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Sample records for spacecraft cells initial

  1. NASA's small spacecraft technology initiative _Clark_ spacecraft

    NASA Astrophysics Data System (ADS)

    Hayduk, Robert J.; Scott, Walter S.; Walberg, Gerald D.; Butts, James J.; Starr, Richard D.

    1996-11-01

    The Small Satellite Technology Initiative (SSTI) is a National Aeronautics and Space Administration (NASA) program to demonstrate smaller, high technology satellites constructed rapidly and less expensively. Under SSTI, NASA funded the development of "Clark," a high technology demonstration satellite to provide 3-m resolution panchromatic and 15-m resolution multispectral images, as well as collect atmospheric constituent and cosmic x-ray data. The 690-Ib. satellite, to be launched in early 1997, will be in a 476 km, circular, sun-synchronous polar orbit. This paper describes the program objectives, the technical characteristics of the sensors and satellite, image processing, archiving and distribution. Data archiving and distribution will be performed by NASA Stennis Space Center and by the EROS Data Center, Sioux Falls, South Dakota, USA.

  2. Small Spacecraft Technology Initiative (SSTI)

    NASA Technical Reports Server (NTRS)

    Reppucci, George

    1995-01-01

    This is the second in a series of semi-annual reports that describe the technology areas being advanced under this contract and the progress achieved to date. The last technology report concentrated on the spacecraft. This report places greater emphasis on the payloads. White papers by several of the payload providers are attached. These are HSI, UCB, PRKE, and CAFE. This report covers the period from January 1995 through June 1995.

  3. Evaluation program for secondary spacecraft cells: Initial evaluation tests of General Electric Company 6.0 ampere hour nickle cadmium spacecraft cells for the dynamic explorer satellite program

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1980-01-01

    Evaluation tests of 10 nickel cadmium cells are described. Although pressures were greater than what normally was exhibited by General Electric cells in the past, it is recommended that these cells be placed on life test simulating the predicted Dynamic Explorer flight profiles.

  4. Evaluation program for secondary spacecraft cells: Initial evaluation tests of Eagel-Picher Industries, Incorporated, 20.0 amphere-hour nickel-cadmium spacecraft cells

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1974-01-01

    An evaluation test of the 20.0 ampere-hour cells was conducted to insure that all cells put into the life cycle program are of high quality. This is accomplished by the screening of cells found to have electrolyte leakage, internal shorts, low capacity, or inability of any cell to recover its open circuit voltage above 1.150 volts during the internal short test. The results obtained in the test are given, as well as the recommendations based on these findings.

  5. Small Spacecraft Technology Initiative Education Program

    NASA Technical Reports Server (NTRS)

    1995-01-01

    A NASA engineer with the Commercial Remote Sensing Program (CRSP) at Stennis Space Center works with students from W.P. Daniels High School in New Albany, Miss., through NASA's Small Spacecraft Technology Initiative Program. CRSP is teaching students to use remote sensing to locate a potential site for a water reservoir to offset a predicted water shortage in the community's future.

  6. Evaluation program for secondary spacecraft cells. Initial evaluation tests of Eagle-Picher Industries, Incorporated 3.0 ampere-hour nickel-cadmium spacecraft cells

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1973-01-01

    The capacity of the cells ranged from 3.58 to 3.97 amperehours during the three capacity tests. Three cells were removed from test, due to high pressure, during the C/10, 24-hour charge at room ambient temperature. The voltage requirement of 1.480 volts was exceeded by the cells during the C/10, 24-hour charge at 20 C, although the end-of-charge voltage was below this value (1.466-1.475 volts). Average capacity out during the 20 C charge efficiency test was 0.84 AH which represents 48% and is below the minimum requirement of 55%. The cells exhibited no pressure decay during the open-circuit stand portion of the pressure versus capacity test, as all cells reached their voltage limit (1.550 volts) before their pressure reached 20 psia with the highest pressure being 8 psia during charge.

  7. Evaluation program for secondary spacecraft cells: Initial evaluation tests of General Electric Company 6.0 ampere-hour nickel-cadmium spacecraft cells for the Improved Tiros Operational Satellite (ITOS)

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1975-01-01

    Quality control measures for Ni-Cd spacecraft cells were analyzed. Cells were examined for electrolyte leakage, internal shorts, low capacity, or inability of any cell to recover its open circuit voltage above 1.50 volts during the internal short test. Test results are given in tabular form.

  8. Advanced spacecraft fuel cell systems

    NASA Technical Reports Server (NTRS)

    Thaller, L. H.

