammatory mechanisms is necessary. PMID:9557653

Nonlinear analysis of a rotor-bearing system using describing functions

NASA Astrophysics Data System (ADS)

Maraini, Daniel; Nataraj, C.

2018-04-01

This paper presents a technique for modelling the nonlinear behavior of a rotor-bearing system with Hertzian contact, clearance, and rotating unbalance. The rotor-bearing system is separated into linear and nonlinear components, and the nonlinear bearing force is replaced with an equivalent describing function gain. The describing function captures the relationship between the amplitude of the fundamental input to the nonlinearity and the fundamental output. The frequency response is constructed for various values of the clearance parameter, and the results show the presence of a jump resonance in bearings with both clearance and preload. Nonlinear hardening type behavior is observed in the case with clearance and softening behavior is observed for the case with preload. Numerical integration is also carried out on the nonlinear equations of motion showing strong agreement with the approximate solution. This work could easily be extended to include additional nonlinearities that arise from defects, providing a powerful diagnostic tool.

48 CFR 801.602-81 - Documents required for business clearance reviews.

Code of Federal Regulations, 2010 CFR

2010-10-01

... business clearance reviews. 801.602-81 Section 801.602-81 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career... reviews. When a bid or offer, proposed contract modification, or proposed lease requires a business...

77 FR 7567 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

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20 CFR 655.150 - Interstate clearance of job order.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

20 CFR 655.150 - Interstate clearance of job order.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

20 CFR 655.150 - Interstate clearance of job order.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

20 CFR 655.150 - Interstate clearance of job order.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

20 CFR 655.150 - Interstate clearance of job order.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

Steady state plasma [3H]-noradrenaline kinetics in quadriplegic chronic spinal cord injury patients.

PubMed

Krum, H; Brown, D J; Rowe, P R; Louis, W J; Howes, L G

1990-08-01

1. Steady state plasma noradrenaline kinetics were measured in eight male quadriplegic patients and in eight age and sex matched controls. 2. Plasma noradrenaline levels were significantly lower in quadriplegic patients compared to controls. Noradrenaline spillover rate was markedly reduced in quadriplegics compared to controls while noradrenaline clearance was similar in both groups. 3. Noradrenaline kinetics in quadriplegic patients differ from peripheral autonomic neuropathy patients where reductions in both the spillover and clearance of noradrenaline are present.

76 FR 30753 - Agency Information Collection Activities: Requests for Comments; Clearance of Renewed Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-26

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Agency Information Collection Activities: Requests for Comments; Clearance of Renewed Approval of Information Collection: Special Awareness...: [email protected] . SUPPLEMENTARY INFORMATION: OMB Control Number: 2120-0734. Title: Special Awareness...

System for Better Spacing of Airplanes En Route

NASA Technical Reports Server (NTRS)

Green, Steven; Erzberger, Heinz

2004-01-01

An improved method of computing the spacing of airplanes en route, and software to implement the method, have been invented. The purpose of the invention is to help air-traffic controllers minimize those deviations of the airplanes from the trajectories preferred by their pilots that are needed to make the airplanes comply with miles-in-trail spacing requirements. The software is meant to be a modular component of the Center TRACON Automation System (CTAS) (TRACON signifies "terminal radar approach control"). The invention reduces controllers workloads and reduces fuel consumption by reducing the number of corrective clearances needed to achieve conformance with specified flow rates, without causing conflicts, while providing for more efficient distribution of spacing workload upstream and across air-traffic-control sectors.

Non-Invasive Assessment of Liver Function

PubMed Central

Helmke, Steve; Colmenero, Jordi; Everson, Gregory T.

2015-01-01

Purpose of review It is our opinion that there is an unmet need in Hepatology for a minimally- or noninvasive test of liver function and physiology. Quantitative liver function tests (QLFTs) define the severity and prognosis of liver disease by measuring the clearance of substrates whose uptake or metabolism is dependent upon liver perfusion or hepatocyte function. Substrates with high affinity hepatic transporters exhibit high “first-pass” hepatic extraction and their clearance measures hepatic perfusion. In contrast, substrates metabolized by the liver have low first-pass extraction and their clearance measures specific drug metabolizing pathways. Recent Findings We highlight one QLFT, the dual cholate test, and introduce the concept of a disease severity index (DSI) linked to clinical outcome that quantifies the simultaneous processes of hepatocyte uptake, clearance from the systemic circulation, clearance from the portal circulation, and portal-systemic shunting. Summary It is our opinion that dual cholate is a relevant test for defining disease severity, monitoring the natural course of disease progression, and quantifying the response to therapy. PMID:25714706

Microgravity human factors workstation development

NASA Technical Reports Server (NTRS)

Whitmore, Mihriban; Wilmington, Robert P.; Morris, Randy B.; Jensen, Dean G.

1992-01-01

Microgravity evaluations of workstation hardware as well as its system components were found to be very useful for determining the expected needs of the Space Station crew and for refining overall workstation design. Research at the Johnson Space Center has been carried out to provide optimal workstation design and human interface. The research included evaluations of hand controller configurations for robots and free flyers, the identification of cursor control device requirements, and the examination of anthropometric issues of workstation design such as reach, viewing distance, and head clearance.

Estradiol and weight are covariates of paracetamol clearance in young women.

PubMed

Beleyn, B; Vermeersch, S; Kulo, A; Smits, A; Verbesselt, R; de Hoon, J N; Van Calsteren, K; Allegaert, K

2014-01-01

Paracetamol clearance differs between pregnant and non-pregnant women and between women with or without specific oral contraceptives (OCs). However, an association between female sex hormones and paracetamol clearance has never been explored. In total, 49 women at delivery, 8 female control subjects without OC use, historical data of 14 women taking OCs, and 15 postpartum observations with and without OCs were pooled to explore covariates of paracetamol clearance. All received a single intravenous 2-gram paracetamol dose, and blood samples were collected up to 6 h after dosing. High-performance liquid chromatography was used to quantify paracetamol. The area under the curve to time infinity (AUC0-∞) was determined and clearance (l/h·m(2)) was calculated by dose/ AUC0-∞. In addition, estradiol and progesterone were quantified by ELISA with electro-chemiluminescence. Median paracetamol clearance at delivery was significantly higher when compared to postpartum or non-pregnant women (11.9 vs. 6.42 and 8.4 l/h·m(2), at least p < 0.05), while an association between paracetamol clearance and estradiol was observed (R = 0.494, p < 0.0001). In non-pregnant subjects, there was no impact of OC exposure on paracetamol clearance. Multiple regression revealed a linear association (Radj = 0.41, p < 0.001) between paracetamol clearance and weight (p = 0.0462) and estradiol (p < 0.0001). Estradiol and weight in part explain the variation in paracetamol clearance in young women. © 2014 S. Karger AG, Basel.

Reduced erythrocyte susceptibility and increased host clearance of young parasites slows Plasmodium growth in a murine model of severe malaria

NASA Astrophysics Data System (ADS)

Khoury, David S.; Cromer, Deborah; Best, Shannon E.; James, Kylie R.; Sebina, Ismail; Haque, Ashraful; Davenport, Miles P.

2015-05-01

The best correlate of malaria severity in human Plasmodium falciparum (Pf) infection is the total parasite load. Pf-infected humans could control parasite loads by two mechanisms, either decreasing parasite multiplication, or increasing parasite clearance. However, few studies have directly measured these two mechanisms in vivo. Here, we have directly quantified host clearance of parasites during Plasmodium infection in mice. We transferred labelled red blood cells (RBCs) from Plasmodium infected donors into uninfected and infected recipients, and tracked the fate of donor parasites by frequent blood sampling. We then applied age-based mathematical models to characterise parasite clearance in the recipient mice. Our analyses revealed an increased clearance of parasites in infected animals, particularly parasites of a younger developmental stage. However, the major decrease in parasite multiplication in infected mice was not mediated by increased clearance alone, but was accompanied by a significant reduction in the susceptibility of RBCs to parasitisation.

Adiponectin modulates inflammatory reactions via calreticulin receptor–dependent clearance of early apoptotic bodies

PubMed Central

Takemura, Yukihiro; Ouchi, Noriyuki; Shibata, Rei; Aprahamian, Tamar; Kirber, Michael T.; Summer, Ross S.; Kihara, Shinji; Walsh, Kenneth

2007-01-01

Obesity and type 2 diabetes are associated with chronic inflammation. Adiponectin is an adipocyte-derived hormone with antidiabetic and antiinflammatory actions. Here, we demonstrate what we believe to be a previously undocumented activity of adiponectin, facilitating the uptake of early apoptotic cells by macrophages, an essential feature of immune system function. Adiponectin-deficient (APN-KO) mice were impaired in their ability to clear apoptotic thymocytes in response to dexamethasone treatment, and these animals displayed a reduced ability to clear early apoptotic cells that were injected into their intraperitoneal cavities. Conversely, adiponectin administration promoted the clearance of apoptotic cells by macrophages in both APN-KO and wild-type mice. Adiponectin overexpression also promoted apoptotic cell clearance and reduced features of autoimmunity in lpr mice whereas adiponectin deficiency in lpr mice led to a further reduction in apoptotic cell clearance, which was accompanied by exacerbated systemic inflammation. Adiponectin was capable of opsonizing apoptotic cells, and phagocytosis of cell corpses was mediated by the binding of adiponectin to calreticulin on the macrophage cell surface. We propose that adiponectin protects the organism from systemic inflammation by promoting the clearance of early apoptotic cells by macrophages through a receptor-dependent pathway involving calreticulin. PMID:17256056

Simple geometric algorithms to aid in clearance management for robotic mechanisms

NASA Technical Reports Server (NTRS)

Copeland, E. L.; Ray, L. D.; Peticolas, J. D.

1981-01-01

Global geometric shapes such as lines, planes, circles, spheres, cylinders, and the associated computational algorithms which provide relatively inexpensive estimates of minimum spatial clearance for safe operations were selected. The Space Shuttle, remote manipulator system, and the Power Extension Package are used as an example. Robotic mechanisms operate in quarters limited by external structures and the problem of clearance is often of considerable interest. Safe clearance management is simple and suited to real time calculation, whereas contact prediction requires more precision, sophistication, and computational overhead.

Experimental Evaluation of CTAS/FMS Integration in TRACON Airspace

NASA Technical Reports Server (NTRS)

Romahn, Stephen; Palmer, Everett; Null, Cynthia H. (Technical Monitor)

1999-01-01

A CTAS/FMS integration project at Ames Research Center addresses extensions to the CTAS air traffic management concept, among them the introduction of arrival routes specially designed for the use with a Flight Management System. These FMS arrival routes shall allow for the use of the INS' lateral and vertical navigation capabilities throughout the arrival until final approach. For the use in this project CTAS controller support tools that compliment the concept have been created. These tools offer controllers access to CTAS' prediction and planning capabilities in terms of speed and route advisories. The objective is to allow for a more strategic way of controlling aircraft. Expected benefits are an increase in arrival rate and a reduction of average travel times through TRACER airspace. A real time simulation is being conducted at Ames to investigate how FMS arrivals and approach transitions - with and without the support of CTAS tools - effect the flow of arriving traffic within TRACER airspace and the controllers' task performance. Four conditions will be investigated and compared to today's technique of controlling traffic with tactical vectoring: 1. FMS arrivals and approach transitions are available for controllers to issue to equipped aircraft - traffic permitting; 2. Speed advisories that match CTAS' runway balancing and sequencing plan are displayed to Feeder controllers; 3. Approach transition advisories (e.g., location of the base turn point) are displayed to Final controllers for tactical clearances ("Turn base now"); and 4. Approach transition advisories (voice and data link) are generated by CTAS and displayed to final controllers for strategic voice clearances ("Turn base five miles after waypoint xyz") or prepared in terms of a trajectory description for strategic data link clearance. Scenarios used in the study will represent current traffic and vary in density of arriving traffic and the kind and mix of equipage of arriving aircraft. Data will be collected from experiment runs with active TRACON controllers on the final approach spacing, the aircraft's speed profiles, the controllers interaction with CTAS tools, and number and timing of pilot controllers communications under the described conditions.

Innate (inherent) control of brain infection, brain inflammation and brain repair: the role of microglia, astrocytes, "protective" glial stem cells and stromal ependymal cells.

PubMed

Hauwel, Mathieu; Furon, Emeline; Canova, Cecile; Griffiths, Mark; Neal, Jim; Gasque, Philippe

2005-04-01

In invertebrates and primitive vertebrates, the brain contains large numbers of "professional" macrophages associated with neurones, ependymal tanycytes and radial glia to promote robust regenerative capacity. In higher vertebrates, hematogenous cells are largely excluded from the brain, and innate immune molecules and receptors produced by the resident "amateur" macrophages (microglia, astrocytes and ependymal cells) control pathogen infiltration and clearance of toxic cell debris. However, there is minimal capacity for regeneration. The transfer of function from hematogenous cells to macroglia and microglia is associated with the sophistication of a yet poorly-characterized neurone-glia network. This evolutionary pattern may have been necessary to reduce the risk of autoimmune attack while preserving the neuronal web but the ability to repair central nervous system damage may have been sacrificed in the process. We herein argue that it may be possible to re-educate and stimulate the resident phagocytes to promote clearance of pathogens (e.g., Prion), toxic cell debris (e.g., amyloid fibrils and myelin) and apoptotic cells. Moreover, as part of this greater division of labour between cell types in vertebrate brains, it may be possible to harness the newly described properties of glial stem cells in neuronal protection (revitalization) rather than replacement, and to control brain inflammation. We will also highlight the emerging roles of stromal ependymal cells in controlling stem cell production and migration into areas of brain damage. Understanding the mechanisms involved in the nurturing of damaged neurons by protective glial stem cells with the safe clearance of cell debris could lead to remedial strategies for chronic brain diseases.

78 FR 22022 - Agency Information Collection Activities: Requests for Comments; Clearance of Renewed Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-12

... Activities: Requests for Comments; Clearance of Renewed Approval of Information Collection: Airport Noise... respondents are those airport operators voluntarily submitting noise exposure maps and noise compatibility....gov . SUPPLEMENTARY INFORMATION: OMB Control Number: 2120-0517. Title: Airport Noise Compatibility...

Comparison of trout hepatocytes and liver S9 fractions as in ...

EPA Pesticide Factsheets

Isolated hepatocytes and liver S9 fractions have been used to collect in vitro biotransformation data for fish as a means of improving modeled estimates of chemical bioaccumulation. To date, however, there have been few direct comparisons of these two methods. In the present study, cryopreserved trout hepatocytes were used to measure in vitro intrinsic clearance rates for 6 polycyclic aromatic hydrocarbons (PAHs). These rates were extrapolated to estimates of in vivo intrinsic clearance and used as inputs to a well-stirred liver model to predict hepatic clearance. Predicted rates of hepatic clearance were then evaluated by comparison to measured rates determined previously using isolated perfused livers. Hepatic clearance rates predicted using hepatocytes were in good agreement with measured values (< 2.1 fold difference for 5 of 6 compounds) under two competing binding assumptions. These findings, which may be attributed in part to high rates of PAH metabolism, are similar to those obtained previously using data from liver S9 fractions. For one compound (benzo[a]pyrene), the in vivo intrinsic clearance rate calculated using S9 data was 10-fold higher than that determined using hepatocytes, possibly due to a diffusion limitation on cellular uptake. Generally, however, there was good agreement between calculated in vivo intrinsic clearance rates obtained using either in vitro test system. These results suggest that both systems can be used to improve

Hemolytic performance of a MagLev disposable rotary blood pump (MedTech Dispo): effects of MagLev gap clearance and surface roughness.

PubMed

Hoshi, Hideo; Asama, Junichi; Hijikata, Wataru; Hara, Chikara; Shinshi, Tadahiko; Yasuda, Toshitaka; Ohuchi, Katsuhiro; Shimokohbe, Akira; Takatani, Setsuo

2006-12-01

Mechanical shaft seal bearing incorporated in the centrifugal blood pumps contributes to hemolysis and thrombus formation. In addition, the problem of durability and corrosion of mechanical shaft seal bearing has been recently reported from the safety point of view. To amend the shortcomings of the blood-immersed mechanical bearings, a magnetic levitated centrifugal rotary blood pump (MedTech Dispo Model 1; Tokyo Medical and Dental University, Tokyo, Japan) has been developed for extracorporeal disposable application. In this study, the hemolytic performance of the MedTech Dispo Model 1 centrifugal blood pump system was evaluated, with special focus on the narrow blood path clearance at the magnetic bearing between rotor and stator, and on the pump housing surface roughness. A pump flow of 5 L/min against the head pressure of 100 mm Hg for 4 h was included in the hemolytic test conditions. Anticoagulated fresh porcine blood was used as a working fluid. The clearance of blood path at the magnetic bearing was in the range of 100-250 micro m. Pump housing surface roughness was controlled to be around Ra = 0.1-1.5 micro m. The lowest hemolytic results were obtained at the clearance of 250 micro m and with the polished surface (Ra = 0.1 micro m) yielding the normalized index of hemolysis (NIH) of less than 0.001 g/100 L, which was 1/5 of the Biopump BP-80 (Medtronic Inc., Minneapolis, MN, USA, and 1/4 of the BPX-80. In spite of rough surface and narrow blood path, NIH levels were less than clinically acceptable level of 0.005 g/100 L. The noncontact, levitated impeller system is useful to improve pump performance in blood environment.

Dynamic stability and handling qualities tests on a highly augmented, statically unstable airplane

NASA Technical Reports Server (NTRS)

Gera, Joseph; Bosworth, John T.

1987-01-01

Initial envelope clearance and subsequent flight testing of a new, fully augmented airplane with an extremely high degree of static instability can place unusual demands on the flight test approach. Previous flight test experience with these kinds of airplanes is very limited or nonexistent. The safe and efficient flight testing may be further complicated by a multiplicity of control effectors that may be present on this class of airplanes. This paper describes some novel flight test and analysis techniques in the flight dynamics and handling qualities area. These techniques were utilized during the initial flight envelope clearance of the X-29A aircraft and were largely responsible for the completion of the flight controls clearance program without any incidents or significant delays.

Development of A New Automotive Active Suspension System

NASA Astrophysics Data System (ADS)

Yousef Abdulhammed, Eng.; Eng. Hisham Elsherif, Dr, Prof.

2017-12-01

The main objective was to develop a smart new vehicle suspension system that minimizes the road irregularities impact on the driver, also to increase performance and stability of the vehicle at high speeds. The central idea is based on modifying the normal passive suspension system into a computer controller hydraulic actuated active suspension system simply by adding a new component such as a hydraulic cylinder on a normal passive system. The new suspension system is economical to be wildly used in consumer’s cars with low prices. The new added components was analytically tested and modeled according to different parameters. A new test rig was implemented to simulate a real quarter suspension system. The new suspension model was controlled by feedback controller according to the road conditions; the controller output controls the cylinder actuator to compensate the road oscillations and increases the vehicle stability for the passenger. Finally, to maximize the aerodynamics coefficients of the vehicle during high speeds by controlling the vehicle clearance level from the ground to achieve full stability, steering and fuel economy.

Performance Optimization of a Rotor Alone Nacelle for Acoustic Fan Testing

NASA Technical Reports Server (NTRS)

Cunningham, C. C.; Thompson, W. K.; Hughes, C. E.

2000-01-01

This paper describes the techniques, equipment, and results from the optimization of a two-axis traverse actuation system used to maintain concentricity between a sting-mounted fan and a wall-mounted nacelle in the 9 x 15 (9 Foot by 15 Foot Test Section) Low Speed Wind Tunnel (LSWT) at the NASA Glenn Research Center (GRC). The Rotor Alone Nacelle (RAN) system, developed at GRC by the Engineering Design and Analysis Division (EDAD) and the Acoustics Branch, used nacelle-mounted lasers and an automated control system to maintain concentricity as thermal and thrust operating loads displace the fan relative to the nacelle. This effort was critical to ensuring rig/facility safety and experimental consistency of the acoustic data from a statorless, externally supported nacelle configuration. Although the tip clearances were originally predicted to be about 0.020 in. at maximum rotor (fan) operating speed, proximity probe measurements showed that the nominal clearance was less than 0.004 in. As a result, the system was optimized through control-loop modifications, active laser cooling, data filtering and averaging, and the development of strict operational procedures. The resultant concentricity error of RAN was reduced to +/- 0.0031 in. in the Y-direction (horizontal) and +0.0035 in./-0.001 3 in. in the Z-direction (vertical), as determined by error analysis and experimental results. Based on the success of this project, the RAN system will be transitioned to other wind tunnel research programs at NASA GRC.

NASA aviation safety reporting system

NASA Technical Reports Server (NTRS)

1977-01-01

During the third quarter of operation of the Aviation Safety Reporting System (ASRS), 1429 reports concerning aviation safety were received from pilots, air traffic controllers, and others in the national aviation system. Details of the administration and results of the program are discussed. The design and construction of the ASRS data base are briefly presented. Altitude deviations and potential aircraft conflicts associated with misunderstood clearances were studied and the results are discussed. Summary data regarding alert bulletins, examples of alert bulletins and responses to them, and a sample of deidentified ASRS reports are provided.

A microprocessor-controlled tracheal insufflation-assisted total liquid ventilation system.

PubMed

Parker, James Courtney; Sakla, Adel; Donovan, Francis M; Beam, David; Chekuri, Annu; Al-Khatib, Mohammad; Hamm, Charles R; Eyal, Fabien G

2009-09-01

A prototype time cycled, constant volume, closed circuit perfluorocarbon (PFC) total liquid ventilator system is described. The system utilizes microcontroller-driven display and master control boards, gear motor pumps, and three-way solenoid valves to direct flow. A constant tidal volume and functional residual capacity (FRC) are maintained with feedback control using end-expiratory and end-inspiratory stop-flow pressures. The system can also provide a unique continuous perfusion (bias flow, tracheal insufflation) through one lumen of a double-lumen endotracheal catheter to increase washout of dead space liquid. FRC and arterial blood gases were maintained during ventilation with Rimar 101 PFC over 2-3 h in normal piglets and piglets with simulated pulmonary edema induced by instillation of albumin solution. Addition of tracheal insufflation flow significantly improved the blood gases and enhanced clearance of instilled albumin solution during simulated edema.

Changes in toe clearance during treadmill walking after long-duration spaceflight.

PubMed

Miller, Christopher A; Peters, Brian T; Brady, Rachel R; Richards, Jason R; Ploutz-Snyder, Robert J; Mulavara, Ajitkumar P; Bloomberg, Jacob J

2010-10-01

Astronauts exhibit sensorimotor changes upon return from long-duration spaceflight that can result in altered gait kinematics and possibly an increased risk of tripping. Toe trajectory during locomotion is a precise motor control task involving both legs, thus providing a composite metric of locomotor control. The purpose of this study was to determine whether astronauts are at an increased risk of tripping after their return from long-duration spaceflight. This was accomplished by assessing the pre- to postflight changes in toe clearance during treadmill walking. Ten crewmembers walked on a treadmill while performing a visual-acuity task pre- and postflight. In the three subjects on whom landing day data were available, each exhibited a characteristic of increased tripping risk on landing day: either a decreased median toe clearance or an increased interquartile range (a measure of variance). For all crewmembers, toe clearance median and interquartile range were not significantly different from preflight for the other postflight sessions (the earliest being 1 d after landing). A follow-up analysis showed that changes in foot pitch, ankle dorsiflexion, and pelvis roll angles were significant predictors of changes in toe clearance. The landing-day observations indicated an increased risk of tripping, which may pose a hazard during locomotion immediately upon return to Earth, especially in an emergency scenario. However, tripping risk on subsequent days was not different than preflight. The joint angle analysis suggested that the crewmembers tried to reestablish their normal walking pattern postflight, instead of developing a new motor control strategy.

77 FR 47491 - Agency Information Collection Activities: Requests for Comments; Clearance of Renewed Approval of...

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2012-08-08

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2007 NASA Seal/Secondary Air System Workshop. Volume 1

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M.; Hendricks, Robert C.; Delgado, Irebert

2008-01-01

The 2007 NASA Seal/Secondary Air System workshop covered the following topics: (i) Overview of NASA's new Orion project aimed at developing a new spacecraft that will fare astronauts to the International Space Station, the Moon, Mars, and beyond; (ii) Overview of NASA's fundamental aeronautics technology project; (iii) Overview of NASA Glenn s seal project aimed at developing advanced seals for NASA's turbomachinery, space, and reentry vehicle needs; (iv) Reviews of NASA prime contractor, vendor, and university advanced sealing concepts, test results, experimental facilities, and numerical predictions; and (v) Reviews of material development programs relevant to advanced seals development. Turbine engine studies have shown that reducing seal leakage as well as high-pressure turbine (HPT) blade tip clearances will reduce fuel burn, lower emissions, retain exhaust gas temperature margin, and increase range. Turbine seal development topics covered include a method for fast-acting HPT blade tip clearance control, noncontacting low-leakage seals, intershaft seals, and a review of engine seal performance requirements for current and future Army engine platforms.

Energy efficient engine. Low pressure turbine test hardware detailed design report

NASA Technical Reports Server (NTRS)

Cherry, D. G.; Gay, C. H.; Lenahan, D. T.

1982-01-01

The low pressure turbine for the energy efficient engine is a five-stage configuration with moderate aerodynamic loading incorporating advanced features of decambered airfoils and extended blade overlaps at platforms and shrouds. Mechanical integrity of 18,000 hours on flowpath components and 36,000 hours on all other components is achieved along with no aeromechanical instabilities within the steady-state operating range. Selection of a large number (156) of stage 4 blades, together with an increased stage 4 vane-to-blade gap, assists in achieving FAR 36 acoustic goals. Active clearance control (ACC) of gaps at blade tips and interstage seals is achieved by fan air cooling judiciously applied at responsive locations on the casing. This ACC system is a major improvement in preventing deterioration of the 0.0381 cm (0.015 in.) clearances required to meet the integrated-core/low-spool turbine efficiency goal of 91.1% and the light propulsion system efficiency goal of 91.7%.

2008 NASA Seal/Secondary Air System Workshop

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M. (Editor); Hendricks, Robert C. (Editor); Delgado, Irebert R. (Editor)

2009-01-01

The 2008 NASA Seal/Secondary Air System Workshop covered the following topics: (i) Overview of NASA s new Orion project aimed at developing a new spacecraft that will fare astronauts to the International Space Station, the Moon, Mars, and beyond; (ii) Overview of NASA s fundamental aeronautics technology project; (iii) Overview of NASA Glenn s seal project aimed at developing advanced seals for NASA s turbomachinery, space, and reentry vehicle needs; (iv) Reviews of NASA prime contractor, vendor, and university advanced sealing concepts, test results, experimental facilities, and numerical predictions; and (v) Reviews of material development programs relevant to advanced seals development. Turbine engine studies have shown that reducing seal leakage as well as high-pressure turbine (HPT) blade tip clearances will reduce fuel burn, lower emissions, retain exhaust gas temperature margin, and increase range. Turbine seal development topics covered include a method for fast-acting HPT blade tip clearance control, noncontacting low-leakage seals, intershaft seals, and a review of engine seal performance requirements for current and future Army engine platforms.

78 FR 72139 - Forms Submitted to the Office of Management and Budget for Extension of Clearance

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2013-12-02

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2011-11-15

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2011-10-11

... should be sent to the Office of Information and Regulatory Affairs, Attention: Desk Officer, Selective... SELECTIVE SERVICE SYSTEM Form Submitted to the Office of Management and Budget for Extension of Clearance AGENCY: Selective Service System. ACTION: Notice. The following form has been submitted to the...

Implementation of an Interorganizational System: The Case of Medical Insurance E-Clearance

ERIC Educational Resources Information Center

Bose, Indranil; Liu, Han; Ye, Alex

2012-01-01

The patients receiving treatment from a hospital need to interact with multiple entities when claiming reimbursements. The complexities of the medical service supply chain can be simplified with an electronic clearance management system that allows hospitals, medical insurance bureau, bank, and patients to interact in a seamless and cashless…

Low-density lipoprotein receptor-related protein 1: a physiological Aβ homeostatic mechanism with multiple therapeutic opportunities

PubMed Central

Sagare, Abhay P.; Deane, Rashid; Zlokovic, Berislav V.

2012-01-01

Low-density lipoprotein receptor-related protein-1 (LRP1) is the main cell surface receptor involved in brain and systemic clearance of the Alzheimer's disease (AD) toxin amyloid-beta (Aβ). In plasma, a soluble form of LRP1 (sLRP1) is the major transport protein for peripheral Aβ. LRP1 in brain endothelium and mural cells mediates Aβ efflux from brain by providing a transport mechanism for A across the blood-brain barrier (BBB). sLRP1 maintains a plasma ‘sink’ activity for Aβ through binding of peripheral Aβ which in turn inhibits re-entry of free plasma Aβ into the brain. LRP1 in the liver mediates systemic clearance of Aβ. In AD, LRP1 expression at the BBB is reduced and Aβ binding to circulating sLRP1 is compromised by oxidation. Cell surface LRP1 and circulating sLRP1 represent druggable targets which can be therapeutically modified to restore the physiological mechanisms of brain Aβ homeostasis. In this review, we discuss how increasing LRP1 expression at the BBB and liver with lifestyle changes, statins, plant-based active principles and/or gene therapy on one hand, and how replacing dysfunctional plasma sLRP1 on the other regulate Aβ clearance from brain ultimately controlling the onset and/or progression of AD. PMID:22820095

77 FR 27799 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-11

.... ADDRESSES: Send comments to Nora Kincaid, BLS Clearance Officer, Division of Management Systems, Bureau of... INFORMATION CONTACT: Nora Kincaid, BLS Clearance Officer, 202-691-7628 (this is not a toll free number). (See...

The EVERT (effective verruca treatments) trial protocol: a randomised controlled trial to evaluate cryotherapy versus salicylic acid for the treatment of verrucae.

PubMed

Cockayne, E Sarah

2010-02-08

Verrucae are a common, infectious and sometimes painful problem. The optimal treatment for verrucae is unclear due to a lack of high quality randomised controlled trials. The primary objective of this study is to compare the clinical effectiveness of two common treatments for verrucae: cryotherapy using liquid nitrogen versus salicylic acid. Secondary objectives include a comparison of the cost-effectiveness of the treatments, and an investigation of time to clearance of verrucae, recurrence/clearance of verrucae at six months, patient satisfaction with treatment, pain associated with treatment, and use of painkillers for the treatments. This is an open, pragmatic, multicentre, randomised controlled trial with two parallel groups: cryotherapy using liquid nitrogen delivered by a healthcare professional for a maximum of 4 treatments (treatments 2-3 weeks apart) or daily self-treatment with 50% salicylic acid for a maximum of 8 weeks. Two hundred and sixty-six patients aged 12 years and over with a verruca are being enrolled into the study. The primary outcome is complete clearance of all verrucae as observed on digital photographs taken at 12 weeks compared with baseline and assessed by an independent healthcare professional. Secondary outcomes include self-reported time to clearance of verrucae, self-reported clearance of verrucae at 6 months, cost-effectiveness of the treatments compared to one another, and patient acceptability of both treatments including possible side effects such as pain. The primary analysis will be intention to treat. It is planned that recruitment will be completed by December 2009 and results will be available by June 2010. Current Controlled Trials ISRCTN18994246.

