An inlet analysis for the NASA hypersonic research engine aerothermodynamic integration model

NASA Technical Reports Server (NTRS)

Andrews, E. H., Jr.; Russell, J. W.; Mackley, E. A.; Simmonds, A. L.

1974-01-01

A theoretical analysis for the inlet of the NASA Hypersonic Research Engine (HRE) Aerothermodynamic Integration Model (AIM) has been undertaken by use of a method-of-characteristics computer program. The purpose of the analysis was to obtain pretest information on the full-scale HRE inlet in support of the experimental AIM program (completed May 1974). Mass-flow-ratio and additive-drag-coefficient schedules were obtained that well defined the range effected in the AIM tests. Mass-weighted average inlet total-pressure recovery, kinetic energy efficiency, and throat Mach numbers were obtained.

Hypersonic Vehicle Propulsion System Control Model Development Roadmap and Activities

NASA Technical Reports Server (NTRS)

Stueber, Thomas J.; Le, Dzu K.; Vrnak, Daniel R.

2009-01-01

The NASA Fundamental Aeronautics Program Hypersonic project is directed towards fundamental research for two classes of hypersonic vehicles: highly reliable reusable launch systems (HRRLS) and high-mass Mars entry systems (HMMES). The objective of the hypersonic guidance, navigation, and control (GN&C) discipline team is to develop advanced guidance and control algorithms to enable efficient and effective operation of these challenging vehicles. The ongoing work at the NASA Glenn Research Center supports the hypersonic GN&C effort in developing tools to aid the design of advanced control algorithms that specifically address the propulsion system of the HRRLSclass vehicles. These tools are being developed in conjunction with complementary research and development activities in hypersonic propulsion at Glenn and elsewhere. This report is focused on obtaining control-relevant dynamic models of an HRRLS-type hypersonic vehicle propulsion system.

The NASA Ames Hypersonic Combustor-Model Inlet CFD Simulations and Experimental Comparisons

NASA Technical Reports Server (NTRS)

Venkatapathy, E.; Tokarcik-Polsky, S.; Deiwert, G. S.; Edwards, Thomas A. (Technical Monitor)

1995-01-01

Computations have been performed on a three-dimensional inlet associated with the NASA Ames combustor model for the hypersonic propulsion experiment in the 16-inch shock tunnel. The 3-dimensional inlet was designed to have the combustor inlet flow nearly two-dimensional and of sufficient mass flow necessary for combustion. The 16-inch shock tunnel experiment is a short duration test with test time of the order of milliseconds. The flow through the inlet is in chemical non-equilibrium. Two test entries have been completed and limited experimental results for the inlet region of the combustor-model are available. A number of CFD simulations, with various levels of simplifications such as 2-D simulations, 3-D simulations with and without chemical reactions, simulations with and without turbulent conditions, etc., have been performed. These simulations have helped determine the model inlet flow characteristics and the important factors that affect the combustor inlet flow and the sensitivity of the flow field to these simplifications. In the proposed paper, CFD modeling of the hypersonic inlet, results from the simulations and comparison with available experimental results will be presented.

Operative risks of domino liver transplantation for the FAP liver donor and the FAP liver recipient.

PubMed

Azoulay, Daniel; Salloum, Chady; Samuel, Didier; Planté-Bordeneuve, Violaine

2012-06-01

This study aimed at evaluating the operative risks of domino liver transplantation (LT). Two retrospective analyses were conducted (comparison of familial amyloid polyneuropathy (FAP) liver donors [61 patients] versus FAP nondonors [39 patients] and FAP liver recipients [61 patients] versus cadaveric liver recipients [61 patients]). First analysis showed a 60-day mortality of 6.6% for FAP donors and 7.7% for FAP nondonors (p = 1.0). Both groups had similar vascular and biliary complication rates. Both groups had similar 1- and 5-year patient and graft survival rates (83.4 % versus 87.2%, and 79.8 % versus 71.8%, p = 0.7) and (83.3% versus 87.2%, and 79.1% versus 71.8%, p = 0.7). The second analysis showed a 1.6% mortality for FAP liver recipients versus 3.2% of the control group (p = 1). Both groups had similar morbidity and technical complication rates (18.0% versus 13.1%, p = 0.45) and (0.18 versus 0.15, p = 0.65). Domino procedure doesn't add any risk to FAP donor or recipient. It increases the organ pool allowing transplantation of marginal recipients who otherwise are denied cadaveric LT.

X-33 Hypersonic Aerodynamic Characteristics

NASA Technical Reports Server (NTRS)

Murphy, Kelly J.; Nowak, Robert J.; Thompson, Richard A.; Hollis, Brian R.; Prabhu, Ramadas K.

1999-01-01

Lockheed Martin Skunk Works, under a cooperative agreement with NASA, will design, build, and fly the X-33, a half-scale prototype of a rocket-based, single-stage-to-orbit (SSTO), reusable launch vehicle (RLV). A 0.007-scale model of the X-33 604BOO02G configuration was tested in four hypersonic facilities at the NASA Langley Research Center to examine vehicle stability and control characteristics and to populate the aerodynamic flight database for the hypersonic regime. The vehicle was found to be longitudinally controllable with less than half of the total body flap deflection capability across the angle of attack range at both Mach 6 and Mach 10. Al these Mach numbers, the vehicle also was shown to be longitudinally stable or neutrally stable for typical (greater than 20 degrees) hypersonic flight attitudes. This configuration was directionally unstable and the use of reaction control jets (RCS) will be necessary to control the vehicle at high angles of attack in the hypersonic flight regime. Mach number and real gas effects on longitudinal aerodynamics were shown to be small relative to X-33 control authority.

X-33 Hypersonic Aerodynamic Characteristics

NASA Technical Reports Server (NTRS)

Murphy, Kelly J.; Nowak, Robert J.; Thompson, Richard A.; Hollis, Brian R.; Prabhu, Ramadas K.

1999-01-01

Lockheed Martin Skunk Works, under a cooperative agreement with NASA, will build and fly the X-33, a half-scale prototype of a rocket-based, single-stage-to-orbit (SSTO), reusable launch vehicle (RLV). A 0.007-scale model of the X-33 604B0002G configuration was tested in four hypersonic facilities at the NASA Langley Research Center to examine vehicle stability and control characteristics and to populate an aerodynamic flight database i n the hypersonic regime. The vehicle was found to be longitudinally controllable with less than half of the total body flap deflection capability across the angle of attack range at both Mach 6 and Mach 10. At these Mach numbers, the vehicle also was shown to be longitudinally stable or neutrally stable for typical (greater than 20 degrees) hypersonic flight attitudes. This configuration was directionally unstable and the use of reaction control jets (RCS) will be necessary to control the vehicle at high angles of attack in the hypersonic flight regime. Mach number and real gas effects on longitudinal aerodynamics were shown to be small relative to X-33 control authority.

Yb:S-FAP Lasers

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

Schaffers, K I

It has recently been reported that several high power, diode-pumped laser systems have been developed based on crystals of Yb:S-FAP [Yb{sup 3+}:Sr{sub 5}(PO{sub 4}){sub 3}F]. The Mercury Laser, at Lawrence Livermore National Laboratory, is the most prominent system using Yb:S-FAP and is currently producing 23J at 5 Hz in a 15 nsec pulse, based on partial activation of the system. In addition, a regenerative amplifier is being developed at Waseda University in Japan and has produced greater than 12 mJ with high beam quality at 50Hz repetition rate. Q-peak has demonstrated 16 mJ of maximum energy/output pulse in a multi-pass,more » diode side-pumped amplifier and ELSA in France is implementing Yb:S-FAP in a 985 nm pump for an EDFA, producing 250 mW. Growth of high optical quality crystals of Yb:S-FAP is a challenge due to multiple crystalline defects. However, at this time, a growth process has been developed to produce high quality 3.5 cm diameter Yb:S-FAP crystals and a process is under development for producing 6.5 cm diameter crystals.« less

[Therapeutic strategy for familial amyloid polyneuropathy (FAP)].

PubMed

Ikeda, Shu-ichi

2009-11-01

Familial amyloid polyneuropathy (FAP) was long considered to be an incurable disease, but a new therapeutic approach was developed 15 years ago. As the liver produces most of the transthyretin (TTR) in serum, it was assumed that the replacement of a liver expressing an abnormal TTR gene should stop the production of the variant TTR, the serum amyloid precursor in FAP. Until now about 1,500 FAP patients underwent liver transplantation, and the 10-year-survival rate is about 77%. After operation the progression of FAP symptoms certainly stopped, and patients who were in an early stage of the disease and underwent successful operations showed considerable improvement in their quality of life. Electrophysiological study of peripheral nerve function has demonstrated that liver transplantation can halt the progression of peripheral neuropathy in FAP patients, and histopathological regression of amyloid deposits was seen on the patients with long post-transplatation courses. Pharmacological therapies have been considered for FAP patients and among them, diflunisal, one of non-steroidal antiinflammatory drugs, is very promising. TTR tetramer dissociation is an initial step for the process of TTR-derived amyloid fibril formation associated with FAP and diflinisal can inhibit this process by stabilization of the TTR tetramer. Clinical trial of this drug for FAP patients is now going worldwide.

The Mothball, Sustainment, and Proposed Reactivation of the Hypersonic Tunnel Facility (HTF) at NASA Glenn Research Center Plum Brook Station

NASA Technical Reports Server (NTRS)

Thomas, Scott R.; Lee, Jinho; Stephens, John W.; Hostler, Robert W., Jr.; VonKamp, William D.

2010-01-01

The Hypersonic Tunnel Facility (HTF) located at the NASA Glenn Research Center s Plum Brook Station in Sandusky, Ohio, is the nation s only large-scale, non-vitiated, hypersonic propulsion test facility. The HTF, with its 4-story graphite induction heater, is capable of duplicating Mach 5, 6, and 7 flight conditions. This unique propulsion system test facility has experienced several standby and reactivation cycles. The intent of the paper is to overview the HTF capabilities to the propulsion community, present the current status of HTF, and share the lessons learned from putting a large-scale facility into mothball status for a later restart

Hypersonic propulsion. [scramjet technology

NASA Technical Reports Server (NTRS)

Anderson, G. Y.

1975-01-01

The NASA research on scramjet technology for speeds above Mach 5 is reported. A brief overview of the NASA Hypersonic Research Engine (HRE) project is presented with emphasis on the most significant contributions on the HRE to scramjet technology. The work on high-performance airframe-integrated scramjet engines is described, and a new versatile research airplane is discussed with emphasis on propulsion.

Survey of Aerothermodynamics Facilities Useful for the Design of Hypersonic Vehicles Using Air-Breathing Propulsion

NASA Technical Reports Server (NTRS)

Arnold, James O.; Deiwert, George S.

1997-01-01

This paper surveys the use of aerothermodynamic facilities which have been useful in the study of external flows and propulsion aspects of hypersonic, air-breathing vehicles. While the paper is not a survey of all facilities, it covers the utility of shock tunnels and conventional hypersonic blow-down facilities which have been used for hypersonic air-breather studies. The problems confronting researchers in the field of aerothermodynamics are outlined. Results from the T5 GALCIT tunnel for the shock-on lip problem are outlined. Experiments on combustors and short expansion nozzles using the semi-free jet method have been conducted in large shock tunnels. An example which employed the NASA Ames 16-Inch shock tunnel is outlined, and the philosophy of the test technique is described. Conventional blow-down hypersonic wind tunnels are quite useful in hypersonic air-breathing studies. Results from an expansion ramp experiment, simulating the nozzle on a hypersonic air-breather from the NASA Ames 3.5 Foot Hypersonic wind tunnel are summarized. Similar work on expansion nozzles conducted in the NASA Langley hypersonic wind tunnel complex is cited. Free-jet air-frame propulsion integration and configuration stability experiments conducted at Langley in the hypersonic wind tunnel complex on a small generic model are also summarized.

A Rare Case of FAP in Kashmir Valley.

PubMed

Sameer, A Syed; Pandith, Arshad A; Syeed, Nidda; Siddiqi, Mushtaq A; Chowdri, Nissar A

2011-06-01

Familial adenomatous polyposis (FAP) is the commonest form of inherited form of CRC. It comprises of about 5% of all the colorectal cancers (CRCs). FAP patients have a family history of CRC that suggests a genetic contribution, common exposures among family members, or a combination of both. This case report gives a glimpse of the phenotypic manifestation of FAP and the underlying molecular mechanism which leads to FAP, in addition it also sheds a light on the management of FAP in early stages of life.

A Review of Hypersonics Aerodynamics, Aerothermodynamics and Plasmadynamics Activities within NASA's Fundamental Aeronautics Program

NASA Technical Reports Server (NTRS)

Salas, Manuel D.

2007-01-01

The research program of the aerodynamics, aerothermodynamics and plasmadynamics discipline of NASA's Hypersonic Project is reviewed. Details are provided for each of its three components: 1) development of physics-based models of non-equilibrium chemistry, surface catalytic effects, turbulence, transition and radiation; 2) development of advanced simulation tools to enable increased spatial and time accuracy, increased geometrical complexity, grid adaptation, increased physical-processes complexity, uncertainty quantification and error control; and 3) establishment of experimental databases from ground and flight experiments to develop better understanding of high-speed flows and to provide data to validate and guide the development of simulation tools.

Research and educational initiatives at the Syracuse University Center for Hypersonics

NASA Technical Reports Server (NTRS)

Spina, E.; Lagraff, J.; Davidson, B.; Bogucz, E.; Dang, T.

1995-01-01

The Department of Mechanical, Aerospace, and Manufacturing Engineering and the Northeast Parallel Architectures Center of Syracuse University have been funded by NASA to establish a program to educate young engineers in the hypersonic disciplines. This goal is being achieved through a comprehensive five-year program that includes elements of undergraduate instruction, advanced graduate coursework, undergraduate research, and leading-edge hypersonics research. The research foci of the Syracuse Center for Hypersonics are three-fold; high-temperature composite materials, measurements in turbulent hypersonic flows, and the application of high-performance computing to hypersonic fluid dynamics.

Phoenix Missile Hypersonic Testbed (PMHT): Project Concept Overview

NASA Technical Reports Server (NTRS)

Jones, Thomas P.

2007-01-01

An over view of research into a low cost hypersonic research flight test capability to increase the amount of hypersonic flight data to help bridge the large developmental gap between ground testing/analysis and major flight demonstrator Xplanes is provided. The major objectives included: develop an air launched missile booster research testbed; accurately deliver research payloads through programmable guidance to hypersonic test conditions; low cost; a high flight rate minimum of two flights per year and utilize surplus air launched missiles and NASA aircraft.

Selective Homogeneous Assay for Circulating Endopeptidase Fibroblast Activation Protein (FAP).

PubMed

Bainbridge, Travis W; Dunshee, Diana Ronai; Kljavin, Noelyn M; Skelton, Nicholas J; Sonoda, Junichiro; Ernst, James A

2017-10-02

Fibroblast Activation Protein (FAP) is a membrane-bound serine protease whose expression is often elevated in activated fibroblasts associated with tissue remodeling in various common diseases such as cancer, arthritis and fibrosis. Like the closely related dipeptidyl peptidase DPPIV, the extracellular domain of FAP can be released into circulation as a functional enzyme, and limited studies suggest that the circulating level of FAP correlates with the degree of tissue fibrosis. Here we describe a novel homogeneous fluorescence intensity assay for circulating FAP activity based on a recently identified natural substrate, FGF21. This assay is unique in that it can effectively distinguish endopeptidase activity of FAP from that of other related enzymes such as prolyl endopeptidase (PREP) and was validated using Fap-deficient mice. Structural modeling was used to elucidate the mechanistic basis for the observed specificity in substrate recognition by FAP, but not by DPPIV or PREP. Finally, the assay was used to detect elevated FAP activity in human patients diagnosed with liver cirrhosis and to determine the effectiveness of a chemical inhibitor for FAP in mice. We propose that the assay presented here could thus be utilized for diagnosis of FAP-related pathologies and for the therapeutic development of FAP inhibitors.

Hypersonic propulsion: Status and challenge

NASA Technical Reports Server (NTRS)

Guy, R. Wayne

1990-01-01

Scientists in the U.S. are again focusing on the challenge of hypersonic flight with the proposed National Aerospace Plane (NASP). This renewed interest has led to an expansion of research related to high speed airbreathing propulsion, in particular, the supersonic combustion ramjet, or scramjet. The history is briefly traced of scramjet research in the U.S., with emphasis on NASA sponsored efforts, from the Hypersonic Research Engine (HRE) to the current status of today's airframe integrated scramjets. The challenges of scramjet technology development from takeover to orbital speeds are outlined. Existing scramjet test facilities such as NASA Langley's Scramjet Test Complex as well as new high Mach number pulse facilities are discussed. The important partnership role of experimental methods and computational fluid dynamics is emphasized for the successful design of single stage to orbit vehicles.

Dataset on FAP-induced emergence of spontaneous metastases and on the preparation of activatable FAP-targeting immunoliposomes to detect the metastases.

PubMed

Tansi, Felista L; Rüger, Ronny; Böhm, Claudia; Kontermann, Roland E; Teichgraeber, Ulf K; Fahr, Alfred; Hilger, Ingrid

2016-12-01

The underlying data demonstrates that fibroblast activation protein (FAP) paves the way for fibrosarcoma cells, which require the proteolysis of the extracellular matrix (ECM) and basement membranes to intravasate from implanted subcutaneous primary tumors into blood vessels, be transported to distant organs where they extravasate from the blood vessels, reattach and proliferate to metastases. The data additionally shows that FAP, when overexpressed on fibrosarcoma cells induces their invasion and formation of spontaneous metastases in multiple organs, particularly after subcutaneous co-implantation of the FAP-expressing and wildtype fibrosarcoma. The raw and processed data presented herein is related to a research article entitled "Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases" (F.L. Tansi, R. Rüger, C. Böhm, R.E. Kontermann, U.K. Teichgraeber, A. Fahr, I. Hilger, 2016) [1]. Furthermore, evidence for the detection of FAP-expressing tumor cells and cells of the tumor stroma by activatable FAP-targeting liposomes is presented in this dataset.

Hypersonic transport aircraft

NASA Technical Reports Server (NTRS)

1987-01-01

A hypersonic transport aircraft design project was selected as a result of interactions with NASA Lewis Research Center personnel and fits the Presidential concept of the Orient Express. The Graduate Teaching Assistant (GTA) and an undergraduate student worked at the NASA Lewis Research Center during the 1986 summer conducting a literature survey, and relevant literature and useful software were collected. The computer software was implemented in the Computer Aided Design Laboratory of the Mechanical and Aerospace Engineering Department. In addition to the lectures by the three instructors, a series of guest lectures was conducted. The first of these lectures 'Anywhere in the World in Two Hours' was delivered by R. Luidens of NASA Lewis Center. In addition, videotaped copies of relevant seminars obtained from NASA Lewis were also featured. The first assignment was to individually research and develop the mission requirements and to discuss the findings with the class. The class in consultation with the instructors then developed a set of unified mission requirements. Then the class was divided into three design groups (1) Aerodynamics Group, (2) Propulsion Group, and (3) Structures and Thermal Analyses Group. The groups worked on their respective design areas and interacted with each other to finally come up with an integrated conceptual design. The three faculty members and the GTA acted as the resource persons for the three groups and aided in the integration of the individual group designs into the final design of a hypersonic aircraft.

The Syracuse University Center for Training and Research in Hypersonics

NASA Technical Reports Server (NTRS)

LaGraff, John; Blankson, Isaiah (Technical Monitor); Robinson, Stephen K. (Technical Monitor); Walsh, Michael J. (Technical Monitor); Anderson, Griffin Y. (Technical Monitor)

2000-01-01

In Fall 1993, NASA Headquarters established Centers for Hypersonics at the University of Maryland, the University of Texas-Arlington, and Syracuse University. These centers are dedicated to research and education in hypersonic technologies and have the objective of educating the next generation of engineers in this critical field. At the Syracuse University Center for Hypersonics this goal is being realized by focusing resources to: Provide an environment in which promising undergraduate students can learn the fundamental engineering principles of hypersonics so that they may make a seamless transition to graduate study and research in this field; Provide graduate students with advanced training in hypersonics and an opportunity to interact with leading authorities in the field in both research and instructional capacities; and Perform fundamental research in areas that will impact hypersonic vehicle design and development.

The X-43A hypersonic research aircraft and its modified Pegasus booster rocket mounted to NASA's NB

NASA Technical Reports Server (NTRS)

2001-01-01

The first of three X-43A hypersonic research aircraft and its modified Pegasus booster rocket recently underwent combined systems testing while mounted to NASA's NB-52B carrier aircraft at the Dryden Flight Research Center, Edwards, California. The combined systems test was one of the last major milestones in the Hyper-X research program before the first X-43A flight. One of the major goals of the Hyper-X program is flight validation of airframe-integrated, air-breathing propulsion system, which so far have only been tested in ground facilities, such as wind tunnels. The X-43A flights will be the first actual flight tests of an aircraft powered by a revolutionary supersonic-combustion ramjet ('scramjet') engine capable of operating at hypersonic speeds above Mach 5 (five times the speed of sound). The X-43A design uses the underbody of the aircraft to form critical elements of the engine. The forebody shape helps compress the intake airflow, while the aft section acts as a nozzle to direct thrust. The 12-foot, unpiloted research vehicle was developed and built by MicroCraft Inc., Tullahoma, Tenn., under NASA contract. The booster, built by Orbital Sciences Corp., Dulles, Va., will accelerate the X-43A after the X-43A/booster 'stack' is air-launched from NASA's venerable NB-52 mothership. The X-43A will separate from the rocket at a predetermined altitude and speed and fly a pre-programmed trajectory, conducting aerodynamic and propulsion experiments until it descends into the Pacific Ocean. Three research flights are planned, two at Mach 7 and one at Mach 10.

Experimental aerothermodynamic research of hypersonic aircraft

NASA Technical Reports Server (NTRS)

Cleary, Joseph W.

1987-01-01

The 2-D and 3-D advance computer codes being developed for use in the design of such hypersonic aircraft as the National Aero-Space Plane require comparison of the computational results with a broad spectrum of experimental data to fully assess the validity of the codes. This is particularly true for complex flow fields with control surfaces present and for flows with separation, such as leeside flow. Therefore, the objective is to provide a hypersonic experimental data base required for validation of advanced computational fluid dynamics (CFD) computer codes and for development of more thorough understanding of the flow physics necessary for these codes. This is being done by implementing a comprehensive test program for a generic all-body hypersonic aircraft model in the NASA/Ames 3.5 foot Hypersonic Wind Tunnel over a broad range of test conditions to obtain pertinent surface and flowfield data. Results from the flow visualization portion of the investigation are presented.

Comparison of sporadic and FAP-associated desmoid-type fibromatoses.

PubMed

Koskenvuo, Laura; Ristimäki, Ari; Lepistö, Anna

2017-11-01

Desmoid-type fibromatosis is a rare disease of which 7.5-16% have been reported to be related to familial adenomatous polyposis (FAP). We sought to compare the characteristics and treatment of sporadic and FAP-related desmoid-type fibromatoses. Altogether 220 patients were included in the study after receiving a diagnosis of desmoid-type fibromatosis by the Pathology Department of Helsinki University Hospital, with adequate follow-up. Patients were included from January 1, 1980 until April 30, 2015. FAP-related tumors were found in 22 (10%) patients. FAP-related desmoid-type fibromatoses were larger, more commonly multiple, and more often intra-abdominally situated. Surgery was the treatment of choice for 179 (90%) of the sporadic patients and for 18 (82%) of FAP-related patients. Resections with non-involved margins (R0) were more common in sporadic desmoid-type fibromatoses (55% vs. 23%, P = 0.048). The risk of recurrence was 25% in sporadic- and 44% in the FAP-related group. Three (14%) patients with FAP-related desmoid-type fibromatoses died from the disease. The predictors for FAP occurrence among desmoid tumor patients are large tumor size, intra-abdominal location, multiple tumors, and patient's young age. Desmoid-type fibromatosis patients suffer a high recurrence rate, also among those experiencing sporadic tumors, but the risk of death due to the tumor is low. Conversely, desmoid disease represents a substantial cause of death among FAP patients. © 2017 Wiley Periodicals, Inc.

Restoration of the Hypersonic Tunnel Facility at NASA Glenn Research Center, Plum Brook Station

NASA Technical Reports Server (NTRS)

Woodling, Mark A.

2000-01-01

The NASA Glenn Research Center's Hypersonic Tunnel Facility (HTF), located at the Plum Brook Station in Sandusky, Ohio, is a non-vitiated, free-jet facility, capable of testing large-scale propulsion systems at Mach Numbers from 5 to 7. As a result of a component failure in September of 1996, a restoration project was initiated in mid- 1997 to repair the damage to the facility. Following the 2-1/2 year effort, the HTF has been returned to an operational condition. Significant repairs and operational improvements have been implemented in order to ensure facility reliability and personnel safety. As of January 2000, this unique, state-of-the-art facility was ready for integrated systems testing.

Turbulence measurements in hypersonic boundary layers using constant-temperature anemometry and Reynolds stress measurements in hypersonic boundary layers

NASA Technical Reports Server (NTRS)

Spina, Eric F.

1995-01-01

The primary objective in the two research investigations performed under NASA Langley sponsorship (Turbulence measurements in hypersonic boundary layers using constant temperature anemometry and Reynolds stress measurements in hypersonic boundary layers) has been to increase the understanding of the physics of hypersonic turbulent boundary layers. The study began with an extension of constant-temperature thermal anemometry techniques to a Mach 11 helium flow, including careful examinations of hot-wire construction techniques, system response, and system calibration. This was followed by the application of these techniques to the exploration of a Mach 11 helium turbulent boundary layer (To approximately 290 K). The data that was acquired over the course of more than two years consists of instantaneous streamwise mass flux measurements at a frequency response of about 500 kHz. The data are of exceptional quality in both the time and frequency domain and possess a high degree of repeatability. The data analysis that has been performed to date has added significantly to the body of knowledge on hypersonic turbulence, and the data reduction is continuing. An attempt was then made to extend these thermal anemometry techniques to higher enthalpy flows, starting with a Mach 6 air flow with a stagnation temperature just above that needed to prevent liquefaction (To approximately 475 F). Conventional hot-wire anemometry proved to be inadequate for the selected high-temperature, high dynamic pressure flow, with frequent wire breakage and poor system frequency response. The use of hot-film anemometry has since been investigated for these higher-enthalpy, severe environment flows. The difficulty with using hot-film probes for dynamic (turbulence) measurements is associated with construction limitations and conduction of heat into the film substrate. Work continues under a NASA GSRP grant on the development of a hot film probe that overcomes these shortcomings for hypersonic

Gastric tumours in FAP.

PubMed

Walton, Sarah-Jane; Frayling, Ian M; Clark, Susan K; Latchford, Andrew

2017-07-01

Gastric cancer is not a recognised extra-colonic manifestation of FAP, except in countries with a high prevalence of gastric cancer. Data regarding gastric adenomas in FAP are sparse. The aim of this study was to review the clinical characteristics of gastric tumours occurring within an FAP population from the largest European polyposis registry. All patients that developed a gastric adenoma or carcinoma were identified from a prospectively maintained registry database. The primary outcome measure was the occurrence of gastric adenoma or adenocarcinoma. Secondary outcomes included APC mutation, tumour stage, management and survival. Eight patients developed gastric cancer and 21 an adenoma (median age 52 and 44 years, respectively). Regular oesophagogastroduodenoscopy surveillance was performed in 6/8 patients who developed cancer. Half were advanced T3/4 tumours and 6/8 had nodal or metastatic spread at diagnosis. All cancer cases died within a median of 13.5 months from diagnosis. Gastric adenomas were evenly distributed: 11/21 (52%) in the distal and 10/21 (48%) proximal stomach, whereas 5/8 (63%) cancers were located proximally. An association between gastric tumour and desmoid development was observed; 7/8 (88%) cancer and 11/21 (52%) adenoma cases had a personal or family history of desmoid. It would appear from this small, retrospective study that gastric cancer is not a prominent extra-colonic feature of FAP in the Western world. It seems to present at an advanced stage with a poor prognosis. There may be an association between gastric tumour and desmoid occurrence but a large multicentre cohort is necessary to investigate this further.

RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent, Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis.

PubMed

Brünker, Peter; Wartha, Katharina; Friess, Thomas; Grau-Richards, Sandra; Waldhauer, Inja; Koller, Claudia Ferrara; Weiser, Barbara; Majety, Meher; Runza, Valeria; Niu, Huifeng; Packman, Kathryn; Feng, Ningping; Daouti, Sherif; Hosse, Ralf J; Mössner, Ekkehard; Weber, Thomas G; Herting, Frank; Scheuer, Werner; Sade, Hadassah; Shao, Cuiying; Liu, Bin; Wang, Peng; Xu, Gary; Vega-Harring, Suzana; Klein, Christian; Bosslet, Klaus; Umaña, Pablo

2016-05-01

Dysregulated cellular apoptosis and resistance to cell death are hallmarks of neoplastic initiation and disease progression. Therefore, the development of agents that overcome apoptosis dysregulation in tumor cells is an attractive therapeutic approach. Activation of the extrinsic apoptotic pathway is strongly dependent on death receptor (DR) hyperclustering on the cell surface. However, strategies to activate DR5 or DR4 through agonistic antibodies have had only limited clinical success. To pursue an alternative approach for tumor-targeted induction of apoptosis, we engineered a bispecific antibody (BsAb), which simultaneously targets fibroblast-activation protein (FAP) on cancer-associated fibroblasts in tumor stroma and DR5 on tumor cells. We hypothesized that bivalent binding to both FAP and DR5 leads to avidity-driven hyperclustering of DR5 and subsequently strong induction of apoptosis in tumor cells but not in normal cells. Here, we show that RG7386, an optimized FAP-DR5 BsAb, triggers potent tumor cell apoptosis in vitro and in vivo in preclinical tumor models with FAP-positive stroma. RG7386 antitumor efficacy was strictly FAP dependent, was independent of FcR cross-linking, and was superior to conventional DR5 antibodies. In combination with irinotecan or doxorubicin, FAP-DR5 treatment resulted in substantial tumor regression in patient-derived xenograft models. FAP-DR5 also demonstrated single-agent activity against FAP-expressing malignant cells, due to cross-binding of FAP and DR5 across tumor cells. Taken together, these data demonstrate that RG7386, a novel and potent antitumor agent in both mono- and combination therapies, overcomes limitations of previous DR5 antibodies and represents a promising approach to conquer tumor-associated resistance to apoptosis. Mol Cancer Ther; 15(5); 946-57. ©2016 AACR. ©2016 American Association for Cancer Research.

Hypersonic nozzle design

NASA Technical Reports Server (NTRS)

Griffith, Wayland C.

1989-01-01

Possible experimental facilities appropriate to a university environment that could make meaningful contributions to the solution of problems in hypersonic aerodynamics are investigated. Needs for the National Aerospace Plane and interplanetary flights with atmospheric aerobraking are used to scope the problem. Relevant events of the past two decades in universities and at the national laboratories are examined for their implications regarding both problems and prospects. Most striking is the emergence of computational fluid dynamics, which is viewed here as an equal partner with laboratory experimentation and flight test in relating theory with reality. Also significant are major advances in instrumentation and data processing methods, especially optical techniques. The direction of the study was guided by the concept of a companion program, i.e., the university effort should complement a major area of endeavor at NASA-Langley. Through this, both faculty and student participants gain a natural and effective working relationship. Existing and proposed major hypersonic aerodynamic facilities in industry and at the national laboratories are examined by type; hypersonic wind tunnels, arc-heated tunnels, shock tubes and tunnels, and ballistic ranges. Of these, the free piston tunnel and shock tube/tunnel are most appropriate for a university.

Focus on autonomic dysfunction in familial amyloidotic polyneuropathy (FAP).

PubMed

Obayashi, Konen; Ando, Yukio

2012-06-01

It is well known that autonomic dysfunction in familial amyloidotic polyneuropathy (FAP) is the most serious problem, because it restricts the daily life of these patients. The detail mechanisms of the onset are not well understood in FAP and domino liver transplantation-induced amyloid neuropathy. As autonomic disturbances play an important role in the symptomatology of FAP, further studies of autonomic dysfunction in these patients may lead the pathogenesis of FAP. Autonomic dysfunction is often observed before sensory and motor nerve dysfunction in FAP. This can be attributed to the morphological characteristics of the nerves. Unmyelinated, small myelinated, and large myelinated fibers tend to become impaired in that order. Although the reasons of susceptibility to amyloid infiltration and injury are not known, studies of autopsied FAP patients have revealed heavy infiltration of amyloid in autonomic ganglions. Moreover, spinal ganglion and posterior loot of the spine had severe amyloid deposits than did the anterior root of the spine or the motor nerves. It is well known that autonomic dysfunction is the most serious problem, because it restricts the daily life of FAP patients. However, we have four major questions about autonomic dysfunction in clinical. In this manuscript, we discuss about the answers of these questions.

Fibro/Adipogenic Progenitors (FAPs): Isolation by FACS and Culture.

PubMed

Low, Marcela; Eisner, Christine; Rossi, Fabio

2017-01-01

Fibro/adipogenic progenitors (FAPs ) are tissue-resident mesenchymal stromal cells (MSCs). Current literature supports a role for these cells in the homeostasis and repair of multiple tissues suggesting that FAPs may have extensive therapeutic potential in the treatment of numerous diseases. In this context, it is crucial to establish efficient and reproducible procedures to purify FAP populations from various tissues. Here, we describe a protocol for the isolation and cell culture of FAPs from murine skeletal muscle using fluorescence -activated cell sorting (FACS), which is particularly useful for experiments where high cell purity is an essential requirement. Identification, isolation, and cell culture of FAPs represent powerful tools that will help us to understand the role of these cells in different conditions and facilitate the development of safe and effective new treatments for diseases.

Mutation analysis of the APC gene in Taiwanese FAP families: low incidence of APC germline mutation in a distinct subgroup of FAP families.

PubMed

Chiang, J M; Chen, H W; Tang, R P; Chen, J S; Changchien, C R; Hsieh, P S; Wang, J Y

2010-06-01

Familial adenomatous polyposis (FAP) is an autosomal-dominant disease caused by germline mutations in the adenomatous polyposis coli (APC) gene. The affected individuals develop colorectal polyposis and show various extra-colonic manifestations. In this study, we aimed to investigate the genetic and clinical characteristics of FAP in Taiwanese families and analyze the genotype-phenotype correlations. Blood samples were obtained from 66 FAP patients registered in the hereditary colorectal cancer database. Then, germline mutations in the APC genes of these 66 polyposis patients from 47 unrelated FAP families were analyzed. The germline-mutation-negative cases were analyzed by performing multiplex ligation-dependent probe amplification (MLPA) and single-strand conformation polymorphism (SSCP) analysis of the MUTYH gene. Among the analyzed families, 79% (37/47) of the families showed 28 APC mutations, including 19 frameshift mutations, 4 nonsense mutations, 3 genomic deletion mutations, 1 missense mutation, and 1 splice-site mutation. In addition, we identified 15 novel mutations in 32% (15/47) of the families. The cases in which APC mutations were not identified showed significantly lower incidence of profuse polyposis (P = 0.034) and gastroduodenal polyps (P = 0.027). Furthermore, FAP families in which some affected individuals had less than 100 polyps showed significant association with low incidence of APC germline mutations (P = 0.002). We have added the APC germline-mutation data for Taiwanese FAP patients and indicated the presence of an FAP subgroup comprising affected individuals with nonadenomatous polyps or less than 100 adenomatous polyps; this form of FAP is less frequently caused by germline mutations of the APC gene.

Family Violence Measurement: A Sourcebook for FAP.

DTIC Science & Technology

1998-02-26

child abuse ? (6) What information can FAP gain from the source of referral? This document will serve several purposes: (1) to teach some basic research methods; (2) to help FAP managers gather and analyze information from subordinates, and (3) to help people in the field analyze their own unique

Acylated Gly-(2-cyano)pyrrolidines as inhibitors of fibroblast activation protein (FAP) and the issue of FAP/prolyl oligopeptidase (PREP)-selectivity.

PubMed

Ryabtsova, Oxana; Jansen, Koen; Van Goethem, Sebastiaan; Joossens, Jurgen; Cheng, Jonathan D; Lambeir, Anne-Marie; De Meester, Ingrid; Augustyns, Koen; Van der Veken, Pieter

2012-05-15

A series of N-acylated glycyl-(2-cyano)pyrrolidines were synthesized with the aim of generating structure-activity relationship (SAR) data for this class of compounds as inhibitors of fibroblast activation protein (FAP). Specifically, the influence of (1) the choice of the N-acyl group and (2) structural modification of the 2-cyanopyrrolidine residue were investigated. The inhibitors displayed inhibitory potency in the micromolar to nanomolar range and showed good to excellent selectivity with respect to the proline selective dipeptidyl peptidases (DPPs) DPP IV, DPP9 and DPP II. Additionally, selectivity for FAP with respect to prolyl oligopeptidase (PREP) is reported. Not unexpectedly, the latter data suggest significant overlap in the pharmacophoric features that define FAP or PREP-inhibitory activity and underscore the importance of systematically evaluating the FAP/PREP-selectivity index for inhibitors of either of these two enzymes. Finally, this study forwards several compounds that can serve as leads or prototypic structures for future FAP-selective-inhibitor discovery. Copyright © 2012 Elsevier Ltd. All rights reserved.

Tumor-promoting desmoplasia is disrupted by depleting FAP-expressing stromal cells

PubMed Central

Scholler, John; Monslow, James; Avery, Diana; Newick, Kheng; O'Brien, Shaun; Evans, Rebecca A.; Bajor, David J.; Clendenin, Cynthia; Durham, Amy C; Buza, Elizabeth L; Vonderheide, Robert H; June, Carl H

2015-01-01

Malignant cells drive the generation of a desmoplastic and immunosuppressive tumor microenvironment. Cancer-associated stromal cells (CASCs) are a heterogeneous population that provides both negative and positive signals for tumor cell growth and metastasis. Fibroblast activation protein (FAP) is a marker of a major subset of CASCs in virtually all carcinomas. Clinically, FAP expression serves as an independent negative prognostic factor for multiple types of human malignancies. Prior studies established that depletion of FAP+ cells inhibits tumor growth by augmenting anti-tumor immunity. However, the potential for immune-independent effects on tumor growth have not been defined. Herein, we demonstrate that FAP+ CASCs are required for maintenance of the provisional tumor stroma since depletion of these cells, by adoptive transfer of FAP-targeted chimeric antigen receptor (CAR) T cells, reduced extracellular matrix proteins and glycosaminoglycans. Adoptive transfer of FAP-CAR T cells also decreased tumor vascular density and restrained growth of desmoplastic human lung cancer xenografts and syngeneic murine pancreatic cancers in an immune-independent fashion. Adoptive transfer of FAP-CAR T cells also restrained autochthonous pancreatic cancer growth. These data distinguish the function of FAP+ CASCs from other CASC subsets and provide support for further development of FAP+ stromal cell-targeted therapies for the treatment of solid tumors. PMID:25979873

Tumor-Promoting Desmoplasia Is Disrupted by Depleting FAP-Expressing Stromal Cells.

PubMed

Lo, Albert; Wang, Liang-Chuan S; Scholler, John; Monslow, James; Avery, Diana; Newick, Kheng; O'Brien, Shaun; Evans, Rebecca A; Bajor, David J; Clendenin, Cynthia; Durham, Amy C; Buza, Elizabeth L; Vonderheide, Robert H; June, Carl H; Albelda, Steven M; Puré, Ellen

2015-07-15

Malignant cells drive the generation of a desmoplastic and immunosuppressive tumor microenvironment. Cancer-associated stromal cells (CASC) are a heterogeneous population that provides both negative and positive signals for tumor cell growth and metastasis. Fibroblast activation protein (FAP) is a marker of a major subset of CASCs in virtually all carcinomas. Clinically, FAP expression serves as an independent negative prognostic factor for multiple types of human malignancies. Prior studies established that depletion of FAP(+) cells inhibits tumor growth by augmenting antitumor immunity. However, the potential for immune-independent effects on tumor growth have not been defined. Herein, we demonstrate that FAP(+) CASCs are required for maintenance of the provisional tumor stroma because depletion of these cells, by adoptive transfer of FAP-targeted chimeric antigen receptor (CAR) T cells, reduced extracellular matrix proteins and glycosaminoglycans. Adoptive transfer of FAP-CAR T cells also decreased tumor vascular density and restrained growth of desmoplastic human lung cancer xenografts and syngeneic murine pancreatic cancers in an immune-independent fashion. Adoptive transfer of FAP-CAR T cells also restrained autochthonous pancreatic cancer growth. These data distinguish the function of FAP(+) CASCs from other CASC subsets and provide support for further development of FAP(+) stromal cell-targeted therapies for the treatment of solid tumors. ©2015 American Association for Cancer Research.

[FAP Expression and Its Association with the Prognosis of Gastric Stromal Tumors].

PubMed

Tang, Su-Min; Shen, Chao-Yong; Yin, Yuan; Yin, Xiao-Nan; Cai, Zhao-Lun; Chen, Zhi-Xin; Zhang, Bo

2017-03-01

To determine the association of FAP expression with the prognosis of gastric stromal tumors (GSTs). Paraffin-embedded GSTs samples were collected from January 2010 to December 2013 in the department of pathology of our hospital. FAP expression was examined by immunohistochemistry staining. Its correlations with clinical pathological characteristics and prognosis of GSTs were analyzed. A total of 98 cases were included in this study. FAP was expressed in the cytoplasm of GSTs cells, with a positive rate of 42.9%. No FAP expression was found in normal gastric tissues. No differences of FAP expression were found in patients with different gender, age and tumor mitotic counts ( P >0.05). Tumor diameter and risk classification were associated with FAP expression ( P <0.05). Higher levels of FAP expression were found in larger and higher risk tumors. No significant correlations between FAP expression and routine immunohistochemical markers were found. Log-rank univariate survival analysis showed that mitotic counts, tumor size, postoperative IM and FAP expression were associated with recurrence free survival of GSTs patients with intermediate-high risks ( P <0.05). Cox multivariate survival analysis showed that mitotic counts, tumor size, postoperative IM and FAP were independent predictors for the prognosis of GSTs patients with intermediate-high risks ( P <0.05). FAP is expressed in the cytoplasm of gastric GIST cells, but not in normal gastric tissues. FAP is a predictor for the prognosis of GSTs patients with intermediate-high risks.

Discrete Roughness Transition for Hypersonic Flight Vehicles

NASA Technical Reports Server (NTRS)

Berry, Scott A.; Horvath, Thomas J.

2007-01-01

The importance of discrete roughness and the correlations developed to predict the onset of boundary layer transition on hypersonic flight vehicles are discussed. The paper is organized by hypersonic vehicle applications characterized in a general sense by the boundary layer: slender with hypersonic conditions at the edge of the boundary layer, moderately blunt with supersonic, and blunt with subsonic. This paper is intended to be a review of recent discrete roughness transition work completed at NASA Langley Research Center in support of agency flight test programs. First, a review is provided of discrete roughness wind tunnel data and the resulting correlations that were developed. Then, results obtained from flight vehicles, in particular the recently flown Hyper-X and Shuttle missions, are discussed and compared to the ground-based correlations.

The NASA-sponsored Maryland center for hypersonic education and research

NASA Technical Reports Server (NTRS)

Lewis, Mark J.; Gupta, Ashwani K.

1995-01-01

The Office of Aeronautics of the National Aeronautics and Space Administration has established a program to support university programs in the field of hypersonic flight. Beginning in the fall of 1993, three universities, including the University of Maryland at College Park, were selected to participate in this activity. The program at the University of Maryland includes faculty in the Department of Aerospace Engineering and Department of Mechanical Engineering, and provides a multidisciplinary environment for graduate and undergraduate students to study and conduct research in the field of hypersonic flight. Ongoing projects cover the range of applications from cruisers through transatmospheric and reentry vehicles. Research activities, focused on propulsion, fluid dynamics, inverse design, and vehicle optimization and integration, are conducted in conjuntion with industrial partners and government laboratories.

NASA's B-52B launch aircraft takes off carrying the second X-43A hypersonic research vehicle attached to a modified Pegasus rocket, on March 27, 2004

NASA Image and Video Library

2004-03-27

The second X-43A hypersonic research aircraft and its modified Pegasus booster rocket left the runway, carried aloft by NASA's B-52B launch aircraft from the NASA Dryden Flight Research Center at Edwards Air Force Base, Calif., on March 27, 2004. About an hour later the Pegasus booster was launched from the B-52 to accelerate the X-43A to its intended speed of Mach 7.

NASA's B-52B launch aircraft takes off carrying the third X-43A hypersonic research vehicle attached to a modified Pegasus rocket, on November 16, 2004

NASA Image and Video Library

2004-11-16

The third X-43A hypersonic research aircraft and its modified Pegasus booster rocket left the runway, carried aloft by NASA's B-52B launch aircraft from the NASA Dryden Flight Research Center at Edwards Air Force Base, California, on November 16, 2004. About an hour later the Pegasus booster was launched from the B-52 to accelerate the X-43A to its intended speed of Mach 10.

RNA Mimicry by the Fap7 Adenylate Kinase in Ribosome Biogenesis

PubMed Central

Réty, Stéphane; Lebaron, Simon; Deschamps, Patrick; Bareille, Joseph; Jombart, Julie; Robert-Paganin, Julien; Delbos, Lila; Chardon, Florian; Zhang, Elodie; Charenton, Clément; Tollervey, David; Leulliot, Nicolas

2014-01-01

During biogenesis of the 40S and 60S ribosomal subunits, the pre-40S particles are exported to the cytoplasm prior to final cleavage of the 20S pre-rRNA to mature 18S rRNA. Amongst the factors involved in this maturation step, Fap7 is unusual, as it both interacts with ribosomal protein Rps14 and harbors adenylate kinase activity, a function not usually associated with ribonucleoprotein assembly. Human hFap7 also regulates Cajal body assembly and cell cycle progression via the p53–MDM2 pathway. This work presents the functional and structural characterization of the Fap7–Rps14 complex. We report that Fap7 association blocks the RNA binding surface of Rps14 and, conversely, Rps14 binding inhibits adenylate kinase activity of Fap7. In addition, the affinity of Fap7 for Rps14 is higher with bound ADP, whereas ATP hydrolysis dissociates the complex. These results suggest that Fap7 chaperones Rps14 assembly into pre-40S particles via RNA mimicry in an ATP-dependent manner. Incorporation of Rps14 by Fap7 leads to a structural rearrangement of the platform domain necessary for the pre-rRNA to acquire a cleavage competent conformation. PMID:24823650

Advances in Computational Capabilities for Hypersonic Flows

NASA Technical Reports Server (NTRS)

Kumar, Ajay; Gnoffo, Peter A.; Moss, James N.; Drummond, J. Philip

1997-01-01

The paper reviews the growth and advances in computational capabilities for hypersonic applications over the period from the mid-1980's to the present day. The current status of the code development issues such as surface and field grid generation, algorithms, physical and chemical modeling, and validation is provided. A brief description of some of the major codes being used at NASA Langley Research Center for hypersonic continuum and rarefied flows is provided, along with their capabilities and deficiencies. A number of application examples are presented, and future areas of research to enhance accuracy, reliability, efficiency, and robustness of computational codes are discussed.

Fibroblast activation protein (FAP) as a novel metabolic target.

PubMed

Sánchez-Garrido, Miguel Angel; Habegger, Kirk M; Clemmensen, Christoffer; Holleman, Cassie; Müller, Timo D; Perez-Tilve, Diego; Li, Pengyun; Agrawal, Archita S; Finan, Brian; Drucker, Daniel J; Tschöp, Matthias H; DiMarchi, Richard D; Kharitonenkov, Alexei

2016-10-01

Fibroblast activation protein (FAP) is a serine protease belonging to a S9B prolyl oligopeptidase subfamily. This enzyme has been implicated in cancer development and recently reported to regulate degradation of FGF21, a potent metabolic hormone. Using a known FAP inhibitor, talabostat (TB), we explored the impact of FAP inhibition on metabolic regulation in mice. To address this question we evaluated the pharmacology of TB in various mouse models including those deficient in FGF21, GLP1 and GIP signaling. We also studied the ability of FAP to process FGF21 in vitro and TB to block FAP enzymatic activity. TB administration to diet-induced obese (DIO) animals led to profound decreases in body weight, reduced food consumption and adiposity, increased energy expenditure, improved glucose tolerance and insulin sensitivity, and lowered cholesterol levels. Total and intact plasma FGF21 were observed to be elevated in TB-treated DIO mice but not lean animals where the metabolic impact of TB was significantly attenuated. Furthermore, and in stark contrast to naïve DIO mice, the administration of TB to obese FGF21 knockout animals demonstrated no appreciable effect on body weight or any other measures of metabolism. In support of these results we observed no enzymatic degradation of human FGF21 at either end of the protein when FAP was inhibited in vitro by TB. We conclude that pharmacological inhibition of FAP enhances levels of FGF21 in obese mice to provide robust metabolic benefits not observed in lean animals, thus validating this enzyme as a novel drug target for the treatment of obesity and diabetes.

Fibroblast Activation Protein (FAP) Accelerates Collagen Degradation and Clearance from Lungs in Mice*

PubMed Central

Fan, Ming-Hui; Zhu, Qiang; Li, Hui-Hua; Ra, Hyun-Jeong; Majumdar, Sonali; Gulick, Dexter L.; Jerome, Jacob A.; Madsen, Daniel H.; Christofidou-Solomidou, Melpo; Speicher, David W.; Bachovchin, William W.; Feghali-Bostwick, Carol; Puré, Ellen

2016-01-01

Idiopathic pulmonary fibrosis is a disease characterized by progressive, unrelenting lung scarring, with death from respiratory failure within 2–4 years unless lung transplantation is performed. New effective therapies are clearly needed. Fibroblast activation protein (FAP) is a cell surface-associated serine protease up-regulated in the lungs of patients with idiopathic pulmonary fibrosis as well as in wound healing and cancer. We postulate that FAP is not only a marker of disease but influences the development of pulmonary fibrosis after lung injury. In two different models of pulmonary fibrosis, intratracheal bleomycin instillation and thoracic irradiation, we find increased mortality and increased lung fibrosis in FAP-deficient mice compared with wild-type mice. Lung extracellular matrix analysis reveals accumulation of intermediate-sized collagen fragments in FAP-deficient mouse lungs, consistent with in vitro studies showing that FAP mediates ordered proteolytic processing of matrix metalloproteinase (MMP)-derived collagen cleavage products. FAP-mediated collagen processing leads to increased collagen internalization without altering expression of the endocytic collagen receptor, Endo180. Pharmacologic FAP inhibition decreases collagen internalization as expected. Conversely, restoration of FAP expression in the lungs of FAP-deficient mice decreases lung hydroxyproline content after intratracheal bleomycin to levels comparable with that of wild-type controls. Our findings indicate that FAP participates directly, in concert with MMPs, in collagen catabolism and clearance and is an important factor in resolving scar after injury and restoring lung homeostasis. Our study identifies FAP as a novel endogenous regulator of fibrosis and is the first to show FAP's protective effects in the lung. PMID:26663085

Gastric cancer in FAP: a concerning rise in incidence.

PubMed

Mankaney, Gautam; Leone, Pamela; Cruise, Michael; LaGuardia, Lisa; O'Malley, Margaret; Bhatt, Amit; Church, James; Burke, Carol A

2017-07-01

The highest cancer risks in familial adenomatous polyposis (FAP) include colorectal, duodenal, and thyroid for which surveillance is recommended. Nearly all patients with FAP have gastric fundic gland polyposis (FGP), but gastric cancers are rarely reported with a similar incidence as the general population. We describe a recent, sudden increase in the incidence of gastric cancer in FAP. Seven of the ten cases were diagnosed in the last 20 months. Comparing our population to the SEER database for gastric cancer, the standardized incidence ratio is 140. All cases arose in patients with a carpeting of FGP and associated with large mounds of proximal gastric polyps. Nearly all patients were under upper endoscopic surveillance. This is a concerning observation and reflects a change in the phenotypic presentation of FAP in Western patients.

The HIAD stands for Hypersonic Inflatable Aerodynamic Decelerato

NASA Image and Video Library

2013-05-31

The HIAD stands for Hypersonic Inflatable Aerodynamic Decelerator, an inflatable spacecraft technology that allows payloads to survive the harsh conditions of atmospheric re-entry. This photo was taken at NASA Langley in Building 1250 when sensors were being applied.

The HIAD stands for Hypersonic Inflatable Aerodynamic Decelerato

NASA Image and Video Library

2013-04-25

The HIAD stands for Hypersonic Inflatable Aerodynamic Decelerator, an inflatable spacecraft technology that allows payloads to survive the harsh conditions of atmospheric re-entry. This photo was taken at NASA Langley in Building 1250 when sensors were being applied.

Structural insight into the role of Streptococcus parasanguinis Fap1 within oral biofilm formation

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

Garnett, James A.; Simpson, Peter J.; Taylor, Jonathan

2012-01-06

Highlights: Black-Right-Pointing-Pointer Crystal structure of Streptococcus parasanguinis Fap1-NR{sub {alpha}} at pH 5.0. Black-Right-Pointing-Pointer pH-dependent conformational changes mediated through electrostatic potential of Fap1-NR{sub {alpha}}. Black-Right-Pointing-Pointer Fap1 facilitates pH-dependent biofilms. Black-Right-Pointing-Pointer We model inter-Fap1 biofilm interactions. -- Abstract: The fimbriae-associated protein 1 (Fap1) is a major adhesin of Streptococcus parasanguinis, a primary colonizer of the oral cavity that plays an important role in the formation of dental plaque. Fap1 is an extracellular adhesive surface fibre belonging to the serine-rich repeat protein (SRRP) family, which plays a central role in the pathogenesis of streptococci and staphylococci. The N-terminal adhesive region of Fap1 (Fap1-NR)more » is composed of two domains (Fap1-NR{sub {alpha}} and Fap1-NR{sub {beta}}) and is projected away from the bacterial surface via the extensive serine-rich repeat region, for adhesion to the salivary pellicle. The adhesive properties of Fap1 are modulated through a pH switch in which a reduction in pH results in a rearrangement between the Fap1-NR{sub {alpha}} and Fap1-NR{sub {beta}} domains, which assists in the survival of S. parasanguinis in acidic environments. We have solved the structure of Fap1-NR{sub {alpha}} at pH 5.0 at 3.0 A resolution and reveal how subtle rearrangements of the 3-helix bundle combined with a change in electrostatic potential mediates 'opening' and activation of the adhesive region. Further, we show that pH-dependent changes are critical for biofilm formation and present an atomic model for the inter-Fap1-NR interactions which have been assigned an important role in the biofilm formation.« less

Development and Preliminary Evaluation of a FAP Protocol: Brief Relationship Enhancement

ERIC Educational Resources Information Center

Holman, Gareth; Kohlenberg, Robert J.; Tsai, Mavis

2012-01-01

The purpose of this study was to develop a brief Functional Analytic Psychotherapy (FAP) protocol that will facilitate reliable implementation of FAP interventions, thus supporting research on FAP process and outcome. The treatment was a four-session individual therapy for clients who were interested in improving their relationship with their…

Fibroblast Activation Protein (FAP) Accelerates Collagen Degradation and Clearance from Lungs in Mice.

PubMed

Fan, Ming-Hui; Zhu, Qiang; Li, Hui-Hua; Ra, Hyun-Jeong; Majumdar, Sonali; Gulick, Dexter L; Jerome, Jacob A; Madsen, Daniel H; Christofidou-Solomidou, Melpo; Speicher, David W; Bachovchin, William W; Feghali-Bostwick, Carol; Puré, Ellen

2016-04-08

Idiopathic pulmonary fibrosis is a disease characterized by progressive, unrelenting lung scarring, with death from respiratory failure within 2-4 years unless lung transplantation is performed. New effective therapies are clearly needed. Fibroblast activation protein (FAP) is a cell surface-associated serine protease up-regulated in the lungs of patients with idiopathic pulmonary fibrosis as well as in wound healing and cancer. We postulate that FAP is not only a marker of disease but influences the development of pulmonary fibrosis after lung injury. In two different models of pulmonary fibrosis, intratracheal bleomycin instillation and thoracic irradiation, we find increased mortality and increased lung fibrosis in FAP-deficient mice compared with wild-type mice. Lung extracellular matrix analysis reveals accumulation of intermediate-sized collagen fragments in FAP-deficient mouse lungs, consistent within vitrostudies showing that FAP mediates ordered proteolytic processing of matrix metalloproteinase (MMP)-derived collagen cleavage products. FAP-mediated collagen processing leads to increased collagen internalization without altering expression of the endocytic collagen receptor, Endo180. Pharmacologic FAP inhibition decreases collagen internalization as expected. Conversely, restoration of FAP expression in the lungs of FAP-deficient mice decreases lung hydroxyproline content after intratracheal bleomycin to levels comparable with that of wild-type controls. Our findings indicate that FAP participates directly, in concert with MMPs, in collagen catabolism and clearance and is an important factor in resolving scar after injury and restoring lung homeostasis. Our study identifies FAP as a novel endogenous regulator of fibrosis and is the first to show FAP's protective effects in the lung. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Toward an Evaluation Strategy for FAP-Day Care.

ERIC Educational Resources Information Center

Datta, Lois-ellin, Ed.

This report presents the findings of an invitational conference sponsored by the Office of Child Development to assess the implications of Family Assistance Plan (FAP) day care provisions from the viewpoint of program evaluation. The first section outlines the features of FAP day care, and the second section identifies accountability issues for…

Overview of X-38 Hypersonic Aerothermodynamic Wind Tunnel Data and Comparison with Numerical Results

NASA Technical Reports Server (NTRS)

Campbell, C.; Caram, J.; Berry, S.; Horvath, T.; Merski, N.; Loomis, M.; Venkatapathy, E.

2004-01-01

A NASA team of engineers has been organized to design a crew return vehicle for returning International Space Station crew members from orbit. The hypersonic aerothermodynamic characteristics of the X-23/X-24A derived X-38 crew return vehicle are being evaluated in various wind tunnels in support of this effort. Aerothermodynamic data from two NASA hypersonic tunnels at Mach 6 and Mach 10 has been obtained with cast ceramic models and a thermographic phosphorus digital imaging system. General windward surface heating features are described based on experimental surface heating images and surface oil flow patterns for the nominal hypersonic aerodynamic orientation. Body flap reattachment heating levels are examined. Computational Fluid Dynamics tools have been applied at the appropriate wind tunnel conditions to make comparisons with this data.

Computation of hypersonic flows with finite rate condensation and evaporation of water

NASA Technical Reports Server (NTRS)

Perrell, Eric R.; Candler, Graham V.; Erickson, Wayne D.; Wieting, Alan R.

1993-01-01

A computer program for modelling 2D hypersonic flows of gases containing water vapor and liquid water droplets is presented. The effects of interphase mass, momentum and energy transfer are studied. Computations are compared with existing quasi-1D calculations on the nozzle of the NASA Langley Eight Foot High Temperature Tunnel, a hypersonic wind tunnel driven by combustion of natural gas in oxygen enriched air.

The X-43A hypersonic research aircraft and its modified Pegasus® booster rocket recently underwent combined systems testing while mounted to NASA's NB-52B carrier aircraft

NASA Image and Video Library

2001-03-15

The first of three X-43A hypersonic research aircraft and its modified Pegasus® booster rocket recently underwent combined systems testing while mounted to NASA's NB-52B carrier aircraft at the Dryden Flight Research Center, Edwards, Calif. The combined systems test was one of the last major milestones in the Hyper-X research program before the first X-43A flight. The X-43A flights will be the first actual flight tests of an aircraft powered by a revolutionary supersonic-combustion ramjet ("scramjet") engine capable of operating at hypersonic speeds (above Mach 5, or five times the speed of sound). The 12-foot, unpiloted research vehicle was developed and built by MicroCraft Inc., Tullahoma, Tenn., under NASA contract. The booster was built by Orbital Sciences Corp., Dulles, Va.,After being air-launched from NASA's venerable NB-52 mothership, the booster will accelerate the X-43A to test speed and altitude. The X-43A will then separate from the rocket and fly a pre-programmed trajectory, conducting aerodynamic and propulsion experiments until it descends into the Pacific Ocean. Three research flights are planned, two at Mach 7 and one at Mach 10.

Specific inhibition of fibroblast activation protein (FAP)-alpha prevents tumor progression in vitro.

PubMed

Teichgräber, Volker; Monasterio, Carmen; Chaitanya, Krishna; Boger, Regina; Gordon, Katrin; Dieterle, Thomas; Jäger, Dirk; Bauer, Stefan

2015-09-01

Solid tumors modulate their environment to keep non-malignant stromal cells in a tumor-promoting state. The main cells in the stroma of epithelial derived tumors are cancer associated fibroblasts (CAF) that are critical to tumorigenesis and angiogenesis. CAFs also supply the tumor cells with growth factors and extracellular matrix (ECM) degrading enzymes. They are thus essential for tumor initiation as well as tumor progression and metastasis, suggesting that they represent an ideal cellular target of an integrative tumor therapy. Fibroblast activation protein (FAP) is a well-defined marker, expressed at high levels on the cell surface of CAFs. FAP, a constitutively active serine peptidase with both dipeptidyl peptidase IV (DPP IV) and collagenase/gelatinase activity, promotes malignant and invasive behavior of epithelial cancers. High stromal expression levels of FAP correlate with poor prognosis. FAP is difficult to detect in non-diseased adult tissue, but it is generally expressed at sites of tissue remodeling. In our experiments, we aimed for a reduction of the pro-tumorigenic activities of CAFs by depleting FAP from fibroblasts growing in a composite environment with epithelial tumor cells. FAP depletion was achieved by two therapeutically relevant approaches: a novel internalizing anti-FAP IgG1 antibody and FAP gene knock-down by siRNA delivery. The antibody effectively removed FAP from the cell surface and was capable of reversing the FAP mediated migratory and invasive capacity. FAP RNA interference was equally effective when compared to the antibody. Thus, targeting FAP on CAF suppresses pro-tumorigenic activities and may result in a clinically effective reduction of tumor progression and dissemination. Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The Val30Met familial amyloid polyneuropathy specific Rasch-built overall disability scale (FAP-RODS(©) ).

PubMed

Pruppers, Mariëlle H J; Merkies, Ingemar S J; Faber, Catharina G; Da Silva, Ana M; Costa, Vanessa; Coelho, Teresa

2015-09-01

Familial amyloid polyneuropathy (FAP) is a chronic debilitating multi-organic disorder, mainly assessed using ordinal-based impairment measures. To date, no outcome measure at the activity and participation level has been constructed in FAP. The current study aimed to design an interval activity/participation scale for FAP through Rasch methodology. A preliminary FAP Rasch-built overall disability scale (pre-FAP-RODS) containing 146 activity/participation items was assessed twice (interval: 2-4 week; test-retest reliability) in 248 patients with Val30Met FAP examined in Porto, Portugal, of which 65.7% have received liver transplantation. An ordinal-based 24-item FAP-symptoms inventory questionnaire (FAP-SIQ) was also assessed (validity purposes). The pre-FAP-RODS and FAP-SIQ data were subjected to Rasch analyses. The pre-FAP-RODS did not meet model's expectations. On the basis of requirements such as misfit statistics, differential item functioning, and local dependency, items were systematically removed until a final 34-item FAP-RODS(©) was constructed fulfilling all Rasch requirements. Acceptable reliability/validity scores were demonstrated. In conclusion, the 34-item FAP-RODS(©) is a disease-specific interval measure suitable for detecting activity and participation restrictions in patients with FAP. The use of the FAP-RODS(©) is recommended for future international clinical trials in patients with Val30Met FAP determining its responsiveness and its cross-cultural validation. Its expansion to other forms of FAP should also be focus of future clinical studies. © 2015 Peripheral Nerve Society.

[A Case of Metachronous Multiple Thyroid Papillary Carcinoma with FAP].

PubMed

Tajima, Yusuke; Kumamoto, Kensuke; Yamamoto, Azusa; Chika, Noriyasu; Watanabe, Yuichiro; Matsuzawa, Takeaki; Ishibashi, Keiichiro; Mochiki, Erito; Iwama, Takeo; Akagi, Kiwamu; Ishida, Hideyuki

2015-11-01

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder, the result of a germ line mutation in the adenomatous polyposis coli (APC) gene. FAP can be associated with various extracolonic lesions, including thyroid cancer, which frequently occurs in women. We report the case of a 36-year-old woman diagnosed as having FAP with multiple metachronous thyroid papillary carcinomas. She underwent left thyroidectomy at the age of 19 years without a diagnosis of FAP. Multiple polyps in her stomach were detected by medical examination and more than 100 polyps in the colon were found by colonoscopy. She was referred to our hospital after a diagnosis of non-profuse FAP. Multiple tumors with a maximum diameter of 10mm were detected in the right lobe of the thyroid gland during the preoperative examination. Papillary carcinoma was suspected based on fine-needle aspiration cytology. We performed a right thyroidectomy after prophylactic colectomy. Pathological findings revealed a cribriform-morula variant of papillary thyroid carcinoma. The patient remains well after 2 year 6 months with no recurrence.