    1972-01-01

    The development and characteristics of advanced spacecraft fuel cell systems are discussed. The system is designed to operate on low pressure, propulsion grade hydrogen and oxygen. The specific goals are 10,000 hours of operation with refurbishment, 20 pounds per kilowatt at a sustained power of 7 KW, and 21 KW peaking capability for durations of two hours. The system rejects waste heat to the spacecraft cooling system at power levels up to 7 KW. At higher powers, the system automatically transfers to open cycle operation with overboard steam venting.

  9. Cycle life test. [of secondary spacecraft cells

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1977-01-01

    Statistical information concerning cell performance characteristics and limitations of secondary spacecraft cells is presented. Weaknesses in cell design as well as battery weaknesses encountered in various satellite programs are reported. Emphasis is placed on improving the reliability of space batteries.

  10. Multi-Objective Online Initialization of Spacecraft Formations

    NASA Technical Reports Server (NTRS)

    Jeffrey, Matthew; Breger, Louis; How, Jonathan P.

    2007-01-01

    This paper extends a previously developed method for finding spacecraft initial conditions (ICs) that minimize the drift resulting from J2 disturbances while also minimizing the fuel required to attain those ICs. It generalizes the single spacecraft optimization to a formation-wide optimization valid for an arbitrary number of vehicles. Additionally, the desired locations of the spacecraft, separate from the starting location, can be specified, either with respect to a reference orbit, or relative to the other spacecraft in the formation. The three objectives (minimize drift, minimize fuel, and maintain a geometric template) are expressed as competing costs in a linear optimization, and are traded against one another through the use of scalar weights. By carefully selecting these weights and re-initializing the formation at regular intervals, a closed-loop, formation-wide control system is created. This control system can be used to reconfigure the formations on the fly, and creates fuel-efficient plans by placing the spacecraft in semi-invariant orbits. The overall approach is demonstrated through nonlinear simulations for two formations a GEO orbit, and an elliptical orbit.

  11. Evaluation program for secondary spacecraft cells

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1978-01-01

    The results of life cycle tests of secondary spacecraft cells are summarized. Cells consisted of seven sample classifications ranging from 3.0 to 20 ampere-hours, 1326 nlc nickel cadmium, 183 silver cadmium, and 125 silver zinc sealed cells. Variables examined include load, charge control, and temperature conditions.

  12. Evaluation program for secondary spacecraft cells

    NASA Technical Reports Server (NTRS)

    Christy, D. E.; Harkness, J. D.

    1973-01-01

    A life cycle test of secondary electric batteries for spacecraft applications was conducted. A sample number of nickel cadmium batteries were subjected to general performance tests to determine the limit of their actual capabilities. Weaknesses discovered in cell design are reported and aid in research and development efforts toward improving the reliability of spacecraft batteries. A statistical analysis of the life cycle prediction and cause of failure versus test conditions is provided.

  13. Evaluation program for secondary spacecraft cells. Initial evaluation tests of General Electric Company 4.0 ampere-hour nickel-cadmium spacecraft cells for the AMPTE satellite program

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1984-01-01

    Cells found to have electrolyte leakage, internal shorts, low capacity, or inability of any cell to recover its open circuit voltage above 1.150 volts during the internal short test are addressed. The Active Magnetic Particle Tracer Explorer (AMPTE) cell design was characterized and the effects of specific mission parameters on cell life were demonstrated.

  14. Investigation of fast initialization of spacecraft bubble memory systems

    NASA Technical Reports Server (NTRS)

    Looney, K. T.; Nichols, C. D.; Hayes, P. J.

    1984-01-01

    Bubble domain technology offers significant improvement in reliability and functionality for spacecraft onboard memory applications. In considering potential memory systems organizations, minimization of power in high capacity bubble memory systems necessitates the activation of only the desired portions of the memory. In power strobing arbitrary memory segments, a capability of fast turn on is required. Bubble device architectures, which provide redundant loop coding in the bubble devices, limit the initialization speed. Alternate initialization techniques are investigated to overcome this design limitation. An initialization technique using a small amount of external storage is demonstrated.

  15. Evaluation program for secondary spacecraft cells: Initial evaluation tests of Gulton Industries, Incorporated, 9.0 ampere-hour nickel-cadmium spacecraft cells with auxiliary electrodes for the small astronomy Satellite (SAS-C)

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1975-01-01

    An evaluation test program was conducted to insure that all cells put into the life cycle program are of high quality by the screening of cells found to have electrolyte leakage, internal shorts, low capacity, or inability of any cell to recover its open-circuit voltage above 1.150 volts during the internal short test. Tests and results are described.