CD200 Receptor Controls Sex-Specific TLR7 Responses to Viral Infection

PubMed Central

Raaben, Matthijs; Grinwis, Guy C. M.; Coenjaerts, Frank E.; Ressing, Maaike E.; Rottier, Peter J. M.; de Haan, Cornelis A. M.; Meyaard, Linde

2012-01-01

Immunological checkpoints, such as the inhibitory CD200 receptor (CD200R), play a dual role in balancing the immune system during microbial infection. On the one hand these inhibitory signals prevent excessive immune mediated pathology but on the other hand they may impair clearance of the pathogen. We studied the influence of the inhibitory CD200-CD200R axis on clearance and pathology in two different virus infection models. We find that lack of CD200R signaling strongly enhances type I interferon (IFN) production and viral clearance and improves the outcome of mouse hepatitis corona virus (MHV) infection, particularly in female mice. MHV clearance is known to be dependent on Toll like receptor 7 (TLR7)-mediated type I IFN production and sex differences in TLR7 responses previously have been reported for humans. We therefore hypothesize that CD200R ligation suppresses TLR7 responses and that release of this inhibition enlarges sex differences in TLR7 signaling. This hypothesis is supported by our findings that in vivo administration of synthetic TLR7 ligand leads to enhanced type I IFN production, particularly in female Cd200−/− mice and that CD200R ligation inhibits TLR7 signaling in vitro. In influenza A virus infection we show that viral clearance is determined by sex but not by CD200R signaling. However, absence of CD200R in influenza A virus infection results in enhanced lung neutrophil influx and pathology in females. Thus, CD200-CD200R and sex are host factors that together determine the outcome of viral infection. Our data predict a sex bias in both beneficial and pathological immune responses to virus infection upon therapeutic targeting of CD200-CD200R. PMID:22615569

78 FR 38794 - Agency Information Collection Activities: Requests for Comments; Clearance of Renewed Approval of...

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2013-06-27

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2011-08-26

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2013-12-12

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2013-04-12

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2011-06-21

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An investigation of air transportation technology at the Massachusetts Institute of Technology, 1990-1991

NASA Technical Reports Server (NTRS)

Simpson, Robert W.

1991-01-01

Brief summaries are given of research activities at the Massachusetts Institute of Technology (MIT) under the sponsorship of the FAA/NASA Joint University Program. Topics covered include hazard assessment and cockpit presentation issues for microburst alerting systems; the situational awareness effect of automated air traffic control (ATC) datalink clearance amendments; a graphical simulation system for adaptive, automated approach spacing; an expert system for temporal planning with application to runway configuration management; deterministic multi-zone ice accretion modeling; alert generation and cockpit presentation for an integrated microburst alerting system; and passive infrared ice detection for helicopter applications.

Application of a minicomputer-based system in measuring intraocular fluid dynamics

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

Bronzino, J.D.; D'Amato, D.P.; O'Rourke, J.

A complete, computerized system has been developed to automate and display radionuclide clearance studies in an ophthalmology clinical laboratory. The system is based on a PDP-8E computer with a 16-k core memory and includes a dual-drive Decassette system and an interactive display terminal. The software controls the acquisition of data from an NIM scaler, times the procedures, and analyzes and simultaneously displays logarithmically converted data on a fully annotated graph. Animal studies and clinical experiments are presented to illustrate the nature of these displays and the results obtained using this automated eye physiometer.

The Handling of Immunoreactive Vasopressin by the Isolated Perfused Rat Kidney

PubMed Central

Rabkin, Ralph; Share, Leonard; Payne, Paul A.; Young, Judy; Crofton, Joan

1979-01-01

Using the isolated rat kidney perfused with an artificial medium containing glucose as the sole fuel, we studied the renal handling of immunoreactive arginine vasopressin (AVP) and determined the effect of various factors on the ability of the kidney to remove AVP. In control kidneys perfused with AVP at concentrations below 116 μU/ml, the organ clearance of AVP (OCAVP) was 1,145±47 (SE) μl/min, whereas glomerular filtration rate (GFR) averaged 515±37 μl/min. Filtration could thus account for up to 45% of the OCAVP, the balance presumably being cleared from the peritubular circulation. Of the AVP filtered, only 38% could be recovered in the urine (urinary clearance AVP averaged 205±12 μl/min) suggesting that the balance was taken up by the tubular epithelium and degraded. Fractional excretion of filtered AVP rose significantly in the presence of anoxia and cold (10°C) to 49 and 59%, respectively, but was not affected by ouabain or high levels of AVP (458±58 μU/ml). The OCAVP was not significantly altered by the absence of glucose in the perfusate, anoxia, or ureteral ligation, maneuvers that were associated with significant reductions in GFR. In these and the control experiments, there was a significant inverse correlation between GFR and peritubular clearance emphasizing the importance of the latter (r = −0.749; P < 0.001). Cold, ouabain, and high concentrations of AVP reduced the clearance of AVP by the kidneys. On the basis of these studies we conclude that the kidney clears AVP from the circulation via two pathways, glomerular clearance and peritubular clearance. This exposes both the luminal and contraluminal surfaces of the tubular cells to the hormone, allowing these cells to remove AVP from the filtrate and the peritubular compartment. Noteworthy is the observation that under several conditions when GFR falls reducing the glomerular clearance of AVP, peritubular clearance increases and the total clearance of AVP by the kidney remains constant. PMID:762248

Low ground clearance vehicle detection and warning.

DOT National Transportation Integrated Search

2015-06-01

A Low Ground Clearance Vehicle Detection : System (LGCVDS) determines if a commercial : motor vehicle can successfully clear a highwayrail : grade crossing and notifies the driver when : his or her vehicle cannot safely traverse the : crossing. That ...

Tip Clearance Control Using Plasma Actuators

DTIC Science & Technology

2007-03-01

Clearance Control Using Plasma Actuators 4 posed by Denton (1993). A number of investigators have used partial shrouds, or " winglet " designs to...main molded blade with a span of 3.42 in., a removable molded blade segment with a span of 0.1875 in., and removable blade tip winglets made of glass...segment and the main blade to vary the distance between the blade end and the front wall of the cascade section. The winglets were machined using a

Enhanced efficacy of sequential administration of Albendazole for the clearance of Wuchereria bancrofti infection: Double blind RCT.

PubMed

De Britto, R L; Vanamail, P; Sankari, T; Vijayalakshmi, G; Das, L K; Pani, S P

2015-06-01

Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier - NCT02005653).

A Blade Tip Timing Method Based on a Microwave Sensor

PubMed Central

Zhang, Jilong; Duan, Fajie; Niu, Guangyue; Jiang, Jiajia; Li, Jie

2017-01-01

Blade tip timing is an effective method for blade vibration measurements in turbomachinery. This method is increasing in popularity because it is non-intrusive and has several advantages over the conventional strain gauge method. Different kinds of sensors have been developed for blade tip timing, including optical, eddy current and capacitance sensors. However, these sensors are unsuitable in environments with contaminants or high temperatures. Microwave sensors offer a promising potential solution to overcome these limitations. In this article, a microwave sensor-based blade tip timing measurement system is proposed. A patch antenna probe is used to transmit and receive the microwave signals. The signal model and process method is analyzed. Zero intermediate frequency structure is employed to maintain timing accuracy and dynamic performance, and the received signal can also be used to measure tip clearance. The timing method uses the rising and falling edges of the signal and an auto-gain control circuit to reduce the effect of tip clearance change. To validate the accuracy of the system, it is compared experimentally with a fiber optic tip timing system. The results show that the microwave tip timing system achieves good accuracy. PMID:28492469

A Blade Tip Timing Method Based on a Microwave Sensor.

PubMed

Zhang, Jilong; Duan, Fajie; Niu, Guangyue; Jiang, Jiajia; Li, Jie

2017-05-11

Blade tip timing is an effective method for blade vibration measurements in turbomachinery. This method is increasing in popularity because it is non-intrusive and has several advantages over the conventional strain gauge method. Different kinds of sensors have been developed for blade tip timing, including optical, eddy current and capacitance sensors. However, these sensors are unsuitable in environments with contaminants or high temperatures. Microwave sensors offer a promising potential solution to overcome these limitations. In this article, a microwave sensor-based blade tip timing measurement system is proposed. A patch antenna probe is used to transmit and receive the microwave signals. The signal model and process method is analyzed. Zero intermediate frequency structure is employed to maintain timing accuracy and dynamic performance, and the received signal can also be used to measure tip clearance. The timing method uses the rising and falling edges of the signal and an auto-gain control circuit to reduce the effect of tip clearance change. To validate the accuracy of the system, it is compared experimentally with a fiber optic tip timing system. The results show that the microwave tip timing system achieves good accuracy.

48 CFR 52.247-52 - Clearance and Documentation Requirements-Shipments to DOD Air or Water Terminal Transshipment...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Clearance and Documentation Requirements-Shipments to DOD Air or Water Terminal Transshipment Points. 52.247-52 Section 52.247-52 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES...

Dynamic clearance measure to evaluate locomotor and perceptuo-motor strategies used for obstacle circumvention in a virtual environment.

PubMed

Darekar, Anuja; Lamontagne, Anouk; Fung, Joyce

2015-04-01

Circumvention around an obstacle entails a dynamic interaction with the obstacle to maintain a safe clearance. We used a novel mathematical interpolation method based on the modified Shepard's method of Inverse Distance Weighting to compute dynamic clearance that reflected this interaction as well as minimal clearance. This proof-of-principle study included seven young healthy, four post-stroke and four healthy age-matched individuals. A virtual environment designed to assess obstacle circumvention was used to administer a locomotor (walking) and a perceptuo-motor (navigation with a joystick) task. In both tasks, participants were asked to navigate towards a target while avoiding collision with a moving obstacle that approached from either head-on, or 30° left or right. Among young individuals, dynamic clearance did not differ significantly between obstacle approach directions in both tasks. Post-stroke individuals maintained larger and smaller dynamic clearance during the locomotor and the perceptuo-motor task respectively as compared to age-matched controls. Dynamic clearance was larger than minimal distance from the obstacle irrespective of the group, task and obstacle approach direction. Also, in contrast to minimal distance, dynamic clearance can respond differently to different avoidance behaviors. Such a measure can be beneficial in contrasting obstacle avoidance behaviors in different populations with mobility problems. Copyright © 2015 Elsevier B.V. All rights reserved.

Rectenna System Design. [energy conversion solar power satellites

NASA Technical Reports Server (NTRS)

Woodcock, G. R.; Andryczyk, R. W.

1980-01-01

The fundamental processes involved in the operation of the rectenna system designed for the solar power satellite system are described. The basic design choices are presented based on the desired microwave rf field concentration prior to rectification and based on the ground clearance requirements for the rectenna structure. A nonconcentrating inclined planar panel with a 2 meter minimum clearance configuration is selected as a representative of the typical rectenna.

Impairment of the glymphatic system after diabetes.

PubMed

Jiang, Quan; Zhang, Li; Ding, Guangliang; Davoodi-Bojd, Esmaeil; Li, Qingjiang; Li, Lian; Sadry, Neema; Nedergaard, Maiken; Chopp, Michael; Zhang, Zhenggang

2017-04-01

The glymphatic system has recently been shown to clear brain extracellular solutes and abnormalities in glymphatic clearance system may contribute to both initiation and progression of neurological diseases. Despite that diabetes is known as a risk factor for vascular diseases, little is known how diabetes affects the glymphatic system. The current study is the first investigation of the effect of diabetes on the glymphatic system and the link between alteration of glymphatic clearance and cognitive impairment in Type-2 diabetes mellitus rats. MRI analysis revealed that clearance of cerebrospinal fluid contrast agent Gd-DTPA from the interstitial space was slowed by a factor of three in the hippocampus of Type-2 diabetes mellitus rats compared to the non-DM rats and confirmed by florescence imaging analysis. Cognitive deficits detected by behavioral tests were highly and inversely correlated to the retention of Gd-DTPA contrast and fluorescent tracer in the hippocampus of Type-2 diabetes mellitus rats. Type-2 diabetes mellitus suppresses clearance of interstitial fluid in the hippocampus and hypothalamus, suggesting that an impairment of the glymphatic system contributes to Type-2 diabetes mellitus-induced cognitive deficits. Whole brain MRI provides a sensitive, non-invasive tool to quantitatively evaluate cerebrospinal fluid and interstitial fluid exchange in Type-2 diabetes mellitus and possibly in other neurological disorders, with potential clinical application.

Impairment of the glymphatic system after diabetes

PubMed Central

Zhang, Li; Ding, Guangliang; Davoodi-Bojd, Esmaeil; Li, Qingjiang; Li, Lian; Sadry, Neema; Nedergaard, Maiken; Chopp, Michael; Zhang, Zhenggang

2016-01-01

The glymphatic system has recently been shown to clear brain extracellular solutes and abnormalities in glymphatic clearance system may contribute to both initiation and progression of neurological diseases. Despite that diabetes is known as a risk factor for vascular diseases, little is known how diabetes affects the glymphatic system. The current study is the first investigation of the effect of diabetes on the glymphatic system and the link between alteration of glymphatic clearance and cognitive impairment in Type-2 diabetes mellitus rats. MRI analysis revealed that clearance of cerebrospinal fluid contrast agent Gd-DTPA from the interstitial space was slowed by a factor of three in the hippocampus of Type-2 diabetes mellitus rats compared to the non-DM rats and confirmed by florescence imaging analysis. Cognitive deficits detected by behavioral tests were highly and inversely correlated to the retention of Gd-DTPA contrast and fluorescent tracer in the hippocampus of Type-2 diabetes mellitus rats. Type-2 diabetes mellitus suppresses clearance of interstitial fluid in the hippocampus and hypothalamus, suggesting that an impairment of the glymphatic system contributes to Type-2 diabetes mellitus-induced cognitive deficits. Whole brain MRI provides a sensitive, non-invasive tool to quantitatively evaluate cerebrospinal fluid and interstitial fluid exchange in Type-2 diabetes mellitus and possibly in other neurological disorders, with potential clinical application. PMID:27306755

NASA aviation safety reporting system

NASA Technical Reports Server (NTRS)

1978-01-01

The study deals with 165 inadvertent operations on or into inappropriate portions of the aircraft areas at controlled airports. Pilot-initiated and controller-initiated incursions are described and discussed. It was found that a majority of the pilot-initiated occurrences involved operation without a clearance; controller-initiated occurrences usually involved failure to maintain assured separation. The factors associated with these occurrences are analyzed. It appears that a major problem in these occurrences is inadequate coordination among the various system participants. Reasons for this, and some possible solutions to various aspects of the problem, are discussed. A sample of reports from pilots and controllers is presented. These relate to undesired occurrences in air transport, general aviation, and air traffic control operations; to ATC coordination problems; and to a recurrent problem in ASRS reports, parachuting operations. A sample of alert bulletins and responses to them is presented.

Association of KIR genotypes and haplotypes with susceptibility to chronic hepatitis B virus infection in Chinese Han population.

PubMed

Lu, Zhiming; Zhang, Bingchang; Chen, Shijun; Gai, Zhongtao; Feng, Zhaolei; Liu, Xiangdong; Liu, Yiqing; Wen, Xin; Li, Li; Jiao, Yulian; Ma, Chunyan; Shao, Song; Cui, Xiangfa; Chen, Guojian; Li, Jianfeng; Zhao, Yueran

2008-12-01

Killer immunoglobulin-like receptor (KIR) genes can regulate the activation of NK and T cells upon interaction with HLA class I molecules. Hepatitis B virus (HBV) infection has been regarded as a multi-factorial disorder disease. Previous studies revealed that KIRs were involved in HCV and HIV infection or clearance. The aim of this study was to explore the possibility of the inheritance of KIR genotypes and haplotypes as a candidate for susceptibility to persistent HBV infection or HBV clearance. The sequence specific primer polymerase chain reaction (SSP-PCR) was employed to identify the KIR genes and pseudogenes in 150 chronic hepatitis B (CHB) patients, 251 spontaneously recovered (SR) controls, and 412 healthy controls. The frequencies of genotype G, M, FZ1 increased in CHB patients compared with healthy control subjects. The frequency of genotype AH was higher in SR controls than that in both CHB patients and healthy controls. The carriage frequencies of genotype G and AH were higher; while, the frequencies of AF and AJ were lower in SR controls than those in healthy control subjects. The frequency of A haplotype was lower, whereas, the frequency of B haplotype was higher in CHB patients and SR controls than those in healthy controls. In healthy controls, haplotype 4 was found lower compared with that in CHB patients and SR controls and the frequency of haplotype 5 was higher in SR controls than that in other two groups. Based on these findings, it seems that the genotypes M and FZ1 are HBV susceptive genotypes; AH, on the other hand, may be protective genotypes that facilitate the clearance of HBV. It appears that the haplotype 4 is HBV susceptive haplotype, whereas, haplotype 5 may be the protective haplotype that facilitates the clearance of HBV.

Post-secretory fate of host defence components in mucus.

PubMed

Salathe, Matthias; Forteza, Rosanna; Conner, Gregory E

2002-01-01

Airway mucus is a complex mixture of secretory products that provide a multifaceted defence against infection. Among many antimicrobial substances, mucus contains a peroxidase identical to milk lactoperoxidase (LPO) that is produced by goblet cells and submucosal glands. Airway secretions contain the substrates for LPO, namely thiocyanate and hydrogen peroxide, at concentrations sufficient for production of the biocidal compound hypothiocyanite, a fact confirmed by us in vitro. In vivo, inhibition of airway LPO in sheep significantly inhibits bacterial clearance, suggesting that the LPO system is a major contributor to host defences. Since secretory products including LPO are believed to be steadily removed by mucociliary clearance, their amount and availability on the surface is thought to be controlled solely by secretion. In contrast to this paradigm, new data suggest that LPO and other substances are retained at the ciliary border of the airway epithelium by binding to surface-associated hyaluronan, thereby providing an apical, fully active enzyme pool. Thus, hyaluronan, secreted from submucosal gland cells, plays a previously unrecognized pivotal role in mucosal host defence by retaining LPO and possibly other substances important for first line host defence at the apical surface 'ready for use' and protected from ciliary clearance.

Visual Confirmation of Voice Takeoff Clearance (VICON) Alternative Study

DOT National Transportation Integrated Search

1980-05-01

This report presents the results of a program undertaken to study potential alternatives to the VICON (Visual Confirmation of Voice Takeoff Clearance) System which has undergone operational field tests at Bradley International Airport, Windsor Locks,...

Robust Optimization Design for Turbine Blade-Tip Radial Running Clearance using Hierarchically Response Surface Method

NASA Astrophysics Data System (ADS)

Zhiying, Chen; Ping, Zhou

2017-11-01

Considering the robust optimization computational precision and efficiency for complex mechanical assembly relationship like turbine blade-tip radial running clearance, a hierarchically response surface robust optimization algorithm is proposed. The distribute collaborative response surface method is used to generate assembly system level approximation model of overall parameters and blade-tip clearance, and then a set samples of design parameters and objective response mean and/or standard deviation is generated by using system approximation model and design of experiment method. Finally, a new response surface approximation model is constructed by using those samples, and this approximation model is used for robust optimization process. The analyses results demonstrate the proposed method can dramatic reduce the computational cost and ensure the computational precision. The presented research offers an effective way for the robust optimization design of turbine blade-tip radial running clearance.

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Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-30

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Milk fat globule E-8 and interleukin 17 in systemic lupus erythematosus: partners in crime?

PubMed Central

Elgengehy, Fatema; Niazy, Marwa; Ghoneim, Shada

2016-01-01

Objectives Systemic lupus erythematosus (SLE) is a multi-factorial, autoimmune disease with a wide array of manifestations. The pro-inflammatory cytokine interleukin (IL)-17 has been implicated in the inflammatory response and tissue damage in SLE; however, its correlation with disease activity is still questionable. Meanwhile, efficient clearance of apoptotic cells is required for immune tolerance. An abnormally low or high level of milk fat globule (MFG-E8) can result in impaired apoptotic cell clearance and the subsequent autoimmune response. In this study, we endeavoured to compare the levels of MFG-E8 and IL-17 in SLE patients and healthy controls and to reveal the alleged association of these levels with SLE disease activity. Material and methods Serum samples from 57 SLE patients and 30 healthy control subjects were examined for quantitation of MFG-E8 and IL-17 levels using ELISA. Systemic lupus erythematosus disease activity was calculated using the SLE Disease Activity Index (SLEDAI). Clinical manifestations and laboratory findings of the patients were also recorded. Results We report that serum MFG-E8 levels were significantly elevated in the sera of SLE patients compared to healthy controls (p-value = 0.019). Likewise, IL-17 levels were higher in SLE patients (p-value < 0.001). A positive correlation was revealed between MFG-E8 level and proteinuria. Surprisingly, there was a poor correlation between disease activity and the levels of either IL-17 or MFG-E8. Conclusions Although serum MFG-E8 and IL-17 levels were higher in SLE patients than in normal controls, our results indicate that they cannot accurately reflect the disease activity. Meanwhile, further studies are needed to assess MFG-E8 and IL-17 as potential therapeutic targets in SLE patients. PMID:27407263

Impairment of aminopyrine clearance in aspirin-damaged canine gastric mucosa

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

Miller, T.A.; Henagan, J.M.; Loy, T.M.

Using an in vivo canine chambered stomach preparation, the clearance of (/sup 14/C)aminopyrine across mucosa when intravenously infused and the back-diffusion of this substance from gastric lumen to mucosa when topically applied to gastric epithelium were evaluated in aspirin-damaged gastric epithelium. In mucosa damaged by either 20 mM or 40 mM aspirin, the recovery of (/sup 14/C)aminopyrine, when topically mixed with acid (pH . 1.1) perfusate solution, was not significantly different from nondamaged control mucosa. In addition, the degree of ''trapping'' of this substance from back-diffusion was not different in damaged mucosa from that observed in nondamaged epithelium. In contrast,more » when (/sup 14/C)aminopyrine was intravenously infused, its clearance was significantly impaired in aspirin-damaged mucosa when compared with control studies, as evidenced by the increased ''trapping'' of this substance in injured epithelium. These findings indicate that movement of aminopyrine from plasma to gastric lumen is impaired in damaged epithelium, making the aminopyrine clearance technique an unreliable method to accurately measure absolute gastric blood flow in this experimental setting.« less

Mechanism of the stationary canalicular excretion of tributylmethyl ammonium in rats with a CCl4-induced acute hepatic injury.

PubMed

Choi, Min-Koo; Song, Im-Sook; Park, So-Ra; Hong, Soon-Sun; Kim, Dae-Duk; Chung, Suk-Jae; Shim, Chang-Koo

2005-02-01

The in vivo canalicular excretion clearance of tributylmethyl ammonium (TBuMA), a P-glycoprotein (P-gp) substrate, was previously reported to be unaffected by the induction of an experimental hepatic injury (EHI) by CCl(4) despite the increased expression of P-gp in the EHI liver. The objective of this study, therefore, was to elucidate the mechanism for the unchanged canalicular excretion clearance of TBuMA in EHI rats. TBuMA uptake was increased in cLPM vesicles from EHI rats compared with that from control rats. The total bile salt concentration in EHI liver was significantly reduced compared with that in a control liver. Because, in our previous studies, the uptake of TBuMA by cLPM vesicles was found to be significantly enhanced in the presence of bile salts, the reduction in bile salt levels in the EHI liver may be related to the unaltered TBuMA clearance. Despite the fact that the uptake of TBuMA by cLPM vesicles was increased by the addition of an EHI liver extract, the extent of the increase was comparatively less compared to the addition of a control liver extract. The in vivo excretion clearance of TBuMA was increased in a taurodeoxycholate dose-dependent manner in EHI rats. These observations suggest, therefore, that despite the induction of P-gp expression by the EHI, the in vivo canalicular excretion clearance of TBuMA remains unaltered as the result of an offset by reduced levels of bile salt(s). Copyright 2004 Wiley-Liss, Inc.

Work experience mitigated age-related differences in balance and mobility during surface accommodation.

PubMed

Rietdyk, Shirley; McGlothlin, James D; Knezovich, Mark J

2005-12-01

Locomotor behavior at the roofing worksite is challenged by factors such as sloped surfaces, wind gusts and handling loads. Chronic exposure to this environment may result in enhanced locomotor strategies that are resistant to aging effects. The purpose of this study was to determine if roofers demonstrated enhanced locomotor strategies and if the strategies were maintained with age. The gait of ten younger roofers (mean age 27.2 years), eight older roofers (55.4 years), ten younger controls (25.4 years) and nine older controls (57.6 years) was examined during level gait and stepping up onto a wooden surface (0.15m high). Subjects either carried no load, an empty box or the same box loaded to the equivalent of 5% body mass. Work by age interactions were observed for toe clearance, step width, net angular momentum of the head, arms and trunk segment and gait speed (P<0.0001). Younger roofers demonstrated the greatest toe clearance; older roofers had a smaller lead clearance but decreased variability. Older control groups had the greatest risk of tripping due to low lead toe clearance and high variability, and were least likely to recover if they did trip due to faster gait speed and increased net angular momentum. Work experience resulted in enhanced changes in lead toe clearance and mitigated age-related changes in step width and net angular momentum. Challenging environments show promise for maintaining balance skills in older adults; however care should be taken when introducing inexperienced older adults to a challenging environment.

Reliability of ⁵¹Cr-EDTA plasma and urinary clearance as a measure of residual renal function in dialysis patients.

PubMed

Kjaergaard, Krista D; Jensen, Jens D; Jespersen, Bente; Rehling, Michael

2011-12-01

In dialysis patients, longer survival is associated with a higher residual renal function. Randomized controlled trials are conducted to clarify how residual renal function can be preserved. However, existing methods for measuring residual renal function are uncertain and there is a need for establishing a standard for measurements of glomerular filtration rate (GFR) in dialysis patients. ⁵¹Cr-EDTA clearances in plasma, urine, and dialysate were evaluated in a sample of 12 hemodialysis and 12 peritoneal dialysis patients. The patients' condition was generally stable, and all patients were investigated twice within 4-10 days. Plasma clearances of ⁵¹Cr-EDTA for all patients ranged between 2.1 and 30.8 mL/min/1.73 m², whereas urinary ⁵¹Cr-EDTA clearances ranged from 0.7-20.0 mL/min/1.73 m². This difference was statistically significant (p < 0.001). Week-to-week reproducibility expressed as coefficients of variation were below or equal to 10% for plasma clearances and 13% for urinary clearances in hemodialysis patients and 14% in peritoneal dialysis patients. This study demonstrated a difference between ⁵¹Cr-EDTA plasma and urinary clearances in dialysis patients. Plasma clearance of ⁵¹Cr-EDTA had the best reproducibility. For repeated measurements as in clinical prospective trials, we recommend ⁵¹Cr-EDTA plasma clearance based on blood sampling at 5 + 24 hours with subtraction of ⁵¹Cr-EDTA dialysate clearance in peritoneal dialysis patients. Further studies are needed to corroborate our findings.

Scrambled Eggs: Apoptotic Cell Clearance by Non-Professional Phagocytes in the Drosophila Ovary.

PubMed

Serizier, Sandy B; McCall, Kimberly

2017-01-01

For half of a century, it has been known that non-professional phagocytes, such as fibroblasts, endothelial, and epithelial cells, are capable of efferocytosis (engulfment of apoptotic cells). Non-professional phagocytes differ from professional phagocytes in the range and efficiency of engulfment. Much of the recognition and underlying signaling machinery between non-professional and professional phagocytes is the same, but it is not known how the engulfment capacity of non-professional phagocytes is controlled. Moreover, the signaling networks involved in cell corpse recognition, engulfment, and phagosome maturation are only partially understood. The Drosophila ovary provides an excellent system to investigate the regulation of phagocytic activity by epithelial cells, a major class of non-professional phagocytes. During Drosophila oogenesis, mid-stage egg chambers undergo apoptosis of the germline in response to nutrient deprivation. Epithelial follicle cells then undergo major cell shape changes and concomitantly engulf the germline material. Our previous work has established that Draper and the integrin α-PS3/β-PS heterodimer are required in follicle cells for germline cell clearance. In addition, we have characterized phagosome maturation pathways, and found that the JNK pathway amplifies the engulfment response. In this review, we discuss recent advances on the interplay between engulfment pathways in the follicular epithelium for cell clearance in the Drosophila ovary. We also provide a comparison to apoptotic cell clearance mechanisms in C. elegans and mammals, illustrating strong conservation of efferocytosis mechanisms by non-professional phagocytes.

Scrambled Eggs: Apoptotic Cell Clearance by Non-Professional Phagocytes in the Drosophila Ovary

PubMed Central

Serizier, Sandy B.; McCall, Kimberly

2017-01-01

For half of a century, it has been known that non-professional phagocytes, such as fibroblasts, endothelial, and epithelial cells, are capable of efferocytosis (engulfment of apoptotic cells). Non-professional phagocytes differ from professional phagocytes in the range and efficiency of engulfment. Much of the recognition and underlying signaling machinery between non-professional and professional phagocytes is the same, but it is not known how the engulfment capacity of non-professional phagocytes is controlled. Moreover, the signaling networks involved in cell corpse recognition, engulfment, and phagosome maturation are only partially understood. The Drosophila ovary provides an excellent system to investigate the regulation of phagocytic activity by epithelial cells, a major class of non-professional phagocytes. During Drosophila oogenesis, mid-stage egg chambers undergo apoptosis of the germline in response to nutrient deprivation. Epithelial follicle cells then undergo major cell shape changes and concomitantly engulf the germline material. Our previous work has established that Draper and the integrin α-PS3/β-PS heterodimer are required in follicle cells for germline cell clearance. In addition, we have characterized phagosome maturation pathways, and found that the JNK pathway amplifies the engulfment response. In this review, we discuss recent advances on the interplay between engulfment pathways in the follicular epithelium for cell clearance in the Drosophila ovary. We also provide a comparison to apoptotic cell clearance mechanisms in C. elegans and mammals, illustrating strong conservation of efferocytosis mechanisms by non-professional phagocytes. PMID:29238344

Role of Chemokines and Trafficking of Immune Cells in Parasitic Infections

PubMed Central

McGovern, Kathryn E.; Wilson, Emma H.

2014-01-01

Parasites are diverse eukaryotic pathogens that can have complex life cycles. Their clearance, or control within a mammalian host requires the coordinated effort of the immune system. The cell types recruited to areas of infection can combat the disease, promote parasite replication and survival, or contribute to disease pathology. Location and timing of cell recruitment can be crucial. In this review, we explore the role chemokines play in orchestrating and balancing the immune response to achieve optimal control of parasite replication without promoting pathology. PMID:25383073

The Role of Radial Clearance on the Performance of Foil Air Bearings

NASA Technical Reports Server (NTRS)

Radil, Kevin; Howard, Samuel; Dykas, Brian

2002-01-01

Load capacity tests were conducted to determine how radial clearance variations affect the load capacity coefficient of foil air bearings. Two Generation III foil air bearings with the same design but possessing different initial radial clearances were tested at room temperature against an as-ground PS304 coated journal operating at 30,000 rpm. Increases in radial clearance were accomplished by reducing the journal's outside diameter via an in-place grinding system. From each load capacity test the bearing load capacity coefficient was calculated from the rule-of-thumb (ROT) model developed for foil air bearings. The test results indicate that, in terms of the load capacity coefficient, radial clearance has a direct impact on the performance of the foil air bearing. Each test bearing exhibited an optimum radial clearance that resulted in a maximum load capacity coefficient. Relative to this optimum value are two separate operating regimes that are governed by different modes of failure. Bearings operating with radial clearances less than the optimum exhibit load capacity coefficients that are a strong function of radial clearance and are prone to a thermal runaway failure mechanism and bearing seizure. Conversely, a bearing operating with a radial clearance twice the optimum suffered only a 20 percent decline in its maximum load capacity coefficient and did not experience any thermal management problems. However, it is unknown to what degree these changes in radial clearance had on other performance parameters, such as the stiffness and damping properties of the bearings.