Transthyretin familial amyloid polyneuropathy (TTR-FAP): Parameters for early diagnosis.

PubMed

Escolano-Lozano, Fabiola; Barreiros, Ana Paula; Birklein, Frank; Geber, Christian

2018-01-01

Familial transthyretin amyloidosis is a life-threatening disease presenting with sensorimotor and autonomic polyneuropathy. Delayed diagnosis has a detrimental effect on treatment and prognosis. To facilitate diagnosis, we analyzed data patterns of patients with transthyretin familial amyloid polyneuropathy (TTR-FAP) and compared them to polyneuropathies of different etiology for clinical and electrophysiological discriminators. Twenty-four patients with TTR-FAP and 48 patients with diabetic polyneuropathy (dPNP) were investigated (neurological impairment score NIS; neurological disability score NDS) in a cross-sectional design. Both groups were matched for gender and presence of pain. Quantitative sensory testing (QST), sympathetic skin response (SSR), heart rate variability (HRV), and nerve conduction studies (NCV) were performed. Both groups were compared using univariate analysis. In a stepwise discriminant analysis, discriminators between both neuropathies were identified. These discriminators were validated comparing TTR-FAP patients with a cohort of patients with chemotherapy-induced polyneuropathy (CIN) and chronic inflammatory demyelinating neuropathy (CIDP). TTR-FAP patients scored higher in NDS and NIS and had impaired cold detection (CDT, p  = .024), cold-warm discrimination (TSL, p  = .019) and mechanical hyperalgesia (MPT, p  = .029) at the hands, SSR (upper limb, p  = .022) HRV and ulnar and sural NCS (all p  < .05) were more affected in TTR-FAP. Ulnar nerve sensory NCV, CDT, and the MPT but not the other parameters discriminated TTR-FAP from dPNP (82% of cases), from CIN (86.7%) and from CIDP (68%; only ulnar sNCV). Low ulnar SNCV, impaired cold perception, and mechanical hyperalgesia at the hands seem to characterize TTR-FAP and might help to differentiate from other polyneuropathies.

Testing of the NASA Hypersonics Project Combined Cycle Engine Large Scale Inlet Mode Transition Experiment (CCE LlMX)

NASA Technical Reports Server (NTRS)

Saunders, J. D.; Stueber, T. J.; Thomas, S. R.; Suder, K. L.; Weir, L. J.; Sanders, B. W.

2012-01-01

Status on an effort to develop Turbine Based Combined Cycle (TBCC) propulsion is described. This propulsion technology can enable reliable and reusable space launch systems. TBCC propulsion offers improved performance and safety over rocket propulsion. The potential to realize aircraft-like operations and reduced maintenance are additional benefits. Among most the critical TBCC enabling technologies are: 1) mode transition from turbine to scramjet propulsion, 2) high Mach turbine engines and 3) TBCC integration. To address these TBCC challenges, the effort is centered on a propulsion mode transition experiment and includes analytical research. The test program, the Combined-Cycle Engine Large Scale Inlet Mode Transition Experiment (CCE LIMX), was conceived to integrate TBCC propulsion with proposed hypersonic vehicles. The goals address: (1) dual inlet operability and performance, (2) mode-transition sequences enabling a switch between turbine and scramjet flow paths, and (3) turbine engine transients during transition. Four test phases are planned from which a database can be used to both validate design and analysis codes and characterize operability and integration issues for TBCC propulsion. In this paper we discuss the research objectives, features of the CCE hardware and test plans, and status of the parametric inlet characterization testing which began in 2011. This effort is sponsored by the NASA Fundamental Aeronautics Hypersonics project

APC+/− alters colonic fibroblast proteome in FAP

PubMed Central

Dixon, Maketa P.; Blagoi, Elena L.; Nicolas, Emmanuelle; Seeholzer, Steven H.; Cheng, David; He, Yin A.; Coudry, Renata A.; Howard, Sharon D.; Riddle, Dawn M.; Cooper, Harry S.; Boman, Bruce M.; Conrad, Peggy; Crowell, James A.; Bellacosa, Alfonso; Knudson, Alfred; Yeung, Anthony T.; Kopelovich, Levy

2011-01-01

Here we compared the proteomes of primary fibroblast cultures derived from morphologically normal colonic mucosa of familial adenomatous polyposis (FAP) patients with those obtained from unaffected controls. The expression signature of about 19% of total fibroblast proteins separates FAP mutation carriers from unaffected controls (P < 0.01). More than 4,000 protein spots were quantified by 2D PAGE analysis, identifying 368 non-redundant proteins and 400 of their isoforms. Specifically, all three classes of cytoskeletal filaments and their regulatory proteins were altered as were oxidative stress response proteins. Given that FAP fibroblasts showed heightened sensitivity to transformation by KiMSV and SV40 including elevated levels of the p53 protein, events controlled in large measure by the Ras suppressor protein-1 (RSU-1) and oncogenic DJ-1, here we show decreased RSU1 and augmented DJ-1 expression in both fibroblasts and crypt-derived epithelial cells from morphologically normal colonic mucosa of FAP gene-carriers. The results indicate that heterozygosity for a mutant APC tumor suppressor gene alters the proteomes of both colon-derived normal fibroblasts in a gene-specific manner, consistent with a “one-hit” effect. PMID:21411865

Supersonic investigation of two dimensional hypersonic exhaust nozzles

NASA Technical Reports Server (NTRS)

Carboni, Jeanne D.; Shyne, Rickey J.; Leavitt, Laurence D.; Taylor, John G.; Lamb, Milton

1992-01-01

An experimental investigation was conducted in the NASA Lewis 10 x 10 ft supersonic Wind Tunnel to determine the performance characteristics of 2D hypersonic exhaust nozzles/afterbodies at low supersonic conditions. Generally, this type of application requires a single expansion ramp nozzle (SERN) that is highly integrated with the airframe of the hypersonic vehicle. At design conditions (hypersonic speeds), the nozzle generally exhibits acceptable performance. At off-design conditions (transonic to mid-supersonic speeds), nozzle performance of a fixed geometry configuration is generally poor. Various 2-D nozzle configurations were tested at off-design conditions from Mach 2.0 to 3.5. Performance data is presented at nozzle pressure ratios from 1 to 35. Jet exhaust was simulated with high-pressure air. To study performance of different geometries, nozzle configurations were varied by interchanging the following model parts: internal upstream contour, expansion ramp, sidewalls, and cowl.

Thermal-Mechanical Testing of Hypersonic Vehicle Structures

NASA Technical Reports Server (NTRS)

Hudson, Larry; Stephens, Craig

2007-01-01

A viewgraph presentation describing thermal-mechanical tests on the structures of hypersonic vehicles is shown. The topics include: 1) U.S. Laboratories for Hot Structures Testing; 2) NASA Dryden Flight Loads Laboratory; 3) Hot Structures Test Programs; 4) Typical Sequence for Hot Structures Testing; 5) Current Hot Structures Testing; and 6) Concluding Remarks.

Hypersonic drone design: A multidisciplinary experience

NASA Technical Reports Server (NTRS)

1988-01-01

Efforts were focused on design problems of an unmanned hypersonic vehicle. It is felt that a scaled hypersonic drone is necessary to bridge the gap between present theory on hypersonics and the future reality of the National Aerospace Plane (NASP) for two reasons: to fulfill a need for experimental data in the hypersonic regime, and to provide a testbed for the scramjet engine which is to be the primary mode of propulsion for the NASP. Three areas of great concern to NASP design were examined: propulsion, thermal management, and flight systems. Problem solving in these areas was directed towards design of the drone with the idea that the same design techniques could be applied to the NASP. A seventy degree swept double delta wing configuration, developed in the 70's at NASA Langley, was chosen as the aerodynamic and geometric model for the drone. This vehicle would be air-launched from a B-1 at Mach 0.8 and 48,000 feet, rocket boosted by two internal engines to Mach 10 and 100,000 feet, and allowed to cruise under power of the scramjet engine until burnout. It would then return to base for an unpowered landing. Preliminary energy calculations based upon the flight requirements give the drone a gross launch weight of 134,000 lb. and an overall length of 85 feet.

IBS and FAPS in children: a comparison of psychological and clinical characteristics.

PubMed

Rutten, Juliette M T M; Benninga, Marc A; Vlieger, Arine M

2014-10-01

It has been suggested that different subcategories of childhood abdominal pain-related functional gastrointestinal disorders (AP-FGIDs) are not separate clinical entities, but represent variable expressions of the same FGID. The aim of the present study was to compare clinical and psychological characteristics of children with irritable bowel syndrome (IBS), functional abdominal pain (FAP), and functional abdominal pain syndrome (FAPS). A total of 259 children, ages 8 to 18 years, fulfilling Rome III criteria for IBS or FAPS were included in a randomized controlled trial evaluating the effect of hypnotherapy. At inclusion, questionnaires assessed demographics, clinical features, abdominal pain frequency and intensity, depression and anxiety, somatization, health-related quality of life, pain beliefs, and coping strategies. No differences were found between children with IBS and those with FAPS with respect to the main outcomes: frequency and intensity of abdominal pain, symptoms of depression and anxiety, somatization, health-related quality of life, pain beliefs, and coping strategies. A significantly higher percentage of patients with IBS had a positive family history for AP-FGIDs (56.8% vs 37.8%; P = 0.00). Characteristics of patients with IBS subtypes did not differ. Patients with FAP or FAPS differed only with respect to problem-focused coping strategy (2.21 ± 0.61 vs 2.52 ± 0.49; P = 0.00). Pediatric patients with IBS and those with FAPS have similar psychosocial profiles. These results may explain why treatment response of psychological therapies in these AP-FGIDs is similar. These results may indicate that pediatric IBS and FAPS are different expressions of 1 underlying functional disorder, but similarities in psychosocial characteristics do not exclude the possibility that these disorders are different entities, because these similarities can exist between disorders of various causes. Therefore, future research is required on the role of other

Operating capability and current status of the reactivated NASA Lewis Research Center Hypersonic Tunnel Facility

NASA Technical Reports Server (NTRS)

Thomas, Scott R.; Trefny, Charles J.; Pack, William D.

1995-01-01

The NASA Lewis Research Center's Hypersonic Tunnel Facility (HTF) is a free-jet, blowdown propulsion test facility that can simulate up to Mach-7 flight conditions with true air composition. Mach-5, -6, and -7 nozzles, each with a 42 inch exit diameter, are available. Previously obtained calibration data indicate that the test flow uniformity of the HTF is good. The facility, without modifications, can accommodate models approximately 10 feet long. The test gas is heated using a graphite core induction heater that generates a nonvitiated flow. The combination of clean-air, large-scale, and Mach-7 capabilities is unique to the HTF and enables an accurate propulsion performance determination. The reactivation of the HTF, in progress since 1990, includes refurbishing the graphite heater, the steam generation plant, the gaseous oxygen system, and all control systems. All systems were checked out and recertified, and environmental systems were upgraded to meet current standards. The data systems were also upgraded to current standards and a communication link with NASA-wide computers was added. In May 1994, the reactivation was complete, and an integrated systems test was conducted to verify facility operability. This paper describes the reactivation, the facility status, the operating capabilities, and specific applications of the HTF.

[Expression of FAP and alpha-SMA during the incised wound healing in mice skin].

PubMed

Gao, Yang; Peng, Xue; Jin, Zhan-Fen; Fu, Zhi-Jun

2009-12-01

OBJECTIVE To investigate the time-dependent expression of fibroblast activation protein (FAP) and alpha-smooth muscle actin(alpha-SMA) during the incised wound healing of the skin in mice. The expression of FAP and alpha-SMA in incised wound of mice skin was detected by immunohistochemistry and Western blot. By immunohistochemistry, the expression of FAP and alpha-SMA in the normal skin and the skin 1 h after injury maintained at a very low level, but the positive cells expressing FAP and alpha-SMA started to elevate 6 h after injury and reached its peak on 5 d for FAP and on 3 d for alpha-SMA, then gradually decreased to the normal level on 14 d. The expression of FAP and alpha-SMA was observed throughout the wound healing stages 1 d after injuries by Western blot as well with a peak expression occurring on 5 d for FAP and on 3 d for alpha-SMA after injury. FAP may be a potentially useful marker for wound age determination and alpha-SMA may be used as an effective indicator for the mid- and late stage incised wound of mice skin. The combination use of FAP and alpha-SMA may be potentially effective indicators for wound age determination.

A case report of desmoid tumour-a forgotten aspect of FAP?

PubMed

Xuereb, Sarah; Xuereb, Rachel; Buhagiar, Chiara; Gauci, Jonathan; Magri, Claude

2017-01-01

Desmoid tumours are locally aggressive tumours which are common in Familial Adenomatous Polyposis (FAP). A 20-year old Familial Adenomatous Polyposis (FAP) patient presented with abdominal pain and distention. Abdominal imaging showed small bowel obstruction and hydronephrosis due to a pelvic mass. This mass showed significant enlargement on repeat imaging, and a diagnostic biopsy confirmed desmoid tumour. The mass was deemed unresectable and he was initially started on sulindac and raloxifene. Repeat imaging however showed further enlargement of the tumour, and therefore vinblastine+methotrexate chemotherapy was commenced, with a good response. FAP is an autosomal dominant condition caused by a germline mutation in the adenomatous polyposis coli (APC) gene. Gardner's syndrome is also caused by a mutation in the APC gene, and is now considered a different phenotypic presentation of FAP. Desmoid tumours are initially kept under observation while their size remains stable. Treatment options for enlarging desmoids tumours include surgery (first-line), radiotherapy, and systemic therapy with non-cytotoxic and cytotoxic therapy. FAP patients should be examined regularly post-panprocotocolectomy, since desmoid tumours may arise. The presence of epidermal cysts in this FAP patient suggests a diagnosis of Gardner's syndrome. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

X-43A Project Overview: Adventures in Hypersonics

NASA Technical Reports Server (NTRS)

Davis, Mark; Grindle, Laurie

2007-01-01

A viewgraph presentation describing the hypersonics program at NASA Dryden Flight Research Center is shown. The topics include: 1) X-43A Program Overview; 2) Vehicle Description; 3) Flight 1, MIB & Return to Flight; 4) Flight 2 and Results; 5) Flight 3 and Results; and 6) Concluding Remarks

A feasibility study of a hypersonic real-gas facility

NASA Technical Reports Server (NTRS)

Gully, J. H.; Driga, M. D.; Weldon, W. F.

1987-01-01

A four month feasibility study of a hypersonic real-gas free flight test facility for NASA Langley Research Center (LARC) was performed. The feasibility of using a high-energy electromagnetic launcher (EML) to accelerate complex models (lifting and nonlifting) in the hypersonic, real-gas facility was examined. Issues addressed include: design and performance of the accelerator; design and performance of the power supply; design and operation of the sabot and payload during acceleration and separation; effects of high current, magnetic fields, temperature, and stress on the sabot and payload; and survivability of payload instrumentation during acceleration, flight, and soft catch.

Airbreathing Hypersonic Systems Focus at NASA Langley Research Center

NASA Technical Reports Server (NTRS)

Hunt, James L.; Rausch, Vincent L.

1998-01-01

This paper presents the status of the airbreathing hypersonic airplane and space-access vehicle design matrix, reflects on the synergies and issues, and indicates the thrust of the effort to resolve the design matrix and to focus/advance systems technology maturation. Priority is given to the design of the vision operational vehicles followed by flow-down requirements to flight demonstrator vehicles and their design for eventual consideration in the Future-X Program.

Cribriform-morular variant of papillary thyroid carcinoma: an indication to screen for occult FAP.

PubMed

Levy, Rachel A; Hui, Vanessa W; Sood, Rupa; Fish, Stephanie; Markowitz, Arnold J; Wong, Richard J; Guillem, José G

2014-12-01

Cribriform-morular variant (CMV) is a rare subtype of papillary thyroid carcinoma (PTC) that is associated with familial adenomatous polyposis (FAP). Given the high likelihood for multi-organ malignancies in FAP patients, this study explores the yield of diagnosing occult FAP among CMV-PTC patients. Institutional database was searched in order to identify patients with pathologically-confirmed CMV-PTC from 2000 to 2012. Medical records were reviewed, and clinical and pathological features were analyzed. Eleven cases of CMV were identified from 6,901 patients with PTC, for a prevalence of 0.16 %. All 11 patients were female. The median age at CMV-PTC diagnosis was 36 years (range 18-46). Two patients had pre-existing FAP at the time of PTC diagnosis. The other nine patients were referred for colonoscopy and/or genetic testing. Six patients underwent colonoscopy and one (17 %) was diagnosed with FAP based on polyposis phenotype and genetic testing. The mean age of patients at the time of CMV-PTC diagnosis was younger in the FAP group (23 years, range 18-34) than in the sporadic group (37 years, range 25-46). All three patients with FAP-associated CMV-PTC had multicentric tumors, while all five sporadic patients did not. Our study found that approximately one-sixth of patients with CMV-PTC may have occult FAP. Patients with FAP-associated CMV-PTC appear to be younger and more likely to have multicentric tumors than those with sporadic CMV-PTC. Due to the increased risk of malignancy in patients with FAP, patients with CMV-PTC should be referred for colonoscopy and/or genetic evaluation for FAP.

The X-43A hypersonic research aircraft and its modified Pegasus® booster rocket nestled under the wing of NASA's NB-52B carrier aircraft during pre-flight systems testing

NASA Image and Video Library

2001-03-15

The X-43A hypersonic research aircraft and its modified Pegasus® booster rocket are nestled under the wing of NASA's NB-52B carrier aircraft during pre-flight systems testing at the Dryden Flight Research Center, Edwards, Calif. The combined systems test was one of the last major milestones in the Hyper-X research program before the first X-43A flight. The X-43A flights will be the first actual flight tests of an aircraft powered by a revolutionary supersonic-combustion ramjet ("scramjet") engine capable of operating at hypersonic speeds (above Mach 5, or five times the speed of sound). The 12-foot, unpiloted research vehicle was developed and built by MicroCraft Inc., Tullahoma, Tenn., under NASA contract. The booster was built by Orbital Sciences Corp., Dulles, Va. After being air-launched from NASA's venerable NB-52 mothership, the booster will accelerate the X-43A to test speed and altitude. The X-43A will then separate from the rocket and fly a pre-programmed trajectory, conducting aerodynamic and propulsion experiments until it descends into the Pacific Ocean. Three research flights are planned, two at Mach 7 and one at Mach 10.

1059 and 1328nm LD pumped Nd:S-FAP solid state laser

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

Sun Lianke; Zhang Shaojun; Zhao Shengzhi

In this paper the authors introduce a new laser crystal--Nd{sup 3+}:Sr{sub 5}(PO{sub 4}){sub 3}F, Nd:S-FAP, and present its optical and physical characteristics. Based on the experiment lasing performance of CW LD pumped Nd:S-FAP crystal is reported here: the threshold and slope efficiency of 1059 nm Nd:S-FAP laser pumped by CW LD at 805nm are 7mW and 41%, and that of 1328nm Nd:S-FAP laser are 19mW and 35%. The comparison between experimental result and theoretical calculation is also discussed in this paper.

Analysis of experimental results of the inlet for the NASA hypersonic research engine aerothermodynamic integration model. [wind tunnel tests of ramjet engine hypersonic inlets

NASA Technical Reports Server (NTRS)

Andrews, E. H., Jr.; Mackley, E. A.

1976-01-01

An aerodynamic engine inlet analysis was performed on the experimental results obtained at nominal Mach numbers of 5, 6, and 7 from the NASA Hypersonic Research Engine (HRE) Aerothermodynamic Integration Model (AIM). Incorporation on the AIM of the mixed-compression inlet design represented the final phase of an inlet development program of the HRE Project. The purpose of this analysis was to compare the AIM inlet experimental results with theoretical results. Experimental performance was based on measured surface pressures used in a one-dimensional force-momentum theorem. Results of the analysis indicate that surface static-pressure measurements agree reasonably well with theoretical predictions except in the regions where the theory predicts large pressure discontinuities. Experimental and theoretical results both based on the one-dimensional force-momentum theorem yielded inlet performance parameters as functions of Mach number that exhibited reasonable agreement. Previous predictions of inlet unstart that resulted from pressure disturbances created by fuel injection and combustion appeared to be pessimistic.

Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs.

PubMed

Keane, Fiona M; Yao, Tsun-Wen; Seelk, Stefanie; Gall, Margaret G; Chowdhury, Sumaiya; Poplawski, Sarah E; Lai, Jack H; Li, Youhua; Wu, Wengen; Farrell, Penny; Vieira de Ribeiro, Ana Julia; Osborne, Brenna; Yu, Denise M T; Seth, Devanshi; Rahman, Khairunnessa; Haber, Paul; Topaloglu, A Kemal; Wang, Chuanmin; Thomson, Sally; Hennessy, Annemarie; Prins, John; Twigg, Stephen M; McLennan, Susan V; McCaughan, Geoffrey W; Bachovchin, William W; Gorrell, Mark D

2013-01-01

The protease fibroblast activation protein (FAP) is a specific marker of activated mesenchymal cells in tumour stroma and fibrotic liver. A specific, reliable FAP enzyme assay has been lacking. FAP's unique and restricted cleavage of the post proline bond was exploited to generate a new specific substrate to quantify FAP enzyme activity. This sensitive assay detected no FAP activity in any tissue or fluid of FAP gene knockout mice, thus confirming assay specificity. Circulating FAP activity was ∼20- and 1.3-fold less in baboon than in mouse and human plasma, respectively. Serum and plasma contained comparable FAP activity. In mice, the highest levels of FAP activity were in uterus, pancreas, submaxillary gland and skin, whereas the lowest levels were in brain, prostate, leukocytes and testis. Baboon organs high in FAP activity included skin, epididymis, bladder, colon, adipose tissue, nerve and tongue. FAP activity was greatly elevated in tumours and associated lymph nodes and in fungal-infected skin of unhealthy baboons. FAP activity was 14- to 18-fold greater in cirrhotic than in non-diseased human liver, and circulating FAP activity was almost doubled in alcoholic cirrhosis. Parallel DPP4 measurements concorded with the literature, except for the novel finding of high DPP4 activity in bile. The new FAP enzyme assay is the first to be thoroughly characterised and shows that FAP activity is measurable in most organs and at high levels in some. This new assay is a robust tool for specific quantitation of FAP enzyme activity in both preclinical and clinical samples, particularly liver fibrosis.

Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs☆

PubMed Central

Keane, Fiona M.; Yao, Tsun-Wen; Seelk, Stefanie; Gall, Margaret G.; Chowdhury, Sumaiya; Poplawski, Sarah E.; Lai, Jack H.; Li, Youhua; Wu, Wengen; Farrell, Penny; Vieira de Ribeiro, Ana Julia; Osborne, Brenna; Yu, Denise M.T.; Seth, Devanshi; Rahman, Khairunnessa; Haber, Paul; Topaloglu, A. Kemal; Wang, Chuanmin; Thomson, Sally; Hennessy, Annemarie; Prins, John; Twigg, Stephen M.; McLennan, Susan V.; McCaughan, Geoffrey W.; Bachovchin, William W.; Gorrell, Mark D.

2013-01-01

The protease fibroblast activation protein (FAP) is a specific marker of activated mesenchymal cells in tumour stroma and fibrotic liver. A specific, reliable FAP enzyme assay has been lacking. FAP's unique and restricted cleavage of the post proline bond was exploited to generate a new specific substrate to quantify FAP enzyme activity. This sensitive assay detected no FAP activity in any tissue or fluid of FAP gene knockout mice, thus confirming assay specificity. Circulating FAP activity was ∼20- and 1.3-fold less in baboon than in mouse and human plasma, respectively. Serum and plasma contained comparable FAP activity. In mice, the highest levels of FAP activity were in uterus, pancreas, submaxillary gland and skin, whereas the lowest levels were in brain, prostate, leukocytes and testis. Baboon organs high in FAP activity included skin, epididymis, bladder, colon, adipose tissue, nerve and tongue. FAP activity was greatly elevated in tumours and associated lymph nodes and in fungal-infected skin of unhealthy baboons. FAP activity was 14- to 18-fold greater in cirrhotic than in non-diseased human liver, and circulating FAP activity was almost doubled in alcoholic cirrhosis. Parallel DPP4 measurements concorded with the literature, except for the novel finding of high DPP4 activity in bile. The new FAP enzyme assay is the first to be thoroughly characterised and shows that FAP activity is measurable in most organs and at high levels in some. This new assay is a robust tool for specific quantitation of FAP enzyme activity in both preclinical and clinical samples, particularly liver fibrosis. PMID:24371721

Surgical considerations in FAP-related pouch surgery: Could we do better?

PubMed

Möslein, Gabriela

2016-07-01

The ileoanal pouch has become the standard restorative procedure of choice for patients with the classical phenotype in FAP (familial adenomatous polyposis) and also for ulcerative colitis (UC). Whilst we tend to encounter descriptive analyses comparing functional outcome, fertility and quality of life (QOL) between series in literature, there may be an urgent need to discuss the subtle technical modifications that may be pivotal for improving long-term QOL in FAP patients. Our aim is to review the current literature and discuss the aspects of ileal pouch-anal anastomosis that may require specific reevaluation for FAP. Surgical strategies aimed at minimizing post-interventional desmoid growth is one of the most important aspects. For this study, the following topics of interest were selected: Timing of surgery, IRA or ileoanal pouch for classical FAP, laparoscopic or conventional surgery, TME or mesenteric dissection, preservation of the ileocolic vessels, handsewn or double-staple anastomosis, shape and size of pouch, protective ileostomy, Last and definitely not least: how to manage desmoid plaques or desmoids at the time of prophylactic surgery. For the depicted technicalities of the procedure, a review of recent literature was performed and evaluated. For the topics selected, only sparse reference in literature was identified that was focused on the specific condition situation of FAP. Almost all pouch literature focusses on the procedural aspects, and FAP patients are always a very minor number. Therefore it becomes obvious that the specific entity is not adequately taken into account. This is a serious bias for identification of important steps in the procedure that may be beneficial for patients with either of the diseases. The results of this study demonstrate that several technical differences for construction of ileoanal pouches in FAP patients deserve more attention and prospective evaluation-perhaps even randomized trials. The role, importance and

FAP positive fibroblasts induce immune checkpoint blockade resistance in colorectal cancer via promoting immunosuppression.

PubMed

Chen, Lingling; Qiu, Xiangting; Wang, Xinhua; He, Jian

2017-05-20

Immune checkpoint blockades that significantly prolonged survival of melanoma patients have been less effective on colorectal cancer (CRC) patients. Growing evidence suggested that fibroblast activation protein-alpha (FAP) on cancer associate fibroblasts (CAFs) has critical roles in regulating antitumor immune response by inducing tumor-promoting inflammation. In this study, we explored the roles of FAP in regulating the tumor immunity and immune checkpoint blockades resistance in CRC experimental systems. We found that CAFs with high FAP expression could induce immune checkpoint blockade resistance in CRC mouse model. Mechanistically, CAFs with high FAP expression promoted immunosuppression in the CRC tumor immune microenvironment by up-regulating CCL2 secretion, recruiting myeloid cells, and decreasing T-cell activity. In human CRC samples, FAP expression was proportional to myeloid cells number, but inversely related to T-cell number. High FAP expression also predicted poor survival of CRC patients. Taken together, our study suggested that high FAP expression in CAFs is one reason leading to immune checkpoint blockades resistance in CRC patients and FAP is an optional target for reversing immune checkpoint blockades resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

A Flying Qualities Study of Longitudinal Long-Term Dynamics of Hypersonic Planes

NASA Technical Reports Server (NTRS)

Cox, Timothy H.; Sachs, G.; Knoll, A.; Stich, R.

1995-01-01

The NASA Dryden Flight Research Center and the Technical University of Munich are cooperating in a research program to assess the impact of unstable long-term dynamics on the flying qualities of planes in hypersonic flight. These flying qualities issues are being investigated with a dedicated flight simulator for hypersonic vehicles located at NASA Dryden. Several NASA research pilots have flown the simulator through well defined steady-level turns with varying phugoid and height mode instabilities. The data collected include Pilot ratings and comments, performance measurements, and Pilot workload measurements. The results presented in this paper include design guidelines for height and Phugoid mode instabilities, an evaluation of the tapping method used to measure pilot workload, a discussion of techniques developed by the pilots to control large instabilities, and a discussion of how flying qualities of unstable long-term dynamics influence control Power design requirements.

A flying qualities study of longitudinal long-term dynamics of hypersonic planes

NASA Technical Reports Server (NTRS)

Cox, T.; Sachs, G.; Knoll, A.; Stich, R.

1995-01-01

The NASA Dryden Flight Research Center and the Technical University of Munich are cooperating in a research program to assess the impact of unstable long-term dynamics on the flying qualities of planes in hypersonic flight. These flying qualities issues are being investigated with a dedicated flight simulator for hypersonic vehicles located at NASA Dryden. Several NASA research pilots have flown the simulator through well-defined steady-level turns with varying phugoid and height mode instabilities. Th data collected include pilot ratings and comments, performance measurements, and pilot workload measurements. The results presented in this paper include design guidelines for height and phugoid mode instabilities, an evaluation of the tapping method used to measure pilot workload, a discussion of techniques developed by the pilots to control large instabilities, and a discussion of how flying qualities of unstable long-term dynamics influence control power design requirements.

A specific, transmembrane interface regulates fibroblast activation protein (FAP) homodimerization, trafficking and exopeptidase activity.

PubMed

Wonganu, Benjamaporn; Berger, Bryan W

2016-08-01

Fibroblast activation protein (FAP) is a cell-surface serine protease which promotes invasiveness of certain epithelial cancers and is therefore a potential target for cancer drug development and delivery. Unlike dipeptidyl peptidase IV (DPPIV), FAP exhibits prolyl endopeptidase activity and is active as a homodimer with specificity for type I collagen. The mechanism that regulates FAP homodimerization and its relation to prolyl endopeptidase activity is not completely understood. Here, we investigate key residues in the FAP TM domain that may be significant for FAP homodimerization. Mutations to predicted TM interfacial residues (G10L, S14L, and A18L) comprising a small-X3-small motif reduced FAP TM-CYTO dimerization relative to wild type as measured using the AraTM assay, whereas predicted off-interface residues showed no significant change from wild type. The results implied that the predicted small-X3-small dimer interface affect stabilization of FAP TM-CYTO homodimerization. Compared with FAPwild-type, the interfacial TM residue G10L significantly decreased FAP endopeptidase activity more than 25%, and also reduced cell-surface versus intracellular expression relative to other interfacial residues S14L and A18L. Thus, our results suggest FAP dimerization is important for both trafficking and protease activity, and is dependent on a specific TM interface. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of a Multi-Disciplinary Aerothermostructural Model Applicable to Hypersonic Flight

NASA Technical Reports Server (NTRS)

Kostyk, Chris; Risch, Tim

2013-01-01

The harsh and complex hypersonic flight environment has driven design and analysis improvements for many years. One of the defining characteristics of hypersonic flight is the coupled, multi-disciplinary nature of the dominant physics. In an effect to examine some of the multi-disciplinary problems associated with hypersonic flight engineers at the NASA Dryden Flight Research Center developed a non-linear 6 degrees-of-freedom, full vehicle simulation that includes the necessary model capabilities: aerothermal heating, ablation, and thermal stress solutions. Development of the tool and results for some investigations will be presented. Requirements and improvements for future work will also be reviewed. The results of the work emphasize the need for a coupled, multi-disciplinary analysis to provide accurate

Hypersonic research engine/aerothermodynamic integration model: Experimental results. Volume 3: Mach 7 component integration and performance

NASA Technical Reports Server (NTRS)

Andrews, E. H., Jr.; Mackley, E. A.

1976-01-01

The NASA Hypersonic Research Engine Project was undertaken to design, develop, and construct a hypersonic research ramjet engine for high performance and to flight test the developed concept on the X-15-2A airplane over the speed range from Mach 3 to 8. Computer program results are presented here for the Mach 7 component integration and performance tests.

Compendium of NASA Langley reports on hypersonic aerodynamics

NASA Technical Reports Server (NTRS)

Sabo, Frances E.; Cary, Aubrey M.; Lawson, Shirley W.

1987-01-01

Reference is made to papers published by the Langley Research Center in various areas of hypersonic aerodynamics for the period 1950 to 1986. The research work was performed either in-house by the Center staff or by other personnel supported entirely or in part by grants or contracts. Abstracts have been included with the references when available. The references are listed chronologically and are grouped under the following general headings: (1) Aerodynamic Measurements - Single Shapes; (2) Aerodynamic Measurements - Configurations; (3) Aero-Heating; (4) Configuration Studies; (5) Propulsion Integration Experiment; (6) Propulsion Integration - Study; (7) Analysis Methods; (8) Test Techniques; and (9) Airframe Active Cooling Systems.

Expression of Fap amyloids in Pseudomonas aeruginosa, P. fluorescens, and P. putida results in aggregation and increased biofilm formation

PubMed Central

Dueholm, Morten S; Søndergaard, Mads T; Nilsson, Martin; Christiansen, Gunna; Stensballe, Allan; Overgaard, Michael T; Givskov, Michael; Tolker-Nielsen, Tim; Otzen, Daniel E; Nielsen, Per H

2013-01-01

The fap operon, encoding functional amyloids in Pseudomonas (Fap), is present in most pseudomonads, but so far the expression and importance for biofilm formation has only been investigated for P. fluorescens strain UK4. In this study, we demonstrate the capacity of P. aeruginosa PAO1, P. fluorescens Pf-5, and P. putida F1 to express Fap fibrils, and investigated the effect of Fap expression on aggregation and biofilm formation. The fap operon in all three Pseudomonas species conferred the ability to express Fap fibrils as shown using a recombinant approach. This Fap overexpression consistently resulted in highly aggregative phenotypes and in increased biofilm formation. Detailed biophysical investigations of purified fibrils confirmed FapC as the main fibril monomer and supported the role of FapB as a minor, nucleating constituent as also indicated by bioinformatic analysis. Bioinformatics analysis suggested FapF and FapD as a potential β-barrel membrane pore and protease, respectively. Manipulation of the fap operon showed that FapA affects monomer composition of the final amyloid fibril, and that FapB is an amyloid protein, probably a nucleator for FapC polymerization. Our study highlights the fap operon as a molecular machine for functional amyloid formation. PMID:23504942

Stability of hypersonic compression cones

NASA Astrophysics Data System (ADS)

Reed, Helen; Kuehl, Joseph; Perez, Eduardo; Kocian, Travis; Oliviero, Nicholas

2012-11-01

Our activities focus on the identification and understanding of the second-mode instability for representative configurations in hypersonic flight. These include the Langley 93-10 flared cone and the Purdue compression cone, both at 0 degrees angle of attack at Mach 6. Through application of nonlinear parabolized stability equations (NPSE) and linear parabolized stability equations (PSE) to both geometries, it is concluded that mean-flow distortion tends to amplify frequencies less than the peak frequency and stabilize those greater by modifying the boundary-layer thickness. As initial disturbance amplitude is increased and/or a broad spectrum disturbance is introduced, direct numerical simulations (DNS) or NPSE appear to be the proper choices to model the evolution, and relative evolution, because these computational tools include these nonlinear effects (mean-flow distortion). Support from AFOSR/NASA National Center for Hypersonic Research in Laminar-Turbulent Transition through Grant FA9550-09-1-0341 is gratefully acknowledged. The authors also thank Pointwise, AeroSoft, and Texas Advanced Computing Center (TACC).

Familial Adenomatous Polyposis (FAP)-A Case Study and Review of Literature.

PubMed

Dalavi, Santosh Bhimrao; Vedpalsingh, Tanwar Harshwardhan; Bankar, Sanket Subhash; Ahmed, Mohd Hamid Shafique; Bhosale, Dattatray Nivrutti

2015-03-01

Familial adenomatous polyposis (FAP) is a syndrome characteristically having numerous (hundreds to thousands) polyps in the epithelium of the large intestines with an autosomal dominant inheritance caused by germ line mutations in adenomatous polyposis coli (APC) gene in chromosome 5q21. Most FAP patients have a family history of colorectal polyps and cancer but 25-30% of them are "de novo", without any clinical or genetic evidence of FAP in family members. Prophylactic proctocolectomy is required in almost all patients since all affected patients inevitably develop cancer. We report a case of a 32-year-old man who presented with vague abdominal complaints without any family history, which on evaluation as found to have multiple colorectal polyps and underwent a prophylactic proctocolectomy with end continent ileostomy. Two of his children were evaluated and found to have multiple colorectal polyps on colonoscopy and have been advised regular follow up annually. In conclusion, patients with FAP may present with vague abdominal complaints and without any family history, hence need to be carefully evaluated. Good patient compliance is of prime importance in deciding the treatment and surveillance modality subsequently determining the prognosis of patients with FAP.

Application of CFD to a generic hypersonic flight research study

NASA Technical Reports Server (NTRS)

Green, Michael J.; Lawrence, Scott L.; Dilley, Arthur D.; Hawkins, Richard W.; Walker, Mary M.; Oberkampf, William L.

1993-01-01

Computational analyses have been performed for the initial assessment of flight research vehicle concepts that satisfy requirements for potential hypersonic experiments. Results were obtained from independent analyses at NASA Ames, NASA Langley, and Sandia National Labs, using sophisticated time-dependent Navier-Stokes and parabolized Navier-Stokes methods. Careful study of a common problem consisting of hypersonic flow past a slightly blunted conical forebody was undertaken to estimate the level of uncertainty in the computed results, and to assess the capabilities of current computational methods for predicting boundary-layer transition onset. Results of this study in terms of surface pressure and heat transfer comparisons, as well as comparisons of boundary-layer edge quantities and flow-field profiles are presented here. Sensitivities to grid and gas model are discussed. Finally, representative results are presented relating to the use of Computational Fluid Dynamics in the vehicle design and the integration/support of potential experiments.

Predictive values of FAP and HGF for tumor angiogenesis and metastasis in colorectal cancer.

PubMed

Ma, T H; Gao, C C; Xie, R; Yang, X Z; Dai, W J; Zhang, J L; Yan, W; Wu, S N

2017-01-01

This study aims to explore the correlation of hepatocyte growth factor (HGF) and fibroblast activation protein (FAP) expressions with the angiogenesis and metastasis in colorectal cancer (CRC). The immunohistochemical SABC method was used to detect HGF and FAP expressions in 127 CRC tissues, 51 colorectal polyp tissues and 28 normal tissues. HGF and FAP expressions in liver metastasis were detected using western blot to analyze the correlation of their expressions with lymph node metastasis and liver metastasis. Micro-vessel density (MVD) and clinic-pathologic information of CRC patients were recorded and analyzed. In CRC group, HGF and FAP expressions were greatly higher than those in normal group and colorectal polyps group (P < 0.05). Moreover, the positive rates of HGF and FAP expressions in lymph node metastasis were evidently higher than those in non-lymph node metastasis (P < 0.05). In liver metastasis group, HGF and FAP expressions were obviously higher than non-liver metastasis group (P < 0.05). CRC group had much more MVD in comparison with normal group and colorectal polyps group (P < 0.05).When compared with negative group, MVD was significantly higher than that in CRC tissue with positive HGF and FAP (P < 0.05). Spearman rank correlation analysis showed that HGF and FAP were in positive correlation with MVD (r = 0.542, P < 0.001; r = 0.753, P < 0.001). These results indicate that FAP and HGF play an important role in CRC angiogenesis, and their expression levels are valuable to predict CRC liver metastasis and lymph node metastasis.

Sixty years of transthyretin familial amyloid polyneuropathy (TTR-FAP) in Europe: where are we now? A European network approach to defining the epidemiology and management patterns for TTR-FAP.

PubMed

Parman, Yesim; Adams, David; Obici, Laura; Galán, Lucía; Guergueltcheva, Velina; Suhr, Ole B; Coelho, Teresa

2016-02-01

Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a highly disabling, life-threatening disease characterized by progressive sensorimotor and autonomic neuropathy. The profile of the disease across Europe is inadequately understood at present. The incidence and clinical presentation of TTR-FAP varies widely within Europe, with early and late-onset disease subtypes. In those regions in which the disease is endemic (Portugal, Sweden, Cyprus, and Majorca), a Val30Met substitution in the TTR gene is the predominant genetic cause, whereas in the rest of Europe, cases of TTR-FAP are mainly sporadic with genetic heterogeneity. Current management strategies lack cohesion and patients can experience years of misdiagnosis and suboptimal treatment. The article aims to disseminate the findings and recommendations from two recent meetings of the European Network for TTR-FAP (ATTReuNET), a panel comprising representatives from 10 European countries (Bulgaria, Cyprus, France, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, and Turkey) with expertise in the diagnosis and management of TTR-FAP. We explore the epidemiology and genetic mark of TTR-FAP across Europe and assess current management strategies, with a view to developing an alternative framework - a networked approach to disease management with an emphasis on collaboration and sharing of best practice.

Cleavage-site specificity of prolyl endopeptidase FAP investigated with a full-length protein substrate.

PubMed

Huang, Chih-Hsiang; Suen, Ching-Shu; Lin, Ching-Ting; Chien, Chia-Hui; Lee, Hsin-Ying; Chung, Kuei-Min; Tsai, Ting-Yueh; Jiaang, Weir-Tong; Hwang, Ming-Jing; Chen, Xin

2011-06-01

Fibroblast activation protein (FAP) is a prolyl-cleaving endopeptidase proposed as an anti-cancer drug target. It is necessary to define its cleavage-site specificity to facilitate the identification of its in vivo substrates and to understand its biological functions. We found that the previously identified substrate of FAP, α(2)-anti-plasmin, is not a robust substrate in vitro. Instead, an intracellular protein, SPRY2, is cleavable by FAP and more suitable for investigation of its substrate specificity in the context of the full-length globular protein. FAP prefers uncharged residues, including small or bulky hydrophobic amino acids, but not charged amino acids, especially acidic residue at P1', P3 and P4 sites. Molecular modelling analysis shows that the substrate-binding site of FAP is surrounded by multiple tyrosine residues and some negatively charged residues, which may exert least preference for substrates with acidic residues. This provides an explanation why FAP cannot cleave interleukins, which have a glutamate at either P4 or P2', despite their P3-P2-P1 sites being identical to SPRY2 or α-AP. Our study provided new information on FAP cleavage-site specificity, which differs from the data obtained by profiling with a peptide library or with the denatured protein, gelatin, as the substrate. Furthermore, our study suggests that negatively charged residues should be avoided when designing FAP inhibitors.

Understanding fibroblast activation protein (FAP): substrates, activities, expression and targeting for cancer therapy.

PubMed

Hamson, Elizabeth J; Keane, Fiona M; Tholen, Stefan; Schilling, Oliver; Gorrell, Mark D

2014-06-01

Fibroblast activation protein (FAP) is best known for its heightened expression in tumour stroma. This atypical serine protease has both dipeptidyl peptidase and endopeptidase activities, cleaving substrates at a post-proline bond. FAP expression is difficult to detect in non-diseased adult organs, but is greatly upregulated in sites of tissue remodelling, which include liver fibrosis, lung fibrosis, atherosclerosis, arthritis, tumours and embryonic tissues. Due to its restricted expression pattern and dual enzymatic activities, FAP is emerging as a unique therapeutic target. However, methods to exploit and target this protease are advancing more rapidly than knowledge of the fundamental biology of FAP. This review highlights this imbalance, emphasising the need to better define the substrate repertoire and expression patterns of FAP to elucidate its role in biological and pathological processes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quality of life and consequences for daily life of familial adenomatous polyposis (FAP) family members.

PubMed

Douma, K F L; Bleiker, E M A; Vasen, H F A; Gundy, C M; Aaronson, N K

2011-06-01

The study aimed to document the impact of familial adenomatous polyposis (FAP) on health-related quality of life (HRQOL) and several practical aspects of daily life, and to identify factors significantly associated with HRQOL. This study is the first to compare HRQOL between patients with FAP, at-risk individuals and noncarriers. A total of 525 individuals (response rate 64%) from 145 families at high risk for FAP completed a battery of self-report questionnaires assessing generic- and condition-specific HRQOL and the consequences of FAP for daily life. HRQOL was comparable to that of the general Dutch population. Surgically treated patients with FAP had significantly lower scores on several HRQOL domains compared with at-risk individuals, noncarriers and nonsurgically treated patients with FAP. Type of surgery was not significantly associated with HRQOL. Within the surgically treated group, postsurgical complications and comorbidity significantly affected HRQOL. Forty-one percent of patients reported that FAP had affected their working life. Surgically treated patients with FAP have significantly poorer HRQOL than other groups. The type of surgery and age at time of first surgery were not associated with HRQOL but surgical complications and comorbidity were. Patients should be informed of the consequences of FAP for work and other life domains. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

Experimental and computational surface and flow-field results for an all-body hypersonic aircraft

NASA Technical Reports Server (NTRS)

Lockman, William K.; Lawrence, Scott L.; Cleary, Joseph W.

1990-01-01

The objective of the present investigation is to establish a benchmark experimental data base for a generic hypersonic vehicle shape for validation and/or calibration of advanced computational fluid dynamics computer codes. This paper includes results from the comprehensive test program conducted in the NASA/Ames 3.5-foot Hypersonic Wind Tunnel for a generic all-body hypersonic aircraft model. Experimental and computational results on flow visualization, surface pressures, surface convective heat transfer, and pitot-pressure flow-field surveys are presented. Comparisons of the experimental results with computational results from an upwind parabolized Navier-Stokes code developed at Ames demonstrate the capabilities of this code.

NASA's NB-52B carrier aircraft rolls down a taxiway with the X-43A hypersonic research aircraft and its modified Pegasus® booster rocket attached to a pylon under its right wing.

NASA Image and Video Library

2001-03-15

As part of a combined systems test conducted by NASA Dryden Flight Research Center, NASA's NB-52B carrier aircraft rolls down a taxiway at Edwards Air Force Base with the X-43A hypersonic research aircraft and its modified Pegasus® booster rocket attached to a pylon under its right wing. The taxi test was one of the last major milestones in the Hyper-X research program before the first X-43A flight. The X-43A flights will be the first actual flight tests of an aircraft powered by a revolutionary supersonic-combustion ramjet ("scramjet") engine capable of operating at hypersonic speeds (above Mach 5, or five times the speed of sound). The 12-foot, unpiloted research vehicle was developed and built by MicroCraft Inc., Tullahoma, Tenn., under NASA contract. The booster was built by Orbital Sciences Corp., Dulles, Va. After being air-launched from NASA's venerable NB-52 mothership, the booster will accelerate the X-43A to test speed and altitude. The X-43A will then separate from the rocket and fly a pre-programmed trajectory, conducting aerodynamic and propulsion experiments until it descends into the Pacific Ocean. Three research flights are planned, two at Mach 7 and one at Mach 10.

NASA Hypersonic Propulsion: Overview of Progress from 1995 to 2005

NASA Technical Reports Server (NTRS)

Cikanek, Harry A., III; Bartolotta, Paul A.; Klem, Mark D.; Rausch, Vince L.

2007-01-01

Hypersonic propulsion work supported by the United States National Aeronautics and Space Administration had a primary focus on Space Transportation during the period from 1995 to 2005. The framework for these advances was established by policy and pursued with substantial funding. Many noteworthy advances were made, highlighted by the pinnacle flights of the X-43. This paper reviews and summarizes the programs and accomplishments of this era. The accomplishments are compared to the goals and objectives to lend an overarching perspective to what was achieved. At least dating back to the early days of the Space Shuttle program, NASA has had the objective of reducing the cost of access to space and concurrently improving safety and reliability. National Space Transportation Policy in 1994 coupled with a base of prior programs such as the National Aerospace Plane and the need to look beyond the Space Shuttle program set the stage for NASA to pursue Space Transportation Advances. Programs defined to pursue the advances represented a broad approach addressing classical rocket propulsion as well as airbreathing propulsion in various combinations and forms. The resulting portfolio of activities included systems analysis and design studies, discipline research and technology, component technology development, propulsion system ground test demonstration and flight demonstration. The types of propulsion systems that were pursued by these programs included classical rocket engines, "aerospike" rocket engines, high performance rocket engines, scram jets, rocket based combined cycles, and turbine based combined cycles. Vehicle architectures included single and two stage vehicles. Either single types of propulsion systems or combinations of the basic propulsion types were applied to both single and two stage vehicle design concepts. Some of the propulsion system design concepts were built and tested at full scale, large scale and small scale. Many flight demonstrators were

Center for Hypersonic Combined Cycle Flow Physics

DTIC Science & Technology

2015-03-24

team of expert experimentalists and numerical and chemical kinetic modelers. Flowfields were examined in the turbine /ramjet dual inlet mode transition...using data from the NASA Glenn IMX facility and RANS calculations. In the ramjet/scramjet mode regime a dual-mode combustion wind tunnel was developed...SUBJECT TERMS Hypersonic combined cycle propulsion, turbine /ram dual-inlet transition, ram/scram dual-mode transition, hypervelocity regime, RANS, Hybrid

Portable Fluorescence Imaging System for Hypersonic Flow Facilities

NASA Technical Reports Server (NTRS)

Wilkes, J. A.; Alderfer, D. W.; Jones, S. B.; Danehy, P. M.

2003-01-01

A portable fluorescence imaging system has been developed for use in NASA Langley s hypersonic wind tunnels. The system has been applied to a small-scale free jet flow. Two-dimensional images were taken of the flow out of a nozzle into a low-pressure test section using the portable planar laser-induced fluorescence system. Images were taken from the center of the jet at various test section pressures, showing the formation of a barrel shock at low pressures, transitioning to a turbulent jet at high pressures. A spanwise scan through the jet at constant pressure reveals the three-dimensional structure of the flow. Future capabilities of the system for making measurements in large-scale hypersonic wind tunnel facilities are discussed.

Functional Analytic Psychotherapy (FAP) in Ibero-America: Review of Current Status and Some Proposals

ERIC Educational Resources Information Center

Munoz-Martinez, Amanda; Novoa-Gomez, Monica; Gutierrez, Rochy Vargas

2012-01-01

Functional Analytic Psychotherapy (FAP) has been making an important rise in Ibero-America in recent years. This paper presents a review of different contributions, problems and some proposals. Three principal topics are reviewed: (a) general characteristics and theoretical bases of FAP, (b) the uses of FAP and its relationship with other…

Hypersonic drone vehicle design: A multidisciplinary experience

NASA Technical Reports Server (NTRS)

1988-01-01

UCLA's Advanced Aeronautic Design group focussed their efforts on design problems of an unmanned hypersonic vehicle. It is felt that a scaled hypersonic drone is necesary to bridge the gap between present theory on hypersonics and the future reality of the National Aerospace Plane (NASP) for two reasons: (1) to fulfill a need for experimental data in the hypersonic regime, and (2) to provide a testbed for the scramjet engine which is to be the primary mode of propulsion for the NASP. The group concentrated on three areas of great concern to NASP design: propulsion, thermal management, and flight systems. Problem solving in these areas was directed toward design of the drone with the idea that the same design techniques could be applied to the NASP. A 70 deg swept double-delta wing configuration, developed in the 70's at the NASA Langley, was chosen as the aerodynamic and geometric model for the drone. This vehicle would be air launched from a B-1 at Mach 0.8 and 48,000 feet, rocket boosted by two internal engines to Mach 10 and 100,000 feet, and allowed to cruise under power of the scramjet engine until burnout. It would then return to base for an unpowered landing. Preliminary energy calculations based on flight requirements give the drone a gross launch weight of 134,000 pounds and an overall length of 85 feet.

Hypersonic nozzle/afterbody CFD code validation. I - Experimental measurements

NASA Technical Reports Server (NTRS)

Spaid, Frank W.; Keener, Earl R.

1993-01-01

This study was conducted to obtain a detailed experimental description of the flow field created by the interaction of a single-expansion-ramp-nozzle flow with a hypersonic external stream. Data were obtained from a generic nozzle/afterbody model in the 3.5-Foot Hypersonic Wind Tunnel of the NASA Ames Research Center in a cooperative experimental program involving Ames and the McDonnell Douglas Research Laboratories. This paper presents experimental results consisting primarily of surveys obtained with a five-hole total-pressure/flow-direction probe and a total-temperature probe. These surveys were obtained in the flow field created by the interaction between the underexpanded jet plume and the external flow.

New Air-Launched Small Missile (ALSM) Flight Testbed for Hypersonic Systems

NASA Technical Reports Server (NTRS)

Bui, Trong T.; Lux, David P.; Stenger, Mike; Munson, Mike; Teate, George

2006-01-01

A new testbed for hypersonic flight research is proposed. Known as the Phoenix air-launched small missile (ALSM) flight testbed, it was conceived to help address the lack of quick-turnaround and cost-effective hypersonic flight research capabilities. The Phoenix ALSM testbed results from utilization of two unique and very capable flight assets: the United States Navy Phoenix AIM-54 long-range, guided air-to-air missile and the NASA Dryden F-15B testbed airplane. The U.S. Navy retirement of the Phoenix AIM-54 missiles from fleet operation has presented an excellent opportunity for converting this valuable flight asset into a new flight testbed. This cost-effective new platform will fill an existing gap in the test and evaluation of current and future hypersonic systems for flight Mach numbers ranging from 3 to 5. Preliminary studies indicate that the Phoenix missile is a highly capable platform. When launched from a high-performance airplane, the guided Phoenix missile can boost research payloads to low hypersonic Mach numbers, enabling flight research in the supersonic-to-hypersonic transitional flight envelope. Experience gained from developing and operating the Phoenix ALSM testbed will be valuable for the development and operation of future higher-performance ALSM flight testbeds as well as responsive microsatellite small-payload air-launched space boosters.

Computational Modeling and Validation for Hypersonic Inlets

NASA Technical Reports Server (NTRS)

Povinelli, Louis A.

1996-01-01

Hypersonic inlet research activity at NASA is reviewed. The basis for the paper is the experimental tests performed with three inlets: the NASA Lewis Research Center Mach 5, the McDonnell Douglas Mach 12, and the NASA Langley Mach 18. Both three-dimensional PNS and NS codes have been used to compute the flow within the three inlets. Modeling assumptions in the codes involve the turbulence model, the nature of the boundary layer, shock wave-boundary layer interaction, and the flow spilled to the outside of the inlet. Use of the codes and the experimental data are helping to develop a clearer understanding of the inlet flow physics and to focus on the modeling improvements required in order to arrive at validated codes.

Hypersonic Boost Glider

NASA Image and Video Library

1957-04-15

Hypersonic Boost Glider in 11 Inch Hypersonic Tunnel L57-1681 In 1957 Langley tested its HYWARDS design in the 11 Inch Hypersonic Tunnel. Photograph published in Engineer in Charge: A History of the Langley Aeronautical Laboratory, 1917-1958 by James R. Hansen. Page 369.

Experimental and computational flow-field results for an all-body hypersonic aircraft

NASA Technical Reports Server (NTRS)

Cleary, Joseph W.

1989-01-01

A comprehensive test program is defined which is being implemented in the NASA/Ames 3.5 foot Hypersonic Wind Tunnel for obtaining data on a generic all-body hypersonic vehicle for computational fluid dynamics (CFD) code validation. Computational methods (approximate inviscid methods and an upwind parabolized Navier-Stokes code) currently being applied to the all-body model are outlined. Experimental and computational results on surface pressure distributions and Pitot-pressure surveys for the basic sharp-nose model (without control surfaces) at a free-stream Mach number of 7 are presented.

Interactions in the ionic liquid [EMIM][FAP]: a coupled experimental and computational analysis.

PubMed

Voroshylova, Iuliia V; Teixeira, Filipe; Costa, Renata; Pereira, Carlos M; Cordeiro, M Natália D S

2016-01-28

Gas-phase electronic and structural properties of the room temperature ionic liquid 1-ethyl-3-methylimidazolium tris(perfluoroethyl)trifluorophosphate ([EMIM][FAP]) were studied using density functional theory, and confirmed with results from infrared spectroscopy. A conformational analysis allowed the identification of several plausible conformers of the ion pairs. For the detected conformers, the infrared spectra were predicted and their thermodynamic properties were evaluated. The topology of the electronic density of the most stable conformers of [EMIM][FAP] ion pairs were characterised using the quantum theory of atoms in molecules. A number of possible hydrogen bonds between the cations and anions of the ionic liquid were identified. Excellent correspondence was found between the predicted spectra of gas-phase [EMIM][FAP] conformers and the experimental infrared spectrum, which in turn allowed a clear attribution of the vibration modes of [EMIM][FAP]. Finally, the contribution of the various conformers of both isomers of the [FAP](-) anion to the ionic liquid macro-properties is shown.

Hypersonic research engine/aerothermodynamic integration model, experimental results. Volume 1: Mach 6 component integration

NASA Technical Reports Server (NTRS)

Andrews, E. H., Jr.; Mackley, E. A.

1976-01-01

The NASA Hypersonic Research Engine (HRE) Project was initiated for the purpose of advancing the technology of airbreathing propulsion for hypersonic flight. A large component (inlet, combustor, and nozzle) and structures development program was encompassed by the project. The tests of a full-scale (18 in. diameter cowl and 87 in. long) HRE concept, designated the Aerothermodynamic Integration Model (AIM), at Mach numbers of 5, 6, and 7. Computer program results for Mach 6 component integration tests are presented.

Design and Fabrication of the ISTAR Direct-Connect Combustor Experiment at the NASA Hypersonic Tunnel Facility

NASA Technical Reports Server (NTRS)

Lee, Jin-Ho; Krivanek, Thomas M.

2005-01-01

The Integrated Systems Test of an Airbreathing Rocket (ISTAR) project was a flight demonstration project initiated to advance the state of the art in Rocket Based Combined Cycle (RBCC) propulsion development. The primary objective of the ISTAR project was to develop a reusable air breathing vehicle and enabling technologies. This concept incorporated a RBCC propulsion system to enable the vehicle to be air dropped at Mach 0.7 and accelerated up to Mach 7 flight culminating in a demonstration of hydrocarbon scramjet operation. A series of component experiments was planned to reduce the level of risk and to advance the technology base. This paper summarizes the status of a full scale direct connect combustor experiment with heated endothermic hydrocarbon fuels. This is the first use of the NASA GRC Hypersonic Tunnel facility to support a direct-connect test. The technical and mechanical challenges involved with adapting this facility, previously used only in the free-jet configuration, for use in direct connect mode will be also described.

Fibronectin Attachment Protein (FAP) From Bacillus Calmette-Guerin As Targeting Agent For Bladder Tumor Cells

PubMed Central

Coon, Brian G.; Crist, Scott; González-Bonet, Andrés M.; Kim, Hee-Kwon; Sowa, Jennifer; Thompson, David H.; Ratliff, Timothy L.; Aguilar, R. Claudio

2011-01-01

The adjuvant therapy of choice for superficial bladder cancer is the intravesical instillation of live Mycobacterium bovis Bacillus Calmette-Guerin (BCG). In spite of the fact that this therapy is the most effective treatment for superficial bladder cancer, intravesical administration of BCG is associated with high local morbidity and the potential for systemic infection. Therefore, there is a need for the development of safer, less toxic approaches to fight this disease. Since fibronectin attachment protein (FAP) is a key element in BCG retention and targeting to cells, we hypothesize that this protein can be used as targeting agent to deliver cytotoxic cargo for the treatment of bladder tumors. Here we evaluated the ability of bladder tumor cells to bind and endocytose FAP via fibronectin-integrin complexes. We found that microaggregation induced by an anti-FAP polyclonal antibody accelerated FAP uptake by T24 bladder tumor cells. FAP was determined to be internalized via a clathrin-independent, caveolae-dependent mechanism. Further, once within the endosomal compartment, FAP was targeted to the lysosomal compartment with negligible recycling to the plasma membrane. Importantly, we demonstrated that FAP microaggregation and internalization could also be triggered by multivalent Ni2+NTA-bearing liposomes. Overall, our studies validate the use of FAP as a targeting vector and provide the foundation for the design of more effective, less toxic bladder cancer therapeutics. PMID:21901746

Overview of X-38 Hypersonic Wind Tunnel Data and Comparison with Numerical Results

NASA Technical Reports Server (NTRS)

Campbell, Charles H.; Caram, Jose; Berry, Scott; DiFulvio, Michael; Horvath, Tom

1997-01-01

A NASA team of engineers has been organized to design a crew return vehicle for returning International Space Station crew members from orbit. The hypersonic characteristics of this X-23/X-2&4 derived crew return vehicle (designated X-38) are being evaluated in various wind tunnels in support of this effort. Aerodynamic data has been acquired in three NASA hypersonic facilities at Mach 20, and Mach 6. Computational Fluid Dynamics tools have been applied at the appropriate wind tunnel conditions to make comparisons with portions of this data. Experimental data from the Mach 6 Air and CF4 facilities illustrate a net positive pitching moment increment due to density ratio, as well as increased elevon effectiveness. Chemical nonequilibrium computational fluid dynamics solutions at flight conditions reinforce this conclusion.

Engineers and technicians in the control room at the Dryden Flight Research Center must constantly monitor critical operations and checks during research projects like NASA's hypersonic X-43A

NASA Image and Video Library

2004-01-24

Engineers and technicians in the control room at the Dryden Flight Research Center must constantly monitor critical operations and checks during research projects like NASA's hypersonic X-43A. Visible in the photo, taken two days before the X-43's captive carry flight in January 2004, are [foreground to background]; Tony Kawano (Range Safety Officer), Brad Neal (Mission Controller), and Griffin Corpening (Test Conductor).

NASA's NB-52B carrier aircraft rolls down a taxiway with the X-43A hypersonic research aircraft and its modified Pegasus® booster rocket slung from a pylon under its right wing

NASA Image and Video Library

2001-03-15

NASA's NB-52B carrier aircraft rolls down a taxiway at Edwards Air Force Base with the X-43A hypersonic research aircraft and its modified Pegasus® booster rocket slung from a pylon under its right wing. Part of a combined systems test conducted by NASA's Dryden Flight Research Center at Edwards, the taxi test was one of the last major milestones in the Hyper-X research program before the first X-43A flight. The X-43A flights will be the first actual flight tests of an aircraft powered by a revolutionary supersonic-combustion ramjet ("scramjet") engine capable of operating at hypersonic speeds (above Mach 5, or five times the speed of sound). The 12-foot, unpiloted research vehicle was developed and built by MicroCraft Inc., Tullahoma, Tenn., under NASA contract. The booster was built by Orbital Sciences Corp., Dulles, Va.,After being air-launched from NASA's venerable NB-52 mothership, the booster will accelerate the X-43A to test speed and altitude. The X-43A will then separate from the rocket and fly a pre-programmed trajectory, conducting aerodynamic and propulsion experiments until it descends into the Pacific Ocean. Three research flights are planned, two at Mach 7 and one at Mach 10, with the first tentatively scheduled for late spring to early summer, 2001.

Stromal Expression of Fibroblast Activation Protein Alpha (FAP) Predicts Platinum Resistance and Shorter Recurrence in patients with Epithelial Ovarian Cancer.

PubMed

Mhawech-Fauceglia, Paulette; Yan, Li; Sharifian, Maryam; Ren, Xing; Liu, Song; Kim, Grace; Gayther, Simon A; Pejovic, Tanja; Lawrenson, Kate

2015-04-01

The microenvironment plays an important role in tumorigenesis. Fibroblast activation protein alpha (FAP) is overexpressed by fibroblasts present in the microenvironment of many tumors. High FAP expression is a negative prognostic factor in several malignancies, but this has not been investigated in epithelial ovarian cancer (EOC). The aim of this study is to define the value of FAP in EOC. Immunohistochemical staining using an anti-FAP antibody was performed on 338 EOC tissues. mRNA levels in cancer cell lines and FAP silencing using siRNA was also done. FAP immunoexpression by tumor stroma was a significant predictive factor for platinum resistance (p = 0.0154). In survival analysis of days to recurrence, FAP stoma (+) was associated with shorter recurrence than those with FAP (-) stroma (p = 0.0247). In 21.8 % of tumors, FAP protein was expressed by the tumor epithelium, and FAP mRNA was more highly expressed in tumors (n = 489) than in normal tissues (n = 8) (p = 3.88 × 10(-4)). In vitro, addition of FAP to EOC cells induced a 10-12 % increase in cell viability both in the presence and absence of cisplatin. Conversely, siRNA silencing of FAP resulted in ~10 % reduction in EOC cell proliferation. We have shown that FAP expression in EOC is associated with poorer clinical outcomes. FAP may have novel cell-autonomous effects suggesting that targeting FAP could have pleiotropic anti-tumor effects, and anti-FAP therapy could be a highly effective novel treatment for EOC, especially in cisplatinum-resistant cases.

Expression of Fap amyloids in Pseudomonas aeruginosa, P. fluorescens, and P. putida results in aggregation and increased biofilm formation.