  16. Evaluation program for secondary spacecraft cells: Initial evaluation tests of Eagle-Picher Industries, Incorporated 6.0 ampere-hour, nickel-cadmium spacecraft cells for separator material evaluation

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1975-01-01

    Several groups of nickel cadmium cells were tested for the durability of their separator materials. The cells were rated at 6.0 ampere-hours, and contained double ceramic seals. Two cells in each group were fitted with pressure gauge assemblies. Results are presented for various brands of separator materials.

  17. Evaluation program for secondary spacecraft cells: Initial evaluation tests of General Electric Company 12.0 ampere-hour nickel-cadmium spacecraft cells for the international ultraviolet explorer

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1976-01-01

    An evaluation test program was conducted to insure that all cells put into the life cycle program are of high quality by the screening of cells found to have electrolyte leakage, internal shorts, low capacity, or inability of any cell to recover its open-circuit voltage above 1.150 volts during the internal short test. The 20 cells were manufactured for the National Aeronautics and Space Administration, Goddard Space Flight Center (GSFC). The cells are from a lot of 175 cells procured for the International Ultraviolet Explorer project. Due to a change in requirements, the project selected to use 6.0 ampere-hour cells. Therefore, the remaining cells of this lot have been placed in storage at GSFC for use on a future GSFC project. All the cells are rated at 12.0 ampere-hours and contain double ceramic seals. Test limits specify those values in which a cell is to be terminated from a particular charge or discharge. Requirements are referred to as normally expected values based on past performance of aerospace nickel cadmium cells with demonstrated life characteristics.

  18. Evaluation program for secondary spacecraft cells. Initial evaluation tests of General Electric Company standard and teflonated negative electrode 20.0 ampere-hour, nickel-cadmium spacecraft cells with auxiliary electrodes

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The standard plate cells exhibited higher average end-of-charge (EOC) voltages than the cells with teflonated negative plates; they also delivered a higher capacity output in ampere hours following these charges. All the cells reached a pressure of 20 psia before reaching the voltage limit of 1.550 volts during the pressure versus capacity test. The average ampere hours in and voltages at this pressure were 33.6 and 1.505 volts respectively for the teflonated negative plate cells and 35.5 and 1.523 volts for the standard plate cells. All cells exhibited pressure decay in the range of 1 to 7 psia during the last 30 minutes of the 1-hour open circuit stand. Average capacity out for the teflonated and standard negative plate cells was 29.4 and 29.9 ampere hours respectively.

  19. Evaluation program for secondary spacecraft cells: Initial evaluation tests of General Electric Company 40.0 ampere hour nickel cadmium spacecraft cells for the tracking data relay satellite system

    NASA Technical Reports Server (NTRS)

    Hall, S. W.

    1980-01-01

    Average end of charge voltages and pressures, and capacity output in ampere hours are presented. Test limits specify those values at which a cell is to be terminated from charge or discharge. Requirements are based on past cell performance data. The requirement does not constitute a limit for discontinuance from testing. The nickel cadmium batteries were screened for internal shorts, low capacity, electrolyte leakage, or inability of any cell to recover its open circuit voltage above 1.150 volts during the internal short test.

  20. Evaluation program for secondary spacecraft cells: Initial evaluation tests of General Electric Company 6.0 ampere hour nickel-cadmium spacecraft cells with auxiliary electrodes for the atmospheric Explorer satellite C and D. [quality control testing

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1974-01-01

    The capacity of the cells ranged from 6.6 to 7.6 ampere hours during the three capacity tests. No voltage requirements or limits were exceeded during any portion of the test. All cells recovered to a voltage in excess of 1.193 volts during the 24-hour open-circuit portion of the internal short test. All the cells reached a pressure of 20 psia before reaching the voltage limit of 1.550 volts during the pressure versus capacity test. The average ampere/hours in and voltages at this pressure were 9.1 and 1.513, respectively. All cells exhibited pressure decay in the range of 1 to 5 psia during the last 30 minutes of the 1-hour open circuit stand. Average capacity out was 7.2 ampere/hours.

  1. Evaluation program for secondary spacecraft cells: Initial evaluation tests of General Electric Company 40.0 ampere-hour nickel-cadmium spacecraft cells for the tracking data relay satellite system

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1978-01-01

    Five cells provided by NASA's Goddard Space Flight Center were evaluated at room temperature and pressure (25 C plus or minus 2 C) with discharges at the 2 hour rate. Measurements of the cell containers following test, indicated an average increase of .006 inches at the plate thickness. Average end of charge voltages and pressures, and capacity output in ampere hours were determined. Three cells exceeded the voltage requirements of 1.52 volts during both c/10 charges at 20 C. All cells exceeded the voltage requirement of 1.52 volts during the 0 C overcharge test, although their end charges were below 1.50 volts. The pressure requirement of 65 psia was exceeded by both pressure transducer cells during c/10 charges at 25 C and 20 C and also during the 0 C overcharge test. The cells with pressure transducers reached a pressure of 20 psia before reaching the voltage limit of 1.550 volts during the pressure versus capacity test, and exhibited a pressure decay of 2 psia during the last 30 minutes of the 1 hour open circuit stand. Average capacity was 51.3 ampere hours.