HDAC6 is a Regulator of CTL Function through Control of Lytic Granule Dynamics

PubMed Central

Nunez-Andrade, Norman

2016-01-01

Viral infections involve specific stress exposure that can influence the quality and average lifespan of an organism. The immune system acts through virus clearance from the organism. Many aspects of immune cells accounting for this response are still under study. Here, we review recent aspects of the molecular mechanisms involved in the delivery of the lethal hit by Cytotoxic T lymphocytes. PMID:27595053

The Effects of Vaccination and Immunity on Bacterial Infection Dynamics In Vivo

PubMed Central

Coward, Chris; Restif, Olivier; Dybowski, Richard; Grant, Andrew J.; Maskell, Duncan J.; Mastroeni, Pietro

2014-01-01

Salmonella enterica infections are a significant global health issue, and development of vaccines against these bacteria requires an improved understanding of how vaccination affects the growth and spread of the bacteria within the host. We have combined in vivo tracking of molecularly tagged bacterial subpopulations with mathematical modelling to gain a novel insight into how different classes of vaccines and branches of the immune response protect against secondary Salmonella enterica infections of the mouse. We have found that a live Salmonella vaccine significantly reduced bacteraemia during a secondary challenge and restrained inter-organ spread of the bacteria in the systemic organs. Further, fitting mechanistic models to the data indicated that live vaccine immunisation enhanced both the bacterial killing in the very early stages of the infection and bacteriostatic control over the first day post-challenge. T-cell immunity induced by this vaccine is not necessary for the enhanced bacteriostasis but is required for subsequent bactericidal clearance of Salmonella in the blood and tissues. Conversely, a non-living vaccine while able to enhance initial blood clearance and killing of virulent secondary challenge bacteria, was unable to alter the subsequent bacterial growth rate in the systemic organs, did not prevent the resurgence of extensive bacteraemia and failed to control the spread of the bacteria in the body. PMID:25233077

Time-of-Flight Tip-Clearance Measurements

NASA Technical Reports Server (NTRS)

Dhadwal, H. S.; Kurkov, A. P.; Janetzke, D. C.

1999-01-01

In this paper a time-of-flight probe system incorporating the two integrated fiber optic probes which are tilted equally relative to the probe holder centerline, is applied for the first time to measure the tip clearance of an advanced fan prototype. Tip clearance is largely independent of the signal amplitude and it relies on timing measurement. This work exposes optical effects associated with the fan blade stagger angle that were absent during the original spin-rig experiment on the zero stagger rotor. Individual blade tip clearances were measured with accuracy of +/- 127-mm (+/- 0.005-in). Probe features are discussed and improvements to the design are suggested.

Emergency Department Medical Clearance of Patients with Psychiatric or Behavioral Emergencies, Part 1.

PubMed

Tucci, Veronica Theresa; Moukaddam, Nidal; Alam, Al; Rachal, James

2017-09-01

Patients presenting to the emergency department with mental illness or behavioral complaints merit workup for underlying physical conditions that can trigger, mimic, or worsen psychiatric symptoms. However, interdisciplinary consensus on medical clearance is lacking, leading to wide variations in quality of care and, quite often, poor medical care. Psychiatry and emergency medicine specialty guidelines support a tailored, customized approach. This article summarizes best-practice approaches to the medical clearance of patients with psychiatric illness, tips on history taking, system reviews, clinical or physical examination, and common pitfalls in the medical clearance process. Copyright © 2017 Elsevier Inc. All rights reserved.

What you see is what you step: the horizontal-vertical illusion increases toe clearance in older adults during stair ascent.

PubMed

Foster, Richard J; Whitaker, David; Scally, Andrew J; Buckley, John G; Elliott, David B

2015-05-01

Falls on stairs are a significant cause of morbidity and mortality in elderly people. A simple safety strategy to avoid tripping on stairs is increasing foot clearance. We determined whether a horizontal-vertical illusion superimposed onto stairs to create an illusory perceived increase in stair-riser height would increase stair ascent foot clearance in older participants. Preliminary experiments determined the optimum parameters for the horizontal-vertical illusion. Fourteen older adults (mean age ± 1 SD, 68.5 ± 7.4 years) ascended a three-step staircase with the optimized version of the horizontal-vertical illusion (spatial frequency: 12 cycles per stair riser) positioned either on the bottom or top stair only, or on the bottom and top stair simultaneously. These were compared to a control condition, which had a plain stair riser with edge highlighters positioned flush with each stair-tread edge. Foot clearance and measures of postural stability were compared across conditions. The optimized illusion on the bottom and top stair led to a significant increase in foot clearance over the respective stair edge, compared to the control condition. There were no significant decreases in postural stability. An optimized horizontal-vertical visual illusion led to significant increases in foot clearance in older adults when ascending a staircase, but the effects did not destabilize their postural stability. Inclusion of the horizontal-vertical illusion on raised surfaces (e.g., curbs) or the bottom and top stairs of staircases could improve stair ascent safety in older adults.

Sequential assessment of pulmonary epithelial diethylene triamine penta-acetate clearance and intrapulmonary transferrin accumulation during Escherichia coli peritonitis

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

Ishizaka, A.; Stephens, K.E.; Segall, G.M.

1990-03-01

The individual roles of pulmonary capillary endothelial and alveolar epithelial permeability in the pathogenesis of the adult respiratory distress syndrome (ARDS) are unclear. We developed a method for the sequential assessment of pulmonary macromolecule accumulation and small solute clearance in vivo using a gamma camera. We measured the exponential clearance coefficient of 111In-labeled diethylene triamine penta-acetate (111In-DTPA) to assess airway clearance of small solutes. We also calculated the exponential equilibration coefficient of 111In-labeled transferrin (111In-TF) to assess intrapulmonary accumulation of transferrin. We determined these parameters in guinea pigs with Escherichia coli peritonitis and compared them with a saline-treated control group,more » oleic-acid-treated groups, and a group treated with low molecular weight dextran Ringer solution. The pulmonary DTPA clearance and the intrapulmonary transferrin accumulation were significantly increased in the peritonitis group (29.4 +/- 8.2 x 10(-3) min-1, p less than 0.02, and 15.1 +/- 3.1 x 10(-3) min-1, p less than 0.02) when compared with the control group (3.1 +/- 0.8 x 10(-3) min-1 and 4.5 +/- 0.5 x 10(-3) min-1). These changes developed within 5.5 h of the initial insult. Neither increased extravascular lung water nor elevated pulmonary artery and left atrial pressures were detected in the peritonitis group. The low molecular weight dextran Ringer group did not show a significant increase in the pulmonary DTPA clearance and the intrapulmonary transferrin accumulation.« less

A biomimetic vision-based hovercraft accounts for bees' complex behaviour in various corridors.

PubMed

Roubieu, Frédéric L; Serres, Julien R; Colonnier, Fabien; Franceschini, Nicolas; Viollet, Stéphane; Ruffier, Franck

2014-09-01

Here we present the first systematic comparison between the visual guidance behaviour of a biomimetic robot and those of honeybees flying in similar environments. We built a miniature hovercraft which can travel safely along corridors with various configurations. For the first time, we implemented on a real physical robot the 'lateral optic flow regulation autopilot', which we previously studied computer simulations. This autopilot inspired by the results of experiments on various species of hymenoptera consists of two intertwined feedback loops, the speed and lateral control loops, each of which has its own optic flow (OF) set-point. A heading-lock system makes the robot move straight ahead as fast as 69 cm s(-1) with a clearance from one wall as small as 31 cm, giving an unusually high translational OF value (125° s(-1)). Our biomimetic robot was found to navigate safely along straight, tapered and bent corridors, and to react appropriately to perturbations such as the lack of texture on one wall, the presence of a tapering or non-stationary section of the corridor and even a sloping terrain equivalent to a wind disturbance. The front end of the visual system consists of only two local motion sensors (LMS), one on each side. This minimalistic visual system measuring the lateral OF suffices to control both the robot's forward speed and its clearance from the walls without ever measuring any speeds or distances. We added two additional LMSs oriented at +/-45° to improve the robot's performances in stiffly tapered corridors. The simple control system accounts for worker bees' ability to navigate safely in six challenging environments: straight corridors, single walls, tapered corridors, straight corridors with part of one wall moving or missing, as well as in the presence of wind.

Impulsive response of an automatic transmission system with multiple clearances: Formulation, simulation and experiment

NASA Astrophysics Data System (ADS)

Crowther, Ashley R.; Singh, Rajendra; Zhang, Nong; Chapman, Chris

2007-10-01

Impulsive responses in geared systems with multiple clearances are studied when the mean torque excitation and system load change abruptly, with application to a vehicle driveline with an automatic transmission. First, torsional lumped-mass models of the planetary and differential gear sets are formulated using matrix elements. The model is then reduced to address tractable nonlinear problems while successfully retaining the main modes of interest. Second, numerical simulations for the nonlinear model are performed for transient conditions and a typical driving situation that induces an impulsive behaviour simulated. However, initial conditions and excitation and load profiles have to be carefully defined before the model can be numerically solved. It is shown that the impacts within the planetary or differential gears may occur under combinations of engine, braking and vehicle load transients. Our analysis shows that the shaping of the engine transient by the torque converter before reaching the clearance locations is more critical. Third, a free vibration experiment is developed for an analogous driveline with multiple clearances and three experiments that excite different response regimes have been carried out. Good correlations validate the proposed methodology.

Steady-State Dynamic Behavior of a Flexible Rotor With Auxiliary Support From a Clearance Bearing

NASA Technical Reports Server (NTRS)

Xie, Huajun; Flowers, George T.; Feng, Li; Lawrence, Charles T.

1996-01-01

This paper investigates the steady-state responses of a rotor system supported by auxiliary bearings in which there is a clearance between the rotor and the inner race of the bearing. A simulation model based upon the rotor of a production jet engine is developed and its steady-state behavior is explored over a wide range of operating conditions for various parametric configurations. Specifically, the influence of rotor imbalance, clearance, support stiffness and damping is studied. Bifurcation diagrams are used as a tool to examine the dynamic behavior of this system as a function of the afore mentioned parameters. The harmonic balance method is also employed for synchronous response cases. The observed dynamical responses is discussed and some insights into the behavior of such systems are presented.

B747/JT9D flight loads and their effect on engine running clearances and performance deterioration; BCAC NAIL/P and WA JT9D engine diagnostics programs

NASA Technical Reports Server (NTRS)

Olsson, W. J.; Martin, R. L.

1982-01-01

Flight loads on the 747 propulsion system and resulting JT9D blade to outer airseal running clearances during representative acceptance flight and revenue flight sequences were measured. The resulting rub induced clearance changes, and engine performance changes were then analyzed to validate and refine the JT9D-7A short term performance deterioration model.

Effects of lighting illuminance levels on stair negotiation performance in individuals with visual impairment.

PubMed

Shaheen, Aliah F; Sourlas, Alexandros; Horton, Khim; McLean, Christopher; Ewins, David; Gould, David; Ghoussayni, Salim

2018-04-01

Stair-related falls of older people cause a substantial financial and social burden. Deterioration of the visual system amongst other factors put older people at a high risk of falling. Improved lighting is often recommended. The aim of this study was to investigate the effect of lighting illuminance on stair negotiation performance in older individuals with visual impairment. Eleven participants aged 60 or over with a vision of 6/18 or worse ascended and descended a staircase under: 50 lx, 100 lx, 200 lx, 300 lx and distributed 200 lx lighting. A motion capture system was used to measure movements of the lower limb. Clearance, clearance variability, temporal and spatial parameters and joint/segment kinematics were computed. There was no effect on clearance or clearance variability. Participants had lower speed, cadence, increased cycle time and stance time in the 50 lx compared to 300 lx and distributed 200 lx lighting in descent. The minimum hip angle in ascent was increased in the 200 lx lighting. Clearance was found to be moderately correlated with balance scores. Individuals with visual impairment adopt precautionary gait in dim lighting conditions. This does not always result in improvements in the parameters associated with risk of falling (e.g. clearance). Copyright © 2018 Elsevier Ltd. All rights reserved.

Estimation of end point foot clearance points from inertial sensor data.

PubMed

Santhiranayagam, Braveena K; Lai, Daniel T H; Begg, Rezaul K; Palaniswami, Marimuthu

2011-01-01

Foot clearance parameters provide useful insight into tripping risks during walking. This paper proposes a technique for the estimate of key foot clearance parameters using inertial sensor (accelerometers and gyroscopes) data. Fifteen features were extracted from raw inertial sensor measurements, and a regression model was used to estimate two key foot clearance parameters: First maximum vertical clearance (m x 1) after toe-off and the Minimum Toe Clearance (MTC) of the swing foot. Comparisons are made against measurements obtained using an optoelectronic motion capture system (Optotrak), at 4 different walking speeds. General Regression Neural Networks (GRNN) were used to estimate the desired parameters from the sensor features. Eight subjects foot clearance data were examined and a Leave-one-subject-out (LOSO) method was used to select the best model. The best average Root Mean Square Errors (RMSE) across all subjects obtained using all sensor features at the maximum speed for m x 1 was 5.32 mm and for MTC was 4.04 mm. Further application of a hill-climbing feature selection technique resulted in 0.54-21.93% improvement in RMSE and required fewer input features. The results demonstrated that using raw inertial sensor data with regression models and feature selection could accurately estimate key foot clearance parameters.

Enzyme-inducing anticonvulsants increase plasma clearance of dexmedetomidine: a pharmacokinetic and pharmacodynamic study.

PubMed

Flexman, Alana M; Wong, Harvey; Riggs, K Wayne; Shih, Tina; Garcia, Paul A; Vacas, Susana; Talke, Pekka O

2014-05-01

Dexmedetomidine is useful during mapping of epileptic foci as it facilitates electrocorticography unlike most other anesthetic agents. Patients with seizure disorders taking enzyme-inducing anticonvulsants appear to be resistant to its sedative effects. The objective of the study was to compare the pharmacokinetic and pharmacodynamic profile of dexmedetomidine in healthy volunteers with volunteers with seizure disorders receiving enzyme-inducing anticonvulsant medications. Dexmedetomidine was administered using a step-wise, computer-controlled infusion to healthy volunteers (n = 8) and volunteers with seizure disorders (n = 8) taking phenytoin or carbamazapine. Sedation and dexmedetomidine plasma levels were assessed at baseline, during the infusion steps, and after discontinuation of the infusion. Sedation was assessed by using the Observer's Assessment of Alertness/Sedation Scale, Ramsay Sedation Scale, and Visual Analog Scale and processed electroencephalography (entropy) monitoring. Pharmacokinetic analysis was performed on both groups, and differences between groups were determined using the standard two-stage approach. A two-compartment model was fit to dexmedetomidine concentration-time data. Dexmedetomidine plasma clearance was 43% higher in the seizure group compared with the control group (42.7 vs. 29.9 l/h; P = 0.007). In contrast, distributional clearance and the volume of distribution of the central and peripheral compartments were similar between the groups. No difference in sedation was detected between the two groups during a controlled range of target plasma concentrations. This study demonstrates that subjects with seizure disorders taking enzyme-inducing anticonvulsant medications have an increased plasma clearance of dexmedetomidine as compared with healthy control subjects.

75 FR 67761 - Proposed Information Collection; OMB Control Number 1018-0095; Endangered and Threatened Wildlife...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-03

...: Send your comments on the IC to Hope Grey, Information Collection Clearance Officer, U.S. Fish and...); take in defense of human life; take related to defense of property (if authorized); or take in the form... to do so. Dated: October 28, 2010. Hope Grey, Information Collection Clearance Officer, Fish and...

5 CFR 1320.10 - Clearance of collections of information, other than those contained in proposed rules or in...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Clearance of collections of information, other than those contained in proposed rules or in current rules. 1320.10 Section 1320.10 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET OMB DIRECTIVES CONTROLLING PAPERWORK BURDENS ON THE PUBLIC § 1320...

A Probabilistic System Analysis of Intelligent Propulsion System Technologies

NASA Technical Reports Server (NTRS)

Tong, Michael T.

2007-01-01

NASA s Intelligent Propulsion System Technology (Propulsion 21) project focuses on developing adaptive technologies that will enable commercial gas turbine engines to produce fewer emissions and less noise while increasing reliability. It features adaptive technologies that have included active tip-clearance control for turbine and compressor, active combustion control, turbine aero-thermal and flow control, and enabling technologies such as sensors which are reliable at high operating temperatures and are minimally intrusive. A probabilistic system analysis is performed to evaluate the impact of these technologies on aircraft CO2 (directly proportional to fuel burn) and LTO (landing and takeoff) NO(x) reductions. A 300-passenger aircraft, with two 396-kN thrust (85,000-pound) engines is chosen for the study. The results show that NASA s Intelligent Propulsion System technologies have the potential to significantly reduce the CO2 and NO(x) emissions. The results are used to support informed decisionmaking on the development of the intelligent propulsion system technology portfolio for CO2 and NO(x) reductions.

Fluxgate Magnetometer system mounted on UAS system: First field test at Dominga IOCG deposit, Chile

NASA Astrophysics Data System (ADS)

Yanez, G. A.; Banchero, L.; Marco, A.; Figueroa, R.

2016-12-01

With the support of Fundacion Chile (FCH) grant, we developed an airborne magnetic system (GeoMagDrone GFDAS) mounted on a UAS octodrone platform (DJI, S1000), based on a low cost/light-weight fluxgate magnetometer (FGM-301) and a robust/light-weight data logger for position, temperature, radar altimeter and 3 magnetic components at 16 Hz recording. Fluxgate magnetometer is hanging from the UAS platform at a distance of 2.5m where the EM noise is reduced to less than 2 nT. The whole geophysical system, including batteries, weights 650 gr., with an autonomy of 2 hours. Magnetometer calibration includes the 9 coefficients of amplitude, offset, and orthogonality, and temperature correction. We test the system over the IOCG deposit of Dominga-Chile, a magnetite ore (40%) (a block of 2x3 km with NS lines separated every 50m and a clearance of 40m, the mineral deposit buried 50-100m from the surface, where a ground magnetic survey was conducted previously. Ground conditions includes relatively rough topography with slopes of 10-20%, and some windy days. We use the digital terrain model SRTM30 to define the drape flight shape Average flight performance includes a mean speed of 35-40 km/hour, and an UAS battery consumption of 18-12 minutes depending on the wind conditions. A good correspondence was found between plan deployment and survey results in terms of line direction/separation/clearance. Line path were flown with errors less than 5 meters, whereas clearance of 40m was kept depending on the amount of control points used. The comparison between ground survey and GeoMagDrone results show a perfect match (anomaly amplitude/shape and noise envelope), validating in this way the system developed. Main concern for the productive application of this technology in unmanned geophysical platforms is the battery performance and the quality of digital terrain models to follow the topography.

X-31 high angle of attack control system performance

NASA Technical Reports Server (NTRS)

Huber, Peter; Seamount, Patricia

1994-01-01

The design goals for the X-31 flight control system were: (1) level 1 handling qualities during post-stall maneuvering (30 to 70 degrees angle-of-attack); (2) thrust vectoring to enhance performance across the flight envelope; and (3) adequate pitch-down authority at high angle-of-attack. Additional performance goals are discussed. A description of the flight control system is presented, highlighting flight control system features in the pitch and roll axes and X-31 thrust vectoring characteristics. The high angle-of-attack envelope clearance approach will be described, including a brief explanation of analysis techniques and tools. Also, problems encountered during envelope expansion will be discussed. This presentation emphasizes control system solutions to problems encountered in envelope expansion. An essentially 'care free' envelope was cleared for the close-in-combat demonstrator phase. High angle-of-attack flying qualities maneuvers are currently being flown and evaluated. These results are compared with pilot opinions expressed during the close-in-combat program and with results obtained from the F-18 HARV for identical maneuvers. The status and preliminary results of these tests are discussed.

Supine lung clearance of Tc-99m DTPA and HMPAO aerosols

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

Chia-Hung Kao; Hui-Tzu Lin; Shu-Ling Yu

1995-07-01

The speed of Tc-99m DTPA/HMPAO radioaerosol clearance from the lungs that is represented as a slope from lungs to blood was measured in 23 male normal controls using commercial lung radioaerosol delivery units in the supine position in order to avoid the influences of gravity. The right lung was selected and three regions of interest were created for equal subdivisions of the upper, middle, and lower third. The results show that the clearance of Tc-99m DTPA/HMPAO aerosols in the upper lung is lowest. The difference between upper and lower lungs for Tc-99m DTPA/HMPAO aerosol clearances are significant. The clearance ofmore » Tc-99m DTPA aerosols was significantly faster than those of Tc-99m HMPAO in any region. The authors conclude that, although the effect of gravity disappears in the supine position in our study, the differences of aerosol clearance in different regions are still significant. Lipophilic Tc-99m HMPAO aerosols were slower than those of hydrophilic Tc-99m DTPA, which suggests there are at least two different mechanisms. 22 refs., 2 figs., 1 tab.« less

76 FR 17710 - Proposed Collection, Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-30

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28 CFR 524.74 - Activities clearance.

Code of Federal Regulations, 2013 CFR

2013-07-01

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28 CFR 524.74 - Activities clearance.

Code of Federal Regulations, 2010 CFR

2010-07-01

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28 CFR 524.74 - Activities clearance.

Code of Federal Regulations, 2014 CFR

2014-07-01

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28 CFR 524.74 - Activities clearance.

Code of Federal Regulations, 2012 CFR

2012-07-01

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Federal Register 2010, 2011, 2012, 2013, 2014

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Design highwater clearances for highway pavements appendix : volume II, appendix, August 2008.

DOT National Transportation Integrated Search

2008-08-01

High groundwater table exerts detrimental effects on the roadway base and the whole pavement. Base clearance guidelines have been developed to prevent water from entering the pavement system in order to reduce its detrimental effects. In these guidel...

Design highwater clearances for highway pavements : volume I, final report, August 2008.

DOT National Transportation Integrated Search

2008-08-01

High groundwater table exerts detrimental effects on the roadway base and the whole pavement. Base : clearance guidelines have been developed to prevent water from entering the pavement system in order to : reduce its detrimental effects. In these gu...

The effects of 2100-MHz radiofrequency radiation on nasal mucosa and mucociliary clearance in rats.

PubMed

Aydoğan, Filiz; Aydın, Emine; Koca, Gökhan; Özgür, Elçin; Atilla, Pergin; Tüzüner, Arzu; Demirci, Şule; Tomruk, Arin; Öztürk, Göknur Güler; Seyhan, Nesrin; Korkmaz, Meliha; Müftüoğlu, Sevda; Samim, Ethem Erdal

2015-07-01

Nasal mucociliary clearance has an important role in voiding the airways from inhaled foreign substances. This activity could be disturbed by environmental factors such as radiofrequency radiation. The aim of the present study was to investigate short-term and relatively long-term effects of 2100-MHz radiofrequency radiation emitted by a generator, simulating a 3G-mobile phone, on the nasal septal mucosa and mucociliary clearance in rats. Thirty Wistar albino rats were divided into 4 groups. There were 6 rats in Group A and Group B, which served as the control groups (10-day and 40-day groups, respectively). Groups C (10-day exposure) and D (40-day exposure) were both composed of 9 rats; they comprised the radiofrequency radiation exposure groups. The rats in groups C and D were exposed to 2100-MHz radiofrequency radiation emitted by a generator, simulating a 3G-mobile phone, 6 hours/day, for 10 or 40 days, respectively. After exposure, nasal mucociliary clearance was measured by rhinoscintigraphy. After euthanization, the nasal septa of the animals were removed, and tissue samples of the nasal mucosa were examined using a transmission electron microscope. The differences in mucociliary clearances between groups A and C, groups B and D, and groups C and D were found to be statistically significant (p = 0.005, p < 0.001, p < 0.001, respectively). Although there were no histopathological abnormalities in the control groups, the exposure groups showed a number of degenerated and apoptotic cells, ciliary disorganization and ciliary loss in the epithelial cells, epithelial metaplasia, alteration of normal chromatin distribution and karyolysis in nuclei, changes in the basal cells, and lymphocytic infiltration. The histopathological changes were more severe in group D. Radiofrequency radiation at 2100 MHz damaged the nasal septal mucosa, and disturbed the mucociliary clearance. Ciliary disorganization and ciliary loss in the epithelial cells resulted in deterioration of nasal mucociliary clearance. © 2015 ARS-AAOA, LLC.

Supersonic cruise research aircraft structural studies: Methods and results

NASA Technical Reports Server (NTRS)

Sobieszczanski-Sobieski, J.; Gross, D.; Kurtze, W.; Newsom, J.; Wrenn, G.; Greene, W.

1981-01-01

NASA Langley Research Center SCAR in-house structural studies are reviewed. In methods development, advances include a new system of integrated computer programs called ISSYS, progress in determining aerodynamic loads and aerodynamically induced structural loads (including those due to gusts), flutter optimization for composite and metal airframe configurations using refined and simplified mathematical models, and synthesis of active controls. Results given address several aspects of various SCR configurations. These results include flutter penalties on composite wing, flutter suppression using active controls, roll control effectiveness, wing tip ground clearance, tail size effect on flutter, engine weight and mass distribution influence on flutter, and strength and flutter optimization of new configurations. The ISSYS system of integrated programs performed well in all the applications illustrated by the results, the diversity of which attests to ISSYS' versatility.

Emergency Department Medical Clearance of Patients with Psychiatric or Behavioral Emergencies, Part 2: Special Psychiatric Populations and Considerations.

PubMed

Alam, Al; Rachal, James; Tucci, Veronica Theresa; Moukaddam, Nidal

2017-09-01

Patients who present to the emergency department (ED) with mental illness or behavioral complaints merit workup for underlying physical conditions that can trigger, mimic, or worsen psychiatric symptoms. However, there are wide variations in quality of care for these individuals. Psychiatry and emergency medicine specialty guidelines support a tailored, customized approach to patients. Our group has long advocated a dynamic comanagement approach for medical clearance in the ED, and this article summarizes best-practice approaches to the medical clearance of patients with psychiatric illness, tips on history taking, system reviews, clinical/physical examination, and common pitfalls in the medical clearance process. Copyright © 2017 Elsevier Inc. All rights reserved.

Use of radioisotopic esophageal transit in the assessment of patients with symptoms of reflux and non-specific esophageal motor disorders.

PubMed

Iascone, C; Di Giulio, E; Maffi, C; Ruperto, M

2004-01-01

The purposes of this study were to assess the esophageal clearance of a radioisotopic bolus in patients with symptoms of reflux and evaluate the impact of manometric abnormalities on scintigraphic esophageal transit. Esophageal clearance was assessed in a supine position and indicated by the retained radioactivity in the esophagus at 10, 20, 30 and 40 s after the ingestion of a liquid bolus labeled with 2 mCi 99 mTc-SC. The study included 214 consecutive patients with symptoms of reflux and 11 normal controls. The results were compared to the motility findings detected on manometry performed on a separate occasion. Esophageal manometry was normal in 93 patients. Nonspecific esophageal motor disorders were identified in 121 patients and were classified into: 'predominantly nonpropagated activity', 'predominantly low-amplitude peristaltic contractions' and 'miscellaneous disorders' diagnosed in 27, 47 and 47 patients, respectively. The radionuclide clearance was significantly delayed in the overall group of patients compared with that of normal controls (P < 0.001); in patients with reflux symptoms and nonspecific esophageal motor disorders compared with patients with reflux symptoms and 'normal manometry' (P < 0.01 at 20 s); and in patients with reflux symptoms and 'normal manometry' compared with the control group (P < 0.01 at 20 s). Abnormal radioisotope clearances were detected in 88% of patients with 'predominantly nonpropagated activity', in 70% of patients with 'predominantly low-amplitude peristaltic contractions' and in 57% of patients with 'miscellaneous disorders'. Radioisotopic esophageal clearance abnormalities are frequently observed in patients with reflux symptoms and are more likely to be associated to hypomotility disorders, i.e. nonpropagated motor activity or low-amplitude contractions.

Cholecystectomy Reduces Recurrent Pancreatitis and Improves Survival After Endoscopic Sphincterotomy.

PubMed

Young, Shih-Hao; Peng, Yen-Ling; Lin, Xi-Hsuan; Chen, Yung-Tai; Luo, Jiing-Chyuan; Wang, Yen-Po; Hou, Ming-Chih; Lee, Fa-Yauh

2017-02-01

The aim of this study was to assess whether cholecystectomy can decrease the recurrent pancreatitis in the elderly patients who received endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST) and successful clearance of bile duct (BD) stones after gallstone-related acute pancreatitis. We analyzed data from National Health Insurance Research Database of Taiwan. Elderly patients (age ≧70 years old) who had gallstone-related acute pancreatitis and underwent successful EST with BD stones clearance were eligible for enrollment. This nationwide, population-based, propensity score (PS)-matched cohort study involved two cohorts: (1) patients who underwent cholecystectomy after ERCP with BD stone clearance as study group and (2) those who adopted wait-and-see strategy (without cholecystectomy) after ERCP with BD stone clearance as control group. The primary and secondary endpoints were recurrent acute pancreatitis and all-cause mortality, respectively. During the study period, a total of 670 elderly patients (male 291, female 379) with a mean age of 79.1 was enrolled for analysis after PS matching. The incidence rate of recurrent acute pancreatitis was 12.39 per 1000 person-years in the cholecystectomy cohort and 23.94 per 1000 person-years in the PS-matched control cohort. The risk of recurrent acute pancreatitis was significantly lower in the cholecystectomy cohort (HR, 0.56; 95 % confidence interval [CI], 0.34-0.91; P = 0.021). The HR for all-cause mortality among the cholecystectomy cohort was 0.75 (95 % CI, 0.59-0.95; P = 0.016) compared with the control cohort. Cholecystectomy decreased the subsequent recurrent acute pancreatitis and the all-cause mortality in elderly patients with EST and clearance of BD stones after gallstone-related acute pancreatitis.

Effect of amiloride and saline on nasal mucociliary clearance and potential difference in cystic fibrosis and normal subjects.

PubMed Central

Middleton, P. G.; Geddes, D. M.; Alton, E. W.