PubMed

Dueholm, Morten S; Søndergaard, Mads T; Nilsson, Martin; Christiansen, Gunna; Stensballe, Allan; Overgaard, Michael T; Givskov, Michael; Tolker-Nielsen, Tim; Otzen, Daniel E; Nielsen, Per H

2013-06-01

The fap operon, encoding functional amyloids in Pseudomonas (Fap), is present in most pseudomonads, but so far the expression and importance for biofilm formation has only been investigated for P. fluorescens strain UK4. In this study, we demonstrate the capacity of P. aeruginosa PAO1, P. fluorescens Pf-5, and P. putida F1 to express Fap fibrils, and investigated the effect of Fap expression on aggregation and biofilm formation. The fap operon in all three Pseudomonas species conferred the ability to express Fap fibrils as shown using a recombinant approach. This Fap overexpression consistently resulted in highly aggregative phenotypes and in increased biofilm formation. Detailed biophysical investigations of purified fibrils confirmed FapC as the main fibril monomer and supported the role of FapB as a minor, nucleating constituent as also indicated by bioinformatic analysis. Bioinformatics analysis suggested FapF and FapD as a potential β-barrel membrane pore and protease, respectively. Manipulation of the fap operon showed that FapA affects monomer composition of the final amyloid fibril, and that FapB is an amyloid protein, probably a nucleator for FapC polymerization. Our study highlights the fap operon as a molecular machine for functional amyloid formation. © 2013 The Authors. Microbiology Open published by John Wiley & Sons Ltd.

The genetics of familial adenomatous polyposis (FAP) and MutYH-associated polyposis (MAP).

PubMed

Claes, Kathleen; Dahan, Karin; Tejpar, S; De Paepe, Anne; Bonduelle, Maryse; Abramowicz, Marc; Verellen, Christine; Franchimont, Denis; Van Cutsem, Eric; Kartheuser, Alex

2011-09-01

FAP is characterized by 100-1000s of adenomatous polyps in colon and rectum, and is in 70% of the patients associated with extracolonic manifestations. Attenuated FAP (AFAP) is a less severe form of FAP, marked by the presence of < 100 polyps and a later onset of colorectal cancer (CRC). (A)FAP is caused by autosomal dominantly inherited mutations in the APC (Adenomatous polyposis coli) gene, a tumour suppressor gene that controls beta-catenin turnover in the Wnt pathway. De novo occurrence is reported in 30-40% of the patients. Mutations are detected in 85% of classical FAP families, while only 20%-30% of AFAP cases will exhibit a germline APC mutation. MUTYH is the second (A)FAP-related gene and is involved with base-excision repair of DNA damaged by oxidative stress. MUTYH mutations are inherited in an autosomal recessive way and account for 10%-20% of classical FAP cases without an APC mutation and for 30% of AFAP cases. Genotype-phenotype correlations exist for mutations in the APC gene, however, contradictions in the literature caution against the sole use of the genotype for decisions regarding clinical management. Once the family's specific APC mutation is identified in the proband, predictive testing for first degree relatives is possible from the age of 10 to 12 years on. For AFAP, relatives are tested at age 18 and older. Opinions about the appropriate ages at which to initiate genetic testing may vary. Physicians must have a discussion about prenatal testing with patients in childbearing age. They may either opt for conventional prenatal diagnosis (amniocentesis or chorionic villous sampling) or for preimplantation genetic diagnosis (PGD).

Expression of the FAP gene in non-fibroblast human cell lines. Development of cancer-associated fibroblast models.

PubMed

Tyulkina, D V; Pleshkan, V V; Alekseenko, I V; Kopantseva, M R; Sverdlov, E D

2016-09-01

The fibroblast activation protein (FAP) is selectively expressed in cancer-associated fibroblasts (CAFs) and facilitates tumor progression, which makes this protein an attractive therapeutic target. There are difficulties in obtaining CAFs for studying the function and suppression of FAP. In this work, the expression level of FAP was determined by PCR assay in 25 human cell lines and 8 surgical samples of tumor stroma. The expression of FAP was observed in all tumor stroma samples and in four cell lines: NGP-127, SJCRH30, SJSA-1, and A375. The level of FAP expression in NGP-127, SJCRH30, and SJSA-1 lines as well as in CAFs of patients was comparable, which makes these cell lines a possible model for studying FAP.

A unique high heat flux facility for testing hypersonic engine components

NASA Technical Reports Server (NTRS)

Melis, Matthew E.; Gladden, Herbert J.

1990-01-01

This paper describes the Hot Gas Facility, a unique, reliable, and cost-effective high-heat-flux facility for testing hypersonic engine components developed at the NASA Lewis Research Center. The Hot Gas Facility is capable of providing heat fluxes ranging from 200 Btu/sq ft per sec on flat surfaces up to 8000 Btu/sq ft per sec at a leading edge stagnation point. The usefulness of the Hot Gas Facility for the NASP community was demonstrated by testing hydrogen-cooled structures over a range of temperatures and pressures. Ranges of the Reynolds numbers, Prandtl numbers, enthalpy, and heat fluxes similar to those expected during hypersonic flights were achieved.

Aerothermodynamic Testing of Aerocapture and Planetary Probe Geometries in Hypersonic Ballistic-Range Environments

NASA Technical Reports Server (NTRS)

Wilder, M. C.; Reda, D. C.; Bogdanoff, D. W.; Olejniczak, J.

2005-01-01

A viewgraph presentation on aerothermodynamic testing of aerocapture and planetary probe design methods in hypersonic ballistic range environments is shown. The topics include: 1) Ballistic Range Testing; 2) NASA-Ames Hypervelocity Free Flight Facility; and 3) Representative Results.

The role of illness perceptions in adherence to surveillance in patients with familial adenomatous polyposis (FAP).

PubMed

Eriksson, Lars E; Fritzell, Kaisa; Rixon, Lorna; Björk, Jan; Wettergren, Lena

2016-06-01

The aim of the study was to examine patients' beliefs about having familial adenomatous polyposis (FAP), a hereditary colorectal cancer syndrome, and how these beliefs are associated with adherence to endoscopic surveillance. Adult patients diagnosed with FAP on the national Swedish polyposis register who had undergone prophylactic colorectal surgery (n 209, response rate 76%) completed the Illness Perception Questionnaire (IPQ). Logistic regression analysis was used to investigate the relationships between illness perceptions and adherence, when controlling for demographic and clinical factors. FAP was less distressing in men and those with fewer symptoms, reporting less serious consequences and more coherent understanding of FAP. Non-adherence (14%) to surveillance was associated with being older, having undergone surgery less recently and no history of malignancy. Patients' beliefs about their FAP were able to explain unique variance in non-adherence, in particular those who believed FAP was less distressing. Patients who were non-adherent to endoscopic surveillance had more positive perceptions about their FAP and, in particular, were less emotionally affected compared to those who adhered. As non-adherence implies a greater risk of future malignancies, special efforts are required to effectively prevent cancer in all patients with FAP. Those who have lived with the condition for a long time, and are not troubled by gastrointestinal symptoms or worried about their FAP, may be in need of specific information and support. Further prospective research is required to examine emotional predictors and consequences of non-adherence. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis.

PubMed

Wikberg, Maria L; Edin, Sofia; Lundberg, Ida V; Van Guelpen, Bethany; Dahlin, Anna M; Rutegård, Jörgen; Stenling, Roger; Oberg, Ake; Palmqvist, Richard

2013-04-01

An active stroma is important for cancer cell invasion and metastasis. We investigated the expression of fibroblast activation protein (FAP) in relation to patient prognosis in colorectal cancer. Colorectal cancer specimens from 449 patients were immunohistochemically stained with a FAP antibody and evaluated in the tumor center and tumor front using a semiquantitative four-level scale. FAP was expressed by fibroblasts in 85-90 % of the tumors examined. High versus no/low expression in the tumor center was associated with poor prognosis (multivariate hazard ratio, HR = 1.72; 95 % CI 1.07-2.77, p = 0.025). FAP expression in the tumor front, though more frequent than in the tumor center, was not associated with prognosis. FAP expression in the tumor center was more common in specimens with positive microsatellite instability (MSI) screening status and in patients with high CpG island methylator phenotype (CIMP) status. However, inclusion of MSI screening status and CIMP status in the multivariate analysis strengthened the risk estimates for high FAP expression in the tumor center (HR = 1.89; 95 % CI 1.13-3.14; p = 0.014), emphasizing the role of FAP as an independent prognostic factor. Stromal FAP expression is common in colorectal cancer, and we conclude that high FAP expression in the tumor center, but not the tumor front, is an independent negative prognostic factor.

FAP-overexpressing fibroblasts produce an extracellular matrix that enhances invasive velocity and directionality of pancreatic cancer cells

PubMed Central

2011-01-01

Background Alterations towards a permissive stromal microenvironment provide important cues for tumor growth, invasion, and metastasis. In this study, Fibroblast activation protein (FAP), a serine protease selectively produced by tumor-associated fibroblasts in over 90% of epithelial tumors, was used as a platform for studying tumor-stromal interactions. We tested the hypothesis that FAP enzymatic activity locally modifies stromal ECM (extracellular matrix) components thus facilitating the formation of a permissive microenvironment promoting tumor invasion in human pancreatic cancer. Methods We generated a tetracycline-inducible FAP overexpressing fibroblastic cell line to synthesize an in vivo-like 3-dimensional (3D) matrix system which was utilized as a stromal landscape for studying matrix-induced cancer cell behaviors. A FAP-dependent topographical and compositional alteration of the ECM was characterized by measuring the relative orientation angles of fibronectin fibers and by Western blot analyses. The role of FAP in the matrix-induced permissive tumor behavior was assessed in Panc-1 cells in assorted matrices by time-lapse acquisition assays. Also, FAP+ matrix-induced regulatory molecules in cancer cells were determined by Western blot analyses. Results We observed that FAP remodels the ECM through modulating protein levels, as well as through increasing levels of fibronectin and collagen fiber organization. FAP-dependent architectural/compositional alterations of the ECM promote tumor invasion along characteristic parallel fiber orientations, as demonstrated by enhanced directionality and velocity of pancreatic cancer cells on FAP+ matrices. This phenotype can be reversed by inhibition of FAP enzymatic activity during matrix production resulting in the disorganization of the ECM and impeded tumor invasion. We also report that the FAP+ matrix-induced tumor invasion phenotype is β1-integrin/FAK mediated. Conclusion Cancer cell invasiveness can be affected by

WD60/FAP163 is a dynein intermediate chain required for retrograde intraflagellar transport in cilia

PubMed Central

Patel-King, Ramila S.; Gilberti, Renée M.; Hom, Erik F. Y.; King, Stephen M.

2013-01-01

Retrograde intraflagellar transport (IFT) is required for assembly of cilia. We identify a Chlamydomonas flagellar protein (flagellar-associated protein 163 [FAP163]) as being closely related to the D1bIC(FAP133) intermediate chain (IC) of the dynein that powers this movement. Biochemical analysis revealed that FAP163 is present in the flagellar matrix and is actively trafficked by IFT. Furthermore, FAP163 copurified with D1bIC(FAP133) and the LC8 dynein light chain, indicating that it is an integral component of the retrograde IFT dynein. To assess the functional role of FAP163, we generated an RNA interference knockdown of the orthologous protein (WD60) in planaria. The Smed-wd60(RNAi) animals had a severe ciliary assembly defect that dramatically compromised whole-organism motility. Most cilia were present as short stubs that had accumulated large quantities of IFT particle–like material between the doublet microtubules and the membrane. The few remaining approximately full-length cilia had a chaotic beat with a frequency reduced from 24 to ∼10 Hz. Thus WD60/FAP163 is a dynein IC that is absolutely required for retrograde IFT and ciliary assembly. PMID:23864713

Hypersonics. Volume 1 - Defining the hypersonic environment; Proceedings of the First Joint Europe/U.S. Short Course on Hypersonics, Paris, France, Dec. 7-11, 1987

NASA Astrophysics Data System (ADS)

Bertin, John J.; Glowinski, Roland; Periaux, Jacques

1989-05-01

The present work discusses the general characterization of hypersonic flows, the hypersonic phenomena to be encountered by the Hermes spacecraft, industrial methodologies for the design of hypersonic vehicles, the definition of aerodynamic methodology, and hypersonic airbreathing-propulsion vehicle design practices applicable to the U.S. National Aerospace Plane. Also discussed are real gas effects in the hypersonic regime, the influence of thermochemistry and of nonequilibrium and surface catalysis on hypersonic vehicle design, the modelling of nonequilibrium effects in high speed flows, air-dissociation thermochemistry, and rarefied gas dynamics effects for spacecraft.

Hyper-X: Flight Validation of Hypersonic Airbreathing Technology

NASA Technical Reports Server (NTRS)

Rausch, Vincent L.; McClinton, Charles R.; Crawford, J. Larry

1997-01-01

This paper provides an overview of NASA's focused hypersonic technology program, i.e. the Hyper-X program. This program is designed to move hypersonic, air breathing vehicle technology from the laboratory environment to the flight environment, the last stage preceding prototype development. This paper presents some history leading to the flight test program, research objectives, approach, schedule and status. Substantial experimental data base and concept validation have been completed. The program is concentrating on Mach 7 vehicle development, verification and validation in preparation for wind tunnel testing in 1998 and flight testing in 1999. It is also concentrating on finalization of the Mach 5 and 10 vehicle designs. Detailed evaluation of the Mach 7 vehicle at the flight conditions is nearing completion, and will provide a data base for validation of design methods once flight test data are available.

FAP finds FGF21 easy to digest.

PubMed

Gillum, Matthew P; Potthoff, Matthew J

2016-05-01

Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates carbohydrate and lipid metabolism. In humans, circulating FGF21 is inactivated by proteolytic cleavage of its C-terminus, thereby preventing signalling through a receptor complex. The mechanism for this cleavage event and the factors contributing to the post-translational regulation of FGF21 activity has previously been unknown. In a recent issue of the Biochemical Journal, Zhen et al. have identified fibroblast activation protein (FAP) as the endopeptidase responsible for this site-specific cleavage of human FGF21 (hFGF21), and propose that inhibition of FAP may be a therapeutic strategy to increase endogenous levels of active FGF21. © 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Hypersonic Inflatable Aerodynamic Decelerator (HIAD) Technology Development Overview

NASA Technical Reports Server (NTRS)

Hughes, Stephen J.; Cheatwood, F. McNeil; Calomino, Anthony M.; Wright, Henry S.; Wusk, Mary E.; Hughes, Monica F.

2013-01-01

The successful flight of the Inflatable Reentry Vehicle Experiment (IRVE)-3 has further demonstrated the potential value of Hypersonic Inflatable Aerodynamic Decelerator (HIAD) technology. This technology development effort is funded by NASA's Space Technology Mission Directorate (STMD) Game Changing Development Program (GCDP). This paper provides an overview of a multi-year HIAD technology development effort, detailing the projects completed to date and the additional testing planned for the future.

Unstructured Mesh Methods for the Simulation of Hypersonic Flows

NASA Technical Reports Server (NTRS)

Peraire, Jaime; Bibb, K. L. (Technical Monitor)

2001-01-01

This report describes the research work undertaken at the Massachusetts Institute of Technology. The aim of this research is to identify effective algorithms and methodologies for the efficient and routine solution of hypersonic viscous flows about re-entry vehicles. For over ten years we have received support from NASA to develop unstructured mesh methods for Computational Fluid Dynamics. As a result of this effort a methodology based on the use, of unstructured adapted meshes of tetrahedra and finite volume flow solvers has been developed. A number of gridding algorithms flow solvers, and adaptive strategies have been proposed. The most successful algorithms developed from the basis of the unstructured mesh system FELISA. The FELISA system has been extensively for the analysis of transonic and hypersonic flows about complete vehicle configurations. The system is highly automatic and allows for the routine aerodynamic analysis of complex configurations starting from CAD data. The code has been parallelized and utilizes efficient solution algorithms. For hypersonic flows, a version of the, code which incorporates real gas effects, has been produced. One of the latest developments before the start of this grant was to extend the system to include viscous effects. This required the development of viscous generators, capable of generating the anisotropic grids required to represent boundary layers, and viscous flow solvers. In figures I and 2, we show some sample hypersonic viscous computations using the developed viscous generators and solvers. Although these initial results were encouraging, it became apparent that in order to develop a fully functional capability for viscous flows, several advances in gridding, solution accuracy, robustness and efficiency were required. As part of this research we have developed: 1) automatic meshing techniques and the corresponding computer codes have been delivered to NASA and implemented into the GridEx system, 2) a finite

Expression and role of the cell surface protease seprase/fibroblast activation protein-α (FAP-α) in astroglial tumors.

PubMed

Mentlein, Rolf; Hattermann, Kirsten; Hemion, Charles; Jungbluth, Achim A; Held-Feindt, Janka

2011-03-01

Seprase or fibroblast activation protein-α (FAP-α) is a cell-surface serine protease that was previously described nearly exclusively on reactive and tumor stromal fibroblasts and thought to be involved in tissue remodeling. We investigated the expression and significance of FAP-α in astrocytomas/glioblastomas. As shown by quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, FAP-α was elevated in whole glioblastoma tissues and in particular in most glioma cells in situ and in vitro. In glioma stem-like cells (gliospheres), FAP-α was detected at low levels; however, FAP-α was considerably induced upon differentiation with 10% fetal calf serum. To explore its functional role, FAP-α was silenced by siRNA transfection. In Boyden chamber assays, FAP-α silenced cells migrated similar as control cells through non-coated or Matrigel (basal lamina)-coated porous membranes, but significantly slower through membranes coated with gelatin or brevican, a major component of brain extracellular matrix. Furthermore, FAP-α-silenced glioma cells migrated through murine brain slices much slower under the conditions tested than differentially fluorescent-labeled control cells. Thus, FAP-α is highly expressed on the surface of glioma cells and contributes to diffuse glioma invasion through extracellular matrix components.

Flight simulator for hypersonic vehicle and a study of NASP handling qualities

NASA Technical Reports Server (NTRS)

Ntuen, Celestine A.; Park, Eui H.; Deeb, Joseph M.; Kim, Jung H.

1992-01-01

The research goal of the Human-Machine Systems Engineering Group was to study the existing handling quality studies in aircraft with sonic to supersonic speeds and power in order to understand information requirements needed for a hypersonic vehicle flight simulator. This goal falls within the NASA task statements: (1) develop flight simulator for hypersonic vehicle; (2) study NASP handling qualities; and (3) study effects of flexibility on handling qualities and on control system performance. Following the above statement of work, the group has developed three research strategies. These are: (1) to study existing handling quality studies and the associated aircraft and develop flight simulation data characterization; (2) to develop a profile for flight simulation data acquisition based on objective statement no. 1 above; and (3) to develop a simulator and an embedded expert system platform which can be used in handling quality experiments for hypersonic aircraft/flight simulation training.

FAP-related desmoid tumors: a series of 44 patients evaluated in a cancer referral center.

PubMed

Colombo, Chiara; Foo, Wai Chin; Whiting, David; Young, Eric D; Lusby, Kristelle; Pollock, Raphael E; Lazar, Alexander J; Lev, Dina

2012-05-01

Desmoid tumors (DTs), the commonest extra-intestinal manifestation of familial adenomatosis polyposis (FAP), are monoclonal neoplasms demonstrating fibroblastic - myofibroblastic differentiation; they are locally invasive without metastatic capacity. FAP-associated DT natural history knowledge is limited; we examined patient and tumor characteristics for a FAP-DT cohort and evaluated anti-DT therapy molecular target expression levels (immunohistochemical analyses, FAP-DT tissue microarray; TMA). Forty-four patients were classified as intra-abdominal (IA; n=26), abdominal wall (AW)/extra-abdominal (EA; n=12) or concomitant IA/AW (n=6) based on DT primary diagnosis location. Positive family histories were found in 62% of FAP versus 10% of DT patients. Surgery was the mainstay therapy for AW/EW patients, whereas IA DTs received surgery, chemotherapy, radiotherapy, tamoxifen, NSAIDs, and/or imatinib. Eight of 20 completely resected DTs in the IA and AW/EA groups recurred; 12 of 38 patients in these groups (33%) developed secondary lesions elsewhere. Two intestinal mesenteric DT patients died of disease, three from other cancers, 27 are alive with disease and 12 are alive without disease. All evaluable FAP-DT exhibited nuclear β-catenin, 65% were positive for cyclin D1, and 66% expressed nuclear p53. No ERα expression was observed, but ERβ was expressed in 72%. COX2 was expressed in all evaluable FAP-DTs. KIT was rarely found in DTs but both PDGFRs and their ligands were expressed. Comparing biomarker expression (IA vs. EA DTs), only nuclear ER-ß staining was significantly higher in EA lesions (p=0.0070); no other markers were site informative. Enhanced knowledge of FAP-DT molecular underpinnings will facilitate development of novel therapeutic strategies.

Fibroblast Activation Protein (FAP) Is Essential for the Migration of Bone Marrow Mesenchymal Stem Cells through RhoA Activation

PubMed Central

Chung, Kuei-Min; Hsu, Shu-Ching; Chu, Yue-Ru; Lin, Mei-Yao; Jiaang, Weir-Tong; Chen, Ruey-Hwa; Chen, Xin

2014-01-01

Background The ability of human bone marrow mesenchymal stem cells (BM-MSCs) to migrate and localize specifically to injured tissues is central in developing therapeutic strategies for tissue repair and regeneration. Fibroblast activation protein (FAP) is a cell surface serine protease expressed at sites of tissue remodeling during embryonic development. It is also expressed in BM-MSCs, but not in normal tissues or cells. The function of FAP in BM-MSCs is not known. Principal Findings We found that depletion of FAP proteins significantly inhibited the migration of BM-MSCs in a transwell chemotaxis assay. Such impaired migration ability of BM-MSCs could be rescued by re-expressing FAP in these cells. We then demonstrated that depletion of FAP activated intracellular RhoA GTPase. Consistently, inhibition of RhoA activity using a RhoA inhibitor rescued its migration ability. Inhibition of FAP activity with an FAP-specific inhibitor did not affect the activation of RhoA or the migration of BM-MSCs. Furthermore, the inflammatory cytokines interleukin-1beta (IL-1β) and transforming growth factor-beta (TGF-β) upregulated FAP expression, which coincided with better BM-MSC migration. Conclusions Our results indicate FAP plays an important role in the migration of BM-MSCs through modulation of RhoA GTPase activity. The peptidase activity of FAP is not essential for such migration. Cytokines IL-1β and TGF-β upregulate the expression level of FAP and thus enhance BM-MSC migration. PMID:24551161

Fibroblast activation protein (FAP) is essential for the migration of bone marrow mesenchymal stem cells through RhoA activation.

PubMed

Chung, Kuei-Min; Hsu, Shu-Ching; Chu, Yue-Ru; Lin, Mei-Yao; Jiaang, Weir-Tong; Chen, Ruey-Hwa; Chen, Xin

2014-01-01

The ability of human bone marrow mesenchymal stem cells (BM-MSCs) to migrate and localize specifically to injured tissues is central in developing therapeutic strategies for tissue repair and regeneration. Fibroblast activation protein (FAP) is a cell surface serine protease expressed at sites of tissue remodeling during embryonic development. It is also expressed in BM-MSCs, but not in normal tissues or cells. The function of FAP in BM-MSCs is not known. We found that depletion of FAP proteins significantly inhibited the migration of BM-MSCs in a transwell chemotaxis assay. Such impaired migration ability of BM-MSCs could be rescued by re-expressing FAP in these cells. We then demonstrated that depletion of FAP activated intracellular RhoA GTPase. Consistently, inhibition of RhoA activity using a RhoA inhibitor rescued its migration ability. Inhibition of FAP activity with an FAP-specific inhibitor did not affect the activation of RhoA or the migration of BM-MSCs. Furthermore, the inflammatory cytokines interleukin-1beta (IL-1β) and transforming growth factor-beta (TGF-β) upregulated FAP expression, which coincided with better BM-MSC migration. Our results indicate FAP plays an important role in the migration of BM-MSCs through modulation of RhoA GTPase activity. The peptidase activity of FAP is not essential for such migration. Cytokines IL-1β and TGF-β upregulate the expression level of FAP and thus enhance BM-MSC migration.

FAP-overexpressing fibroblasts produce an extracellular matrix that enhances invasive velocity and directionality of pancreatic cancer cells.

PubMed

Lee, Hyung-Ok; Mullins, Stefanie R; Franco-Barraza, Janusz; Valianou, Matthildi; Cukierman, Edna; Cheng, Jonathan D

2011-06-13

Alterations towards a permissive stromal microenvironment provide important cues for tumor growth, invasion, and metastasis. In this study, Fibroblast activation protein (FAP), a serine protease selectively produced by tumor-associated fibroblasts in over 90% of epithelial tumors, was used as a platform for studying tumor-stromal interactions. We tested the hypothesis that FAP enzymatic activity locally modifies stromal ECM (extracellular matrix) components thus facilitating the formation of a permissive microenvironment promoting tumor invasion in human pancreatic cancer. We generated a tetracycline-inducible FAP overexpressing fibroblastic cell line to synthesize an in vivo-like 3-dimensional (3D) matrix system which was utilized as a stromal landscape for studying matrix-induced cancer cell behaviors. A FAP-dependent topographical and compositional alteration of the ECM was characterized by measuring the relative orientation angles of fibronectin fibers and by Western blot analyses. The role of FAP in the matrix-induced permissive tumor behavior was assessed in Panc-1 cells in assorted matrices by time-lapse acquisition assays. Also, FAP+ matrix-induced regulatory molecules in cancer cells were determined by Western blot analyses. We observed that FAP remodels the ECM through modulating protein levels, as well as through increasing levels of fibronectin and collagen fiber organization. FAP-dependent architectural/compositional alterations of the ECM promote tumor invasion along characteristic parallel fiber orientations, as demonstrated by enhanced directionality and velocity of pancreatic cancer cells on FAP+ matrices. This phenotype can be reversed by inhibition of FAP enzymatic activity during matrix production resulting in the disorganization of the ECM and impeded tumor invasion. We also report that the FAP+ matrix-induced tumor invasion phenotype is β1-integrin/FAK mediated. Cancer cell invasiveness can be affected by alterations in the tumor

Functional Analytic Psychotherapy (FAP): A Review of Publications from 1990 to 2010

ERIC Educational Resources Information Center

Mangabeira, Victor; Kanter, Jonathan; Del Prette, Giovana

2012-01-01

Functional Analytic Psychotherapy (FAP), a therapy based on radical behaviorism, establishes the priority of the therapeutic interaction as a mechanism of change in psychotherapy. Since the first book on FAP appeared in 1991, it has been the focus of many papers and has been incorporated by the community of behavior therapists. This paper is a…

FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3-CCL2 Signaling.

PubMed

Yang, Xuguang; Lin, Yuli; Shi, Yinghong; Li, Bingji; Liu, Weiren; Yin, Wei; Dang, Yongjun; Chu, Yiwei; Fan, Jia; He, Rui

2016-07-15

Cancer-associated fibroblasts (CAF) are components of the tumor microenvironment whose contributions to malignant progression are not fully understood. Here, we show that the fibroblast activation protein (FAP) triggers induction of a CAF subset with an inflammatory phenotype directed by STAT3 activation and inflammation-associated expression signature marked by CCL2 upregulation. Enforcing FAP expression in normal fibroblasts was sufficient to endow them with an inflammatory phenotype similar to FAP(+)CAFs. We identified FAP as a persistent activator of fibroblastic STAT3 through a uPAR-dependent FAK-Src-JAK2 signaling pathway. In a murine liver tumor model, we found that FAP(+)CAFs were a major source of CCL2 and that fibroblastic STAT3-CCL2 signaling in this setting promoted tumor growth by enhancing recruitment of myeloid-derived suppressor cells (MDSC). The CCL2 receptor CCR2 was expressed on circulating MDSCs in tumor-bearing subjects and FAP(+)CAF-mediated tumor promotion and MDSC recruitment was abrogated in Ccr2-deficient mice. Clinically, we observed a positive correlation between stromal expression of FAP, p-STAT3, and CCL2 in human intrahepatic cholangiocarcinoma, a highly aggressive liver cancer with dense desmoplastic stroma, where elevated levels of stromal FAP predicted a poor survival outcome. Taken together, our results showed how FAP-STAT3-CCL2 signaling in CAFs was sufficient to program an inflammatory component of the tumor microenvironment, which may have particular significance in desmoplasia-associated cancers. Cancer Res; 76(14); 4124-35. ©2016 AACR. ©2016 American Association for Cancer Research.

X-43A hypersonic research aircraft mated to its modified Pegasus booster rocket.

NASA Technical Reports Server (NTRS)

2001-01-01

The first of three X-43A hypersonic research aircraft was mated to its modified Pegasus booster rocket in late January at NASA's Dryden Flight Research Center, Edwards, Calif. FIRST X-43A MATED TO BOOSTER -- The first of three X-43A hypersonic research aircraft was mated to its modified Pegasus booster rocket in late January at NASA's Dryden Flight Research Center, Edwards, Calif. Mating of the X-43A and its specially-designed adapter to the first stage of the booster rocket marks a major milestone in the Hyper-X hypersonic research program. The 12-foot, unpiloted research vehicle was developed and built by MicroCraft Inc., Tullahoma, Tenn., for NASA. The booster, built by Orbital Sciences Corp., Dulles, Va., will accelerate the X-43A after the X-43A booster 'stack' is air-launched from NASA's venerable NB-52 mothership. The X-43A will separate from the rocket at a predetermined altitude and speed and fly a pre-programmed trajectory, conducting aerodynamic and propulsion experiments until it impacts into the Pacific Ocean. Three research flights are planned, two at Mach 7 and one at Mach 10 (seven and 10 times the speed of sound respectively) with the first tentatively scheduled for early summer of 2001. The X-43A is powered by a revolutionary supersonic-combustion ramjet ('scramjet') engine, and will use the underbody of the aircraft to form critical elements of the engine. The forebody shape helps compress the intake airflow, while the aft section acts as a nozzle to direct thrust. The X-43A flights will be the first actual flight tests of an aircraft powered by an air-breathing scramjet engine.

Bispecific single-chain diabody-immunoliposomes targeting endoglin (CD105) and fibroblast activation protein (FAP) simultaneously.

PubMed

Rabenhold, Markus; Steiniger, Frank; Fahr, Alfred; Kontermann, Roland E; Rüger, Ronny

2015-03-10

Liposomes are well-established drug delivery systems with cancer chemotherapy as main focus. To increase the cellular drug delivery, liposomes can be endowed with ligands, e.g. recombinant antibody fragments, which ensure specific cell interaction. Multispecific immunoliposomes can be prepared to improve the liposome to cell interaction by targeting multiple different targets at the same time, for instance by coupling two or more different ligands to the liposomal surface, resulting in a synergistic or additive increase in binding. An alternative approach is the use of bispecific ligands to address at least two different targets. For this purpose we cloned a single-chain diabody fragment (scDb`), a bispecific molecule targeting two antigens, endoglin (CD105) and fibroblast activation protein (FAP), expressed on cells of the tumor microenvironment. As model cell system, a human fibrosarcoma cell line was used expressing endoglin and FAP simultaneously. Monospecific immunoliposomes directed either against endoglin or FAP were compared in vitro for cell binding and cytotoxic activity with bispecific dual-targeted scFv`-IL (bispecific scFv`FAP/CD105-IL) and bispecific single-chain diabody`-IL (scDb`CD105/FAP-IL) targeting endoglin and FAP simultaneously. In the underlying study, bispecific scFv`FAP/CD105-IL interacted stronger with cells expressing FAP and endoglin (both targets simultaneously) compared to the monospecific immunoliposomes. Furthermore, bispecific scDb`-immunoliposomes increased the cell interaction massively and showed enhanced cytotoxicity against target cells using doxorubicin-loaded immunoliposomes. The use of recombinant bispecific ligands as scDb`-molecules facilitates the generation of bispecific immunoliposomes by using the established post-insertion technique, enabling an extension of the ligand specificity spectrum via genetic modification. Copyright © 2015 Elsevier B.V. All rights reserved.

New Air-Launched Small Missile (ALSM) Flight Testbed for Hypersonic Systems

NASA Technical Reports Server (NTRS)

Bui, Trong T.; Lux, David P.; Stenger, Michael T.; Munson, Michael J.; Teate, George F.

2007-01-01

The Phoenix Air-Launched Small Missile (ALSM) flight testbed was conceived and is proposed to help address the lack of quick-turnaround and cost-effective hypersonic flight research capabilities. The Phoenix ALSM testbed results from utilization of the United States Navy Phoenix AIM-54 (Hughes Aircraft Company, now Raytheon Company, Waltham, Massachusetts) long-range, guided air-to-air missile and the National Aeronautics and Space Administration (NASA) Dryden Flight Research Center (Edwards, California) F-15B (McDonnell Douglas, now the Boeing Company, Chicago, Illinois) testbed airplane. The retirement of the Phoenix AIM-54 missiles from fleet operation has presented an opportunity for converting this flight asset into a new flight testbed. This cost-effective new platform will fill the gap in the test and evaluation of hypersonic systems for flight Mach numbers ranging from 3 to 5. Preliminary studies indicate that the Phoenix missile is a highly capable platform; when launched from a high-performance airplane, the guided Phoenix missile can boost research payloads to low hypersonic Mach numbers, enabling flight research in the supersonic-to-hypersonic transitional flight envelope. Experience gained from developing and operating the Phoenix ALSM testbed will assist the development and operation of future higher-performance ALSM flight testbeds as well as responsive microsatellite-small-payload air-launched space boosters.

Evaluation of the radiolabeled boronic acid-based FAP inhibitor MIP-1232 for atherosclerotic plaque imaging.

PubMed

Meletta, Romana; Müller Herde, Adrienne; Chiotellis, Aristeidis; Isa, Malsor; Rancic, Zoran; Borel, Nicole; Ametamey, Simon M; Krämer, Stefanie D; Schibli, Roger

2015-01-27

Research towards the non-invasive imaging of atherosclerotic plaques is of high clinical priority as early recognition of vulnerable plaques may reduce the incidence of cardiovascular events. The fibroblast activation protein alpha (FAP) was recently proposed as inflammation-induced protease involved in the process of plaque vulnerability. In this study, FAP mRNA and protein levels were investigated by quantitative polymerase chain reaction and immunohistochemistry, respectively, in human endarterectomized carotid plaques. A published boronic-acid based FAP inhibitor, MIP-1232, was synthetized and radiolabeled with iodine-125. The potential of this radiotracer to image plaques was evaluated by in vitro autoradiography with human carotid plaques. Specificity was assessed with a xenograft with high and one with low FAP level, grown in mice. Target expression analyses revealed a moderately higher protein level in atherosclerotic plaques than normal arteries correlating with plaque vulnerability. No difference in expression was determined on mRNA level. The radiotracer was successfully produced and accumulated strongly in the FAP-positive SK-Mel-187 melanoma xenograft in vitro while accumulation was negligible in an NCI-H69 xenograft with low FAP levels. Binding of the tracer to endarterectomized tissue was similar in plaques and normal arteries, hampering its use for atherosclerosis imaging.

Hypersonic Airbreathing Propulsion: An Aerodynamics, Aerothermodynamics, and Acoustics Competency White Paper

NASA Technical Reports Server (NTRS)

Drummond, J. Philip; Cockrell, Charles E., Jr.; Pellett, Gerald L.; Diskin, Glenn S.; Auslender, Aaron H.; Exton, Reginald J.; Guy, R. Wayne; Hoppe, John C.; Puster, Richard L.; Rogers, R. Clayton

2002-01-01

This White Paper examines the current state of Hypersonic Airbreathing Propulsion at the NASA Langley Research Center and the factors influencing this area of work and its personnel. Using this knowledge, the paper explores beyond the present day and suggests future directions and strategies for the field. Broad views are first taken regarding potential missions and applications of hypersonic propulsion. Then, candidate propulsion systems that may be applicable to these missions are suggested and discussed. Design tools and experimental techniques for developing these propulsion systems are then described, and approaches for applying them in the design process are considered. In each case, current strategies are reviewed and future approaches that may improve the techniques are considered. Finally, the paper concentrates on the needs to be addressed in each of these areas to take advantage of the opportunities that lay ahead for both the NASA Langley Research Center and the Aerodynamic Aerothermodynamic, and Aeroacoustics Competency. Recommendations are then provided so that the goals set forth in the paper may be achieved.

Female sexual and pelvic floor muscles dysfunctions in familial amyloidotic polyneuropathy (FAP-Portuguese type).

PubMed

Gomes, Mario João; Martins da Silva, Antonio; Salinas, Jesus; Silva, Maria Carolina; Figueiredo, Arnaldo; Cavadas, Vitor; Coelho, Teresa

2012-05-01

The aim of this study was to investigate the prevalence of Sexual and Pelvic Floor Dysfunctions associated with familial type 1 Portuguese amyloid polyneuropathy (FAP). We studied women with FAP in three stages of the disease: asymptomatic women (n=12), women in the early stage of the disease (n=8) and 3 women in the most progressive stage of the disease. We hypothesize that women with FAP suffer from pelvic floor hypotonicity, which may hinder orgasmic function and as such, lead to deteriorated sexual function. Twenty-three women with FAP were studied. Clinical examinations were performed using the following scales: Clinical Evaluation Scale (CES), Visual Analog Scale of Quality of Life (VAS), Female Sexual Function Index (FSFI) and Pelvic Floor Manometry (PFM). Of the women, 5 (21.7%) had a score of < 26 on the FSFI, suggesting sexual dysfunction, 3 of which had FAP at the most progressive stage. None of the asymptomatic women had low FSFI scores. The manometrical rates (PFM) of tonus and strength of the pelvic floor showed significant differences between groups. Female sexual dysfunction (FSD) may occur in the initial stages of the disease but is more prevalent in women in the advanced stages of the disease. There is an increasing incidence of FSD as FAP disease progresses, namely in terms of HSDD and orgasmic sensation. In the asymptomatic group, the females revealed PFM alterations without stress urinary incontinence, which is regarded to be a discrete deterioration of pelvic floor muscle function.

Congenital Hypertrophy of Retinal Pigment Epithelium for Diagnosis of Familial Adenomatous Polyposis - the First FAP registry in Iran

PubMed

Mirinezhad, Seyed Kazem; Mousavi, Farideh; Baghri, Masood; Sepehri, Bita; Ghavidel, Ali; Ghojazadeh, Morteza; Somi, Mohammad Hossein

2018-01-27

Objective: Familial adenomatous polyposis (FAP), an autosomal dominant inherited disorder is characterized by the presence of multiple adenomatous colorectal polyps, which can develop into cancer during early adulthood. Therefore, early diagnosis is essential. Most FAP patients have several extracolonic manifestations, including congenital hypertrophy of the retinal pigment epithelium (CHRPE). Whereas genetic markers may provide the main route to detection of ‘‘at risk’’ subjects , at present this approach is clearly limited and searches for a noninvasive phenotypic marker continue to be high priority.The aim of this study was to describe the pattern of distribution of CHRPE lesions and evaluate their diagnostic value in FAP patients and their family members in a local population. Methods: A total of 23 FAP patients and 26 relatives belonging to 12 families at high risk of developing FAP were subjected to colonoscopic and ophthalmological examination. Result: Retinal examinations demonstrated prevalences of CHRPE in FAP patents and their siblings of 78% and 38%, respectively. We were able to illustrate a significant correlation between FAP disease and the presence of retinal lesions. Sensitivity and specificity of CHRPE as a screening test to detect the presence of FAP are 78.3% and 61.5%, respectively, with a positive predictive value of 64.3% and a negative predictive value of 76.2 %. A “lesion form” significant difference was found between FAP and normal participants.Spearman nonparametric analysis revealed no correlation between age and number or size of lesions. Conclusion: Multiple CHRPE lesions are a diagnostic feature of FAP patients They are specific and sensitive clinical markers of this disease (specificity 60% and sensitivity 77%). Creative Commons Attribution License

NASA's Integrated Space Transportation Plan — 3 rd generation reusable launch vehicle technology update

NASA Astrophysics Data System (ADS)

Cook, Stephen; Hueter, Uwe

2003-08-01

NASA's Integrated Space Transportation Plan (ISTP) calls for investments in Space Shuttle safety upgrades, second generation Reusable Launch Vehicle (RLV) advanced development and third generation RLV and in-space research and technology. NASA's third generation launch systems are to be fully reusable and operation by 2025. The goals for third generation launch systems are to reduce cost by a factor of 100 and improve safety by a factor of 10,000 over current systems. The Advanced Space Transportation Program Office (ASTP) at NASA's Marshall Space Flight Center in Huntsville, AL has the agency lead to develop third generation space transportation technologies. The Hypersonics Investment Area, part of ASTP, is developing the third generation launch vehicle technologies in two main areas, propulsion and airframes. The program's major investment is in hypersonic airbreathing propulsion since it offers the greatest potential for meeting the third generation launch vehicles. The program will mature the technologies in three key propulsion areas, scramjets, rocket-based combined cycle and turbine-based combination cycle. Ground and flight propulsion tests are being planned for the propulsion technologies. Airframe technologies will be matured primarily through ground testing. This paper describes NASA's activities in hypersonics. Current programs, accomplishments, future plans and technologies that are being pursued by the Hypersonics Investment Area under the Advanced Space Transportation Program Office will be discussed.

Hypersonic technology-approach to an expanded program

NASA Technical Reports Server (NTRS)

Hearth, D. P.; Preyss, A. E.

1976-01-01

An overview of research, testing, and technology in the hypersonic range. Military and civilian hypersonic flight systems envisaged, ground testing facilities under development, methods for cooling the heated airframe, and use of hydrogen as fuel and coolant are discussed extensively. Air-breathing hypersonic cruise systems are emphasized, the airframe-integrated scramjet configuration is discussed and illustrated, materials proposed for hypersonic vehicles are reviewed, and test results on hypersonic flight (X-15 research aircraft) are indicated. Major advances and major problems in hypersonic flight and hypersonic technology are outlined, and the need for a hypersonic flying-laboratory research craft is stressed.

Rekindled vision of hypersonic travel

NASA Technical Reports Server (NTRS)

Colladay, Raymond S.

1987-01-01

NASA has joined with the DOD to conduct the National Aerospace Plane (NASP) program, whose experimental test vehicle will be designated the X-30. NASP will study the X-30's takeoff from a runway under its own power, acceleration to high Mach number on the basis of airbreathing propulsion, emergence into LEO, reentry into the earth atmosphere, and descent to a powered horizontal landing. NASP will thereby generate technology base data for three distinct types of aircraft: upper-atmosphere hypersonic-cruise aircraft, LEO space transports, and military transatmospheric vehicles. The current concept-validation phase of NASP focuses on airbreathing propulsion, lightweight/high-strength heat-resistant materials, and computational fluid dynamics.

Global strike hypersonic weapons

NASA Astrophysics Data System (ADS)

Lewis, Mark J.

2017-11-01

Beginning in the 1940's, the United States has pursued the development of hypersonic technologies, enabling atmospheric flight in excess of five times the speed of sound. Hypersonic flight has application to a range of military and civilian applications, including commercial transport, space access, and various weapons and sensing platforms. A number of flight tests of hypersonic vehicles have been conducted by countries around the world, including the United States, Russia, and China, that could lead the way to future hypersonic global strike weapon systems. These weapons would be especially effective at penetrating conventional defenses, and could pose a significant risk to national security.

Modification of NASA Langley 8 foot high temperature tunnel to provide a unique national research facility for hypersonic air-breathing propulsion systems

NASA Technical Reports Server (NTRS)

Kelly, H. N.; Wieting, A. R.

1984-01-01

A planned modification of the NASA Langley 8-Foot High Temperature Tunnel to make it a unique national research facility for hypersonic air-breathing propulsion systems is described, and some of the ongoing supporting research for that modification is discussed. The modification involves: (1) the addition of an oxygen-enrichment system which will allow the methane-air combustion-heated test stream to simulate air for propulsion testing; and (2) supplemental nozzles to expand the test simulation capability from the current nominal Mach number to 7.0 include Mach numbers 3.0, 4.5, and 5.0. Detailed design of the modifications is currently underway and the modified facility is scheduled to be available for tests of large scale propulsion systems by mid 1988.

An Upgrade of the Imaging for Hypersonic Experimental Aeroheating Testing (IHEAT) Software

NASA Technical Reports Server (NTRS)

Mason, Michelle L.; Rufer, Shann J.

2015-01-01

The Imaging for Hypersonic Experimental Aeroheating Testing (IHEAT) code is used at NASA Langley Research Center to analyze global aeroheating data on wind tunnel models tested in the Langley Aerothermodynamics Laboratory. One-dimensional, semi-infinite heating data derived from IHEAT are used to design thermal protection systems to mitigate the risks due to the aeroheating loads on hypersonic vehicles, such as re-entry vehicles during descent and landing procedures. This code was originally written in the PV-WAVE programming language to analyze phosphor thermography data from the two-color, relativeintensity system developed at Langley. To increase the efficiency, functionality, and reliability of IHEAT, the code was migrated to MATLAB syntax and compiled as a stand-alone executable file labeled version 4.0. New features of IHEAT 4.0 include the options to batch process all of the data from a wind tunnel run, to map the two-dimensional heating distribution to a three-dimensional computer-aided design model of the vehicle to be viewed in Tecplot, and to extract data from a segmented line that follows an interesting feature in the data. Results from IHEAT 4.0 were compared on a pixel level to the output images from the legacy code to validate the program. The differences between the two codes were on the order of 10-5 to 10-7. IHEAT 4.0 replaces the PV-WAVE version as the production code for aeroheating experiments conducted in the hypersonic facilities at NASA Langley.

FAP-1 and NF-κB expressions in oral squamous cell carcinoma as potential markers for chemo-radio sensitivity and prognosis.

PubMed

Nariai, Y; Mishima, K; Yoshimura, Y; Sekine, J

2011-04-01

This study was designed to investigate the feasibility of using Fas-associated phosphatase-1 (FAP-1), nuclear factor kappa B (NF-κB) and p53 as markers for chemo-radio sensitivity in oral squamous cell carcinoma (OSCC). FAP-1 plays a role as an anti-apoptotic factor through Fas-dependent apoptosis after chemo-radiotherapy. NF-κB and p53 might be involved in modulation of FAP-1 expression. FAP-1, NF-κB and p53 expression were immunohistochemically examined using biopsy specimens in 50 OSCC patients treated with chemotherapy and/or radiotherapy. FAP-1 was expressed in 52%, NF-κB in 52% and p53 in 46% of patients. There was no significant difference in FAP-1, p53 or NF-κB expression according to the clinicopathological features. No correlation was found among FAP-1, p53 or NF-κB expression. FAP-1-positive cases showed a poorer survival rate than FAP-1-negative cases (P = 0.0409) and NF-κB-positive cases showed a poorer survival rate than NF-κB-negative cases (P = 0.0018). Multivariate analysis showed that FAP-1 expression, NF-κB expression, clinical stage and age were significant independent variables for survival (clinical stage: P = 0.0016; age: P = 0.0016; NF-κB: P = 0.0314; FAP-1: P = 0.0366). These results suggest that FAP-1 and NF-κB might play a role as chemo-radioresistant factor during chemo-radiotherapy, and FAP-1 and NF-κB expression in OSCC would be feasible markers for chemo-radio sensitivity and prognosis. Copyright © 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Results of heat transfer tests of an 0.0175-scale space shuttle vehicle model 22 OTS in the NASA-Ames 3.5-foot hypersonic wind tunnel (IH3), volume 4

NASA Technical Reports Server (NTRS)

Foster, T. F.; Lockman, W. K.

1975-01-01

Heat-transfer data for the 0.0175-scale Space Shuttle Vehicle 3 are presented. Interference heating effects were investigated by a model build-up technique of Orbiter alone, tank alone, second, and first stage configurations. The test program was conducted in the NASA-Ames 3.5-Foot Hypersonic Wind Tunnel at Mach 5.3 for nominal free-stream Reynolds number per foot values of 1.5 x 1,000,000 and 5.0 x 1,000,000.

Hypersonic missile propulsion system

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

Kazmar, R.R.

1998-11-01

Pratt and Whitney is developing the technology for hypersonic components and engines. A supersonic combustion ramjet (scramjet) database was developed using hydrogen fueled propulsion systems for space access vehicles and serves as a point of departure for the current development of hydrocarbon scramjets. The Air Force Hypersonic Technology (HyTech) Program has put programs in place to develop the technologies necessary to demonstrate the operability, performance and structural durability of an expendable, liquid hydrocarbon fueled scramjet system that operates from Mach 4 to 8. This program will culminate in a flight type engine test at representative flight conditions. The hypersonic technologymore » base that will be developed and demonstrated under HyTech will establish the foundation to enable hypersonic propulsion systems for a broad range of air vehicle applications from missiles to space access vehicles. A hypersonic missile flight demonstration is planned in the DARPA Affordable Rapid Response Missile Demonstrator (ARRMD) program in 2001.« less

Exhaust-gas measurements from NASAs HYMETS arc jet.

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

Miller, Paul Albert

Arc-jet wind tunnels produce conditions simulating high-altitude hypersonic flight such as occurs upon entry of space craft into planetary atmospheres. They have traditionally been used to study flight in Earth's atmosphere, which consists mostly of nitrogen and oxygen. NASA is presently using arc jets to study entry into Mars' atmosphere, which consists of carbon dioxide and nitrogen. In both cases, a wide variety of chemical reactions take place among the gas constituents and with test articles placed in the flow. In support of those studies, we made measurements using a residual gas analyzer (RGA) that sampled the exhaust stream ofmore » a NASA arc jet. The experiments were conducted at the HYMETS arc jet (Hypersonic Materials Environmental Test System) located at the NASA Langley Research Center, Hampton, VA. This report describes our RGA measurements, which are intended to be used for model validation in combination with similar measurements on other systems.« less

Experimental results for a hypersonic nozzle/afterbody flow field

NASA Technical Reports Server (NTRS)

Spaid, Frank W.; Keener, Earl R.; Hui, Frank C. L.

1995-01-01

This study was conducted to experimentally characterize the flow field created by the interaction of a single-expansion ramp-nozzle (SERN) flow with a hypersonic external stream. Data were obtained from a generic nozzle/afterbody model in the 3.5 Foot Hypersonic Wind Tunnel at the NASA Ames Research Center, in a cooperative experimental program involving Ames and McDonnell Douglas Aerospace. The model design and test planning were performed in close cooperation with members of the Ames computational fluid dynamics (CFD) team for the National Aerospace Plane (NASP) program. This paper presents experimental results consisting of oil-flow and shadow graph flow-visualization photographs, afterbody surface-pressure distributions, rake boundary-layer measurements, Preston-tube skin-friction measurements, and flow field surveys with five-hole and thermocouple probes. The probe data consist of impact pressure, flow direction, and total temperature profiles in the interaction flow field.

Selective Inhibitors of Fibroblast Activation Protein (FAP) with a (4-Quinolinoyl)-glycyl-2-cyanopyrrolidine Scaffold.

PubMed

Jansen, Koen; Heirbaut, Leen; Cheng, Jonathan D; Joossens, Jurgen; Ryabtsova, Oxana; Cos, Paul; Maes, Louis; Lambeir, Anne-Marie; De Meester, Ingrid; Augustyns, Koen; Van der Veken, Pieter

2013-05-09

Fibroblast activation protein (FAP) is a serine protease that is generally accepted to play an important role in tumor growth and other diseases involving tissue remodeling. Currently there are no FAP inhibitors with reported selectivity toward both the closely related dipeptidyl peptidases (DPPs) and prolyl oligopeptidase (PREP). We present the discovery of a new class of FAP inhibitors with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold. We have explored the effects of substituting the quinoline ring and varying the position of its sp(2) hybridized nitrogen atom. The most promising inhibitors combined low nanomolar FAP inhibition and high selectivity indices (>10(3)) with respect to both the DPPs and PREP. Preliminary experiments on a representative inhibitor demonstrate that plasma stability, kinetic solubility, and log D of this class of compounds can be expected to be satisfactory.

Coupled Radiation-Gasdynamic Solution Method for Hypersonic Shock Layers in Thermochemical Nonequilibrium

DTIC Science & Technology

2011-12-01

Dissertation, North Carolina State University, 1991. Heppenheimer , T. A ., ―Facing the Heat Barrier: a History of Hypersonics,‖ NASA SP- 2007-4232...States Government. This material is declared a work of the U.S. Government and is not subject to copyright protection in the United States...Lofthouse, PhD (Member) Date Accepted: ______________________________ M. U. THOMAS Date Dean, Graduate

UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins-TGF-β1-FAP-α.

PubMed

Wäster, Petra; Orfanidis, Kyriakos; Eriksson, Ida; Rosdahl, Inger; Seifert, Oliver; Öllinger, Karin

2017-08-08

Ultraviolet radiation (UVR) is the major risk factor for development of malignant melanoma. Fibroblast activation protein (FAP)-α is a serine protease expressed on the surface of activated fibroblasts, promoting tumour invasion through extracellular matrix (ECM) degradation. The signalling mechanism behind the upregulation of FAP-α is not yet completely revealed. Expression of FAP-α was analysed after UVR exposure in in vitro co-culture systems, gene expression arrays and artificial skin constructs. Cell migration and invasion was studied in relation to cathepsin activity and secretion of transforming growth factor (TGF)-β1. Fibroblast activation protein-α expression was induced by UVR in melanocytes of human skin. The FAP-α expression was regulated by UVR-induced release of TGF-β1 and cathepsin inhibitors prevented such secretion. In melanoma cell culture models and in a xenograft tumour model of zebrafish embryos, FAP-α mediated ECM degradation and facilitated tumour cell dissemination. Our results provide evidence for a sequential reaction axis from UVR via cathepsins, TGF-β1 and FAP-α expression, promoting cancer cell dissemination and melanoma metastatic spread.

Congenital hypertrophy of retinal pigment epithelium (CHRPE) in patients with familial adenomatous polyposis (FAP); a polyposis registry experience.

PubMed

Nusliha, Anwer; Dalpatadu, Ushantha; Amarasinghe, Binara; Chandrasinghe, Pramodh Chitral; Deen, Kemal Ismail

2014-10-18

Familial Adenomatous Polyposis (FAP) is an autosomal dominant condition giving rise to multiple adenomatous polyps in the colon which invariably become malignant by the fourth decade. Congenital hypertrophy of retinal pigment epithelium (CHRPE) is one of its extra intestinal manifestations early in childhood seen, present in 90% of FAP population and is easy to detect. Patients diagnosed with FAP and at risk first degree family members were screened for CHRPE using a slit lamp and indirect ophthalmoscopy. The retina of 17 diagnosed FAP patients and 13 individuals at risk were examined. The site and size of CHRPE lesions were documented. Thirteen (76%) of 17 FAP patients (male-10, female - 7, median age - 30 years; range 15-55 years) had CHRPE lesions; seven (54%) had bilateral CHRPE lesions and six (46%) had unilateral lesions. A single lesion was detected in 6 (46%) while 7 (54%) patients had multiple lesions. Of 13 at risk individuals (7- male, female-6 ; median age 34; range 16-52 years), one was positive for CHRPE and 12 were free of retinal lesions. The sensitivity of the presence of a CHRPE lesion in association with colonic polyps in FAP was 76%, specificity 92%, positive predictive value 93%, and negative predictive value 75%. This study found a high sensitivity and specificity for a CHRPE lesion to be associated with colonic polyps of FAP and hence a useful screening method in a burdened health-care system. The method is minimally invasive and simple and would be of particular value in screening children at risk for FAP.

Drug Combo Decreases Colorectal Polyps in People with FAP

Cancer.gov

In people with familial adenomatous polyposis, or FAP, a combination treatment of erlotinib (Tarceva) and sulindac (Aflodac) decreased the number of precancerous colorectal polyps, according to recently published clinical trial results.

Cancer in an unexpected site post pouch surgery for familial adenomatous polyposis (FAP).

PubMed

Alwahbi, Omar A; Abduljabbar, Alaa S; Anwer, Lucman A

2018-01-01

Familial Adenomatous Polyposis (FAP) is a hereditary condition characterized by multiple colorectal adenomatous polyps. FAP is the most common adenomatous polyposis syndrome. Restorative proctocolectomy is the most commonly performed surgical procedure performed for patients suffering from FAP with different options for anastomosis, namely ileorectal anastomosis (IRA) or ileal pouch anal anastomosis (IPAA). The occurrence of adenomas is a common finding during follow up and surveillance post surgery for these patients. Although there are a few cases of carcinoma that were namely at the anal transitional zone (ATZ), there are only a few cases of ileal pouch related adenocarcinoma reported. This work has been reported in line with the SCARE criteria (Agha et al., 2016) [1]. We report a case of a 34-year-old man diagnosed with FAP who underwent proctocolectomy with IPAA, and subsequently referred to our center, who, despite appropriate measures and surveillance, developed adenocarcinoma in the ileal pouch. Restorative proctocolectomy for Familial Adenomatous Polyposis (FAP) is the mainstay of treatment. There are different surgical options, each with its own set of advantages and disadvantages. The most favored option is proctocolectomy with ileal pouch anal anastomosis (IPAA) due to because it involves resection of the rectum. Despite these interventions, adenomas and/or carcinomas have been reported on follow up post surgery. Although the risk of developing adenomas or carcinomas in the ileal pouch post proctocolectomy with IPAA is low it should not be neglected as cancer occurrence or recurrence is unpredictable even with appropriate measures. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The X-43A hypersonic research aircraft and its modified Pegasus® booster rocket mounted to NASA's NB-52B carrier aircraft at the Dryden Flight Research Center, Edwards, California

NASA Image and Video Library

2001-03-13

The first of three X-43A hypersonic research aircraft and its modified Pegasus® booster rocket recently underwent combined systems testing while mounted to NASA's NB-52B carrier aircraft at the Dryden Flight Research Center, Edwards, California. The combined systems test was one of the last major milestones in the Hyper-X research program before the first X-43A flight. One of the major goals of the Hyper-X program is flight validation of airframe-integrated, air-breathing propulsion system, which so far have only been tested in ground facilities, such as wind tunnels. The X-43A flights will be the first actual flight tests of an aircraft powered by a revolutionary supersonic-combustion ramjet ("scramjet") engine capable of operating at hypersonic speeds above Mach 5 (five times the speed of sound). The X-43A design uses the underbody of the aircraft to form critical elements of the engine. The forebody shape helps compress the intake airflow, while the aft section acts as a nozzle to direct thrust. The 12-foot, unpiloted research vehicle was developed and built by MicroCraft Inc., Tullahoma, Tenn., under NASA contract. The booster, built by Orbital Sciences Corp., Dulles, Va., will accelerate the X-43A after the X-43A/booster "stack" is air-launched from NASA's venerable NB-52 mothership. The X-43A will separate from the rocket at a predetermined altitude and speed and fly a pre-programmed trajectory, conducting aerodynamic and propulsion experiments until it descends into the Pacific Ocean. Three research flights are planned, two at Mach 7 and one at Mach 10.

Synthesis and characterization of fluorapatite-titania (FAp-TiO 2) nanocomposite via mechanochemical process

NASA Astrophysics Data System (ADS)

Ebrahimi-Kahrizsangi, Reza; Nasiri-Tabrizi, Bahman; Chami, Akbar

2010-09-01

In this paper, synthesis of bionanocomposite of fluorapatite-titania (FAp-TiO 2) was studied by using one step mechanochemical process. Characterization of the products was accomplished by X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, energy dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) techniques. Based on XRD patterns and FT-IR spectroscopy, correlation between the structural features of the nanostructured FAp-TiO 2 and the process conditions was discussed. Variations in crystallite size, lattice strain, and volume fraction of grain boundary were investigated during milling and the following heat treatment. Crystallization of the nanocomposite occurred after thermal treatment at 650 °C. Morphological features of powders were influenced by the milling time. The resulting FAp-20 wt.%TiO 2 nanocomposite powder exhibited an average particle size of 15 nm after 20 h of milling. The results show that the one step mechanosynthesis technique is an effective route to prepare FAp-based nanocomposites with excellent morphological and structural features.

Review and assessment of turbulence models for hypersonic flows

NASA Astrophysics Data System (ADS)

Roy, Christopher J.; Blottner, Frederick G.

2006-10-01

Accurate aerodynamic prediction is critical for the design and optimization of hypersonic vehicles. Turbulence modeling remains a major source of uncertainty in the computational prediction of aerodynamic forces and heating for these systems. The first goal of this article is to update the previous comprehensive review of hypersonic shock/turbulent boundary-layer interaction experiments published in 1991 by Settles and Dodson (Hypersonic shock/boundary-layer interaction database. NASA CR 177577, 1991). In their review, Settles and Dodson developed a methodology for assessing experiments appropriate for turbulence model validation and critically surveyed the existing hypersonic experiments. We limit the scope of our current effort by considering only two-dimensional (2D)/axisymmetric flows in the hypersonic flow regime where calorically perfect gas models are appropriate. We extend the prior database of recommended hypersonic experiments (on four 2D and two 3D shock-interaction geometries) by adding three new geometries. The first two geometries, the flat plate/cylinder and the sharp cone, are canonical, zero-pressure gradient flows which are amenable to theory-based correlations, and these correlations are discussed in detail. The third geometry added is the 2D shock impinging on a turbulent flat plate boundary layer. The current 2D hypersonic database for shock-interaction flows thus consists of nine experiments on five different geometries. The second goal of this study is to review and assess the validation usage of various turbulence models on the existing experimental database. Here we limit the scope to one- and two-equation turbulence models where integration to the wall is used (i.e., we omit studies involving wall functions). A methodology for validating turbulence models is given, followed by an extensive evaluation of the turbulence models on the current hypersonic experimental database. A total of 18 one- and two-equation turbulence models are reviewed

Optimization of the cooling profile to achieve crack-free Yb:S-FAP crystals

NASA Astrophysics Data System (ADS)

Fang, H. S.; Qiu, S. R.; Zheng, L. L.; Schaffers, K. I.; Tassano, J. B.; Caird, J. A.; Zhang, H.

2008-08-01

Yb:S-FAP [Yb 3+:Sr 5(PO 4) 3F] crystals are an important gain medium for diode-pumped laser applications. Growth of 7.0 cm diameter Yb:S-FAP crystals utilizing the Czochralski (CZ) method from SrF 2-rich melts often encounters cracks during the post-growth cool-down stage. To suppress cracking during cool-down, a numerical simulation of the growth system was used to understand the correlation between the furnace power during cool-down and the radial temperature differences within the crystal. The critical radial temperature difference, above which the crystal cracks, has been determined by benchmarking the simulation results against experimental observations. Based on this comparison, an optimal three-stage ramp-down profile was implemented, which produced high-quality, crack-free Yb:S-FAP crystals.

MDCT distinguishing features of focal aortic projections (FAP) in acute clinical settings.

PubMed

Valente, Tullio; Rossi, Giovanni; Lassandro, Francesco; Rea, Gaetano; Marino, Maurizio; Urciuolo, Salvatore; Tortora, Giovanni; Muto, Maurizio

2015-01-01

Focal aortic projections (FAP) are protrusion images of the contrast medium (focal contour irregularity, breaks in the intimal contour, outward lumen bulging or localized blood-filled outpouching) projecting beyond the aortic lumen in the aortic wall and are commonly seen on multidetector computed tomography (MDCT) scans of the chest and abdomen. FAP include several common and uncommon etiologies, which can be demonstrated both in the native aorta, mainly in acute aortic syndromes, and in the post-surgical aorta or after endovascular therapy. They are also found in some types of post-traumatic injuries and in impending rupture of the aneurysms. The expanding, routine use of millimetric or submillimetric collimation of current state-of-the-art MDCT scanners (16 rows and higher) all the time allows the identification and characterization of these small ulcer-like lesions or irregularities in the entire aorta, as either an incidental or expected finding, and provides detailed three-dimensional pictures of these pathologic findings. In this pictorial review, we illustrate the possible significance of FAP and the discriminating MDCT features that help to distinguish among different types of aortic protrusions and their possible evolution. Awareness of some related and distinctive radiologic features in FAP may improve our understanding of aortic diseases, provide further insight into the pathophysiology and natural history, and guide the appropriate management of these lesions.

Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases.