  2. Spacecraft

    NASA Technical Reports Server (NTRS)

    Feoktistov, K. P.

    1974-01-01

    The task of building a spacecraft is compared to the construction of an artificial cybernetic system able to acquire and process information. Typical features for future spacecraft are outlined and the assignment of duties in spacecraft control between automatic devices and the crew is analyzed.

  3. System Critical Design Audit (CDA). Books 1, 2 and 3; [Small Satellite Technology Initiative (SSTI Lewis Spacecraft Program)

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Small Satellite Technology Initiative (SSTI) Lewis Spacecraft Program is evaluated. Spacecraft integration, test, launch, and spacecraft bus are discussed. Payloads and technology demonstrations are presented. Mission data management system and ground segment are also addressed.

  4. Spacecraft attitude pulse-width control at initial, service and emergency modes

    NASA Astrophysics Data System (ADS)

    Somov, Sergey

    2012-11-01

    Problems of nonlinear modeling, dynamic analysis and simulation of spatial motion by a spacecraft with a flexible weak damping structure, are considered. Attitude motion of a flexible spacecraft with pulse-width control, spin-up rotors of six single-gimbal control moment gyros (CMGs) at the initial, service and emergency modes, is studied. Results on analysis of the spacecraft nutation and flexible oscillations, are represented.

  5. Voyager spacecraft radio observations of Jupiter: Initial cruise results

    NASA Technical Reports Server (NTRS)

    Kaiser, M. L.; Desch, M. D.; Riddle, A. C.; Lecacheux, A.; Pearce, J. B.; Alexander, J. K.; Warwick, J. W.; Thieman, J. R.

    1979-01-01

    Jupiter's low-frequency radio emission were detected by the planetary radio astronomy instruments onboard the two Voyager spacecraft. The emission is surprisingly similar in morphology but opposite in polarization to the high-frequency Jovian radio noise that were observed with ground-based telescopes for more than two decades. Several possible explanations for the behavior of the low-frequency emission are examined, but none of them is completely satisfactory.

  6. Cycle life test of secondary spacecraft cells

    NASA Astrophysics Data System (ADS)

    Harkness, J. D.

    1980-04-01

    The results of the life cycling program on rechargeable calls are reported. Information on required data, the use of which the data will be put, application details, including orbital description, charge control methods, load rquirements, etc., are given. Cycle tests were performed on 660 sealed, nickel cadmium cells. The cells consisted of seven sample classifications ranging form 3.0 to 20 amp. hours. Nickel cadmium, silver cadmium, and silver zinc sealed cells, excluding synchronous orbit and accelerated test packs were added. The capacities of the nickel cadmium cells, the silver cadmium and the silver zinc cells differed in range of amp hrs. The cells were cylced under different load, charge control, and temperature conditions. All cell packs are recharged by use of a pack voltage limit. All charging is constant current until the voltage limit is reached.

  7. Cycle life test of secondary spacecraft cells

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1980-01-01

    The results of the life cycling program on rechargeable calls are reported. Information on required data, the use of which the data will be put, application details, including orbital description, charge control methods, load rquirements, etc., are given. Cycle tests were performed on 660 sealed, nickel cadmium cells. The cells consisted of seven sample classifications ranging form 3.0 to 20 amp. hours. Nickel cadmium, silver cadmium, and silver zinc sealed cells, excluding synchronous orbit and accelerated test packs were added. The capacities of the nickel cadmium cells, the silver cadmium and the silver zinc cells differed in range of amp hrs. The cells were cylced under different load, charge control, and temperature conditions. All cell packs are recharged by use of a pack voltage limit. All charging is constant current until the voltage limit is reached.

  8. Evaluation program for secondary spacecraft cells

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1975-01-01

    The cycle life tests to determine the performance capabilities of packs of cells under different loads and temperature conditions are reported. Results are summarized, and the failure of 14 failed cells is analyzed. It was found that the main cause of failure was separator deterioration and migration of the negative plate material.

  9. Evaluation program for secondary spacecraft cells: Cycle life test

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1979-01-01

    The service life and storage stability for several storage batteries were determined. The batteries included silver-zinc batteries, nickel-cadmium batteries, and silver-cadmium batteries. The cell performance characteristics and limitations are to be used by spacecraft power systems planners and designers. A statistical analysis of the life cycle prediction and cause of failure versus test conditions is presented.