1993-01-01

BACKGROUND--Mucociliary clearance is an important component of pulmonary defence. Maximum clearance is thought to depend on an optimal depth of the sol layer, allowing the most efficient interaction between the cilia and the overlying mucus layer. Sodium absorption, the major ion transport in human airways, is thought to be important in the regulation of the depth of the sol layer. In the airways of patients with cystic fibrosis sodium absorption is increased and mucociliary clearance decreased. Amiloride, a sodium channel blocker, has been shown to improve pulmonary mucociliary clearance in patients with cystic fibrosis. However, its effects on nasal mucociliary clearance in either normal subjects or those with cystic fibrosis are unknown. A study was therefore performed to investigate whether nebulised amiloride improves nasal mucociliary clearance in normal or cystic fibrosis subjects. METHODS--Nasal mucociliary clearance was measured by the saccharin clearance technique in 12 normal subjects and 12 with cystic fibrosis. For the control study measurements were made on two consecutive days and the mean time for each subject averaged. For the drug study measurements were also made on two consecutive days, after administration of nasally nebulised amiloride or placebo (saline) in a double blind manner. Nasal potential difference was measured in eight patients with cystic fibrosis after the administration of amiloride or placebo to assess the efficacy of deposition and duration of action. RESULTS--Baseline values of mucociliary clearance were significantly faster in the normal subjects than in those with cystic fibrosis. In both groups mucociliary clearance was increased after both saline and amiloride, with no significant difference between either treatment. As previously reported, baseline nasal potential difference was significantly more negative in the subjects with cystic fibrosis. Amiloride significantly reduced the potential difference for at least 60 minutes in these subjects. CONCLUSIONS--Nebulised saline significantly improves nasal mucociliary clearance in both normal subjects and those with cystic fibrosis. Amiloride did not appear to exert any additional effects in either group of subjects, despite evidence of its efficacy of deposition. PMID:8211871

Infection with the Lyme disease pathogen suppresses innate immunity in mice with diet‐induced obesity

PubMed Central

Zlotnikov, Nataliya; Javid, Ashkan; Ahmed, Mijhgan; Eshghi, Azad; Tang, Tian Tian; Arya, Anoop; Bansal, Anil; Matar, Fatima; Parikh, Maitry; Ebady, Rhodaba; Koh, Adeline; Gupta, Nupur; Song, Peng; Zhang, Yang; Newbigging, Susan; Wormser, Gary P.; Schwartz, Ira; Inman, Robert; Glogauer, Michael

2016-01-01

Abstract Obesity is a major global public health concern. Immune responses implicated in obesity also control certain infections. We investigated the effects of high‐fat diet‐induced obesity (DIO) on infection with the Lyme disease bacterium Borrelia burgdorferi in mice. DIO was associated with systemic suppression of neutrophil‐ and macrophage‐based innate immune responses. These included bacterial uptake and cytokine production, and systemic, progressive impairment of bacterial clearance, and increased carditis severity. B. burgdorferi‐infected mice fed normal diet also gained weight at the same rate as uninfected mice fed high‐fat diet, toll‐like receptor 4 deficiency rescued bacterial clearance defects, which greater in female than male mice, and killing of an unrelated bacterium (Escherichia coli) by bone marrow‐derived macrophages from obese, B. burgdorferi‐infected mice was also affected. Importantly, innate immune suppression increased with infection duration and depended on cooperative and synergistic interactions between DIO and B. burgdorferi infection. Thus, obesity and B. burgdorferi infection cooperatively and progressively suppressed innate immunity in mice. PMID:27794208

Infection with the Lyme disease pathogen suppresses innate immunity in mice with diet-induced obesity.

PubMed

Zlotnikov, Nataliya; Javid, Ashkan; Ahmed, Mijhgan; Eshghi, Azad; Tang, Tian Tian; Arya, Anoop; Bansal, Anil; Matar, Fatima; Parikh, Maitry; Ebady, Rhodaba; Koh, Adeline; Gupta, Nupur; Song, Peng; Zhang, Yang; Newbigging, Susan; Wormser, Gary P; Schwartz, Ira; Inman, Robert; Glogauer, Michael; Moriarty, Tara J

2017-05-01

Obesity is a major global public health concern. Immune responses implicated in obesity also control certain infections. We investigated the effects of high-fat diet-induced obesity (DIO) on infection with the Lyme disease bacterium Borrelia burgdorferi in mice. DIO was associated with systemic suppression of neutrophil- and macrophage-based innate immune responses. These included bacterial uptake and cytokine production, and systemic, progressive impairment of bacterial clearance, and increased carditis severity. B. burgdorferi-infected mice fed normal diet also gained weight at the same rate as uninfected mice fed high-fat diet, toll-like receptor 4 deficiency rescued bacterial clearance defects, which greater in female than male mice, and killing of an unrelated bacterium (Escherichia coli) by bone marrow-derived macrophages from obese, B. burgdorferi-infected mice was also affected. Importantly, innate immune suppression increased with infection duration and depended on cooperative and synergistic interactions between DIO and B. burgdorferi infection. Thus, obesity and B. burgdorferi infection cooperatively and progressively suppressed innate immunity in mice. © 2016 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd.

Intelligent Engine Systems: Thermal Management and Advanced Cooling

NASA Technical Reports Server (NTRS)

Bergholz, Robert

2008-01-01

The objective of the Advanced Turbine Cooling and Thermal Management program is to develop intelligent control and distribution methods for turbine cooling, while achieving a reduction in total cooling flow and assuring acceptable turbine component safety and reliability. The program also will develop embedded sensor technologies and cooling system models for real-time engine diagnostics and health management. Both active and passive control strategies will be investigated that include the capability of intelligent modulation of flow quantities, pressures, and temperatures both within the supply system and at the turbine component level. Thermal management system concepts were studied, with a goal of reducing HPT blade cooling air supply temperature. An assessment will be made of the use of this air by the active clearance control system as well. Turbine component cooling designs incorporating advanced, high-effectiveness cooling features, will be evaluated. Turbine cooling flow control concepts will be studied at the cooling system level and the component level. Specific cooling features or sub-elements of an advanced HPT blade cooling design will be downselected for core fabrication and casting demonstrations.

Evaluation of lung epithelial permeability in the volatile substance abuse using Tc-99m DTPA aerosol scintigraphy.

PubMed

Cayir, Derya; Demirel, Koray; Korkmaz, Meliha; Koca, Gokhan

2011-10-01

Chronic inhalant use is associated with significant toxic effects, including neurological, renal, hepatic, and pulmonary damage. However, there is a paucity of reports regarding respiratory complications in inhalant abusers. The aim of this study was to evaluate pulmonary epithelial permeability in the volatile substance abuse (VSA) using Tc-99m DTPA aerosol scintigraphy. This study included 18 patients with volatile substance abuse and 18 volunteer controls. All of patients and controls were smokers. Tc-99m DTPA aerosol scintigraphy was performed in all cases. Time-activity curves from each lung were generated and clearance half-time (T(1/2)) of Tc-99m DTPA were calculated. T(1/2) of whole lung was calculated as a mean of the T(1/2) of left and right lung. The T(1/2) values of Tc-99m DTPA clearance in the substance abusers were significantly decreased as compared to the control group with respective mean values of 28.86 ± 8.44, and 62.14 ± 26.12 min (p = 0.001). It was seen Tc-99m DTPA clearance from lung was faster as the duration of substance abuse was increased. Tc-99m DTPA pulmonary clearance is markedly accelerated in the volatile substance abuse. This suggests that inhalant abuse of substance may produce abnormalities in pulmonary alveolo-capillary membrane function.

The effect of insulin deficiency on the plasma clearance and exchange of high-density-lipoprotein phosphatidylcholine in rats.

PubMed Central

Martins, I J; Redgrave, T G

1992-01-01

Triolein/cholesteryl oleate/cholesterol/phosphatidylcholine emulsions designed to model the lipid composition of chylomicrons were injected intravenously into control and streptozotocin-treated insulin-deficient rats. As previously described for lymph chylomicrons, the emulsion triolein was hydrolysed and phosphatidylcholine was transferred to the plasma high-density lipoproteins (HDL). This mechanism was used to introduce a phospholipid label into HDL in vivo. The subsequent clearance of phospholipid radioactivity from the plasma of insulin-deficient rats was significantly slower than in controls (P less than 0.025). Plasma clearance was similarly slower in insulin-deficient rats after injection of HDL that was previously labelled with radioactive phospholipids. After injection, the phospholipid label redistributed rapidly between the large-particle fraction of plasma lipoproteins (very-low- and low-density lipoproteins), and the lighter and heavier fractions of HDL. Compared with control rats, in insulin-deficient rats less of the phospholipid label was distributed to the lighter HDL fraction and more to the heavier HDL fraction, and this difference was not due to changes in activity of lecithin: cholesterol acyltransferase or in the apparent activity of phospholipid transfer protein. In insulin-deficient rats the changes in HDL phospholipid clearance and exchange appeared to be secondary to the associated hypertriglyceridaemia and the related changes in distribution of phospholipids between classes of plasma lipoproteins. PMID:1536661

The CF6 engine performance improvement

NASA Technical Reports Server (NTRS)

Fasching, W. A.

1982-01-01

As part of the NASA-sponsored Engine Component Improvement (ECI) Program, a feasibility analysis of performance improvement and retention concepts for the CF6-6 and CF6-50 engines was conducted and seven concepts were identified for development and ground testing: new fan, new front mount, high pressure turbine aerodynamic performance improvement, high pressure turbine roundness, high pressure turbine active clearance control, low pressure turbine active clearance control, and short core exhaust nozzle. The development work and ground testing are summarized, and the major test results and an enomic analysis for each concept are presented.

Capacitance-type blade-tip clearance measurement system using a dual amplifier with ramp/dc inputs and integration

NASA Technical Reports Server (NTRS)

Sarma, Garimella R.; Barranger, John P.

1992-01-01

The analysis and prototype results of a dual-amplifier circuit for measuring blade-tip clearance in turbine engines are presented. The capacitance between the blade tip and mounted capacitance electrode within a guard ring of a probe forms one of the feedback elements of an operational amplifier (op amp). The differential equation governing the circuit taking into consideration the nonideal features of the op amp was formulated and solved for two types of inputs (ramp and dc) that are of interest for the application. Under certain time-dependent constraints, it is shown that (1) with a ramp input the circuit has an output voltage proportional to the static tip clearance capacitance, and (2) with a dc input, the output is proportional to the derivative of the clearance capacitance, and subsequent integration recovers the dynamic capacitance. The technique accommodates long cable lengths and environmentally induced changes in cable and probe parameters. System implementation for both static and dynamic measurements having the same high sensitivity is also presented.

Capacitance-type blade-tip clearance measurement system using a dual amplifier with ramp/dc inputs and integration

NASA Astrophysics Data System (ADS)

Sarma, Garimella R.; Barranger, John P.

1992-10-01

The analysis and prototype results of a dual-amplifier circuit for measuring blade-tip clearance in turbine engines are presented. The capacitance between the blade tip and mounted capacitance electrode within a guard ring of a probe forms one of the feedback elements of an operational amplifier (op amp). The differential equation governing the circuit taking into consideration the nonideal features of the op amp was formulated and solved for two types of inputs (ramp and dc) that are of interest for the application. Under certain time-dependent constraints, it is shown that (1) with a ramp input the circuit has an output voltage proportional to the static tip clearance capacitance, and (2) with a dc input, the output is proportional to the derivative of the clearance capacitance, and subsequent integration recovers the dynamic capacitance. The technique accommodates long cable lengths and environmentally induced changes in cable and probe parameters. System implementation for both static and dynamic measurements having the same high sensitivity is also presented.

Multi-camera and structured-light vision system (MSVS) for dynamic high-accuracy 3D measurements of railway tunnels.

PubMed

Zhan, Dong; Yu, Long; Xiao, Jian; Chen, Tanglong

2015-04-14

Railway tunnel 3D clearance inspection is critical to guaranteeing railway operation safety. However, it is a challenge to inspect railway tunnel 3D clearance using a vision system, because both the spatial range and field of view (FOV) of such measurements are quite large. This paper summarizes our work on dynamic railway tunnel 3D clearance inspection based on a multi-camera and structured-light vision system (MSVS). First, the configuration of the MSVS is described. Then, the global calibration for the MSVS is discussed in detail. The onboard vision system is mounted on a dedicated vehicle and is expected to suffer from multiple degrees of freedom vibrations brought about by the running vehicle. Any small vibration can result in substantial measurement errors. In order to overcome this problem, a vehicle motion deviation rectifying method is investigated. Experiments using the vision inspection system are conducted with satisfactory online measurement results.

Hypoglycemic depression of hepatic phagocytosis in vivo and in the in situ perfused rat liver.

PubMed

Kober, P M; Filkins, J P

1981-01-01

Depression of the phagocytic function of the reticuloendothelial system (RES) during endotoxic hypoglycemia has been implicated in the pathogenesis of endotoxin shock. The present study evaluated the in vivo effects of hypoglycemia on RES function and assessed the effects of an vivo bout of hypoglycemia on phagocytosis in the in situ perfused rat liver. Hypoglycemia was produced in male Holtzman rats using either 1 U of regular insulin (RI) (ILETIN, Lilly) or 0.75 U of long-acting insulin (LAI) (85% LENTE/15% ULTRALENTE, Lilly). RES function was quantitated by intravascular clearance of 8 mg/100 gm body weight colloidal carbon (CC). Two hr after RI and 2.5 hr after LAI, the intravascular halftimes of CC clearance were 19 +/- 2 min (N = 22) and 18 +/- 1 min (N = 19), respectively, as compared to control, 11.3 +/- 0.4 min (N = 53, P less than 0.001). The corresponding plasma glucose (PG) levels were 95 +/- 2 mg/dl in control, 14.4 +/- 0.9 for the RI group, and 17 +/- 1 for LAI. Two hr after RI, livers were perfused for 10 min in situ with 50 mg/liter CC in saline 5% rat serum. PG for control liver donors were 90 +/- 3 mg/dl, while those for hypoglycemic liver donors were 15 +/- 2. CC uptake was decreased from 22 micrograms/min/gm liver in the control (+ serum, n = 19) to 11 +/- 2 in hypoglycemia livers (N = 6); no effect of serum on hypoglycemic depression of the RES was seen. There were no differences in flow rates in the 2 groups. These results indicate that hypoglycemia directly impairs RES function and that the in vivo depression of intravascular clearance is not related to either the presence or absence of serum factors or total hepatic blood flow. Thus, the characteristic hypoglycemia of endotoxin shock may contribute to RES depression and the lethal shock syndrome.

Respiratory Protection Program medical clearance for respirator use

NASA Technical Reports Server (NTRS)

1993-01-01

Background on occupational exposure to various inhalents is discussed including on-site hazard control measures, procedures, physiological effects, and interpretation of results for the medical clearance of employee for use of personal respiratory protection devices. The purpose of the Respiratory Protection Program at LeRC is outlined, and the specifics of the Medical Surveillance Program for Respiratory Protection at LeRC are discussed.

Mechanisms of phagocytosis and host clearance of Pseudomonas aeruginosa

PubMed Central

Lovewell, Rustin R.; Patankar, Yash R.

2014-01-01

Pseudomonas aeruginosa is an opportunistic bacterial pathogen responsible for a high incidence of acute and chronic pulmonary infection. These infections are particularly prevalent in patients with chronic obstructive pulmonary disease and cystic fibrosis: much of the morbidity and pathophysiology associated with these diseases is due to a hypersusceptibility to bacterial infection. Innate immunity, primarily through inflammatory cytokine production, cellular recruitment, and phagocytic clearance by neutrophils and macrophages, is the key to endogenous control of P. aeruginosa infection. In this review, we highlight recent advances toward understanding the innate immune response to P. aeruginosa, with a focus on the role of phagocytes in control of P. aeruginosa infection. Specifically, we summarize the cellular and molecular mechanisms of phagocytic recognition and uptake of P. aeruginosa, and how current animal models of P. aeruginosa infection reflect clinical observations in the context of phagocytic clearance of the bacteria. Several notable phenotypic changes to the bacteria are consistently observed during chronic pulmonary infections, including changes to mucoidy and flagellar motility, that likely enable or reflect their ability to persist. These traits are likewise examined in the context of how the bacteria avoid phagocytic clearance, inflammation, and sterilizing immunity. PMID:24464809

Mechanisms of phagocytosis and host clearance of Pseudomonas aeruginosa.

PubMed

Lovewell, Rustin R; Patankar, Yash R; Berwin, Brent

2014-04-01

Pseudomonas aeruginosa is an opportunistic bacterial pathogen responsible for a high incidence of acute and chronic pulmonary infection. These infections are particularly prevalent in patients with chronic obstructive pulmonary disease and cystic fibrosis: much of the morbidity and pathophysiology associated with these diseases is due to a hypersusceptibility to bacterial infection. Innate immunity, primarily through inflammatory cytokine production, cellular recruitment, and phagocytic clearance by neutrophils and macrophages, is the key to endogenous control of P. aeruginosa infection. In this review, we highlight recent advances toward understanding the innate immune response to P. aeruginosa, with a focus on the role of phagocytes in control of P. aeruginosa infection. Specifically, we summarize the cellular and molecular mechanisms of phagocytic recognition and uptake of P. aeruginosa, and how current animal models of P. aeruginosa infection reflect clinical observations in the context of phagocytic clearance of the bacteria. Several notable phenotypic changes to the bacteria are consistently observed during chronic pulmonary infections, including changes to mucoidy and flagellar motility, that likely enable or reflect their ability to persist. These traits are likewise examined in the context of how the bacteria avoid phagocytic clearance, inflammation, and sterilizing immunity.

The relationship of systemic markers of renal function and vascular function with retinal blood vessel responses.

PubMed

Heitmar, R; Varma, C; De, P; Lau, Y C; Blann, A D

2016-11-01

To test the hypothesis of a significant relationship between systemic markers of renal and vascular function (processes linked to cardiovascular disease and its development) and retinal microvascular function in diabetes and/or cardiovascular disease. Ocular microcirculatory function was measured in 116 patients with diabetes and/or cardiovascular disease using static and continuous retinal vessel responses to three cycles of flickering light. Endothelial function was evaluated by von Willebrand factor (vWf), endothelial microparticles and soluble E selectin, renal function by serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR). HbA1c was used as a control index. Central retinal vein equivalence and venous maximum dilation to flicker were linked to HbA1c (both p < 0.05). Arterial reaction time was linked to serum creatinine (p = 0.036) and eGFR (p = 0.039); venous reaction time was linked to creatinine clearance (p = 0.018). Creatinine clearance and eGFR were linked to arterial maximum dilatation (p < 0.001 and p = 0.003, respectively) and the dilatation amplitude (p = 0.038 and p = 0.048, respectively) responses in the third flicker cycle. Of venous responses to the first flicker cycle, HbA1c was linked to the maximum dilation response (p = 0.004) and dilatation amplitude (p = 0.017), vWf was linked to the maximum constriction response (p = 0.016), and creatinine clearance to the baseline diameter fluctuation (p = 0.029). In the second flicker cycle, dilatation amplitude was linked to serum creatinine (p = 0.022). Several retinal blood vessel responses to flickering light are linked to glycaemia and renal function, but only one index is linked to endothelial function. Renal function must be considered when interpreting retinal vessel responses.

Disk/Shaft Vibration Induced by Bearing Clearance Effects: Analysis and Experiment

NASA Technical Reports Server (NTRS)

Flowers, George T.; Wu, Fangsheng

1996-01-01

This study presents an investigation of the dynamics of a rotor system with bearing clearance. Of particular interest is the influence of such effects on coupled disk/shaft vibration. Experimental results for a rotor system with a flexible disk are presented and compared to predictions from a simulation model. Some insights and conclusions are obtained with regard to the conditions under which such vibration may be significant.

Dexamethasone exposure and asparaginase antibodies affect relapse risk in acute lymphoblastic leukemia

PubMed Central

Kawedia, Jitesh D.; Liu, Chengcheng; Pei, Deqing; Cheng, Cheng; Fernandez, Christian A.; Howard, Scott C.; Campana, Dario; Panetta, John C.; Bowman, W. Paul; Evans, William E.; Pui, Ching-Hon

2012-01-01

We have previously hypothesized that higher systemic exposure to asparaginase may cause increased exposure to dexamethasone, both critical chemotherapeutic agents for acute lymphoblastic leukemia. Whether interpatient pharmaco-kinetic differences in dexamethasone contribute to relapse risk has never been studied. The impact of plasma clearance of dexamethasone and anti–asparaginase antibody levels on risk of relapse was assessed in 410 children who were treated on a front-line clinical trial for acute lymphoblastic leukemia and were evaluable for all pharmacologic measures, using multivariate analyses, adjusting for standard clinical and biologic prognostic factors. Dexamethasone clearance (mean ± SD) was higher (P = 3 × 10−8) in patients whose sera was positive (17.7 ± 18.6 L/h per m2) versus nega-tive (10.6 ± 5.99 L/h per m2) for anti–asparaginase antibodies. In multivariate analyses, higher dexamethasone clearance was associated with a higher risk of any relapse (P = .01) and of central nervous system relapse (P = .014). Central nervous system relapse was also more common in patients with anti–asparaginase antibodies (P = .019). In conclusion, systemic clearance of dexamethasone is higher in patients with anti–asparaginase antibodies. Lower exposure to both drugs was associated with an increased risk of relapse. PMID:22117041

Radial Clearance Found To Play a Key Role in the Performance of Compliant Foil Air Bearings

NASA Technical Reports Server (NTRS)

Radil, Kevin C.

2003-01-01

Compliant foil air bearings are at the forefront of the Oil-Free turbomachinery revolution, which supports gas turbine engines with hydrodynamic bearings that use air instead of oil as the working fluid. These types of bearings have been around for almost 50 years and have found a home in several commercial applications, such as in air cycle machines, turbocompressors, and microturbines, but are now being aggressively pursued for use in small and midrange aircraft gas turbine engines. Benefits include higher operating speeds and temperatures, lower maintenance costs, and greater reliability. The Oil-Free Turbomachinery team at the NASA Glenn Research Center is working to foster the transition of Oil-Free technology into gas turbine engines by performing in-house experiments on foil air bearings in order to gain a greater insight into their complex operating principles. A research program recently undertaken at Glenn focused on the concept of radial clearance and its influence on bearing performance. The tests were conducted on foil bearings with different radial clearances. As defined for a foil bearing, radial clearance is a measure of the small amount of shaft radial motion that is present from play that exists in the elastic support structure, such as between the top and bump foils and the bump foils and bearing shell (see the drawing). With an insufficient amount of radial clearance, the bearing imparts a high preload on the shaft, which when excessive, can reduce the loadcarrying capability of the bearing. On the other hand, systems using foil bearings with excessive radial clearance may experience rotordynamic instabilities because of low bearing preload. Therefore, without a more thorough understanding of radial clearance, it is difficult to accurately predict the performance of a given bearing design. The test program demonstrated that there is a direct correlation between radial clearance and the performance of foil air bearings. As shown in the graph, an optimum radial clearance exists that will maximize the amount of load that the bearing is capable of supporting. With respect to this optimum, two different performance regimes were observed that are a function of the amount of radial clearance. Tests showed that bearings with radial clearances below the optimum in regime I were susceptible to sudden seizure, a failure mode indicative of thermal runaway caused by high preload. The high preload is in response to an insufficient amount of radial clearance available to accommodate the thermal growth of the bearing and shaft. However, radial clearances greater than the optimum in regime II resulted in low bearing preloads that did not cause any heat-related problems, and the failure mode was due to fluid-film breakdown. In fact, bearings operating with radial clearances twice as much as the optimum suffered a decrease in the maximum load capacity of only about 20 percent. Therefore, special attention has to be given to the range of operating conditions expected in the bearing/shaft system since changes in temperature, centrifugal, and hydrodynamic effects can all affect radial clearance. This enhanced understanding of foil air bearing behavior will greatly aid our efforts to transition Oil-Free technology to future aircraft engines.

Immunoreactive serum opsonic alpha 2 sb glycoprotein as a noninvasive index of RES systemic defense after trauma.

PubMed

Kaplan, J E; Saba, T M

1979-01-01

Reticuloendothelial system (RES) depression has been correlated with diminished resistance to trauma, shock, and sepsis in man and animals. Previous studies have related the depression of RES hepatic Kupffer cell phagocytic function after trauma to diminished bioassayable opsonic activity. The present study determined if the loss of biological activity and RES alteration correlated with immunoreactive serum opsonic alpha 2 SB glycoprotein levels after trauma. Serum opsonic activity was measured by liver slice bioassay, and immunoreactive opsonic protein was measured by rocket electroimmunoassay. RE function was determined by colloid clearance over a 24-hour post-trauma period. Anesthetized rats (250-300 gm) subjected to sublethal or severe (greater than LD50) whole-body NCD trauma were the shock models investigated. Immunoreactive levels in 63 rats prior to injury were 518 +/- 24 microgram/ml. Neither biological nor immunoreactive levels were altered over 24 hours in anesthetized sham-traumatized controls. Temporal alteration in the initial decrease and recovery pattern of biologically active and immunoreactive opsonic protein levels significantly correlated following both sublethal and severe injury. Moreover, the patterns of immunoreactive levels of the opsonic protein correlated with the functional phagocytic activity of the RES as determined by vascular clearance of a test dose of blood-borne radiolabeled particulates. This glycoprotein falls after trauma, and the magnitude and duration of the decline increases with severity of injury. Immunoreactive opsonic alpha 2 SB glycoprotein appears to be an accurate measurement of circulating opsonic activity and RE Kupffer cell function after trauma, especially with respect to clearance. Thus, immunoreactive opsonic protein warrants clinical consideration as a noninvasive measure of reticuloendothelial systemic defense in patients after trauma and burn.

Phosphate Removal by Peritoneal Dialysis: The Effect of Transporter Status and Peritoneal Dialysis Prescription.

PubMed

Courivaud, Cecile; Davenport, Andrew

2016-01-01

♦ Interventional trials failed to demonstrate that increasing urea clearance improved peritoneal dialysis (PD) patient survival. Hyperphosphatemia is a well-recognized predictor of cardiovascular and all-cause mortality in PD patients. Simplification of PD small solute clearance targets focuses away from larger solutes, including phosphate. In the US and UK, increasing use of automated peritoneal dialysis (APD) cyclers with shorter dwell times could also potentially reduce peritoneal phosphate removal compared to continuous ambulatory peritoneal dialysis (CAPD). ♦ Total phosphate and peritoneal phosphate clearances were measured in a prospective observational cohort of 380 adult PD patients attending a tertiary university hospital between 1996 and 2013 for routine assessment of PD adequacy. ♦ Eighty-seven patients (22.9%) were hyperphosphatemic. Taking the mean 4-hour dialysate to plasma (D/P) ratio for phosphate, 193 (50.8%) were fast and fast-average transporters and 187 (49.2%) were slow and slow-average transporters (compared to 276 [72.6%] and 104 [27.4%], respectively, for peritoneal creatinine transporter status). Faster peritoneal phosphate transporter status was associated with over-hydration (odds ratio [OR] = 2.45 [1.43 - 4.20], p = 0.001). Whereas the 4-hour D/P creatinine and peritoneal weekly creatinine clearance did not differ between those who were hyperphosphatemic or not, the hyperphosphatemic patients had lower 4-hour D/P phosphate and lower peritoneal weekly phosphate clearance (p = 0.019, and p = 0.06 respectively). We found greater peritoneal phosphate clearance for patients choosing CAPD compared to APD, irrespective of the peritoneal phosphate transporter status. ♦ Peritoneal creatinine transporter status and creatinine clearance cannot be used as surrogate markers of peritoneal phosphate transport and clearance. Hyperphosphatemia was more common in PD patients with slower peritoneal transporter status and lower peritoneal phosphate clearance. Greater peritoneal phosphate clearance was achieved with CAPD prescriptions. Slower peritoneal transporters should be advised to choose CAPD to improve serum phosphate control. Copyright © 2016 International Society for Peritoneal Dialysis.

Phosphate Removal by Peritoneal Dialysis: The Effect of Transporter Status and Peritoneal Dialysis Prescription

PubMed Central

Courivaud, Cecile; Davenport, Andrew

2016-01-01

♦ Background: Interventional trials failed to demonstrate that increasing urea clearance improved peritoneal dialysis (PD) patient survival. Hyperphosphatemia is a well-recognized predictor of cardiovascular and all-cause mortality in PD patients. Simplification of PD small solute clearance targets focuses away from larger solutes, including phosphate. In the US and UK, increasing use of automated peritoneal dialysis (APD) cyclers with shorter dwell times could also potentially reduce peritoneal phosphate removal compared to continuous ambulatory peritoneal dialysis (CAPD). ♦ Methods: Total phosphate and peritoneal phosphate clearances were measured in a prospective observational cohort of 380 adult PD patients attending a tertiary university hospital between 1996 and 2013 for routine assessment of PD adequacy. ♦ Results: Eighty-seven patients (22.9%) were hyperphosphatemic. Taking the mean 4-hour dialysate to plasma (D/P) ratio for phosphate, 193 (50.8%) were fast and fast-average transporters and 187 (49.2%) were slow and slow-average transporters (compared to 276 [72.6%] and 104 [27.4%], respectively, for peritoneal creatinine transporter status). Faster peritoneal phosphate transporter status was associated with over-hydration (odds ratio [OR] = 2.45 [1.43 – 4.20], p = 0.001). Whereas the 4-hour D/P creatinine and peritoneal weekly creatinine clearance did not differ between those who were hyperphosphatemic or not, the hyperphosphatemic patients had lower 4-hour D/P phosphate and lower peritoneal weekly phosphate clearance (p = 0.019, and p = 0.06 respectively). We found greater peritoneal phosphate clearance for patients choosing CAPD compared to APD, irrespective of the peritoneal phosphate transporter status. ♦ Conclusion: Peritoneal creatinine transporter status and creatinine clearance cannot be used as surrogate markers of peritoneal phosphate transport and clearance. Hyperphosphatemia was more common in PD patients with slower peritoneal transporter status and lower peritoneal phosphate clearance. Greater peritoneal phosphate clearance was achieved with CAPD prescriptions. Slower peritoneal transporters should be advised to choose CAPD to improve serum phosphate control. PMID:26224788

Minimum toe clearance events in divided attention treadmill walking in older and young adults: a cross-sectional study.

PubMed

Santhiranayagam, Braveena K; Lai, Daniel T H; Sparrow, W A; Begg, Rezaul K

2015-07-12

Falls in older adults during walking frequently occur while performing a concurrent task; that is, dividing attention to respond to other demands in the environment. A particularly hazardous fall-related event is tripping due to toe-ground contact during the swing phase of the gait cycle. The aim of this experiment was to determine the effects of divided attention on tripping risk by investigating the gait cycle event Minimum Toe Clearance (MTC). Fifteen older adults (mean 73.1 years) and 15 young controls (mean 26.1 years) performed three walking tasks on motorized treadmill: (i) at preferred walking speed (preferred walking), (ii) while carrying a glass of water at a comfortable walking speed (dual task walking), and (iii) speed-matched control walking without the glass of water (control walking). Position-time coordinates of the toe were acquired using a 3 dimensional motion capture system (Optotrak NDI, Canada). When MTC was present, toe height at MTC (MTC_Height) and MTC timing (MTC_Time) were calculated. The proportion of non-MTC gait cycles was computed and for non-MTC gait cycles, toe-height was extracted at the mean MTC_Time. Both groups maintained mean MTC_Height across all three conditions. Despite greater MTC_Height SD in preferred gait, the older group reduced their variability to match the young group in dual task walking. Compared to preferred speed walking, both groups attained MTC earlier in dual task and control conditions. The older group's MTC_Time SD was greater across all conditions; in dual task walking, however, they approximated the young group's SD. Non-MTC gait cycles were more frequent in the older group across walking conditions (for example, in preferred walking: young - 2.9 %; older - 18.7 %). In response to increased attention demands older adults preserve MTC_Height but exercise greater control of the critical MTC event by reducing variability in both MTC_Height and MTC_Time. A further adaptive locomotor control strategy to reduce the likelihood of toe-ground contacts is to attain higher mid-swing clearance by eliminating the MTC event, i.e. demonstrating non-MTC gaits cycles.

Nano-Advantage in Enhanced Drug Delivery with Biodegradable Nanoparticles: Contribution of Reduced Clearance

PubMed Central

Kadam, Rajendra S.; Bourne, David W. A.

2012-01-01

The aim of this study was to investigate the contribution of reduced apparent clearance to the enhanced exposure reported for biodegradable nanoparticles after extravascular and intravascular routes of administration. Plasma concentration profiles for drug and nanoparticle formulations after administration by intravenous, intraduodenal, and oral routes were extracted from the literature. Data were fit to pharmacokinetic models using BOOMER. The compartmental pharmacokinetic analysis of literature data for six drugs (camptothecin, 9-nitrocamptothecin, epirubicin, vinpocetine, clozapine, and cyclosporine) showed that the encapsulation of drug molecules in nanoparticles significantly reduced the apparent clearance and prolonged the apparent circulation half-life compared with those for the plain drug. Positively charged nanoparticles assessed in this study had lower apparent clearance, lower elimination rate constant values, and longer apparent circulation half-life than neutral and negatively charged nanoparticles. After oral administration, a reduction in apparent clearance contributed substantially to elevations in plasma drug exposure with nanoparticles. For the drugs and delivery systems examined, the nano-advantage in drug delivery enhancement can be explained, in part, by reduced clearance. PMID:22498894

Experimental studies on the effect of automation on pilot situational awareness in the datalink ATC environment

NASA Technical Reports Server (NTRS)

Hahn, Edward C.; Hansman, R. J., Jr.