PubMed

Tansi, Felista L; Rüger, Ronny; Böhm, Claudia; Kontermann, Roland E; Teichgraeber, Ulf K; Fahr, Alfred; Hilger, Ingrid

2016-05-01

Despite intensive research and medical advances met, metastatic disease remains the most common cause of death in cancer patients. This results from late diagnosis, poor therapeutic response and undetected micrometastases and tumor margins during surgery. One approach to overcome these challenges involves fluorescence imaging, which exploits the properties of fluorescent probes for diagnostic detection of molecular structures at the onset of transformation and for intraoperative detection of metastases and tumor margins in real time. Considering these benefits, many contrast agents suitable for fluorescence imaging have been reported. However, most reports only demonstrate the detection of primary tumors and not the detection of metastases or their application in models of image-guided surgery. In this work, we demonstrate the influence of fibroblast activation protein (FAP) on the metastatic potential of fibrosarcoma cells and elucidate the efficacy of activatable FAP-targeting immunoliposomes (FAP-IL) for image-guided detection of the spontaneous metastases in mice models. Furthermore, we characterized the biodistribution and cellular localization of the liposomal fluorescent components in mice organs and traced their excretion over time in urine and feces. Taken together, activatable FAP-IL enhances intraoperative imaging of metastases. Their high accumulation in metastases, subsequent localization in the bile canaliculi and liver kupffer cells and suitable excretion in feces substantiates their potency as contrast agents for intraoperative imaging. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

CFD for hypersonic airbreathing aircraft

NASA Technical Reports Server (NTRS)

Kumar, Ajay

1989-01-01

A general discussion is given on the use of advanced computational fluid dynamics (CFD) in analyzing the hypersonic flow field around an airbreathing aircraft. Unique features of the hypersonic flow physics are presented and an assessment is given of the current algorithms in terms of their capability to model hypersonic flows. Several examples of advanced CFD applications are then presented.

Features of the Upgraded Imaging for Hypersonic Experimental Aeroheating Testing (IHEAT) Software

NASA Technical Reports Server (NTRS)

Mason, Michelle L.; Rufer, Shann J.

2016-01-01

The Imaging for Hypersonic Experimental Aeroheating Testing (IHEAT) software is used at the NASA Langley Research Center to analyze global aeroheating data on wind tunnel models tested in the Langley Aerothermodynamics Laboratory. One-dimensional, semi-infinite heating data derived from IHEAT are used in the design of thermal protection systems for hypersonic vehicles that are exposed to severe aeroheating loads, such as reentry vehicles during descent and landing procedures. This software program originally was written in the PV-WAVE(Registered Trademark) programming language to analyze phosphor thermography data from the two-color, relative-intensity system developed at Langley. To increase the efficiency, functionality, and reliability of IHEAT, the program was migrated to MATLAB(Registered Trademark) syntax and compiled as a stand-alone executable file labeled version 4.0. New features of IHEAT 4.0 include the options to perform diagnostic checks of the accuracy of the acquired data during a wind tunnel test, to extract data along a specified multi-segment line following a feature such as a leading edge or a streamline, and to batch process all of the temporal frame data from a wind tunnel run. Results from IHEAT 4.0 were compared on a pixel level to the output images from the legacy software to validate the program. The absolute differences between the heat transfer data output from the two programs were on the order of 10(exp -5) to 10(exp -7). IHEAT 4.0 replaces the PV-WAVE(Registered Trademark) version as the production software for aeroheating experiments conducted in the hypersonic facilities at NASA Langley.

Pharmacokinetics and Toxicology of a Fibroblast Activation Protein (FAP)-activated Prodrug in Murine Xenograft Models of Human Cancer

PubMed Central

Brennen, W. Nathaniel; Rosen, D. Marc; Chaux, Alcides; Netto, George J.; Isaacs, John T.; Denmeade, Samuel R.

2014-01-01

Background As carcinoma progresses, the stroma undergoes a variety of phenotypic changes, including the presence of carcinoma-associated fibroblasts (CAFs) that express fibroblast activation protein (FAP). FAP is a post-prolyl endopeptidase whose expression in a healthy adult is largely restricted to the cancer-associated stroma. FAP-targeted prodrugs with a 100-fold greater therapeutic window over the parent compound were previously generated. Methods Prodrugs and non-cleavable controls were incubated in the presence of FAP. Plasma and tumor half-lives (t1/2) of the full-length and active forms of the prodrugs were determined using LCMS. Biodistribution studies of prodrug activation were performed. Histopathological analysis of tissues from treated animals were compared to vehicle-treated controls. Toxicity and efficacy studies were performed in human breast (MDA-MB-231 and MCF-7) and prostate (LNCaP) cancer xenografts models. Results These FAP-activated prodrugs have a significantly slower clearance from tumor tissue than the circulation (~12 vs. ~4.5 hrs). Micromolar concentrations of active drug persist in the tumor. Active drug is detected in non-target tissues; however, histopathologic evaluation reveals no evidence of drug-induced toxicity. A FAP-activated prodrug (ERGETGP-S12ADT) inhibits tumor growth in multiple human breast and prostate cancer xenograft models. The anti-tumor effect is comparable to that observed with docetaxel, but results in significantly less toxicity. Conclusion FAP-activated prodrugs are a viable strategy for the management of prostate and other cancers. These prodrugs exhibit less toxicity than a commonly used chemotherapeutic agent. Further refinement of the FAP cleavage site for greater specificity may reduce prodrug activation in non-target tissues and enhance clinical benefit. PMID:25053236

Pharmacokinetics and toxicology of a fibroblast activation protein (FAP)-activated prodrug in murine xenograft models of human cancer.

PubMed

Brennen, W Nathaniel; Rosen, D Marc; Chaux, Alcides; Netto, George J; Isaacs, John T; Denmeade, Samuel R

2014-09-01

As carcinoma progresses, the stroma undergoes a variety of phenotypic changes, including the presence of carcinoma-associated fibroblasts (CAFs) that express fibroblast activation protein (FAP). FAP is a post-prolyl endopeptidase whose expression in a healthy adult is largely restricted to the cancer-associated stroma. FAP-targeted prodrugs with a 100-fold greater therapeutic window over the parent compound were previously generated. Prodrugs and non-cleavable controls were incubated in the presence of FAP. Plasma and tumor half-lives (t1/2) of the full-length and active forms of the prodrugs were determined using LCMS. Biodistribution studies of prodrug activation were performed. Histopathological analysis of tissues from treated animals were compared to vehicle-treated controls. Toxicity and efficacy studies were performed in human breast (MDA-MB-231 and MCF-7) and prostate (LNCaP) cancer xenografts models. These FAP-activated prodrugs have a significantly slower clearance from tumor tissue than the circulation (∼12 vs. ∼4.5 hr). Micromolar concentrations of active drug persist in the tumor. Active drug is detected in non-target tissues; however, histopathologic evaluation reveals no evidence of drug-induced toxicity. A FAP-activated prodrug (ERGETGP-S12ADT) inhibits tumor growth in multiple human breast and prostate cancer xenograft models. The anti-tumor effect is comparable to that observed with docetaxel, but results in significantly less toxicity. FAP-activated prodrugs are a viable strategy for the management of prostate and other cancers. These prodrugs exhibit less toxicity than a commonly used chemotherapeutic agent. Further refinement of the FAP cleavage site for greater specificity may reduce prodrug activation in non-target tissues and enhance clinical benefit. © 2014 Wiley Periodicals, Inc.

Purification, crystallization and characterization of the Pseudomonas outer membrane protein FapF, a functional amyloid transporter.

PubMed

Rouse, Sarah L; Hawthorne, Wlliam J; Lambert, Sebastian; Morgan, Marc L; Hare, Stephen A; Matthews, Stephen

2016-12-01

Bacteria often produce extracellular amyloid fibres via a multi-component secretion system. Aggregation-prone, unstructured subunits cross the periplasm and are secreted through the outer membrane, after which they self-assemble. Here, significant progress is presented towards solving the high-resolution crystal structure of the novel amyloid transporter FapF from Pseudomonas, which facilitates the secretion of the amyloid-forming polypeptide FapC across the bacterial outer membrane. This represents the first step towards obtaining structural insight into the products of the Pseudomonas fap operon. Initial attempts at crystallizing full-length and N-terminally truncated constructs by refolding techniques were not successful; however, after preparing FapF 106-430 from the membrane fraction, reproducible crystals were obtained using the sitting-drop method of vapour diffusion. Diffraction data have been processed to 2.5 Å resolution. These crystals belonged to the monoclinic space group C121, with unit-cell parameters a = 143.4, b = 124.6, c = 80.4 Å, α = γ = 90, β = 96.32° and three monomers in the asymmetric unit. It was found that the switch to complete detergent exchange into C8E4 was crucial for forming well diffracting crystals, and it is suggested that this combined with limited proteolysis is a potentially useful protocol for membrane β-barrel protein crystallography. The three-dimensional structure of FapF will provide invaluable information on the mechanistic differences of biogenesis between the curli and Fap functional amyloid systems.

Pegasus hypersonic flight research

NASA Technical Reports Server (NTRS)

Curry, Robert E.; Meyer, Robert R., Jr.; Budd, Gerald D.

1992-01-01

Hypersonic aeronautics research using the Pegasus air-launched space booster is described. Two areas are discussed in the paper: previously obtained results from Pegasus flights 1 and 2, and plans for future programs. Proposed future research includes boundary-layer transition studies on the airplane-like first stage and also use of the complete Pegasus launch system to boost a research vehicle to hypersonic speeds. Pegasus flight 1 and 2 measurements were used to evaluate the results of several analytical aerodynamic design tools applied during the development of the vehicle as well as to develop hypersonic flight-test techniques. These data indicated that the aerodynamic design approach for Pegasus was adequate and showed that acceptable margins were available. Additionally, the correlations provide insight into the capabilities of these analytical tools for more complex vehicles in which design margins may be more stringent. Near-term plans to conduct hypersonic boundary-layer transition studies are discussed. These plans involve the use of a smooth metallic glove at about the mid-span of the wing. Longer-term opportunities are proposed which identify advantages of the Pegasus launch system to boost large-scale research vehicles to the real-gas hypersonic flight regime.

Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma

PubMed Central

Wang, H; Wu, Q; Liu, Z; Luo, X; Fan, Y; Liu, Y; Zhang, Y; Hua, S; Fu, Q; Zhao, M; Chen, Y; Fang, W; Lv, X

2014-01-01

It is largely recognized that fibroblast activation protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) of many human carcinomas. Furthermore, FAP was recently also reported to be expressed in carcinoma cells of the breast, stomach, pancreatic ductal adenocarcinoma, colorectum, and uterine cervix. The carcinoma cell expression pattern of FAP has been described in several types of cancers, but the role of FAP in oral squamous cell carcinoma (OSCC) is unknown. The role of endogenous FAP in epithelium-derived tumors and molecular mechanisms has also not been reported. In this study, FAP was found to be expressed in carcinoma cells of OSCC and was upregulated in OSCC tissue samples compared with benign tissue samples using immunohistochemistry. In addition, its expression level was closely correlated with overall survival of patients with OSCC. Silencing FAP inhibited the growth and metastasis of OSCC cells in vitro and in vivo. Mechanistically, knockdown of FAP inactivated PTEN/PI3K/AKT and Ras-ERK and its downstream signaling regulating proliferation, migration, and invasion in OSCC cells, as the inhibitory effects of FAP on the proliferation and metastasis could be rescued by PTEN silencing. Our study suggests that FAP acts as an oncogene and may be a potential therapeutic target for patients with OSCC. PMID:24722280

Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma.

PubMed

Wang, H; Wu, Q; Liu, Z; Luo, X; Fan, Y; Liu, Y; Zhang, Y; Hua, S; Fu, Q; Zhao, M; Chen, Y; Fang, W; Lv, X

2014-04-10

It is largely recognized that fibroblast activation protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) of many human carcinomas. Furthermore, FAP was recently also reported to be expressed in carcinoma cells of the breast, stomach, pancreatic ductal adenocarcinoma, colorectum, and uterine cervix. The carcinoma cell expression pattern of FAP has been described in several types of cancers, but the role of FAP in oral squamous cell carcinoma (OSCC) is unknown. The role of endogenous FAP in epithelium-derived tumors and molecular mechanisms has also not been reported. In this study, FAP was found to be expressed in carcinoma cells of OSCC and was upregulated in OSCC tissue samples compared with benign tissue samples using immunohistochemistry. In addition, its expression level was closely correlated with overall survival of patients with OSCC. Silencing FAP inhibited the growth and metastasis of OSCC cells in vitro and in vivo. Mechanistically, knockdown of FAP inactivated PTEN/PI3K/AKT and Ras-ERK and its downstream signaling regulating proliferation, migration, and invasion in OSCC cells, as the inhibitory effects of FAP on the proliferation and metastasis could be rescued by PTEN silencing. Our study suggests that FAP acts as an oncogene and may be a potential therapeutic target for patients with OSCC.

Hypersonic Navier Stokes Comparisons to Orbiter Flight Data

NASA Technical Reports Server (NTRS)

Campbell, Charles H.; Nompelis, Ioannis; Candler, Graham; Barnhart, Michael; Yoon, Seokkwan

2009-01-01

Hypersonic chemical nonequilibrium simulations of low earth orbit entry flow fields are becoming increasingly commonplace as software and computational capabilities become more capable. However, development of robust and accurate software to model these environments will always encounter a significant barrier in developing a suite of high quality calibration cases. The US3D hypersonic nonequilibrium Navier Stokes analysis capability has been favorably compared to a number of wind tunnel test cases. Extension of the calibration basis for this software to Orbiter flight conditions will provide an incremental increase in confidence. As part of the Orbiter Boundary Layer Transition Flight Experiment and the Hypersonic Thermodynamic Infrared Measurements project, NASA is performing entry flight testing on the Orbiter to provide valuable aerothermodynamic heating data. An increase in interest related to orbiter entry environments is resulting from this activity. With the advent of this new data, comparisons of the US3D software to the new flight testing data is warranted. This paper will provide information regarding the framework of analyses that will be applied with the US3D analysis tool. In addition, comparisons will be made to entry flight testing data provided by the Orbiter BLT Flight Experiment and HYTHIRM projects. If data from digital scans of the Orbiter windward surface become available, simulations will also be performed to characterize the difference in surface heating between the CAD reference OML and the digitized surface provided by the surface scans.

FAP Associated Papillary Thyroid Carcinoma: A Peculiar Subtype of Familial Nonmedullary Thyroid Cancer.

PubMed

Cetta, Francesco

2015-01-01

Familial Nonmedullary Thyroid Carcinoma (FNMTC) makes up to 5-10% of all thyroid cancers, also including those FNMTC occurring as a minor component of familial cancer syndromes, such as Familial Adenomatous Polyposis (FAP). We give evidence that this extracolonic manifestation of FAP is determined by the same germline mutation of the APC gene responsible for colonic polyps and cancer but also shows some unusual features (F : M ratio = 80 : 1, absence of LOH for APC in the thyroid tumoral tissue, and indolent biological behaviour, despite frequent multicentricity and lymph nodal involvement), suggesting that the APC gene confers only a generic susceptibility to thyroid cancer, but perhaps other factors, namely, modifier genes, sex-related factors, or environmental factors, are also required for its phenotypic expression. This great variability is against the possibility of classifying all FNMTC as a single entity, not only with a unique or prevalent causative genetic factor, but also with a unique or common biological behavior and a commonly dismal prognosis. A new paradigm is also suggested that could be useful (1) for a proper classification of FAP associated PTC within the larger group of FNMTC and (2) for making inferences to sporadic carcinogenesis, based on the lesson from FAP.

Wind-Tunnel Balance Characterization for Hypersonic Research Applications

NASA Technical Reports Server (NTRS)

Lynn, Keith C.; Commo, Sean A.; Parker, Peter A.

2012-01-01

Wind-tunnel research was recently conducted at the NASA Langley Research Center s 31-Inch Mach 10 Hypersonic Facility in support of the Mars Science Laboratory s aerodynamic program. Researchers were interested in understanding the interaction between the freestream flow and the reaction control system onboard the entry vehicle. A five-component balance, designed for hypersonic testing with pressurized flow-through capability, was used. In addition to the aerodynamic forces, the balance was exposed to both thermal gradients and varying internal cavity pressures. Historically, the effect of these environmental conditions on the response of the balance have not been fully characterized due to the limitations in the calibration facilities. Through statistical design of experiments, thermal and pressure effects were strategically and efficiently integrated into the calibration of the balance. As a result of this new approach, researchers were able to use the balance continuously throughout the wide range of temperatures and pressures and obtain real-time results. Although this work focused on a specific application, the methodology shown can be applied more generally to any force measurement system calibration.

Airframe Research and Technology for Hypersonic Airbreathing Vehicles

NASA Technical Reports Server (NTRS)

Glass, David E.; Merski, N. Ronald; Glass, Christopher E.

2002-01-01

The Hypersonics Investment Area (HIA) within NASA's Advanced Space Transportation Program (ASTP) has the responsibility to develop hypersonic airbreathing vehicles for access to space. The Airframe Research and Technology (AR and T) Project, as one of six projects in the HIA, will push the state-of-the-art in airframe and vehicle systems for low-cost, reliable, and safe space transportation. The individual technologies within the project are focused on advanced, breakthrough technologies in airframe and vehicle systems and cross-cutting activities that are the basis for improvements in these disciplines. Both low and medium technology readiness level (TRL) activities are being pursued. The key technical areas that will be addressed by the project include analysis and design tools, integrated vehicle health management (IVHM), composite (polymer, metal, and ceramic matrix) materials development, thermal/structural wall concepts, thermal protection systems, seals, leading edges, aerothermodynamics, and airframe/propulsion flowpath technology. Each of the technical areas or sub-projects within the Airframe R and T Project is described in this paper.

Optimization of the cooling profile to achieve crack-free Yb:S-FAP crystals

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

Fang, H; Qiu, S; Kheng, L

Yb:S-FAP [Yb{sup 3+}:Sr{sub 5}(PO{sub 4}){sub 3}F] crystals are an important gain medium for diode-pumped laser applications. Growth of 7.0 cm diameter Yb:S-FAP crystals utilizing the Czochralski (CZ) method from SrF{sub 2}-rich melts often encounter cracks during the post growth cool down stage. To suppress cracking during cool down, a numerical simulation of the growth system was used to understand the correlation between the furnace power during cool down and the radial temperature differences within the crystal. The critical radial temperature difference, above which the crystal cracks, has been determined by benchmarking the simulation results against experimental observations. Based on thismore » comparison, an optimal three-stage ramp-down profile was implemented and produced high quality, crack-free Yb:S-FAP crystals.« less

Configuration development study of the X-24C hypersonic research airplane, phase 3

NASA Technical Reports Server (NTRS)

Combs, H. G.

1977-01-01

The conclusion evolved from the three phased study on the configuration development of the X-24C Hypersonic Research Airplane makes it evident that it is practical to design and build the high performance National Hypersonic Flight Research Facility airplane with today's state of the art within the cost and operational constraints established by NASA. The vehicle launched at 31.75 Mg from the B-52 can cruise for 40 seconds at Mach 6.78 on scramjets. Without scramjets it can approach Mach 8 with a 453.6 Kg payload or do 70 seconds of cruise at Mach 6 with a 2.27 Mg payload. Reduction in cost is possible with a vehicle scaled to a lesser mass and capability.

Gastrointestinal permeability (GIPerm) is increased in family members of children with functional abdominal pain (FAP) and irritable bowel syndrome (IBS)

USDA-ARS?s Scientific Manuscript database

Increased GIPerm has been described in children with FAP/IBS and adults with IBS. We sought to determine if baseline GIPerm is increased and if ibuprofen induces a greater increase in GIPerm in parents and siblings of children with FAP/IBS vs. control families without children with FAP/IBS. Site spe...

The X-43A hypersonic research aircraft and its modified Pegasus booster rocket recently underwent c

NASA Technical Reports Server (NTRS)

2001-01-01

The first of three X-43A hypersonic research aircraft and its modified Pegasus booster rocket recently underwent combined systems testing while mounted to NASA's NB-52B carrier aircraft at the Dryden Flight Research Center, Edwards, Calif. The combined systems test was one of the last major milestones in the Hyper-X research program before the first X-43A flight. The X-43A flights will be the first actual flight tests of an aircraft powered by a revolutionary supersonic-combustion ramjet ('scramjet') engine capable of operating at hypersonic speeds (above Mach 5, or five times the speed of sound). The 12-foot, unpiloted research vehicle was developed and built by MicroCraft Inc., Tullahoma, Tenn., under NASA contract. The booster was built by Orbital Sciences Corp., Dulles, Va.,After being air-launched from NASA's venerable NB-52 mothership, the booster will accelerate the X-43A to test speed and altitude. The X-43A will then separate from the rocket and fly a pre-programmed trajectory, conducting aerodynamic and propulsion experiments until it descends into the Pacific Ocean. Three research flights are planned, two at Mach 7 and one at Mach 10.

Modeling, Measurements, and Fundamental Database Development for Nonequilibrium Hypersonic Aerothermodynamics

NASA Technical Reports Server (NTRS)

Bose, Deepak

2012-01-01

The design of entry vehicles requires predictions of aerothermal environment during the hypersonic phase of their flight trajectories. These predictions are made using computational fluid dynamics (CFD) codes that often rely on physics and chemistry models of nonequilibrium processes. The primary processes of interest are gas phase chemistry, internal energy relaxation, electronic excitation, nonequilibrium emission and absorption of radiation, and gas-surface interaction leading to surface recession and catalytic recombination. NASAs Hypersonics Project is advancing the state-of-the-art in modeling of nonequilibrium phenomena by making detailed spectroscopic measurements in shock tube and arcjets, using ab-initio quantum mechanical techniques develop fundamental chemistry and spectroscopic databases, making fundamental measurements of finite-rate gas surface interactions, implementing of detailed mechanisms in the state-of-the-art CFD codes, The development of new models is based on validation with relevant experiments. We will present the latest developments and a roadmap for the technical areas mentioned above

Air Breathing Propulsion Controls and Diagnostics Research at NASA Glenn Under NASA Aeronautics Research Mission Programs

NASA Technical Reports Server (NTRS)

Garg, Sanjay

2014-01-01

The Intelligent Control and Autonomy Branch (ICA) at NASA (National Aeronautics and Space Administration) Glenn Research Center (GRC) in Cleveland, Ohio, is leading and participating in various projects in partnership with other organizations within GRC and across NASA, the U.S. aerospace industry, and academia to develop advanced controls and health management technologies that will help meet the goals of the NASA Aeronautics Research Mission Directorate (ARMD) Programs. These efforts are primarily under the various projects under the Fundamental Aeronautics Program (FAP) and the Aviation Safety Program (ASP). The ICA Branch is focused on advancing the state-of-the-art of aero-engine control and diagnostics technologies to help improve aviation safety, increase efficiency, and enable operation with reduced emissions. This paper describes the various ICA research efforts under the NASA Aeronautics Research Mission Programs with a summary of motivation, background, technical approach, and recent accomplishments for each of the research tasks.

Aerothermodynamics research at NASA Ames Research Center

NASA Technical Reports Server (NTRS)

Deiwert, George S.

1987-01-01

Research activity in the aerothermodynamics branch at the NASA Ames Research Center is reviewed. Advanced concepts and mission studies relating to the next generation aerospace transportation systems are summarized and directions for continued research identified. Theoretical and computational studies directed at determining flow fields and radiative and convective heating loads in real gases are described. Included are Navier-Stokes codes for equilibrium and thermochemical nonequilibrium air. Experimental studies in the 3.5-ft hypersonic wind tunnel, the ballistic ranges, and the electric arc driven shock tube are described. Tested configurations include generic hypersonic aerospace plane configurations, aeroassisted orbital transfer vehicle shapes and Galileo probe models.

FAP-α (Fibroblast activation protein-α) is involved in the control of human breast cancer cell line growth and motility via the FAK pathway

PubMed Central

2014-01-01

Background Fibroblast Activation Protein alpha (FAP-α) or seprase is an integral membrane serine peptidase. Previous work has not satisfactorily explained both the suppression and promotion effects that have been observed in cancer. The purpose of this work was to investigate the role of FAP-α in human breast cancer. Expression of FAP-α was characterized in primary tumour samples and in cell lines, along with the effects of FAP-α expression on in vitro growth, invasion, attachment and migration. Furthermore the potential interaction of FAP-α with other signalling pathways was investigated. Results FAP-α was significantly increased in patients with poor outcome and survival. In vitro results showed that breast cancer cells over expressing FAP-α had increased growth ability and impaired migratory ability. The growth of MDA-MB-231 cells and the adhesion and invasion ability of both MCF-7 cells and MDA-MB-231 cells were not dramatically influenced by FAP-α expression. Over-expression of FAP-α resulted in a reduction of phosphorylated focal adhesion kinase (FAK) level in both cells cultured in normal media and serum-free media. An inhibitor to FAK restored the reduced motility ability of both MCF-7exp cells and MDA-MB-231exp cells and prevented the change in phosphorylated FAK levels. However, inhibitors to PI3K, ERK, PLCϒ, NWASP, ARP2/3, and ROCK had no influence this. Conclusions FAP-α in significantly associated with poor outcome in patients with breast cancer. In vitro, FAP-α promotes proliferation and inhibits migration of breast cancer cells, potentially by regulating the FAK pathway. These results suggest FAP-α could be a target for future therapies. PMID:24885257

FAP-α (Fibroblast activation protein-α) is involved in the control of human breast cancer cell line growth and motility via the FAK pathway.

PubMed

Jia, Jun; Martin, Tracey Amanda; Ye, Lin; Jiang, Wen Guo

2014-05-21

Fibroblast Activation Protein alpha (FAP-α) or seprase is an integral membrane serine peptidase. Previous work has not satisfactorily explained both the suppression and promotion effects that have been observed in cancer. The purpose of this work was to investigate the role of FAP-α in human breast cancer. Expression of FAP-α was characterized in primary tumour samples and in cell lines, along with the effects of FAP-α expression on in vitro growth, invasion, attachment and migration. Furthermore the potential interaction of FAP-α with other signalling pathways was investigated. FAP-α was significantly increased in patients with poor outcome and survival. In vitro results showed that breast cancer cells over expressing FAP-α had increased growth ability and impaired migratory ability. The growth of MDA-MB-231 cells and the adhesion and invasion ability of both MCF-7 cells and MDA-MB-231 cells were not dramatically influenced by FAP-α expression. Over-expression of FAP-α resulted in a reduction of phosphorylated focal adhesion kinase (FAK) level in both cells cultured in normal media and serum-free media. An inhibitor to FAK restored the reduced motility ability of both MCF-7exp cells and MDA-MB-231exp cells and prevented the change in phosphorylated FAK levels. However, inhibitors to PI3K, ERK, PLCΥ, NWASP, ARP2/3, and ROCK had no influence this. FAP-α in significantly associated with poor outcome in patients with breast cancer. In vitro, FAP-α promotes proliferation and inhibits migration of breast cancer cells, potentially by regulating the FAK pathway. These results suggest FAP-α could be a target for future therapies.

Alteration of the Tumor Stroma Using a Consensus DNA Vaccine Targeting Fibroblast Activation Protein (FAP) Synergizes with Antitumor Vaccine Therapy in Mice.

PubMed

Duperret, Elizabeth K; Trautz, Aspen; Ammons, Dylan; Perales-Puchalt, Alfredo; Wise, Megan C; Yan, Jian; Reed, Charles; Weiner, David B

2018-03-01

Purpose: Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts and is an interesting target for cancer immune therapy, with prior studies indicating a potential to affect the tumor stroma. Our aim was to extend this earlier work through the development of a novel FAP immunogen with improved capacity to break tolerance for use in combination with tumor antigen vaccines. Experimental Design: We used a synthetic consensus (SynCon) sequence approach to provide MHC class II help to support breaking of tolerance. We evaluated immune responses and antitumor activity of this novel FAP vaccine in preclinical studies, and correlated these findings to patient data. Results: This SynCon FAP DNA vaccine was capable of breaking tolerance and inducing both CD8 + and CD4 + immune responses. In genetically diverse, outbred mice, the SynCon FAP DNA vaccine was superior at breaking tolerance compared with a native mouse FAP immunogen. In several tumor models, the SynCon FAP DNA vaccine synergized with other tumor antigen-specific DNA vaccines to enhance antitumor immunity. Evaluation of the tumor microenvironment showed increased CD8 + T-cell infiltration and a decreased macrophage infiltration driven by FAP immunization. We extended this to patient data from The Cancer Genome Atlas, where we find high FAP expression correlates with high macrophage and low CD8 + T-cell infiltration. Conclusions: These results suggest that immune therapy targeting tumor antigens in combination with a microconsensus FAP vaccine provides two-fisted punch-inducing responses that target both the tumor microenvironment and tumor cells directly. Clin Cancer Res; 24(5); 1190-201. ©2018 AACR . ©2018 American Association for Cancer Research.

Center of Excellence for Hypersonics Research

DTIC Science & Technology

2012-01-25

detailed simulations of actual combustor configurations, and ultimately for the optimization of hypersonic air - breathing propulsion system flow paths... vehicle development programs. The Center engaged leading experts in experimental and computational analysis of hypersonic flows to provide research...advanced hypersonic vehicles and space access systems will require significant advances in the design methods and ground testing techniques to ensure

Experimental and finite element investigation of the buckling characteristics of a beaded skin panel for a hypersonic aircraft. Ph.D. Thesis. Final Report

NASA Technical Reports Server (NTRS)

Siegel, W. H.

1978-01-01

As part of NASA's continuing research into hypersonics and 85 square foot hypersonic wing test section of a proposed hypersonic research airplane was laboratory tested. The project reported on in this paper has carried the hypersonic wing test structure project one step further by testing a single beaded panel to failure. The primary interest was focused upon the buckling characteristics of the panel under pure compression with boundary conditions similar to those found in a wing mounted condition. Three primary phases of analysis are included in the report. These phases include: experimental testing of the beaded panel to failure; finite element structural analysis of the beaded panel with the computer program NASTRAN; a summary of the semiclassical buckling equations for the beaded panel under purely compressive loads. Comparisons between each of the analysis methods are also included.

Hypersonic transport technology

NASA Technical Reports Server (NTRS)

Kirkham, F. S.; Hunt, J. L.

1977-01-01

The possibility of developing a hypersonic commercial transport (HST) for the early 21st century is explored in terms of potential performance characteristics and recent advances in propulsion and structures technology. Range-gross weight characteristics indicate that a 200 passenger, Mach 6 aircraft with a range of 9200 km (5000 n.mi.) would have a gross take-off weight not too different from that of current wide-body subsonic transports. The low cruise sonic boom overpressures generated by the HST opens the possibility of supersonic overland flight which, if permitted, would greatly increase the attractiveness of this type of aircraft. Recent advances in hypersonic propulsion systems and long-lived hypersonic aircraft structure are also discussed. The airframe-integrated scramjet and the actively-cooled airframe structure are identified as the most promising candidates for the HST and current approaches are described in some detail.

Retrospective study of a TTR FAP cohort to modify NIS+7 for therapeutic trials.

PubMed

Suanprasert, N; Berk, J L; Benson, M D; Dyck, P J B; Klein, C J; Gollob, J A; Bettencourt, B R; Karsten, V; Dyck, P J

2014-09-15

Protein stabilization and oligonucleotide therapies are being tested in transthyretin amyloid polyneuropathy (TTR FAP) trials. From retrospective analysis of 97 untreated TTR FAP patients, we test the adequacy of Neuropathy Impairment Score+7 tests (NIS+7) and modifications to comprehensively score impairments for use in such therapeutic trials. Our data confirms that TTR FAP usually is a sensorimotor polyneuropathy with autonomic features which usually is symmetric, length dependent, lower limb predominant and progressive. NIS+7 adequately assesses weakness and muscle stretch reflexes without ceiling effects but not sensation loss, autonomic dysfunction or nerve conduction abnormalities. Three modifications of NIS+7 are suggested: 1) use of Smart Somatotopic Quantitative Sensation Testing (S ST QSTing); 2) choice of new autonomic assessments, e.g., sudomotor testing of distributed anatomical sites; and 3) use of only compound muscle action potential amplitudes (of ulnar, peroneal and tibial nerves) and sensory nerve action potentials of ulnar and sural nerve - than the previously recommended attributes suggested for the sensitive detection of diabetic sensorimotor polyneuropathy. These modifications of NIS+7 if used in therapeutic trials should improve characterization and quantification of sensation and autonomic impairment in TTR FAP and provide better nerve conduction tests. Copyright © 2014 Elsevier B.V. All rights reserved.

NASA aeronautics research and technology

NASA Technical Reports Server (NTRS)

1986-01-01

The technical accomplishments and research highlights of 1986 are featured, along with information on possible areas of future research. These include hypersonic, supersonic, high performance, subsonic, and rotorcraft vehicle technology. Fundamental disciplinary research areas discussed include aerodynamics, propulsion, materials and structures, information sciences and human factors, and flight systems/safety. A description of the NASA organization and facilities is given.

Intestinal flora of FAP patients containing APC-like sequences.

PubMed

Hainova, K; Adamcikova, Z; Ciernikova, S; Stevurkova, V; Tyciakova, S; Zajac, V

2014-01-01

Colorectal cancer mortality is one of the most common cause of cancer-related mortality. A multiple risk factors are associated with colorectal cancer, including hereditary, enviromental and inflammatory syndromes affecting the gastrointestinal tract. Familial adenomatous polyposis (FAP) is characterized by the emergence of hundreds to thousands of colorectal adenomatous polyps and FAP syndrome is caused by mutations within the adenomatous polyposis coli (APC) tumor suppressor gene. We analyzed 21 rectal bacterial subclones isolated from FAP patient 41-1 with confirmed 5bp ACAAA deletion within codons 1060-1063 for the presence of APC-like sequences in longest exon 15. The studied section was defined by primers 15Efor-15Erev, what correlates with mutation cluster region (MCR) in which the 75% of all APC germline mutations were detected. More than 90% homology was showed by sequencing and subsequent software comparison. The expression of APC-like sequences was demostrated by Western blot analysis using monoclonal and polyclonal antibodies against APC protein. To study missing link between the DNA analysis (PCR, DNA sequencing) and protein expresion experiments (Western blotting) we analyzed bacterial transcripts containing the 15Efor-15Erev sequence of APC gene by reverse transcription-PCR, what indicated that an APC gene derived fragment may be produced. We observed 97-100 % homology after computer comparison of cDNA PCR products. Our results suggest that presence of APC-like sequences in intestinal/rectal bacteria is enrichment of bacterial genetic information in which horizontal gene transfer between humans and microflora play an important role.

Airbreathing Hypersonic Technology Vision Vehicles and Development Dreams

NASA Technical Reports Server (NTRS)

McClinton, C. R.; Hunt, J. L.; Ricketts, R. H.; Reukauf, P.; Peddie, C. L.

1999-01-01

Significant advancements in hypersonic airbreathing vehicle technology have been made in the country's research centers and industry over the past 40 years. Some of that technology is being validated with the X-43 flight tests. This paper presents an overview of hypersonic airbreathing technology status within the US, and a hypersonic technology development plan. This plan builds on the nation's large investment in hypersonics. This affordable, incremental plan focuses technology development on hypersonic systems, which could be operating by the 2020's.

The X-43A hypersonic research aircraft and its modified Pegasus booster rocket nestled under the wi

NASA Technical Reports Server (NTRS)

2001-01-01

The X-43A hypersonic research aircraft and its modified Pegasus booster rocket are nestled under the wing of NASA's NB-52B carrier aircraft during pre-flight systems testing at the Dryden Flight Research Center, Edwards, Calif. The combined systems test was one of the last major milestones in the Hyper-X research program before the first X-43A flight. The X-43A flights will be the first actual flight tests of an aircraft powered by a revolutionary supersonic-combustion ramjet ('scramjet') engine capable of operating at hypersonic speeds (above Mach 5, or five times the speed of sound). The 12-foot, unpiloted research vehicle was developed and built by MicroCraft Inc., Tullahoma, Tenn., under NASA contract. The booster was built by Orbital Sciences Corp., Dulles, Va. After being air-launched from NASA's venerable NB-52 mothership, the booster will accelerate the X-43A to test speed and altitude. The X-43A will then separate from the rocket and fly a pre-programmed trajectory, conducting aerodynamic and propulsion experiments until it descends into the Pacific Ocean. Three research flights are planned, two at Mach 7 and one at Mach 10.

Fracture behavior of the Fe-8Al alloy FAP-Y

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

Alexander, D.J.

The tensile and impact properties of two heats of the reduced aluminum alloy FAP-Y have been measured and compared to the Fe{sub 3}Al alloy FA-129. The FAP-Y material has similar yield strengths up to 400{degrees}C, and much better ductility and impact properties, as compared to the FA-129. Despite excellent room-temperature ductility, the ductile-to-brittle transition temperature is still quite high, around 150{degrees}C. The material is found to be strain-rate sensitive, with a significant increase in the yield strength at strain rates of about 10{sup 3} s{sup {minus}1}. It is believed that this strain-rate sensitivity is responsible, at least in part, formore » the high ductile-to-brittle transition temperature.« less

Mapping the low palmitate fap1 mutation and validation of its effects in soybean oil and agronomic traits in three soybean populations.

PubMed

Cardinal, Andrea J; Whetten, Rebecca; Wang, Sanbao; Auclair, Jérôme; Hyten, David; Cregan, Perry; Bachlava, Eleni; Gillman, Jason; Ramirez, Martha; Dewey, Ralph; Upchurch, Greg; Miranda, Lilian; Burton, Joseph W

2014-01-01

fap 1 mutation is caused by a G174A change in GmKASIIIA that disrupts a donor splice site recognition and creates a GATCTG motif that enhanced its expression. Soybean oil with reduced palmitic acid content is desirable to reduce the health risks associated with consumption of this fatty acid. The objectives of this study were: to identify the genomic location of the reduced palmitate fap1 mutation, determine its molecular basis, estimate the amount of phenotypic variation in fatty acid composition explained by this locus, determine if there are epistatic interactions between the fap1 and fap nc loci and, determine if the fap1 mutation has pleiotropic effects on seed yield, oil and protein content in three soybean populations. This study detected two major QTL for 16:0 content located in chromosome 5 (GmFATB1a, fap nc) and chromosome 9 near BARCSOYSSR_09_1707 that explained, with their interaction, 66-94 % of the variation in 16:0 content in the three populations. Sequencing results of a putative candidate gene, GmKASIIIA, revealed a single unique polymorphism in the germplasm line C1726, which was predicted to disrupt the donor splice site recognition between exon one and intron one and produce a truncated KASIIIA protein. This G to A change also created the GATCTG motif that enhanced gene expression of the mutated GmKASIIIA gene. Lines homozygous for the GmKASIIIA mutation (fap1) had a significant reduction in 16:0, 18:0, and oil content; and an increase in unsaturated fatty acids content. There were significant epistatic interactions between GmKASIIIA (fap1) and fap nc for 16:0 and oil contents, and seed yield in two populations. In conclusion, the fap1 phenotype is caused by a single unique SNP in the GmKASIIIA gene.

Our experience of treatment of cribriform morular variant of papillary thyroid carcinoma; difference in clinicopathological features of FAP-associated and sporadic patients.

PubMed

Ito, Yasuhiro; Miyauchi, Akira; Ishikawa, Hideki; Hirokawa, Mitsuhiro; Kudo, Takumi; Tomoda, Chisato; Miya, Akihiro

2011-01-01

Cribriform-morular variant (CMV) is a comparably rare histological subtype of papillary thyroid carcinoma (PTC). This can be associated with familial adenomatous polyposis (FAP) due to APC gene mutations. In this study, we investigated the difference in the biological characteristics between FAP-associated and sporadic CMV. Between 1991 and 2010, 32 patients with CMV were treated in Kuma Hospital. Thirty-one of these underwent initial surgery for CMV in Kuma Hospital. Twelve patients were FAP-associated and the remaining 19 were sporadic CMV. All patients were female. Tumors of FAP-associated CMV were more frequently multiple than those of sporadic CMV. Patient age and tumor size did not differ between the two groups. Of 12 FAP-associated CMV, 5 were detected by thyroid nodule (thyroid precedent group) and 7 were detected by FAP (polyposis precedent group) as an initial manifestation. Patient age was younger and tumor size was smaller in the polyposis group than in the thyroid nodule group. All patients lacked extrathyroid extension on intraoperative finding and were node-negative on pathological examination. To date, two patients with FAP-associated CMV who initially underwent hemithyroidectomy (one in Kuma Hospital and one in another hospital) showed recurrence to the remnant thyroid during follow-up. None of the patients showed recurrence to other regions or died of carcinoma. Taken together, CMV is considered an indolent disease in our series. FAP-associated CMV showed multiple tumors more frequently than sporadic CMV. Total thyroidectomy is recommended for FAP-associated CMV, but extensive lymph node dissection is not necessary.

Configuration development study of the X-24C hypersonic research airplane, phase 1

NASA Technical Reports Server (NTRS)

Combs, H. G.

1976-01-01

Four hypersonic research airplane configurations found to be the most cost effective were selected for further refinement. The selection was based on a systematic analysis and evaluation of realistic designs, involving nine different configurations, evolving from three different structural/thermal concepts, coupled with existing rocket and sustainer engines. All configurations were constrained by the mission profiles, research requirements, aerodynamic envelope and maximum launch weight established by NASA.

X-43A Hypersonic Experimental Vehicle - Artist Concept in Flight

NASA Technical Reports Server (NTRS)

1999-01-01

An artist's conception of the X-43A Hypersonic Experimental Vehicle, or 'Hyper-X' in flight. The X-43A was developed to flight test a dual-mode ramjet/scramjet propulsion system at speeds from Mach 7 up to Mach 10 (7 to 10 times the speed of sound, which varies with temperature and altitude). Hyper-X, the flight vehicle for which is designated as X-43A, is an experimental flight-research program seeking to demonstrate airframe-integrated, 'air-breathing' engine technologies that promise to increase payload capacity for future vehicles, including hypersonic aircraft (faster than Mach 5) and reusable space launchers. This multiyear program is currently underway at NASA Dryden Flight Research Center, Edwards, California. The Hyper-X schedule calls for its first flight later this year (2000). Hyper-X is a joint program, with Dryden sharing responsibility with NASA's Langley Research Center, Hampton, Virginia. Dryden's primary role is to fly three unpiloted X-43A research vehicles to validate engine technologies and hypersonic design tools as well as the hypersonic test facility at Langley. Langley manages the program and leads the technology development effort. The Hyper-X Program seeks to significantly expand the speed boundaries of air-breathing propulsion by being the first aircraft to demonstrate an airframe-integrated, scramjet-powered free flight. Scramjets (supersonic-combustion ramjets) are ramjet engines in which the airflow through the whole engine remains supersonic. Scramjet technology is challenging because only limited testing can be performed in ground facilities. Long duration, full-scale testing requires flight research. Scramjet engines are air-breathing, capturing their oxygen from the atmosphere. Current spacecraft, such as the Space Shuttle, are rocket powered, so they must carry both fuel and oxygen for propulsion. Scramjet technology-based vehicles need to carry only fuel. By eliminating the need to carry oxygen, future hypersonic vehicles will

The NASA Ames 16-Inch Shock Tunnel Nozzle Simulations and Experimental Comparison

NASA Technical Reports Server (NTRS)

TokarcikPolsky, S.; Papadopoulos, P.; Venkatapathy, E.; Delwert, G. S.; Edwards, Thomas A. (Technical Monitor)

1995-01-01

The 16-Inch Shock Tunnel at NASA Ames Research Center is a unique test facility used for hypersonic propulsion testing. To provide information necessary to understand the hypersonic testing of the combustor model, computational simulations of the facility nozzle were performed and results are compared with available experimental data, namely static pressure along the nozzle walls and pitot pressure at the exit of the nozzle section. Both quasi-one-dimensional and axisymmetric approaches were used to study the numerous modeling issues involved. The facility nozzle flow was examined for three hypersonic test conditions, and the computational results are presented in detail. The effects of variations in reservoir conditions, boundary layer growth, and parameters of numerical modeling are explored.

High-speed Imaging of Global Surface Temperature Distributions on Hypersonic Ballistic-Range Projectiles

NASA Technical Reports Server (NTRS)

Wilder, Michael C.; Reda, Daniel C.

2004-01-01

The NASA-Ames ballistic range provides a unique capability for aerothermodynamic testing of configurations in hypersonic, real-gas, free-flight environments. The facility can closely simulate conditions at any point along practically any trajectory of interest experienced by a spacecraft entering an atmosphere. Sub-scale models of blunt atmospheric entry vehicles are accelerated by a two-stage light-gas gun to speeds as high as 20 times the speed of sound to fly ballistic trajectories through an 24 m long vacuum-rated test section. The test-section pressure (effective altitude), the launch velocity of the model (flight Mach number), and the test-section working gas (planetary atmosphere) are independently variable. The model travels at hypersonic speeds through a quiescent test gas, creating a strong bow-shock wave and real-gas effects that closely match conditions achieved during actual atmospheric entry. The challenge with ballistic range experiments is to obtain quantitative surface measurements from a model traveling at hypersonic speeds. The models are relatively small (less than 3.8 cm in diameter), which limits the spatial resolution possible with surface mounted sensors. Furthermore, since the model is in flight, surface-mounted sensors require some form of on-board telemetry, which must survive the massive acceleration loads experienced during launch (up to 500,000 gravities). Finally, the model and any on-board instrumentation will be destroyed at the terminal wall of the range. For these reasons, optical measurement techniques are the most practical means of acquiring data. High-speed thermal imaging has been employed in the Ames ballistic range to measure global surface temperature distributions and to visualize the onset of transition to turbulent-flow on the forward regions of hypersonic blunt bodies. Both visible wavelength and infrared high-speed cameras are in use. The visible wavelength cameras are intensified CCD imagers capable of integration

Interplay between Ret and Fap-1 regulates CD95-mediated apoptosis in medullary thyroid cancer cells.

PubMed

Nicolini, Valentina; Cassinelli, Giuliana; Cuccuru, Giuditta; Bongarzone, Italia; Petrangolini, Giovanna; Tortoreto, Monica; Mondellini, Piera; Casalini, Patrizia; Favini, Enrica; Zaffaroni, Nadia; Zunino, Franco; Lanzi, Cinzia

2011-10-01

Emerging evidence suggests that Ret oncoproteins expressed in medullary thyroid cancer (MTC) might evade the pro-apoptotic function of the dependence receptor proto-Ret by directly impacting the apoptosis machinery. Identification of the molecular determinants of the interplay between Ret signaling and apoptosis might provide a relevant contribution to the optimization of Ret-targeted therapies. Here, we describe the cross-talk between Ret-M918T oncogenic mutant responsible for type 2B multiple endocrine syndrome (MEN2B), and components of death receptor-mediated extrinsic apoptosis pathway. In the human MEN2B-type MTC cell line MZ-CRC-1 expressing Ret-M918T, Ret was found associated with Fap-1, known as inhibitor of the CD95 death receptor trafficking to the cell membrane, and with procaspase-8, the initiator pro-form caspase in the extrinsic apoptosis pathway. Cell treatment with the anti-tumor Ret kinase inhibitor RPI-1 inhibited tyrosine phosphorylation of procaspase-8, likely inducing its local activation, followed by downregulation of both Ret and Fap-1, and translocation of CD95 into lipid rafts. According to the resulting increase of CD95 cell surface expression, the CD95 agonist antibody CH11 enhanced RPI-1-induced cell growth inhibition and apoptosis. RET RNA interference downregulated Fap-1 protein in MZ-CRC-1 cells, whereas exogenous RET-M918T upregulated Fap-1 in HEK293 cells. Overall, these data indicate that the Ret oncoprotein exerts opposing controls on Fap-1 and CD95, increasing Fap-1 expression and decreasing CD95 cell surface expression. The functional interplay of the Ret mutant with the extrinsic apoptosis pathway provides a mechanism possibly contributing to MTC malignant phenotype and a rational basis for novel therapeutic strategies combining Ret inhibitors and CD95 agonists. Copyright © 2011 Elsevier Inc. All rights reserved.

A Photogrammetric System for Model Attitude Measurement in Hypersonic Wind Tunnels

NASA Technical Reports Server (NTRS)

Jones, Thomas W.; Lunsford, Charles B.

2007-01-01

A series of wind tunnel tests have been conducted to evaluate a multi-camera videogrammetric system designed to measure model attitude in hypersonic facilities. The technique utilizes processed video data and photogrammetric principles for point tracking to compute model position including pitch, roll and yaw. A discussion of the constraints encountered during the design, and a review of the measurement results obtained from the NASA Langley Research Center (LaRC) 31-Inch Mach 10 tunnel are presented.

The NASA Hyper-X Program

NASA Technical Reports Server (NTRS)

Freeman, Delman C., Jr.; Reubush, Daivd E.; McClinton, Charles R.; Rausch, Vincent L.; Crawford, J. Larry

1997-01-01

This paper provides an overview of NASA's Hyper-X Program; a focused hypersonic technology effort designed to move hypersonic, airbreathing vehicle technology from the laboratory environment to the flight environment. This paper presents an overview of the flight test program, research objectives, approach, schedule and status. Substantial experimental database and concept validation have been completed. The program is currently concentrating on the first, Mach 7, vehicle development, verification and validation in preparation for wind-tunnel testing in 1998 and flight testing in 1999. Parallel to this effort the Mach 5 and 10 vehicle designs are being finalized. Detailed analytical and experimental evaluation of the Mach 7 vehicle at the flight conditions is nearing completion, and will provide a database for validation of design methods once flight test data are available.

The role of mutation analysis of the APC gene in the management of FAP patients. A controversial issue.

PubMed

Dodaro, Concetta; Grifasi, Carlo; Florio, Jole; Santangelo, Michele L; Duraturo, Francesca; De Rosa, Marina; Izzo, Paola; Renda, Andrea

A correlation between the location of mutation in the adenomatous polyposis coli (APC) gene and clinical manifestations of familial adenomatous polyposis (FAP) has repeatedly been reported. Some Authors suggest the use of mutational analysis as a guide to select the best surgical option in FAP patients. However, data coming from studies on large series have raised questions on this issue. The aim of this study is to discuss the role of the genetic tests in the management of FAP. A literature review was performed considering only peer-reviewed articles published between 1991-2015. All the studies examined the role of genetic as a guide for surgical management of FAP. Of 363 articles identified, 21 were selected for full-text review. We found different positions with regard the use of genetic tests to determine surgical management of FAP. In particular, while consistent correlations between the APC mutation site and FAP phenotype were observed in large series, 8 studies reported a wide variation of genotypephenotype correlation in patients with the same mutation and they recommended that decisions regarding surgical strategy should be based not only on genotype but also on the clinical factors and the will of the patient who must be fully informed. The decision on the type and the timing of surgery should be based on the assessment of many factors and genotype assessment should be used in combination with clinical data. Disease severity, Familial adenomatous polyposis, Genetic tests, Genotype-phenotype correlations, Surgical management.

Overview of CMC Research at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Grady, Joseph E.

2011-01-01

CMC technology development in the Ceramics Branch at NASA Glenn Research Center addresses Aeronautics propulsion goals across subsonic, supersonic and hypersonic flight regimes. Combustor, turbine and exhaust nozzle applications of CMC materials will enable NASA to demonstrate reduced fuel consumption, emissions, and noise in advanced gas turbine engines. Applications ranging from basic Fundamental Aeronautics research activities to technology demonstrations in the new Integrated Systems Research Program will be discussed.

New Hypersonic Shock Tunnel at the Laboratory of Aerothermodynamics and Hypersonics Prof. Henry T. Nagamatsu

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

Toro, P. G. P.; Minucci, M. A. S.; Chanes, J. B. Jr

The new 0.60-m. nozzle exit diameter hypersonic shock tunnel was designed to study advanced air-breathing propulsion system such as supersonic combustion and/or laser technologies. In addition, it may be used for hypersonic flow studies and investigations of the electromagnetic (laser) energy addition for flow control. This new hypersonic shock tunnel was designed and installed at the Laboratory for of Aerothermodynamics and Hypersonics Prof. Henry T. Nagamatsu, IEAv-CTA, Brazil. The design of the tunnel enables relatively long test times, 2-10 milliseconds, suitable for the experiments performed at the laboratory. Free stream Mach numbers ranging from 6 to 25 can be producedmore » and stagnation pressures and temperatures up to 360 atm. and up to 9,000 K, respectively, can be generated. Shadowgraph and schlieren optical techniques will be used for flow visualization.« less

A survey of heating and turbulent boundary layer characteristics of several hypersonic research aircraft configurations

NASA Technical Reports Server (NTRS)

Lawing, P. L.

1981-01-01

Four of the configurations investigated during a proposed NASA-Langley hypersonic research aircraft program were selected for phase-change-paint heat-transfer testing and forebody boundary layer pitot surveys. In anticipation of future hypersonic aircraft, both published and unpublished data and results are reviewed and presented with the purpose of providing a synoptic heat-transfer data base from the research effort. Engineering heat-transfer predictions are compared with experimental data on both a global and a local basis. The global predictions are shown to be sufficient for purposes of configuration development, and even the local predictions can be adequate when interpreted in light of the proper flow field. In that regard, cross flow in the forebody boundary layers was examined for significant heating and aerodynamic effect on the scramjet engines. A design philosophy which evolved from the research airplane effort is used to design a forebody shape that produces thin, uniform, forebody boundary layers on a hypersonic airbreathing missile. Finally, heating/boundary layer phenomena which are not predictable with state-of-the-art knowledge and techniques are shown and discussed.

A Patient With Desmoid Tumors and Familial FAP Having Frame Shift Mutation of the APC Gene.

PubMed

Sadighi, Sanambar; Ghaffari-Moghaddam, Mahsa; Saffari, Mojtaba; Mohagheghi, Mohammad Ali; Shirkoohi, Reza

2017-02-01

Desmoids tumors, characterized by monoclonal proliferation of myofibroblasts, could occur in 5-10% of patients with familial adenomatous polyposis (FAP) as an extra-colonic manifestation of the disease. FAP can develop when there is a germ-line mutation in the adenomatous polyposis coli gene. Although mild or attenuated FAP may follow mutations in 5΄ extreme of the gene, it is more likely that 3΄ extreme mutations haveamore severe manifestation of thedisease. A 28-year-old woman was admitted to the Cancer Institute of Iran with an abdominal painful mass. She had strong family history of FAP and underwent prophylactic total colectomy. Pre-operative CT scans revealed a large mass. Microscopic observation showed diffuse fibroblast cell infiltration of the adjacent tissue structures. Peripheral blood DNA extraction followed by adenomatous polyposis coli gene exon by exon sequencing was performed to investigate the mutation in adenomatous polyposis coli gene. Analysis of DNA sequencing demonstrated a mutation of 4 bpdeletions at codon 1309-1310 of the exon 16 of adenomatous polyposis coli gene sequence which was repeated in 3 members of the family. Some of them had desmoid tumor without classical FAP history. Even when there is no familial history of adenomatous polyposis, the adenomatous polyposis coli gene mutation should be investigated in cases of familial desmoids tumors for a suitable prevention. The 3΄ extreme of the adenomatous polyposis coli gene is still the best likely location in such families.

The HYTHIRM Project: Flight Thermography of the Space Shuttle During the Hypersonic Re-entry

NASA Technical Reports Server (NTRS)

Horvath, Thomas J.; Tomek, Deborah M.; Berger, Karen T.; Zalameda, Joseph N.; Splinter, Scott C.; Krasa, Paul W.; Schwartz, Richard J.; Gibson, David M.; Tietjen, Alan B.; Tack, Steve

2010-01-01

This report describes a NASA Langley led endeavor sponsored by the NASA Engineering Safety Center, the Space Shuttle Program Office and the NASA Aeronautics Research Mission Directorate to demonstrate a quantitative thermal imaging capability. A background and an overview of several multidisciplinary efforts that culminated in the acquisition of high resolution calibrated infrared imagery of the Space Shuttle during hypervelocity atmospheric entry is presented. The successful collection of thermal data has demonstrated the feasibility of obtaining remote high-resolution infrared imagery during hypersonic flight for the accurate measurement of surface temperature. To maximize science and engineering return, the acquisition of quantitative thermal imagery and capability demonstration was targeted towards three recent Shuttle flights - two of which involved flight experiments flown on Discovery. In coordination with these two Shuttle flight experiments, a US Navy NP-3D aircraft was flown between 26-41 nautical miles below Discovery and remotely monitored surface temperature of the Orbiter at Mach 8.4 (STS-119) and Mach 14.7 (STS-128) using a long-range infrared optical package referred to as Cast Glance. This same Navy aircraft successfully monitored the Orbiter Atlantis traveling at approximately Mach 14.3 during its return from the successful Hubble repair mission (STS-125). The purpose of this paper is to describe the systematic approach used by the Hypersonic Thermodynamic Infrared Measurements team to develop and implement a set of mission planning tools designed to establish confidence in the ability of an imaging platform to reliably acquire, track and return global quantitative surface temperatures of the Shuttle during entry. The mission planning tools included a pre-flight capability to predict the infrared signature of the Shuttle. Such tools permitted optimization of the hardware configuration to increase signal-to-noise and to maximize the available

Experimental program for real gas flow code validation at NASA Ames Research Center

NASA Technical Reports Server (NTRS)

Deiwert, George S.; Strawa, Anthony W.; Sharma, Surendra P.; Park, Chul

1989-01-01

The experimental program for validating real gas hypersonic flow codes at NASA Ames Rsearch Center is described. Ground-based test facilities used include ballistic ranges, shock tubes and shock tunnels, arc jet facilities and heated-air hypersonic wind tunnels. Also included are large-scale computer systems for kinetic theory simulations and benchmark code solutions. Flight tests consist of the Aeroassist Flight Experiment, the Space Shuttle, Project Fire 2, and planetary probes such as Galileo, Pioneer Venus, and PAET.

Hyper-X and Pegasus Launch Vehicle: A Three-Foot Model of the Hypersonic Experimental Research Vehic

NASA Technical Reports Server (NTRS)

1997-01-01

A close-up view of the X-43A Hypersonic Experimental Research Vehicle, or Hyper-X, portion of a three-foot-long model of the vehicle/booster combination at NASA's Dryden Flight Research Center, Edwards, California. Hyper-X, the flight vehicle for which is designated as X-43A, is an experimental flight-research program seeking to demonstrate airframe-integrated, 'air-breathing' engine technologies that promise to increase payload capacity for future vehicles, including hypersonic aircraft (faster than Mach 5) and reusable space launchers. This multiyear program is currently underway at NASA Dryden Flight Research Center, Edwards, California. The Hyper-X schedule calls for its first flight later this year (2000). Hyper-X is a joint program, with Dryden sharing responsibility with NASA's Langley Research Center, Hampton, Virginia. Dryden's primary role is to fly three unpiloted X-43A research vehicles to validate engine technologies and hypersonic design tools as well as the hypersonic test facility at Langley. Langley manages the program and leads the technology development effort. The Hyper-X Program seeks to significantly expand the speed boundaries of air-breathing propulsion by being the first aircraft to demonstrate an airframe-integrated, scramjet-powered free flight. Scramjets (supersonic-combustion ramjets) are ramjet engines in which the airflow through the whole engine remains supersonic. Scramjet technology is challenging because only limited testing can be performed in ground facilities. Long duration, full-scale testing requires flight research. Scramjet engines are air-breathing, capturing their oxygen from the atmosphere. Current spacecraft, such as the Space Shuttle, are rocket powered, so they must carry both fuel and oxygen for propulsion. Scramjet technology-based vehicles need to carry only fuel. By eliminating the need to carry oxygen, future hypersonic vehicles will be able to carry heavier payloads. Another unique aspect of the X-43A vehicle is

Hyper-X and Pegasus Launch Vehicle: A Three-Foot Model of the Hypersonic Experimental Research Vehic

NASA Technical Reports Server (NTRS)

1997-01-01

The configuration of the X-43A Hypersonic Experimental Research Vehicle, or Hyper-X, attached to a Pegasus launch vehicle is displayed in this three-foot-long model at NASA's Dryden Flight Research Center, Edwards, California. Hyper-X, the flight vehicle for which is designated as X-43A, is an experimental flight-research program seeking to demonstrate airframe-integrated, 'air-breathing' engine technologies that promise to increase payload capacity for future vehicles, including hypersonic aircraft (faster than Mach 5) and reusable space launchers. This multiyear program is currently underway at NASA Dryden Flight Research Center, Edwards, California. The Hyper-X schedule calls for its first flight later this year (2000). Hyper-X is a joint program, with Dryden sharing responsibility with NASA's Langley Research Center, Hampton, Virginia. Dryden's primary role is to fly three unpiloted X-43A research vehicles to validate engine technologies and hypersonic design tools as well as the hypersonic test facility at Langley. Langley manages the program and leads the technology development effort. The Hyper-X Program seeks to significantly expand the speed boundaries of air-breathing propulsion by being the first aircraft to demonstrate an airframe-integrated, scramjet-powered free flight. Scramjets (supersonic-combustion ramjets) are ramjet engines in which the airflow through the whole engine remains supersonic. Scramjet technology is challenging because only limited testing can be performed in ground facilities. Long duration, full-scale testing requires flight research. Scramjet engines are air-breathing, capturing their oxygen from the atmosphere. Current spacecraft, such as the Space Shuttle, are rocket powered, so they must carry both fuel and oxygen for propulsion. Scramjet technology-based vehicles need to carry only fuel. By eliminating the need to carry oxygen, future hypersonic vehicles will be able to carry heavier payloads. Another unique aspect of the X-43

An Overview of the NASA Fundamental Aeronautics Program Subsonic Fixed Wing Project and Ultra High Bypass Partnership Research Goals

NASA Technical Reports Server (NTRS)

Hughes, Christopher E.

2009-01-01

An overview of the NASA Fundamental Aeronautics Program (FAP) mission and goals is presented. One of the subprograms under the FAP, the Subsonic Fixed Wing Project (SFW), is the focus of the presentation. The SFW system environmental metrics are discussed, along with highlights of planned, systematic approach to research to reduce the environmental impact of commercial aircraft in the areas of acoustics, fuel burn and emissions. The presentation then focuses on collaborative research being conducted with U.S. Industry on the Ultra High Bypass (UHB) engine cycle, the propulsion cycle selected by the SFW to meet the system goals. The partnerships with General Electric Aviation to investigate Open Rotor propulsion concepts and with Pratt & Whitney to investigate the Geared Turbofan UHB engine are highlighted, including current and planned future collaborative research activities with NASA and each organization.

Hypersonic Materials and Structures

NASA Technical Reports Server (NTRS)

Glass, David E.

2016-01-01

Thermal protection systems (TPS) and hot structures are required for a range of hypersonic vehicles ranging from ballistic reentry to hypersonic cruise vehicles, both within Earth's atmosphere and non-Earth atmospheres. The focus of this presentation is on air breathing hypersonic vehicles in the Earth's atmosphere. This includes single-stage to orbit (SSTO), two-stage to orbit (TSTO) accelerators, access to space vehicles, and hypersonic cruise vehicles. This paper will start out with a brief discussion of aerodynamic heating and thermal management techniques to address the high heating, followed by an overview of TPS for rocket-launched and air-breathing vehicles. The argument is presented that as we move from rocket-based vehicles to air-breathing vehicles, we need to move away from the insulated airplane approach used on the Space Shuttle Orbiter to a wide range of TPS and hot structure approaches. The primary portion of the paper will discuss issues and design options for CMC TPS and hot structure components, including leading edges, acreage TPS, and control surfaces. The current state-of-the-art will be briefly discussed for some of the components.

First Steps in FAP: Experiences of Beginning Functional Analytic Psychotherapy Therapist with an Obsessive-Compulsive Personality Disorder Client

ERIC Educational Resources Information Center

Manduchi, Katia; Schoendorff, Benjamin

2012-01-01

Practicing Functional Analytic Psychotherapy (FAP) for the first time can seem daunting to therapists. Establishing a deep and intense therapeutic relationship, identifying FAP's therapeutic targets of clinically relevant behaviors, and using contingent reinforcement to help clients emit more functional behavior in the therapeutic relationship all…

miR-204 reverses temozolomide resistance and inhibits cancer initiating cells phenotypes by degrading FAP-α in glioblastoma.