  10. Annular Arrays Of Solar Cells For Spinning Spacecraft

    NASA Technical Reports Server (NTRS)

    Spilker, Thomas R.

    1995-01-01

    Report proposes annular arrays of solar photovoltaic cells installed on spin-stabilized spacecraft. Annular array faces Sun. Typical array consists of two stacked annuli of solar cells: one annulus fixed about spin axis, while other divided into deployable sectors mounted on dual swing arms and stowed by folding them atop fixed annulus. Once released, deployable sectors swing outward under spring or centrifugal force and expose fixed array so it generates additional power.

  11. Ultraviolet imaging spectrometer (UVS) experiment on board the NOZOMI spacecraft: Instrumentation and initial results

    NASA Astrophysics Data System (ADS)

    Taguchi, M.; Fukunishi, H.; Watanabe, S.; Okano, S.; Takahashi, Y.; Kawahara, T. D.

    2000-01-01

    An ultraviolet imaging spectrometer (UVS) on board the PLANET-B (NOZOMI) spacecraft has been developed. The UVS instrument consists of a grating spectrometer (UVS-G), an absorption cell photometer (UVS-P) and an electronics unit (UVS-E). The UVS-G features a flat-field type spectrometer measuring emissions in the FUV and MUV range between 110 nm and 310 nm with a spectral resolution of 2-3 nm. The UVS-P is a photometer separately detecting hydrogen (H) and deuterium (D) Lyman aemissions by the absorption cell technique. They take images using the spin and orbital motion of the spacecraft. The major scientific objectives of the UVS experiment at Mars and the characteristics of the UVS are described. The MUV spectra of geocoronal and interplanetary Lyman aemissions and lunar images taken at wavelength of hydrogen Lyman a and the background at 170 nm are presented as representative examples of the UVS observations during the Earth orbiting phase and the Mars transfer phase.

  12. Initial evaluation tests of General Electric Company 26.5 ampere-hour nickel-cadmium spacecraft cells with auxiliary electrodes for the TIROS-N and NOAA-A satellites

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1978-01-01

    This evaluation test program had the purpose to insure that all cells put into the life cycle program are of high quality by the screening of cells found to have electrolyte leakage, internal shorts, low capacity, or inability of any cell to recover its open-circuit voltage above 1.150 volts during the internal short test. Test limits specify those values at which a cell is to be terminated from charge or discharge. Requirements are referenced to as normally expected values based on past performance of aerospace nickel-cadmium cells with demonstrated life characteristics. A requirement does not constitute a limit for discontinuance from test.

  13. Multi-Functional Sandwich Composites for Spacecraft Applications: An Initial Assessment

    NASA Technical Reports Server (NTRS)

    Adams, Daniel O.; Webb, Nicholas Jason; Yarger, Cody B.; Hunter, Abigail; Oborn, Kelli D.

    2007-01-01

    Current spacecraft implement relatively uncoupled material and structural systems to address a variety of design requirements, including structural integrity, damage tolerance, radiation protection, debris shielding and thermal insulation. This investigation provided an initial assessment of multi-functional sandwich composites to integrate these diverse requirements. The need for radiation shielding was addressed through the selection of polymeric constituents with high hydrogen content. To provide increased damage tolerance and debris shielding, manufacturing techniques were developed to incorporate transverse stitching reinforcement, internal layers, and a self-healing ionomer membrane. To assess the effects of a space environment, thermal expansion behavior of the candidate foam materials was investigated under a vacuum and increasing temperature. Finally, a thermal expansion model was developed for foam under vacuum conditions and its predictive capability assessed.

  14. Initial evaluation tests of Eagle-Picher Industries 9.0 ampere-hour nickel-cadmium spacecraft cells for the heat capacity mapping mission satellite and the stratospheric aerosol and gas experiment satellite

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1978-01-01

    The results of tests to insure that all cells put into the life cycle program are of high quality are reported. The tests consisted of the following: phenolptalein leak tests, internal short test, charge efficiency test, and overcharge tests. The results of tests for 10 cells are tabulated.