1992-01-01

An experiment to study how automation, when used in conjunction with datalink for the delivery of ATC clearance amendments, affects the situational awareness of aircrews was conducted. The study was focused on the relationship of situational awareness to automated Flight Management System (FMS) programming of datalinked clearances and the readback of ATC clearances. Situational awareness was tested by issuing nominally unacceptable ATC clearances and measuring whether the error was detected by the subject pilots. The experiment also varied the mode of clearance delivery: Verbal, Textual, and Graphical. The error detection performance and pilot preference results indicate that the automated programming of the FMS may be superior to manual programming. It is believed that automated FMS programming may relieve some of the cognitive load, allowing pilots to concentrate on the strategic implications of a clearance amendment. Also, readback appears to have value, but the small sample size precludes a definite conclusion. Furthermore, because textual and graphical modes of delivery offer different but complementary advantages for cognitive processing, a combination of these modes of delivery may be advantageous in a datalink presentation.

Ingress clearance requirements and seat positioning for automatic belt systems

DOT National Transportation Integrated Search

1981-06-01

The purposes of this study were (1) to determine how much clearance between a seat belt and seat cushion is needed for a driver to enter the front seat of an automobile equipped with automatic seat belts---without his/her having to lift the webbing, ...

An on-line calibration technique for improved blade by blade tip clearance measurement

NASA Astrophysics Data System (ADS)

Sheard, A. G.; Westerman, G. C.; Killeen, B.

A description of a capacitance-based tip clearance measurement system which integrates a novel technique for calibrating the capacitance probe in situ is presented. The on-line calibration system allows the capacitance probe to be calibrated immediately prior to use, providing substantial operational advantages and maximizing measurement accuracy. The possible error sources when it is used in service are considered, and laboratory studies of performance to ascertain their magnitude are discussed. The 1.2-mm diameter FM capacitance probe is demonstrated to be insensitive to variations in blade tip thickness from 1.25 to 1.45 mm. Over typical compressor blading the probe's range was four times the variation in blade to blade clearance encountered in engine run components.

Hypercapnia shortens emergence time from inhaled anesthesia in pigs.

PubMed

Gopalakrishnan, Nishant A; Sakata, Derek J; Orr, Joseph A; McJames, Scott; Westenskow, Dwayne R

2007-04-01

Anesthetic clearance from the lungs and the circle rebreathing system can be maximized using hyperventilation and high fresh gas flows. However, the concomitant clearance of CO2 decreases PAco2, thereby decreasing cerebral blood flow and slowing the clearance of anesthetic from the brain. This study shows that in addition to hyperventilation, hypercapnia (CO2 infusion or rebreathing) is a significant factor in decreasing emergence time from inhaled anesthesia. We anesthetized seven pigs with 2 MACPIG of isoflurane and four with 2 MACPIG of sevoflurane. After 2 h, anesthesia was discontinued, and the animals were hyperventilated. The time to movement of multiple limbs was measured under hypocapnic (end-tidal CO2 = 22 mm Hg) and hypercapnic (end-tidal CO2 = 55 mm Hg) conditions. The time between turning off the vaporizer and to movement of multiple limbs was faster with hypercapnia during hyperventilation. Emergence time from isoflurane and sevoflurane anesthesia was shortened by an average of 65% with rebreathing or with the use of a CO2 controller (P < 0.05). Hypercapnia, along with hyperventilation, may be used clinically to decrease emergence time from inhaled anesthesia. These time savings might reduce drug costs. In addition, higher PAco2 during emergence may enhance respiratory drive and airway protection after tracheal extubation.

A Helix-Stabilizing Linker Improves Subcutaneous Bioavailability of a Helical Peptide Independent of Linker Lipophilicity.

PubMed

Zhang, Liang; Navaratna, Tejas; Thurber, Greg M

2016-07-20

Stabilized peptides address several limitations to peptide-based imaging agents and therapeutics such as poor stability and low affinity due to conformational flexibility. There is also active research in developing these compounds for intracellular drug targeting, and significant efforts have been invested to determine the effects of helix stabilization on intracellular delivery. However, much less is known about the impact on other pharmacokinetic parameters such as plasma clearance and bioavailability. We investigated the effect of different fluorescent helix-stabilizing linkers with varying lipophilicity on subcutaneous (sc) bioavailability using the glucagon-like peptide-1 (GLP-1) receptor ligand exendin as a model system. The stabilized peptides showed significantly higher protease resistance and increased bioavailability independent of linker hydrophilicity, and all subcutaneously delivered conjugates were able to successfully target the islets of Langerhans with high specificity. The lipophilic peptide variants had slower absorption and plasma clearance than their respective hydrophilic conjugates, and the absolute bioavailability was also lower likely due to the longer residence times in the skin. Their ease and efficiency make double-click helix stabilization chemistries a useful tool for increasing the bioavailability of peptide therapeutics, many of which suffer from rapid in vivo protease degradation. Helix stabilization using linkers of varying lipophilicity can further control sc absorption and clearance rates to customize plasma pharmacokinetics.

Simple sampling strategy for measuring inulin renal clearance.

PubMed

Horio, Masaru; Imai, Enyu; Yasuda, Yoshinari; Hishida, Akira; Matsuo, Seiichi

2009-02-01

In the standard method of inulin clearance (Cin), three sets of serum and urine samples are collected during a 2-hour clearance period. For a practical use of this method, sampling should be the minimal number allowable while still providing enough accuracy. The aim of this study was to evaluate the validity of inulin renal clearance with assumed single urine collection with a period such as 30, 60 or 90 minutes. Inulin clearance data collected by the standard method from 737 individuals were used. Changes of serum inulin concentrations between 45 and 105 minutes after the start of the infusion were analyzed. We used first urine collection to calculate the inulin clearance with single urine collection (Cin-30 min). We assumed single urine collection for 60 or 90 minutes by combining the urine data of the consecutive 30-minute periods. Inulin clearances (Cin-60 min, Cin-90 min) were calculated from the assumed single urine collections, respectively. Serum inulin concentration did not reach equilibrium during the clearance period. It increased in subjects with low glomerular filtration rate (GFR) and decreased in subjects with normal GFR. The amount of the change was small and -0.5 +/- 12.6% in subjects with GFR over 30 ml/min per 1.73 m(2). Cin-30 min, Cin-60 min and Cin-90 min showed high correlation coefficients against Cin-ST (0.962, 0.988 and 0.998, respectively). Systemic biases in these clearances were negligible (under 1 ml/min per 1.73 m(2)). Root mean square error (RMSE) were 10.4, 5.3 and 2.3 ml/min per 1.73 m(2) for Cin-30 min, Cin-60 min and Cin-90 min, respectively. These data indicated that accuracy of inulin clearance depends on the duration of the urine collection period. Inulin clearance with a single urine collection is a convenient method. We showed that single urine collection for 30 minutes or a longer period has reasonable accuracy in calculation of inulin clearance. We propose a method of inulin clearance with single urine collection for 60 minutes.

Experimental study on the sealing clearance between the labyrinth sealing displacer and cylinder in the 10 K G-M refrigerator

NASA Astrophysics Data System (ADS)

Hao, X. H.; Ju, Y. L.; Lu, Y. J.

2011-05-01

The labyrinth sealing displacer has been optimal designed to improve the operating stability and life-time of 10 K G-M refrigerator. The displacer was made of stainless steel 304 or inconel 718, coated with PTFE on its outer surface. Compared to the traditional piston-ring sealing displacer, the sealing clearance between the ridge of the labyrinth sealing displacer and cylinder is critical to the cooling performance of the G-M refrigerator. The displacers with different sealing clearances were experimentally studied, and the optimal clearance was given. The effects of the materials of the displacers and the system charge pressures on the performance of the labyrinth sealing were also tested and analyzed.

Triglyceride kinetics in fasted and fed E. coli septic rats

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

Lanza-Jacoby, S.; Tabares, A.

1990-02-26

The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studies by examining the liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess the liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant intravenous infusion of (2-{sup 3}H) glycerol-labeled VLDL in fasted control, fasted E. coli-treated, fed control, and fed E.coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 {times} 10{sup 7} live E.coli colonies per 100 g body weight. Twenty-four hours following E.coli injection serum TG of fasted E.coli-treated rats was elevated by 170% which was attributedmore » to a 67% decrease in the clearance rate of VLDL-TG in fasted E.coli-treated rats compared with their fasted controls. The secretion of VLDL-TG declined by 31% in the livers of the fasted E.coli-treated rats which was accompanied by a 2-fold increase in the composition of liver TG. In a second series of experiments control and E.coli-treated rats were fed intragastrically (IG) a balanced solution containing glucose plus fat as the sources of nonprotein calories. Serum TG were 26% lower in the fed E.coli-treated rats because the clearance rate increased by 86%. The secretion of TG in the fed septic rats increased by 40% but this difference was not significant. In the septic rat the ability to clear triglycerides from the plasma depends upon the nutritional state.« less

Immune Mechanisms Responsible for Vaccination against and Clearance of Mucosal and Lymphatic Norovirus Infection

PubMed Central

Chachu, Karen A.; LoBue, Anna D.; Strong, David W.; Baric, Ralph S.; Virgin, Herbert W.

2008-01-01

Two cardinal manifestations of viral immunity are efficient clearance of acute infection and the capacity to vaccinate against secondary viral exposure. For noroviruses, the contributions of T cells to viral clearance and vaccination have not been elucidated. We report here that both CD4 and CD8 T cells are required for efficient clearance of primary murine norovirus (MNV) infection from the intestine and intestinal lymph nodes. Further, long-lasting protective immunity was generated by oral live virus vaccination. Systemic vaccination with the MNV capsid protein also effectively protected against mucosal challenge, while vaccination with the capsid protein of the distantly related human Lordsdale virus provided partial protection. Fully effective vaccination required a broad immune response including CD4 T cells, CD8 T cells, and B cells, but the importance of specific immune cell types varied between the intestine and intestinal lymph nodes. Perforin, but not interferon gamma, was required for clearance of MNV infection by adoptively transferred T lymphocytes from vaccinated hosts. These studies prove the feasibility of both mucosal and systemic vaccination against mucosal norovirus infection, demonstrate tissue specificity of norovirus immune cells, and indicate that efficient vaccination strategies should induce potent CD4 and CD8 T cell responses. PMID:19079577

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI.

PubMed

Iliff, Jeffrey J; Lee, Hedok; Yu, Mei; Feng, Tian; Logan, Jean; Nedergaard, Maiken; Benveniste, Helene

2013-03-01

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer's disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer's disease susceptibility and progression in the live human brain.

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI

PubMed Central

Iliff, Jeffrey J.; Lee, Hedok; Yu, Mei; Feng, Tian; Logan, Jean; Nedergaard, Maiken; Benveniste, Helene

2013-01-01

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer’s disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer’s disease susceptibility and progression in the live human brain. PMID:23434588

Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone

PubMed Central

Mostafa, Heba H.; Vogel, Peter; Srinivasan, Ashok; Russell, Charles J.

2016-01-01

In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus—specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential. PMID:27589232

Intra- and inter-laboratory reliability of a cryopreserved trout hepatocyte assay for the prediction of chemical bioaccumulation potential

EPA Science Inventory

Cryopreserved trout hepatocytes provide a convenient in vitro system for measuring the intrinsic clearance of xenobiotics. Measured clearance rates can then be extrapolated to the whole animal as a means of improving modeled bioaccumulation predictions. To date, however, the in...

20 CFR 655.103 - Overview of this subpart and definition of terms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (combined) in the States or regions as published annually by the U.S. Department of Agriculture (USDA) based... intra-state job clearance systems based on the employer's Agricultural and Food Processing Clearance... Employment Certification. Office of Foreign Labor Certification (OFLC). OFLC means the organizational...

77 FR 40403 - Agency Information Collection Activities: Requests for Comments; Clearance of Renewed Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-09

... Information Collection Clearance Officer, IT Enterprises Business Services Division, AES-200. [FR Doc. 2012... Management System (FAAAMS) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice and request for... about our intention to request the Office of Management and Budget (OMB) approval to renew an...

Defining the ATC Controller Interface for Data Link Clearances

NASA Technical Reports Server (NTRS)

Rankin, James

1998-01-01

The Controller Interface (CI) is the primary method for Air Traffic Controllers to communicate with aircraft via Controller-Pilot Data Link Communications (CPDLC). The controller, wearing a microphone/headset, aurally gives instructions to aircraft as he/she would with today's voice radio systems. The CI's voice recognition system converts the instructions to digitized messages that are formatted according to the RTCA DO-219 Operational Performance Standards for ATC Two-Way Data Link Communications. The DO-219 messages are transferred via RS-232 to the ATIDS system for uplink using a Mode-S datalink. Pilot acknowledgments of controller messages are downlinked to the ATIDS system and transferred to the Cl. A computer monitor is used to convey information to the controller. Aircraft data from the ARTS database are displayed on flight strips. The flight strips are electronic versions of the strips currently used in the ATC system. Outgoing controller messages cause the respective strip to change color to indicate an unacknowledged transmission. The message text is shown on the flight strips for reference. When the pilot acknowledges the message, the strip returns to its normal color. A map of the airport can also be displayed on the monitor. In addition to voice recognition, the controller can enter messages using the monitor's touch screen or by mouse/keyboard.

The Multifaceted Role of T-Helper Responses in Host Defense against Aspergillus fumigatus.

PubMed

Dewi, Intan M W; van de Veerdonk, Frank L; Gresnigt, Mark S

2017-10-04

The ubiquitous opportunistic fungal pathogen Aspergillus fumigatus rarely causes infections in immunocompetent individuals. A healthy functional innate immune system plays a crucial role in preventing Aspergillus -infection. This pivotal role for the innate immune system makes it a main research focus in studying the pathogenesis of aspergillosis. Although sometimes overshadowed by the innate immune response, the adaptive immune response, and in particular T-helper responses, also represents a key player in host defense against Aspergillus . Virtually all T-helper subsets have been described to play a role during aspergillosis, with the Th1 response being crucial for fungal clearance. However; morbidity and mortality of aspergillosis can also be partly attributed to detrimental immune responses resulting from adaptive immune activation. Th2 responses benefit fungal persistence; and are the foundation of allergic forms of aspergillosis. The Th17 response has two sides; although crucial for granulocyte recruitment, it can be involved in detrimental immunopathology. Regulatory T-cells, the endogenous regulators of inflammatory responses, play a key role in controlling detrimental inflammatory responses during aspergillosis. The current knowledge of the adaptive immune response against A. fumigatus is summarized in this review. A better understanding on how T-helper responses facilitate clearance of Aspergillus -infection and control inflammation can be the fundamental basis for understanding the pathogenesis of aspergillosis and for the development of novel host-directed therapies.

A comparison of experimental and theoretical results for labyrinth gas seals with honeycomb stators. M.S. Thesis

NASA Technical Reports Server (NTRS)

Hawkins, Lawrence Allen

1988-01-01

Experimental results for the rotordynamic stiffness and damping coefficients of a labyrinth -rotor honeycomb-stator seal are presented. The coefficients are compared to the coefficients of a labyrinth-rotor smooth-stator seal having the same geometry. The coefficients are compared to analytical results from a two-control-volume compressible flow model. The experimental results show that the honeycomb stator configuration is more stable than the smooth stator configuration at low rotor speeds. At high rotor speeds and low clearance, the smooth stator seal is more stable. The theoretical model predicts the cross-coupled stiffness of the honeycomb stator seal correctly within 25 percent of measured values. The model provides accurate predictions of direct damping for large clearance seals. Overall, the model does not perform as well for low clearance seals as for high clearance seals.

Adaptive control of theophylline therapy: importance of blood sampling times.

PubMed

D'Argenio, D Z; Khakmahd, K

1983-10-01

A two-observation protocol for estimating theophylline clearance during a constant-rate intravenous infusion is used to examine the importance of blood sampling schedules with regard to the information content of resulting concentration data. Guided by a theory for calculating maximally informative sample times, population simulations are used to assess the effect of specific sampling times on the precision of resulting clearance estimates and subsequent predictions of theophylline plasma concentrations. The simulations incorporated noise terms for intersubject variability, dosing errors, sample collection errors, and assay error. Clearance was estimated using Chiou's method, least squares, and a Bayesian estimation procedure. The results of these simulations suggest that clinically significant estimation and prediction errors may result when using the above two-point protocol for estimating theophylline clearance if the time separating the two blood samples is less than one population mean elimination half-life.

Method to improve the blade tip-timing accuracy of fiber bundle sensor under varying tip clearance

NASA Astrophysics Data System (ADS)

Duan, Fajie; Zhang, Jilong; Jiang, Jiajia; Guo, Haotian; Ye, Dechao

2016-01-01

Blade vibration measurement based on the blade tip-timing method has become an industry-standard procedure. Fiber bundle sensors are widely used for tip-timing measurement. However, the variation of clearance between the sensor and the blade will bring a tip-timing error to fiber bundle sensors due to the change in signal amplitude. This article presents methods based on software and hardware to reduce the error caused by the tip clearance change. The software method utilizes both the rising and falling edges of the tip-timing signal to determine the blade arrival time, and a calibration process suitable for asymmetric tip-timing signals is presented. The hardware method uses an automatic gain control circuit to stabilize the signal amplitude. Experiments are conducted and the results prove that both methods can effectively reduce the impact of tip clearance variation on the blade tip-timing and improve the accuracy of measurements.

Clearance Prediction Methodology Needs Fundamental Improvement: Trends Common to Rat and Human Hepatocytes/Microsomes and Implications for Experimental Methodology.

PubMed

Wood, F L; Houston, J B; Hallifax, D

2017-11-01

Although prediction of clearance using hepatocytes and liver microsomes has long played a decisive role in drug discovery, it is widely acknowledged that reliably accurate prediction is not yet achievable despite the predominance of hepatically cleared drugs. Physiologically mechanistic methodology tends to underpredict clearance by several fold, and empirical correction of this bias is confounded by imprecision across drugs. Understanding the causes of prediction uncertainty has been slow, possibly reflecting poor resolution of variables associated with donor source and experimental methods, particularly for the human situation. It has been reported that among published human hepatocyte predictions there was a tendency for underprediction to increase with increasing in vivo intrinsic clearance, suggesting an inherent limitation using this particular system. This implied an artifactual rate limitation in vitro, although preparative effects on cell stability and performance were not yet resolved from assay design limitations. Here, to resolve these issues further, we present an up-to-date and comprehensive examination of predictions from published rat as well as human studies (where n = 128 and 101 hepatocytes and n = 71 and 83 microsomes, respectively) to assess system performance more independently. We report a clear trend of increasing underprediction with increasing in vivo intrinsic clearance, which is similar both between species and between in vitro systems. Hence, prior concerns arising specifically from human in vitro systems may be unfounded and the focus of investigation in the future should be to minimize the potential in vitro assay limitations common to whole cells and subcellular fractions. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Blade tip clearance measurement of the turbine engines based on a multi-mode fiber coupled laser ranging system

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

Guo, Haotian; Duan, Fajie; Wu, Guoxiu

2014-11-15

The blade tip clearance is a parameter of great importance to guarantee the efficiency and safety of the turbine engines. In this article, a laser ranging system designed for blade tip clearance measurement is presented. Multi-mode fiber is utilized for optical transmission to guarantee that enough optical power is received by the sensor probe. The model of the tiny sensor probe is presented. The error brought by the optical path difference of different modes of the fiber is estimated and the length of the fiber is limited to reduce this error. The measurement range in which the optical power receivedmore » by the probe remains essentially unchanged is analyzed. Calibration experiments and dynamic experiments are conducted. The results of the calibration experiments indicate that the resolution of the system is about 0.02 mm and the range of the system is about 9 mm.« less

Transforming the NAS: The Next Generation Air Traffic Control System

NASA Technical Reports Server (NTRS)

Erzberger, Heinz

2004-01-01

The next-generation air traffic control system must be designed to safely and efficiently accommodate the large growth of traffic expected in the near future. It should be sufficiently scalable to contend with the factor of 2 or more increase in demand expected by the year 2020. Analysis has shown that the current method of controlling air traffic cannot be scaled up to provide such levels of capacity. Therefore, to achieve a large increase in capacity while also giving pilots increased freedom to optimize their flight trajectories requires a fundamental change in the way air traffic is controlled. The key to achieving a factor of 2 or more increase in airspace capacity is to automate separation monitoring and control and to use an air-ground data link to send trajectories and clearances directly between ground-based and airborne systems. In addition to increasing capacity and offering greater flexibility in the selection of trajectories, this approach also has the potential to increase safety by reducing controller and pilot errors that occur in routine monitoring and voice communication tasks.

New digital capacitive measurement system for blade clearances

NASA Astrophysics Data System (ADS)

Moenich, Marcel; Bailleul, Gilles

This paper presents a totally new concept for tip blade clearance evaluation in turbine engines. This system is able to detect exact 'measurands' even under high temperature and severe conditions like ionization. The system is based on a heavy duty probe head, a miniaturized thick-film hybrid electronic circuit and a signal processing unit for real time computing. The high frequency individual measurement values are digitally filtered and linearized in real time. The electronic is built in hybrid technology and therefore can be kept extremely small and robust, so that the system can be used on actual flights.

Integrated viral clearance strategies-reflecting on the present, projecting to the future.

PubMed

Roush, David J

2018-01-20

Viral clearance and inactivation are critical steps in ensuring the safety of biological products derived from mammalian cell culture and are a component of an adventitious agent control strategy which spans both upstream and downstream processes. Although these approaches have been sufficient to support the development of biologics to date, the empirical and semi-quantitative nature of the approach leaves some potential gaps. For example, the concept of performing a quantitative risk assessment for the downstream components of virus safety was introduced in ICH Q5A for XMuLV. An ideal future state would be to perform a similar quantitative risk assessment for a range of viruses based on an assessment of potential virus risk in both upstream and downstream processes. This assessment combined with an integrated control strategy (including monitoring) would be extremely beneficial in minimizing potential adventitious agent risks. Significant progress has been achieved towards this goal in the last several years including recent advances in quantification of virus sequences in cell banks (ADVTIG), development of truly modular or generic viral clearance claims for specific unit operations, enhanced controls of upstream media (HTST/nanofiltration) and the use of RVLP for in-process monitoring. The recent shift towards continuous processing has the potential to enhance the criticality of in-line monitoring and the complexity of viral clearance and inactivation (owing to a wide range of potential 'worst case' viral clearance scenarios). However, gaps exist in, firstly, the ability to quantify potential virus risk levels in process streams in real-time, secondly, mechanistic understanding of virus/chromatography media interactions, and thirdly, mechanistic understanding of virus/filter interactions. Some new technologies may also need to be developed to allow for real-time confirmation of virus inactivation and clearance to support process development (both batch and continuous) and assessment of the impact of process deviations during manufacturing. This review paper provides an overview of the current state of an overall integrated control strategy for upstream and downstream processing and highlights the investments that could be pursued to achieve the future state of a quantitative virus risk assessment for a range of viruses. One potential approach to address these gaps is the use of data mining from large, comprehensive and diverse data sets to establish heuristic rules for virus detection, clearance and inactivation followed by specific hypothesis-driven experiments for cases that fall outside of the normal paradigm. Once this approach reaches a mature state suitable for implementation, there is an opportunity to update regulatory guidance (e.g. ICH Q5A) accordingly. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of experimental hypothyroidism on glomerular filtration rate and plasma creatinine concentration in dogs.

PubMed

Panciera, D L; Lefebvre, H P

2009-01-01

Hypothyroidism affects renal function in a manner opposite the effects of hyperthyroidism. To evaluate the effects of experimentally induced hypothyroidism on glomerular filtration rate (GFR) and basal plasma creatinine concentration in dogs. Sixteen anestrous, female dogs. Hypothyroidism was induced by administration of (131)I in 8 dogs, and 8 healthy euthyroid dogs acted as controls. Exogenous plasma creatinine clearance (an estimate of GFR) was measured in all dogs before (control period) and 43-50 weeks after induction of hypothyroidism (posttreatment period). Other pharmacokinetic parameters of creatinine were also determined. No significant difference was observed for basal plasma creatinine concentration and creatinine clearance between control and hypothyroid dogs in the control period. In the posttreatment period, mean + or - SD creatinine clearance in the hypothyroid group (2.13 + or - 0.48 mL/min/kg) was lower (P < .001) than that of the control group (3.20 + or - 0.42 mL/kg/min). Nevertheless, basal plasma creatinine concentrations were not significantly different between the hypothyroid and control groups (0.74 + or - 0.18 versus 0.70 + or - 0.08 mg/dL, respectively) because endogenous production of creatinine was decreased in hypothyroid dogs (22 + or - 3 versus 32 + or - 5 mg/kg/d, P=.001). Hypothyroidism causes a substantial decrease in GFR without altering plasma creatinine concentrations, indicating that GFR evaluation is needed to identify renal dysfunction in such patients.

A preliminary study of the effect of guaiphenesin on mucociliary clearance from the human lung

PubMed Central

Thomson, M. L.; Pavia, D.; McNicol, M. W.

1973-01-01

Thomson, M. L., Pavia, D., and McNicol, M. W. (1973).Thorax, 28, 742-747. A preliminary study of the effect of guaiphenesin on mucociliary clearance from the human lung. The effect of guaiphenesin (administered as Robitussin1) on mucociliary clearance has been assessed in 15 subjects from the rate of removal from the lung of previously inhaled radioactive tracer particles. The guaiphenesin was compared with a positive control preparation consisting of the guaiphenesin vehicle only in two double-blind crossover trials. The first trial examined eight aged `healthy' volunteer subjects and the second trial examined seven chronic bronchitic patients. Sequential gamma counts were made from the whole lung by scintillation counters for 6 hours after inhalation and the chest was also scanned rectilinearly. In the first 5 hours after inhalation the mean rate of removal of particles and therefore of secretions was faster after guaiphenesin than after the control preparation. This difference was not statistically significant in the healthy volunteers but achieved significance (P <0·05) in the chronic bronchitic patients. Lung scans after inhaling the tracer aerosol indicated that on average the initial penetration of the particles into the lung was similar in the guaiphenesin and control runs. The faster clearance after guaiphenesin was unlikely to be due to bulk movements of mucus caused by coughing since the mean frequency of coughing during the experiment was somewhat less after the drug. PMID:4595814

Clinical evaluation of plasma insulin and C-peptide levels with 3 different high-flux dialyzers in diabetic patients on hemodialysis.

PubMed

Abe, M; Okada, K; Maruyama, T; Inoshita, A; Ikeda, K; Uto, E; Kikuchi, F; Matsumoto, K

2008-10-01

Changes in plasma immunoreactive insulin (IRI) and connecting-peptide immunoreactivity (CPR) concentrations during hemodialysis (HD) were evaluated in diabetic HD patients with 3 different high-flux membranes. The removal properties of the membranes were compared. In this prospective controlled study, 15 stable diabetic patients on HD were randomly selected for 6 HD sessions with 3 different membranes: polysulfone (PS), cellulose triacetate (CTA), and polymethylmethacrylate (PMMA). Blood samples were obtained from the blood tubing at the arterial (A) site at the beginning and end of the sixth HD session. At 60 minutes after dialysis initiation, blood samples were obtained from both the A and venous (V) sites of the dialyzer to investigate the clearance and removal properties of the membranes. The plasma IRI and CPR levels decreased significantly at each time point with all 3 membranes. IRI clearance with the PS membrane was significantly higher than that with the CTA and PMMA membranes. No difference was observed in the IRI reduction rate between the 3 membranes. CPR clearance and reduction rate with the PMMA membrane were lower than with the PS and CTA membranes. No significant difference was observed in serum creatinine clearance and reduction rates between the 3 membranes; however, serum urea nitrogen clearance was significantly lower with the PMMA membrane compared with the PS and CTA membranes. A significantly high beta2-microglobulin clearance and reduction rate was achieved in the order PS > CTA > PMMA. Plasma IRI and CPR are cleared by HD; their clearance rates differ with the dialyzer membranes. Plasma IRI clearance with the PS membrane is higher than that with the CTA and PMMA membranes.

LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-β.

PubMed

Kanekiyo, Takahisa; Liu, Chia-Chen; Shinohara, Mitsuru; Li, Jie; Bu, Guojun

2012-11-14

Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer's disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-density lipoprotein receptor-related protein 1 (LRP1), is abundantly expressed in cerebrovasculature, in particular in vascular smooth muscle cells. Previous studies have indicated a role of LRP1 in endothelial cells in transcytosing Aβ out of the brain across the BBB; however, whether this represents a significant pathway for brain Aβ clearance remains controversial. Here, we demonstrate that Aβ can be cleared locally in the cerebrovasculature by an LRP1-dependent endocytic pathway in smooth muscle cells. The uptake and degradation of both endogenous and exogenous Aβ were significantly reduced in LRP1-suppressed human brain vascular smooth muscle cells. Conditional deletion of Lrp1 in vascular smooth muscle cell in amyloid model APP/PS1 mice accelerated brain Aβ accumulation and exacerbated Aβ deposition as amyloid plaques and CAA without affecting Aβ production. Our results demonstrate that LRP1 is a major Aβ clearance receptor in cerebral vascular smooth muscle cell and a disturbance of this pathway contributes to Aβ accumulation. These studies establish critical functions of the cerebrovasculature system in Aβ metabolism and identify a new pathway involved in the pathogenesis of both AD and CAA.

Fiber-optic laser Doppler turbine tip clearance probe

NASA Astrophysics Data System (ADS)

Büttner, Lars; Pfister, Thorsten; Czarske, Jürgen

2006-05-01

A laser Doppler based method for in situ single blade tip clearance measurements of turbomachines with high precision is presented for what we believe is the first time. The sensor is based on two superposed fanlike interference fringe systems generated by two laser wavelengths from a fiber-coupled, passive, and therefore compact measurement head employing diffractive optics. Tip clearance measurements at a transonic centrifugal compressor performed during operation at 50,000 rpm (833 Hz, 586 m/s tip speed) are reported. At these speeds the measured uncertainty of the tip position was less than 20 μm, a factor of 2 more accurate than that of capacitive probes. The sensor offers great potential for in situ and online high-precision tip clearance measurements of metallic and nonmetallic turbine blades.

Fiber-optic laser Doppler turbine tip clearance probe.

PubMed

Büttner, Lars; Pfister, Thorsten; Czarske, Jürgen

2006-05-01

A laser Doppler based method for in situ single blade tip clearance measurements of turbomachines with high precision is presented for what we believe is the first time. The sensor is based on two superposed fanlike interference fringe systems generated by two laser wavelengths from a fiber-coupled, passive, and therefore compact measurement head employing diffractive optics. Tip clearance measurements at a transonic centrifugal compressor performed during operation at 50,000 rpm (833 Hz, 586 m/s tip speed) are reported. At these speeds the measured uncertainty of the tip position was less than 20 microm, a factor of 2 more accurate than that of capacitive probes. The sensor offers great potential for in situ and online high-precision tip clearance measurements of metallic and nonmetallic turbine blades.

Effects of airborne pollutants on mucociliary clearance.