PubMed

Yang, Yun-Na; Zhang, Xiang-Hua; Wang, Yan-Ming; Zhang, Xi; Gu, Zheng

2018-05-01

Malignant gliomas are treated with temozolomide (TMZ) at present, but often exhibit resistance to this agent. Cancer-initiating cells (CICs) have been suggested to lead to TMZ resistance. The mechanisms underlying CICs-based TMZ resistance are not fully understood. MicroRNAs (miRNAs) have been demonstrated to serve important roles in tumorigenesis and TMZ resistance. In the present study, a sphere forming assay and western blot analysis were performed to detect the formation of CICs and fibroblast activation protein α (FAP-α) protein expression. It was revealed that TMZ resistance promoted the formation of CICs and upregulated FAP-α expression in glioblastoma cells. Over-expressing FAP-α was also demonstrated to promote TMZ resistance and induce the formation of CICs in U251MG cells. In addition, using a reverse transcription-quantitative polymerase chain reaction, it was observed that miR-204 was downregulated in U251MG-resistant (-R) cells. miR-204 expression negatively correlated with the FAP-α levels in human glioblastoma tissues, and it may inhibit the formation of CICs and reverse TMZ resistance in U251MG-R cells. Therefore, it was concluded that miR-204 reversed temozolomide resistance and inhibited CICs phenotypes by degrading FAP-α in glioblastoma.

miR-204 reverses temozolomide resistance and inhibits cancer initiating cells phenotypes by degrading FAP-α in glioblastoma

PubMed Central

Yang, Yun-Na; Zhang, Xiang-Hua; Wang, Yan-Ming; Zhang, Xi; Gu, Zheng

2018-01-01

Malignant gliomas are treated with temozolomide (TMZ) at present, but often exhibit resistance to this agent. Cancer-initiating cells (CICs) have been suggested to lead to TMZ resistance. The mechanisms underlying CICs-based TMZ resistance are not fully understood. MicroRNAs (miRNAs) have been demonstrated to serve important roles in tumorigenesis and TMZ resistance. In the present study, a sphere forming assay and western blot analysis were performed to detect the formation of CICs and fibroblast activation protein α (FAP-α) protein expression. It was revealed that TMZ resistance promoted the formation of CICs and upregulated FAP-α expression in glioblastoma cells. Over-expressing FAP-α was also demonstrated to promote TMZ resistance and induce the formation of CICs in U251MG cells. In addition, using a reverse transcription-quantitative polymerase chain reaction, it was observed that miR-204 was downregulated in U251MG-resistant (-R) cells. miR-204 expression negatively correlated with the FAP-α levels in human glioblastoma tissues, and it may inhibit the formation of CICs and reverse TMZ resistance in U251MG-R cells. Therefore, it was concluded that miR-204 reversed temozolomide resistance and inhibited CICs phenotypes by degrading FAP-α in glioblastoma. PMID:29725461

Conceptual Study on Hypersonic Turbojet Experimental Vehicle (HYTEX)

NASA Astrophysics Data System (ADS)

Taguchi, Hideyuki; Murakami, Akira; Sato, Tetsuya; Tsuchiya, Takeshi

Pre-cooled turbojet engines have been investigated aiming at realization of reusable space transportation systems and hypersonic airplanes. Evaluation methods of these engine performances have been established based on ground tests. There are some plans on the demonstration of hypersonic propulsion systems. JAXA focused on hypersonic propulsion systems as a key technology of hypersonic transport airplane. Demonstrations of Mach 5 class hypersonic technologies are stated as a development target at 2025 in the long term vision. In this study, systems analyses of hypersonic turbojet experiment (HYTEX) with Mach 5 flight capability is performed. Aerodynamic coefficients are obtained by CFD analyses and wind tunnel tests. Small Pre-cooled turbojet is fabricated and tested using liquid hydrogen as fuel. As a result, characteristics of the baseline vehicle shape is clarified, . and effects of pre-cooling are confirmed at the firing test.

Planar laser-induced fluorescence (PLIF) investigation of hypersonic flowfields in a Mach 10 wind tunnel

NASA Technical Reports Server (NTRS)

Danehy, Paul M.; Wilkes, Jennifer A.; Aderfer, David W.; Jones, Stephen B.; Robbins, Anthony W.; Pantry, Danny P.; Schwartz, Richard J.

2006-01-01

Planar laser-induced fluorescence (PLIF) of nitric oxide (NO) was used to visualize four different hypersonic flowfields in the NASA Langley Research Center 31-Inch Mach 10 Air wind tunnel. The four configurations were: (1) the wake flowfield of a fuselage-only X-33 lifting body, (2) flow over a flat plate containing a rectangular cavity, (3) flow over a 70deg blunted cone with a cylindrical afterbody, formerly studied by an AGARD working group, and (4) an Apollo-geometry entry capsule - relevant to the Crew Exploration Vehicle currently being developed by NASA. In all cases, NO was seeded into the flowfield through tubes inside or attached to the model sting and strut. PLIF was used to visualize the NO in the flowfield. In some cases pure NO was seeded into the flow while in other cases a 5% NO, 95% N2 mix was injected. Several parameters were varied including seeding method and location, seeding mass flow rate, model angle of attack and tunnel stagnation pressure, which varies the unit Reynolds number. The location of the laser sheet was as also varied to provide three dimensional flow information. Virtual Diagnostics Interface (ViDI) technology developed at NASA Langley was used to visualize the data sets in post processing. The measurements demonstrate some of the capabilities of the PLIF method for studying hypersonic flows.

Parametric Analysis of a Hypersonic Inlet using Computational Fluid Dynamics

NASA Astrophysics Data System (ADS)

Oliden, Daniel

For CFD validation, hypersonic flow fields are simulated and compared with experimental data specifically designed to recreate conditions found by hypersonic vehicles. Simulated flow fields on a cone-ogive with flare at Mach 7.2 are compared with experimental data from NASA Ames Research Center 3.5" hypersonic wind tunnel. A parametric study of turbulence models is presented and concludes that the k-kl-omega transition and SST transition turbulence model have the best correlation. Downstream of the flare's shockwave, good correlation is found for all boundary layer profiles, with some slight discrepancies of the static temperature near the surface. Simulated flow fields on a blunt cone with flare above Mach 10 are compared with experimental data from CUBRC LENS hypervelocity shock tunnel. Lack of vibrational non-equilibrium calculations causes discrepancies in heat flux near the leading edge. Temperature profiles, where non-equilibrium effects are dominant, are compared with the dissociation of molecules to show the effects of dissociation on static temperature. Following the validation studies is a parametric analysis of a hypersonic inlet from Mach 6 to 20. Compressor performance is investigated for numerous cowl leading edge locations up to speeds of Mach 10. The variable cowl study showed positive trends in compressor performance parameters for a range of Mach numbers that arise from maximizing the intake of compressed flow. An interesting phenomenon due to the change in shock wave formation for different Mach numbers developed inside the cowl that had a negative influence on the total pressure recovery. Investigation of the hypersonic inlet at different altitudes is performed to study the effects of Reynolds number, and consequently, turbulent viscous effects on compressor performance. Turbulent boundary layer separation was noted as the cause for a change in compressor performance parameters due to a change in Reynolds number. This effect would not be

Iterative design of emetine-based prodrug targeting fibroblast activation protein (FAP) and dipeptidyl peptidase IV DPPIV using a tandem enzymatic activation strategy.

PubMed

Akinboye, Emmanuel S; Brennen, W Nathaniel; Rosen, D Marc; Bakare, Oladapo; Denmeade, Samuel R

2016-06-01

There is an urgent need to develop new agents for treating metastatic prostate cancer to overcome multiple drug resistance to the current standard targeted cancer therapy. Emetine is a highly cytotoxic natural product protein synthesis inhibitor, which is toxic to all cell types. Its cytotoxicity can be blocked by derivatizing its N-2' position. Thus emetine can be selectively delivered to cancer cells in the region of metastatic cancer as a prodrug that will be activated by an enzyme selectively overexpressed within the metastatic tumor microenvironment. In this work, we convert emetine to a prodrug activatable by the fibroblast activation protein (FAP), a serine protease overexpressed by the carcinoma associated fibroblasts. By using an iterative structure-activity relationship strategy, several peptidyl emetine prodrug analogs (1-11) were synthesized by chemical derivatization of emetine at its N-2' position and tested for in-vitro activation by FAP. The lead prodrug 11 is made up of a DPPIV activatable prodrug precursor 10 (Ala-Pro-PABC-Emetine) coupled to FAP substrate (Ala-Ser-Gly-Pro-Ala-Gly-Pro). Activation assays of the prodrugs were performed in purified FAP, DPPIV, FBS, and human serum and were analyzed by LCMS. In vitro cytotoxicity assays of these prodrugs are carried out in prostate (LNCaP, PC3) and breast (MCF7 and MDA-MB-231) cancer cell lines. The prodrugs are also tested in normal immortalized human prostatic epithelial cell line (PrEC). The lead FAP activated emetine prodrug 11 is activated to emetine in tandem by FAP and DPPIV in about 70% conversion within 24 hr. In prostate and breast cancer cell lines treated with prodrug 11, it is found to be equipotent with emetine in the presence of FAP and DPPIV. However, in the PrEC cell line grown in serum free media, prodrug 11 is more than 200-fold less cytotoxic than emetine in the absence of FAP and DPPIV. This FAP activated prodrug of cytotoxic agent emetine further shows the crucial role of the

Upper GI tract lesions in familial adenomatous polyposis (FAP): enrichment of pyloric gland adenomas and other gastric and duodenal neoplasms.

PubMed

Wood, Laura D; Salaria, Safia N; Cruise, Michael W; Giardiello, Francis M; Montgomery, Elizabeth A

2014-03-01

Patients with familial adenomatous polyposis (FAP), an autosomal dominant cancer predisposition syndrome caused by mutations in the APC gene, develop neoplasms in both the upper and lower gastrointestinal (GI) tract. To clarify the upper GI tract lesions in FAP patients in a tertiary care setting, we reviewed specimens from 321 endoscopies in 66 patients with FAP. Tubular adenomas in the small bowel were the most common neoplasms (present in 89% of patients), although only 1 patient developed invasive carcinoma of the small bowel. Several types of gastric neoplasms were identified--65% of patients had at least 1 fundic gland polyp, and 23% of patients had at least 1 gastric foveolar-type gastric adenoma. Pyloric gland adenomas were also enriched, occurring in 6% of patients--this is a novel finding in FAP patients. Despite the high frequency of gastric neoplasms, only 1 patient developed carcinoma in the stomach. The very low frequency of carcinoma in these patients suggests that current screening procedures prevent the vast majority of upper GI tract carcinomas in patients with FAP, at least in the tertiary care setting.

Flight Control Laws for NASA's Hyper-X Research Vehicle

NASA Technical Reports Server (NTRS)

Davidson, J.; Lallman, F.; McMinn, J. D.; Martin, J.; Pahle, J.; Stephenson, M.; Selmon, J.; Bose, D.

1999-01-01

The goal of the Hyper-X program is to demonstrate and validate technology for design and performance predictions of hypersonic aircraft with an airframe-integrated supersonic-combustion ramjet propulsion system. Accomplishing this goal requires flight demonstration of a hydrogen-fueled scramjet powered hypersonic aircraft. A key enabling technology for this flight demonstration is flight controls. Closed-loop flight control is required to enable a successful stage separation, to achieve and maintain the design condition during the engine test, and to provide a controlled descent. Before the contract award, NASA developed preliminary flight control laws for the Hyper-X to evaluate the feasibility of the proposed scramjet test sequence and descent trajectory. After the contract award, a Boeing/NASA partnership worked to develop the current control laws. This paper presents a description of the Hyper-X Research Vehicle control law architectures with performance and robustness analyses. Assessments of simulated flight trajectories and stability margin analyses demonstrate that these control laws meet the flight test requirements.

Characterisation of serum transthyretin by electrospray ionisation-ion mobility mass spectrometry: Application to familial amyloidotic polyneuropathy type I (FAP-I).

PubMed

Pont, Laura; Benavente, Fernando; Vilaseca, Marta; Giménez, Estela; Sanz-Nebot, Victoria

2015-11-01

Transthyretin (TTR) is a homotetrameric protein which is known to misfold and aggregate causing different types of amyloidosis, such as familial amyloidotic polyneuropathy type I (FAP-I). FAP-I is associated with a specific TTR mutant variant (TTR (Met30)) that can be easily detected analysing the monomeric forms of the mutant protein. Meanwhile, the mechanism of protein aggregation onset, which could be triggered by structural changes on the native tetrameric protein complex, remains uncertain. We developed and described herein a new sample pretreatment based on immunoprecipitation (IP) to purify TTR from serum under non-denaturing conditions. Later, a nano-electrospray ionization-ion mobility mass spectrometry (nano-ESI-IM-MS or IM-MS) method was optimised to analyse the protein complexes in serum samples from healthy controls and FAP-I patients. IM-MS allowed separation and characterisation of tetrameric, trimeric and dimeric TTR gas ions due to their differential drift time, which is related to ion size and charge. The tetramer-to-dimer abundance ratio was differential between healthy controls and FAP-I patients (asymptomatic, symptomatic and an iatrogenic patient originally without the mutation who received a liver transplant from an FAP-I patient), and was also indicative of the effectiveness of liver transplantation as a treatment for FAP-I. Copyright © 2015 Elsevier B.V. All rights reserved.

Saying good goodbyes to your clients: A functional analytic psychotherapy (FAP) perspective.

PubMed

Tsai, Mavis; Gustafsson, Tore; Kanter, Jonathan; Plummer Loudon, Mary; Kohlenberg, Robert J

2017-03-01

Functional analytic psychotherapy (FAP) promotes client growth by shaping clients' daily life problems that also show up in session with their therapists. FAP therapists create evocative contexts within therapy that afford clients the opportunity to practice, refine, and be reinforced for new, more adaptive behaviors which then can be generalized into their outside lives. In FAP, the termination process will vary from client to client depending on the nature of the client's problems and targets. For many clients, the process can be a rich, multifaceted, final opportunity to evoke, reinforce, and promote generalization of clients' in-session improvements, particularly improvements related to vulnerable self-expression in the service of intimate and close relationships. By making explicit agreements at the outset of therapy to participate in an intentional termination process, and by later providing an evocative structure for ending therapy with vulnerable emotional expression, clients have the opportunity to develop more adaptive behaviors in the context of relationship endings which can be a painful part of the human experience. Equipped with the skills of open-hearted communication developed from an authentic relationship with their therapist, clients can leave therapy on a trajectory of further growth in interpersonal connection and living more boldly. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Human microRNA expression in sporadic and FAP-associated desmoid tumors and correlation with beta-catenin mutations.

PubMed

Cavallini, Aldo; Rotelli, Maria Teresa; Lippolis, Catia; Piscitelli, Domenico; Digennaro, Rosa; Covelli, Claudia; Carella, Nicola; Accetturo, Matteo; Altomare, Donato Francesco

2017-06-27

Desmoid tumors (DT) are rare, benign, fibroblastic neoplasm with challenging histological diagnosis. DTs can occur sporadically or associated with the familial adenomatous polyposis coli (FAP). Most sporadic DTs are associated with β-catenin gene (CTNNB1) mutations, while mutated APC gene causes FAP disease. microRNAs (miRNAs) are involved in many human carcinogenesis.The miRNA profile was analyzed by microarray in formalin-fixed, paraffin-embedded (FFPE) specimens of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls. One hundred and one mRNAs resulted dysregulated, of which 98 in sporadic DTs and 8 in FAP-associated DTs, 5 were shared by both tumors. Twenty-six miRNAs were then validated by RT-qPCR in 23 sporadic and 7 FAP-associated DT samples matched with healthy controls. The qPCR method was also used to evaluate the CTNNB1 mutational status in sporadic DTs. The correlation between sporadic DTs and miRNA expression showed that miR-21-3p increased in mutated versus wild-type DTs, while miR-197-3p was decreased. The mRNA expression of Tetraspanin3 and Serpin family A member 3, as miR-21-3p targets, and L1 Cell Adhesion Molecule, as miR-197-3p target, was also evaluate. CTNNB1 mutations associated to miRNA dysregulation could affect the genesis and the progression of this disease and help histological diagnosis of sporadic DTs.

Characterisation of FAP-1 expression and CD95 mediated apoptosis in the A818-6 pancreatic adenocarcinoma differentiation system.

PubMed

Winterhoff, Boris J N; Arlt, Alexander; Duttmann, Angelika; Ungefroren, Hendrik; Schäfer, Heiner; Kalthoff, Holger; Kruse, Marie-Luise

2012-03-01

The present study investigated the expression and localisation of FAP-1 (Fas associated phosphatase-1) and CD95 in a 3D differentiation model in comparison to 2D monolayers of the pancreatic adenocarcinoma cell line A818-6. Under non-adherent growth conditions, A818-6 cells differentiate into 3D highly organised polarised epithelial hollow spheres, resembling duct-like structures. A818-6 cells showed a differentiation-dependent FAP-1 localisation. Cells grown as 2D monolayers revealed FAP-1 staining in a juxtanuclear cisternal position, as well as localisation in the nucleus. After differentiation into hollow spheres, FAP-1 was relocated towards the actin cytoskeleton beneath the outer plasma membrane of polarised cells and no further nuclear localisation was observed. CD95 surface staining was found only in a subset of A818-6 monolayer cells, while differentiated hollow spheres appeared to express CD95 in all cells of a given sphere. We rarely observed co-localisation of CD95 and FAP-1 in A818-6 monolayer cells, but strong co-localisation beneath the outer plasma membrane in polarised cells. Analysis of surface expression by flow cytometry revealed that only a subset (36%) of monolayer cells showed CD95 surface expression, and after induction of hollow spheres, CD95 presentation at the outer plasma membrane was reduced to 13% of hollow spheres. Induction of apoptosis by stimulation with agonistic anti-CD95 antibodies, resulted in increased caspase activity in both, monolayer cells and hollow spheres. Knock down of FAP-1 mRNA in A818-6 monolayer cells did not alter resposiveness to CD95 agonistic antibodies. These data suggested that CD95 signal transduction was not affected by FAP-1 expression in A818-6 monolayer cells. In differentiated 3D hollow spheres, we found a polarisation-induced co-localisation of CD95 and FAP-1. A tight control of receptor surface representation and signalling induced apoptosis ensures controlled removal of individual cells instead of a

The importance of a large sample cohort for studies on modifier genes influencing disease severity in FAP patients.

PubMed

Talseth-Palmer, Bente A; Wijnen, Juul T; Andreassen, Eva K; Barker, Daniel; Jagmohan-Changur, Shantie; Tops, Carli M; Meldrum, Cliff; Spigelman, Allan; Hes, Frederik J; Van Wezel, Tom; Vasen, Hans Fa; Scott, Rodney J

2013-12-29

Familial adenomatous polyposis (FAP) is usually characterised by the appearance of hundreds-to-thousands of adenomas throughout the colon and rectum and if left untreated the condition will develop into CRC with close to 100% penetrance. Germline mutations in the APC gene, which plays an integral role in the Wnt-signalling pathway, have been found to be responsible for 70-90% of FAP cases. Several studies suggest that modifier genes may play an important role in the development of CRC and possible modifiers for FAP have been suggested. Interestingly, a study has found that SNPs within ATP5A1 is associated with raised levels of ATP5A1 expression and high expression levels may facilitate CRC development. We aimed to determine if SNPs in ATP5A1 modify the risk of developing CRC/adenomas in FAP patients. Genomic DNA from 139 Australian FAP patients with a germline APC mutation underwent genotyping at the Australian Genome Research Facility (AGRF) utilising iPLEX GOLD chemistry with Sequenom MassArray on an Autoflex Spectrometer for 16 SNPs in the ATP5A1 gene. Association between ages of diagnosis/risk of CRC/adenomas was tested with Kaplan-Meier estimator analysis, logistic regression and cox proportional hazard regression. An association between age of diagnosis of CRC and genotypes was observed for SNP rs2578189 (p = 0.0014), with individuals harbouring the variant genotype developing CRC 29 years earlier than individuals harbouring the wildtype genotype. Individuals harbouring the variant genotype of SNP rs2578189 were also at increased risk of CRC (HR = 13.79, 95% CI = 2.36-80.64, p = 0.004). We used an independent Dutch FAP cohort (n = 427) to validate our results; no association between SNP rs2578189 and CRC was observed. These results highlight the difficulties in studying a disease that has a high degree of intervention and also emphasize the importance of large sample sizes when searching for modifier genes in patients with an inherited

Anisotropic power spectrum of refractive-index fluctuation in hypersonic turbulence.

PubMed

Li, Jiangting; Yang, Shaofei; Guo, Lixin; Cheng, Mingjian

2016-11-10

An anisotropic power spectrum of the refractive-index fluctuation in hypersonic turbulence was obtained by processing the experimental image of the hypersonic plasma sheath and transforming the generalized anisotropic von Kármán spectrum. The power spectrum suggested here can provide as good a fit to measured spectrum data for hypersonic turbulence as that recorded from the nano-planar laser scattering image. Based on the newfound anisotropic hypersonic turbulence power spectrum, Rytov approximation was employed to establish the wave structure function and the spatial coherence radius model of electromagnetic beam propagation in hypersonic turbulence. Enhancing the anisotropy characteristics of the hypersonic turbulence led to a significant improvement in the propagation performance of electromagnetic beams in hypersonic plasma sheath. The influence of hypersonic turbulence on electromagnetic beams increases with the increase of variance of the refractive-index fluctuation and the decrease of turbulence outer scale and anisotropy parameters. The spatial coherence radius was much smaller than that in atmospheric turbulence. These results are fundamental to understanding electromagnetic wave propagation in hypersonic turbulence.

A distinct variant of papillary thyroid carcinoma indicating familial adenomatous polyposis (FAP): a case report and brief review.

PubMed

Liyanapathirana, Nishantha; Seneviratne, Sanjeewa Anuruddha; Samarasekera, Dharmabandhu Nandadeva

2015-12-17

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited intestinal polyposis syndrome with an incidence of about 1/8300 births and accounts for about 1% of all colorectal cancers. It has a spectrum of extra-intestinal manifestations including thyroid carcinoma which occur in 1-2% of affected. The cribriform morular variant (CMV) is a rare but distinct histological subtype of papillary thyroid carcinoma (PTC) associated with FAP. Most of the reported cases describe the above entity in the background of well-established FAP. We report a case where both entities presenting simultaneously in a previously undiagnosed patient with FAP without a family history of polyposis. A 24 year old Asian female presented to the surgical clinic with a goitre of eight months duration and recent onset of altered bowel habits with features of anaemia. She was previously healthy and there was no family history of adenomatous polyposis, colorectal carcinoma or thyroid neoplasms. Colonoscopy revealed large bowel polyposis and fine needle aspiration of thyroid revealed a smear suspicious for malignancy. She underwent total thyroidectomy which revealed CMV PTC. Histology was characterized by a prominent cribriform pattern of growth with interspersed cell clusters arranged as morules along with papillary structures which are the key features of this subtype. Diagnosis of CMV warrants ruling out of underlying FAP, irrespective of family history or gastrointestinal symptoms.

Perspectives on hypersonic viscous flow research

NASA Technical Reports Server (NTRS)

Cheng, H. K.

1993-01-01

Issues and advances in current hypersonic flow research perceived to be of interest in theoretical fluid/gas dynamics are reviewed. Particular attention is given to the hypersonic aircraft as waverider, computational methods and theoretical development in the study of viscous interaction, and boundary-layer instability and transition studies. In the present framework the study of viscous hypersonic flow faces transition problems of two kinds which represent the two major areas of current research: the turbulence transition in the high Re range and the transition to the free-molecule limit.

Photogrammetry of a Hypersonic Inflatable Aerodynamic Decelerator

NASA Technical Reports Server (NTRS)

Kushner, Laura Kathryn; Littell, Justin D.; Cassell, Alan M.

2013-01-01

In 2012, two large-scale models of a Hypersonic Inflatable Aerodynamic decelerator were tested in the National Full-Scale Aerodynamic Complex at NASA Ames Research Center. One of the objectives of this test was to measure model deflections under aerodynamic loading that approximated expected flight conditions. The measurements were acquired using stereo photogrammetry. Four pairs of stereo cameras were mounted inside the NFAC test section, each imaging a particular section of the HIAD. The views were then stitched together post-test to create a surface deformation profile. The data from the photogram- metry system will largely be used for comparisons to and refinement of Fluid Structure Interaction models. This paper describes how a commercial photogrammetry system was adapted to make the measurements and presents some preliminary results.

Evidence of a reverse side-chain effect of tris(pentafluoroethyl)trifluorophosphate [FAP]-based ionic liquids against pathogenic bacteria.

PubMed

Weyhing-Zerrer, Nadine; Kalb, Roland; Oßmer, Rolf; Rossmanith, Peter; Mester, Patrick

2018-02-01

Increased interest in ionic liquids (ILs) is due to their designable and tunable unique physicochemical properties, which are utilized for a wide variety of chemical and biotechnological applications. ILs containing the tris(pentafluoroethyl)trifluorophosphate ([FAP]) anion have been shown to have excellent hydrolytic, electrochemical and thermal stability and have been successfully used in various applications. In the present study the influence of the cation on the toxicity of the [FAP] anion was investigated. Due to the properties of [FAP] ILs, the IL-toxicity of seven cations with [FAP] compared to [Cl] was examined by determination of minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) on six Gram-positive and six Gram-negative clinically-relevant bacteria. For the first time, to our knowledge, the results provide evidence for a decrease in toxicity with increasing alkyl side-chain length, indicating that the combination of both ions is responsible for this 'reverse side-chain effect'. These findings could portend development of new non-toxic ILs as green alternatives to conventional organic solvents. Copyright © 2017 Elsevier Inc. All rights reserved.

Experimental Stage Separation Tool Development in NASA Langley's Aerothermodynamics Laboratory

NASA Technical Reports Server (NTRS)

Murphy, Kelly J.; Scallion, William I.

2005-01-01

As part of the research effort at NASA in support of the stage separation and ascent aerothermodynamics research program, proximity testing of a generic bimese wing-body configuration was conducted in NASA Langley's Aerothermodynamics Laboratory in the 20-Inch Mach 6 Air Tunnel. The objective of this work is the development of experimental tools and testing methodologies to apply to hypersonic stage separation problems for future multi-stage launch vehicle systems. Aerodynamic force and moment proximity data were generated at a nominal Mach number of 6 over a small range of angles of attack. The generic bimese configuration was tested in a belly-to-belly and back-to-belly orientation at 86 relative proximity locations. Over 800 aerodynamic proximity data points were taken to serve as a database for code validation. Longitudinal aerodynamic data generated in this test program show very good agreement with viscous computational predictions. Thus a framework has been established to study separation problems in the hypersonic regime using coordinated experimental and computational tools.

Hyper-X and Pegasus Launch Vehicle: A Three-Foot Model of the Hypersonic Experimental Research Vehic

NASA Technical Reports Server (NTRS)

1997-01-01

The configuration of the X-43A Hypersonic Experimental Research Vehicle, or Hyper-X, attached to a Pegasus launch vehicle is displayed in this side view of a three-foot-long model of the vehicle/booster combination at NASA's Dryden Flight Research Center, Edwards, California. Hyper-X, the flight vehicle for which is designated as X-43A, is an experimental flight-research program seeking to demonstrate airframe-integrated, 'air-breathing' engine technologies that promise to increase payload capacity for future vehicles, including hypersonic aircraft (faster than Mach 5) and reusable space launchers. This multiyear program is currently underway at NASA Dryden Flight Research Center, Edwards, California. The Hyper-X schedule calls for its first flight later this year (2000). Hyper-X is a joint program, with Dryden sharing responsibility with NASA's Langley Research Center, Hampton, Virginia. Dryden's primary role is to fly three unpiloted X-43A research vehicles to validate engine technologies and hypersonic design tools as well as the hypersonic test facility at Langley. Langley manages the program and leads the technology development effort. The Hyper-X Program seeks to significantly expand the speed boundaries of air-breathing propulsion by being the first aircraft to demonstrate an airframe-integrated, scramjet-powered free flight. Scramjets (supersonic-combustion ramjets) are ramjet engines in which the airflow through the whole engine remains supersonic. Scramjet technology is challenging because only limited testing can be performed in ground facilities. Long duration, full-scale testing requires flight research. Scramjet engines are air-breathing, capturing their oxygen from the atmosphere. Current spacecraft, such as the Space Shuttle, are rocket powered, so they must carry both fuel and oxygen for propulsion. Scramjet technology-based vehicles need to carry only fuel. By eliminating the need to carry oxygen, future hypersonic vehicles will be able to carry

Three dimensional viscous analysis of a hypersonic inlet

NASA Technical Reports Server (NTRS)

Reddy, D. R.; Smith, G. E.; Liou, M.-F.; Benson, Thomas J.

1989-01-01

The flow fields in supersonic/hypersonic inlets are currently being studied at NASA Lewis Research Center using 2- and 3-D full Navier-Stokes and Parabolized Navier-Stokes solvers. These tools have been used to analyze the flow through the McDonnell Douglas Option 2 inlet which has been tested at Calspan in support of the National Aerospace Plane Program. Comparisons between the computational and experimental results are presented. These comparisons lead to better overall understanding of the complex flows present in this class of inlets. The aspects of the flow field emphasized in this work are the 3-D effects, the transition from laminar to turbulent flow, and the strong nonuniformities generated within the inlet.

Hypersonic transports - Economics and environmental effects.

NASA Technical Reports Server (NTRS)

Petersen, R. H.; Waters, M. H.

1973-01-01

An economic analysis of hypersonic transports is presented to show projected operating costs (direct and indirect) and return on investment. Important assumptions are varied to determine the probable range of values for operating costs and return on investment. The environmental effects of hypersonic transports are discussed and compared to current supersonic transports. Estimates of sideline and flyover noise are made for a typical hypersonic transport, and the sonic boom problem is analyzed and discussed. Since the exhaust products from liquid hydrogen-fueled engines differ from those of kerosene-fueled aircraft, a qualitative assessment of air pollution effects is made.

Hypersonic transports - Economics and environmental effects.

NASA Technical Reports Server (NTRS)

Petersen, R. H.; Waters, M. H.

1972-01-01

An economic analysis of hypersonic transports is presented to show projected operating costs (direct and indirect) and return on investment. Important assumptions are varied to determine the probable range of values for operating costs and return on investment. The environmental effects of hypersonic transports are discussed and compared to current supersonic transports. Estimates of sideline and flyover noise are made for a typical hypersonic transport, and the sonic boom problem is analyzed and discussed. Since the exhaust products from liquid hydrogen-fueled engines differ from those of kerosene-fueled aircraft, a qualitative assessment of air pollution effects is made.

Hypersonic transports: Economics and environmental effects

NASA Technical Reports Server (NTRS)

Petersen, R. H.; Waters, M. H.

1972-01-01

An economic analysis of hypersonic transports is presented to show projected operating costs (direct and indirect) and return on investment. Important assumptions are varied to determine the probable range of values for operating costs and return on investment. The environmental effects of hypersonic transports are discussed and compared to current supersonic transports. Estimates of sideline and fly-over noise are made for a typical hypersonic transport, and the sonic boom problem is analyzed and discussed. Since the exhaust products from liquid hydrogen-fueled engines differ from those of kerosene-fueled aircraft, a qualitative assessment of air pollution effects is made.

Hypersonic flow analysis

NASA Technical Reports Server (NTRS)

Chow, Chuen-Yen; Ryan, James S.

1987-01-01

While the zonal grid system of Transonic Navier-Stokes (TNS) provides excellent modeling of complex geometries, improved shock capturing, and a higher Mach number range will be required if flows about hypersonic aircraft are to be modeled accurately. A computational fluid dynamics (CFD) code, the Compressible Navier-Stokes (CNS), is under development to combine the required high Mach number capability with the existing TNS geometry capability. One of several candidate flow solvers for inclusion in the CNS is that of F3D. This upwinding flow solver promises improved shock capturing, and more accurate hypersonic solutions overall, compared to the solver currently used in TNS.

The second X-43A hypersonic research aircraft, shown here in its protective shipping jig, arrives at NASA's Dryden Flight Research Center

NASA Image and Video Library

2001-01-31

The second of three X-43A hypersonic research aircraft, shown here in its protective shipping jig, arrived at NASA's Dryden Flight Research Center, Edwards, California, on January 31, 2001. The arrival of the second X-43A from its manufacturer, MicroCraft, Inc., of Tullahoma, Tenn., followed by only a few days the mating of the first X-43A and its specially-designed adapter to the first stage of a modified Pegasus® booster rocket. The booster, built by Orbital Sciences Corp., Dulles, Va., will accelerate the 12-foot-long, unpiloted research aircraft to a predetermined altitude and speed after the X-43A/booster "stack" is air-launched from NASA's venerable NB-52 mothership. The X-43A will then separate from the rocket and fly a pre-programmed trajectory, conducting aerodynamic and propulsion experiments until it impacts into the Pacific Ocean. Three research flights are planned, two at Mach 7 and one at Mach 10 (seven and 10 times the speed of sound respectively) with the first tentatively scheduled for early summer, 2001. The X-43A is powered by a revolutionary supersonic-combustion ramjet ("scramjet") engine, and will use the underbody of the aircraft to form critical elements of the engine. The forebody shape helps compress the intake airflow, while the aft section acts as a nozzle to direct thrust. The X-43A flights will be the first actual flight tests of an aircraft powered by an air-breathing scramjet engine.

Hypersonic Flight Test Windows for Technology Development Testing

DTIC Science & Technology

2013-11-01

used. 2.1 Propulsion and Controls Test Window The technologies dealing with scramjet propulsion (inlets, fuel injection, etc.) and hypersonic ...AFRL-RQ-WP-TM-2013-0260 HYPERSONIC FLIGHT TEST WINDOWS FOR TECHNOLOGY DEVELOPMENT TESTING Barry M. Hellman Vehicle Technology Branch...DATES COVERED (From - To) November 2013 Final 01 November 2013 – 25 November 2013 4. TITLE AND SUBTITLE HYPERSONIC FLIGHT TEST WINDOWS FOR

A methodology for hypersonic transport technology planning

NASA Technical Reports Server (NTRS)

Repic, E. M.; Olson, G. A.; Milliken, R. J.

1973-01-01

A systematic procedure by which the relative economic value of technology factors affecting design, configuration, and operation of a hypersonic cruise transport can be evaluated is discussed. Use of the methodology results in identification of first-order economic gains potentially achievable by projected advances in each of the definable, hypersonic technologies. Starting with a baseline vehicle, the formulas, procedures and forms which are integral parts of this methodology are developed. A demonstration of the methodology is presented for one specific hypersonic vehicle system.

mir-200c Regulates Induction of Apoptosis through CD95 by Targeting FAP-1

PubMed Central

Schickel, Robert; Park, Sun-Mi; Murmann, Andrea E.; Peter, Marcus E.

2010-01-01

SUMMARY Tumor progression shares many characteristics with the process of epithelial-to-mesenchymal transition (EMT). Cells that have undergone an EMT are known to have an increased resistance to apoptosis. CD95/Fas is an apoptosis-inducing receptor expressed on many tissues and tumor cells. During tumor progression CD95 is frequently downregulated, and tumor cells lose apoptosis sensitivity. miR-200 microRNAs repress both the EMT-inducing ZEB1 and ZEB2 transcription factors. We now demonstrate that miR-200c sensitizes cells to apoptosis mediated by CD95. We have identified the apoptosis inhibitor FAP-1 as a target for miR-200c. FAP-1 was demonstrated to be responsible for the reduced sensitivity to CD95-mediated apoptosis in cells with inhibited miR-200. The identification of FAP-1 as a miR-200c target provides a molecular mechanism to explain both the downregulation of CD95 expression and the reduction in sensitivity of cells to CD95-mediated apoptosis that is observed in the context of reduced miR-200 expression during tumor progression. PMID:20620960

Epigallocatechin-3-gallate as a potential therapeutic drug for TTR-related amyloidosis: "in vivo" evidence from FAP mice models.

PubMed

Ferreira, Nelson; Saraiva, Maria João; Almeida, Maria Rosário

2012-01-01

Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disease caused by the extracellular deposition of mutant transthyretin (TTR), with special involvement of the peripheral nervous system (PNS). Currently, hepatic transplantation is considered the most efficient therapy to halt the progression of clinical symptoms in FAP since more than 95% of TTR is produced by the liver. However, less invasive and more reliable therapeutic approaches have been proposed for FAP therapy, namely based on drugs acting as inhibitors of amyloid formation or as amyloid disruptors. We have recently reported that epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, is able to inhibit TTR aggregation and fibril formation, "in vitro" and in a cellular system, and is also able to disrupt pre-formed amyloid fibrils "in vitro". In the present study, we assessed the effect of EGCG subchronic administration on TTR amyloidogenesis "in vivo", using well characterized animal models for FAP. Semiquantitative immunohistochemistry (SQ-IHC) and Western blot analysis of mice tissues after treatment demonstrated that EGCG inhibits TTR toxic aggregates deposition in about 50% along the gastrointestinal tract (GI) and peripheral nervous system (PNS). Moreover EGCG treatment considerably lowered levels of several biomarkers associated with non-fibrillar TTR deposition, namely endoplasmic reticulum (ER)-stress, protein oxidation and apoptosis markers. Treatment of old FAP mice with EGCG resulted not only in the decrease of non-fibrillar TTR deposition but also in disaggregation of amyloid deposits. Consistently, matrix metalloproteinase (MMP)-9 and serum amyloid P component (SAP), both markers of amyloid deposition, were also found reduced in treated old FAP mice. The dual effect of EGCG both as TTR aggregation inhibitor and amyloid fibril disruptor together with the high tolerability and low toxicity of EGCG in humans, point towards the potential use of this compound, or

[A Case in Which a Patient Was Operated for Intra-Abdominal Desmoid Tumors after Total Colectomy in FAP].

PubMed

Hoshi, Minako; Ikeda, Kimimasa; Higashiguchi, Kimiya; Kobayashi, Teruyuki; Sakai, Kenji; Koyama, Taichi; Doi, Takasi; Taniguchi, Hirokazu; Murakami, Masakazu; Kurokawa, Eiji; Nakamichi, Itsuko

2015-11-01

The patient was a 22-year-old woman with FAP, who had undergone laparoscopic total colectomy 3 years previously. She presented to our hospital with a high fever and abdominal pain. Large hard tumors were palpated in the right lower abdomen and pelvis. Blood examination showed an inflammatory response. CT scan revealed 17 cm diameter solid tumors. At surgery, 2 tumors arising from the mesentery of the small intestine were found, neither of which invaded any organs. We performed tumor extirpation with partial resection of the duodenum, ileum, right fallopian tube and rectum. A jejunal stoma was formed, leaving a length of remnant intestine of about 120 cm. The histopathological diagnosis was given as desmoid tumor with infection. The patient was discharged from the hospital on the 9th postoperative day. Desmoid tumor is the second most common cause of death in FAP patients. Although desmoids can also occur in the extremities, most FAP patients develop intra-abdominal tumors. Despite being histologically benign, they are locally infiltrative and can cause death through invasion and destruction of adjacent vital structures and organs. Here, we report a case of desmoid tumors with FAP with reference to the literature.

Free volume dependence of an ionic molecular rotor in Fluoroalkylphosphate (FAP) based ionic liquids

NASA Astrophysics Data System (ADS)

Singh, Prabhat K.; Mora, Aruna K.; Nath, Sukhendu

2016-01-01

The emission properties of Thioflavin-T (ThT), a cationic molecular rotor, have been investigated in two fluoroalkylphosphate ([FAP]) anion based ionic liquids, namely, 1-ethyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate and 1-(2-hydroxyethyl)-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate, over a wide temperature range. The micro-viscosities of ionic liquids around ThT, measured from the emission quantum yield, are found to be quite different from their bulk viscosities. The temperature dependence of the viscosity and the emission quantum yield reveals that, despite the very low shear viscosity of these ILs, the non-radiative torsional relaxation has a strong dependence on the free volume of these [FAP] anion based ILs.

On Parametric Sensitivity of Reynolds-Averaged Navier-Stokes SST Turbulence Model: 2D Hypersonic Shock-Wave Boundary Layer Interactions

NASA Technical Reports Server (NTRS)

Brown, James L.

2014-01-01

Examined is sensitivity of separation extent, wall pressure and heating to variation of primary input flow parameters, such as Mach and Reynolds numbers and shock strength, for 2D and Axisymmetric Hypersonic Shock Wave Turbulent Boundary Layer interactions obtained by Navier-Stokes methods using the SST turbulence model. Baseline parametric sensitivity response is provided in part by comparison with vetted experiments, and in part through updated correlations based on free interaction theory concepts. A recent database compilation of hypersonic 2D shock-wave/turbulent boundary layer experiments extensively used in a prior related uncertainty analysis provides the foundation for this updated correlation approach, as well as for more conventional validation. The primary CFD method for this work is DPLR, one of NASA's real-gas aerothermodynamic production RANS codes. Comparisons are also made with CFL3D, one of NASA's mature perfect-gas RANS codes. Deficiencies in predicted separation response of RANS/SST solutions to parametric variations of test conditions are summarized, along with recommendations as to future turbulence approach.

Computational mechanics and physics at NASA Langley Research Center

NASA Technical Reports Server (NTRS)

South, Jerry C., Jr.

1987-01-01

An overview is given of computational mechanics and physics at NASA Langley Research Center. Computational analysis is a major component and tool in many of Langley's diverse research disciplines, as well as in the interdisciplinary research. Examples are given for algorithm development and advanced applications in aerodynamics, transition to turbulence and turbulence simulation, hypersonics, structures, and interdisciplinary optimization.

CFD applications in hypersonic flight

NASA Technical Reports Server (NTRS)

Edwards, T. A.

1992-01-01

Design studies are underway for a variety of hypersonic flight vehicles. The National Aero-Space Plane will provide a reusable, single-stage-to-orbit capability for routine access to low earth orbit. Flight-capable satellites will dip into the atmosphere to maneuver to new orbits, while planetary probes will decelerate at their destination by atmospheric aerobraking. To supplement limited experimental capabilities in the hypersonic regime, CFD is being used to analyze the flow about these configurations. The governing equations include fluid dynamic as well as chemical species equations, which are solved with robust upwind differencing schemes. Examples of CFD applications to hypersonic vehicles suggest an important role this technology will play in the development of future aerospace systems. The computational resources needed to obtain solutions are large, but various strategies are being exploited to reduce the time required for complete vehicle simulations.

Yb:FAP and related materials, laser gain medium comprising same, and laser systems using same

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

Krupke, William F.; Payne, Stephen A.; Chase, Lloyd L.

An ytterbium doped laser material remarkably superior to all others, including Yb:YAG, comprises Ytterbium doped apatite (Yb:Ca.sub.5 (PO.sub.4).sub.3 F) or Yb:FAP, or ytterbium doped crystals that are structurally related to FAP. The new laser material is used in laser systems pumped by diode pump sources having an output near 0.905 microns or 0.98 microns, such as InGaAs and AlInGaAs, or other narrowband pump sources near 0.905 microns or 0.98 microns. The laser systems are operated in either the conventional or ground state depletion mode.

Yb:FAP and related materials, laser gain medium comprising same, and laser systems using same

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

Krupke, W.F.; Payne, S.A.; Chase, L.L.

An ytterbium doped laser material remarkably superior to all others, including Yb:YAG, comprises ytterbium doped apatite (Yb:Ca{sub 5}(PO{sub 4}){sub 3}F) or Yb:FAP, or ytterbium doped crystals structurally related to FAP. The new laser material is used in laser systems pumped by diode pump sources having an output near 0.905 microns or 0.98 microns, such as InGaAs and AlInGaAs, or other narrowband pump sources near 0.905 microns or 0.98 microns. The laser systems are operated in either the conventional or ground state depletion mode.

Impact of antibodies against amyloidogenic transthyretin (ATTR) on phenotypes of patients with familial amyloidotic polyneuropathy (FAP) ATTR Valine30Methionine.

PubMed

Obayashi, Konen; Tasaki, Masayoshi; Jono, Hirofumi; Ueda, Mitsuharu; Shinriki, Satoru; Misumi, Yohei; Yamashita, Taro; Oshima, Toshinori; Nakamura, Teruya; Ikemizu, Shinji; Anan, Intissar; Suhr, Ole; Ando, Yukio

2013-04-18

This study investigated whether a relationship exists between the presence of de novo antibodies and the clinical manifestations of familial amyloidotic polyneuropathy (FAP). Serum samples were collected from 25 Japanese and 6 Swedish FAP amyloidogenic transthyretin (ATTR) Valine30Methionine (V30M) patients, 4 asymptomatic Japanese ATTR V30M gene carriers, and 24 Japanese healthy volunteers. Study methods included enzyme-linked immunosorbent assay (ELISA) and mass spectrometry. Three Japanese and 5 Swedish patients had significantly higher levels of antibodies against ATTR than did healthy volunteers and asymptomatic gene carriers (P<0.05). All 8 patients with higher antibody levels were late-onset cases. The ratio of wild-type TTR to ATTR V30M in serum from the high-antibody group was higher than that of the low-antibody group. ELISA results revealed two epitopes at positions 24-35 and 105-115 of ATTR V30M. We found a significant positive correlation between levels of the antibody at positions 24-35 and the age at FAP onset (r=0.751, P<0.05). An age-dependent increase in the occurrence of antibodies was observed in these patients with an epitope at positions 24-35. These findings may help explain the differences in early- and late-onset FAP and/or the progression of FAP. Copyright © 2013 Elsevier B.V. All rights reserved.

Low expression of miR-30a-5p induced the proliferation and invasion of oral cancer via promoting the expression of FAP

PubMed Central

Ruan, Peng; Tao, Zezhang

2017-01-01

The study aimed at investigating the effects of miR-30a-5p on the biological functions of oral cancer cells and figuring out the potential mechanism. We first verified the low expression of miR-30a-5p and high expression of FAP (Homo sapiens fibroblast activation protein α) in oral cancerous tissues and their negative correlation. Then, the target relationship between miR-30a-5p and FAP was validated by dual luciferase reporter assay and biotin-coupled miRNA pulldown assay. After transfection in Tca-8113 cells and SCC-15 cells, MTT, colony formation, Transwell, and wound healing assays were performed to investigate how miR-30a-5p and FAP adjusted propagation, invasiveness, and migration, respectively. Mounting evidence supported that miR-30a-5p directly targetted FAP and suppressed its expression in oral cavity cancer cells (OSCCs). By suppressing FAP expression, miR-30a-5p significantly inhibited cell propagation, migration, and invasion. Therefore, miR-30a-5p might be a new therapeutic target for oral cancer treatment. PMID:29026005

Hypersonic research at Stanford University

NASA Technical Reports Server (NTRS)

Candler, Graham; Maccormack, Robert

1988-01-01

The status of the hypersonic research program at Stanford University is discussed and recent results are highlighted. The main areas of interest in the program are the numerical simulation of radiating, reacting and thermally excited flows, the investigation and numerical solution of hypersonic shock wave physics, the extension of the continuum fluid dynamic equations to the transition regime between continuum and free-molecule flow, and the development of novel numerical algorithms for efficient particulate simulations of flowfields.

Scramjet integration on hypersonic research airplane concepts

NASA Technical Reports Server (NTRS)

Weidner, J. P.; Small, W. J.; Penland, J. A.

1976-01-01

Several rocket-boosted research airplane concepts were evaluated with a research scramjet engine to determine their potential to provide research on critical aspects of airframe-integrated hypersonic systems. Extensive calculations to determine the force and moment contributions of the scramjet inlet, combustor, nozzle, and airframe were conducted to evaluate the overall performance of the combined engine/airframe system at hypersonic speeds. Results of both wind-tunnel tests and analysis indicate that it is possible to develop a research airplane configuration that will cruise at hypersonic speed on scramjet power alone, and will also have acceptable low-speed aerodynamic characteristics for landing.

2nd NASA CFD Validation Workshop

NASA Technical Reports Server (NTRS)

1990-01-01

The purpose of the workshop was to review NASA's progress in CFD validation since the first workshop (held at Ames in 1987) and to affirm the future direction of the NASA CFD validation program. The first session consisted of overviews of CFD validation research at each of the three OAET research centers and at Marshall Space Flight Center. The second session consisted of in-depth technical presentations of the best examples of CFD validation work at each center (including Marshall). On the second day the workshop divided into three working groups to discuss CFD validation progress and needs in the subsonic, high-speed, and hypersonic speed ranges. The emphasis of the working groups was on propulsion.

PTT analysis of polyps from FAP patients reveals a great majority of APC truncating mutations

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

Luijt, R.B. van der; Khan, P.M.; Tops, C.M.J.

The adenomatous polyposis coli (APC) gene plays an important role in colorectal carcinogenesis. Germline APC mutations are associated with familial adenomatous polyposis (FAP), an autosomal dominantly inherited predisposition to colorectal cancer, characterized by the development of numerous adenomatous polyps in the large intestine. In order to investigate whether somatic inactivation of the remaining APC allele is necessary for adenoma formation, we collected multiple adenomatous polyps from individual FAP patients and investigated the presence of somatic mutations in the APC gene. The analysis of somatic APC mutations in these tumor samples was performed using a rapid and sensitive assay, called themore » protein truncation test (PTT). Chain-terminating somatic APC mutations were detected in the great majority of the tumor samples investigated. As expected, these mutations were mainly located in the mutation cluster region (MCR) in exon 15. Our results confirm that somatic mutation of the second APC allele is required for adenoma formation in FAP. Interestingly, in the polyps investigated in our study, the second APC allele is somatically inactivated through point mutation leading to a stop codon rather than by loss of heterozygosity. The observation that somatic second hits in APC are required for tumor development in FAP is in apparent accordance with the Knudson hypothesis for classical tumor suppressor genes. However, it is yet unknown whether chain-terminating APC mutations lead to a truncated protein exerting a dominant-negative effect or whether these mutations result in a null allele. Further investigation of this important issue will hopefully provide a better understanding of the mechanism of action of the mutated APC alleles in colorectal carcinogenesis.« less

Magnetic Control of Hypersonic Flow

NASA Astrophysics Data System (ADS)

Poggie, Jonathan; Gaitonde, Datta

2000-11-01

Electromagnetic control is an appealing possibility for mitigating the thermal loads that occur in hypersonic flight, in particular for the case of atmospheric entry. There was extensive research on this problem between about 1955 and 1970,(M. F. Romig, ``The Influence of Electric and Magnetic Fields on Heat Transfer to Electrically Conducting Fluids,'' \\underlineAdvances In Heat Transfer), Vol. 1, Academic Press, NY, 1964. and renewed interest has arisen due to developments in the technology of super-conducting magnets and the understanding of the physics of weakly-ionized, non-equilibrium plasmas. In order to examine the physics of this problem, and to evaluate the practicality of electromagnetic control in hypersonic flight, we have developed a computer code to solve the three-dimensional, non-ideal magnetogasdynamics equations. We have applied the code to the problem of magnetically-decelerated hypersonic flow over a sphere, and observed a reduction, with an applied dipole field, in heat flux and skin friction near the nose of the body, as well as an increase in shock standoff distance. The computational results compare favorably with the analytical predictions of Bush.(W. B. Bush, ``Magnetohydrodynamic-Hypersonic Flow Past a Blunt Body'', Journal of the Aero/Space Sciences, Vol. 25, No. 11, 1958; ``The Stagnation-Point Boundary Layer in the Presence of an Applied Magnetic Field'', Vol. 28, No. 8, 1961.)

Yb:FAP and related materials, laser gain medium comprising same, and laser systems using same

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

Krupke, W.F.; Payne, S.A.; Chase, L.L.

An ytterbium doped laser material remarkably superior to all others, including Yb:YAG, comprises ytterbium doped apatite (Yb:Ca[sub 5](PO[sub 4])[sub 3]F) or Yb:FAP, or ytterbium doped crystals that are structurally related to FAP. The new laser material is used in laser systems pumped by diode pump sources having an output near 0.905 microns or 0.98 microns, such as InGaAs and AlInGaAs, or other narrowband pump sources near 0.905 microns or 0.98 microns. The laser systems are operated in either the conventional or ground state depletion mode. 9 figures.

Yb:FAP and related materials, laser gain medium comprising same, and laser systems using same

DOEpatents

Krupke, W.F.; Payne, S.A.; Chase, L.L.; Smith, L.K.

1994-01-18

An ytterbium doped laser material remarkably superior to all others, including Yb:YAG, comprises ytterbium doped apatite (Yb:Ca[sub 5](PO[sub 4])[sub 3]F) or Yb:FAP, or ytterbium doped crystals that are structurally related to FAP. The new laser material is used in laser systems pumped by diode pump sources having an output near 0.905 microns or 0.98 microns, such as InGaAs and AlInGaAs, or other narrowband pump sources near 0.905 microns or 0.98 microns. The laser systems are operated in either the conventional or ground state depletion mode. 9 figures.

Artist Concept of X-43A/Hyper-X Hypersonic Experimental Research Vehicle in Flight

NASA Technical Reports Server (NTRS)

1998-01-01

An artist's conception of the X-43A Hypersonic Experimental Vehicle, or 'Hyper-X' in flight. The X-43A was developed to flight test a dual-mode ramjet/scramjet propulsion system at speeds from Mach 7 up to Mach 10 (7 to 10 times the speed of sound, which varies with temperature and altitude). Hyper-X, the flight vehicle for which is designated as X-43A, is an experimental flight-research program seeking to demonstrate airframe-integrated, 'air-breathing' engine technologies that promise to increase payload capacity for future vehicles, including hypersonic aircraft (faster than Mach 5) and reusable space launchers. This multiyear program is currently underway at NASA Dryden Flight Research Center, Edwards, California. The Hyper-X schedule calls for its first flight later this year (2000). Hyper-X is a joint program, with Dryden sharing responsibility with NASA's Langley Research Center, Hampton, Virginia. Dryden's primary role is to fly three unpiloted X-43A research vehicles to validate engine technologies and hypersonic design tools as well as the hypersonic test facility at Langley. Langley manages the program and leads the technology development effort. The Hyper-X Program seeks to significantly expand the speed boundaries of air-breathing propulsion by being the first aircraft to demonstrate an airframe-integrated, scramjet-powered free flight. Scramjets (supersonic-combustion ramjets) are ramjet engines in which the airflow through the whole engine remains supersonic. Scramjet technology is challenging because only limited testing can be performed in ground facilities. Long duration, full-scale testing requires flight research. Scramjet engines are air-breathing, capturing their oxygen from the atmosphere. Current spacecraft, such as the Space Shuttle, are rocket powered, so they must carry both fuel and oxygen for propulsion. Scramjet technology-based vehicles need to carry only fuel. By eliminating the need to carry oxygen, future hypersonic vehicles will

Overview of hypersonic CFD code calibration studies

NASA Technical Reports Server (NTRS)

Miller, Charles G.

1987-01-01

The topics are presented in viewgraph form and include the following: definitions of computational fluid dynamics (CFD) code validation; climate in hypersonics and LaRC when first 'designed' CFD code calibration studied was initiated; methodology from the experimentalist's perspective; hypersonic facilities; measurement techniques; and CFD code calibration studies.

Limitations of the method of characteristics when applied to axisymmetric hypersonic nozzle design

NASA Technical Reports Server (NTRS)

Edwards, Anne C.; Perkins, John N.; Benton, James R.

1990-01-01

A design study of axisymmetric hypersonic wind tunnel nozzles was initiated by NASA Langley Research Center with the objective of improving the flow quality of their ground test facilities. Nozzles for Mach 6 air, Mach 13.5 nitrogen, and Mach 17 nitrogen were designed using the Method of Characteristics/Boundary Layer (MOC/BL) approach and were analyzed with a Navier-Stokes solver. Results of the analysis agreed well with design for the Mach 6 case, but revealed oblique shock waves of increasing strength originating from near the inflection point of the Mach 13.5 and Mach 17 nozzles. The findings indicate that the MOC/BL design method has a fundamental limitation that occurs at some Mach number between 6 an 13.5. In order to define the limitation more exactly and attempt to discover the cause, a parametric study of hypersonic ideal air nozzles designed with the current MOC/BL method was done. Results of this study indicate that, while stagnations conditions have a moderate affect on the upper limit of the method, the method fails at Mach numbers above 8.0.

Space shuttle orbiter rear mounted reaction control system jet interaction study. [hypersonic wind tunnel tests

NASA Technical Reports Server (NTRS)

Rausch, J. R.

1977-01-01

The effect of interaction between the reaction control system (RCS) jets and the flow over the space shuttle orbiter in the atmosphere was investigated in the NASA Langley 31-inch continuous flow hypersonic tunnel at a nominal Mach number of 10.3 and in the AEDC continuous flow hypersonic tunnel B at a nominal Mach number of 6, using 0.01 and .0125 scale force models with aft RCS nozzles mounted both on the model and on the sting of the force model balance. The data show that RCS nozzle exit momentum ratio is the primary correlating parameter for effects where the plume impinges on an adjacent surface and mass flow ratio is the parameter when the plume interaction is primarily with the external stream. An analytic model of aft mounted RCS units was developed in which the total reaction control moments are the sum of thrust, impingement, interaction, and cross-coupling terms.

Low expression of miR-30a-5p induced the proliferation and invasion of oral cancer via promoting the expression of FAP.

PubMed

Ruan, Peng; Tao, Zezhang; Tan, Aili

2018-02-28

The study aimed at investigating the effects of miR-30a-5p on the biological functions of oral cancer cells and figuring out the potential mechanism. We first verified the low expression of miR-30a-5p and high expression of FAP ( Homo sapiens fibroblast activation protein α) in oral cancerous tissues and their negative correlation. Then, the target relationship between miR-30a-5p and FAP was validated by dual luciferase reporter assay and biotin-coupled miRNA pulldown assay. After transfection in Tca-8113 cells and SCC-15 cells, MTT, colony formation, Transwell, and wound healing assays were performed to investigate how miR-30a-5p and FAP adjusted propagation, invasiveness, and migration, respectively. Mounting evidence supported that miR-30a-5p directly targetted FAP and suppressed its expression in oral cavity cancer cells (OSCCs). By suppressing FAP expression, miR-30a-5p significantly inhibited cell propagation, migration, and invasion. Therefore, miR-30a-5p might be a new therapeutic target for oral cancer treatment. © 2018 The Author(s).

Stereoscopic Imaging in Hypersonics Boundary Layers using Planar Laser-Induced Fluorescence

NASA Technical Reports Server (NTRS)

Danehy, Paul M.; Bathel, Brett; Inman, Jennifer A.; Alderfer, David W.; Jones, Stephen B.

2008-01-01

Stereoscopic time-resolved visualization of three-dimensional structures in a hypersonic flow has been performed for the first time. Nitric Oxide (NO) was seeded into hypersonic boundary layer flows that were designed to transition from laminar to turbulent. A thick laser sheet illuminated and excited the NO, causing spatially-varying fluorescence. Two cameras in a stereoscopic configuration were used to image the fluorescence. The images were processed in a computer visualization environment to provide stereoscopic image pairs. Two methods were used to display these image pairs: a cross-eyed viewing method which can be viewed by naked eyes, and red/blue anaglyphs, which require viewing through red/blue glasses. The images visualized three-dimensional information that would be lost if conventional planar laser-induced fluorescence imaging had been used. Two model configurations were studied in NASA Langley Research Center's 31-Inch Mach 10 Air Wind tunnel. One model was a 10 degree half-angle wedge containing a small protuberance to force the flow to transition. The other model was a 1/3-scale, truncated Hyper-X forebody model with blowing through a series of holes to force the boundary layer flow to transition to turbulence. In the former case, low flowrates of pure NO seeded and marked the boundary layer fluid. In the latter, a trace concentration of NO was seeded into the injected N2 gas. The three-dimensional visualizations have an effective time resolution of about 500 ns, which is fast enough to freeze this hypersonic flow. The 512x512 resolution of the resulting images is much higher than high-speed laser-sheet scanning systems with similar time response, which typically measure 10-20 planes.

Hypersonic Inflatable Aerodynamic Decelerator Ground Test Development

NASA Technical Reports Server (NTRS)

Del Corso, Jospeh A.; Hughes, Stephen; Cheatwood, Neil; Johnson, Keith; Calomino, Anthony

2015-01-01

Hypersonic Inflatable Aerodynamic Decelerator (HIAD) technology readiness levels have been incrementally matured by NASA over the last thirteen years, with most recent support from NASA's Space Technology Mission Directorate (STMD) Game Changing Development Program (GCDP). Recently STMD GCDP has authorized funding and support through fiscal year 2015 (FY15) for continued HIAD ground developments which support a Mars Entry, Descent, and Landing (EDL) study. The Mars study will assess the viability of various EDL architectures to enable a Mars human architecture pathfinder mission planned for mid-2020. At its conclusion in November 2014, NASA's first HIAD ground development effort had demonstrated success with fabricating a 50 W/cm2 modular thermal protection system, a 400 C capable inflatable structure, a 10-meter scale aeroshell manufacturing capability, together with calibrated thermal and structural models. Despite the unquestionable success of the first HIAD ground development effort, it was recognized that additional investment was needed in order to realize the full potential of the HIAD technology capability to enable future flight opportunities. The second HIAD ground development effort will focus on extending performance capability in key technology areas that include thermal protection system, lifting-body structures, inflation systems, flight control, stage transitions, and 15-meter aeroshell scalability. This paper presents an overview of the accomplishments under the baseline HIAD development effort and current plans for a follow-on development effort focused on extending those critical technologies needed to enable a Mars Pathfinder mission.

Diagnostic pitfalls in sporadic transthyretin familial amyloid polyneuropathy (TTR-FAP).

PubMed

Planté-Bordeneuve, V; Ferreira, A; Lalu, T; Zaros, C; Lacroix, C; Adams, D; Said, G

2007-08-14

Transthyretin familial amyloid polyneuropathies (TTR-FAPs) are autosomal dominant neuropathies of fatal outcome within 10 years after inaugural symptoms. Late diagnosis in patients who present as nonfamilial cases delays adequate management and genetic counseling. Clinical data of the 90 patients who presented as nonfamilial cases of the 300 patients of our cohort of patients with TTR-FAP were reviewed. They were 21 women and 69 men with a mean age at onset of 61 (extremes: 38 to 78 years) and 17 different mutations of the TTR gene including Val30Met (38 cases), Ser77Tyr (16 cases), Ile107Val (15 cases), and Ser77Phe (5 cases). Initial manifestations included mainly limb paresthesias (49 patients) or pain (17 patients). Walking difficulty and weakness (five patients) and cardiac or gastrointestinal manifestations (five patients), were less common at onset. Mean interval to diagnosis was 4 years (range 1 to 10 years); 18 cases were mistaken for chronic inflammatory demyelinating polyneuropathy, which was the most common diagnostic error. At referral a length-dependent sensory loss affected the lower limbs in 2, all four limbs in 20, and four limbs and anterior trunk in 77 patients. All sensations were affected in 60 patients (67%), while small fiber dysfunction predominated in the others. Severe dysautonomia affected 80 patients (90%), with postural hypotension in 52, gastrointestinal dysfunction in 50, impotence in 58 of 69 men, and sphincter disturbance in 31. Twelve patients required a cardiac pacemaker. Nerve biopsy was diagnostic in 54 of 65 patients and salivary gland biopsy in 20 of 30. Decreased nerve conduction velocity, increased CSF protein, negative biopsy findings, and false immunolabeling of amyloid deposits were the main causes of diagnostic errors. We conclude that DNA testing, which is the most reliable test for TTR-FAP, should be performed in patients with a progressive length-dependent small fiber polyneuropathy of unknown origin, especially when

Unstart coupling mechanism analysis of multiple-modules hypersonic inlet.

PubMed

Hu, Jichao; Chang, Juntao; Wang, Lei; Cao, Shibin; Bao, Wen

2013-01-01

The combination of multiplemodules in parallel manner is an important way to achieve the much higher thrust of scramjet engine. For the multiple-modules scramjet engine, when inlet unstarted oscillatory flow appears in a single-module engine due to high backpressure, how to interact with each module by massflow spillage, and whether inlet unstart occurs in other modules are important issues. The unstarted flowfield and coupling characteristic for a three-module hypersonic inlet caused by center module II and side module III were, conducted respectively. The results indicate that the other two hypersonic inlets are forced into unstarted flow when unstarted phenomenon appears on a single-module hypersonic inlet due to high backpressure, and the reversed flow in the isolator dominates the formation, expansion, shrinkage, and disappearance of the vortexes, and thus, it is the major factor of unstart coupling of multiple-modules hypersonic inlet. The coupling effect among multiple modules makes hypersonic inlet be more likely unstarted.

Unstart Coupling Mechanism Analysis of Multiple-Modules Hypersonic Inlet

PubMed Central

Wang, Lei; Cao, Shibin

2013-01-01

The combination of multiplemodules in parallel manner is an important way to achieve the much higher thrust of scramjet engine. For the multiple-modules scramjet engine, when inlet unstarted oscillatory flow appears in a single-module engine due to high backpressure, how to interact with each module by massflow spillage, and whether inlet unstart occurs in other modules are important issues. The unstarted flowfield and coupling characteristic for a three-module hypersonic inlet caused by center module II and side module III were, conducted respectively. The results indicate that the other two hypersonic inlets are forced into unstarted flow when unstarted phenomenon appears on a single-module hypersonic inlet due to high backpressure, and the reversed flow in the isolator dominates the formation, expansion, shrinkage, and disappearance of the vortexes, and thus, it is the major factor of unstart coupling of multiple-modules hypersonic inlet. The coupling effect among multiple modules makes hypersonic inlet be more likely unstarted. PMID:24348146

An experimental investigation of the NASA space shuttle external tank at hypersonic Mach numbers

NASA Technical Reports Server (NTRS)

Wittliff, C. E.

1975-01-01

Pressure and heat transfer tests were conducted simulating flight conditions which the space shuttle external tank will experience prior to break-up. The tests were conducted in the Calspan 48-inch Hypersonic Shock Tunnel and simulated entry conditions for nominal, abort-once-around (AOA), and return to launch site (RTLS) launch occurrences. Surface pressure and heat-transfer-rate distributions were obtained with and without various protuberences (or exterior hardware) on the model at Mach numbers from 15.2 to 17.7 at angles of attack from -15 deg to -180 deg and at several roll angles. The tests were conducted over a Reynolds number range from 1300 to 58,000, based on model length.