  15. Particle-In-Cell simulations on spacecraft charging mitigation by plasma injection

    NASA Astrophysics Data System (ADS)

    Usui, Hideyuki; Imasato, Koujirou; Kuninaka, Hitoshi

    By performing three-dimensional Particle-In-Cell simulations, we have been investigating the time-dependent process of spacecraft charging mitigation by plasma injection. We particularly focus on the differential charging occurring between solar panel and spacecraft conducting part of spacecraft in the polar environment. In the presence of aurora electron beam, the absolute charging of spacecraft becomes the order of KeV as the worst case and the differential charging between the conducting surface of the spacecraft and the dielectric material on the solar panel can become several hundreds volts. To mitigate the charging, active plasma release from a plasma contactor onboard the spacecraft is proposed as one of the effective methods. In order to understand the charging mitigation process we started to examine the transient plasma process in terms of electron/ion flux to the spacecraft surface and the corresponding potential variation by performing 3D PIC simulations. In the simulation space, we set a spacecraft consisting of conducting body and dielectric film on the solar panels. This spacecraft system is immersed in isothermal magnetized plasma environment. We assume the aurora beam energy is around 100 eV. We started a simulation with no plasma emission from the body in order for the spacecraft to achieve a floating potential. Then, we start emitting plasma from the spacecraft surface from one side of the spacecraft. Due to the aurora current, the conducting part of the spacecraft was negatively charged around -50 V while the dielectric surface of the solar panel is about -30 V because of ion flux impinging at the ram side. In this case, approximately 20V differential charging occurs at the dielectric surface. In such a situation, we started emitting electrons from the spacecraft surface. Because of negative charge emission, the spacecraft potential increases and approaches to the plasma potential. This implies the absolute charging of spacecraft has been

  16. Pigment developed to protect spacecraft/solar cells from Sun's harmful rays.

    NASA Technical Reports Server (NTRS)

    1995-01-01

    A pigment (phthalocyanine) is studied at the Marshall Materials and Processes Lab. The pigment has the ability to protect spacecraft against the harmful effects of the Sun's ultraviolet rays, and to increase the efficiency and life of solar cells.

  17. Spacecraft Hybrid Control At NASA: A Look Back, Current Initiatives, and Some Future Considerations

    NASA Technical Reports Server (NTRS)

    Dennehy, Neil

    2014-01-01

    There is a heightened interest within NASA for the design, development, and flight implementation of mixed actuator hybrid attitude control systems for science spacecraft that have less than three functional reaction wheel actuators. This interest is driven by a number of recent reaction wheels failures on aging, but still scientifically productive, NASA spacecraft. This paper describes the highlights of the first NASA Cross-Center Hybrid Control Workshop that was held in Greenbelt, Maryland in April of 2013 under the sponsorship of the NASA Engineering and Safety Center (NESC). A brief historical summary of NASA's past experiences with spacecraft mixed actuator hybrid attitude control approaches, some of which were implemented on-orbit, will be provided. This paper will also convey some of the lessons learned and best practices captured at that workshop. Some relevant recent and current hybrid control activities will be described with an emphasis on work in support of a repurposed Kepler spacecraft. Specific technical areas for future considerations regarding spacecraft hybrid control will also be identified.

  18. Accelerated test program for sealed nickel-cadmium spacecraft batteries/cells

    NASA Technical Reports Server (NTRS)

    Goodman, L. A.

    1976-01-01

    The feasibility was examined of inducing an accelerated test on sealed Nickel-Cadmium batteries or cells as a tool for spacecraft projects and battery users to determine: (1) the prediction of life capability; (2) a method of evaluating the effect of design and component changes in cells; and (3) a means of reducing time and cost of cell testing.

  19. Initial Investigation of Reaction Control System Design on Spacecraft Handling Qualities for Earth Orbit Docking

    NASA Technical Reports Server (NTRS)

    Bailey, Randall E.; Jackson, E. Bruce; Goodrich, Kenneth H.; Ragsdale, W. Al; Neuhaus, Jason; Barnes, Jim

    2008-01-01

    A program of research, development, test, and evaluation is planned for the development of Spacecraft Handling Qualities guidelines. In this first experiment, the effects of Reaction Control System design characteristics and rotational control laws were evaluated during simulated proximity operations and docking. Also, the influence of piloting demands resulting from varying closure rates was assessed. The pilot-in-the-loop simulation results showed that significantly different spacecraft handling qualities result from the design of the Reaction Control System. In particular, cross-coupling between translational and rotational motions significantly affected handling qualities as reflected by Cooper-Harper pilot ratings and pilot workload, as reflected by Task-Load Index ratings. This influence is masked but only slightly by the rotational control system mode. While rotational control augmentation using Rate Command Attitude Hold can reduce the workload (principally, physical workload) created by cross-coupling, the handling qualities are not significantly improved. The attitude and rate deadbands of the RCAH introduced significant mental workload and control compensation to evaluate when deadband firings would occur, assess their impact on docking performance, and apply control inputs to mitigate that impact.