PubMed

Wolff, R K

1986-04-01

The mucociliary clearance system is a first line of defense against inhaled agents, and so its compromise can adversely affect health. The purpose of this paper is to provide a review of data on the effect of in vivo air pollutant exposures on the clearance of test particles from airways. Data from both animals and humans are compared whenever possible, so that estimates of human health effects may be made. Mechanisms of action are also discussed, presenting the view that for low level exposures, changes in secretions are probably responsible for most observed changes in clearance. The pollutants pertinent to this review are those that are common in the environment and most likely to have impacts on large numbers of people: sulfur oxides, sulfuric acid mist, O3, NO2, particulates, diesel exhaust, and cigarette smoke.

30 CFR 27.36 - Test for adequacy of electrical insulation and clearances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Test for adequacy of electrical insulation and clearances. 27.36 Section 27.36 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS METHANE-MONITORING SYSTEMS Test Requirements § 27.36...

78 FR 5859 - Agency Information Collection Activities: Requests for Comments; Clearance of Renewed Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-28

... Personnel Management online USAJOBS system and the FAA's Automated Vacancy Information Access Tool for... (202) 395-6974, or mailed to the Office of Information and Regulatory Affairs, Office of Management and... Information Collection Clearance Officer, IT Enterprises Business Services Division, AES-200. [FR Doc. 2013...

Evaluation of a Microwave Blade Tip Clearance Sensor for Propulsion Health Monitoring

NASA Technical Reports Server (NTRS)

Woike, Mark R.

2013-01-01

The NASA Glenn Research Center has investigated a microwave blade tip clearance system for the structural health monitoring of gas turbine engines. This presentation describes the sensors and the experiments that have been conducted to evaluate their performance along with future plans for their use on an engine ground test.

30 CFR 27.36 - Test for adequacy of electrical insulation and clearances.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Test for adequacy of electrical insulation and clearances. 27.36 Section 27.36 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS METHANE-MONITORING SYSTEMS Test Requirements § 27.36...

Interaction between blood-brain barrier and glymphatic system in solute clearance.

PubMed

Verheggen, I C M; Van Boxtel, M P J; Verhey, F R J; Jansen, J F A; Backes, W H

2018-03-30

Neurovascular pathology concurs with protein accumulation, as the brain vasculature is important for waste clearance. Interstitial solutes, such as amyloid-β, were previously thought to be primarily cleared from the brain by blood-brain barrier transport. Recently, the glymphatic system was discovered, in which cerebrospinal fluid is exchanged with interstitial fluid, facilitated by the aquaporin-4 water channels on the astroglial endfeet. Glymphatic flow can clear solutes from the interstitial space. Blood-brain barrier transport and glymphatic clearance likely serve complementary roles with partially overlapping mechanisms providing a well-conditioned neuronal environment. Disruption of these mechanisms can lead to protein accumulation and may initiate neurodegenerative disorders, for instance amyloid-β accumulation and Alzheimer's disease. Although both mechanisms seem to have a similar purpose, their interaction has not been clearly discussed previously. This review focusses on this interaction in healthy and pathological conditions. Future health initiatives improving waste clearance might delay or even prevent onset of neurodegenerative disorders. Defining glymphatic flow kinetics using imaging may become an alternative way to identify those at risk of Alzheimer's disease. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Study of nanometer-level precise phase-shift system used in electronic speckle shearography and phase-shift pattern interferometry

NASA Astrophysics Data System (ADS)

Jing, Chao; Liu, Zhongling; Zhou, Ge; Zhang, Yimo

2011-11-01

The nanometer-level precise phase-shift system is designed to realize the phase-shift interferometry in electronic speckle shearography pattern interferometry. The PZT is used as driving component of phase-shift system and translation component of flexure hinge is developed to realize micro displacement of non-friction and non-clearance. Closed-loop control system is designed for high-precision micro displacement, in which embedded digital control system is developed for completing control algorithm and capacitive sensor is used as feedback part for measuring micro displacement in real time. Dynamic model and control model of the nanometer-level precise phase-shift system is analyzed, and high-precision micro displacement is realized with digital PID control algorithm on this basis. It is proved with experiments that the location precision of the precise phase-shift system to step signal of displacement is less than 2nm and the location precision to continuous signal of displacement is less than 5nm, which is satisfied with the request of the electronic speckle shearography and phase-shift pattern interferometry. The stripe images of four-step phase-shift interferometry and the final phase distributed image correlated with distortion of objects are listed in this paper to prove the validity of nanometer-level precise phase-shift system.

The impact of intrarenal nitric oxide synthase inhibition on renal blood flow and function in mild and severe hyperdynamic sepsis.

PubMed

Ishikawa, Ken; Bellomo, Rinaldo; May, Clive N

2011-04-01

In experimental hyperdynamic sepsis, renal function deteriorates despite renal vasodilatation and increased renal blood flow. Because nitric oxide is increased in sepsis and participates in renal blood flow control, we investigated the effects of intrarenal Nω-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase inhibitor, in mild and severe sepsis. Prospective crossover and randomized control interventional studies. University-affiliated research institute. Thirty-two merino ewes. Examination of responses to intrarenal infusion of Nω-nitro-L-arginine methyl ester for 8 hrs in unilaterally nephrectomized normal sheep and in sheep administered Escherichia coli. : In normal sheep, Nω-nitro-L-arginine methyl ester decreased renal blood flow (301 ± 30 to 228 ± 26 mL/min) and creatinine clearance (40.0 ± 5.8 to 31.1 ± 2.8 mL/min), whereas plasma creatinine increased, but fractional excretion of sodium was unchanged. In sheep with nonhypotensive hyperdynamic sepsis, plasma creatinine increased and there were decreases in creatinine clearance (34.5 ± 4.6 to 20.1 ± 3.7 mL/min) and fractional excretion of sodium despite increased renal blood flow. Infusion of Nω-nitro-L-arginine methyl ester normalized renal blood flow and increased urine output, but creatinine clearance did not improve and plasma creatinine and fractional excretion of sodium increased. In sheep with severe hypotensive sepsis, creatinine clearance decreased further (31.1 ± 5.4 to 16.0 ± 1.7 mL/min) despite increased renal blood flow. Infusion of Nω-nitro-L-arginine methyl ester restored mean arterial pressure and reduced renal blood flow but did not improve plasma creatinine or creatinine clearance. In hyperdynamic sepsis, with or without hypotension, creatinine clearance decreased despite increasing renal blood flow. Intrarenal Nω-nitro-L-arginine methyl ester infusion reduced renal blood flow but did not improve creatinine clearance. These data indicate that septic acute kidney injury is not the result of decreased renal blood flow nor is it improved by nonspecific nitric oxide synthase inhibition.

Elucidation of the pharmacokinetics of prednisone and prednisolone: elimination and the effect of estrogen

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

Gustavson, L.E.

Several aspects of the pharmacokinetics of the interconvertible glucocorticoids prednisone and prednisolone have been studied. The pharmacokinetics of prednisolone were examined in postmenopausal women taking conjugated estrogens and age-matched control women. The subjects received iv bolus doses of 0.14 and 0.55 mg/kg prednisolone. Expected increases in clearance and volume of distribution with increasing dose were observed for total prednisolone in all subjects. At both doses, significant decreases in total and unbound prednisolone clearance were observed in the women taking estrogen compared to the controls. Volume of distribution was unchanged. The decreases in clearance are smaller than those observed in youngmore » women taking oral contraceptives indicating that factors other than estrogen administration may influence prednisolone clearance in oral contraceptive users. While the protein binding of prednisolone is well characterized, little is known about the protein binding of prednisone. Equilibrium dialysis employing (/sup 3/H)prednisone was used to study the binding of prednisone in human plasma containing endogenous hydrocortisone. Plasma was obtained from volunteers with normal and elevated transcortin binding capacities (CAP/sub T/). Prednisolone binding exhibits marked concentration dependence and sensitivity to CAP/sub T/. In contrast, prednisone binding is independent of concentration and CAP/sub T/.« less

Plasma interferon-gamma-inducible protein-10 (IP-10) levels during acute hepatitis C virus infection

PubMed Central

Grebely, Jason; Feld, Jordan J.; Applegate, Tanya; Matthews, Gail V.; Hellard, Margaret; Sherker, Alana; Petoumenos, Kathy; Zang, Geng; Shaw, Ineke; Yeung, Barbara; George, Jacob; Teutsch, Suzy; Kaldor, John M.; Cherepanov, Vera; Bruneau, Julie; Shoukry, Naglaa H.; Lloyd, Andrew R.; Dore, Gregory J.

2013-01-01

Systemic levels of interferon-gamma-inducible protein-10 (IP-10) are predictive of treatment-induced clearance in chronic HCV. In the present study, factors associated with plasma IP-10 levels at the time of acute HCV detection and the association between IP-10 levels and spontaneous clearance were assessed in three cohorts of acute HCV infection. Among 300 individuals, 245 (181 male, 47 HIV+) were HCV RNA+ at acute HCV detection. In adjusted analysis, factors independently associated with IP-10 levels ≥150 pg/mL (median level) included HCV RNA levels >6 log IU/mL, HIV co-infection and non-Aboriginal ethnicity. Among 245 HCV RNA+ at acute HCV detection, 214 were untreated (n=137) or had persistent infection (infection duration ≥26 weeks) at treatment initiation (n=77). Spontaneous clearance occurred in 14% (29 of 214). Individuals without spontaneous clearance had significantly higher mean plasma IP-10 levels at the time of acute HCV detection than those with clearance (248±32 vs. 142±22 pg/mL, P=0.008). The proportion of individuals with spontaneous clearance was 0% (0 of 22, P=0.048) and 16% (27 of 165) and in those in those with and without plasma IP-10 levels ≥380 pg/mL. In adjusted analyses, favourable IL28B genotype was associated with spontaneous clearance, while higher HCV RNA level was independently associated with lower odds of spontaneous clearance. Conclusion High IP-10 levels at acute HCV detection were associated with failure to spontaneously clear HCV. Patients with acute HCV and high baseline IP-10 levels, particularly >380 pg/mL, should be considered for early therapeutic intervention, and those with low levels should defer therapy for potential spontaneous clearance. PMID:23325615

Improved drainage with active chest tube clearance.

PubMed

Shiose, Akira; Takaseya, Tohru; Fumoto, Hideyuki; Arakawa, Yoko; Horai, Tetsuya; Boyle, Edward M; Gillinov, A Marc; Fukamachi, Kiyotaka

2010-05-01

This study was performed to evaluate the efficacy of a novel chest drainage system. This system employs guide wire-based active chest tube clearance to improve drainage and maintain patency. A 32 Fr chest tube was inserted into pleural cavities of five pigs. On the left, a tube was connected to the chest canister, and on the right, the new system was inserted between the chest tube and chest canister. Acute bleeding was mimicked by periodic infusion of blood. The amount of blood drained from each chest cavity was recorded every 15 min for 2 h. After completion of the procedure, all residual blood and clots in each chest cavity were assessed. The new system remained widely patent, and the amount of drainage achieved with this system (670+/-105 ml) was significantly (P=0.01) higher than that with the standard tube (239+/-131 ml). The amount of retained pleural blood and clots with this system (150+/-107 ml) was significantly (P=0.04) lower than that with the standard tube (571+/-248 ml). In conclusion, a novel chest drainage system with active tube clearance significantly improved drainage without tube manipulations. 2010 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.

Optimizing home dialysis: role of hemodiafiltration.

PubMed

Vilar, Enric; Farrington, Ken; Bates, Chris; Mumford, Carol; Greenwood, Roger

2011-01-01

Over the last 40 years the technical obstacles which prevented a convective contribution to diffusive dialysis have been overcome. Hemodiafiltration represents a natural evolution of intermittent extracorporeal blood purification and the technology is now available to offer this as standard treatment in-center. The first randomized control trial of dialysis dose (National Cooperative Dialysis Study) showed that for three times weekly dialysis a critical level of urea clearance was necessary to ensure complication-free survival, the effect being noticeable by 3 months. Following this, observational studies suggested that higher doses improved longer term outcome. In a second large randomized controlled study (HEMO), higher small molecule clearance did not further improve outcome, but high-flux membranes, which permitted enhanced clearance of middle molecules, appeared to confer survival benefit in patients who had already been on dialysis > 3.7 years. Recently, outcomes from the Membrane Permeability Outcome study confirmed a survival benefit of high-flux membranes in high-risk patients. These studies indicate that in the medium term survival is critically dependent on achieving a minimum level of small solute removal. However, longer term survival (measured in years or decades) not only requires better small solute clearance but also enhanced clearance of middle molecules, the toxicity of which manifest over longer time scales. The rationale for convective treatment is strongest, therefore in those patients who have the greatest potential for long-term survival. Patients who opt for self-care at home to allow frequent dialysis generally are constituents of this group. Hemodiafiltration is likely to become standard therapy in-center and in the home. Copyright © 2011 S. Karger AG, Basel.

Swing limb mechanics and minimum toe clearance in people with knee osteoarthritis.

PubMed

Levinger, Pazit; Lai, Daniel T H; Menz, Hylton B; Morrow, Adam D; Feller, Julian A; Bartlett, John R; Bergman, Neil R; Begg, Rezaul

2012-02-01

Knee osteoarthritis (OA) has been shown to be a risk factor for falls. Reductions in foot clearance during the swing phase of walking can cause a trip and potentially lead to a fall. This study examined the swing phase mechanics of people with and without knee OA during walking. Minimum toe clearance (MTC) height, joint angles at the time of MTC and the influence of the angular changes of the hip, knee and ankle of the swing leg on foot clearance using sensitivity analysis were investigated in 50 knee OA participants and 28 age-matched asymptomatic controls. Although both groups had a similar MTC height (controls: 12.8±6.7 mm, knee OA: 13.4±7.0 mm), the knee OA group used a different strategy to achieve the same foot clearance, as evidenced by greater knee flexion (52.5±5.3° vs 49.4±4.8°, p=0.007), greater hip abduction (-3.6±3.3° vs -1.8±3.3°, p=0.03) and less ankle adduction (2.8±1.9° vs 4.2±2.1°, p=0.01). MTC height was comparable between the groups, however a different swing phase mechanism was used by the knee OA. Although adequate MTC is an important component of safe locomotion, it does not appear to be impaired in people with knee OA. Other factors, such as inadequate responses to postural perturbation, may be responsible for falls in this group. Copyright © 2011 Elsevier B.V. All rights reserved.

Traffic control procedures for emergency responders.

DOT National Transportation Integrated Search

2006-10-01

The objective of this study was to develop a training course and handbook to guide on-scene emergency responders responsible for controlling traffic during a roadway crash and subsequent clearance. : Traffic control is an essential component of incid...

Study of Command and Control (C&C) Structures on Integrating Unmanned Autonomous Systems (UAS) into Manned Environments

DTIC Science & Technology

2012-09-01

and traveled all the way around Lake Tahoe. The self - driving cars have logged over 140,000 miles since October 9, 2010 (Google 2010) pictured here...UNDERWATER VEHICLES (AUV) STARFISH is the name given to a small team of autonomous robotic fish - a project carried out by the Acoustic Research...www.scribd.com/doc/42245301/Manual-Mine- Clearance-Book1. Accessed July 23, 2012. Google. The Self - Driving Car Logs more Miles on New Wheels. August 7

Prototype Stop Bar System Evaluation at John F. Kennedy International Airport

DTIC Science & Technology

1992-09-01

2 Red Stop Bar Visual Presentation 4 3 Green Stop Bar Visual Presentation 5 4 Photographs of Red and Green Inset Stop Bar Lights 6 5 Photographs of...to green. This provides pilots with a visual confirmation of the controller’s verbal clearance and is intended to prevent runway incursions. The Port...34 colocated with the red lights. The visual presentation of an individual stop bar appears as either five red lights (see figure 2), or five green

Cervicovestibular rehabilitation in sport-related concussion: a randomised controlled trial.

PubMed

Schneider, Kathryn J; Meeuwisse, Willem H; Nettel-Aguirre, Alberto; Barlow, Karen; Boyd, Lara; Kang, Jian; Emery, Carolyn A

2014-09-01

Concussion is a common injury in sport. Most individuals recover in 7-10 days but some have persistent symptoms. The objective of this study was to determine if a combination of vestibular rehabilitation and cervical spine physiotherapy decreased the time until medical clearance in individuals with prolonged postconcussion symptoms. This study was a randomised controlled trial. Consecutive patients with persistent symptoms of dizziness, neck pain and/or headaches following a sport-related concussion (12-30 years, 18 male and 13 female) were randomised to the control or intervention group. Both groups received weekly sessions with a physiotherapist for 8 weeks or until the time of medical clearance. Both groups received postural education, range of motion exercises and cognitive and physical rest until asymptomatic followed by a protocol of graded exertion. The intervention group also received cervical spine and vestibular rehabilitation. The primary outcome of interest was medical clearance to return to sport, which was evaluated by a study sport medicine physician who was blinded to the treatment group. In the treatment group, 73% (11/15) of the participants were medically cleared within 8 weeks of initiation of treatment, compared with 7% (1/14) in the control group. Using an intention to treat analysis, individuals in the treatment group were 3.91 (95% CI 1.34 to 11.34) times more likely to be medically cleared by 8 weeks. A combination of cervical and vestibular physiotherapy decreased time to medical clearance to return to sport in youth and young adults with persistent symptoms of dizziness, neck pain and/or headaches following a sport-related concussion. NCT01860755. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clearance of psoriasis: the impact of private versus public insurance.

PubMed

Buzney, Catherine D; Peterman, Caitlin; Saraiya, Ami; Au, Shiu-chung; Dumont, Nicole; Mansfield, Ryan; Gottlieb, Alice B

2015-02-01

Psoriasis treatments and therapeutic response as they relate to private versus public patient insurance in the United States have not yet been reviewed. Improved understanding could clarify factors challenging optimal psoriasis management and offer insight for dermatologists treating psoriasis within our healthcare system. 258 subjects were included from a database of psoriasis patients seen at Tufts Medical Center (Boston, MA) during 2008-2014. Insurance was classified as primarily private or public (Medicare or MassHealth/Medicaid). Patients required a minimum of two consecutive visits per treatment and at least 8 weeks within one of four treatment categories: biologics, oral systemics/ phototherapy, combined biologics and oral systemics/phototherapy, or topicals only. Primary endpoint was the Simple-Measure for Assessing Psoriasis Activity (S-MAPA) calculated by multiplying Physician Global Assessment by Body Surface Area. S-MAPA<3 constituted absolute clearance. Insurance type was evaluated as a predictor of prescribed treatment categories, maximum S-MAPA improvement from baseline, and total drugs used per treatment course (“drug-switching”). 80.2% (n=207) and 19.8% (n=51) had primarily private and public insurance, respectively. 69.6% with private insurance were prescribed biologics versus 66.7% (public insurance) (P=0.689). 54% (private) versus 49% (public) achieved clearance (P=0.514). However, S-MAPA decreased 78.35% from baseline in those with private insurance compared to 61.48% (public) (P=0.036). On average, privately insured patients used at least twice as many same-category treatments, most commonly biologics, than publicly insured individuals (P=0.003). Drug-switching was significantly associated with clearance (P=0.024). Multivariate analysis demonstrated no significant differences in prescribed treatment categories, drug efficacy, clearance, S-MAPA, or drugswitching with respect to patient age. Treatment categories were comparably prescribed between insurance subgroups. However, privately insured patients achieved significantly greater degrees of clearance and switched between more medications within biologic and systemic categories, potentially explaining their overall improved therapeutic response. Further studies including cost-analysis could clarify any difference in the effectiveness of prescribed therapy for these two patient populations.

A comprehensive assessment of repaglinide metabolic pathways: impact of choice of in vitro system and relative enzyme contribution to in vitro clearance.

PubMed

Säll, Carolina; Houston, J Brian; Galetin, Aleksandra

2012-07-01

Repaglinide is presently recommended by the U.S. Food and Drug Administration as a clinical CYP2C8 probe, yet current in vitro and clinical data are inconsistent concerning the role of this enzyme in repaglinide elimination. The aim of the current study was to perform a comprehensive investigation of repaglinide metabolic pathways and assess their contribution to the overall clearance. Formation of four repaglinide metabolites was characterized using in vitro systems with differential complexity. Full kinetic profiles for the formation of M1, M2, M4, and repaglinide glucuronide were obtained in pooled cryopreserved human hepatocytes, human liver microsomes, human S9 fractions, and recombinant cytochrome P450 enzymes. Distinct differences in clearance ratios were observed between CYP3A4 and CYP2C8 for M1 and M4 formation, resulting in a 60-fold M1/M4 ratio in recombinant (r) CYP3A4, in contrast to 0.05 in rCYP2C8. Unbound K(m) values were within 2-fold for each metabolite across all in vitro systems investigated. A major system difference was seen in clearances for the formation of M2, which is suggested to be a main metabolite of repaglinide in vivo. An approximately 7-fold higher unbound intrinsic clearance was observed in hepatocytes and S9 fractions in comparison to microsomes; the involvement of aldehyde dehydrogenase in M2 formation was shown for the first time. This systematic analysis revealed a comparable in vitro contribution from CYP2C8 and CYP3A4 to the metabolism of repaglinide (<50%), whereas the contribution of glucuronidation ranged from 2 to 20%, depending on the in vitro system used. The repaglinide M4 metabolic pathway is proposed as a specific CYP2C8 probe for the assessment of drug-drug interactions.

Domiciliary humidification improves lung mucociliary clearance in patients with bronchiectasis.

PubMed

Hasani, A; Chapman, T H; McCool, D; Smith, R E; Dilworth, J P; Agnew, J E

2008-01-01

Inspired air humidification has been reported to show some benefit in bronchiectatic patients. We have investigated the possibility that one effect might be to enhance mucociliary clearance. Such enhancement might, if it occurs, help to lessen the risks of recurrent infective episodes. Using a radioaerosol technique, we measured lung mucociliary clearance before and after 7 days of domiciliary humidification. Patients inhaled high flow saturated air at 37 degrees C via a patient-operated humidification nasal inhalation system for 3 h per day. We assessed tracheobronchial mucociliary clearance from the retention of (99m)Tc-labelled polystyrene tracer particles monitored for 6 h, with a follow-up 24-h reading. Ten out of 14 initially recruited patients (age 37-75 years; seven females) completed the study (two withdrew after their initial screening and two prior to the initial clearance test). Seven patients studied were non-smokers; three were ex-smokers (1-9 pack-years). Initial tracer radioaerosol distribution was closely similar between pre- and post-treatment. Following humidification, lung mucociliary clearance significantly improved, the area under the tracheobronchial retention curve decreased from 319 +/- 50 to 271 +/- 46%h (p < 0.07). Warm air humidification treatment improved lung mucociliary clearance in our bronchiectatic patients. Given this finding plus increasing laboratory and clinical interest in humidification mechanisms and effects, we believe further clinical trials of humidification therapy are desirable, coupled with analysis of humidification effects on mucus properties and transport.

Depressed reticuloendothelial clearance of platelets in rats after trauma.

PubMed

Kaplan, J E; Moon, D G; Minnear, F L; Saba, T M

1984-02-01

Platelet microembolization may contribute to microcirculatory and organ damage following trauma and shock. It is hypothesized that posttraumatic reticuloendothelial depression predisposes to such microembolization by failure to clear altered platelets from the circulation. The present study evaluated the short-term (1 h) clearance and organ localization of radiolabeled homologous damaged platelets in normal rats and in rats following sublethal Noble-Collip drum trauma. Platelets were collected in citrated platelet-rich plasma from normal rats and labeled with 51Cr in citrated saline. Platelets were altered by repeated centrifugation in protein-free medium. These platelets differed functionally and morphologically from normal platelets. Disappearance of iv injected damaged platelets conformed to a two-compartment exponential clearance. Velocity of clearance in the rapid compartment correlated with hepatic platelet localization, whereas velocity of clearance in the second compartment correlated with splenic platelet localization. Clearance rate of the rapid compartment was depressed at 1 h after trauma and elevated at 24 h. These changes were associated with a decrease in hepatic platelet localization at 1 h and an increase above normal at 24 h. Splenic platelet localization was decreased by 3 h following trauma. Pulmonary platelet localization was increased at all times following trauma. It is concluded that the posttrauma state is associated with a defect in the reticuloendothelial system clearance of altered platelets, which may augment embolization of platelets in the lung.

Germ Line IgM Is Sufficient, but Not Required, for Antibody-Mediated Alphavirus Clearance from the Central Nervous System.

PubMed

Nilaratanakul, Voraphoj; Chen, Jie; Tran, Oanh; Baxter, Victoria K; Troisi, Elizabeth M; Yeh, Jane X; Griffin, Diane E

2018-04-01

Sindbis virus (SINV) infection of neurons in the brain and spinal cord in mice provides a model system for investigating recovery from encephalomyelitis and antibody-mediated clearance of virus from the central nervous system (CNS). To determine the roles of IgM and IgG in recovery, we compared the responses of immunoglobulin-deficient activation-induced adenosine deaminase-deficient (AID -/- ), secretory IgM-deficient (sIgM -/- ), and AID -/- sIgM -/- double-knockout (DKO) mice with those of wild-type (WT) C57BL/6 mice for disease, clearance of infectious virus and viral RNA from brain and spinal cord, antibody responses, and B cell infiltration into the CNS. Because AID is essential for immunoglobulin class switch recombination and somatic hypermutation, AID -/- mice produce only germ line IgM, while sIgM -/- mice secrete IgG but no IgM and DKO mice produce no secreted immunoglobulin. After intracerebral infection with the TE strain of SINV, most mice recovered. Development of neurologic disease occurred slightly later in sIgM -/- mice, but disease severity, weight loss, and survival were similar between the groups. AID -/- mice produced high levels of SINV-specific IgM, while sIgM -/- mice produced no IgM and high levels of IgG2a compared to WT mice. All mice cleared infectious virus from the spinal cord, but DKO mice failed to clear infectious virus from brain and had higher levels of viral RNA in the CNS late after infection. The numbers of infected cells and the amount of cell death in brain were comparable. We conclude that antibody is required and that either germ line IgM or IgG is sufficient for clearance of virus from the CNS. IMPORTANCE Mosquito-borne alphaviruses that infect neurons can cause fatal encephalomyelitis. Recovery requires a mechanism for the immune system to clear virus from infected neurons without harming the infected cells. Antiviral antibody has previously been shown to be a noncytolytic means for alphavirus clearance. Antibody-secreting cells enter the nervous system after infection and produce antiviral IgM before IgG. Clinical studies of human viral encephalomyelitis suggest that prompt production of IgM is associated with recovery, but it was not known whether IgM is effective for clearance. Our studies used mice deficient in production of IgM, IgG, or both to characterize the antibody necessary for alphavirus clearance. All mice developed similar signs of neurologic disease and recovered from infection. Antibody was necessary for virus clearance from the brain, and either early germ line IgM or IgG was sufficient. These studies support the clinical observation that prompt production of antiviral antibody is a determinant of outcome. Copyright © 2018 American Society for Microbiology.

The Effect of a Six-Month Dancing Program on Motor-Cognitive Dual-Task Performance in Older Adults.

PubMed

Hamacher, Dennis; Hamacher, Daniel; Rehfeld, Kathrin; Hökelmann, Anita; Schega, Lutz

2015-10-01

Dancing is a complex sensorimotor activity involving physical and mental elements which have positive effects on cognitive functions and motor control. The present randomized controlled trial aims to analyze the effects of a dancing program on the performance on a motor-cognitive dual task. Data of 35 older adults, who were assigned to a dancing group or a health-related exercise group, are presented in the study. In pretest and posttest, we assessed cognitive performance and variability of minimum foot clearance, stride time, and stride length while walking. Regarding the cognitive performance and the stride-to-stride variability of minimum foot clearance, interaction effects have been found, indicating that dancing lowers gait variability to a higher extent than conventional health-related exercise. The data show that dancing improves minimum foot clearance variability and cognitive performance in a dual-task situation. Multi-task exercises (like dancing) might be a powerful tool to improve motor-cognitive dual-task performance.

A randomized controlled trial of verapamil on cyclosporine nephrotoxicity in heart and lung transplant recipients.

PubMed

Chan, C; Maurer, J; Cardella, C; Cattran, D; Pei, Y

1997-05-27

Cyclosporine (CsA) is a potent immunosuppressive drug widely used in organ transplantation and in the treatment of autoimmune diseases (1, 2). However, its common nephrotoxic effect is a major limiting factor. Short-term CsA treatment has been shown to cause reversible renal vasoconstriction, whereas long-term treatment can lead to an afferent arteriolopathy and chronic renal failure. We performed a randomized controlled trial to examine the short-term renal effects of verapamil in 32 CsA-treated heart or lung transplant recipients. Sixteen patients each were randomized to receive a 6-week course of verapamil or control treatment (atenolol in hypertensive patients and placebo in normotensive patients) 1-2 months after transplantation. An 8-hr sequential clearance study of inulin and p-aminohippuric acid for estimating glomerular filtration rate and renal plasma flow, respectively, was performed at baseline and at completion of study. The integral area under the curve of the clearance parameter over 8 hr was then calculated to generate a clearance-time index. There was no difference in the clearance-time indices for inulin and p-aminohippuric acid between the two groups at baseline. However, at the completion of study, the within-group change in the glomerular filtration rate clearance-time index was different between the verapamil and control groups (48+/-20 vs. -35+/-17 ml/min/1.73 m2 x hr, respectively; P=0.0038). A similar trend was seen for renal plasma flow, but did not reach statistical significance. Mean arterial blood pressure and whole-blood CsA levels did not differ between the two groups during the study. Verapamil treatment was also associated with a decrease in CsA dose requirement (7.6+/-0.58 mg/kg/day at baseline vs. 4.6+/-0.40 mg/kg/day at completion; P<0.001) without any significant change in trough whole blood CsA levels. Rejection episodes did not differ between the two groups. The use of verapamil in the heart or lung transplant recipients may therefore provide both renal protective effects and cost savings.

A Near-Term Concept for Trajectory Based Operations with Air/Ground Data Link Communication

NASA Technical Reports Server (NTRS)

McNally, David; Mueller, Eric; Thipphavong, David; Paielli, Russell; Cheng, Jinn-Hwei; Lee, Chuhan; Sahlman, Scott; Walton, Joe

2010-01-01

An operating concept and required system components for trajectory-based operations with air/ground data link for today's en route and transition airspace is proposed. Controllers are fully responsible for separation as they are today, and no new aircraft equipage is required. Trajectory automation computes integrated solutions to problems like metering, weather avoidance, traffic conflicts and the desire to find and fly more time/fuel efficient flight trajectories. A common ground-based system supports all levels of aircraft equipage and performance including those equipped and not equipped for data link. User interface functions for the radar controller's display make trajectory-based clearance advisories easy to visualize, modify if necessary, and implement. Laboratory simulations (without human operators) were conducted to test integrated operation of selected system components with uncertainty modeling. Results are based on 102 hours of Fort Worth Center traffic recordings involving over 37,000 individual flights. The presence of uncertainty had a marginal effect (5%) on minimum-delay conflict resolution performance, and windfavorable routes had no effect on detection and resolution metrics. Flight plan amendments and clearances were substantially reduced compared to today s operations. Top-of-descent prediction errors are the largest cause of failure indicating that better descent predictions are needed to reliably achieve fuel-efficient descent profiles in medium to heavy traffic. Improved conflict detections for climbing flights could enable substantially more continuous climbs to cruise altitude. Unlike today s Conflict Alert, tactical automation must alert when an altitude amendment is entered, but before the aircraft starts the maneuver. In every other failure case tactical automation prevented losses of separation. A real-time prototype trajectory trajectory-automation system is running now and could be made ready for operational testing at an en route Center in 1-2 years.

Circadian Clearance of a Fungal Pathogen from the Lung Is Not Based on Cell-intrinsic Macrophage Rhythms.