Scaled Rocket Testing in Hypersonic Flow

NASA Technical Reports Server (NTRS)

Dufrene, Aaron; MacLean, Matthew; Carr, Zakary; Parker, Ron; Holden, Michael; Mehta, Manish

2015-01-01

NASA's Space Launch System (SLS) uses four clustered liquid rocket engines along with two solid rocket boosters. The interaction between all six rocket exhaust plumes will produce a complex and severe thermal environment in the base of the vehicle. This work focuses on a recent 2% scale, hot-fire SLS base heating test. These base heating tests are short-duration tests executed with chamber pressures near the full-scale values with gaseous hydrogen/oxygen engines and RSRMV analogous solid propellant motors. The LENS II shock tunnel/Ludwieg tube tunnel was used at or near flight duplicated conditions up to Mach 5. Model development was strongly based on the Space Shuttle base heating tests with several improvements including doubling of the maximum chamber pressures and duplication of freestream conditions. Detailed base heating results are outside of the scope of the current work, rather test methodology and techniques are presented along with broader applicability toward scaled rocket testing in supersonic and hypersonic flow.

Further Investigations of Hypersonic Engine Seals

NASA Technical Reports Server (NTRS)

Dunlap, Patrick H., Jr.; Steinetz, Bruce M.; DeMange, Jeffrey J.

2004-01-01

Durable, flexible sliding seals are required in advanced hypersonic engines to seal the perimeters of movable engine ramps for efficient, safe operation in high heat flux environments at temperatures of 2000 to 2500 F. Current seal designs do not meet the demanding requirements for future engines, so NASA's Glenn Research Center is developing advanced seals and preloading devices to overcome these shortfalls. An advanced ceramic wafer seal design and two silicon nitride compression spring designs were evaluated in a series of compression, scrub, and flow tests. Silicon nitride wafer seals survived 2000 in. (50.8 m) of scrubbing at 2000 F against a silicon carbide rub surface with no chips or signs of damage. Flow rates measured for the wafers before and after scrubbing were almost identical and were up to 32 times lower than those recorded for the best braided rope seal flow blockers. Silicon nitride compression springs showed promise conceptually as potential seal preload devices to help maintain seal resiliency.

FAP-1-mediated activation of NF-kappaB induces resistance of head and neck cancer to Fas-induced apoptosis.

PubMed

Wieckowski, Eva; Atarashi, Yoshinari; Stanson, Joanna; Sato, Taka-Aki; Whiteside, Theresa L

2007-01-01

Molecular mechanisms responsible for tumor resistance to apoptosis often involve the Fas/FasL pathway. While squamous cell carcinomas of the head and neck (SCCHN) express both Fas and FasL, their resistance to self-induced apoptosis or apoptosis mediated by Fas agonistic antibody (CH-11Ab) was independent of the level of Fas surface expression or the presence of soluble Fas in supernatants of primary or metastatic SCCHN cell lines. By in vitro immunoselection, using PCI-15A cell line treated with successive cycles of CH-11 Ab, Fas-resistant sublines with the parental genotype were selected. Such sublines failed to cleave caspase-8 upon Fas engagement and were resistant to CH-11 Ab, although they remained sensitive to VP-16 or staurosporin. In the presence of cycloheximide, the selected SCCHN sublines become susceptible to CH-11 Ab, and showed cleavage of caspase-8, suggesting that apoptosis resistance was mediated by an inhibitory protein(s) acting upstream of caspase-8. Overexpression of Fas-associated phosphatase 1 (FAP-1), but not cellular FLICE-inhibitory protein (cFLIP) in SCCHN sublines was documented by Western blots and RT-PCR analyses. The FAP-1+ selected sublines also downregulated cell surface Fas. A high phosphorylation level of IkappaB kappa, NFkappaB activation and upregulation of Bcl-2 expression were observed in the FAP-1+ sublines. Treatment with the phosphatase inhibitor, orthovanadate, or silencing of FAP-1 with siRNA abolished their resistance to apoptosis, suggesting that FAP-1 phosphatase activity could be responsible for NF-kappaB activation and resistance of SCCHN cells to Fas-mediated apoptosis. 2006 Wiley-Liss, Inc.

Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer.

PubMed

Feig, Christine; Jones, James O; Kraman, Matthew; Wells, Richard J B; Deonarine, Andrew; Chan, Derek S; Connell, Claire M; Roberts, Edward W; Zhao, Qi; Caballero, Otavia L; Teichmann, Sarah A; Janowitz, Tobias; Jodrell, Duncan I; Tuveson, David A; Fearon, Douglas T

2013-12-10

An autochthonous model of pancreatic ductal adenocarcinoma (PDA) permitted the analysis of why immunotherapy is ineffective in this human disease. Despite finding that PDA-bearing mice had cancer cell-specific CD8(+) T cells, the mice, like human patients with PDA, did not respond to two immunological checkpoint antagonists that promote the function of T cells: anti-cytotoxic T-lymphocyte-associated protein 4 (α-CTLA-4) and α-programmed cell death 1 ligand 1 (α-PD-L1). Immune control of PDA growth was achieved, however, by depleting carcinoma-associated fibroblasts (CAFs) that express fibroblast activation protein (FAP). The depletion of the FAP(+) stromal cell also uncovered the antitumor effects of α-CTLA-4 and α-PD-L1, indicating that its immune suppressive activity accounts for the failure of these T-cell checkpoint antagonists. Three findings suggested that chemokine (C-X-C motif) ligand 12 (CXCL12) explained the overriding immunosuppression by the FAP(+) cell: T cells were absent from regions of the tumor containing cancer cells, cancer cells were coated with the chemokine, CXCL12, and the FAP(+) CAF was the principal source of CXCL12 in the tumor. Administering AMD3100, a CXCL12 receptor chemokine (C-X-C motif) receptor 4 inhibitor, induced rapid T-cell accumulation among cancer cells and acted synergistically with α-PD-L1 to greatly diminish cancer cells, which were identified by their loss of heterozygosity of Trp53 gene. The residual tumor was composed only of premalignant epithelial cells and inflammatory cells. Thus, a single protein, CXCL12, from a single stromal cell type, the FAP(+) CAF, may direct tumor immune evasion in a model of human PDA.

Modeling of Electron Transpiration Cooling for Leading Edges of Hypersonic Vehicles

NASA Astrophysics Data System (ADS)

Hanquist, Kyle Matthew

The development of aeronautics has been largely driven by the passion to fly faster. From the flight of the Wright Flyer that flew 48 km/hr to the recent advances in hypersonic flight, most notably NASA's X-43A that flew at over 3 km/s, the velocity of flight has steadily increased. However, as these hypersonic speeds are reached and increased, contradicting aerothermodynamic design requirements present themselves. For example, a hypersonic cruise vehicle requires sharp leading edges to decrease the drag in order to maximize the range. However, the aerodynamic performance gains obtained by having a sharp leading edge come at the cost of very high, localized heating rates. There is currently no ideal way to manage these heating loads for sustained hypersonic flight, especially as flight velocities continue to increase. An approach that has been recently proposed involves using thermo-electric materials on these sharp leading edges to manage the heating loads. When exposed to high convective heating rates, these materials emit a current of electrons that leads to a cooling effect of the surface of the vehicle called electron transpiration cooling (ETC). This dissertation focuses on developing a modeling approach to investigate this phenomenon. The research includes developing and implementing an approach for ETC into a computational fluid dynamics code for simulation of hypersonic flow that accounts for electron emission from the surface. Models for space-charge-limited emission are also developed and implemented in order to accurately determine the level of emission from the surface. This work involves developing analytic models and assessing them using a direct-kinetic plasma sheath solver. Electric field effects are also implemented in the modeling approach, which accounts for forced diffusion and Joule heating. Finally, the modeling approach is coupled to a material response code in order to model the heat transfer into the material surface. Using this modeling

MiR-200c regulates ROS-induced apoptosis in murine BV-2 cells by targeting FAP-1.

PubMed

Yu, D S; Lv, G; Mei, X F; Cao, Y; Wang, Y F; Wang, Y S; Bi, Y L

2014-12-02

Objective:Reactive oxygen species (ROS) are significantly upregulated after spinal cord injury (SCI). MicroRNAs (miRNAs) are reported to be widely involved in regulating gene expression. This paper aims to explore the correlation between ROS-induced cell apoptosis and abnormal miRNA expression after SCI.Methods:To profile the expression of miRNAs after SCI, miRNA microarray was applied and the result was verified by reverse transcription quantitative PCR (RT-qPCR). ROS production following H 2 O 2 stimulation was examined using dihydroethidium staining and flow cytometry. The levels of miR-200c after H 2 O 2 treatment were determined using RT-qPCR. Cell viability and apoptosis were examined in murine BV-2 cells transfected with miR-200c mimics, inhibitor or negative control. Immunofluorescence and western blot were used to further explore the effects of miR-200c on Fas-associated phosphatase-1 (FAP-1) expression.Results:MiR-200c was showed to be significantly increased after SCI by miRNA microassay and RT-qPCR. ROS production enhanced miR-200c expression in a dose-dependent manner and induced significant apoptosis in BV-2 cells. The upregulation of miR-200c reduced cell viability and induced BV-2 cell apoptosis. MiR-200c negatively regulated the expression of FAP-1, thereby inducing FAS signaling-induced apoptosis. RT-qPCR analysis showed that the FAP-1-targeting small interfering RNA (siRNA) did not affect the level of miR-200c in murine BV-2 cells. In addition, suppression of FAP-1 by siRNA promoted apoptosis, even in cells that were co-transfected with the miR-200c inhibitor.Conclusions:The current data suggested that miR-200c contributes to apoptosis in murine BV-2 cells by regulating the expression of FAP-1. This proposes a therapeutic target for enhancing neural cell functional recovery after SCI.Spinal Cord advance online publication, 2 December 2014; doi:10.1038/sc.2014.185.

Retooling CFD for hypersonic aircraft

NASA Technical Reports Server (NTRS)

Dwoyer, Douglas L.; Kutler, Paul; Povinelli, Louis A.

1987-01-01

The CFD facility requirements of hypersonic aircraft configuration design development are different from those thus far employed for reentry vehicle design, because (1) the airframe and the propulsion system must be fully integrated to achieve the desired performance; (2) the vehicle must be reusable, with minimum refurbishment requirements between flights; and (3) vehicle performance must be optimized for a wide range of Mach numbers. An evaluation is presently made of flow resolution within shock waves, transition and turbulence phenomenon tractability, chemical reaction modeling, and hypersonic boundary layer transition, with state-of-the-art CFD.

Transition Experiments on Large Bluntness Cones with Distributed Roughness in Hypersonic Flight

NASA Technical Reports Server (NTRS)

Reda, Daniel. C.; Wilder, Michael C.; Prabhu, Dinesh K.

2012-01-01

Large bluntness cones with smooth nosetips and roughened frusta were flown in the NASA Ames hypersonic ballistic range at a Mach number of 10 through quiescent air environments. Global surface intensity (temperature) distributions were optically measured and analyzed to determine transition onset and progression over the roughened surface. Real-gas Navier-Stokes calculations of model flowfields, including laminar boundary layer development in these flowfields, were conducted to predict values of key dimensionless parameters used to correlate transition on such configurations in hypersonic flow. For these large bluntness cases, predicted axial distributions of the roughness Reynolds number showed (for each specified freestream pressure) that this parameter was a maximum at the physical beginning of the roughened zone and decreased with increasing run length along the roughened surface. Roughness-induced transition occurred downstream of this maximum roughness Reynolds number location, and progressed upstream towards the beginning of the roughened zone as freestream pressure was systematically increased. Roughness elements encountered at the upstream edge of the roughened frusta thus acted like a finite-extent trip array, consistent with published results concerning the tripping effectiveness of roughness bands placed on otherwise smooth surfaces.

Scramjet exhaust simulation technique for hypersonic aircraft nozzle design and aerodynamic tests

NASA Technical Reports Server (NTRS)

Hunt, J. L.; Talcott, N. A., Jr.; Cubbage, J. M.

1977-01-01

Current design philosophy for scramjet-powered hypersonic aircraft results in configurations with the entire lower fuselage surface utilized as part of the propulsion system. The lower aft-end of the vehicle acts as a high expansion ratio nozzle. Not only must the external nozzle be designed to extract the maximum possible thrust force from the high energy flow at the combustor exit, but the forces produced by the nozzle must be aligned such that they do not unduly affect aerodynamic balance. The strong coupling between the propulsion system and aerodynamics of the aircraft makes imperative at least a partial simulation of the inlet, exhaust, and external flows of the hydrogen-burning scramjet in conventional facilities for both nozzle formulation and aerodynamic-force data acquisition. Aerodynamic testing methods offer no contemporary approach for such vehicle design requirements. NASA-Langley has pursued an extensive scramjet/airframe integration R&D program for several years and has recently developed a promising technique for simulation of the scramjet exhaust flow for hypersonic aircraft. Current results of the research program to develop a scramjet flow simulation technique through the use of substitute gas blends are described in this paper.

Aerothermodynamic shape optimization of hypersonic blunt bodies

NASA Astrophysics Data System (ADS)

Eyi, Sinan; Yumuşak, Mine

2015-07-01

The aim of this study is to develop a reliable and efficient design tool that can be used in hypersonic flows. The flow analysis is based on the axisymmetric Euler/Navier-Stokes and finite-rate chemical reaction equations. The equations are coupled simultaneously and solved implicitly using Newton's method. The Jacobian matrix is evaluated analytically. A gradient-based numerical optimization is used. The adjoint method is utilized for sensitivity calculations. The objective of the design is to generate a hypersonic blunt geometry that produces the minimum drag with low aerodynamic heating. Bezier curves are used for geometry parameterization. The performances of the design optimization method are demonstrated for different hypersonic flow conditions.

eLaunch Hypersonics: An Advanced Launch System

NASA Technical Reports Server (NTRS)

Starr, Stanley

2010-01-01

This presentation describes a new space launch system that NASA can and should develop. This approach can significantly reduce ground processing and launch costs, improve reliability, and broaden the scope of what we do in near earth orbit. The concept (not new) is to launch a re-usable air-breathing hypersonic vehicle from a ground based electric track. This vehicle launches a final rocket stage at high altitude/velocity for the final leg to orbit. The proposal here differs from past studies in that we will launch above Mach 1.5 (above transonic pinch point) which further improves the efficiency of air breathing, horizontal take-off launch systems. The approach described here significantly reduces cost per kilogram to orbit, increases safety and reliability of the boost systems, and reduces ground costs due to horizontal-processing. Finally, this approach provides significant technology transfer benefits for our national infrastructure.

Design and Development of a Real-Time Model Attitude Measurement System for Hypersonic Facilities

NASA Technical Reports Server (NTRS)

Jones, Thomas W.; Lunsford, Charles B.

2005-01-01

A series of wind tunnel tests have been conducted to evaluate a multi-camera videogrammetric system designed to measure model attitude in hypersonic facilities. The technique utilizes processed video data and applies photogrammetric principles for point tracking to compute model position including pitch, roll and yaw variables. A discussion of the constraints encountered during the design, development, and testing process, including lighting, vibration, operational range and optical access is included. Initial measurement results from the NASA Langley Research Center (LaRC) 31-Inch Mach 10 tunnel are presented.

Design and Development of a Real-Time Model Attitude Measurement System for Hypersonic Facilities

NASA Technical Reports Server (NTRS)

Jones, Thomas W.; Lunsford, Charles B.

2004-01-01

A series of wind tunnel tests have been conducted to evaluate a multi-camera videogrammetric system designed to measure model attitude in hypersonic facilities. The technique utilizes processed video data and applies photogrammetric principles for point tracking to compute model position including pitch, roll and yaw variables. A discussion of the constraints encountered during the design, development, and testing process, including lighting, vibration, operational range and optical access is included. Initial measurement results from the NASA Langley Research Center (LaRC) 31-Inch Mach 10 tunnel are presented.

Development and Evaluation of TiAl Sheet Structures for Hypersonic Applications

NASA Technical Reports Server (NTRS)

Draper, S. L.; Krause, D.; Lerch, B.; Locci, I. E.; Doehnert, B.; Nigam, R.; Das, G.; Sickles, P.; Tabernig, B.; Reger, N.;

Transition and turbulence measurements in hypersonic flows

NASA Technical Reports Server (NTRS)

Owen, F. K.

1990-01-01

This paper reviews techniques for transitional- and turbulent-flow measurements and describes current research in support of turbulence modeling. Special attention is given to the potential of applying hot wire and laser velocimeter to measuring turbulent fluctuations in hypersonic flow fields. The results of recent experiments conducted in two hypersonic wind tunnels are presented and compared with previous hot-wire turbulence measurements.

Results of a M = 5.3 heat transfer test of the integrated vehicle using phase-change paint techniques on the 0.0175-scale model 56-OTS in the NASA/Ames Research Center 3.5-foot hypersonic wind tunnel

NASA Technical Reports Server (NTRS)

Marroquin, J.

1985-01-01

An experimental investigation was performed in the NASA/Ames Research Center 3.5-foot Hypersonic Wind Tunnel to obtain supersonic heat-distribution data in areas between the orbiter and external tank using phase-change paint techniques. The tests used Novamide SSV Model 56-OTS in the first and second-stage ascent configurations. Data were obtained at a nominal Mach number of 5.3 and a Reynolds number per foot of 5 x 10 to the 6th power with angles of attack of 0 deg, +/- 5 deg, and sideslip angles of 0 deg and +/- 5 deg.

The Fas/Fap-1/Cav-1 complex regulates IL-1RA secretion in mesenchymal stem cells to accelerate wound healing.

PubMed

Kou, Xiaoxing; Xu, Xingtian; Chen, Chider; Sanmillan, Maria Laura; Cai, Tao; Zhou, Yanheng; Giraudo, Claudio; Le, Anh; Shi, Songtao

2018-03-14

Mesenchymal stem cells (MSCs) are capable of secreting exosomes, extracellular vesicles, and cytokines to regulate cell and tissue homeostasis. However, it is unknown whether MSCs use a specific exocytotic fusion mechanism to secrete exosomes and cytokines. We show that Fas binds with Fas-associated phosphatase-1 (Fap-1) and caveolin-1 (Cav-1) to activate a common soluble N -ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE)-mediated membrane fusion mechanism to release small extracellular vesicles (sEVs) in MSCs. Moreover, we reveal that MSCs produce and secrete interleukin-1 receptor antagonist (IL-1RA) associated with sEVs to maintain rapid wound healing in the gingiva via the Fas/Fap-1/Cav-1 cascade. Tumor necrosis factor-α (TNF-α) serves as an activator to up-regulate Fas and Fap-1 expression via the nuclear factor κB pathway to promote IL-1RA release. This study identifies a previously unknown Fas/Fap-1/Cav-1 axis that regulates SNARE-mediated sEV and IL-1RA secretion in stem cells, which contributes to accelerated wound healing. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

FAP Group Supervision: Reporting Educational Experiences at the University of Sao Paulo, Brazil

ERIC Educational Resources Information Center

Wielenska, Regina Christina; Oshiro, Claudia Kami Bastos

2012-01-01

The present article describes and analyzes educational experiences related to the teaching of FAP for psychology graduate students and psychiatry residents at the University of Sao Paulo. The first experience involved psychology graduate students and includes an example of the shaping process occurring within the supervisor-supervisee…

Overview of Transonic to Hypersonic Stage Separation Tool Development for Multi-Stage-to-Orbit Concepts

NASA Technical Reports Server (NTRS)

Murphy, Kelly J.; Bunning, Pieter G.; Pamadi, Bandu N.; Scallion, William I.; Jones, Kenneth M.

2004-01-01

An overview of research efforts at NASA in support of the stage separation and ascent aerothermodynamics research program is presented. The objective of this work is to develop a synergistic suite of experimental, computational, and engineering tools and methods to apply to vehicle separation across the transonic to hypersonic speed regimes. Proximity testing of a generic bimese wing-body configuration is on-going in the transonic (Mach numbers 0.6, 1.05, and 1.1), supersonic (Mach numbers 2.3, 3.0, and 4.5) and hypersonic (Mach numbers 6 and 10) speed regimes in four wind tunnel facilities at the NASA Langley Research Center. An overset grid, Navier-Stokes flow solver has been enhanced and demonstrated on a matrix of proximity cases and on a dynamic separation simulation of the bimese configuration. Steady-state predictions with this solver were in excellent agreement with wind tunnel data at Mach 3 as were predictions via a Cartesian-grid Euler solver. Experimental and computational data have been used to evaluate multi-body enhancements to the widely-used Aerodynamic Preliminary Analysis System, an engineering methodology, and to develop a new software package, SepSim, for the simulation and visualization of vehicle motions in a stage separation scenario. Web-based software will be used for archiving information generated from this research program into a database accessible to the user community. Thus, a framework has been established to study stage separation problems using coordinated experimental, computational, and engineering tools.

Conjugate Heat Transfer Study in Hypersonic Flows

NASA Astrophysics Data System (ADS)

Sahoo, Niranjan; Kulkarni, Vinayak; Peetala, Ravi Kumar

2018-04-01

Coupled and decoupled conjugate heat transfer (CHT) studies are carried out to imitate experimental studies for heat transfer measurement in hypersonic flow regime. The finite volume based solvers are used for analyzing the heat interaction between fluid and solid domains. Temperature and surface heat flux signals are predicted by both coupled and decoupled CHT analysis techniques for hypersonic Mach numbers. These two methodologies are also used to study the effect of different wall materials on surface parameters. Effectiveness of these CHT solvers has been verified for the inverse problem of wall heat flux recovery using various techniques reported in the literature. Both coupled and decoupled CHT techniques are seen to be equally useful for prediction of local temperature and heat flux signals prior to the experiments in hypersonic flows.

CFD on hypersonic flow geometries with aeroheating

NASA Astrophysics Data System (ADS)

Sohail, Muhammad Amjad; Chao, Yan; Hui, Zhang Hui; Ullah, Rizwan

2012-11-01

The hypersonic flowfield around a blunted cone and cone-flare exhibits some of the major features of the flows around space vehicles, e.g. a detached bow shock in the stagnation region and the oblique shock wave/boundary layer interaction at the cone-flare junction. The shock wave/boundary layer interaction can produce a region of separated flow. This phenomenon may occur, for example, at the upstream-facing corner formed by a deflected control surface on a hypersonic entry vehicle, where the length of separation has implications for control effectiveness. Computational fluid-dynamics results are presented to show the flowfield around a blunted cone and cone-flare configurations in hypersonic flow with separation. This problem is of particular interest since it features most of the aspects of the hypersonic flow around planetary entry vehicles. The region between the cone and the flare is particularly critical with respect to the evaluation of the surface pressure and heat flux with aeroheating. Indeed, flow separation is induced by the shock wave boundary layer interaction, with subsequent flow reattachment, that can dramatically enhance the surface heat transfer. The exact determination of the extension of the recirculation zone is a particularly delicate task for numerical codes. Laminar flow and turbulent computations have been carried out using a full Navier-Stokes solver, with freestream conditions provided by the experimental data obtained at Mach 6, 8, and 16.34 wind tunnel. The numerical results are compared with the measured pressure and surface heat flux distributions in the wind tunnel and a good agreement is found, especially on the length of the recirculation region and location of shock waves. The critical physics of entropy layer, boundary layers, boundary layers and shock wave interaction and flow behind shock are properly captured and elaborated.. Hypersonic flows are characterized by high Mach number and high total enthalpy. An elevated

NASA thrusts in high-speed aeropropulsion research and development: An overview

NASA Technical Reports Server (NTRS)

Ziemianski, Joseph A.

1990-01-01

NASA is conducting aeronautical research over a broad range of Mach numbers. In addition to the advanced conventional takeoff or landing (CTOL) propulsion research described elsewhere, NASA Lewis has intensified its efforts towards propulsion technology for selected high speed flight applications. In a companion program, NASA Langley has also accomplished significant research in supersonic combustion ramjet (SCRAM) propulsion. An unclassified review is presented of the propulsion research results that are applicable for supersonic to hypersonic vehicles. This overview not only provides a preview of the more detailed presentations which follow, it also presents a viewpoint on future research directions by calling attention to the unique cycles, components, and facilities involved in this expanding area of work.

A comparative study of turbulence models in predicting hypersonic inlet flows

NASA Technical Reports Server (NTRS)

Kapoor, Kamlesh

1993-01-01

A computational study has been conducted to evaluate the performance of various turbulence models. The NASA P8 inlet, which represents cruise condition of a typical hypersonic air-breathing vehicle, was selected as a test case for the study; the PARC2D code, which solves the full two dimensional Reynolds-averaged Navier-Stokes equations, was used. Results are presented for a total of six versions of zero- and two-equation turbulence models. Zero-equation models tested are the Baldwin-Lomax model, the Thomas model, and a combination of the two. Two-equation models tested are low-Reynolds number models (the Chien model and the Speziale model) and a high-Reynolds number model (the Launder and Spalding model).

Assessment of nonequilibrium radiation computation methods for hypersonic flows

NASA Technical Reports Server (NTRS)

Sharma, Surendra

1993-01-01

The present understanding of shock-layer radiation in the low density regime, as appropriate to hypersonic vehicles, is surveyed. Based on the relative importance of electron excitation and radiation transport, the hypersonic flows are divided into three groups: weakly ionized, moderately ionized, and highly ionized flows. In the light of this division, the existing laboratory and flight data are scrutinized. Finally, an assessment of the nonequilibrium radiation computation methods for the three regimes in hypersonic flows is presented. The assessment is conducted by comparing experimental data against the values predicted by the physical model.

Depletion of FAP+ cells reduces immunosuppressive cells and improves metabolism and functions CD8+T cells within tumors

PubMed Central

Zhang, Ying; Ertl, Hildegund C.J.

2016-01-01

The tumor stroma, which is essential to support growth and metastasis of malignant cells, provides targets for active immunotherapy of cancer. Previous studies have shown that depleting fibroblast activation protein (FAP)-expressing stromal cells reduces tumor progression and concomitantly increases tumor antigen (TA)-specific T cell responses. However the underlying pathways remain ill defined. Here we identify that immunosuppressive cells (ISCs) from tumor-bearing mice impose metabolic stress on CD8+T cells, which is associated with increased expression of the co-inhibitor PD-1. In two mouse melanoma models, depleting FAP+ stroma cells from the tumor microenvironment (TME) upon vaccination with an adenoviral-vector reduces frequencies and functions of ISCs. This is associated with changes in the cytokine/chemokine milieu in the TME and decreased activity of STAT6 signaling within ISCs. Decreases in ISCs upon FAP+stromal cell depletion is associated with reduced metabolic stress of vaccine-induced tumor infiltrating CD8+T cells and their delayed progression towards functional exhaustion, resulting in prolonged survival of tumor-bearing mice. PMID:26943036

Depletion of FAP+ cells reduces immunosuppressive cells and improves metabolism and functions CD8+T cells within tumors.

PubMed

Zhang, Ying; Ertl, Hildegund C J

2016-04-26

The tumor stroma, which is essential to support growth and metastasis of malignant cells, provides targets for active immunotherapy of cancer. Previous studies have shown that depleting fibroblast activation protein (FAP)-expressing stromal cells reduces tumor progression and concomitantly increases tumor antigen (TA)-specific T cell responses. However the underlying pathways remain ill defined. Here we identify that immunosuppressive cells (ISCs) from tumor-bearing mice impose metabolic stress on CD8+T cells, which is associated with increased expression of the co-inhibitor PD-1. In two mouse melanoma models, depleting FAP+ stroma cells from the tumor microenvironment (TME) upon vaccination with an adenoviral-vector reduces frequencies and functions of ISCs. This is associated with changes in the cytokine/chemokine milieu in the TME and decreased activity of STAT6 signaling within ISCs. Decreases in ISCs upon FAP+stromal cell depletion is associated with reduced metabolic stress of vaccine-induced tumor infiltrating CD8+T cells and their delayed progression towards functional exhaustion, resulting in prolonged survival of tumor-bearing mice.

Exclusion of the APC gene as the cause of a variant form of familial adenomatous polyposis (FAP)

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

Stella, A.; Resta, N.; Susca, F.

Familial adenomatous polyposis (FAP) is a premalignant disease inherited as an autosomal dominant trait, characterized by hundreds to thousands of polyps in the colorectal tract. Recently, the syndrome has been shown to be caused by mutations in the APC (adenomatous polyposis coli) gene located on chromosome 5q21. The authors studied two families that both presented a phenotype different from that of the classical form of FAP. The most important findings observed in these two kindreds are (a) low and variable number of colonic polyps (from 5 to 100) and (b) a slower evolution of the disease, with colon cancer occurringmore » at a more advanced age than in FAP in spite of the early onset of intestinal manifestations. To determine whether mutations of the APC gene are also responsible for this variant syndrome, linkage studies were performed by using a series of markers both intragenic and tightly linked to the APC gene. The results provide evidence for exclusion of the APC gene as the cause of the variant form of polyposis present in the two families described. 30 refs., 1 fig., 1 tab.« less

Highlights from a Mach 4 Experimental Demonstration of Inlet Mode Transition for Turbine-Based Combined Cycle Hypersonic Propulsion

NASA Technical Reports Server (NTRS)

Foster, Lancert E.; Saunders, John D., Jr.; Sanders, Bobby W.; Weir, Lois J.

2012-01-01

NASA is focused on technologies for combined cycle, air-breathing propulsion systems to enable reusable launch systems for access to space. Turbine Based Combined Cycle (TBCC) propulsion systems offer specific impulse (Isp) improvements over rocket-based propulsion systems in the subsonic takeoff and return mission segments along with improved safety. Among the most critical TBCC enabling technologies are: 1) mode transition from the low speed propulsion system to the high speed propulsion system, 2) high Mach turbine engine development and 3) innovative turbine based combined cycle integration. To address these challenges, NASA initiated an experimental mode transition task including analytical methods to assess the state-of-the-art of propulsion system performance and design codes. One effort has been the Combined-Cycle Engine Large Scale Inlet Mode Transition Experiment (CCE-LIMX) which is a fully integrated TBCC propulsion system with flowpath sizing consistent with previous NASA and DoD proposed Hypersonic experimental flight test plans. This experiment was tested in the NASA GRC 10 by 10-Foot Supersonic Wind Tunnel (SWT) Facility. The goal of this activity is to address key hypersonic combined-cycle engine issues including: (1) dual integrated inlet operability and performance issues-unstart constraints, distortion constraints, bleed requirements, and controls, (2) mode-transition sequence elements caused by switching between the turbine and the ramjet/scramjet flowpaths (imposed variable geometry requirements), and (3) turbine engine transients (and associated time scales) during transition. Testing of the initial inlet and dynamic characterization phases were completed and smooth mode transition was demonstrated. A database focused on a Mach 4 transition speed with limited off-design elements was developed and will serve to guide future TBCC system studies and to validate higher level analyses.

Seal Technology for Hypersonic Vehicle and Propulsion: An Overview

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M.

2008-01-01

Hypersonic vehicles and propulsion systems pose an extraordinary challenge for structures and materials. Airframes and engines require lightweight, high-temperature materials and structural configurations that can withstand the extreme environment of hypersonic flight. Some of the challenges posed include very high temperatures, heating of the whole vehicle, steady-state and transient localized heating from shock waves, high aerodynamic loads, high fluctuating pressure loads, potential for severe flutter, vibration, and acoustic loads and erosion. Correspondingly high temperature seals are required to meet these aggressive requirements. This presentation reviews relevant seal technology for both heritage (e.g. Space Shuttle, X-15, and X-38) vehicles and presents several seal case studies aimed at providing lessons learned for future hypersonic vehicle seal development. This presentation also reviews seal technology developed for the National Aerospace Plane propulsion systems and presents several seal case studies aimed at providing lessons learned for future hypersonic propulsion seal development.

Diagnostic values of dual focus narrow band imaging and probe-based confocal laser endomicroscopy in FAP-related duodenal adenoma.

PubMed

Pittayanon, Rapat; Rerknimitr, Rungsun; Imraporn, Boonlert; Wisedopas, Naruemon; Kullavanijaya, Pinit

2015-10-01

Familial adenomatous polyposis (FAP) is associated with an increased risk of development of periampullary and nonampullary adenoma. Either routine biopsy or endoscopic removal of the lesion is generally required to identify the presence of adenoma. Because the risk of tissue sampling from the ampulla is high and nonampullary polyps are sometimes numerous, resection of all the lesions is time-consuming. This study aimed to evaluate the diagnostic values of duodenal adenoma by dual focus NBI (dNBI) and probe-based confocal endomicroscopy (pCLE) in FAP patients. The authors conducted a diagnostic study in a single tertiary-care referral center. Surveillance esophagogastroduodenoscopy with dNBI and pCLE was performed on 26 patients with FAP for real-time adenoma diagnosis by two different endoscopists; one used dNBI and the other pCLE. Histology from the matched lesion was used as the gold standard. A total of 55 matched biopsies (25 ampullas, 30 nonampullas) were performed. The sensitivity, specificity, post predictive value (PPV), negative predictive value (NPV), and accuracy of dNBI vs. pCLE from all duodenal lesions were 96.9 % vs. 93.8 %, 78.3 % vs. 81 %, 86.1 % vs. 88.2 %, 94.7 vs. 89.5 %, and 92.4 % vs. 88.6 %, respectively. For surveillance of periampullary and nonampullary adenoma in patients with FAP, the real-time readings provided a high degree of diagnostic value when histology was used as the gold standard. ( NCT02162173).

Multiple Velocity Profile Measurements in Hypersonic Flows using Sequentially-Imaged Fluorescence Tagging

NASA Technical Reports Server (NTRS)

Bathel, Brett F.; Danehy, Paul M.; Inmian, Jennifer A.; Jones, Stephen B.; Ivey, Christopher B.; Goyne, Christopher P.

2010-01-01

Nitric-oxide planar laser-induced fluorescence (NO PLIF) was used to perform velocity measurements in hypersonic flows by generating multiple tagged lines which fluoresce as they convect downstream. For each laser pulse, a single interline, progressive scan intensified CCD camera was used to obtain separate images of the initial undelayed and delayed NO molecules that had been tagged by the laser. The CCD configuration allowed for sub-microsecond acquisition of both images, resulting in sub-microsecond temporal resolution as well as sub-mm spatial resolution (0.5-mm x 0.7-mm). Determination of axial velocity was made by application of a cross-correlation analysis of the horizontal shift of individual tagged lines. Quantification of systematic errors, the contribution of gating/exposure duration errors, and influence of collision rate on fluorescence to temporal uncertainty were made. Quantification of the spatial uncertainty depended upon the analysis technique and signal-to-noise of the acquired profiles. This investigation focused on two hypersonic flow experiments: (1) a reaction control system (RCS) jet on an Orion Crew Exploration Vehicle (CEV) wind tunnel model and (2) a 10-degree half-angle wedge containing a 2-mm tall, 4-mm wide cylindrical boundary layer trip. The experiments were performed at the NASA Langley Research Center's 31-inch Mach 10 wind tunnel.

Effect of Sidewall Configurations on Hypersonic Intake Performance

NASA Astrophysics Data System (ADS)

Kim, Seihwan; Park, Ji Hyun; Jeung, In-Seuck; Lee, Hyoung Jin

For reusable space launchers and hypersonic flight vehicles, use of an air-breathing propulsion system with supersonic combustion is the most promising option in terms of cost effectiveness. At this point, only the scramjet propulsion system provides a real alternative to expensive rocket driven systems, which currently are the only way to reach a hypersonics speeds.

Vibrational relaxation in hypersonic flow fields

NASA Technical Reports Server (NTRS)

Meador, Willard E.; Miner, Gilda A.; Heinbockel, John H.

1993-01-01

Mathematical formulations of vibrational relaxation are derived from first principles for application to fluid dynamic computations of hypersonic flow fields. Relaxation within and immediately behind shock waves is shown to be substantially faster than that described in current numerical codes. The result should be a significant reduction in nonequilibrium radiation overshoot in shock layers and in radiative heating of hypersonic vehicles; these results are precisely the trends needed to bring theoretical predictions more in line with flight data. Errors in existing formulations are identified and qualitative comparisons are made.

Hypersonic aeroheating test of space shuttle vehicle configuration 3 (model 22-OTS) in the NASA-Ames 3.5-foot hypersonic wind tunnel (IH20), volume 1

NASA Technical Reports Server (NTRS)

Kingsland, R. B.; Lockman, W. K.

1975-01-01

The results of hypersonic wind tunnel testing of an 0.0175 scale version of the vehicle 3 space shuttle configuration are presented. Temperature measurements were made on the launch configuration, orbiter plus tank, orbiter alone, tank alone, and solid rocket booster alone to provide heat transfer data. The test was conducted at free-stream Mach numbers of 5.3 and 7.3 and at free-stream Reynolds numbers of 1.5 million, 3.7 million, 5.0 million, and 7.0 million per foot. The model was tested at angles of attack from -5 deg to 20 deg and side slip angles of -5 deg and 0 deg.

Configuration development study of the OSU 1 hypersonic research vehicle

NASA Technical Reports Server (NTRS)

Stein, Matthew D.; Frankhauser, Chris; Zee, Warner; Kosanchick, Melvin, III; Nelson, Nick; Hunt, William

1993-01-01

In an effort to insure the future development of hypersonic cruise aircraft, the possible vehicle configurations were examined to develop a single-stage-to-orbit hypersonic research vehicle (HRV). Based on the needs of hypersonic research and development, the mission goals and requirements are determined. A body type is chosen. Three modes of propulsion and two liquid rocket fuels are compared, followed by the optimization of the body configuration through aerodynamic, weight, and trajectory studies. A cost analysis is included.

Development of an aerodynamic measurement system for hypersonic rarefied flows

NASA Astrophysics Data System (ADS)

Ozawa, T.; Fujita, K.; Suzuki, T.

2015-01-01

A hypersonic rarefied wind tunnel (HRWT) has lately been developed at Japan Aerospace Exploration Agency in order to improve the prediction of rarefied aerodynamics. Flow characteristics of hypersonic rarefied flows have been investigated experimentally and numerically. By conducting dynamic pressure measurements with pendulous models and pitot pressure measurements, we have probed flow characteristics in the test section. We have also improved understandings of hypersonic rarefied flows by integrating a numerical approach with the HRWT measurement. The development of the integration scheme between HRWT and numerical approach enables us to estimate the hypersonic rarefied flow characteristics as well as the direct measurement of rarefied aerodynamics. Consequently, this wind tunnel is capable of generating 25 mm-core flows with the free stream Mach number greater than 10 and Knudsen number greater than 0.1.

Hypersonic research engine project. Phase 2: Preliminary report on the performance of the HRE/AIM at Mach 6

NASA Technical Reports Server (NTRS)

Sun, Y. H.; Sainio, W. C.

1975-01-01

Test results of the Aerothermodynamic Integration Model are presented. A program was initiated to develop a hydrogen-fueled research-oriented scramjet for operation between Mach 3 and 8. The primary objectives were to investigate the internal aerothermodynamic characteristics of the engine, to provide realistic design parameters for future hypersonic engine development as well as to evaluate the ground test facility and testing techniques. The engine was tested at the NASA hypersonic tunnel facility with synthetic air at Mach 5, 6, and 7. The hydrogen fuel was heated up to 1500 R prior to injection to simulate a regeneratively cooled system. The engine and component performance at Mach 6 is reported. Inlet performance compared very well both with theory and with subscale model tests. Combustor efficiencies up to 95 percent were attained at an equivalence ratio of unity. Nozzle performance was lower than expected. The overall engine performance was computed using two different methods. The performance was also compared with test data from other sources.

X-43A/Hyper-X Vehicle Arrives at NASA Dryden

NASA Technical Reports Server (NTRS)

1999-01-01

The X-43A Hypersonic Experimental Vehicle, or 'Hyper-X,' carefully packed in a protective shipping framework, is unloaded from a container after its arrival at NASA's Dryden Flight Research Center in October 1999. The X-43A was developed to research a dual-mode ramjet/scramjet propulsion system at speeds from Mach 7 up to Mach 10 (7 to 10 times the speed of sound, which varies with temperature and altitude). Hyper-X, the flight vehicle for which is designated as X-43A, is an experimental flight-research program seeking to demonstrate airframe-integrated, 'air-breathing' engine technologies that promise to increase payload capacity for future vehicles, including hypersonic aircraft (faster than Mach 5) and reusable space launchers. This multiyear program is currently underway at NASA Dryden Flight Research Center, Edwards, California. The Hyper-X schedule calls for its first flight later this year (2000). Hyper-X is a joint program, with Dryden sharing responsibility with NASA's Langley Research Center, Hampton, Virginia. Dryden's primary role is to fly three unpiloted X-43A research vehicles to validate engine technologies and hypersonic design tools as well as the hypersonic test facility at Langley. Langley manages the program and leads the technology development effort. The Hyper-X Program seeks to significantly expand the speed boundaries of air-breathing propulsion by being the first aircraft to demonstrate an airframe-integrated, scramjet-powered free flight. Scramjets (supersonic-combustion ramjets) are ramjet engines in which the airflow through the whole engine remains supersonic. Scramjet technology is challenging because only limited testing can be performed in ground facilities. Long duration, full-scale testing requires flight research. Scramjet engines are air-breathing, capturing their oxygen from the atmosphere. Current spacecraft, such as the Space Shuttle, are rocket powered, so they must carry both fuel and oxygen for propulsion. Scramjet

Aerodynamic Characteristics of Two Waverider-Derived Hypersonic Cruise Configurations

NASA Technical Reports Server (NTRS)

Cockrell, Charles E., Jr.; Huebner, Lawrence D.; Finley, Dennis B.

1996-01-01

An evaluation was made on the effects of integrating the required aircraft components with hypersonic high-lift configurations known as waveriders to create hypersonic cruise vehicles. Previous studies suggest that waveriders offer advantages in aerodynamic performance and propulsion/airframe integration (PAI) characteristics over conventional non-waverider hypersonic shapes. A wind-tunnel model was developed that integrates vehicle components, including canopies, engine components, and control surfaces, with two pure waverider shapes, both conical-flow-derived waveriders for a design Mach number of 4.0. Experimental data and limited computational fluid dynamics (CFD) solutions were obtained over a Mach number range of 1.6 to 4.63. The experimental data show the component build-up effects and the aerodynamic characteristics of the fully integrated configurations, including control surface effectiveness. The aerodynamic performance of the fully integrated configurations is not comparable to that of the pure waverider shapes, but is comparable to previously tested hypersonic models. Both configurations exhibit good lateral-directional stability characteristics.

Research in robust control for hypersonic aircraft

NASA Technical Reports Server (NTRS)

Calise, A. J.

1993-01-01

The research during the second reporting period has focused on robust control design for hypersonic vehicles. An already existing design for the Hypersonic Winged-Cone Configuration has been enhanced. Uncertainty models for the effects of propulsion system perturbations due to angle of attack variations, structural vibrations, and uncertainty in control effectiveness were developed. Using H(sub infinity) and mu-synthesis techniques, various control designs were performed in order to investigate the impact of these effects on achievable robust performance.

Issues Associated with a Hypersonic Maglev Sled

NASA Technical Reports Server (NTRS)

Haney, Joseph W.; Lenzo, J.

1996-01-01

Magnetic levitation has been explored for application from motors to transportation. All of these applications have been at velocities where the physics of the air or operating fluids are fairly well known. Application of Maglev to hypersonic velocities (Mach greater than 5) presents many opportunities, but also issues that require understanding and resolution. Use of Maglev to upgrade the High Speed Test Track at Holloman Air Force Base in Alamogordo New Mexico is an actual hypersonic application that provides the opportunity to improve test capabilities. However, there are several design issues that require investigation. This paper presents an overview of the application of Maglev to the test track and the issues associated with developing a hypersonic Maglev sled. The focus of this paper is to address the issues with the Maglev sled design, rather than the issues with the development of superconducting magnets of the sled system.

Comparative study of turbulence models in predicting hypersonic inlet flows

NASA Technical Reports Server (NTRS)

Kapoor, Kamlesh; Anderson, Bernhard H.; Shaw, Robert J.

1992-01-01

A numerical study was conducted to analyze the performance of different turbulence models when applied to the hypersonic NASA P8 inlet. Computational results from the PARC2D code, which solves the full two-dimensional Reynolds-averaged Navier-Stokes equation, were compared with experimental data. The zero-equation models considered for the study were the Baldwin-Lomax model, the Thomas model, and a combination of the Baldwin-Lomax and Thomas models; the two-equation models considered were the Chien model, the Speziale model (both low Reynolds number), and the Launder and Spalding model (high Reynolds number). The Thomas model performed best among the zero-equation models, and predicted good pressure distributions. The Chien and Speziale models compared wery well with the experimental data, and performed better than the Thomas model near the walls.

Comparative study of turbulence models in predicting hypersonic inlet flows

NASA Technical Reports Server (NTRS)

Kapoor, Kamlesh; Anderson, Bernhard H.; Shaw, Robert J.

1992-01-01

A numerical study was conducted to analyze the performance of different turbulence models when applied to the hypersonic NASA P8 inlet. Computational results from the PARC2D code, which solves the full two-dimensional Reynolds-averaged Navier-Stokes equation, were compared with experimental data. The zero-equation models considered for the study were the Baldwin-Lomax model, the Thomas model, and a combination of the Baldwin-Lomax and Thomas models; the two-equation models considered were the Chien model, the Speziale model (both low Reynolds number), and the Launder and Spalding model (high Reynolds number). The Thomas model performed best among the zero-equation models, and predicted good pressure distributions. The Chien and Speziale models compared very well with the experimental data, and performed better than the Thomas model near the walls.

NASA Aeronautics: Research and Technology Program Highlights

NASA Technical Reports Server (NTRS)

1990-01-01

This report contains numerous color illustrations to describe the NASA programs in aeronautics. The basic ideas involved are explained in brief paragraphs. The seven chapters deal with Subsonic aircraft, High-speed transport, High-performance military aircraft, Hypersonic/Transatmospheric vehicles, Critical disciplines, National facilities and Organizations & installations. Some individual aircraft discussed are : the SR-71 aircraft, aerospace planes, the high-speed civil transport (HSCT), the X-29 forward-swept wing research aircraft, and the X-31 aircraft. Critical disciplines discussed are numerical aerodynamic simulation, computational fluid dynamics, computational structural dynamics and new experimental testing techniques.

Design Study of Wafer Seals for Future Hypersonic Vehicles

NASA Technical Reports Server (NTRS)

Dunlap, Patrick H.; Finkbeiner, Joshua R.; Steinetz, Bruce M.; DeMange, Jeffrey J.

2005-01-01

Future hypersonic vehicles require high temperature, dynamic seals in advanced hypersonic engines and on the vehicle airframe to seal the perimeters of movable panels, flaps, and doors. Current seals do not meet the demanding requirements of these applications, so NASA Glenn Research Center is developing improved designs to overcome these shortfalls. An advanced ceramic wafer seal design has shown promise in meeting these needs. Results from a design of experiments study performed on this seal revealed that several installation variables played a role in determining the amount of leakage past the seals. Lower leakage rates were achieved by using a tighter groove width around the seals, a higher seal preload, a tighter wafer height tolerance, and a looser groove length. During flow testing, a seal activating pressure acting behind the wafers combined with simulated vibrations to seat the seals more effectively against the sealing surface and produce lower leakage rates. A seal geometry study revealed comparable leakage for full-scale wafers with 0.125 and 0.25 in. thicknesses. For applications in which lower part counts are desired, fewer 0.25-in.-thick wafers may be able to be used in place of 0.125-in.-thick wafers while achieving similar performance. Tests performed on wafers with a rounded edge (0.5 in. radius) in contact with the sealing surface resulted in flow rates twice as high as those for wafers with a flat edge. Half-size wafers had leakage rates approximately three times higher than those for full-size wafers.

Flight testing of airbreathing hypersonic vehicles

NASA Technical Reports Server (NTRS)

Hicks, John W.

1993-01-01

Using the scramjet engine as the prime example of a hypersonic airbreathing concept, this paper reviews the history of and addresses the need for hypersonic flight tests. It also describes how such tests can contribute to the development of airbreathing technology. Aspects of captive-carry and free-flight concepts are compared. An incremental flight envelope expansion technique for manned flight vehicles is also described. Such critical issues as required instrumentation technology and proper scaling of experimental devices are addressed. Lastly, examples of international flight test approaches, existing programs, or concepts currently under study, development, or both, are given.

Progress in modeling hypersonic turbulent boundary layers

NASA Technical Reports Server (NTRS)

Zeman, Otto

1993-01-01

A good knowledge of the turbulence structure, wall heat transfer, and friction in turbulent boundary layers (TBL) at high speeds is required for the design of hypersonic air breathing airplanes and reentry space vehicles. This work reports on recent progress in the modeling of high speed TBL flows. The specific research goal described here is the development of a second order closure model for zero pressure gradient TBL's for the range of Mach numbers up to hypersonic speeds with arbitrary wall cooling requirements.

Aeroelastic Analysis of a Trimmed Generic Hypersonic Vehicle

NASA Technical Reports Server (NTRS)

Nydick, I.; Friedmann, P. P.

1999-01-01

The aeroelastic equations of motion governing a hypersonic vehicle in free flight are derived. The equations of motion for a translating and rotating flexible body using Lagrange's equations in terms of quasi-coordinates are presented. These equations are simplified for the case of a vehicle with pitch and plunge rigid body degrees of freedom and small elastic displacements. The displacements are approximated by a truncated series of the unrestrained mode shapes, which are obtained using equivalent plate theory. Subsequently, the nonlinear equations of motion are linearized about the trim state, which is obtained using a rigid body trim model and steady hypersonic aerodynamics. The appropriate flutter derivatives are calculated from piston theory. Results describing mode shapes, trim behavior, and aeroelastic stability of a generic hypersonic vehicle are presented.

Entry, Descent, and Landing Aerothermodynamics: NASA Langley Experimental Capabilities and Contributions

NASA Technical Reports Server (NTRS)

Hollis, Brian R.; Berger, Karen T.; Berry, Scott A.; Bruckmann, Gregory J.; Buck, Gregory M.; DiFulvio, Michael; Horvath, Thomas J.; Liechty, Derek S.; Merski, N. Ronald; Murphy, Kelly J.;

Transition Experiments on Blunt Bodies with Isolated Roughness Elements in Hypersonic Free Flight

NASA Technical Reports Server (NTRS)

Reda, Daniel C.; Wilder, Michael C.; Prabhu, Dinesh K.

2010-01-01

Smooth titanium hemispheres with isolated three-dimensional (3D) surface roughness elements were flown in the NASA Ames hypersonic ballistic range through quiescent CO2 and air environments. Global surface intensity (temperature) distributions were optically measured and thermal wakes behind individual roughness elements were analyzed to define tripping effectiveness. Real-gas Navier-Stokes calculations of model flowfields, including laminar boundary layer development in these flowfields, were conducted predict key dimensionless parameters used to correlate transition on blunt bodies in hypersonic flow. For isolated roughness elements totally immersed within the laminar boundary layer, critical roughness Reynolds numbers for flights in air were found to be higher than those measured for flights in CO2, i.e., it was easier to trip the CO2 boundary layer to turbulence. Tripping effectiveness was found to be dependent on trip location within the subsonic region of the blunt body flowfield, with effective tripping being most difficult to achieve for elements positioned closest to the stagnation point. Direct comparisons of critical roughness Reynolds numbers for 3D isolated versus 3D distributed roughness elements for flights in air showed that distributed roughness patterns were significantly more effective at tripping the blunt body laminar boundary layer to turbulence.

The gene for fibroblast activation protein {alpha} (FAP), a putative cell surface-bound serine protease expressed in cancer stroma and wound healing, maps to chromosome band 2q23

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

Mathew, S.; Murty, V.V.V.S.; Chaganti, R.S.K.

The human fibroblast activation protein {alpha} (FAP{alpha}) is an inducible cell surface glycoprotein of M{sub r} 95,000 recognized by a number of monoclonal antibodies (mAbs), including the prototype mAb F19. Immunohistochemical studies have shown that FAP{alpha} expression in vivo is tightly regulated, with transient expression in some fetal mesenchymal tissues but absence of expression in most normal adult tissues. Reexpression of FAP{alpha} is observed in the reactive stromal fibroblasts of several common types of epithelial cancers, including >90% of breast, colorectal, and lung carcinomas and healing wounds. Cloning and sequence analysis of an FAP{alpha}-specific cDNA has revealed that the moleculemore » is encoded by a novel gene, FAP, which shows sequence similarity to members of the serine protease family of integral membrane proteins, namely dipeptidyl peptidase IV (DPPIV, also known as lymphocyte activation antigen, CD26, or adenosine dearoinase binding protein) and DPPX, a DPPIV-related molecule of unknown function. 15 refs., 1 fig.« less

Three-Dimensional Aeroelastic and Aerothermoelastic Behavior in Hypersonic Flow

NASA Technical Reports Server (NTRS)

McNamara, Jack J.; Friedmann, Peretz P.; Powell, Kenneth G.; Thuruthimattam, Biju J.; Bartels, Robert E.

2005-01-01

The aeroelastic and aerothermoelastic behavior of three-dimensional configurations in hypersonic flow regime are studied. The aeroelastic behavior of a low aspect ratio wing, representative of a fin or control surface on a generic hypersonic vehicle, is examined using third order piston theory, Euler and Navier-Stokes aerodynamics. The sensitivity of the aeroelastic behavior generated using Euler and Navier-Stokes aerodynamics to parameters governing temporal accuracy is also examined. Also, a refined aerothermoelastic model, which incorporates the heat transfer between the fluid and structure using CFD generated aerodynamic heating, is used to examine the aerothermoelastic behavior of the low aspect ratio wing in the hypersonic regime. Finally, the hypersonic aeroelastic behavior of a generic hypersonic vehicle with a lifting-body type fuselage and canted fins is studied using piston theory and Euler aerodynamics for the range of 2.5 less than or equal to M less than or equal to 28, at altitudes ranging from 10,000 feet to 80,000 feet. This analysis includes a study on optimal mesh selection for use with Euler aerodynamics. In addition to the aeroelastic and aerothermoelastic results presented, three time domain flutter identification techniques are compared, namely the moving block approach, the least squares curve fitting method, and a system identification technique using an Auto-Regressive model of the aeroelastic system. In general, the three methods agree well. The system identification technique, however, provided quick damping and frequency estimations with minimal response record length, and therefore o ers significant reductions in computational cost. In the present case, the computational cost was reduced by 75%. The aeroelastic and aerothermoelastic results presented illustrate the applicability of the CFL3D code for the hypersonic flight regime.

Trajectory Approaches for Launching Hypersonic Flight Tests (Preprint)

DTIC Science & Technology

2014-08-01

This paper presents some approaches toward designing trajectories for hypersonic testing at up to Mach 10 speed using a reusable rocket -powered first...Program to Optimize Simulated Trajectories (POST) code to look at different ways of flying to Mach 10 with a reusable first stage rocket . These trajectories...are good starting points for how to setup a trajectory simulation to meet hypersonic testing needs. 15. SUBJECT TERMS responsive and reusable rocket

Infrared measurement and composite tracking algorithm for air-breathing hypersonic vehicles

NASA Astrophysics Data System (ADS)

Zhang, Zhao; Gao, Changsheng; Jing, Wuxing

2018-03-01

Air-breathing hypersonic vehicles have capabilities of hypersonic speed and strong maneuvering, and thus pose a significant challenge to conventional tracking methodologies. To achieve desirable tracking performance for hypersonic targets, this paper investigates the problems related to measurement model design and tracking model mismatching. First, owing to the severe aerothermal effect of hypersonic motion, an infrared measurement model in near space is designed and analyzed based on target infrared radiation and an atmospheric model. Second, using information from infrared sensors, a composite tracking algorithm is proposed via a combination of the interactive multiple models (IMM) algorithm, fitting dynamics model, and strong tracking filter. During the procedure, the IMMs algorithm generates tracking data to establish a fitting dynamics model of the target. Then, the strong tracking unscented Kalman filter is employed to estimate the target states for suppressing the impact of target maneuvers. Simulations are performed to verify the feasibility of the presented composite tracking algorithm. The results demonstrate that the designed infrared measurement model effectively and continuously observes hypersonic vehicles, and the proposed composite tracking algorithm accurately and stably tracks these targets.

Wind Tunnel Test of Mach 5 Class Hypersonic Airplane

NASA Astrophysics Data System (ADS)

Nakatani, Hiroki; Taguchi, Hideyuki; Fujita, Kazuhisa; Shindo, Shigemi; Honami, Shinji

JAXA is currently performing studies on a Hypersonic Turbojet Experimental Vehicle, which involve a hypersonic flight test of a Small Pre-cooled Turbojet Engine. The aerodynamic performance of this airplane was examined at the JAXA hypersonic, supersonic, and transonic wind tunnel facilities. The 6-degrees-of-freedom forces and pressure distribution around the model were measured and evaluated. This airplane satisfies the lift-to-drag ratio requirement for a flight test at Mach 5. In addition, the results indicate that this airplane has longitudinal and directional static stability if the moment reference point is x/l smaller than 0.35. A separation occurs at the external expanding nozzle. Therefore, a redesign is necessary to solve these problems.

Hypersonic aerospace vehicle leading edge cooling using heat pipe, transpiration and film cooling techniques

NASA Astrophysics Data System (ADS)

Modlin, James Michael

An investigation was conducted to study the feasibility of cooling hypersonic vehicle leading edge structures exposed to severe aerodynamic surface heat fluxes using a combination of liquid metal heat pipes and surface mass transfer cooling techniques. A generalized, transient, finite difference based hypersonic leading edge cooling model was developed that incorporated these effects and was demonstrated on an assumed aerospace plane-type wing leading edge section and a SCRAMJET engine inlet leading edge section. The hypersonic leading edge cooling model was developed using an existing, experimentally verified heat pipe model. Two applications of the hypersonic leading edge cooling model were examined. An assumed aerospace plane-type wing leading edge section exposed to a severe laminar, hypersonic aerodynamic surface heat flux was studied. A second application of the hypersonic leading edge cooling model was conducted on an assumed one-quarter inch nose diameter SCRAMJET engine inlet leading edge section exposed to both a transient laminar, hypersonic aerodynamic surface heat flux and a type 4 shock interference surface heat flux. The investigation led to the conclusion that cooling leading edge structures exposed to severe hypersonic flight environments using a combination of liquid metal heat pipe, surface transpiration, and film cooling methods appeared feasible.

Lagrangian Particle Tracking in a Discontinuous Galerkin Method for Hypersonic Reentry Flows in Dusty Environments

NASA Astrophysics Data System (ADS)

Ching, Eric; Lv, Yu; Ihme, Matthias

2017-11-01

Recent interest in human-scale missions to Mars has sparked active research into high-fidelity simulations of reentry flows. A key feature of the Mars atmosphere is the high levels of suspended dust particles, which can not only enhance erosion of thermal protection systems but also transfer energy and momentum to the shock layer, increasing surface heat fluxes. Second-order finite-volume schemes are typically employed for hypersonic flow simulations, but such schemes suffer from a number of limitations. An attractive alternative is discontinuous Galerkin methods, which benefit from arbitrarily high spatial order of accuracy, geometric flexibility, and other advantages. As such, a Lagrangian particle method is developed in a discontinuous Galerkin framework to enable the computation of particle-laden hypersonic flows. Two-way coupling between the carrier and disperse phases is considered, and an efficient particle search algorithm compatible with unstructured curved meshes is proposed. In addition, variable thermodynamic properties are considered to accommodate high-temperature gases. The performance of the particle method is demonstrated in several test cases, with focus on the accurate prediction of particle trajectories and heating augmentation. Financial support from a Stanford Graduate Fellowship and the NASA Early Career Faculty program are gratefully acknowledged.

Hypersonic Shock/Boundary-Layer Interaction Database

NASA Technical Reports Server (NTRS)

Settles, G. S.; Dodson, L. J.

1991-01-01

Turbulence modeling is generally recognized as the major problem obstructing further advances in computational fluid dynamics (CFD). A closed solution of the governing Navier-Stokes equations for turbulent flows of practical consequence is still far beyond grasp. At the same time, the simplified models of turbulence which are used to achieve closure of the Navier-Stokes equations are known to be rigorously incorrect. While these models serve a definite purpose, they are inadequate for the general prediction of hypersonic viscous/inviscid interactions, mixing problems, chemical nonequilibria, and a range of other phenomena which must be predicted in order to design a hypersonic vehicle computationally. Due to the complexity of turbulence, useful new turbulence models are synthesized only when great expertise is brought to bear and considerable intellectual energy is expended. Although this process is fundamentally theoretical, crucial guidance may be gained from carefully-executed basic experiments. Following the birth of a new model, its testing and validation once again demand comparisons with data of unimpeachable quality. This report concerns these issues which arise from the experimental aspects of hypersonic modeling and represents the results of the first phase of an effort to develop compressible turbulence models.

Pitot pressure analyses in CO2 condensing rarefied hypersonic flows

NASA Astrophysics Data System (ADS)

Ozawa, T.; Suzuki, T.; Fujita, K.

2016-11-01

In order to improve the accuracy of rarefied aerodynamic prediction, a hypersonic rarefied wind tunnel (HRWT) was developed at Japan Aerospace Exploration Agency. While this wind tunnel has been limited to inert gases, such as nitrogen or argon, we recently extended the capability of HRWT to CO2 hypersonic flows for several Mars missions. Compared to our previous N2 cases, the condensation effect may not be negligible for CO2 rarefied aerodynamic measurements. Thus, in this work, we have utilized both experimental and numerical approaches to investigate the condensation and rarefaction effects in CO2 hypersonic nozzle flows.

Heating Augmentation for Short Hypersonic Protuberances

NASA Technical Reports Server (NTRS)

Mazaheri, Ali R.; Wood, William A.

2008-01-01

Computational aeroheating analyses of the Space Shuttle Orbiter plug repair models are validated against data collected in the Calspan University of Buffalo Research Center (CUBRC) 48 inch shock tunnel. The comparison shows that the average difference between computed heat transfer results and the data is about 9.5%. Using CFD and Wind Tunnel (WT) data, an empirical correlation for estimating heating augmentation on short hypersonic protuberances (k/delta less than 0.3) is proposed. This proposed correlation is compared with several computed flight simulation cases and good agreement is achieved. Accordingly, this correlation is proposed for further investigation on other short hypersonic protuberances for estimating heating augmentation.

Optimal trajectories for hypersonic launch vehicles

NASA Technical Reports Server (NTRS)

Ardema, Mark D.; Bowles, Jeffrey V.; Whittaker, Thomas

1994-01-01

In this paper, we derive a near-optimal guidance law for the ascent trajectory from earth surface to earth orbit of a hypersonic, dual-mode propulsion, lifting vehicle. Of interest are both the optical flight path and the optimal operation of the propulsion system. The guidance law is developed from the energy-state approximation of the equations of motion. Because liquid hydrogen fueled hypersonic aircraft are volume sensitive, as well as weight sensitive, the cost functional is a weighted sum of fuel mass and volume; the weighting factor is chosen to minimize gross take-off weight for a given payload mass and volume in orbit.

Hypersonic Viscous Flow Over Large Roughness Elements

NASA Technical Reports Server (NTRS)

Chang, Chau-Lyan; Choudhari, Meelan M.

2009-01-01

Viscous flow over discrete or distributed surface roughness has great implications for hypersonic flight due to aerothermodynamic considerations related to laminar-turbulent transition. Current prediction capability is greatly hampered by the limited knowledge base for such flows. To help fill that gap, numerical computations are used to investigate the intricate flow physics involved. An unstructured mesh, compressible Navier-Stokes code based on the space-time conservation element, solution element (CESE) method is used to perform time-accurate Navier-Stokes calculations for two roughness shapes investigated in wind tunnel experiments at NASA Langley Research Center. It was found through 2D parametric study that at subcritical Reynolds numbers of the boundary layers, absolute instability resulting in vortex shedding downstream, is likely to weaken at supersonic free-stream conditions. On the other hand, convective instability may be the dominant mechanism for supersonic boundary layers. Three-dimensional calculations for a rectangular or cylindrical roughness element at post-shock Mach numbers of 4.1 and 6.5 also confirm that no self-sustained vortex generation is present.

CFD for hypersonic propulsion

NASA Technical Reports Server (NTRS)

Povinelli, Louis A.

1991-01-01

An overview is given of research activity on the application of computational fluid dynamics (CDF) for hypersonic propulsion systems. After the initial consideration of the highly integrated nature of air-breathing hypersonic engines and airframe, attention is directed toward computations carried out for the components of the engine. A generic inlet configuration is considered in order to demonstrate the highly three dimensional viscous flow behavior occurring within rectangular inlets. Reacting flow computations for simple jet injection as well as for more complex combustion chambers are then discussed in order to show the capability of viscous finite rate chemical reaction computer simulations. Finally, the nozzle flow fields are demonstrated, showing the existence of complex shear layers and shock structure in the exhaust plume. The general issues associated with code validation as well as the specific issue associated with the use of CFD for design are discussed. A prognosis for the success of CFD in the design of future propulsion systems is offered.

CFD for hypersonic propulsion

NASA Technical Reports Server (NTRS)

Povinelli, Louis A.