  20. Particle-In-Cell Simulations on Electric Field Antenna Characteristics in the Spacecraft Environment

    NASA Astrophysics Data System (ADS)

    Miyake, Y.; Usui, H.; Kojima, H.; Omura, Y.; Matsumoto, H.

    2006-12-01

    The Solar Terrestrial Physics (STP) group in Japan has organized a new magnetospheric mission named SCOPE whose objective is to investigate the scale-coupling process of plasma dynamics in the Terrestrial magnetosphere. For the sophisticated electric field measurements planned in the SCOPE mission, we have to investigate the antenna characteristics which are essential for the precise calibration of observed data. Particularly, (1) realistic antenna geometries including spacecraft body and (2) inhomogeneous plasma environment created by plasma-spacecraft interactions should be taken into consideration in the antenna analysis for application to the scientific mission. However, the analysis of the antenna impedance is very complex because the plasma is a dispersive and anisotropic medium, and thus it is too difficult to consider the realistic plasma environment near the spacecraft by the theoretical approaches. In the present study, we apply the Particle-In-Cell simulations to the antenna analysis, which enables us to treat the antenna model including a spacecraft body and analyze the effects of photoelectron emission on antenna characteristics. The present antenna model consists of perfect conducting antennas and spacecraft body, and the photoelectron emission from the sunlit surfaces is also modeled. Using these models, we first performed the electrostatic simulations and examined the photoelectron environment around the spacecraft. Next, the antenna impedance under the obtained photoelectron environment was examined by the electromagnetic simulations. Impedance values obtained in photoelectron environment were much different from those in free space, and they were analogous to the impedance characteristics of an equivalent electric circuit consisting of a resistance and capacitance connected in parallel. The validity of the obtained values has been examined by the comparison with the measurements by the scientific spacecraft.

  1. Computing Spacecraft Solar-Cell Damage by Charged Particles

    NASA Technical Reports Server (NTRS)

    Gaddy, Edward M.

    2006-01-01

    General EQFlux is a computer program that converts the measure of the damage done to solar cells in outer space by impingement of electrons and protons having many different kinetic energies into the measure of the damage done by an equivalent fluence of electrons, each having kinetic energy of 1 MeV. Prior to the development of General EQFlux, there was no single computer program offering this capability: For a given type of solar cell, it was necessary to either perform the calculations manually or to use one of three Fortran programs, each of which was applicable to only one type of solar cell. The problem in developing General EQFlux was to rewrite and combine the three programs into a single program that could perform the calculations for three types of solar cells and run in a Windows environment with a Windows graphical user interface. In comparison with the three prior programs, General EQFlux is easier to use.

  2. Initial Results from the Miniature Imager for Neutral Ionospheric Atoms and Magnetospheric Electrons (MINI-ME) on the FASTSAT Spacecraft

    NASA Technical Reports Server (NTRS)

    Collier, Michael R.; Rowland, Douglas; Keller, John W.; Chornay, Dennis; Khazanov, George; Herrero, Federico; Moore, Thomas E.; Kujawski, Joseph; Casas, Joseph C.; Wilson, Gordon

    2011-01-01

    The MINI-ME instrument is a collaborative effort between NASA's Goddard Space Flight Center (GSFC) and the U.S. Naval Academy, funded solely through GSFC Internal Research and Development (IRAD) awards. It detects neutral atoms from about 10 eV to about 700 eV (in 30 energy steps) in its current operating configuration with an approximately 10 degree by 360 degree field-of-view, divided into six sectors. The instrument was delivered on August 3, 2009 to Marshall Space Flight Center (MSFC) for integration with the FASTSAT-HSV01 small spacecraft bus developed by MSFC and a commercial partner, one of six Space Experiment Review Board (SERB) experiments on FASTSAT and one of three GSFC instruments (PISA and TTI being the other two). The FASTSAT spacecraft was launched on November 21, 2010 from Kodiak, Alaska on a Minotaur IV as a secondary payload and inserted into a 650 km, 72 degree inclination orbit, very nearly circular. MINI-ME has been collecting science data, as spacecraft resources would permit, in "optimal science mode" since January 20, 2011. In this presentation, we report initial science results including the potential first observations of neutral molecular ionospheric outflow. At the time of this abstract, we have identified 15 possible molecular outflow events. All these events occur between about 65 and 82 degrees geomagnetic latitude and most map to the auroral oval. The MINI-ME results provide an excellent framework for interpretation of the MILENA data, two instruments almost identical to MINI-ME that will launch on the VISIONS suborbital mission

  3. SSTI- Lewis Spacecraft Nickel-Hydrogen Battery

    NASA Technical Reports Server (NTRS)

    Tobias, R. F.