PubMed

Chen, Shan; Fuller, Kevin K; Dunlap, Jay C; Loros, Jennifer J

2018-02-01

Circadian rhythms govern immune cell function, giving rise to time-of-day variation in the recognition and clearance of bacterial or viral pathogens; to date, however, no such regulation of the host-fungal interaction has been described. In this report, we use murine models to explore circadian control of either fungal-macrophage interactions in vitro or pathogen clearance from the lung in vivo. First, we show that expression of the important fungal pattern recognition receptor Dectin-1 ( clec7a), from either bone marrow-derived or peritoneum-derived macrophages, is not under circadian regulation at either the level of transcript or cell surface protein expression. Consistent with this finding, the phagocytic activity of macrophages in culture against spores of the pathogen Aspergillus fumigatus also did not vary over time. To account for the multiple cell types and processes that may be coordinated in a circadian fashion in vivo, we examined the clearance of A. fumigatus from the lungs of immunocompetent mice. Interestingly, animals inoculated at night demonstrated a 2-fold enhancement in clearance compared with animals inoculated in the morning. Taken together, our data suggest that while molecular recognition of fungi by immune cells may not be circadian, other processes in vivo may still allow for time-of-day differences in fungal clearance from the lung.

Renal ultrafiltration changes induced by focused US.

PubMed

Fischer, Krisztina; McDannold, Nathan J; Zhang, Yongzhi; Kardos, Magdolna; Szabo, Andras; Szabo, Antal; Reusz, Gyorgy S; Jolesz, Ferenc A

2009-12-01

To determine if focused ultrasonography (US) combined with a diagnostic microbubble-based US contrast agent can be used to modulate glomerular ultrafiltration and size selectivity. The experiments were approved by the animal care committee. The left kidney of 17 healthy rabbits was sonicated by using a 260-kHz focused US transducer in the presence of a microbubble-based US contrast agent. The right kidney served as the control. Three acoustic power levels were applied: 0.4 W (six rabbits), 0.9 W (six rabbits), and 1.7 W (five rabbits). Three rabbits were not treated with focused US and served as control animals. The authors evaluated changes in glomerular size selectivity by measuring the clearance rates of 3000- and 70,000-Da fluorescence-neutral dextrans. The creatinine clearance was calculated for estimation of the glomerular filtration rate. The urinary protein-creatinine ratio was monitored during the experiments. The authors assessed tubular function by evaluating the fractional sodium excretion, tubular reabsorption of phosphate, and gamma-glutamyltransferase-creatinine ratio. Whole-kidney histologic analysis was performed. For each measurement, the values obtained before and after sonication were compared by using the paired t test. Significant (P < .05) increases in the relative (ratio of treated kidney value/nontreated kidney value) clearance of small- and large-molecule agents and the urine flow rates that resulted from the focused US treatments were observed. Overall, 1.23-, 1.23-, 1.61-, and 1.47-fold enhancement of creatinine clearance, 3000-Da dextran clearance, 70 000-Da dextran clearance, and urine flow rate, respectively, were observed. Focal tubular hemorrhage and transient functional tubular alterations were observed at only the highest (1.7-W) acoustic power level tested. Glomerular ultrafiltration and size selectivity can be temporarily modified with simultaneous application of US and microbubbles. This method could offer new opportunities for treatment of renal disease.

Bond Strength of Resin Cements to Dentin Using New Universal Bonding Agents

DTIC Science & Technology

2015-06-30

34Bond Strength of Resin Cements to Dentin Using New Universal Bonding Agents" Materials Repaired with Composite Resin" 7. Intended publication...DoD- or US Gov’t-level policy, communications systems or weapons issues review"). *Note: It is DoD policy that clearance of information or material...University-, DoD- or US Gov’t-level policy, communications systems or weapons issues review"). *Note: It is DoD po/icy that clearance of

A Single Mutation in K13 Predominates in Southern China and Is Associated With Delayed Clearance of Plasmodium falciparum Following Artemisinin Treatment.

PubMed

Huang, Fang; Takala-Harrison, Shannon; Jacob, Christopher G; Liu, Hui; Sun, Xiaodong; Yang, Henglin; Nyunt, Myaing M; Adams, Matthew; Zhou, Shuisen; Xia, Zhigui; Ringwald, Pascal; Bustos, Maria Dorina; Tang, Linhua; Plowe, Christopher V

2015-11-15

Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and poses a threat to malaria control and elimination. Mutations in a P. falciparum gene encoding a kelch protein on chromosome 13 have been associated with delayed parasite clearance following artemisinin treatment elsewhere in the region, but not yet in China. Therapeutic efficacy studies of artesunate and dihydroartemisinin-piperaquine were conducted from 2009 to 2012 in the Yunnan Province of China near the border with Myanmar. K13 mutations were genotyped by capillary sequencing of DNA extracted from dried blood spots collected in these clinical trials and in routine surveillance. Associations between K13 mutations and delayed parasite clearance were tested using regression models. Parasite clearance half-lives were prolonged after artemisinin treatment, with 44% of infections having half-lives >5 hours (n = 109). Fourteen mutations in K13 were observed, with an overall prevalence of 47.7% (n = 329). A single mutation, F446I, predominated, with a prevalence of 36.5%. Infections with F446I were significantly associated with parasitemia on day 3 following artemisinin treatment and with longer clearance half-lives. Plasmodium falciparum infections in southern China displayed markedly delayed clearance following artemisinin treatment. F446I was the predominant K13 mutation and was associated with delayed parasite clearance. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Population pharmacokinetic and pharmacogenetic analysis of tacrolimus in paediatric liver transplant patients

PubMed Central

Abdel Jalil, Mariam H; Hawwa, Ahmed F; McKiernan, Patrick J; Shields, Michael D; McElnay, James C

2014-01-01

Aims To build a population pharmacokinetic model that describes the apparent clearance of tacrolimus and the potential demographic, clinical and genetically controlled factors that could lead to inter-patient pharmacokinetic variability within children following liver transplantation. Methods The present study retrospectively examined tacrolimus whole blood pre-dose concentrations (n = 628) of 43 children during their first year post-liver transplantation. Population pharmacokinetic analysis was performed using the non-linear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance and influential covariates. Results The final model identified time post-transplantation and CYP3A5*1 allele as influential covariates on tacrolimus apparent clearance according to the following equation: where TVCL is the typical value for apparent clearance, TPT is time post-transplantation in days and the CYP3A5 is 1 where *1 allele is present and 0 otherwise. The population estimate and inter-individual variability (%CV) of tacrolimus apparent clearance were found to be 0.977 l h−1 kg−1 (95% CI 0.958, 0.996) and 40.0%, respectively, while the residual variability between the observed and predicted concentrations was 35.4%. Conclusion Tacrolimus apparent clearance was influenced by time post-transplantation and CYP3A5 genotypes. The results of this study, once confirmed by a large scale prospective study, can be used in conjunction with therapeutic drug monitoring to recommend tacrolimus dose adjustments that take into account not only body weight but also genetic and time-related changes in tacrolimus clearance. PMID:23738951

Histaminergic regulation of natural killer cell-mediated clearance of tumour cells in mice.

PubMed

Asea, A; Hermodsson, S; Hellstrand, K

1996-01-01

Treatment of Swiss albino mice with histamine enhanced the clearance of natural killer (NK)-cell sensitive YAC-1 lymphoma and B16/F10 melanoma cells from lung tissue in vivo, but did not affect the elimination of NK-cell-insensitive P815 mastocytoma cells. The effect of histamine was apparently mediated by H2-type histamine receptors (H2R) since it was blocked by ranitidine, and H2R antagonist. Histamine did not affect clearance of tumour cells in animals depleted of NK cells in vivo by treatment with antibodies to asialo-GM1 or NK1.1. The effect of histamine was time-dependent: pretreatment with histamine for 3 h significantly augmented the clearance of YAC-1 cells, whereas, pretreatment with histamine for 5 min was ineffective. Histamine potentiated the anti-tumour properties of NK-cell activators such as interleukin-2 (IL-2) or interferon-alpha (IFN-alpha) in vivo. None of these lymphokines significantly affected the clearance of YAC-1 cells unless animals were concomitantly treated with histamine. Treatment with ranitidine alone reduced the in vivo clearance of YAC-1 cells from lungs but did not affect the clearance of NK-cell-insensitive P815 cells. Effects of ranitidine on NK-cell function in vivo were not shared by a chemical control to ranitidine, AH20239AA, thus indicating that the inhibition of NK-cells results from H2R antagonism rather than non-specific toxicity. It is concluded that histaminergic mechanisms may be involved in the regulation of NK cell function in vivo.

Understanding the causes and consequences of measles virus persistence

PubMed Central

Griffin, Diane E.; Lin, Wen-Hsuan W.; Nelson, Ashley N.

2018-01-01

Measles is an acute systemic viral disease with initial amplification of infection in lymphoid tissue and subsequent spread over 10–14 days to multiple organs. Failure of the innate response to control initial measles virus (MeV) replication is associated with the ability of MeV to inhibit the induction of type I interferon and interferon-stimulated antiviral genes. Rather, the innate response is characterized by the expression of proteins regulated by nuclear factor kappa B and the inflammasome. With eventual development of the adaptive response, the rash appears with immune cell infiltration into sites of virus replication to initiate the clearance of infectious virus. However, MeV RNA is cleared much more slowly than recoverable infectious virus and remains present in lymphoid tissue for at least 6 months after infection. Persistence of viral RNA and protein suggests persistent low-level replication in lymphoid tissue that may facilitate maturation of the immune response, resulting in lifelong protection from reinfection, while persistence in other tissues (for example, the nervous system) may predispose to development of late disease such as subacute sclerosing panencephalitis. Further studies are needed to identify mechanisms of viral clearance and to understand the relationship between persistence and development of lifelong immunity. PMID:29560260

Understanding the causes and consequences of measles virus persistence.

PubMed

Griffin, Diane E; Lin, Wen-Hsuan W; Nelson, Ashley N

2018-01-01

Measles is an acute systemic viral disease with initial amplification of infection in lymphoid tissue and subsequent spread over 10-14 days to multiple organs. Failure of the innate response to control initial measles virus (MeV) replication is associated with the ability of MeV to inhibit the induction of type I interferon and interferon-stimulated antiviral genes. Rather, the innate response is characterized by the expression of proteins regulated by nuclear factor kappa B and the inflammasome. With eventual development of the adaptive response, the rash appears with immune cell infiltration into sites of virus replication to initiate the clearance of infectious virus. However, MeV RNA is cleared much more slowly than recoverable infectious virus and remains present in lymphoid tissue for at least 6 months after infection. Persistence of viral RNA and protein suggests persistent low-level replication in lymphoid tissue that may facilitate maturation of the immune response, resulting in lifelong protection from reinfection, while persistence in other tissues (for example, the nervous system) may predispose to development of late disease such as subacute sclerosing panencephalitis. Further studies are needed to identify mechanisms of viral clearance and to understand the relationship between persistence and development of lifelong immunity.

Analysis of Operational Hazards and Safety Requirements for Traffic Aware Strategic Aircrew Requests (TASAR)

NASA Technical Reports Server (NTRS)

Koczo, Stefan, Jr.

2013-01-01

Safety analyses of the Traffic Aware Strategic Aircrew Requests (TASAR) Electronic Flight Bag (EFB) application are provided to establish its Failure Effects Classification which affects certification and operational approval requirements. TASAR was developed by NASA Langley Research Center to offer flight path improvement opportunities to the pilot during flight for operational benefits (e.g., reduced fuel, flight time). TASAR, using own-ship and network-enabled information concerning the flight and its environment, including weather and Air Traffic Control (ATC) system constraints, provides recommended improvements to the flight trajectory that the pilot can choose to request via Change Requests to ATC for revised clearance. This study reviews the Change Request process of requesting updates to the current clearance, examines the intended function of TASAR, and utilizes two safety assessment methods to establish the Failure Effects Classification of TASAR. Considerable attention has been given in this report to the identification of operational hazards potentially associated with TASAR.

Glymphatic clearance controls state-dependent changes in brain lactate concentration.

PubMed

Lundgaard, Iben; Lu, Minh Lon; Yang, Ezra; Peng, Weiguo; Mestre, Humberto; Hitomi, Emi; Deane, Rashid; Nedergaard, Maiken

2017-06-01

Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep-wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport.

Deficits in reticuloendothelial humoral control mechanisms in patients after trauma.

PubMed

Scovill, W A; Saba, T M; Kaplan, J E; Bernard, H; Powers, S

1976-11-01

Plasma opsonic activity as expressed by an alpha-2-globulin which stimulates hepatic Kupffer cell phagocytosis, and thus modulates RES clearance, was determined in patients at varying intervals following whole-body trauma. Plasma opsonic activity decreased markedly following trauma in both nonsurviving (NS) and surviving (S) trauma patients as compared to an age- and sex-matched group of healthy volunteers. The initial post-traumatic hypoopsonemia (0-72 hr) was more severe (p less than 0.01) in nonsurviving patients than surviving patients. Survivors following trauma manifested restoration of opsonin levels with a definite transient rebound hyperopsonemia during the recovery phase (11-30 days); nonsurviving patients exhibited persistent systemic alpha-2-globulin opsonic deficiency. On the basis of previous animal and human studies, the presently observed humoral deficits following trauma in patients could contribute to impairment of reticuloendothelial Kupffer cell clearance of blood-borne particulate matter such as fibrin, damaged platelets, and other altered autologous tissue. The importance of post-trauma RES dysfunction to survival following severe injury warrants further investigation and clinical consideration.

Glymphatic clearance controls state-dependent changes in brain lactate concentration

PubMed Central

Lu, Minh Lon; Yang, Ezra; Peng, Weiguo; Mestre, Humberto; Hitomi, Emi; Deane, Rashid; Nedergaard, Maiken

2016-01-01

Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep–wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport. PMID:27481936

Caspase Activity Is Required for Engulfment of Apoptotic Cells

PubMed Central

Shklyar, Boris; Levy-Adam, Flonia; Mishnaevski, Ketty

2013-01-01

Clearance of apoptotic cells by phagocytic neighbors is crucial for normal development of multicellular organisms. However, how phagocytes discriminate between healthy and dying cells remains poorly understood. We focus on glial phagocytosis of apoptotic neurons during development of the Drosophila central nervous system. We identified phosphatidylserine (PS) as a ligand on apoptotic cells for the phagocytic receptor Six Microns Under (SIMU) and report that PS alone is not sufficient for engulfment. Our data reveal that, additionally to PS exposure, caspase activity is required for clearance of apoptotic cells by phagocytes. Here we demonstrate that SIMU recognizes and binds PS on apoptotic cells through its N-terminal EMILIN (EMI), Nimrod 1 (NIM1), and NIM2 repeats, whereas the C-terminal NIM3 and NIM4 repeats control SIMU affinity to PS. Based on the structure-function analysis of SIMU, we discovered a novel mechanism of internal inhibition responsible for differential affinities of SIMU to its ligand which might prevent elimination of living cells exposing PS on their surfaces. PMID:23754750

A Double-Primary Dead-Weight Tester for Pressures (35-175) kPa in Gage Mode.

PubMed

Jain, Kamlesh; Cen, Yueqin; Bowers, Walter J; Schmidt, James W

2003-01-01

Primary pressure standards in the atmospheric pressure range are often established using mercury manometers. Less frequently, controlled-clearance dead-weight testers in which one component (normally the piston) has been dimensionally measured have also been used. Recent advances in technology on two fronts i) the fabrication of large-diameter pistons and cylinders with good geometry; and ii) the ability to measure the dimensions of these components, have allowed some dead-weight testers at NIST to approach total relative uncertainties (k = 2) in dimensionally-derived effective areas near 5 × 10(-6). This paper describes a single piston/cylinder assembly (NIST-PG201WC/WC) that serves as both a primary gage in which both piston and cylinder are measured dimensionally and a controlled-clearance primary gage (employing the Heydemann-Welch method). Thus it allows some previous assumptions about the modeling of dead-weight testers to be checked. For the gage described in this paper the piston/cylinder clearance obtained from the two analyses have relative differences of 4 × 10(-6) to 7 × 10(-6) over the pressure range 35 kPa to 175 kPa. Some implications of these results will be discussed. From the dimensional characterizations and auxiliary measurements we have determined that the effective area for this gauge at 20 °C is: [Formula: see text]where P is the system pressure and P J is a control pressure. The estimated relative uncertainty in effective area is 8.2 × 10(-6) +1.4 × 10(-11) P/Pa (k = 2). The temperature coefficient for the area was measured and found to be (9.06 ± 0.04) × 10(-6)/K. Thus using the gage at a reference temperature of 23 °C yields an effective area: [Formula: see text]with almost no increase in the uncertainty over that at 20 °C.

Use of Data Comm by Flight Crew to Conduct Interval Management Operations to Parallel Dependent Runways

NASA Technical Reports Server (NTRS)

Baxley, Brian T.; Hubbs, Clay; Shay, Rick; Karanian, James

2011-01-01

The Interval Management (IM) concept is being developed as a method to maintain or increase high traffic density airport arrival throughput while allowing aircraft to conduct near idle thrust descents. The Interval Management with Spacing to Parallel Dependent Runways (IMSPiDR1) experiment at NASA Langley Research Center used 24 commercial pilots to examine IM procedures to conduct parallel dependent runway arrival operations while maintaining safe but efficient intervals behind the preceding aircraft. The use of IM procedures during these operations requires a lengthy and complex clearance from Air Traffic Control (ATC) to the participating aircraft, thereby making the use of Controller Pilot Data Link Communications (CPDLC) highly desirable as the communication method. The use of CPDLC reduces the need for voice transmissions between controllers and flight crew, and enables automated transfer of IM clearance elements into flight management systems or other aircraft avionics. The result is reduced crew workload and an increase in the efficiency of crew procedures. This paper focuses on the subset of data collected related to the use of CPDLC for IM operations into a busy airport. Overall, the experiment and results were very successful, with the mean time under 43 seconds for the flight crew to load the clearance into the IM spacing tool, review the calculated speed, and respond to ATC. An overall mean rating of Moderately Agree was given when the crews were asked if the use of CPDLC was operationally acceptable as simulated in this experiment. Approximately half of the flight crew reported the use of CPDLC below 10,000 for IM operations was unacceptable, with 83% reporting below 5000 was unacceptable. Also described are proposed modifications to the IM operations that may reduce CPDLC Respond time to less than 30 seconds and should significantly reduce the complexity of crew procedures, as well as follow-on research issues for operational use of CPDLC during IM operations.

A comparison of the effect of convection against diffusion in hemodynamics and cytokines clearance in an experimental model of septic shock.

PubMed

Herrera-Gutiérrez, Manuel E; Seller-Pérez, Gemma; Arias-Verdú, Dolores; Granados, Maria M; Dominguez, Juan M; Navarrete, Rocío; Morgaz, Juán; Gómez-Villamandos, Rafael

2012-10-01

Replacement therapies based on the use of convection have value for the removal of inflammatory mediators. Such therapies have been proposed for the management of septic shock, but diffusion has not proved useful in this scenario, unless high-flow membranes are used. The exact role of diffusion in these cases remains to be clarified because continuous replacement therapies are usually delivered with low-flow membranes and mixed convection-diffusion modalities. However, studies specifically addressing this problem have not been performed. Our aim was to define the efficacy of hemofiltration (convection) and hemodialysis (diffusion) in cytokine clearance and hemodynamic improvement in an experimental model of septic shock. Shock was induced in 15 beagle dogs (weight 10-15 kg) by infusion of 1 mg/kg of ultrapure Escherichia coli lipopolysaccharide diluted in 20 mL saline for 10 minutes. Five animals were followed without interventions (controls), five animals were treated with convection (100 mL kg h) for 6 hours, and five animals were treated with diffusion (100 mL kg h) for 6 hours. All subjects in the control group died during the study, whereas all treated subjects survived. Mean arterial pressure, cardiac output, systolic variability volume, systemic vascular resistances, dPMax, and pulmonary compliance improved in treated subjects. However, the differences in mean arterial pressure and cardiac output were significant only in the convection group and not in the diffusion-treated group.Tumor necrosis factor α rose equally in all groups and decreased only in treated subjects. Interleukin 6 rose in the three groups but decreased only in the convection group and remained unchanged in the control and diffusion groups. Convection and diffusion improved survival and hemodynamic parameters in a septic shock model. Improvement was more pronounced with convection, a difference that may be explained by convective clearance of cytokines.

Traffic control concepts for incident clearance

DOT National Transportation Integrated Search

2009-01-01

This document discusses various aspects of traffic control for incidents with the focus on the traffic control roles and responsibilities of the responders as well as the safety of the responders and the motoring public. It also recognizes that activ...

Benefits of Using Pairwise Trajectory Management in the Central East Pacific

NASA Technical Reports Server (NTRS)

Chartrand, Ryan; Ballard, Kathryn

2016-01-01

Pairwise Trajectory Management (PTM) is a concept that utilizes airborne and ground-based capabilities to enable airborne spacing operations in oceanic regions. The goal of PTM is to use enhanced surveillance, along with airborne tools, to manage the spacing between aircraft. Due to the enhanced airborne surveillance of Automatic Dependent Surveillance-Broadcast (ADS-B) information and reduced communication, the PTM minimum spacing distance will be less than distances currently required of an air traffic controller. Reduced minimum distance will increase the capacity of aircraft operations at a given altitude or volume of airspace, thereby increasing time on desired trajectory and overall flight efficiency. PTM is designed to allow a flight crew to resolve a specific traffic conflict (or conflicts), identified by the air traffic controller, while maintaining the flight crew's desired altitude. The air traffic controller issues a PTM clearance to a flight crew authorized to conduct PTM operations in order to resolve a conflict for the pair (or pairs) of aircraft (i.e., the PTM aircraft and a designated target aircraft). This clearance requires the flight crew of the PTM aircraft to use their ADS-B-enabled onboard equipment to manage their spacing relative to the designated target aircraft to ensure spacing distances that are no closer than the PTM minimum distance. When the air traffic controller determines that PTM is no longer required, the controller issues a clearance to cancel the PTM operation.

In-place recalibration technique applied to a capacitance-type system for measuring rotor blade tip clearance

NASA Technical Reports Server (NTRS)

Barranger, J. P.

1978-01-01

The rotor blade tip clearance measurement system consists of a capacitance sensing probe with self contained tuning elements, a connecting coaxial cable, and remotely located electronics. Tests show that the accuracy of the system suffers from a strong dependence on probe tip temperature and humidity. A novel inplace recalibration technique was presented which partly overcomes this problem through a simple modification of the electronics that permits a scale factor correction. This technique, when applied to a commercial system significantly reduced errors under varying conditions of humidity and temperature. Equations were also found that characterize the important cable and probe design quantities.

A gamma-secretase inhibitor decreases amyloid-beta production in the central nervous system

PubMed Central

Bateman, Randall J.; Siemers, Eric R.; Mawuenyega, Kwasi G.; Wen, Guolin; Browning, Karen R.; Sigurdson, Wendy C.; Yarasheski, Kevin E.; Friedrich, Stuart W.; DeMattos, Ronald B.; May, Patrick C.; Paul, Steven M.; Holtzman, David M.

2009-01-01

Objective Accumulation of amyloid-β (Aβ) by over-production or under-clearance in the central nervous system is hypothesized to be a necessary event in the pathogenesis of Alzheimer Disease. However, previously there has not been a method to determine drug effects on Aβ production or clearance in the human central nervous system. The objective of this study was to determine the effects of a gamma-secretase inhibitor on the production of Aβ in the human CNS. Methods We utilized a recently developed method of stable-isotope labeling combined with cerebrospinal fluid sampling to directly measure Aβ production during treatment of a gamma-secretase inhibitor, LY450139. We assessed whether this drug could decrease central nervous system Aβ production in healthy men (age 21–50) at single oral doses of 100mg, 140mg, or 280mg (N=5 per group). Results LY450139 significantly decreased the production of central nervous system Aβ in a dose-dependent fashion, with inhibition of Aβ generation of 47%, 52%, and 84% over a 12 hour period with doses of 100 mg, 140, and 280 mg respectively. There was no difference in Aβ clearance. Interpretation Stable isotope labeling of central nervous system proteins can be utilized to assess the effects of drugs on the production and clearance rates of proteins targeted as potential disease modifying treatments for Alzheimer Disease and other central nervous system disorders. Results from this approach can assist in making decisions about drug dosing and frequency in the design of larger and longer clinical trials for diseases such as Alzheimer Disease, and may accelerate effective drug validation. PMID:19360898

Recent studies of float and stall curves in controlled-clearance deadweight testers with a simple piston.

PubMed

Newhall, D H; Ogawa, I; Zilberstein, V

1979-08-01

The effect of piston rotation speed and fluid viscosity on the performance of free-piston gauges with a controlled clearance was studied as part of an experimental program aiming at the better evaluation of pressure by these primary pressure standards. Calculated effective area is shown to be greatly influenced by both speed of rotation and choice of a fluid. An optimum rpm resulting in the smallest possible uncertainty in effective area should be determined experimentally for each fluid and pressure range involved. When all the pertinent parameters are properly selected an appreciable improvement in accuracy can be achieved.

Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms.

PubMed

Pareja, Maria Eugenia Mansilla; Colombo, Maria I

2013-01-01

Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response. Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments, helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection. In this review we will describe the means used by diverse bacterial pathogens to survive intracellularly and how they are recognized by the autophagic molecular machinery, as well as the mechanisms used to avoid autophagic clearance.

Drug structure–transport relationships

PubMed Central

2010-01-01

Malcolm Rowland has greatly facilitated an understanding of drug structure–pharmacokinetic relationships using a physiological perspective. His view points, covering a wide range of activities, have impacted on my own work and on my appreciation and understanding of our science. This overview summarises some of our parallel activities, beginning with Malcolm’s work on the pH control of amphetamine excretion, his work on the disposition of aspirin and on the application of clearance concepts in describing the disposition of lidocaine. Malcolm also spent a considerable amount of time developing principles that define solute structure and transport/pharmacokinetic relationships using in situ organ studies, which he then extended to involve the whole body. Together, we developed a physiological approach to studying hepatic clearance, introducing the convection–dispersion model in which there was a spread in blood transit times through the liver accompanied by permeation into hepatocytes and removal by metabolism or excretion into the bile. With a range of colleagues, we then further developed the model and applied it to various organs in the body. One of Malcolm’s special interests was in being able to apply this knowledge, together with an understanding of physiological differences in scaling up pharmacokinetics from animals to man. The description of his many other activities, such as the development of clearance concepts, application of pharmacokinetics to the clinical situation and using pharmacokinetics to develop new compounds and delivery systems, has been left to others. PMID:21107662

Central peptidergic mechanisms controlling reproductive hormone secretion: novel methodology reveals a role for the natriuretic peptides.

PubMed

Samson, W K; Alexander, B D; Skala, K D; Huang, F L; Fulton, R J

1992-05-01

A variety of neural factors can influence reproductive hormone secretion by neuromodulatory actions within the hypothalamus or neuroendocrine actions within the anterior pituitary gland. Passive immunoneutralization and antagonist administration protocols have suggested physiological roles for a number of these factors; however, both experimental approaches have severe technical limitations. We have developed novel methodology utilizing cytotoxin cell targeting with neuropeptides linked to the toxic A chain of the plant cytotoxin ricin. With this methodology we can target and destroy in vivo or in vitro cells bearing receptors for that peptide. Ricin A chain conjugated to atrial natriuretic peptide (ANP), a neuropeptide known to pharmacologically inhibit luteinizing hormone-releasing hormone (LHRH) release, was injected into the cerebroventricular system of intact, cycling rats and ovariectomized rats. Cytotoxin conjugate treatment significantly lengthened the estrous cycle. In ovariectomized rats the luteinizing hormone surge induced by steroid priming was completely inhibited. LHRH content of the median eminences of these rats was not significantly altered. These data suggest that ANP binding to clearance receptors in the hypothalamus displaces the C-type natriuretic peptide (CNP) from the shared clearance receptor, making more CNP available to inhibit LHRH release. In the absence of cells bearing the clearance receptor all available CNP binds to the ANPR-B receptor and exerts its effect via an inhibitory interneuron, since LHRH fibers are spared by this treatment.

A Helix-Stabilizing Linker Improves Subcutaneous Bioavailability of a Helical Peptide Independent of Linker Lipophilicity

PubMed Central

Zhang, Liang; Navaratna, Tejas; Thurber, Greg M.

2016-01-01

Stabilized peptides address several limitations to peptide-based imaging agents and therapeutics such as poor stability and low affinity due to conformational flexibility. There is also active research in developing these compounds for intracellular drug targeting, and significant efforts have been invested to determine the effects of helix stabilization on intracellular delivery. However, much less is known about the impact on other pharmacokinetic parameters such as plasma clearance and bioavailability. We investigated the effect of different fluorescent helix-stabilizing linkers with varying lipophilicity on subcutaneous (SC) bioavailability using the glucagon-like peptide-1 (GLP-1) receptor ligand exendin as a model system. The stabilized peptides showed significantly higher protease resistance and increased bioavailability independent of linker hydrophilicity, and all subcutaneously delivered conjugates were able to successfully target the islets of Langerhans with high specificity. The lipophilic peptide variants had slower absorption and plasma clearance than their respective hydrophilic conjugates, and the absolute bioavailability was also lower likely due to the longer residence times in the skin. The ease and efficiency of double-click helix stabilization chemistries is a useful tool for increasing the bioavailability of peptide therapeutics, many of which suffer from rapid in vivo protease degradation. Helix stabilization using linkers of varying lipophilicity can further control SC absorption and clearance rates to customize plasma pharmacokinetics. PMID:27327034

A comparison of the lung clearance kinetics of solid lipid nanoparticles and liposomes by following the 3H-labelled structural lipids after pulmonary delivery in rats.

PubMed

Haque, Shadabul; Whittaker, Michael; McIntosh, Michelle P; Pouton, Colin W; Phipps, Simon; Kaminskas, Lisa M

2018-04-01

The utility of biodegradable nanosized drug carriers for the local and controlled delivery of therapeutics to the lungs has prompted significant interest in the development of inhalable nanomedicines. Still, little is known about how these systems are cleared from the lungs, including the kinetics of the structural lipids. Most preclinical and clinical studies to date have evaluated the lung clearance of loaded drugs, which in many cases poorly reflects the kinetics of the nanocarrier, or the bulk-labelled particles. This study therefore aimed to describe and compare the pulmonary pharmacokinetic behaviour and patterns of lung clearance of two commonly explored inhalable nanocarriers (anionic ∼150 nm liposomes and solid lipid nanoparticles [SLNs]) in rats by following the 3 H-labelled structural lipids (phosphatidylcholine and tristearin respectively). The data showed that SLNs and liposomes were cleared from the lungs at similar rates, despite SLNs being deposited after intratracheal instillation in the upper respiratory track, and primarily via the mucociliary escalator, but this process was more pronounced for SLNs. Structural lipids were mainly associated with plasma proteins rather than nanocarrier in plasma. The lipids also exhibit prolonged lung exposure and are associated with the lung tissue (rather than BALF) over 2 weeks. Copyright © 2018 Elsevier B.V. All rights reserved.

Impaired Urine Dilution Capability in HIV Stable Patients

PubMed Central

Belloso, Waldo H.; de Paz Sierra, Mariana; Navarro, Matilde; Sanchez, Marisa L.; Perelsztein, Ariel G.; Musso, Carlos G.