1990-01-01

An overview is given of research activity on the application of computational fluid dynamics (CDF) for hypersonic propulsion systems. After the initial consideration of the highly integrated nature of air-breathing hypersonic engines and airframe, attention is directed toward computations carried out for the components of the engine. A generic inlet configuration is considered in order to demonstrate the highly three dimensional viscous flow behavior occurring within rectangular inlets. Reacting flow computations for simple jet injection as well as for more complex combustion chambers are then discussed in order to show the capability of viscous finite rate chemical reaction computer simulations. Finally, the nozzle flow fields are demonstrated, showing the existence of complex shear layers and shock structure in the exhaust plume. The general issues associated with code validation as well as the specific issue associated with the use of CFD for design are discussed. A prognosis for the success of CFD in the design of future propulsion systems is offered.

Uncertainty Propagation in Hypersonic Vehicle Aerothermoelastic Analysis

NASA Astrophysics Data System (ADS)

Lamorte, Nicolas Etienne

Hypersonic vehicles face a challenging flight environment. The aerothermoelastic analysis of its components requires numerous simplifying approximations. Identifying and quantifying the effect of uncertainties pushes the limits of the existing deterministic models, and is pursued in this work. An uncertainty quantification framework is used to propagate the effects of identified uncertainties on the stability margins and performance of the different systems considered. First, the aeroelastic stability of a typical section representative of a control surface on a hypersonic vehicle is examined. Variability in the uncoupled natural frequencies of the system is modeled to mimic the effect of aerodynamic heating. Next, the stability of an aerodynamically heated panel representing a component of the skin of a generic hypersonic vehicle is considered. Uncertainty in the location of transition from laminar to turbulent flow and the heat flux prediction is quantified using CFD. In both cases significant reductions of the stability margins are observed. A loosely coupled airframe--integrated scramjet engine is considered next. The elongated body and cowl of the engine flow path are subject to harsh aerothermodynamic loading which causes it to deform. Uncertainty associated with deformation prediction is propagated to the engine performance analysis. The cowl deformation is the main contributor to the sensitivity of the propulsion system performance. Finally, a framework for aerothermoelastic stability boundary calculation for hypersonic vehicles using CFD is developed. The usage of CFD enables one to consider different turbulence conditions, laminar or turbulent, and different models of the air mixture, in particular real gas model which accounts for dissociation of molecules at high temperature. The system is found to be sensitive to turbulence modeling as well as the location of the transition from laminar to turbulent flow. Real gas effects play a minor role in the

Development of a Flexible Framework for Hypersonic Navier-Stoke Space Shuttle Orbiter Meshes

NASA Technical Reports Server (NTRS)

Alter, Stephen J.; Reuthler, James J.; McDaniel, Ryan D.

2004-01-01

A flexible framework constructing block structured volume grids for hypersonic Navier-Strokes flow simulations was developed for the analysis of the Shuttle Orbiter Columbia. The development of the framework, which was partially basedon the requirements of the primary flow solvers used resulted in an ability to directly correlate solutions contributed by participating groups on a common surface mesh. A foundation was built through the assessment of differences between differnt solvers, which provided confidence for independent assessment of other damage scenarios by team members. The framework draws on the experience of NASA Langley and NASA Ames Research Centers in structured grid generation, and consists of a grid generation, and consist of a grid generation process implemented through a division of responsibilities. The nominal division of labor consisted of NASA Johnson Space Center coordinating the damage scenarios to be analyzed by the Aerothermodynamics Columbia Accident Investigation (ACAI) team, Ames developing the surface grids that described the computational volume about the Orbiter, and Langley improving grid quality of Ames generated data and constructing the final computational volume grids. Distributing the work among the participant in th ACAI team resulted in significantl less time required to construct complete meshes than possible by any individual participant. The approach demonstrated that the One-NASA grid generation team could sustain the demand of for five new meshes to explore new damage scenarios within an aggressive time-line.

The NASA Ames Hypervelocity Free Flight Aerodynamic Facility: Experimental Simulation of the Atmospheric Break-Up of Meteors

NASA Technical Reports Server (NTRS)

Wilder, M. C.; Bogdanoff, D. W.

2015-01-01

The Hypervelocity Free Flight Aerodynamic Facility at NASA Ames Research Center provides a potential platform for the experimental simulation of meteor breakup at conditions that closely match full-scale entry condition for select parameters. The poster describes the entry environment simulation capabilities of the Hypervelocity Free Flight Aerodynamic Facility (HFFAF) at NASA Ames Research Center and provides example images of the fragmentation of a hypersonic projectile for which break-up was initiated by mechanical forces (impact with a thin polymer diaphragm).

Phoenix Missile Hypersonic Testbed (PMHT): System Concept Overview

NASA Technical Reports Server (NTRS)

Jones, Thomas P.

2007-01-01

A viewgraph presentation of the Phoenix Missile Hypersonic Testbed (PMHT) is shown. The contents include: 1) Need and Goals; 2) Phoenix Missile Hypersonic Testbed; 3) PMHT Concept; 4) Development Objectives; 5) Possible Research Payloads; 6) Possible Research Program Participants; 7) PMHT Configuration; 8) AIM-54 Internal Hardware Schematic; 9) PMHT Configuration; 10) New Guidance and Armament Section Profiles; 11) Nomenclature; 12) PMHT Stack; 13) Systems Concept; 14) PMHT Preflight Activities; 15) Notional Ground Path; and 16) Sample Theoretical Trajectories.

CFD analysis of hypersonic, chemically reacting flow fields

NASA Technical Reports Server (NTRS)

Edwards, T. A.

1993-01-01

Design studies are underway for a variety of hypersonic flight vehicles. The National Aero-Space Plane will provide a reusable, single-stage-to-orbit capability for routine access to low earth orbit. Flight-capable satellites will dip into the atmosphere to maneuver to new orbits, while planetary probes will decelerate at their destination by atmospheric aerobraking. To supplement limited experimental capabilities in the hypersonic regime, computational fluid dynamics (CFD) is being used to analyze the flow about these configurations. The governing equations include fluid dynamic as well as chemical species equations, which are being solved with new, robust numerical algorithms. Examples of CFD applications to hypersonic vehicles suggest an important role this technology will play in the development of future aerospace systems. The computational resources needed to obtain solutions are large, but solution adaptive grids, convergence acceleration, and parallel processing may make run times manageable.

Control Relevant Modeling and Design of Scramjet-Powered Hypersonic Vehicles

NASA Astrophysics Data System (ADS)

Dickeson, Jeffrey James

This report provides an overview of scramjet-powered hypersonic vehicle modeling and control challenges. Such vehicles are characterized by unstable non-minimum phase dynamics with significant coupling and low thrust margins. Recent trends in hypersonic vehicle research are summarized. To illustrate control relevant design issues and tradeoffs, a generic nonlinear 3DOF longitudinal dynamics model capturing aero-elastic-propulsive interactions for wedge-shaped vehicle is used. Limitations of the model are discussed and numerous modifications have been made to address control relevant needs. Two different baseline configurations are examined over a two-stage to orbit ascent trajectory. The report highlights how vehicle level-flight static (trim) and dynamic properties change over the trajectory. Thermal choking constraints are imposed on control system design as a direct consequence of having a finite FER margin. The implication of this state-dependent nonlinear FER margin constraint, the right half plane (RHP) zero, and lightly damped flexible modes, on control system bandwidth (BW) and FPA tracking has been discussed. A control methodology has been proposed that addresses the above dynamics while providing some robustness to modeling uncertainty. Vehicle closure (the ability to fly a trajectory segment subject to constraints) is provided through a proposed vehicle design methodology. The design method attempts to use open loop metrics whenever possible to design the vehicle. The design method is applied to a vehicle/control law closed loop nonlinear simulation for validation. The 3DOF longitudinal modeling results are validated against a newly released NASA 6DOF code.

A Perspective on Computational Aerothermodynamics at NASA

NASA Technical Reports Server (NTRS)

Gnoffo, Peter A.

2007-01-01

The evolving role of computational aerothermodynamics (CA) within NASA over the past 20 years is reviewed. The presentation highlights contributions to understanding the Space Shuttle pitching moment anomaly observed in the first shuttle flight, prediction of a static instability for Mars Pathfinder, and the use of CA for damage assessment in post-Columbia mission support. In the view forward, several current challenges in computational fluid dynamics and aerothermodynamics for hypersonic vehicle applications are discussed. Example simulations are presented to illustrate capabilities and limitations. Opportunities to advance the state-of-art in algorithms, grid generation and adaptation, and code validation are identified.

Multigrid schemes for viscous hypersonic flows

NASA Technical Reports Server (NTRS)

Swanson, R. C.; Radespiel, R.

1993-01-01

Several multigrid schemes are considered for the numerical computation of viscous hypersonic flows. For each scheme, the basic solution algorithm employs upwind spatial discretization with explicit multistage time stepping. Two-level versions of the various multigrid algorithms are applied to the two-dimensional advection equation, and Fourier analysis is used to determine their damping properties. The capabilities of the multigrid methods are assessed by solving two different hypersonic flow problems. Some new multigrid schemes, based on semicoarsening strategies, are shown to be quite effective in relieving the stiffness caused by the high-aspect-ratio cells required to resolve high Reynolds number flows. These schemes exhibit good convergence rates for Reynolds numbers up to 200 x 10(exp 6).

Research on hypersonic aircraft using pre-cooled turbojet engines

NASA Astrophysics Data System (ADS)

Taguchi, Hideyuki; Kobayashi, Hiroaki; Kojima, Takayuki; Ueno, Atsushi; Imamura, Shunsuke; Hongoh, Motoyuki; Harada, Kenya

2012-04-01

Systems analysis of a Mach 5 class hypersonic aircraft is performed. The aircraft can fly across the Pacific Ocean in 2 h. A multidisciplinary optimization program for aerodynamics, structure, propulsion, and trajectory is used in the analysis. The result of each element model is improved using higher accuracy analysis tools. The aerodynamic performance of the hypersonic aircraft is examined through hypersonic wind tunnel tests. A thermal management system based on the data of the wind tunnel tests is proposed. A pre-cooled turbojet engine is adopted as the propulsion system for the hypersonic aircraft. The engine can be operated continuously from take-off to Mach 5. This engine uses a pre-cooling cycle using cryogenic liquid hydrogen. The high temperature inlet air of hypersonic flight would be cooled by the same liquid hydrogen used as fuel. The engine is tested under sea level static conditions. The engine is installed on a flight test vehicle. Both liquid hydrogen fuel and gaseous hydrogen fuel are supplied to the engine from a tank and cylinders installed within the vehicle. The designed operation of major components of the engine is confirmed. A large amount of liquid hydrogen is supplied to the pre-cooler in order to make its performance sufficient for Mach 5 flight. Thus, fuel rich combustion is adopted at the afterburner. The experiments are carried out under the conditions that the engine is mounted upon an experimental airframe with both set up either horizontally or vertically. As a result, the operating procedure of the pre-cooled turbojet engine is demonstrated.

Research in robust control for hypersonic aircraft

NASA Technical Reports Server (NTRS)

Calise, A. J.

1994-01-01

The research during the third reporting period focused on fixed order robust control design for hypersonic vehicles. A new technique was developed to synthesize fixed order H(sub infinity) controllers. A controller canonical form is imposed on the compensator structure and a homotopy algorithm is employed to perform the controller design. Various reduced order controllers are designed for a simplified version of the hypersonic vehicle model used in our previous studies to demonstrate the capabilities of the code. However, further work is needed to investigate the issue of numerical ill-conditioning for large order systems and to make the numerical approach more reliable.

Body weight of hypersonic aircraft, part 1

NASA Technical Reports Server (NTRS)

Ardema, Mark D.

1988-01-01

The load bearing body weight of wing-body and all-body hypersonic aircraft is estimated for a wide variety of structural materials and geometries. Variations of weight with key design and configuration parameters are presented and discussed. Both hot and cool structure approaches are considered in isotropic, organic composite, and metal matrix composite materials; structural shells are sandwich or skin-stringer. Conformal and pillow-tank designs are investigated for the all-body shape. The results identify the most promising hypersonic aircraft body structure design approaches and their weight trends. Geometric definition of vehicle shapes and structural analysis methods are presented in appendices.

Experimental Supersonic Combustion Research at NASA Langley

NASA Technical Reports Server (NTRS)

Rogers, R. Clayton; Capriotti, Diego P.; Guy, R. Wayne

1998-01-01

Experimental supersonic combustion research related to hypersonic airbreathing propulsion has been actively underway at NASA Langley Research Center (LaRC) since the mid-1960's. This research involved experimental investigations of fuel injection, mixing, and combustion in supersonic flows and numerous tests of scramjet engine flowpaths in LaRC test facilities simulating flight from Mach 4 to 8. Out of this research effort has come scramjet combustor design methodologies, ground test techniques, and data analysis procedures. These technologies have progressed steadily in support of the National Aero-Space Plane (NASP) program and the current Hyper-X flight demonstration program. During NASP nearly 2500 tests of 15 scramjet engine models were conducted in LaRC facilities. In addition, research supporting the engine flowpath design investigated ways to enhance mixing, improve and apply nonintrusive diagnostics, and address facility operation. Tests of scramjet combustor operation at conditions simulating hypersonic flight at Mach numbers up to 17 also have been performed in an expansion tube pulse facility. This paper presents a review of the LaRC experimental supersonic combustion research efforts since the late 1980's, during the NASP program, and into the Hyper-X Program.

Results of test 0A82 in the NASA/LRC 31 inch CFHT on an 0.010-scale model (32-0) of the space shuttle configuration 3 to determine RCS jet flow field interaction and to investigate RT real gas effects

NASA Technical Reports Server (NTRS)

Thornton, D. E.

1975-01-01

Tests were conducted in the NASA Langley Research Center 31-inch Continuous Flow Hypersonic Wind Tunnel to determine RCS jet interaction effects on hypersonic aerodynamic characteristics and to investigate RT (gas constant times temperature) scaling effects on the RCS similitude. The model was an 0.010-scale replica of the Space Shuttle Orbiter Configuration 3. Hypersonic aerodynamic data were obtained from tests at Mach 10.3 and dynamic pressures of 200, 150, 125, and 100 psf. The RCS modes of pitch, yaw, and roll at free flight dynamic pressure simulation of 20 psf were investigated.

Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP.

PubMed

Cheng, Timothy H T; Gorman, Maggie; Martin, Lynn; Barclay, Ella; Casey, Graham; Saunders, Brian; Thomas, Huw; Clark, Sue; Tomlinson, Ian

2015-02-01

The presence of multiple (5-100) colorectal adenomas suggests an inherited predisposition, but the genetic aetiology of this phenotype is undetermined if patients test negative for Mendelian polyposis syndromes such as familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). We investigated whether 18 common colorectal cancer (CRC) predisposition single-nucleotide polymorphisms (SNPs) could help to explain some cases with multiple adenomas who phenocopied FAP or MAP, but had no pathogenic APC or MUTYH variant. No multiple adenoma case had an outlying number of CRC SNP risk alleles, but multiple adenoma patients did have a significantly higher number of risk alleles than population controls (P=5.7 × 10(-7)). The association was stronger in those with ≥10 adenomas. The CRC SNPs accounted for 4.3% of the variation in multiple adenoma risk, with three SNPs (rs6983267, rs10795668, rs3802842) explaining 3.0% of the variation. In FAP patients, the CRC risk score did not differ significantly from the controls, as we expected given the overwhelming effect of pathogenic germline APC variants on the phenotype of these cases. More unexpectedly, we found no evidence that the CRC SNPs act as modifier genes for the number of colorectal adenomas in FAP patients. In conclusion, common colorectal tumour risk alleles contribute to the development of multiple adenomas in patients without pathogenic germline APC or MUTYH variants. This phenotype may have 'polygenic' or monogenic origins. The risk of CRC in relatives of multiple adenoma cases is probably much lower for cases with polygenic disease, and this should be taken into account when counselling such patients.

2-D Air-Breathing Lightcraft Engine Experiments in Hypersonic Conditions

NASA Astrophysics Data System (ADS)

Salvador, Israel I.; Myrabo, Leik N.; Minucci, Marco A. S.; de Oliveira, Antonio C.; Toro, Paulo G. P.; Chanes, José B.; Rego, Israel S.

2011-11-01

Experiments were performed with a 2-D, repetitively-pulsed (RP) laser Lightcraft model in hypersonic flow conditions. The main objective was the feasibility analysis for impulse generation with repetitively-pulsed air-breathing laser Lightcraft engines at hypersonic speeds. The future application of interest for this basic research endeavor is the laser launch of pico-, nano-, and micro-satellites (i.e., 0.1-100 kg payloads) into Low-Earth-Orbit, at low-cost and on-demand. The laser propulsion experiments employed a Hypersonic Shock Tunnel integrated with twin gigawatt pulsed Lumonics 620-TEA CO2 lasers (˜ 1 μs pulses), to produce the required test conditions. This hypersonic campaign was carried out at nominal Mach numbers ranging from 6 to 10. Time-dependent surface pressure distributions were recorded together with Schlieren movies of the flow field structure resulting from laser energy deposition. Results indicated laser-induced pressure increases of 0.7-0.9 bar with laser pulse energies of ˜ 170 J, on off-shroud induced breakdown condition, and Mach number of 7.

Design, Validation, and Testing of a Hot-Film Anemometer for Hypersonic Flow

NASA Astrophysics Data System (ADS)

Sheplak, Mark

The application of constant-temperature hot-film anemometry to hypersonic flow has been reviewed and extended in this thesis. The objective of this investigation was to develop a measurement tool capable of yielding continuous, high-bandwidth, quantitative, normal mass-flux and total -temperature measurements in moderate-enthalpy environments. This research has produced a probe design that represents a significant advancement over existing designs, offering the following improvements: (1) a five-fold increase in bandwidth; (2) true stagnation-line sensor placement; (3) a two order-of-magnitude decrease in sensor volume; and (4) over a 70% increase in maximum film temperature. These improvements were achieved through substrate design, sensor placement, the use of high-temperature materials, and state -of-the-art microphotolithographic fabrication techniques. The experimental study to characterize the probe was performed in four different hypersonic wind tunnels at NASA-Langley Research Center. The initial test consisted of traversing the hot film through a Mach 6, flat-plate, turbulent boundary layer in air. The detailed static-calibration measurements that followed were performed in two different hypersonic flows: a Mach 11 helium flow and Mach 6 air flow. The final test of this thesis consisted of traversing the probe through the Mach 6 wake of a 70^ circ blunt body. The goal of this test was to determine the state (i.e., laminar or turbulent) of the wake. These studies indicate that substrate conduction effects result in instrumentation characteristics that prevent the hot-film anemometer from being used as a quantitative tool. The extension of this technique to providing quantitative information is dependent upon the development of lower thermal-conductivity substrate materials. However, the probe durability, absence of strain gauging, and high bandwidth represent significant improvements over the hot-wire technique for making qualitative measurements. Potential

Acoustic phonon dispersion at hypersonic frequencies in Si and Ge

NASA Astrophysics Data System (ADS)

Kuok, M. H.; Ng, S. C.; Rang, Z. L.; Lockwood, D. J.

2000-11-01

Brillouin spectra of the longitudinal acoustic (LA) mode, traveling along the [001] direction, in silicon and germanium have been recorded in 180° backscattering using 457.9-514.5-nm laser lines. The wave velocity of the LA phonon propagating in the [001] direction was determined at hypersonic frequencies, from the measured acoustic phonon dispersion in silicon and germanium. The elastic modulus c11 of the two semiconductors has been calculated from the respective measured hypersonic wave velocities and the results are compared with values determined from lower-frequency ultrasonic and other measurements. Interestingly, the hypersonic velocities are consistently lower by ~1-2 % than the ultrasonic ones, but they generally agree within the present experimental accuracy.

International Hypersonic Waverider Symposium, 1st, University of Maryland, College Park, MD, Oct. 17-19, 1990, Proceedings

NASA Technical Reports Server (NTRS)

Anderson, John D., Jr. (Editor); Lewis, Mark J. (Editor); Corda, Stephen (Editor); Blankson, Isaiah M. (Editor)

1990-01-01

The papers presented in this volume provide an overview of current theoretical and experimental research in the field of hypersonic waveriders. In particular, attention is given to efficient waveriders from known axisymmetric flow fields, hypersonic waverider design from given shock waves, limitations of waveriders, and aerodynamic stability theory of hypersonic waveriders. The discussion also covers momentum analysis of waverider flow fields, tethered aerothermodynamic research for hypersonic waveriders, simulation of hypersonic waveriders, and an idealized tip-to-tail waverider model.

Hypersonic Engine Leading Edge Experiments in a High Heat Flux, Supersonic Flow Environment

NASA Technical Reports Server (NTRS)

Gladden, Herbert J.; Melis, Matthew E.

1994-01-01

A major concern in advancing the state-of-the-art technologies for hypersonic vehicles is the development of an aeropropulsion system capable of withstanding the sustained high thermal loads expected during hypersonic flight. Three aerothermal load related concerns are the boundary layer transition from laminar to turbulent flow, articulating panel seals in high temperature environments, and strut (or cowl) leading edges with shock-on-shock interactions. A multidisciplinary approach is required to address these technical concerns. A hydrogen/oxygen rocket engine heat source has been developed at the NASA Lewis Research Center as one element in a series of facilities at national laboratories designed to experimentally evaluate the heat transfer and structural response of the strut (or cowl) leading edge. A recent experimental program conducted in this facility is discussed and related to cooling technology capability. The specific objective of the experiment discussed is to evaluate the erosion and oxidation characteristics of a coating on a cowl leading edge (or strut leading edge) in a supersonic, high heat flux environment. Heat transfer analyses of a similar leading edge concept cooled with gaseous hydrogen is included to demonstrate the complexity of the problem resulting from plastic deformation of the structures. Macro-photographic data from a coated leading edge model show progressive degradation over several thermal cycles at aerothermal conditions representative of high Mach number flight.

Numerical simulation of supersonic and hypersonic inlet flow fields

NASA Technical Reports Server (NTRS)

Mcrae, D. Scott; Kontinos, Dean A.

1995-01-01

This report summarizes the research performed by North Carolina State University and NASA Ames Research Center under Cooperative Agreement NCA2-719, 'Numerical Simulation of Supersonic and Hypersonic Inlet Flow Fields". Four distinct rotated upwind schemes were developed and investigated to determine accuracy and practicality. The scheme found to have the best combination of attributes, including reduction to grid alignment with no rotation, was the cell centered non-orthogonal (CCNO) scheme. In 2D, the CCNO scheme improved rotation when flux interpolation was extended to second order. In 3D, improvements were less dramatic in all cases, with second order flux interpolation showing the least improvement over grid aligned upwinding. The reduction in improvement is attributed to uncertainty in determining optimum rotation angle and difficulty in performing accurate and efficient interpolation of the angle in 3D. The CCNO rotational technique will prove very useful for increasing accuracy when second order interpolation is not appropriate and will materially improve inlet flow solutions.

The Mercury Laser System: An Average power, gas-cooled, Yb:S-FAP based system with frequency conversion and wavefront correction

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

Bibeau, C; Bayramian, A; Armstrong, P

We report on the operation of the Mercury laser with fourteen 4 x 6 cm{sup 2} Yb:S-FAP amplifier slabs pumped by eight 100 kW peak power diode arrays. The system was continuously run at 55 J and 10 Hz for several hours, (2 x 10{sup 5} cumulative shots) with over 80% of the energy in a 6 times diffraction limited spot at 1.047 um. Improved optical quality was achieved in Yb:S-FAP amplifiers with magneto-rheological finishing, a deterministic polishing method. In addition, average power frequency conversion employing YCOB was demonstrated at 50% conversion efficiency or 22.6 J at 10 Hz.

Hypersonic engine seal development at NASA Lewis Research Center

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M.

1994-01-01

NASA Lewis Research Center is developing advanced seal concepts and sealing technology for advanced combined cycle ramjet/scramjet engines being designed for the National Aerospace Plane (NASP). Technologies are being developed for both the dynamic seals that seal the sliding interfaces between articulating engine panels and sidewalls, and for the static seals that seal the heat exchanger to back-up structure interfaces. This viewgraph presentation provides an overview of the candidate engine seal concepts, seal material assessments, and unique test facilities used to assess the leakage and thermal performance of the seal concepts.

Hypersonic engine seal development at NASA Lewis Research Center

NASA Astrophysics Data System (ADS)

Steinetz, Bruce M.

1994-07-01

NASA Lewis Research Center is developing advanced seal concepts and sealing technology for advanced combined cycle ramjet/scramjet engines being designed for the National Aerospace Plane (NASP). Technologies are being developed for both the dynamic seals that seal the sliding interfaces between articulating engine panels and sidewalls, and for the static seals that seal the heat exchanger to back-up structure interfaces. This viewgraph presentation provides an overview of the candidate engine seal concepts, seal material assessments, and unique test facilities used to assess the leakage and thermal performance of the seal concepts.

X-43A/Hyper-X Vehicle Arrives at NASA Dryden

NASA Technical Reports Server (NTRS)

1999-01-01

A close-up of the X-43A Hypersonic Experimental Vehicle, or 'Hyper-X,' in its protective shipping framework as it arrives at the Dryden Flight Research Center in October 1999. The X-43A was developed to research a dual-mode ramjet/scramjet propulsion system at speeds from Mach 7 up to Mach 10 (7 to 10 times the speed of sound, which varies with temperature and altitude). Hyper-X, the flight vehicle for which is designated as X-43A, is an experimental flight-research program seeking to demonstrate airframe-integrated, 'air-breathing' engine technologies that promise to increase payload capacity for future vehicles, including hypersonic aircraft (faster than Mach 5) and reusable space launchers. This multiyear program is currently underway at NASA Dryden Flight Research Center, Edwards, California. The Hyper-X schedule calls for its first flight later this year (2000). Hyper-X is a joint program, with Dryden sharing responsibility with NASA's Langley Research Center, Hampton, Virginia. Dryden's primary role is to fly three unpiloted X-43A research vehicles to validate engine technologies and hypersonic design tools as well as the hypersonic test facility at Langley. Langley manages the program and leads the technology development effort. The Hyper-X Program seeks to significantly expand the speed boundaries of air-breathing propulsion by being the first aircraft to demonstrate an airframe-integrated, scramjet-powered free flight. Scramjets (supersonic-combustion ramjets) are ramjet engines in which the airflow through the whole engine remains supersonic. Scramjet technology is challenging because only limited testing can be performed in ground facilities. Long duration, full-scale testing requires flight research. Scramjet engines are air-breathing, capturing their oxygen from the atmosphere. Current spacecraft, such as the Space Shuttle, are rocket powered, so they must carry both fuel and oxygen for propulsion. Scramjet technology-based vehicles need to carry only

The Need for Speed. Hypersonic Aircraft and the Transformation of Long Range Airpower

DTIC Science & Technology

2005-06-01

lxxii Heppenheimer , Thomas A . “Origins of Hypersonic Propulsion: A Personal History.” Air Power History 47, no. 3 (Fall 2000), 14-27. Hicks, John W...early Aerospace plane research. 59 Thomas A . Heippenheimer, “Origins of Hypersonic Propulsion: A Personal History,” Air Power History 47, no. 3 (Fall...experiments with hypersonic engines. 65 Ibid. 66 Thomas A . Heippenheimer, 15. 67 Ibid., 17-18. Lockheed and General Applied Science Laboratories

Mission and Design Sensitivities for Human Mars Landers Using Hypersonic Inflatable Aerodynamic Decelerators

NASA Technical Reports Server (NTRS)

Polsgrove, Tara P.; Thomas, Herbert D.; Dwyer Ciancio, Alicia; Collins, Tim; Samareh, Jamshid

2017-01-01

Landing humans on Mars is one of NASA's long term goals. NASA's Evolvable Mars Campaign (EMC) is focused on evaluating architectural trade options to define the capabilities and elements needed to sustain human presence on the surface of Mars. The EMC study teams have considered a variety of in-space propulsion options and surface mission options. Understanding how these choices affect the performance of the lander will allow a balanced optimization of this complex system of systems problem. This paper presents the effects of mission and vehicle design options on lander mass and performance. Beginning with Earth launch, options include fairing size assumptions, co-manifesting elements with the lander, and Earth-Moon vicinity operations. Capturing into Mars orbit using either aerocapture or propulsive capture is assessed. For entry, descent, and landing both storable as well as oxygen and methane propellant combinations are considered, engine thrust level is assessed, and sensitivity to landed payload mass is presented. This paper focuses on lander designs using the Hypersonic Inflatable Aerodynamic Decelerators, one of several entry system technologies currently considered for human missions.

Evaluation of on-board hydrogen storage methods for hypersonic vehicles

NASA Technical Reports Server (NTRS)

Akyurtlu, Ates; Akyurtlu, J. F.; Adeyiga, A. A.; Perdue, Samara; Northam, G. B.

1989-01-01

Hydrogen is the foremost candidate as a fuel for use in high speed transport. Since any aircraft moving at hypersonic speeds must have a very slender body, means of decreasing the storage volume requirements below that for liquid hydrogen are needed. The total performance of the hypersonic plane needs to be considered for the evaluation of candidate fuel and storage systems. To accomplish this, a simple model for the performance of a hypersonic plane is presented. To allow for the use of different engines and fuels during different phases of flight, the total trajectory is divided into three phases: subsonic-supersonic, hypersonic and rocket propulsion phase. The fuel fraction for the first phase is found be a simple energy balance using an average thrust to drag ratio for this phase. The hypersonic flight phase is investigated in more detail by taking small altitude increments. This approach allowed the use of flight profiles other than the constant dynamic pressure flight. The effect of fuel volume on drag, structural mass and tankage mass was introduced through simplified equations involving the characteristic dimension of the plane. The propellant requirement for the last phase is found by employing the basic rocket equations. The candidate fuel systems such as the cryogenic fuel combinations and solid and liquid endothermic hydrogen generators are first screened thermodynamically with respect to their energy densities and cooling capacities and then evaluated using the above model.

Constrained Aerothermodynamic Design of Hypersonic Vehicles

NASA Technical Reports Server (NTRS)

Gally, Tom; Campbell, Dick

2002-01-01

An investigation was conducted into possible methods of incorporating a hypersonic design capability with aerothermodynamic constraints into the CDISC aerodynamic design tool. The work was divided into two distinct phases: develop relations between surface curvature and hypersonic pressure coefficient which are compatible with CDISC's direct-iterative design method; and explore and implement possible methods of constraining the heat transfer rate over all or portions of the design surface. The main problem in implementing this method has been the weak relationship between surface shape and pressure coefficient at the stagnation point and the need to design around the surface blunt leading edge where there is a slope singularity. The final results show that some success has been achieved, but further improvements are needed.

Heat transfer test of an 0.006-scale thin-skin thermocouple space shuttle model (50-0, 41-T) in the NASA-Ames Research Center 3.5-foot hypersonic wind tunnel at Mach 5.3 (IH28), volume 1

NASA Technical Reports Server (NTRS)

Cummings, J. W.; Foster, T. F.; Lockman, W. K.

1976-01-01

Data obtained from a heat transfer test conducted on an 0.006-scale space shuttle orbiter and external tank in the NASA-Ames Research Center 3.5-foot Hypersonic Wind Tunnel are presented. The purpose of this test was to obtain data under simulated return-to-launch-site abort conditions. Configurations tested were integrated orbiter and external tank, orbiter alone, and external tank alone at angles of attack of 0, + or - 30, + or - 60, + or - 90, and + or - 120 degrees. Runs were conducted at Mach numbers of 5.2 and 5.3 for Reynolds numbers of 1.0 and 4.0 million per foot, respectively. Heat transfer data were obtained from 75 orbiter and 75 external tank iron-constantan thermocouples.

Hypersonic structures: An aerodynamicist's perspective, or one man's dream is another man's nightmare

NASA Technical Reports Server (NTRS)

Watts, J. D.; Jackson, L. R.; Hunt, J. L.

1978-01-01

The relationship between hypersonic aerodynamic and structural design is reviewed. The evolution of the hypersonic vehicle design is presented. Propulsion systems, structural materials, and fuels are emphasized.

Electron-Beam Diagnostic Methods for Hypersonic Flow Diagnostics

NASA Technical Reports Server (NTRS)

1994-01-01

The purpose of this work was the evaluation of the use of electron-bean fluorescence for flow measurements during hypersonic flight. Both analytical and numerical models were developed in this investigation to evaluate quantitatively flow field imaging concepts based upon the electron beam fluorescence technique for use in flight research and wind tunnel applications. Specific models were developed for: (1) fluorescence excitation/emission for nitrogen, (2) rotational fluorescence spectrum for nitrogen, (3) single and multiple scattering of electrons in a variable density medium, (4) spatial and spectral distribution of fluorescence, (5) measurement of rotational temperature and density, (6) optical filter design for fluorescence imaging, and (7) temperature accuracy and signal acquisition time requirements. Application of these models to a typical hypersonic wind tunnel flow is presented. In particular, the capability of simulating the fluorescence resulting from electron impact ionization in a variable density nitrogen or air flow provides the capability to evaluate the design of imaging instruments for flow field mapping. The result of this analysis is a recommendation that quantitative measurements of hypersonic flow fields using electron-bean fluorescence is a tractable method with electron beam energies of 100 keV. With lower electron energies, electron scattering increases with significant beam divergence which makes quantitative imaging difficult. The potential application of the analytical and numerical models developed in this work is in the design of a flow field imaging instrument for use in hypersonic wind tunnels or onboard a flight research vehicle.

Multiple Velocity Profile Measurements in Hypersonic Flows Using Sequentially-Imaged Fluorescence Tagging

NASA Technical Reports Server (NTRS)

Bathel, Brett F.; Danehy, Paul M.; Inman, Jennifer A.; Jones, Stephen B.; Ivey,Christopher b.; Goyne, Christopher P.

2010-01-01

Nitric-oxide planar laser-induced fluorescence (NO PLIF) was used to perform velocity measurements in hypersonic flows by generating multiple tagged lines which fluoresce as they convect downstream. For each laser pulse, a single interline, progressive scan intensified CCD (charge-coupled device) camera was used to obtain two sequential images of the NO molecules that had been tagged by the laser. The CCD configuration allowed for sub-microsecond acquisition of both images, resulting in sub-microsecond temporal resolution as well as sub-mm spatial resolution (0.5-mm horizontal, 0.7-mm vertical). Determination of axial velocity was made by application of a cross-correlation analysis of the horizontal shift of individual tagged lines. A numerical study of measured velocity error due to a uniform and linearly-varying collisional rate distribution was performed. Quantification of systematic errors, the contribution of gating/exposure duration errors, and the influence of collision rate on temporal uncertainty were made. Quantification of the spatial uncertainty depended upon the signal-to-noise ratio of the acquired profiles. This velocity measurement technique has been demonstrated for two hypersonic flow experiments: (1) a reaction control system (RCS) jet on an Orion Crew Exploration Vehicle (CEV) wind tunnel model and (2) a 10-degree half-angle wedge containing a 2-mm tall, 4-mm wide cylindrical boundary layer trip. The experiments were performed at the NASA Langley Research Center's 31-Inch Mach 10 Air Tunnel.

Aerodynamic prediction techniques for hypersonic configuration design

NASA Technical Reports Server (NTRS)

1981-01-01

An investigation of approximate theoretical techniques for predicting aerodynamic characteristics and surface pressures for relatively slender vehicles at moderate hypersonic speeds was performed. Emphasis was placed on approaches that would be responsive to preliminary configuration design level of effort. Potential theory was examined in detail to meet this objective. Numerical pilot codes were developed for relatively simple three dimensional geometries to evaluate the capability of the approximate equations of motion considered. Results from the computations indicate good agreement with higher order solutions and experimental results for a variety of wing, body, and wing-body shapes for values of the hypersonic similarity parameter M delta approaching one.

HASA: Hypersonic Aerospace Sizing Analysis for the Preliminary Design of Aerospace Vehicles

NASA Technical Reports Server (NTRS)

Harloff, Gary J.; Berkowitz, Brian M.

1988-01-01

A review of the hypersonic literature indicated that a general weight and sizing analysis was not available for hypersonic orbital, transport, and fighter vehicles. The objective here is to develop such a method for the preliminary design of aerospace vehicles. This report describes the developed methodology and provides examples to illustrate the model, entitled the Hypersonic Aerospace Sizing Analysis (HASA). It can be used to predict the size and weight of hypersonic single-stage and two-stage-to-orbit vehicles and transports, and is also relevant for supersonic transports. HASA is a sizing analysis that determines vehicle length and volume, consistent with body, fuel, structural, and payload weights. The vehicle component weights are obtained from statistical equations for the body, wing, tail, thermal protection system, landing gear, thrust structure, engine, fuel tank, hydraulic system, avionics, electral system, equipment payload, and propellant. Sample size and weight predictions are given for the Space Shuttle orbiter and other proposed vehicles, including four hypersonic transports, a Mach 6 fighter, a supersonic transport (SST), a single-stage-to-orbit (SSTO) vehicle, a two-stage Space Shuttle with a booster and an orbiter, and two methane-fueled vehicles.

Supersonic Combustion in Air-Breathing Propulsion Systems for Hypersonic Flight

NASA Astrophysics Data System (ADS)

Urzay, Javier

2018-01-01

Great efforts have been dedicated during the last decades to the research and development of hypersonic aircrafts that can fly at several times the speed of sound. These aerospace vehicles have revolutionary applications in national security as advanced hypersonic weapons, in space exploration as reusable stages for access to low Earth orbit, and in commercial aviation as fast long-range methods for air transportation of passengers around the globe. This review addresses the topic of supersonic combustion, which represents the central physical process that enables scramjet hypersonic propulsion systems to accelerate aircrafts to ultra-high speeds. The description focuses on recent experimental flights and ground-based research programs and highlights associated fundamental flow physics, subgrid-scale model development, and full-system numerical simulations.

Overcoming artefact: anticipation in 284 Portuguese kindreds with familial amyloid polyneuropathy (FAP) ATTRV30M.

PubMed

Lemos, Carolina; Coelho, Teresa; Alves-Ferreira, Miguel; Martins-da-Silva, Ana; Sequeiros, Jorge; Mendonça, Denisa; Sousa, Alda

2014-03-01

Early-onset (≤40 years) and later-onset (≥50 years) cases of familial amyloid polyneuropathy (FAP) ATTRV30M are not different entities, often coexisting in the same family, and showing anticipation (earlier age-at-onset (AO) in younger generations, usually associated with more severe phenotype). Historically, anticipation has been ascribed to ascertainment biases. Our aim was to study anticipation in a very large number of FAP kindreds, removing possible biases, and gain further insight into parent-of-origin effects. We analysed 926 parent-offspring pairs (from the Unidade Clínica de Paramiloidose roster, collected in 70 years), both clinically observed and had well-established AO, correcting for intrafamilial correlations. Women had a significantly higher AO, either for daughters (mean: 33.70, SD: 6.84) vs sons (29.43, 6.08); or mothers (39.57, 11.75) vs. fathers (35.62, 11.62). Also, 291 pairs showed marked anticipation (≥10 years); the transmitting parent was the mother in 203 pairs. Mother-son pairs showed larger anticipation (10.43, 9.34), while father-daughter pairs showed only a residual anticipation (1.23, 9.77). Gender of offspring and parents was highly significant (with no interaction). To remove possible biases, we repeated analyses: (1) excluding the proband; (2) removing pairs with simultaneous onset; and (3) excluding offspring born after 1960. Anticipation was found in all subsamples, with the same trend for a parent-of-origin effect. Noteworthy, parents with AO ≤40 years never had offspring with AO ≥50. These findings confirm anticipation as a true biological phenomenon, also in FAP ATTRV30M. Acknowledgment of anticipation may have important clinical implications in genetic counselling of offspring and in follow-up of mutation carriers.

Power-on performance predictions for a complete generic hypersonic vehicle configuration

NASA Technical Reports Server (NTRS)

Bennett, Bradford C.

1991-01-01

The Compressible Navier-Stokes (CNS) code was developed to compute external hypersonic flow fields. It has been applied to various hypersonic external flow applications. Here, the CNS code was modified to compute hypersonic internal flow fields. Calculations were performed on a Mach 18 sidewall compression inlet and on the Lewis Mach 5 inlet. The use of the ARC3D diagonal algorithm was evaluated for internal flows on the Mach 5 inlet flow. The initial modifications to the CNS code involved generalization of the boundary conditions and the addition of viscous terms in the second crossflow direction and modifications to the Baldwin-Lomax turbulence model for corner flows.

Development of a Flexible Framework of Common Hypersonic Navier-Strokes Meshes for the Space Shuttle Orbiter

NASA Technical Reports Server (NTRS)

Alter, Stephen J.; Reuthler, James J.; McDaniel, Ryan D.

2003-01-01

A flexible framework for the development of block structured volume grids for hypersonic Navier-Stokes flow simulations was developed for analysis of the Shuttle Orbiter Columbia. The development of the flexible framework, resulted in an ability to quickly generate meshes to directly correlate solutions contributed by participating groups on a common surface mesh, providing confidence for the extension of the envelope of solutions and damage scenarios. The framework draws on the experience of NASA Langely and NASA Ames Research Centers in structured grid generation, and consists of a grid generation process that is implemented through a division of responsibilities. The nominal division of labor consisted of NASA Johnson Space Center coordinating the damage scenarios to be analyzed by the Aerothermodynamics Columbia Accident Investigation (CAI) team, Ames developing the surface grids that described the computational volume about the orbiter, and Langely improving grid quality of Ames generated data and constructing the final volume grids. Distributing the work among the participants in the Aerothermodynamic CIA team resulted in significantly less time required to construct complete meshes than possible by any individual participant. The approach demonstrated that the One-NASA grid generation team could sustain the demand for new meshes to explore new damage scenarios within a aggressive timeline.

Transition heating rates obtained on a matted and isolated 0.006 scale model (41-OT) space shuttle orbiter and external tank in the NASA/LaRC variable density hypersonic tunnel (IH17)

NASA Technical Reports Server (NTRS)

Cummings, J.

1976-01-01

Model information and data obtained from wind tunnel tests performed on a 0.006 scale model of the Rockwell International space shuttle orbiter and external tank in the 18 inch Variable Density Hypersonic Wind Tunnel (VDHT) at NASA Langley Research Center are presented. Tests were performed at a Mach number of 8.0 over a Reynolds Number range from 0.1 to 10.0 million per foot at 0 deg and -5 deg angle of attack and 0 deg sideslip angle. Transition heating rates were determined using thin skin thermocouples located at various locations on the orbiter and ET. The test was conducted in three stages: orbiter plus external tank (mated configuration); orbiter alone, and external tank alone. The effects of boundary layer trips were also included in the test sequence. The plotted results presented show the effect of configuration interference on the orbiter lower surface and on the ET. Tabulated data are given.

Proceedings of the Seventh Annual Summer Conference. NASA/USRA: University Advanced Design Program

NASA Technical Reports Server (NTRS)

1991-01-01

The Advanced Design Program (ADP) is a unique program that brings together students and faculty from U.S. engineering schools with engineers from the NASA centers through integration of current and future NASA space and aeronautics projects into university engineering design curriculum. The Advanced Space Design Program study topics cover a broad range of projects that could be undertaken during a 20-30 year period beginning with the deployment of the Space Station Freedom. The Advanced Aeronautics Design Program study topics typically focus on nearer-term projects of interest to NASA, covering from small, slow-speed vehicles through large, supersonic passenger transports and on through hypersonic research vehicles. Student work accomplished during the 1990-91 academic year and reported at the 7th Annual Summer Conference is presented.

Molecular mapping of the mutant fap4(A24) allele for elevated palmitate concentration in soybean

USDA-ARS?s Scientific Manuscript database

Soybean [Glycine max L. Merr.] oil with an elevated palmitate concentration is useful for some food and industrial applications. The objective of this study was to map the genetic location of the fap4(A24) allele that controls an increase in palmitate concentration and to identify molecular marker...

Magnetohydrodynamics Accelerator Research Into Advanced Hypersonics (MARIAH). Part 1

NASA Technical Reports Server (NTRS)

Micheletti, David A.; Baughman, Jack A.; Nelson, Gordon L.; Simmons, Gloyd A.

1997-01-01

This report documents the activities, results, conclusions and recommendations of the Magnetohydrodynamics Accelerator Research Into Advanced Hypersonics (MARIAH) Project in which the use of magnetohydrodynamics (MHD) technology is investigated for its applicability to augment hypersonic wind tunnels. The long range objective of this investigation is to advance the development of ground test facilities to support the development of hypervelocity flight vehicles. The MHD accelerator adds kinetic energy directly to the wind tunnel working fluid, thereby increasing its Mach number to hypervelocity levels. Several techniques for MHD augmentation, as well as other physical characteristics of the process are studied to enhance the overall performance of hypersonic wind tunnel design. Specific recommendations are presented to improve the effectiveness of ground test facilities. The work contained herein builds on nearly four decades of research and experimentation by the aeronautics ground test and evaluation community, both foreign and domestic.

Magnetohydrodynamics Accelerator Research into Advanced Hypersonics (MARIAH). Part 2

NASA Technical Reports Server (NTRS)

Baughman, Jack A.; Micheletti, David A.; Nelson, Gordon L.; Simmons, Gloyd A.

1997-01-01

This report documents the activities, results, conclusions and recommendations of the Magnetohydrodynamics Accelerator Research Into Advanced Hypersonics (MARIAH) Project in which the use of magnetohydrodynamics (MHD) technology is investigated for its applicability to augment hypersonic wind tunnels. The long range objective of this investigation is to advance the development of ground test facilities to support the development of hypervelocity flight vehicles. The MHD accelerator adds kinetic energy directly to the wind tunnel working fluid, thereby increasing its Mach number to hypervelocity levels. Several techniques for MHD augmentation, as well as other physical characteristics of the process are studied to enhance the overall performance of hypersonic wind tunnel design. Specific recommendations are presented to improve the effectiveness of ground test facilities. The work contained herein builds on nearly four decades of research and experimentation by the aeronautics ground test and evaluation community, both foreign and domestic.

Day Care in Vermont: An Evaluation of the Vermont Model FAP Child Care Service System.

ERIC Educational Resources Information Center

Siedman, Eileen

This book presents an extensive examination of the organization and operation of the Vermont model day care delivery system which was designed in the context of the proposed Family Assistance Plan (FAP). The model tested the ability of Federal and State employees to work together and share resources in designing a new approach to welfare reform.…

Hypersonic Viscous Flow Over Large Roughness Elements

NASA Technical Reports Server (NTRS)

Chang, Chau-Lyan; Choudhari, Meelan M.

2009-01-01

Viscous flow over discrete or distributed surface roughness has great implications for hypersonic flight due to aerothermodynamic considerations related to laminar-turbulent transition. Current prediction capability is greatly hampered by the limited knowledge base for such flows. To help fill that gap, numerical computations are used to investigate the intricate flow physics involved. An unstructured mesh, compressible Navier-Stokes code based on the space-time conservation element, solution element (CESE) method is used to perform time-accurate Navier-Stokes calculations for two roughness shapes investigated in wind tunnel experiments at NASA Langley Research Center. It was found through 2D parametric study that at subcritical Reynolds numbers, spontaneous absolute instability accompanying by sustained vortex shedding downstream of the roughness is likely to take place at subsonic free-stream conditions. On the other hand, convective instability may be the dominant mechanism for supersonic boundary layers. Three-dimensional calculations for both a rectangular and a cylindrical roughness element at post-shock Mach numbers of 4.1 and 6.5 also confirm that no self-sustained vortex generation from the top face of the roughness is observed, despite the presence of flow unsteadiness for the smaller post-shock Mach number case.

Air-breathing aerospace plane development essential: Hypersonic propulsion flight tests

NASA Technical Reports Server (NTRS)

Mehta, Unmeel B.

1994-01-01

Hypersonic air-breathing propulsion utilizing scramjets can fundamentally change transatmospheric accelerators for low earth-to-orbit and return transportation. The value and limitations of ground tests, of flight tests, and of computations are presented, and scramjet development requirements are discussed. It is proposed that near full-scale hypersonic propulsion flight tests are essential for developing a prototype hypersonic propulsion system and for developing computational-design technology so that it can be used for designing this system. In order to determine how these objectives should be achieved, some lessons learned from past programs are presented. A conceptual two-stage-to-orbit (TSTO) prototype/experimental aerospace plane is recommended as a means of providing access-to-space and for conducting flight tests. A road map for achieving these objectives is also presented.

Computational effects of inlet representation on powered hypersonic, airbreathing models

NASA Technical Reports Server (NTRS)

Huebner, Lawrence D.; Tatum, Kenneth E.

1993-01-01

Computational results are presented to illustrate the powered aftbody effects of representing the scramjet inlet on a generic hypersonic vehicle with a fairing, to divert the external flow, as compared to an operating flow-through scramjet inlet. This study is pertinent to the ground testing of hypersonic, airbreathing models employing scramjet exhaust flow simulation in typical small-scale hypersonic wind tunnels. The comparison of aftbody effects due to inlet representation is well-suited for computational study, since small model size typically precludes the ability to ingest flow into the inlet and perform exhaust simulation at the same time. Two-dimensional analysis indicates that, although flowfield differences exist for the two types of inlet representations, little, if any, difference in surface aftbody characteristics is caused by fairing over the inlet.

Classifier utility modeling and analysis of hypersonic inlet start/unstart considering training data costs

NASA Astrophysics Data System (ADS)

Chang, Juntao; Hu, Qinghua; Yu, Daren; Bao, Wen

2011-11-01

Start/unstart detection is one of the most important issues of hypersonic inlets and is also the foundation of protection control of scramjet. The inlet start/unstart detection can be attributed to a standard pattern classification problem, and the training sample costs have to be considered for the classifier modeling as the CFD numerical simulations and wind tunnel experiments of hypersonic inlets both cost time and money. To solve this problem, the CFD simulation of inlet is studied at first step, and the simulation results could provide the training data for pattern classification of hypersonic inlet start/unstart. Then the classifier modeling technology and maximum classifier utility theories are introduced to analyze the effect of training data cost on classifier utility. In conclusion, it is useful to introduce support vector machine algorithms to acquire the classifier model of hypersonic inlet start/unstart, and the minimum total cost of hypersonic inlet start/unstart classifier can be obtained by the maximum classifier utility theories.

A study of hypersonic small-disturbance theory

NASA Technical Reports Server (NTRS)

Van Dyke, Milton D

1954-01-01

A systematic study is made of the approximate inviscid theory of thin bodies moving at such high supersonic speeds that nonlinearity is an essential feature of the equations of flow. The first-order small-disturbance equations are derived for three-dimensional motions involving shock waves, and estimates are obtained for the order of error involved in the approximation. The hypersonic similarity rule of Tsien and Hayes, and Hayes' unsteady analogy appear in the course of the development. It is shown that the hypersonic theory can be interpreted so that it applies also in the range of linearized supersonic flow theory. Several examples are solved according to the small-disturbance theory, and compared with the full solutions when available.

he second X-43A and its modified Pegasus booster rocket accelerate after launch from NASA's B-52B launch aircraft over the Pacific Ocean

NASA Image and Video Library

2004-03-27

The second X-43A hypersonic research aircraft and its modified Pegasus booster rocket accelerate after launch from NASA's B-52B launch aircraft over the Pacific Ocean on March 27, 2004. The mission originated from the NASA Dryden Flight Research Center at Edwards Air Force Base, Calif. Minutes later the X-43A separated from the Pegasus booster and accelerated to its intended speed of Mach 7.

Multi-Exciter Vibroacoustic Simulation of Hypersonic Flight Vibration

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

GREGORY,DANNY LYNN; CAP,JEROME S.; TOGAMI,THOMAS C.

1999-11-11

Many aerospace structures must survive severe high frequency, hypersonic, random vibration during their flights. The random vibrations are generated by the turbulent boundary layer developed along the exterior of the structures during flight. These environments have not been simulated very well in the past using a fixed-based, single exciter input with an upper frequency range of 2 kHz. This study investigates the possibility of using acoustic ardor independently controlled multiple exciters to more accurately simulate hypersonic flight vibration. The test configuration, equipment, and methodology are described. Comparisons with actual flight measurements and previous single exciter simulations are also presented.

A hypersonic vehicle approach to planetary exploration

NASA Technical Reports Server (NTRS)

Murbach, Marcus S.

1993-01-01

An enhanced Mars network class mission using a lifting hypersonic entry vehicle is proposed. The basic vehicle, derived from a mature hypersonic flight system called SWERVE, offers several advantages over more conventional low L/D or ballistic entry systems. The proposed vehicle has greatly improved lateral and cross range capability (e.g., it is capable of reaching the polar regions during less than optimal mission opportunities), is not limited to surface target areas of low elevation, and is less susceptible to problems caused by Martian dust storms. Further, the integrated vehicle has attractive deployment features and allows for a much improved evolutionary path to larger vehicles with greater science capability. Analysis of the vehicle is aided by the development of a Mars Hypersonic Flight Simulator from which flight trajectories are obtained. Atmospheric entry performance of the baseline vehicle is improved by a deceleration skirt and transpiration cooling system which significantly reduce TPS (Thermal Protection System) and flight battery mass. The use of the vehicle is also attractive in that the maturity of the flight systems make it cost-competitive with the development of a conventional low L/D entry system. Finally, the potential application of similar vehicles to other planetary missions is discussed.

High speed digital holographic interferometry for hypersonic flow visualization

NASA Astrophysics Data System (ADS)

Hegde, G. M.; Jagdeesh, G.; Reddy, K. P. J.

2013-06-01

Optical imaging techniques have played a major role in understanding the flow dynamics of varieties of fluid flows, particularly in the study of hypersonic flows. Schlieren and shadowgraph techniques have been the flow diagnostic tools for the investigation of compressible flows since more than a century. However these techniques provide only the qualitative information about the flow field. Other optical techniques such as holographic interferometry and laser induced fluorescence (LIF) have been used extensively for extracting quantitative information about the high speed flows. In this paper we present the application of digital holographic interferometry (DHI) technique integrated with short duration hypersonic shock tunnel facility having 1 ms test time, for quantitative flow visualization. Dynamics of the flow fields in hypersonic/supersonic speeds around different test models is visualized with DHI using a high-speed digital camera (0.2 million fps). These visualization results are compared with schlieren visualization and CFD simulation results. Fringe analysis is carried out to estimate the density of the flow field.

Frequencies of inaudible high-frequency sounds differentially affect brain activity: positive and negative hypersonic effects.

PubMed

Fukushima, Ariko; Yagi, Reiko; Kawai, Norie; Honda, Manabu; Nishina, Emi; Oohashi, Tsutomu

2014-01-01

The hypersonic effect is a phenomenon in which sounds containing significant quantities of non-stationary high-frequency components (HFCs) above the human audible range (max. 20 kHz) activate the midbrain and diencephalon and evoke various physiological, psychological and behavioral responses. Yet important issues remain unverified, especially the relationship existing between the frequency of HFCs and the emergence of the hypersonic effect. In this study, to investigate the relationship between the hypersonic effect and HFC frequencies, we divided an HFC (above 16 kHz) of recorded gamelan music into 12 band components and applied them to subjects along with an audible component (below 16 kHz) to observe changes in the alpha2 frequency component (10-13 Hz) of spontaneous EEGs measured from centro-parieto-occipital regions (Alpha-2 EEG), which we previously reported as an index of the hypersonic effect. Our results showed reciprocal directional changes in Alpha-2 EEGs depending on the frequency of the HFCs presented with audible low-frequency component (LFC). When an HFC above approximately 32 kHz was applied, Alpha-2 EEG increased significantly compared to when only audible sound was applied (positive hypersonic effect), while, when an HFC below approximately 32 kHz was applied, the Alpha-2 EEG decreased (negative hypersonic effect). These findings suggest that the emergence of the hypersonic effect depends on the frequencies of inaudible HFC.

Optimization of the Upper Surface of Hypersonic Vehicle Based on CFD Analysis

NASA Astrophysics Data System (ADS)

Gao, T. Y.; Cui, K.; Hu, S. C.; Wang, X. P.; Yang, G. W.

2011-09-01

For the hypersonic vehicle, the aerodynamic performance becomes more intensive. Therefore, it is a significant event to optimize the shape of the hypersonic vehicle to achieve the project demands. It is a key technology to promote the performance of the hypersonic vehicle with the method of shape optimization. Based on the existing vehicle, the optimization to the upper surface of the Simplified hypersonic vehicle was done to obtain a shape which suits the project demand. At the cruising condition, the upper surface was parameterized with the B-Spline curve method. The incremental parametric method and the reconstruction technology of the local mesh were applied here. The whole flow field was been calculated and the aerodynamic performance of the craft were obtained by the computational fluid dynamic (CFD) technology. Then the vehicle shape was optimized to achieve the maximum lift-drag ratio at attack angle 3°, 4° and 5°. The results will provide the reference for the practical design.

Detailed modeling of electron emission for transpiration cooling of hypersonic vehicles

NASA Astrophysics Data System (ADS)

Hanquist, Kyle M.; Hara, Kentaro; Boyd, Iain D.

2017-02-01

Electron transpiration cooling (ETC) is a recently proposed approach to manage the high heating loads experienced at the sharp leading edges of hypersonic vehicles. Computational fluid dynamics (CFD) can be used to investigate the feasibility of ETC in a hypersonic environment. A modeling approach is presented for ETC, which includes developing the boundary conditions for electron emission from the surface, accounting for the space-charge limit effects of the near-wall plasma sheath. The space-charge limit models are assessed using 1D direct-kinetic plasma sheath simulations, taking into account the thermionically emitted electrons from the surface. The simulations agree well with the space-charge limit theory proposed by Takamura et al. for emitted electrons with a finite temperature, especially at low values of wall bias, which validates the use of the theoretical model for the hypersonic CFD code. The CFD code with the analytical sheath models is then used for a test case typical of a leading edge radius in a hypersonic flight environment. The CFD results show that ETC can lower the surface temperature of sharp leading edges of hypersonic vehicles, especially at higher velocities, due to the increase in ionized species enabling higher electron heat extraction from the surface. The CFD results also show that space-charge limit effects can limit the ETC reduction of surface temperatures, in comparison to thermionic emission assuming no effects of the electric field within the sheath.

Toward a CFD nose-to-tail capability - Hypersonic unsteady Navier-Stokes code validation

NASA Technical Reports Server (NTRS)

Edwards, Thomas A.; Flores, Jolen

1989-01-01

Computational fluid dynamics (CFD) research for hypersonic flows presents new problems in code validation because of the added complexity of the physical models. This paper surveys code validation procedures applicable to hypersonic flow models that include real gas effects. The current status of hypersonic CFD flow analysis is assessed with the Compressible Navier-Stokes (CNS) code as a case study. The methods of code validation discussed to beyond comparison with experimental data to include comparisons with other codes and formulations, component analyses, and estimation of numerical errors. Current results indicate that predicting hypersonic flows of perfect gases and equilibrium air are well in hand. Pressure, shock location, and integrated quantities are relatively easy to predict accurately, while surface quantities such as heat transfer are more sensitive to the solution procedure. Modeling transition to turbulence needs refinement, though preliminary results are promising.

A modified Pegasus rocket drops steadily away after release from NASA's B-52B, before accelerating the X-43A over the Pacific Ocean on March 27, 2004

NASA Image and Video Library

2004-03-27

The second X-43A hypersonic research aircraft and its modified Pegasus booster rocket drop away from NASA's B-52B launch aircraft over the Pacific Ocean on March 27, 2004. The mission originated from the NASA Dryden Flight Research Center at Edwards Air Force Base, Calif. Moments later the Pegasus booster ignited to accelerate the X-43A to its intended speed of Mach 7.

X-43A/Hyper-X Vehicle Arrives at NASA Dryden

NASA Technical Reports Server (NTRS)

1999-01-01

A head-on view of the X-43A Hypersonic Experimental Vehicle, or 'Hyper-X,' in its protective shipping framework as it arrives at the Dryden Flight Research Center in October 1999. The X-43A was developed to research a dual-mode ramjet/scramjet propulsion system at speeds from Mach 7 up to Mach 10 (7 to 10 times the speed of sound, which varies with temperature and altitude). Hyper-X, the flight vehicle for which is designated as X-43A, is an experimental flight-research program seeking to demonstrate airframe-integrated, 'air-breathing' engine technologies that promise to increase payload capacity for future vehicles, including hypersonic aircraft (faster than Mach 5) and reusable space launchers. This multiyear program is currently underway at NASA Dryden Flight Research Center, Edwards, California. The Hyper-X schedule calls for its first flight later this year (2000). Hyper-X is a joint program, with Dryden sharing responsibility with NASA's Langley Research Center, Hampton, Virginia. Dryden's primary role is to fly three unpiloted X-43A research vehicles to validate engine technologies and hypersonic design tools as well as the hypersonic test facility at Langley. Langley manages the program and leads the technology development effort. The Hyper-X Program seeks to significantly expand the speed boundaries of air-breathing propulsion by being the first aircraft to demonstrate an airframe-integrated, scramjet-powered free flight. Scramjets (supersonic-combustion ramjets) are ramjet engines in which the airflow through the whole engine remains supersonic. Scramjet technology is challenging because only limited testing can be performed in ground facilities. Long duration, full-scale testing requires flight research. Scramjet engines are air-breathing, capturing their oxygen from the atmosphere. Current spacecraft, such as the Space Shuttle, are rocket powered, so they must carry both fuel and oxygen for propulsion. Scramjet technology-based vehicles need to carry

Tomographic PIV investigation of roughness-induced transition in a hypersonic boundary layer

NASA Astrophysics Data System (ADS)

Avallone, F.; Ye, Q.; Schrijer, F. F. J.; Scarano, F.; Cardone, G.

2014-11-01

The disturbance generated by roughness elements in a hypersonic laminar boundary layer is investigated, with attention to its three-dimensional properties. The transition of the boundary layer is inspected with tomographic particle image velocimetry that is applied for the first time at Mach 7.5 inside a short duration hypersonic wind tunnel. A low aspect ratio cylindrical roughness element is installed on a flat plate, and experiments are conducted downstream of the element describing the mean velocity field and the turbulent fluctuations. Details of the experimental procedure needed to realize these measurements are discussed, along with the fluid dynamic behaviour of the perturbed hypersonic boundary layer.

Hypersonic Vehicle Propulsion System Simplified Model Development

NASA Technical Reports Server (NTRS)

Stueber, Thomas J.; Raitano, Paul; Le, Dzu K.; Ouzts, Peter

2007-01-01

This document addresses the modeling task plan for the hypersonic GN&C GRC team members. The overall propulsion system modeling task plan is a multi-step process and the task plan identified in this document addresses the first steps (short term modeling goals). The procedures and tools produced from this effort will be useful for creating simplified dynamic models applicable to a hypersonic vehicle propulsion system. The document continues with the GRC short term modeling goal. Next, a general description of the desired simplified model is presented along with simulations that are available to varying degrees. The simulations may be available in electronic form (FORTRAN, CFD, MatLab,...) or in paper form in published documents. Finally, roadmaps outlining possible avenues towards realizing simplified model are presented.

Hypersonic Boundary Layer Instability Over a Corner

NASA Technical Reports Server (NTRS)

Balakumar, Ponnampalam; Zhao, Hong-Wu; McClinton, Charles (Technical Monitor)

2001-01-01

A boundary-layer transition study over a compression corner was conducted under a hypersonic flow condition. Due to the discontinuities in boundary layer flow, the full Navier-Stokes equations were solved to simulate the development of disturbance in the boundary layer. A linear stability analysis and PSE method were used to get the initial disturbance for parallel and non-parallel flow respectively. A 2-D code was developed to solve the full Navier-stokes by using WENO(weighted essentially non-oscillating) scheme. The given numerical results show the evolution of the linear disturbance for the most amplified disturbance in supersonic and hypersonic flow over a compression ramp. The nonlinear computations also determined the minimal amplitudes necessary to cause transition at a designed location.

Genetic Counselor Practices Involving Pediatric Patients with FAP: an Investigation of their Self-Reported Strategies for Genetic Testing and Hepatoblastoma Screening.

PubMed

Lawson, Caitlin E; Attard, Thomas M; Dai, Hongying; Septer, Seth

2017-06-01

Familial adenomatous polyposis (FAP) is a cancer predisposition syndrome that causes early-onset polyposis and is associated with an increased risk for hepatoblastoma. There is currently a lack of consensus on when to order APC (adenomatous polyposis coli) gene testing or implement surveillance for hepatoblastoma. An online questionnaire was completed by 62 genetic counselors to capture their current practices regarding these questions. Extracolonic findings associated with FAP that were most likely to prompt APC testing in an otherwise asymptomatic 10 year-old child with a negative family history were multiple desmoid tumors, congenital hypertrophy of the retinal pigment epithelium (CHRPE), jaw osteomas, and hepatoblastoma. For hepatoblastoma screening, the majority did recommend this in children less than age five years with known APC mutations. An interval of every 3-6 months was most commonly suggested; however, responses extended to screening on a less than annual basis. These results highlight the need for further investigation into why some genetic counselors do not recommend APC testing in young at-risk children and what factors influence views about the ideal age and indication for APC testing. Studies of these issues would help to define the best clinical practice model for genetic testing and hepatoblastoma screening in pediatric patients with FAP.