2014-01-01

Renal disease is a well-recognized complication among patients with HIV infection. Viral infection itself and the use of some antiretroviral drugs contribute to this condition. The thick ascending limb of Henle's loop (TALH) is the tubule segment where free water clearance is generated, determining along with glomerular filtration rate the kidney's ability to dilute urine. Objective. We analyzed the function of the proximal tubule and TALH in patients with HIV infection receiving or not tenofovir-containing antiretroviral treatment in comparison with healthy seronegative controls, by applying a tubular physiological test, hyposaline infusion test (Chaimowitz' test). Material & Methods. Chaimowitz' test was performed on 20 HIV positive volunteers who had normal renal functional parameters. The control group included 10 healthy volunteers. Results. After the test, both HIV groups had a significant reduction of serum sodium and osmolarity compared with the control group. Free water clearance was lower and urine osmolarity was higher in both HIV+ groups. Proximal tubular function was normal in both studied groups. Conclusion. The present study documented that proximal tubule sodium reabsorption was preserved while free water clearance and maximal urine dilution capability were reduced in stable HIV patients treated or not with tenofovir. PMID:24800076

Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects

PubMed Central

Millard, Steven P.; Lutz, Franziska; Li, Ge; Galasko, Douglas R.; Farlow, Martin R.; Quinn, Joseph F.; Kaye, Jeffrey A.; Leverenz, James B.; Tsuang, Debby; Yu, Chang-En; Peskind, Elaine R.; Bekris, Lynn M.

2013-01-01

Low cerebrospinal fluid (CSF) Aβ42 levels correlate with increased brain Aβ deposition in Alzheimer’s disease (AD), which suggests a disruption in the degradation and clearance of Aβ from the brain. In addition, APOE ε4 carriers have lower CSF Aβ42 levels than non-carriers. The hypothesis of this investigation was that CSF Aβ42 levels correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of Aβ from the brain. CSF Aβ42 levels were tested for associations with Aβ degradation and clearance genes and APOE ε4. Twenty-four SNPs located within the 5′ and 3′ regions of 12 genes were analyzed. The study sample consisted of 99 AD patients and 168 cognitively normal control subjects. CSF Aβ42 levels were associated with APOE ε4 status in controls but not in AD patients; A2M regulatory region SNPs were also associated with CSF Aβ42 levels in controls, but not in AD patients, even after adjusting for APOE ε4. These results suggest that genetic variation within the A2M gene influences CSF Aβ42 levels. PMID:24011543

LRP1 in Brain Vascular Smooth Muscle Cells Mediates Local Clearance of Alzheimer's Amyloid-β

PubMed Central

Kanekiyo, Takahisa; Liu, Chia-Chen; Shinohara, Mitsuru; Li, Jie; Bu, Guojun

2012-01-01

Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer’s disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-density lipoprotein receptor-related protein 1 (LRP1), is abundantly expressed in cerebrovasculature, in particular in vascular smooth muscle cells. Previous studies have indicated a role of LRP1 in endothelial cells in transcytosing Aβ out of the brain across the BBB; however, whether this represents a significant pathway for brain Aβ clearance remains controversial. Here, we demonstrate that Aβ can be cleared locally in the cerebrovasculature by an LRP1-dependent endocytic pathway in smooth muscle cells. The uptake and degradation of both endogenous and exogenous Aβ were significantly reduced in LRP1-suppressed human brain vascular smooth muscle cells. Conditional deletion of Lrp1 in vascular smooth muscle cell in amyloid model APP/PS1 mice accelerated brain Aβ accumulation and exacerbated Aβ deposition as amyloid plaques and CAA without affecting Aβ production. Our results demonstrate that LRP1 is a major Aβ clearance receptor in cerebral vascular smooth muscle cell and a disturbance of this pathway contributes to Aβ accumulation. These studies establish critical functions of the cerebrovasculature system in Aβ metabolism and identify a new pathway involved in the pathogenesis of both AD and CAA. PMID:23152628

Event Classification and Identification Based on the Characteristic Ellipsoid of Phasor Measurement

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

Ma, Jian; Diao, Ruisheng; Makarov, Yuri V.

2011-09-23

In this paper, a method to classify and identify power system events based on the characteristic ellipsoid of phasor measurement is presented. The decision tree technique is used to perform the event classification and identification. Event types, event locations and clearance times are identified by decision trees based on the indices of the characteristic ellipsoid. A sufficiently large number of transient events were simulated on the New England 10-machine 39-bus system based on different system configurations. Transient simulations taking into account different event types, clearance times and various locations are conducted to simulate phasor measurement. Bus voltage magnitudes and recordedmore » reactive and active power flows are used to build the characteristic ellipsoid. The volume, eccentricity, center and projection of the longest axis in the parameter space coordinates of the characteristic ellipsoids are used to classify and identify events. Results demonstrate that the characteristic ellipsoid and the decision tree are capable to detect the event type, location, and clearance time with very high accuracy.« less

Control of oral human papillomavirus (HPV) by medicinal mushrooms, Trametes versicolor and Ganoderma lucidum: a preliminary clinical trial.

PubMed

Donatini, Bruno

2014-01-01

This preliminary randomized study investigated the efficacy of medicinal mushrooms, Trametes versicolor (TV), Ganoderma lucidum (GL), and Laetiporus sulphureus (LS), on the clearance of oral human papillomavirus (HPV, serotypes 16 and 18). Among 472 patients who underwent oral swabs for gingivitis, 61 patients were positive for HPV16 or HPV18. Twenty patients were included in group 1 (LS) and 41 patients were included in group 2 (TV+GL) for 2 months. Polymerase chain reaction (PCR) for HPV was performed at inclusion and after 2 months. In group 1, the clearance was equal to 5% after 2 months of treatment. In group 2, the clearance was equal to 88% (P<0.001). The detection of HPV16 or HPV18 could become relevant in routine since positivity is frequent and because a harmless and costless treatment may exist. The use of TV+GL for the clearance of oral HPV deserves further investigation.

24 CFR 35.820 - Interim controls.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Interim controls. 35.820 Section 35...-Possession Multifamily Property § 35.820 Interim controls. HUD shall conduct interim controls in accordance... accordance with § 35.815. Interim controls are considered completed when clearance is achieved in accordance...

24 CFR 35.820 - Interim controls.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Interim controls. 35.820 Section 35...-Possession Multifamily Property § 35.820 Interim controls. HUD shall conduct interim controls in accordance... accordance with § 35.815. Interim controls are considered completed when clearance is achieved in accordance...

Clinical review: Airway hygiene in the intensive care unit

PubMed Central

Jelic, Sanja; Cunningham, Jennifer A; Factor, Phillip

2008-01-01

Maintenance of airway secretion clearance, or airway hygiene, is important for the preservation of airway patency and the prevention of respiratory tract infection. Impaired airway clearance often prompts admission to the intensive care unit (ICU) and can be a cause and/or contributor to acute respiratory failure. Physical methods to augment airway clearance are often used in the ICU but few are substantiated by clinical data. This review focuses on the impact of oral hygiene, tracheal suctioning, bronchoscopy, mucus-controlling agents, and kinetic therapy on the incidence of hospital-acquired respiratory infections, length of stay in the hospital and the ICU, and mortality in critically ill patients. Available data are distilled into recommendations for the maintenance of airway hygiene in ICU patients. PMID:18423061

A Multiple Agent Model of Human Performance in Automated Air Traffic Control and Flight Management Operations

NASA Technical Reports Server (NTRS)

Corker, Kevin; Pisanich, Gregory; Condon, Gregory W. (Technical Monitor)

1995-01-01

A predictive model of human operator performance (flight crew and air traffic control (ATC)) has been developed and applied in order to evaluate the impact of automation developments in flight management and air traffic control. The model is used to predict the performance of a two person flight crew and the ATC operators generating and responding to clearances aided by the Center TRACON Automation System (CTAS). The purpose of the modeling is to support evaluation and design of automated aids for flight management and airspace management and to predict required changes in procedure both air and ground in response to advancing automation in both domains. Additional information is contained in the original extended abstract.

Hemoadsorption corrects hyperresistinemia and restores anti-bacterial neutrophil function.

PubMed

Bonavia, Anthony; Miller, Lauren; Kellum, John A; Singbartl, Kai

2017-12-01

Mounting evidence suggests that sepsis-induced morbidity and mortality are due to both immune activation and immunosuppression. Resistin is an inflammatory cytokine and uremic toxin. Septic hyperresistinemia (plasma resistin >20 ng/ml) has been associated with greater disease severity and worse outcomes, and it is further exacerbated by concomitant acute kidney injury (AKI). Septic hyperresistinemia disturbs actin polymerization in neutrophils leading to impaired neutrophil migration, a crucial first-line mechanism in host defense to bacterial infection. Our experimental objective was to study the effects of hyperresistinemia on other F-actin-dependent neutrophil defense mechanisms, in particular intracellular bacterial clearance and generation of reactive oxygen species (ROS). We also sought to examine the effects of hemoadsorption on hyperresistinemia and neutrophil dysfunction. Thirteen patients with septic shock and six control patients were analyzed for serum resistin levels and their effects on neutrophil migration. In vitro, following incubation with resistin-spiked serum samples, Pseudomonas aeruginosa clearance and ROS generation in neutrophils were measured. Phosphorylation of 3-phosphoinositide-dependent protein kinase-1 (PDPK1) was assessed using flow cytometry. In vitro hemoadsorption with both Amberchrome™ columns (AC) and CytoSorb® cartridges (CC) were used to test correction of hyperresistinemia. We further tested AC for their effect on cell migration and ROS generation and CC for their effect on bacterial clearance. Patients with septic shock had higher serum resistin levels than control ICU patients and showed a strong, negative correlation between hyperresistinemia and neutrophil transwell migration (ρ= - 0.915, p < 0.001). In vitro, neutrophils exposed to hyperresistinemia exhibited twofold lower intracellular bacterial clearance rates compared to controls. Resistin impaired intracellular signaling and ROS production in a dose-dependent manner. Hemoadsorption with AC reduced serum concentrations of resistin and restored neutrophil migration and generation of ROS to normal levels. Hemoadsorption with CC also corrected hyperresistinemia and reconstituted normal intracellular bacterial clearance. Septic hyperresistinemia strongly correlates with inhibition of neutrophil migration in vitro. Hyperresistinemia itself reversibly impairs neutrophil intracellular bacterial clearance and ROS generation. Hemoadsorption therapy with a clinically approved device corrects hyperresistinemia and neutrophil dysfunction. It may therefore provide a therapeutic option to improve neutrophil function during septic hyperresistinemia and ultimately alleviate immunosuppression in this disease state.

Flight demonstration of integrated airport surface automation concepts

NASA Technical Reports Server (NTRS)

Jones, Denise R.; Young, Steven D.

1995-01-01

A flight demonstration was conducted to address airport surface movement area capacity issues by providing pilots with enhanced situational awareness information. The demonstration showed an integration of several technologies to government and industry representatives. These technologies consisted of an electronic moving map display in the cockpit, a Differential Global Positioning System (DGPS) receiver, a high speed VHF data link, an ASDE-3 radar, and the Airport Movement Area Safety System (AMASS). Aircraft identification was presented to an air traffic controller on AMASS. The onboard electronic map included the display of taxi routes, hold instructions, and clearances, which were sent to the aircraft via data link by the controller. The map also displayed the positions of other traffic and warning information, which were sent to the aircraft automatically from the ASDE-3/AMASS system. This paper describes the flight demonstration in detail, along with preliminary results.

Stable isotope labeling tandem mass spectrometry (SILT) to quantify protein production and clearance rates

PubMed Central

Bateman, Randall J.; Munsell, Ling Y.; Chen, Xianghong; Holtzman, David M.; Yarasheski, Kevin E.

2007-01-01

In all biological systems, protein amount is a function of the rate of production and clearance. The speed of a response to a disturbance in protein homeostasis is determined by turnover rate. Quantifying alterations in protein synthesis and clearance rates is vital to understanding disease pathogenesis (e.g., aging, inflammation). No methods exist for quantifying production and clearance rates of low abundance (femtomole) proteins in vivo. We describe a novel, mass spectrometry-based method for quantitating low abundance protein synthesis and clearance rates in vitro and in vivo in animals and humans. The utility of this method is demonstrated with amyloid-beta (Aß), an important low abundance protein involved in Alzheimer's disease pathogenesis. We used in vivo stable isotope labeling, immunoprecipitation of Aß from cerebrospinal fluid, and quantitative liquid chromatography electrospray-ionization tandem mass spectrometry (LC-ESI-tandem MS) to quantify human Aß protein production and clearance rates. The method is sensitive and specific for stable isotope labeled amino acid incorporation into CNS (± 1% accuracy). This in vivo method can be used to identify pathophysiologic changes in protein metabolism; and may serve as a biomarker for monitoring disease risk, progression, or response to novel therapeutic agents. The technique is adaptable to other macromolecules, such as carbohydrates or lipids. PMID:17383190

Liver heparan sulfate proteoglycans mediate clearance of triglyceride-rich lipoproteins independently of LDL receptor family members

PubMed Central

MacArthur, Jennifer M.; Bishop, Joseph R.; Stanford, Kristin I.; Wang, Lianchun; Bensadoun, André; Witztum, Joseph L.; Esko, Jeffrey D.

2007-01-01

We examined the role of hepatic heparan sulfate in triglyceride-rich lipoprotein metabolism by inactivating the biosynthetic gene GlcNAc N-deacetylase/N-sulfotransferase 1 (Ndst1) in hepatocytes using the Cre-loxP system, which resulted in an approximately 50% reduction in sulfation of liver heparan sulfate. Mice were viable and healthy, but they accumulated triglyceride-rich lipoprotein particles containing apoB-100, apoB-48, apoE, and apoCI-IV. Compounding the mutation with LDL receptor deficiency caused enhanced accumulation of both cholesterol- and triglyceride-rich particles compared with mice lacking only LDL receptors, suggesting that heparan sulfate participates in the clearance of cholesterol-rich lipoproteins as well. Mutant mice synthesized VLDL normally but showed reduced plasma clearance of human VLDL and a corresponding reduction in hepatic VLDL uptake. Retinyl ester excursion studies revealed that clearance of intestinally derived lipoproteins also depended on hepatocyte heparan sulfate. These findings show that under normal physiological conditions, hepatic heparan sulfate proteoglycans play a crucial role in the clearance of both intestinally derived and hepatic lipoprotein particles. PMID:17200715

Effect of Salsalate on Insulin Action, Secretion, and Clearance in Nondiabetic, Insulin-Resistant Individuals: A Randomized, Placebo-Controlled Study

PubMed Central

Liu, Alice; Ariel, Danit; Abbasi, Fahim; Lamendola, Cindy; Grove, Kaylene; Tomasso, Vanessa; Ochoa, Hector; Reaven, Gerald

2014-01-01

OBJECTIVE Salsalate treatment has been shown to improve glucose homeostasis, but the mechanism remains unclear. The aim of this study was to evaluate the effect of salsalate treatment on insulin action, secretion, and clearance rate in nondiabetic individuals with insulin resistance. RESEARCH DESIGN AND METHODS This was a randomized (2:1), single-blind, placebo-controlled study of salsalate (3.5 g daily for 4 weeks) in nondiabetic individuals with insulin resistance. All individuals had measurement of glucose tolerance (75-g oral glucose tolerance test), steady-state plasma glucose (SSPG; insulin suppression test), and insulin secretion and clearance rate (graded-glucose infusion test) before and after treatment. RESULTS Forty-one individuals were randomized to salsalate (n = 27) and placebo (n = 14). One individual from each group discontinued the study. Salsalate improved fasting (% mean change −7% [95% CI −10 to −14] vs. 1% [−3 to 5], P = 0.005) but not postprandial glucose concentration compared with placebo. Salsalate also lowered fasting triglyceride concentration (−25% [−34 to −15] vs. −6% [−26 to 14], P = 0.04). Salsalate had no effect on SSPG concentration or insulin secretion rate but significantly decreased insulin clearance rate compared with placebo (−23% [−30 to −16] vs. 3% [−10 to 15], P < 0.001). Salsalate was well tolerated, but four individuals needed a dose reduction due to symptoms. CONCLUSIONS Salsalate treatment in nondiabetic, insulin-resistant individuals improved fasting, but not postprandial, glucose and triglyceride concentration. These improvements were associated with a decrease in insulin clearance rate without change in insulin action or insulin secretion. PMID:24963111

Ubiquitin proteasome system in Parkinson's disease: a keeper or a witness?

PubMed

Martins-Branco, Diogo; Esteves, Ana R; Santos, Daniel; Arduino, Daniela M; Swerdlow, Russell H; Oliveira, Catarina R; Januario, Cristina; Cardoso, Sandra M

2012-12-01

The aim of this work was to evaluate the role of ubiquitin-proteasome system (UPS) on mitochondrial-driven alpha-synuclein (aSN) clearance in in vitro, ex vivo and in vivo Parkinson's disease (PD) cellular models. We used SH-SY5Y ndufa2 knock-down (KD) cells, PD cybrids and peripheral blood mononuclear cells (PBMC) from patients meeting the diagnostic criteria for PD. We quantified aSN aggregation, proteasome activity and protein ubiquitination levels. In PBMC of PD patient population we evaluated the aSN levels in the plasma and the influence of several demographic characteristics in the above mentioned determinations. We found that ubiquitin-independent proteasome activity was up-regulated in SH-SY5Y ndufa2 KD cells while a downregulation was observed in PD cybrids and PBMC. Moreover, we observed an increase in protein ubiquitination that correlates with a decrease in ubiquitin-dependent proteasome activity. Accordingly, proteasome inhibition prevented ubiquitin-dependent aSN clearance. Ubiquitin-independent proteasome activity was positively correlated with ubiquitination in PBMC. We also report a negative correlation of chymotrypsin-like activity with age in control and late-onset PD groups. Total ubiquitin content is positively correlated with aSN oligomer levels, which leads to an age-dependent increase of aSN ubiquitination in LOPD. Moreover, aSN levels are increased in the plasma of PD patients. aSN oligomers are ubiquitinated and we identified a ubiquitin-dependent clearance insufficiency with the accumulation of both aSN and ubiquitin. However, SH-SY5Y ndufa2 KD cells showed a significant up-regulation of ubiquitin-independent proteasomal enzymatic activity that could mean a cell rescue attempt. Moreover, we identified that UPS function is age-dependent in PBMC. Copyright © 2012 Elsevier Inc. All rights reserved.

Ubiquitin Proteasome System in Parkinson Disease: a keeper or a witness?

PubMed Central

Martins-Branco, Diogo; Esteves, Ana R.; Santos, Daniel; Arduino, Daniela M.; Swerdlow, Russell H.; Oliveira, Catarina R.; Januario, Cristina; Cardoso, Sandra M.

2014-01-01

Objective The aim of this work was to evaluate the role of Ubiquitin-Proteasome System (UPS) on mitochondrial-driven alpha-synuclein (aSN) clearance in in vitro, ex vivo and in vivo Parkinson disease (PD) cellular models. Method We used SH-SY5Y ndufa2 knock-down (KD) cells, PD cybrids and peripheral blood mononuclear cells (PBMC) from patients meeting the diagnostic criteria for PD. We quantified aSN aggregation, proteasome activity and protein ubiquitination levels. In PBMC of PD patients population we evaluated aSN levels in plasma and the influence of several demographic characteristics in the above mentioned determinations. Results We found that ubiquitin-independent proteasome activity was up-regulated in SH-SY5Y ndufa2 KD cells while a down regulation was observed in PD cybrids and PBMC. Moreover, we observed an increase in protein ubiquitination that correlates with a decrease in ubiquitin-dependent proteasome activity. Accordingly, proteasome inhibition prevented ubiquitin-dependent aSN clearance. Ubiquitin-independent proteasome activity was positively correlated with ubiquitination in PBMC. We also report a negative correlation of chymotrypsin-like activity with age in control and late-onset PD groups. Total ubiquitin content is positively correlated with aSN oligomers levels, which leads to an age-dependent increase of aSN ubiquitination in LOPD. Moreover, aSN levels are increased in the plasma of PD patients. Interpretation aSN oligomers are ubiquitinated and we identified an ubiquitin-dependent clearance insufficiency with accumulation of both aSN and ubiquitin. However, SH-SY5Y ndufa2 KD cells showed a significant up-regulation of ubiquitin-independent proteasomal enzymatic activity that could mean a cell rescue attempt. Moreover, we identified that UPS function is age-dependent in PBMC. PMID:22921536

Method and system for measuring gate valve clearances and seating force

DOEpatents

Casada, Donald A.; Haynes, Howard D.; Moyers, John C.; Stewart, Brian K.

1996-01-01

Valve clearances and seating force, as well as other valve operational parameters, are determined by measuring valve stem rotation during opening and closing operations of a translatable gate valve. The magnitude of the stem rotation, and the relative difference between the stem rotation on opening and closing provides valuable data on the valve internals in a non-intrusive manner.

77 FR 57639 - Privacy Act; System of Records: Records of the Office of White House Liaison, State-34

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-18

..., background and security clearance information received from Executive Offices and Bureau of Human Resources... the provisions of the Privacy Act of 1974, as amended (5 U.S.C.552a) and Office of Management and... Liaison Office for the consideration, review, clearance and appointment of an individual to a non-career...

Railway clearance intrusion detection method with binocular stereo vision

NASA Astrophysics Data System (ADS)

Zhou, Xingfang; Guo, Baoqing; Wei, Wei

2018-03-01

In the stage of railway construction and operation, objects intruding railway clearance greatly threaten the safety of railway operation. Real-time intrusion detection is of great importance. For the shortcomings of depth insensitive and shadow interference of single image method, an intrusion detection method with binocular stereo vision is proposed to reconstruct the 3D scene for locating the objects and judging clearance intrusion. The binocular cameras are calibrated with Zhang Zhengyou's method. In order to improve the 3D reconstruction speed, a suspicious region is firstly determined by background difference method of a single camera's image sequences. The image rectification, stereo matching and 3D reconstruction process are only executed when there is a suspicious region. A transformation matrix from Camera Coordinate System(CCS) to Track Coordinate System(TCS) is computed with gauge constant and used to transfer the 3D point clouds into the TCS, then the 3D point clouds are used to calculate the object position and intrusion in TCS. The experiments in railway scene show that the position precision is better than 10mm. It is an effective way for clearance intrusion detection and can satisfy the requirement of railway application.

Mechanosensitive ATP Release Maintains Proper Mucus Hydration of Airways

PubMed Central

Button, Brian; Okada, Seiko F.; Frederick, Charles Brandon; Thelin, William R.; Boucher, Richard C.

2013-01-01

The clearance of mucus from the airways protects the lungs from inhaled noxious and infectious materials. Proper hydration of the mucus layer enables efficient mucus clearance through beating of cilia on airway epithelial cells, and reduced clearance of excessively concentrated mucus occurs in patients with chronic obstructive pulmonary disease and cystic fibrosis. Key steps in the mucus transport process are airway epithelia sensing and responding to changes in mucus hydration. We reported that extracellular adenosine triphosphate (ATP) and adenosine were important luminal auto-crine and paracrine signals that regulated the hydration of the surface of human airway epithelial cultures through their action on apical membrane purinoceptors. Mucus hydration in human airway epithelial cultures was sensed by an interaction between cilia and the overlying mucus layer: Changes in mechanical strain, proportional to mucus hydration, regulated ATP release rates, adjusting fluid secretion to optimize mucus layer hydration. This system provided a feedback mechanism by which airways maintained mucus hydration in an optimum range for cilia propulsion. Understanding how airway epithelia can sense and respond to changes in mucus properties helps us to understand how the mucus clearance system protects the airways in health and how it fails in lung diseases such as cystic fibrosis. PMID:23757023

Dynamic microvesicle release and clearance within the cardiovascular system: triggers and mechanisms.

PubMed

Ayers, Lisa; Nieuwland, Rienk; Kohler, Malcolm; Kraenkel, Nicolle; Ferry, Berne; Leeson, Paul

2015-12-01

Interest in cell-derived microvesicles (or microparticles) within cardiovascular diagnostics and therapeutics is rapidly growing. Microvesicles are often measured in the circulation at a single time point. However, it is becoming clear that microvesicle levels both increase and decrease rapidly in response to certain stimuli such as hypoxia, acute cardiac stress, shear stress, hypertriglyceridaemia and inflammation. Consequently, the levels of circulating microvesicles will reflect the balance between dynamic mechanisms for release and clearance. The present review describes the range of triggers currently known to lead to microvesicle release from different cellular origins into the circulation. Specifically, the published data are used to summarize the dynamic impact of these triggers on the degree and rate of microvesicle release. Secondly, a summary of the current understanding of microvesicle clearance via different cellular systems, including the endothelial cell and macrophage, is presented, based on reported studies of clearance in experimental models and clinical scenarios, such as transfusion or cardiac stress. Together, this information can be used to provide insights into potential underlying biological mechanisms that might explain the increases or decreases in circulating microvesicle levels that have been reported and help to design future clinical studies. © 2015 Authors; published by Portland Press Limited.

Immune Mediators of Rotavirus Antigenemia Clearance in Mice ▿

PubMed Central

Marcelin, Glendie; Miller, Amber D.; Blutt, Sarah E.; Conner, Margaret E.

2011-01-01

The immunological mediators that clear rotavirus antigenemia or viremia remain undefined. Immunodeficient mice and antibody transfer were used to test whether lymphocytes or rotavirus-specific serum antibodies are essential for resolving antigenemia. Clearance of antigenemia required lymphocytes, but neither T nor B lymphocytes were absolutely required. Transfer of convalescent-phase or nonneutralizing rotavirus-specific serum antibodies to the systemic compartment of severe-combined-immunodeficient (SCID) mice temporarily suppressed the onset or level of chronic rotavirus antigenemia. Our findings provide the first report demonstrating that clearance of rotavirus antigenemia and possibly viremia are mediated by multiple effector lymphocyte subsets and serum antibodies. PMID:21593155

Divert to ULTRA: differences in infused volumes and clearance in two on-line hemodiafiltration treatments.

PubMed

Panichi, Vincenzo; De Ferrari, Giacomo; Saffioti, Stefano; Sidoti, Antonino; Biagioli, Marina; Bianchi, Stefano; Imperiali, Patrizio; Gabbrielli, Claudio; Conti, Paolo; Patrone, Pietro; Falqui, Valeria; Rombolà, Giuseppe; Mura, Carlo; Icardi, Andrea; Mulas, Donatella; Rosati, Alberto; Santori, Francesco; Mannarino, Antonio; Tomei, Valeria; Bertucci, Andrea; Steckiph, Denis; Palla, Roberto

2012-06-01

Mixed diffusive-convective dialysis therapies offer greater removal capabilities than conventional dialysis. The aim of this study was to compare two different on-line, post-dilution hemodiafiltration (HDF) treatments with regard to achieved convective volume and middle-molecule dialysis efficiency: standard volume control (sOL-HDF) and automated control of the transmembrane pressure (TMP) (UC-HDF). We enrolled 30 ESRD patients (55.9 ± 14.0 years, 20/10 M/F) in a randomized, prospective, cross-over study. The patients received a 3-month period of sOL-HDF followed by UC-HDF for a further 3 months, or vice versa, using the same dialysis machine. In sOL-HDF, fixed exchange volumes were set according to a filtration fraction greater than or equal to 25%. In UC-HDF therapy, the exchanged volume was driven by a biofeedback system controlling the TMP and its set point in a double loop. Patients maintained their treatment time, dialyzer, blood flow rate, and anticoagulant regimen unchanged throughout the study. Greater convective volumes were achieved in UC-HDF than in sOL-HDF (23.8 ± 3.9 vs.19.8 ± 4.8 L; p<0.001) with high pre-dialysis Ht value (sOL-HDF 34.0 ± 4.5% and UC-HDF 34.0 ± 4.4%; p = 0.91). The average clearance values of ß2m and P were higher in UC-HDF than in sOL-HDF (respectively 123 ± 24 vs. 111 ± 22 ml/min, p<0.002 and 158 ± 26 vs. 152 ± 25 ml/min, p<0.05). Moreover, the UC-HDF mode led to a significantly increased rate of call-free sessions from 88% to 97% (p<0.0001). This study showed that the biofeedback module, applied to the automatic control of TMP in on-line HDF, results in higher convective volumes and correspondingly higher ß2m and P clearances. By making the HDF treatment more automated and less complex to perform, it significantly reduced the staff workload.

Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition

PubMed Central

Ramsey, Laura B.; Bruun, Gitte H.; Yang, Wenjian; Treviño, Lisa R.; Vattathil, Selina; Scheet, Paul; Cheng, Cheng; Rosner, Gary L.; Giacomini, Kathleen M.; Fan, Yiping; Sparreboom, Alex; Mikkelsen, Torben S.; Corydon, Thomas J.; Pui, Ching-Hon; Evans, William E.; Relling, Mary V.

2012-01-01

Methotrexate is used to treat autoimmune diseases and malignancies, including acute lymphoblastic leukemia (ALL). Inter-individual variation in clearance of methotrexate results in heterogeneous systemic exposure, clinical efficacy, and toxicity. In a genome-wide association study of children with ALL, we identified SLCO1B1 as harboring multiple common polymorphisms associated with methotrexate clearance. The extent of influence of rare versus common variants on pharmacogenomic phenotypes remains largely unexplored. We tested the hypothesis that rare variants in SLCO1B1 could affect methotrexate clearance and compared the influence of common versus rare variants in addition to clinical covariates on clearance. From deep resequencing of SLCO1B1 exons in 699 children, we identified 93 SNPs, 15 of which were non-synonymous (NS). Three of these NS SNPs were common, with a minor allele frequency (MAF) >5%, one had low frequency (MAF 1%–5%), and 11 were rare (MAF <1%). NS SNPs (common or rare) predicted to be functionally damaging were more likely to be found among patients with the lowest methotrexate clearance than patients with high clearance. We verified lower function in vitro of four SLCO1B1 haplotypes that were associated with reduced methotrexate clearance. In a multivariate stepwise regression analysis adjusting for other genetic and non-genetic covariates, SLCO1B1 variants accounted for 10.7% of the population variability in clearance. Of that variability, common NS variants accounted for the majority, but rare damaging NS variants constituted 17.8% of SLCO1B1's effects (1.9% of total variation) and had larger effect sizes than common NS variants. Our results show that rare variants are likely to have an important effect on pharmacogenetic phenotypes. PMID:22147369

Apoptosis Modulation in the Immune System Reveals a Role of Neutrophils in Tissue Damage in a Murine Model of Chlamydial Genital Infection.

PubMed

Zortel, Tom; Schmitt-Graeff, Annette; Kirschnek, Susanne; Häcker, Georg

2018-05-05

Chlamydial infection frequently causes damage to the female genital tract. The precise mechanisms of chlamydial clearance and tissue damage are unknown, but studies suggest immunopathology with a particular role of neutrophils. The goal of this study was to understand the contribution of the immune system, in particular neutrophils. Using Chlamydia muridarum, we infected mice with a prolonged immune response due to expression of B-cell lymphoma 2 (Bcl-2) in hematopoietic cells (Bcl-2 mice), and mice where mature neutrophils are lacking due to the deletion of Myeloid cell leukemia 1 (Mcl-1) in myeloid cells (LysM-cre-mcl-1-flox mice; Mcl-1 mice). We monitored bacterial clearance, cellular infiltrate, and long-term tissue damage. Both mutant strains showed slightly delayed clearance of the acute infection. Bcl-2 mice had a strongly increased inflammatory infiltrate concerning almost all cell lineages. The infection of Bcl-2 mice caused increased tissue damage. The loss of neutrophils in Mcl-1 mice was associated with substantial quantitative and qualitative alterations of the inflammatory infiltrate. Mcl-1 mice had higher chlamydial burden and reduced tissue damage, including lower incidence of hydrosalpinx and less uterine dilation. Inhibition of apoptosis in the hematopoietic system increases inflammation and tissue damage. Neutrophils have broad functions, including a role in chlamydial clearance and in tissue destruction.