Transthyretin-Related Familial Amyloid Polyneuropathy (TTR-FAP): A Single-Center Experience in Sicily, an Italian Endemic Area.

PubMed

Mazzeo, Anna; Russo, Massimo; Di Bella, Gianluca; Minutoli, Fabio; Stancanelli, Claudia; Gentile, Luca; Baldari, Sergio; Carerj, Scipione; Toscano, Antonio; Vita, Giuseppe

2015-07-22

Familial amyloid polyneuropathy related to transthyretin gene (TTR-FAP) is a life-threatening disease transmitted as an autosomal dominant trait. Val30Met mutation accounts for the majority of the patients with large endemic foci especially in Portugal, Sweden and Japan. However, more than one hundred other mutations have been described worldwide. A great phenotypic variability among patients with late- and early-onset has been reported. To present a detailed report of TTR-FAP patients diagnosed in our tertiary neuromuscular center, in a 20-year period. Clinical informations were gathered through the database of our center. The study involved 76 individuals carrying a TTR-FAP mutation. Three phenotypes were identified, each corresponding to a different TTR variant, homogeneous within and heterogeneous between each other: i) Glu89Gln mutation, characterised by 5th - 6th decade onset, neuropathy as presenting symptoms, early heart dysfunction, cardiomyopathy as major cause of mortality followed by dysautonomia and cachexia; ii) Phe64Leu mutation, marked by familiarity reported in one-half of cases, late onset, severe peripheral neuropathy, moderate dysautonomia and mild cardiomyopathy, death for wasting syndrome; iii) Thr49Ala mutation, distinguished by onset in the 5th decade, autonomic disturbances as inaugural symptoms which may remain isolated for many years, moderate polyneuropathy, cachexia as major cause of mortality followed by cardiomyopathy. This survey highlighted a prevalence of 8.8/1,000,000 in Sicily Island. Good knowledge of the natural history of the disease according to different TTR mutations allow clinicians to optimise multiprofessional care for patients and to offer carriers a personalized follow-up to reveal first signs of the disease.

Control integration concept for hypersonic cruise-turn maneuvers

NASA Technical Reports Server (NTRS)

Raney, David L.; Lallman, Frederick J.

1992-01-01

Piloting difficulties associated with conducting aircraft maneuvers in hypersonic flight are caused in part by the nonintuitive nature of the aircraft response and the stringent constraints anticipated on allowable angle of attack and dynamic pressure variations. An approach is documented that provides precise, coordinated maneuver control during excursions from a hypersonic cruise flight path and the necessary flight condition constraints. The approach is to achieve specified guidance commands by resolving altitude and cross range errors into a load factor and bank angle command by using a coordinate transformation that acts as an interface between outer and inner loop flight controls. This interface, referred to as a 'resolver', applies constraints on angle of attack and dynamic pressure perturbations while prioritizing altitude regulation over cross range. An unpiloted test simulation, in which the resolver was used to drive inner loop flight controls, produced time histories of responses to guidance commands and atmospheric disturbances at Mach numbers of 6, 10, 15, and 20. Angle of attack and throttle perturbation constraints, combined with high speed flight effects and the desire to maintain constant dynamic pressure, significantly impact the maneuver envelope for a hypersonic vehicle.

Supersonic and hypersonic shock/boundary-layer interaction database

NASA Technical Reports Server (NTRS)

Settles, Gary S.; Dodson, Lori J.

1994-01-01

An assessment is given of existing shock wave/tubulent boundary-layer interaction experiments having sufficient quality to guide turbulence modeling and code validation efforts. Although the focus of this work is hypersonic, experiments at Mach numbers as low as 3 were considered. The principal means of identifying candidate studies was a computerized search of the AIAA Aerospace Database. Several hundred candidate studies were examined and over 100 of these were subjected to a rigorous set of acceptance criteria for inclusion in the data-base. Nineteen experiments were found to meet these criteria, of which only seven were in the hypersonic regime (M is greater than 5).

A technique for measuring hypersonic flow velocity profiles

NASA Technical Reports Server (NTRS)

Gartrell, L. R.

1973-01-01

A technique for measuring hypersonic flow velocity profiles is described. This technique utilizes an arc-discharge-electron-beam system to produce a luminous disturbance in the flow. The time of flight of this disturbance was measured. Experimental tests were conducted in the Langley pilot model expansion tube. The measured velocities were of the order of 6000 m/sec over a free-stream density range from 0.000196 to 0.00186 kg/cu m. The fractional error in the velocity measurements was less than 5 percent. Long arc discharge columns (0.356 m) were generated under hypersonic flow conditions in the expansion-tube modified to operate as an expansion tunnel.

Hypersonic engine component experiments in high heat flux, supersonic flow environment

NASA Technical Reports Server (NTRS)

Gladden, Herbert J.; Melis, Matthew E.

1993-01-01

A major concern in advancing the state-of-the-art technologies for hypersonic vehicles is the development of an aeropropulsion system capable of withstanding the sustained high thermal loads expected during hypersonic flight. Even though progress has been made in the computational understanding of fluid dynamics and the physics/chemistry of high speed flight, there is also a need for experimental facilities capable of providing a high heat flux environment for testing component concepts and verifying/calibrating these analyses. A hydrogen/oxygen rocket engine heat source was developed at the NASA Lewis Research Center as one element in a series of facilities at national laboratories designed to fulfill this need. This 'Hot Gas Facility' is capable of providing heat fluxes up to 450 w/sq cm on flat surfaces and up to 5,000 w/sq cm at the leading edge stagnation point of a strut in a supersonic flow stream. Gas temperatures up to 3050 K can also be attained. Two recent experimental programs conducted in this facility are discussed. The objective of the first experiment is to evaluate the erosion and oxidation characteristics of a coating on a cowl leading edge (or strut leading edge) in a supersonic, high heat flux environment. Macrophotographic data from a coated leading edge model show progressive degradation over several thermal cycles at aerothermal conditions representative of high Mach number flight. The objective of the second experiment is to assess the capability of cooling a porous surface exposed to a high temperature, high velocity flow environment and to provide a heat transfer data base for a design procedure. Experimental results from transpiration cooled surfaces in a supersonic flow environment are presented.

A modified Pegasus rocket drops away after release from NASA's B-52B before accelerating the X-43A over a Pacific Ocean test range on Nov. 16, 2004

NASA Image and Video Library

2004-11-16

The third X-43A hypersonic research aircraft and its modified Pegasus booster rocket drop away from NASA's B-52B launch aircraft over the Pacific Ocean on November 16, 2004. The mission originated from the NASA Dryden Flight Research Center at Edwards Air Force Base, California. Moments later the Pegasus booster ignited to accelerate the X-43A to its intended speed of Mach 10.

A review of design issues specific to hypersonic flight vehicles

NASA Astrophysics Data System (ADS)

Sziroczak, D.; Smith, H.

2016-07-01

This paper provides an overview of the current technical issues and challenges associated with the design of hypersonic vehicles. Two distinct classes of vehicles are reviewed; Hypersonic Transports and Space Launchers, their common features and differences are examined. After a brief historical overview, the paper takes a multi-disciplinary approach to these vehicles, discusses various design aspects, and technical challenges. Operational issues are explored, including mission profiles, current and predicted markets, in addition to environmental effects and human factors. Technological issues are also reviewed, focusing on the three major challenge areas associated with these vehicles: aerothermodynamics, propulsion, and structures. In addition, matters of reliability and maintainability are also presented. The paper also reviews the certification and flight testing of these vehicles from a global perspective. Finally the current stakeholders in the field of hypersonic flight are presented, summarizing the active programs and promising concepts.

International Conference on Hypersonic Flight in the 21st Century, 1st, University of North Dakota, Grand Forks, Sept. 20-23, 1988, Proceedings

NASA Astrophysics Data System (ADS)

Higbea, Mary E.; Vedda, James A.

The present conference on the development status of configurational concepts and component technologies for hypersonic-cruise and transatmospheric vehicles discusses topics relating to the U.S. National Aerospace Plane program, ESA-planned aerospace vehicles, Japanese spaceplane concepts, the integration of hypersonic aircraft into existing infrastructures, hypersonic airframe designs, hypersonic avionics and cockpit AI systems, hypersonic-regime CFD techniques, the economics of hypersonic vehicles, and possible legal implications of hypersonic flight. Also discussed are Soviet spaceplane concepts, propulsion systems involving laser power sources and hypervelocity launch technologies, and the management of support systems operations for hypersonic vehicles.

Second-mode control in hypersonic boundary layers over assigned complex wall impedance

NASA Astrophysics Data System (ADS)

Sousa, Victor; Patel, Danish; Chapelier, Jean-Baptiste; Scalo, Carlo

2017-11-01

The durability and aerodynamic performance of hypersonic vehicles greatly relies on the ability to delay transition to turbulence. Passive aerodynamic flow control devices such as porous acoustic absorbers are a very attractive means to damp ultrasonic second-mode waves, which govern transition in hypersonic boundary layers under idealized flow conditions (smooth walls, slender geometries, small angles of attack). The talk will discuss numerical simulations modeling such absorbers via the time-domain impedance boundary condition (TD-IBC) approach by Scalo et al. in a hypersonic boundary layer flow over a 7-degree wedge at freestream Mach numbers M∞ = 7.3 and Reynolds numbers Rem = 1.46 .106 . A three-parameter impedance model tuned to the second-mode waves is tested first with varying resistance, R, and damping ratio, ζ, revealing complete mode attenuation for R < 20. A realistic IBC is then employed, derived via an inverse Helmholtz solver analysis of an ultrasonically absorbing carbon-fiber-reinforced carbon ceramic sample used in recent hypersonic transition experiments by Dr. Wagner and co-workers at DLR-Göttingen.

Multi Laser Pulse Investigation of the DEAS Concept in Hypersonic Flow

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

Minucci, M.A.S.; Toro, P.G.P.; Oliveira, A.C.

2004-03-30

The present paper presents recent experimental results on the Laser-Supported Directed Energy 'Air Spike' - DEAS in hypersonic flow achieved by the Laboratory of Aerothermodynamics and Hypersonics - LAH, Brazil. Two CO2 TEA lasers, sharing the same optical cavity, have been used in conjunction with the IEAv 0.3m Hypersonic Shock Tunnel - HST to demonstrate the Laser-Supported DEAS concept. A single and double laser pulse, generated during the tunnel useful test time, were focused through a NaCl lens upstream of a Double Apollo Disc model fitted with seven piezoelectric pressure transducers and six platinum thin film heat transfer gauges. Themore » objective being to corroborate previous results as well as to obtain additional pressure and heat flux distributions information when two laser pulses are used.« less

Hypersonic aircraft design

NASA Technical Reports Server (NTRS)

Alkamhawi, Hani; Greiner, Tom; Fuerst, Gerry; Luich, Shawn; Stonebraker, Bob; Wray, Todd

1990-01-01

A hypersonic aircraft is designed which uses scramjets to accelerate from Mach 6 to Mach 10 and sustain that speed for two minutes. Different propulsion systems were considered and it was decided that the aircraft would use one full scale turbofan-ramjet. Two solid rocket boosters were added to save fuel and help the aircraft pass through the transonic region. After considering aerodynamics, aircraft design, stability and control, cooling systems, mission profile, and landing systems, a conventional aircraft configuration was chosen over that of a waverider. The conventional design was chosen due to its landing characteristics and the relative expense compared to the waverider. Fuel requirements and the integration of the engine systems and their inlets are also taken into consideration in the final design. A hypersonic aircraft was designed which uses scramjets to accelerate from Mach 6 to Mach 10 and sustain that speed for two minutes. Different propulsion systems were considered and a full scale turbofan-ramjet was chosen. Two solid rocket boosters were added to save fuel and help the aircraft pass through the transonic reqion. After the aerodynamics, aircraft design, stability and control, cooling systems, mission profile, landing systems, and their physical interactions were considered, a conventional aircraft configuration was chosen over that of a waverider. The conventional design was chosen due to its landing characteristics and the relative expense compared to the waverider. Fuel requirements and the integration of the engine systems and their inlets were also considered in the designing process.

Progress in the Growth of Yb:S-FAP Laser Crystals

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

Schaffers, K I; Tassano, J B; Waide, P A

The crystal growth of Yb:S-FAP [Yb{sup 3+}:Sr{sub 5}(PO{sub 4}){sub 3}F] is being studied for 1.047-{micro}m laser operation. These crystals are not yet routinely available and the growth of high optical quality, low loss crystals poses a challenge due to a number of crystal growth issues, including, cloudiness, bubble core defects, anomalous absorption, low-angle grain boundaries, and cracking. At this time, a growth process has been formulated to simultaneously eliminate or greatly diminish each of the defects yielding high quality material. Laser slabs of dimension 4.0 x 6.0 x 0.75 cm are being fabricated from sub-scale pieces using the diffusion bondingmore » technique.« less

Applied Computational Fluid Dynamics at NASA Ames Research Center

NASA Technical Reports Server (NTRS)

Holst, Terry L.; Kwak, Dochan (Technical Monitor)

1994-01-01

The field of Computational Fluid Dynamics (CFD) has advanced to the point where it can now be used for many applications in fluid mechanics research and aerospace vehicle design. A few applications being explored at NASA Ames Research Center will be presented and discussed. The examples presented will range in speed from hypersonic to low speed incompressible flow applications. Most of the results will be from numerical solutions of the Navier-Stokes or Euler equations in three space dimensions for general geometry applications. Computational results will be used to highlight the presentation as appropriate. Advances in computational facilities including those associated with NASA's CAS (Computational Aerosciences) Project of the Federal HPCC (High Performance Computing and Communications) Program will be discussed. Finally, opportunities for future research will be presented and discussed. All material will be taken from non-sensitive, previously-published and widely-disseminated work.

Perspectives on hypersonic viscous and nonequilibrium flow research

NASA Technical Reports Server (NTRS)

Cheng, H. K.

1992-01-01

An attempt is made to reflect on current focuses in certain areas of hypersonic flow research by examining recent works and their issues. Aspects of viscous interaction, flow instability, and nonequilibrium aerothermodynamics pertaining to theoretical interest are focused upon. The field is a diverse one, and many exciting works may have either escaped the writer's notice or been abandoned for the sake of space. Students of hypersonic viscous flow must face the transition problems towards the two opposite ends of the Reynolds or Knudsen number range, which represents two regimes where unresolved fluid/gas dynamic problems abound. Central to the hypersonic flow studies is high-temperature physical gas dynamics; here, a number of issues on modelling the intermolecular potentials and inelastic collisions remain the obstacles to quantitative predictions. Research in combustion and scramjet propulsion will certainly be benefitted by advances in turbulent mixing and new computational fluid dynamics (CFD) strategies on multi-scaled complex reactions. Even for the sake of theoretical development, the lack of pertinent experimental data in the right energy and density ranges is believed to be among the major obstacles to progress in aerothermodynamic research for hypersonic flight. To enable laboratory simulation of nonequilibrium effects anticipated for transatmospheric flight, facilities capable of generating high enthalpy flow at density levels higher than in existing laboratories are needed (Hornung 1988). A new free-piston shock tunnel capable of realizing a test-section stagnation temperature of 10(exp 5) at Reynolds number 50 x 10(exp 6)/cm is being completed and preliminary tests has begun (H. Hornung et al. 1992). Another laboratory study worthy of note as well as theoretical support is the nonequilibrium flow experiment of iodine vapor which has low activation energies for vibrational excitation and dissociation, and can be studied in a laboratory with modest

Hypersonic flight performance improvements by overfueled ramjet combustion

NASA Astrophysics Data System (ADS)

Sachs, G.; Bayer, R.; Lederer, R.; Schaber, R.

1991-12-01

The performance characteristics of hypersonic airbreathing engines are examined with emphasis on the effect of overfueled combustion on thrust and specific fuel-consumption, as well as on the combustion temperature, real gas effects, and pollution due to exhaust gas. It is shown that overfueled ramjet combustion can provide a means for improving flight performance at hypersonic speed and, consequently, reduce the mission fuel burn and the propulsion system weight. It is also shown that, in the separation flight maneuver, the separation condition for the upper stage can be improved by overfueled ramjet combustion of the first stage, making it possible to increase the payload which the upper stage can deliver into orbit. The flight mechanics modeling considerations are presented.

Combined LAURA-UPS hypersonic solution procedure

NASA Technical Reports Server (NTRS)

Wood, William A.; Thompson, Richard A.

1993-01-01

A combined solution procedure for hypersonic flowfields around blunted slender bodies was implemented using a thin-layer Navier-Stokes code (LAURA) in the nose region and a parabolized Navier-Stokes code (UPS) on the after body region. Perfect gas, equilibrium air, and non-equilibrium air solutions to sharp cones and a sharp wedge were obtained using UPS alone as a preliminary step. Surface heating rates are presented for two slender bodies with blunted noses, having used LAURA to provide a starting solution to UPS downstream of the sonic line. These are an 8 deg sphere-cone in Mach 5, perfect gas, laminar flow at 0 and 4 deg angles of attack and the Reentry F body at Mach 20, 80,000 ft equilibrium gas conditions for 0 and 0.14 deg angles of attack. The results indicate that this procedure is a timely and accurate method for obtaining aerothermodynamic predictions on slender hypersonic vehicles.

The Blunt Plate In Hypersonic Flow

NASA Technical Reports Server (NTRS)

Baradell, Donald L.; Bertram, Mitchel H.

1960-01-01

The sonic-wedge characteristics method has been used to obtain the shock shapes and surface pressure distributions on several blunt two-dimensional shapes in a hypersonic stream for several values of the ratio of specific heats. These shapes include the blunt slab at angle of attack and power profiles of the form yb = a)P, where 0 les than m less than 1, Yb and x are coordinates of the body surface, and a is a constant. These numerical results have been compared with the results of blast-wave theory, and methods of predicting the pressure distributions and shock shapes are proposed in each case. The effects of a free-stream conical-flow gradient on the pressure distribution on a blunt slab in hypersonic flow were investigated by the sonic-wedge characteristics method and were found to be sizable in many cases. Procedures which are satisfactory for reducing pressure data obtained in conical flows with small gradients are presented.

Postoperative outcome and quality of life after surgery for FAP-associated duodenal adenomatosis.

PubMed

Ganschow, Petra; Hackert, Thilo; Biegler, Marcel; Contin, Pietro; Hinz, Ulf; Büchler, Markus W; Kadmon, Martina

2018-02-01

Prophylactic colon surgery has increased life expectancy of familial adenomatous polyposis patients. Extracolonic manifestations are life limiting, above all duodenal adenomas. Severe duodenal adenomatosis or cancer may necessitate pancreas-preserving total duodenectomy or partial pancreatico-duodenectomy, mostly after previous proctocolectomy and often after limited local resections of duodenal adenomas. Scarce information on long-term postoperative outcome and quality of life after surgery for duodenal adenomatosis is available. Aim of the present study was to analyze perioperative and long-term outcome after PD and PPTD for FAP-associated duodenal adenomatosis, including QoL and recurrence of adenomas in the neoduodenum after PPTD. Thirty-eight patients, 27 after pancreas-preserving duodenectomy and 11 after partial pancreaticoduodenectomy, were included. Pancreas-preserving total duodenectomy was associated with shorter operation time and less blood loss than partial pancreatico-duodenectomy. Clinically relevant pancreatic fistula occurred in 31.5%. In-hospital mortality was 5.3%. Long-term follow-up revealed recurrent pancreatitis after pancreas-preserving total duodenectomy in 22% of patients, two (7.4%) required re-operation. Recurrent adenomatosis was detected in 26% of patients. Quality of life was comparable to the German normal population after both surgical procedures. Patients with postoperative complications showed worse results than those without complications. Disease-specific 10-year survival rate with respect to duodenal adenomatosis was 100%. Surgery for FAP-associated duodenal adenomatosis and cancer can be carried out with reasonable morbidity rates despite previous proctocolectomy. Long-term outcome, quality of life, and survival rates are favorable.

Status of Turbulence Modeling for Hypersonic Propulsion Flowpaths

NASA Technical Reports Server (NTRS)

Georgiadis, Nicholas J.; Yoder, Dennis A.; Vyas, Manan A.; Engblom, William A.

2012-01-01

This report provides an assessment of current turbulent flow calculation methods for hypersonic propulsion flowpaths, particularly the scramjet engine. Emphasis is placed on Reynolds-averaged Navier-Stokes (RANS) methods, but some discussion of newer meth- ods such as Large Eddy Simulation (LES) is also provided. The report is organized by considering technical issues throughout the scramjet-powered vehicle flowpath including laminar-to-turbulent boundary layer transition, shock wave / turbulent boundary layer interactions, scalar transport modeling (specifically the significance of turbulent Prandtl and Schmidt numbers) and compressible mixing. Unit problems are primarily used to conduct the assessment. In the combustor, results from calculations of a direct connect supersonic combustion experiment are also used to address the effects of turbulence model selection and in particular settings for the turbulent Prandtl and Schmidt numbers. It is concluded that RANS turbulence modeling shortfalls are still a major limitation to the accuracy of hypersonic propulsion simulations, whether considering individual components or an overall system. Newer methods such as LES-based techniques may be promising, but are not yet at a maturity to be used routinely by the hypersonic propulsion community. The need for fundamental experiments to provide data for turbulence model development and validation is discussed.

Status of turbulence modeling for hypersonic propulsion flowpaths

NASA Astrophysics Data System (ADS)

Georgiadis, Nicholas J.; Yoder, Dennis A.; Vyas, Manan A.; Engblom, William A.

2014-06-01

This report provides an assessment of current turbulent flow calculation methods for hypersonic propulsion flowpaths, particularly the scramjet engine. Emphasis is placed on Reynolds-averaged Navier-Stokes (RANS) methods, but some discussion of newer methods such as large eddy simulation (LES) is also provided. The report is organized by considering technical issues throughout the scramjet-powered vehicle flowpath, including laminar-to-turbulent boundary layer transition, shock wave/turbulent boundary layer interactions, scalar transport modeling (specifically the significance of turbulent Prandtl and Schmidt numbers), and compressible mixing. Unit problems are primarily used to conduct the assessment. In the combustor, results from calculations of a direct connect supersonic combustion experiment are also used to address the effects of turbulence model selection and in particular settings for the turbulent Prandtl and Schmidt numbers. It is concluded that RANS turbulence modeling shortfalls are still a major limitation to the accuracy of hypersonic propulsion simulations, whether considering individual components or an overall system. Newer methods such as LES-based techniques may be promising, but are not yet at a maturity to be used routinely by the hypersonic propulsion community. The need for fundamental experiments to provide data for turbulence model development and validation is discussed.

N-S/DSMC hybrid simulation of hypersonic flow over blunt body including wakes

NASA Astrophysics Data System (ADS)

Li, Zhonghua; Li, Zhihui; Li, Haiyan; Yang, Yanguang; Jiang, Xinyu

2014-12-01

A hybrid N-S/DSMC method is presented and applied to solve the three-dimensional hypersonic transitional flows by employing the MPC (modular Particle-Continuum) technique based on the N-S and the DSMC method. A sub-relax technique is adopted to deal with information transfer between the N-S and the DSMC. The hypersonic flows over a 70-deg spherically blunted cone under different Kn numbers are simulated using the CFD, DSMC and hybrid N-S/DSMC method. The present computations are found in good agreement with DSMC and experimental results. The present method provides an efficient way to predict the hypersonic aerodynamics in near-continuum transitional flow regime.

Assessment of CFD capability for prediction of hypersonic shock interactions

NASA Astrophysics Data System (ADS)

Knight, Doyle; Longo, José; Drikakis, Dimitris; Gaitonde, Datta; Lani, Andrea; Nompelis, Ioannis; Reimann, Bodo; Walpot, Louis

2012-01-01

The aerothermodynamic loadings associated with shock wave boundary layer interactions (shock interactions) must be carefully considered in the design of hypersonic air vehicles. The capability of Computational Fluid Dynamics (CFD) software to accurately predict hypersonic shock wave laminar boundary layer interactions is examined. A series of independent computations performed by researchers in the US and Europe are presented for two generic configurations (double cone and cylinder) and compared with experimental data. The results illustrate the current capabilities and limitations of modern CFD methods for these flows.

Hypersonic propulsion flight tests as essential to air-breathing aerospace plane development

NASA Astrophysics Data System (ADS)

Mehta, U.

Hypersonic air-breathing propulsion utilizing scramjets can fundamentally change transatmospheric acclerators for transportation from low Earth orbits (LEOs). The value and limitations of ground tests, of flight tests, and of computations are presented, and scramjet development requirements are discussed. Near-full-scale hypersonic propulsion flight tests are essential for developing a prototype hypersonic propulsion system and for developing computation-design technology that can be used in designing that system. In order to determine how these objectives should be achieved, some lessons learned from past programs are presented. A conceptual two-stage-to-orbit (TSTO) prototype/experimental aerospace plane is recommended as a means of providing access-to-space and for conducting flight tests. A road map for achieving these objectives is also presented.

Assessment of a flow-through balance for hypersonic wind tunnel models with scramjet exhaust flow simulation

NASA Technical Reports Server (NTRS)

Huebner, Lawrence D.; Kniskern, Marc W.; Monta, William J.

1993-01-01

The purpose of this investigation were twofold: first, to determine whether accurate force and moment data could be obtained during hypersonic wind tunnel tests of a model with a scramjet exhaust flow simulation that uses a representative nonwatercooled, flow-through balance; second, to analyze temperature time histories on various parts of the balance to address thermal effects on force and moment data. The tests were conducted in the NASA Langley Research Center 20-Inch Mach 6 Wind Tunnel at free-stream Reynolds numbers ranging from 0.5 to 7.4 x 10(exp 6)/ft and nominal angles of attack of -3.5 deg, 0 deg, and 5 deg. The simulant exhaust gases were cold air, hot air, and a mixture of 50 percent Argon and 50 percent Freon by volume, which reached stagnation temperatures within the balance of 111, 214, and 283 F, respectively. All force and moment values were unaffected by the balance thermal response from exhaust gas simulation and external aerodynamic heating except for axial-force measurements, which were significantly affected by balance heating. This investigation showed that for this model at the conditions tested, a nonwatercooled, flow-through balance is not suitable for axial-force measurements during scramjet exhaust flow simulation tests at hypersonic speeds. In general, heated exhaust gas may produce unacceptable force and moment uncertainties when used with thermally sensitive balances.

Experimental Study of Hypersonic Wing/Fin Root Heating at Mach 8

DTIC Science & Technology

2012-12-27

at 700%, 200% and 60% for 45?, 55? and 65? of sweep respectively. 15. SUBJECT TERMS Hypersonics, Hypersonic Test Facilities , Shock Tunnels , wing...consisting of a flat plate and a cylinder with an adjustable sweep angle. The tests were conducted in the T4 shock tunnel at conditions simulating Mach 8...root experiment began with an assessment of design considerations for the experiment and the parameters of the T4 shock tunnel facilities. A CAD

The potential for a new era of supersonic and hypersonic aviation

NASA Technical Reports Server (NTRS)

Harris, Roy V.

1990-01-01

A new era of supersonic and hypersonic aviation is envisioned. The potential for supersonic and hypersonic flight vehicles in this new era is analyzed. Technology challenges that must be met in order to bring in this new era of flight are discussed. The current technical status and future potential are cited in the areas of aerodynamics, propulsion, and structural materials. A next major step in the development of high-speed air transportation is suggested.

Revolutionary Materials for Hypersonic Flight

DTIC Science & Technology

2011-10-01

Transactions A (in preparation ). 16. M.D. Novak, CG. Levi, " Silicide Coatings on Niobium Substrates II: Thermodynamic Analysis and Mechanism of...These conditions impose significant challenges to material selection. While metallic materials are favored for their durability to thermal distortion...those of even the most highly-conducting engineering materials. While metallic systems are desirable for use in hypersonic vehicles for durability and

Efficacy and safety of eflornithine (CPP-1X)/sulindac combination therapy versus each as monotherapy in patients with familial adenomatous polyposis (FAP): design and rationale of a randomized, double-blind, Phase III trial.

PubMed

Burke, Carol A; Dekker, Evelien; Samadder, N Jewel; Stoffel, Elena; Cohen, Alfred

2016-08-02

Molecular studies suggest inhibition of colorectal mucosal polyamines (PAs) may be a promising approach to prevent colorectal cancer (CRC). Inhibition of ornithine decarboxylase (ODC) using low-dose eflornithine (DFMO, CPP-1X), combined with maximal PA export using low-dose sulindac, results in greatly reduced levels of normal mucosal PAs. In a clinical trial, this combination (compared with placebo) reduced the 3-year incidence of subsequent high-risk adenomas by >90 %. Familial Adenomatous Polyposis (FAP) is characterized by marked up-regulation of ODC in normal intestinal epithelial and adenoma tissue, and therefore PA reduction might be a potential strategy to control progression of FAP-related intestinal polyposis. CPP FAP-310, a randomized, double-blind, Phase III trial was designed to examine the safety and efficacy of sulindac and DFMO (alone or in combination) for preventing a clinically relevant FAP-related progression event in individuals with FAP. Eligible adults with FAP will be randomized to: CPP-1X 750 mg and sulindac 150 mg, CPP-1X placebo and sulindac 150 mg, or CPP-1X 750 mg and sulindac placebo once daily for 24 months. Patients will be stratified based on time-to-event prognosis into one of the three treatment arms: best (ie, longest time to first FAP-related event [rectal/pouch polyposis]), intermediate (duodenal polyposis) and worst (pre-colectomy). Stage-specific, "delayed time to" FAP-related events are the primary endpoints. Change in polyp burden (upper and/or lower intestine) is a key secondary endpoint. The trial is ongoing. As of February 1, 2016, 214 individuals have been screened; 138 eligible subjects have been randomized to three treatment groups at 15 North American sites and 6 European sites. By disease strata, 26, 80 and 32 patients are included for assessment of polyp burden in the rectum/pouch, duodenal polyposis and pre-colectomy groups, respectively. Median age is 40 years; 59 % are men. The most common reasons for

Detached Eddy Simulations of Hypersonic Transition

NASA Technical Reports Server (NTRS)

Yoon, S.; Barnhardt, M.; Candler, G.

2010-01-01

This slide presentation reviews the use of Detached Eddy Simulation (DES) of hypersonic transistion. The objective of the study was to investigate the feasibility of using CFD in general, DES in particular, for prediction of roughness-induced boundary layer transition to turbulence and the resulting increase in heat transfer.

Results of tests in the NASA/LARC 31-inch CFHT on an 0.010-scale model (32-OT) of the space shuttle configuration 3 to determine the RCS jet flowfield interaction effects on aerodynamic characteristics (IA60/OA105), volume 1

NASA Technical Reports Server (NTRS)

Thornton, D. E.

1974-01-01

Tests were conducted in the NASA Langley Research Center 31-inch continuous Flow Hypersonic Wind Tunnel to determine RCS jet interaction effect on the hypersonic aerodynamic and stability and control characteristics prior to return to launch site (RTLS) abort separation. The model used was an 0.010-scale replica of the Space Shuttle Vehicle Configuration 3. Hypersonic stability data were obtained from tests at Mach 10.3 and dynamic pressure of 150 psf for the integrated Orbiter and external tank and the Orbiter alone. RCS modes of pitch, yaw, and roll at free flight dynamic pressure simulation of 7, 20, and 50 psf were investigated. The effects of speedbrake, bodyflap, elevon, and aileron deflections were also investigated.

Elevator Sizing, Placement, and Control-Relevant Tradeoffs for Hypersonic Vehicles

NASA Technical Reports Server (NTRS)

Dickeson, Jeffrey J.; Rodriguez, Armando A.; Sridharan, Srikanth; Korad, Akshay

2010-01-01

Within this paper, control-relevant vehicle design concepts are examined using a widely used 3 DOF (plus flexibility) nonlinear model for the longitudinal dynamics of a generic carrot-shaped scramjet powered hypersonic vehicle. The impact of elevator size and placement on control-relevant static properties (e.g. level-flight trimmable region, trim controls, Angle of Attack (AOA), thrust margin) and dynamic properties (e.g. instability and right half plane zero associated with flight path angle) are examined. Elevator usage has been examine for a class of typical hypersonic trajectories.

Hypersonic research engine project. Phase 2: Aerothermodynamic Integration Model (AIM) test report

NASA Technical Reports Server (NTRS)

Andersen, W. L.; Kado, L.

1975-01-01

The Hypersonic Research Engine-Aerothermodynamic Integration Model (HRE-AIM) was designed, fabricated, and tested in the Hypersonic Tunnel Facility. The HRE-AIM is described along with its installation in the wind tunnel facility. Test conditions to which the HRE-AIM was subjected and observations made during the tests are discussed. The overall engine performance, component interaction, and ignition limits for the design are evaluated.

A comparison of upwind schemes for computation of three-dimensional hypersonic real-gas flows

NASA Technical Reports Server (NTRS)

Gerbsch, R. A.; Agarwal, R. K.

1992-01-01

The method of Suresh and Liou (1992) is extended, and the resulting explicit noniterative upwind finite-volume algorithm is applied to the integration of 3D parabolized Navier-Stokes equations to model 3D hypersonic real-gas flowfields. The solver is second-order accurate in the marching direction and employs flux-limiters to make the algorithm second-order accurate, with total variation diminishing in the cross-flow direction. The algorithm is used to compute hypersonic flow over a yawed cone and over the Ames All-Body Hypersonic Vehicle. The solutions obtained agree well with other computational results and with experimental data.

Computational analysis of hypersonic flows past elliptic-cone waveriders

NASA Technical Reports Server (NTRS)

Yoon, Bok-Hyun; Rasmussen, Maurice L.

1991-01-01

A comprehensive study for the inviscid numerical calculation of the hypersonic flow past a class of elliptic-cone derived waveriders is presented. The theoretical background associated with hypersonic small-disturbance theory (HSDT) is reviewed. Several approximation formulas for the waverider compression surface are established. A CFD algorithm is used to calculate flow fields for the on-design case and a variety of off-design cases. The results are compared with HSDT, experiment, and other available CFD results. For the waverider shape used in previous investigations, the bow shock for the on-design condition stands off from the leading-edge tip of the waverider. It was found that this occurs because the tip was too thick according to the approximating shape formula that was used to describe the compression surface. When this was corrected, the bow shock became closer to attached as it should be. At Mach numbers greater than the design condition, a lambda-shock configuration develops near the tip of the compression surface. At negative angles of attack, other complicated shock patterns occur near the leading-edge tip. These heretofore unknown flow patterns show the power and utility of CFD for investigating novel hypersonic configurations such as waveriders.

Ceramic Matrix Composite (CMC) Thermal Protection Systems (TPS) and Hot Structures for Hypersonic Vehicles

NASA Technical Reports Server (NTRS)

Glass, David E.

2008-01-01

Thermal protection systems (TPS) and hot structures are required for a range of hypersonic vehicles ranging from ballistic reentry to hypersonic cruise vehicles, both within Earth's atmosphere and non-Earth atmospheres. The focus of this paper is on air breathing hypersonic vehicles in the Earth's atmosphere. This includes single-stage to orbit (SSTO), two-stage to orbit (TSTO) accelerators, access to space vehicles, and hypersonic cruise vehicles. This paper will start out with a brief discussion of aerodynamic heating and thermal management techniques to address the high heating, followed by an overview of TPS for rocket-launched and air-breathing vehicles. The argument is presented that as we move from rocket-based vehicles to air-breathing vehicles, we need to move away from the insulated airplane approach used on the Space Shuttle Orbiter to a wide range of TPS and hot structure approaches. The primary portion of the paper will discuss issues and design options for CMC TPS and hot structure components, including leading edges, acreage TPS, and control surfaces. The current state-of-the-art will be briefly discussed for some of the components. The two primary technical challenges impacting the use of CMC TPS and hot structures for hypersonic vehicles are environmental durability and fabrication, and will be discussed briefly.

Hypersonic Wake Diagnostics Using Laser Induced Fluorescence Techniques

NASA Technical Reports Server (NTRS)

Mills, Jack L.; Sukenik, Charles I.; Balla, Robert J.

2011-01-01

A review of recent research performed in iodine that involves a two photon absorption of light at 193 nm will be discussed, and it's potential application to velocimetry measurements in a hypersonic flow field will be described. An alternative seed atom, Krypton, will be presented as a good candidate for performing nonintrusive hypersonic flow diagnostics. Krypton has a metastable state with a lifetime of approximately 43 s which would prove useful for time of flight measurement (TOF) and a sensitivity to collisions that can be utilized for density measurements. Calculations using modest laser energies and experimental values show an efficiency of excited state production to be on the order of 10(exp -6) for a two photon absorption at 193 nm.

Progress with multigrid schemes for hypersonic flow problems

NASA Technical Reports Server (NTRS)

Radespiel, R.; Swanson, R. C.

1991-01-01

Several multigrid schemes are considered for the numerical computation of viscous hypersonic flows. For each scheme, the basic solution algorithm uses upwind spatial discretization with explicit multistage time stepping. Two level versions of the various multigrid algorithms are applied to the two dimensional advection equation, and Fourier analysis is used to determine their damping properties. The capabilities of the multigrid methods are assessed by solving three different hypersonic flow problems. Some new multigrid schemes based on semicoarsening strategies are shown to be quite effective in relieving the stiffness caused by the high aspect ratio cells required to resolve high Reynolds number flows. These schemes exhibit good convergence rates for Reynolds numbers up to 200 x 10(exp 6) and Mach numbers up to 25.

Surface Heat Flux and Pressure Distribution on a Hypersonic Blunt Body With DEAS

NASA Astrophysics Data System (ADS)

Salvador, I. I.; Minucci, M. A. S.; Toro, P. G. P.; Oliveira, A. C.; Channes, J. B.

2008-04-01

With the currently growing interest for advanced technologies to enable hypersonic flight comes the Direct Energy Air Spike concept, where pulsed beamed laser energy is focused upstream of a blunt flight vehicle to disrupt the flow structure creating a virtual, slender body geometry. This allies in the vehicle both advantages of a blunt body (lower thermal stresses) to that of a slender geometry (lower wave drag). The research conducted at the Henry T. Nagamatsu Laboratory for Aerodynamics and Hypersonics focused on the measurement of the surface pressure and heat transfer rates on a blunt model. The hypersonic flight conditions were simulated at the HTN Laboratory's 0.3 m T2 Hypersonic Shock Tunnel. During the tests, the laser energy was focused upstream the model by an infrared telescope to create the DEAS effect, which was supplied by a TEA CO2 laser. Piezoelectric pressure transducers were used for the pressure measurements and fast response coaxial thermocouples were used for the measurement of surface temperature, which was later used for the estimation of the wall heat transfer using the inverse heat conduction theory.

Hypersonic force measurements using internal balance based on optical micromachined Fabry-Perot interferometry.

PubMed

Qiu, Huacheng; Min, Fu; Zhong, Shaolong; Song, Xin; Yang, Yanguang

2018-03-01

Force measurements using wind tunnel balance are necessary for determining a variety of aerodynamic performance parameters, while the harsh environment in hypersonic flows requires that the measurement instrument should be reliable and robust, in against strong electromagnetic interference, high vacuum, or metal (oxide) dusts. In this paper, we demonstrated a three-component internal balance for hypersonic aerodynamic force measurements, using novel optical micromachined Fabry-Perot interferometric (FPI) strain gauges as sensing elements. The FPI gauges were fabricated using Micro-Opto-Electro-Mechanical Systems (MOEMS) surface and bulk fabrication techniques. High-reflectivity coatings are used to form a high-finesse Fabry-Perot cavity, which benefits a high resolution. Antireflective and passivation coatings are used to reduce unwanted interferences. The FPI strain gauge based balance has been calibrated and evaluated in a Mach 5 hypersonic flow. The results are compared with the traditional technique using the foil resistive strain gauge balance, indicating that the proposed balance based on the MOEMS FPI strain gauge is reliable and robust and is potentially suitable for the hypersonic wind tunnel harsh environment.

Hypersonic force measurements using internal balance based on optical micromachined Fabry-Perot interferometry

NASA Astrophysics Data System (ADS)

Qiu, Huacheng; Min, Fu; Zhong, Shaolong; Song, Xin; Yang, Yanguang

2018-03-01

Force measurements using wind tunnel balance are necessary for determining a variety of aerodynamic performance parameters, while the harsh environment in hypersonic flows requires that the measurement instrument should be reliable and robust, in against strong electromagnetic interference, high vacuum, or metal (oxide) dusts. In this paper, we demonstrated a three-component internal balance for hypersonic aerodynamic force measurements, using novel optical micromachined Fabry-Perot interferometric (FPI) strain gauges as sensing elements. The FPI gauges were fabricated using Micro-Opto-Electro-Mechanical Systems (MOEMS) surface and bulk fabrication techniques. High-reflectivity coatings are used to form a high-finesse Fabry-Perot cavity, which benefits a high resolution. Antireflective and passivation coatings are used to reduce unwanted interferences. The FPI strain gauge based balance has been calibrated and evaluated in a Mach 5 hypersonic flow. The results are compared with the traditional technique using the foil resistive strain gauge balance, indicating that the proposed balance based on the MOEMS FPI strain gauge is reliable and robust and is potentially suitable for the hypersonic wind tunnel harsh environment.

Optical skin friction measurement technique in hypersonic wind tunnel

NASA Astrophysics Data System (ADS)

Chen, Xing; Yao, Dapeng; Wen, Shuai; Pan, Junjie

2016-10-01

Shear-sensitive liquid-crystal coatings (SSLCCs) have an optical characteristic that they are sensitive to the applied shear stress. Based on this, a novel technique is developed to measure the applied shear stress of the model surface regarding both its magnitude and direction in hypersonic flow. The system of optical skin friction measurement are built in China Academy of Aerospace Aerodynamics (CAAA). A series of experiments of hypersonic vehicle is performed in wind tunnel of CAAA. Global skin friction distribution of the model which shows complicated flow structures is discussed, and a brief mechanism analysis and an evaluation on optical measurement technique have been made.

eRapa Restores A Normal Life Span in a FAP Mouse Model

PubMed Central

Hasty, Paul; Livi, Carolina B.; Dodds, Sherry G.; Jones, Diane; Strong, Randy; Javors, Martin; Fischer, Kathleen E.; Sloane, Lauren; Murthy, Kruthi; Hubbard, Gene; Sun, Lishi; Hurez, Vincent; Curiel, Tyler J.; Sharp, Zelton Dave

2014-01-01

Mutation of a single copy of the adenomatous polyposis coli (APC) gene results in familial adenomatous polyposis (FAP), which confers an extremely high risk for colon cancer. ApcMin/+ mice exhibit multiple intestinal neoplasia (MIN) that causes anemia and death from bleeding by 6 months. Mechanistic target of rapamycin complex 1 (mTORC1) inhibitors were shown to improve ApcMin/+ mouse survival when administered by oral gavage or added directly to the chow, but these mice still died from neoplasia well short of a natural life span. The National Institute of Aging Intervention Testing Program showed that enterically targeted rapamycin (eRapa) extended life span for wild type genetically heterogeneous mice in part by inhibiting age-associated cancer. We hypothesized that eRapa would be effective in preventing neoplasia and extend survival of ApcMin/+ mice. We show that eRapa improved survival for ApcMin/+ mice in a dose-dependent manner. Remarkably, and in contrast to previous reports, most of the ApcMin/+ mice fed 42 ppm eRapa lived beyond the median life span reported for wild type syngeneic mice. Furthermore, chronic eRapa did not cause detrimental immune effects in mouse models of cancer, infection or autoimmunity; thus, assuaging concerns that chronic rapamycin treatment suppresses immunity. Our studies suggest that a novel formulation (enteric targeting) of a well-known and widely used drug (rapamycin) can dramatically improve its efficacy in targeted settings. eRapa or other mTORC1 inhibitors could serve as effective cancer preventatives for people with FAP without suppressing the immune system, thus reducing the dependency on surgery as standard therapy. PMID:24282255

Requirements for facilities and measurement techniques to support CFD development for hypersonic aircraft

NASA Technical Reports Server (NTRS)

Sellers, William L., III; Dwoyer, Douglas L.

1992-01-01

The design of a hypersonic aircraft poses unique challenges to the engineering community. Problems with duplicating flight conditions in ground based facilities have made performance predictions risky. Computational fluid dynamics (CFD) has been proposed as an additional means of providing design data. At the present time, CFD codes are being validated based on sparse experimental data and then used to predict performance at flight conditions with generally unknown levels of uncertainty. This paper will discuss the facility and measurement techniques that are required to support CFD development for the design of hypersonic aircraft. Illustrations are given of recent success in combining experimental and direct numerical simulation in CFD model development and validation for hypersonic perfect gas flows.

NASA's B-52B launch aircraft cruises to a test range over the Pacific Ocean carrying the third X-43A vehicle attached to a Pegasus rocket on November 16, 2004

NASA Image and Video Library

2004-11-16

The third X-43A hypersonic research aircraft, attached to a modified Pegasus booster rocket, was taken to launch altitude by NASA's B-52B launch aircraft from the NASA Dryden Flight Research Center at Edwards Air Force Base, California, on November 16, 2004. About an hour later the Pegasus booster was released from the B-52 to accelerate the X-43A to its intended speed of Mach 10.

Remote Infrared Imaging of the Space Shuttle During Hypersonic Flight: HYTHIRM Mission Operations and Coordination

NASA Technical Reports Server (NTRS)

Schwartz, Richard J.; McCrea, Andrew C.; Gruber, Jennifer R.; Hensley, Doyle W.; Verstynen, Harry A.; Oram, Timothy D.; Berger, Karen T.; Splinter, Scott C.; Horvath, Thomas J.; Kerns, Robert V.

2011-01-01

The Hypersonic Thermodynamic Infrared Measurements (HYTHIRM) project has been responsible for obtaining spatially resolved, scientifically calibrated in-flight thermal imagery of the Space Shuttle Orbiter during reentry. Starting with STS-119 in March of 2009 and continuing through to the majority of final flights of the Space Shuttle, the HYTHIRM team has to date deployed during seven Shuttle missions with a mix of airborne and ground based imaging platforms. Each deployment of the HYTHIRM team has resulted in obtaining imagery suitable for processing and comparison with computational models and wind tunnel data at Mach numbers ranging from over 18 to under Mach 5. This paper will discuss the detailed mission planning and coordination with the NASA Johnson Space Center Mission Control Center that the HYTHIRM team undergoes to prepare for and execute each mission.

Gene therapy approach to FAP: in vivo influence of T119M in TTR deposition in a transgenic V30M mouse model.

PubMed

Batista, A R; Gianni, D; Ventosa, M; Coelho, A V; Almeida, M R; Sena-Esteves, M; Saraiva, M J

2014-12-01

Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by extracellular deposition of amyloid fibrils composed by mutated transthyretin (TTR) mainly in the peripheral nervous system. At present, liver transplantation is still the standard treatment to halt the progression of clinical symptoms in FAP, but new therapeutic strategies are emerging, including the use of TTR stabilizers. Here we propose to establish a new gene therapy approach using adeno-associated virus (AAV) vectors to deliver the trans-suppressor TTR T119M variant to the liver of transgenic TTR V30M mice at different ages. This TTR variant is known for its ability to stabilize the tetrameric protein. Analysis of the gastrointestinal tract of AAV-treated animals revealed a significant reduction in deposition of TTR non-fibrillar aggregates in as much as 34% in stomach and 30% in colon, as well as decreased levels of biomarkers associated with TTR deposition, namely the endoplasmic reticulum stress marker BiP and the extracellular matrix protein MMP-9. Moreover, we showed with different studies that our approach leads to an increase in tetrameric and more stable forms of TTR, in favor of destabilized monomers. Altogether our data suggest the possibility to use this gene therapy approach in a prophylactic manner to prevent FAP pathology.

Real Time Detection of Protein Trafficking with High Throughput Flow Cytometry (HTFC) and Fluorogen Activating Protein (FAP) Base Biosensor

PubMed Central

Wu, Yang; Tapia, Phillip H.; Jarvik, Jonathan; Waggoner, Alan S.; Sklar, Larry A.

2014-01-01

We combined fluorogen activating protein (FAP) technology with high-throughput flow cytometry to detect real-time protein trafficking to and from the plasma membrane in living cells. The hybrid platform allows drug discovery for trafficking receptors, such as G-protein coupled receptors, receptor tyrosine kinases and ion channels, that were previously not suitable for high throughput screening by flow cytometry.. The system has been validated using the β2-adrenergic receptor (β2AR) system and extended to other GPCRs. When a chemical library containing ~1,200 off-patent drugs was screened against cells expressing FAP tagged β2AR, all known β2AR active ligands in the library were successfully identified, together with a few compounds that were later confirmed to regulate receptor internalization in a non-traditional manner. The unexpected discovery of new ligands by this approach indicates the potential of using this protocol for GPCR de-orphanization. In addition, screens of multiplexed targets promise improved efficiency with minor protocol modification. PMID:24510772

Intracavity doubling of cw LD pumped Nd:S-FAP laser with KTP

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

Zhang Shaojun; Sun Lianke; Wang Qingpu

In this paper the lasing performance of a intracavity doubling of CW diode-laser end-pumped Nd{sup 3+}:Sr{sub 5}(PO{sub 4}){sub 3}F, Nd:S-FAP, laser with KTP crystal was reported. The authors measured the single output performance of the green laser: the pumping threshold was 8mW; when the pumping light of 210mW was absorbed, the maximum single output at 529.7nm was 4.4mW (TEM{sub 00} mode), corresponding to a total conversion efficiency 2.1%. The comparison between experimental results and theoretical calculation was also discussed in this paper.

Overview of NASA's Integrated Design and Engineering Analysis (IDEA)Environment

NASA Technical Reports Server (NTRS)

Robinson, Jeffrey S.; Martin John G.

2008-01-01

Historically, the design of subsonic and supersonic aircraft has been divided into separate technical disciplines (such as propulsion, aerodynamics and structures) each of which performs their design and analysis in relative isolation from others. This is possible in most cases either because the amount of interdisciplinary coupling is minimal or because the interactions can be treated as linear. The design of hypersonic airbreathing vehicles, like NASA s X-43, is quite the opposite. Such systems are dominated by strong non-linear interactions between disciplines. The design of these systems demands that a multi-disciplinary approach be taken. Furthermore, increased analytical fidelity at the conceptual design phase is highly desirable as many of the non-linearities are not captured by lower fidelity tools. Only when these systems are designed from a true multi-disciplinary perspective can the real performance benefits be achieved and complete vehicle systems be fielded. Toward this end, the Vehicle Analysis Branch at NASA Langley Research Center has been developing the Integrated Design & Engineering Analysis (IDEA) Environment. IDEA is a collaborative environment for parametrically modeling conceptual and preliminary launch vehicle configurations using the Adaptive Modeling Language (AML) as the underlying framework. The environment integrates geometry, configuration, propulsion, aerodynamics, aerothermodynamics, trajectory, closure and structural analysis into a generative, parametric, unified computational model where data is shared seamlessly between the different disciplines. Plans are also in place to incorporate life cycle analysis tools into the environment which will estimate vehicle operability, reliability and cost. IDEA is currently being funded by NASA s Hypersonics Project, a part of the Fundamental Aeronautics Program within the Aeronautics Research Mission Directorate. The environment is currently focused around a two-stage-to-orbit configuration

On two special values of temperature factor in hypersonic flow stagnation point

NASA Astrophysics Data System (ADS)

Bilchenko, G. G.; Bilchenko, N. G.

2018-03-01

The hypersonic aircraft permeable cylindrical and spherical surfaces laminar boundary layer heat and mass transfer control mathematical model properties are investigated. The nonlinear algebraic equations systems are obtained for two special values of temperature factor in the hypersonic flow stagnation point. The mappings bijectivity between heat and mass transfer local parameters and controls is established. The computation experiments results are presented: the domains of allowed values “heat-friction” are obtained.

Computational study of generic hypersonic vehicle flow fields

NASA Technical Reports Server (NTRS)

Narayan, Johnny R.

1994-01-01

The geometric data of the generic hypersonic vehicle configuration included body definitions and preliminary grids for the forebody (nose cone excluded), midsection (propulsion system excluded), and afterbody sections. This data was to be augmented by the nose section geometry (blunt conical section mated with the noncircular cross section of the forebody initial plane) along with a grid and a detailed supersonic combustion ramjet (scramjet) geometry (inlet and combustor) which should be merged with the nozzle portion of the afterbody geometry. The solutions were to be obtained by using a Navier-Stokes (NS) code such as TUFF for the nose portion, a parabolized Navier-Stokes (PNS) solver such as the UPS and STUFF codes for the forebody, a NS solver with finite rate hydrogen-air chemistry capability such as TUFF and SPARK for the scramjet and a suitable solver (NS or PNS) for the afterbody and external nozzle flows. The numerical simulation of the hypersonic propulsion system for the generic hypersonic vehicle is the major focus of this entire work. Supersonic combustion ramjet is such a propulsion system, hence the main thrust of the present task has been to establish a solution procedure for the scramjet flow. The scramjet flow is compressible, turbulent, and reacting. The fuel used is hydrogen and the combustion process proceeds at a finite rate. As a result, the solution procedure must be capable of addressing such flows.

Dynamics Evolution Investigation of Mack Mode Instability in a Hypersonic Boundary Layer by Bicoherence Spectrum Analysis

NASA Astrophysics Data System (ADS)

Han, Jian; Jiang, Nan

2012-07-01

The instability of a hypersonic boundary layer on a cone is investigated by bicoherence spectrum analysis. The experiment is conducted at Mach number 6 in a hypersonic wind tunnel. The time series signals of instantaneous fluctuating surface-thermal-flux are measured by Pt-thin-film thermocouple temperature sensors mounted at 28 stations on the cone surface along streamwise direction to investigate the development of the unstable disturbances. The bicoherence spectrum analysis based on wavelet transform is employed to investigate the nonlinear interactions of the instability of Mack modes in hypersonic laminar boundary layer transition. The results show that wavelet bicoherence is a powerful tool in studying the unstable mode nonlinear interaction of hypersonic laminar-turbulent transition. The first mode instability gives rise to frequency shifts to higher unstable modes at the early stage of hypersonic laminar-turbulent transition. The modulations subsequently lead to the second mode instability occurrence. The second mode instability governs the last stage of instability and final breakdown to turbulence with multi-scale disturbances growth.

Synergy of combined Doxycycline/TUDCA treatment in lowering Transthyretin deposition and associated biomarkers: studies in FAP mouse models

PubMed Central

2010-01-01

Familial Amyloidotic Polyneuropathy (FAP) is a disorder characterized by the extracellular deposition of fibrillar Transthyretin (TTR) amyloid, with a special involvement of the peripheral nerve. We had previously shown that doxycycline administered for 3 months at 40 mg/Kg/ml in the drinking water, was capable of removing TTR amyloid deposits present in stomachs of old TTR-V30M transgenic mice; the removal was accompanied by a decrease in extracellular matrix remodeling proteins that accompany fibrillar deposition, but not of non-fibrillar TTR deposition and/or markers associated with pre-fibrillar deposits. On the other hand, Tauroursodeoxycholic acid (TUDCA), a biliary acid, administrated to the same mouse model was shown to be effective at lowering deposited non-fibrillar TTR, as well as the levels of markers associated with pre-fibrillar TTR, but only at young ages. In the present work we evaluated different doxycycline administration schemes, including different periods of treatment, different dosages and different FAP TTR V30M animal models. Evaluation included CR staining, immunohistochemistry for TTR, metalloproteinase 9 (MMP-9) and serum amyloid P component (SAP). We determined that a minimum period of 15 days of treatment with a 8 mg/Kg/day dosage resulted in fibril removal. The possibility of intermittent treatments was also assessed and a maximum period of 15 days of suspension was determined to maintain tissues amyloid-free. Combined cycled doxycycline and TUDCA administration to mice with amyloid deposition, using two different concentrations of both drugs, was more effective than either individual doxycycline or TUDCA, in significantly lowering TTR deposition and associated tissue markers. The observed synergistic effect of doxycycline/TUDCA in the range of human tolerable quantities, in the transgenic TTR mice models prompts their application in FAP, particularly in the early stages of disease. PMID:20673327

The Center of Excellence for Hypersonics Training and Research at the University of Texas at Austin

NASA Technical Reports Server (NTRS)

Dolling, David S.

1993-01-01

Over the period of this grant (1986-92), 23 graduate students were supported by the Center and received education and training in hypersonics through MS and Ph.D. programs. An additional 8 Ph.D. candidates and 2 MS candidates, with their own fellowship support, were attracted to The University of Texas and were recruited into the hypersonics program because of the Center. Their research, supervised by the 10 faculty involved in the Center, resulted in approximately 50 publications and presentations in journals and at national and international technical conferences. To provide broad-based training, a new hypersonics curriculum was created, enabling students to take 8 core classes in theoretical, computational, and experimental hypersonics, and other option classes over a two to four semester period. The Center also developed an active continuing education program. The Hypersonics Short Course was taught 3 times, twice in the USA and once in Europe. Approximately 300 persons were attracted to hear lectures by more than 25 of the leading experts in the field. In addition, a hypersonic aerodynamics short course was offered through AIAA, as well as short courses on computational fluid dynamics (CFD) and advanced CFD. The existence of the Center also enabled faculty to leverage a substantial volume of additional funds from other agencies, for research and graduate student training. Overall, this was a highly successful and highly visible program.

CARS Temperature Measurements in a Hypersonic Propulsion Test Facility

NASA Technical Reports Server (NTRS)

Jarrett, Olin, Jr.; Smith, M. W.; Antcliff, R. R.; Northam, G. Burt; Cutler, A. D.; Capriotti, D. P.; Taylor, D. J.

1990-01-01

Nonintrusive diagnostic measurements were performed in the supersonic reacting flow of the Hypersonic Propulsion Test Cell 2 at NASA-Langley. A Coherent Anti-stokes Raman Spectroscopy (CARS) system was assembled specifically for the test cell environment. System design considerations were: (1) test cell noise and vibration; (2) contamination from flow field or atmospheric borne dust; (3) unwanted laser or electrically induced combustion (inside or outside the duct); (4) efficient signal collection; (5) signal splitting to span the wide dynamic range present throughout the flow field; (6) movement of the sampling volume in the flow; and (7) modification of the scramjet model duct to permit optical access to the reacting flow with the CARS system. The flow in the duct was a nominal Mach 2 flow with static pressure near one atmosphere. A single perpendicular injector introduced hydrogen into the flow behind a rearward facing step. CARS data was obtained in three planes downstream of the injection region. At least 20 CARS data points were collected at each of the regularly spaced sampling locations in each data plane. Contour plots of scramjet combustor static temperature in a reacting flow region are presented.

Scramjet nozzle design and analysis as applied to a highly integrated hypersonic research airplane

NASA Technical Reports Server (NTRS)

Small, W. J.; Weidner, J. P.; Johnston, P. J.

1974-01-01

The configuration and performance of the propulsion system for the hypersonic research vehicle are discussed. A study of the interactions between propulsion and aerodynamics of the highly integrated vehicle was conducted. The hypersonic research vehicle is configured to test the technology of structural and thermal protection systems concepts and the operation of the propulsion system under true flight conditions for most of the hypersonic flight regime. The subjects considered are: (1) research vehicle and scramjet engine configurations to determine fundamental engine sizing constraints, (2) analytical methods for computing airframe and propulsion system components, and (3) characteristics of a candidate nozzle to investigate vehicle stability and acceleration performance.

Design, calibration and testing of a force balance for a hypersonic shock tunnel

NASA Astrophysics Data System (ADS)

Vadassery, Pravin

The forces acting on a flight vehicle are critical for determining its performance. Of particular interest is the hypersonic regime. Force measurements are much more complex in hypersonic flows, where those speeds are simulated in shock tunnels. A force balance for such facilities contains sensitive gages that measure stress waves and ultimately determine the different components of force acting on the model. An external force balance was designed and fabricated for the UTA Hypersonic shock tunnel to measure drag at Mach 10. Static and dynamic calibrations were performed to find the transfer function of the system. Forces were recovered using a deconvolution procedure. To validate the force balance, experiments were conducted on a blunt cone. The measured forces were compared to Newtonian theory.

Monitoring acute equine visceral pain with the Equine Utrecht University Scale for Composite Pain Assessment (EQUUS-COMPASS) and the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP): A scale-construction study.

PubMed

van Loon, Johannes P A M; Van Dierendonck, Machteld C

2015-12-01

Although recognition of equine pain has been studied extensively over the past decades there is still need for improvement in objective identification of pain in horses with acute colic. This study describes scale construction and clinical applicability of the Equine Utrecht University Scale for Composite Pain Assessment (EQUUS-COMPASS) and the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) in horses with acute colic. A cohort follow-up study was performed using 50 adult horses (n = 25 with acute colic, n = 25 controls). Composite pain scores were assessed by direct observations, Visual Analog Scale (VAS) scores were assessed from video clips. Colic patients were assessed at arrival, and on the first and second mornings after arrival. Both the EQUUS-COMPASS and EQUUS-FAP scores showed high inter-observer reliability (ICC = 0.98 for EQUUS-COMPASS, ICC = 0.93 for EQUUS-FAP, P <0.001), while a moderate inter-observer reliability for the VAS scores was found (ICC = 0.63, P <0.001). The cut-off value for differentiation between healthy and colic horses for the EQUUS-COMPASS was 5, and for differentiation between conservatively treated and surgically treated or euthanased patients it was 11. For the EQUUS-FAP, cut-off values were 4 and 6, respectively. Internal sensitivity and specificity were good for both EQUUS-COMPASS (sensitivity 95.8%, specificity 84.0%) and EQUUS-FAP (sensitivity 87.5%, specificity 88.0%). The use of the EQUUS-COMPASS and EQUUS-FAP enabled repeated and objective scoring of pain in horses with acute colic. A follow-up study with new patients and control animals will be performed to further validate the constructed scales that are described in this study. Copyright © 2015 Elsevier Ltd. All rights reserved.

An assessment of laser velocimetry in hypersonic flow

NASA Technical Reports Server (NTRS)

1992-01-01

Although extensive progress has been made in computational fluid mechanics, reliable flight vehicle designs and modifications still cannot be made without recourse to extensive wind tunnel testing. Future progress in the computation of hypersonic flow fields is restricted by the need for a reliable mean flow and turbulence modeling data base which could be used to aid in the development of improved empirical models for use in numerical codes. Currently, there are few compressible flow measurements which could be used for this purpose. In this report, the results of experiments designed to assess the potential for laser velocimeter measurements of mean flow and turbulent fluctuations in hypersonic flow fields are presented. Details of a new laser velocimeter system which was designed and built for this test program are described.

Multigrid for hypersonic viscous two- and three-dimensional flows

NASA Technical Reports Server (NTRS)

Turkel, E.; Swanson, R. C.; Vatsa, V. N.; White, J. A.

1991-01-01

The use of a multigrid method with central differencing to solve the Navier-Stokes equations for hypersonic flows is considered. The time dependent form of the equations is integrated with an explicit Runge-Kutta scheme accelerated by local time stepping and implicit residual smoothing. Variable coefficients are developed for the implicit process that removes the diffusion limit on the time step, producing significant improvement in convergence. A numerical dissipation formulation that provides good shock capturing capability for hypersonic flows is presented. This formulation is shown to be a crucial aspect of the multigrid method. Solutions are given for two-dimensional viscous flow over a NACA 0012 airfoil and three-dimensional flow over a blunt biconic.

Hypersonic Composites Resist Extreme Heat and Stress

NASA Technical Reports Server (NTRS)

2007-01-01

Through research contracts with NASA, Materials and Electrochemical Research Corporation (MER), of Tucson, Arizona, contributed a number of technologies to record-breaking hypersonic flights. Through this research, MER developed a coating that successfully passed testing to simulate Mach 10 conditions, as well as provide several additional carbon-carbon (C-C) composite components for the flights. MER created all of the leading edges for the X-43A test vehicles at Dryden-considered the most critical parts of this experimental craft. In addition to being very heat resistant, the coating had to be very lightweight and thin, as the aircraft was designed to very precise specifications and could not afford to have a bulky coating. MER patented its carbon-carbon (C-C) composite process and then formed a spinoff company, Frontier Materials Corporation (FMC), also based in Tucson. FMC is using the patent in conjunction with low-cost PAN (polyacrylonitrile)-based fibers to introduce these materials to the commercial markets. The C-C composites are very lightweight and exceptionally strong and stiff, even at very high temperatures. The composites have been used in industrial heating applications, the automotive and aerospace industries, as well as in glass manufacturing and on semiconductors. Applications also include transfer components for glass manufacturing and structural members for carrier support in semiconductor processing.

Gastrointestinal (GI) permeability is associated with trait anxiety in children with functional abdominal pain (FAP) and Irritable Bowel Syndrome (IBS)

USDA-ARS?s Scientific Manuscript database