    1997-01-01

    Topics considered include: NASA-Small Spacecraft Technology Initiative (SSTI) objectives, SSTI-Lewis overview, battery requirement, two cells Common Pressure Vessel (CPV) design summary, CPV electric performance, battery design summary, battery functional description, battery performance.

  4. Spacecraft charging analysis with the implicit particle-in-cell code iPic3D

    SciTech Connect

    Deca, J.; Lapenta, G.; Marchand, R.; Markidis, S.

    2013-10-15

    We present the first results on the analysis of spacecraft charging with the implicit particle-in-cell code iPic3D, designed for running on massively parallel supercomputers. The numerical algorithm is presented, highlighting the implementation of the electrostatic solver and the immersed boundary algorithm; the latter which creates the possibility to handle complex spacecraft geometries. As a first step in the verification process, a comparison is made between the floating potential obtained with iPic3D and with Orbital Motion Limited theory for a spherical particle in a uniform stationary plasma. Second, the numerical model is verified for a CubeSat benchmark by comparing simulation results with those of PTetra for space environment conditions with increasing levels of complexity. In particular, we consider spacecraft charging from plasma particle collection, photoelectron and secondary electron emission. The influence of a background magnetic field on the floating potential profile near the spacecraft is also considered. Although the numerical approaches in iPic3D and PTetra are rather different, good agreement is found between the two models, raising the level of confidence in both codes to predict and evaluate the complex plasma environment around spacecraft.

  5. An 8 x 10 to the 5th bit bubble memory cell for spacecraft applications

    NASA Technical Reports Server (NTRS)

    Becker, F. J.; Murray, G. W.; Bohning, O. D.; Stermer, R. L.

    1980-01-01

    A multiple chip magnetic bubble memory cell design developed for NASA embodies the low power, low weight, environmental tolerance and reliability necessary for successful operation in spacecraft launch and mission environments. Packaging of multiple chips in a common magnetic bias, drive coil assembly reduces weight and volume overhead per chip and also reduces the number of coil drive components required. This 8 x 10 to the 5th bit cell is conduction cooled and provides a metal and ceramic sealed hermetic chip environment.

  6. Three-Dimensional Particle-In-Cell Simulations on Active Mitigation of Spacecraft Charging in the Earth's Polar Region

    NASA Astrophysics Data System (ADS)

    Usui, Hideyuki; Imasato, Koujiro; Kuninaka, Hitoshi

    2008-12-01

    We focus on the mitigation process of absolute and differential charging of spacecraft in the polar environment by plasma release from the spacecraft surface. In the presence of aurora electron beam, the absolute charging of spacecraft sometimes becomes the order of KeV at the worst case and the differential charging between the conducting surface of the spacecraft and the dielectric material on the solar panel can become several hundred volts. To avoid the discharge due to the differential charging at the solar panel, plasma release from a plasma contactor onboard the spacecraft is proposed as one of the effective methods. In the current study, we performed three-dimensional Particle-In-Cell simulations to examine the situation of spacecraft charging and its mitigation process by plasma release from the spacecraft surface. To mitigate the absolute charging, we showed the electron release is effective. The released electrons are accelerated away from the spacecraft by the intense electric field induced in the ion sheath at the spacecraft surface. As to the mitigation of differential voltage at the solar panel surface, we showed that ion release in addition to electrons from the contactor is effective. The released ions can neutralize the charges locally accumulated on the dielectric surface. Their dynamics including gyromotion with respect to the geomagnetic field and acceleration along the geomagnetic field can perturb the field and plasma environment in the spacecraft region.

  7. Advanced Dependent Pressure Vessel (DPV) Nickel-Hydrogen Spacecraft Cell and Battery Design

    NASA Technical Reports Server (NTRS)

    Coates, Dwaine K.; Wright, R. Doug; Repplinger, Ron S.

    1996-01-01

    The dependent pressure vessel (DPV) nickel-hydrogen (Ni-H2) battery is being developed as a potential spacecraft battery design for both military and commercial satellites. Individual pressure vessel (IPV) Ni-H2 batteries are currently flying on more than 70 Earth-orbiting satellites and have accumulated more that 140,000,000 cell-hours in actual spacecraft operation. The limitations of standard Ni-H2 IPV flight battery technology are primarily related to the internal cell design and the battery packaging issues associated with grouping multiple cylindrical cells. The DPV cell design offers higher specific energy and reduced cost, while retaining the established IPV Ni-H2 technology flight heritage and database. A design performance analysis is presented at both the cell and battery level. The DPV is capable of delivering up to 76 Watthours per kilogram (Wh/kg) at the cell level and 70 Wh/kg at the full battery level. This represents a 40 percent increase in specific energy at the cell level and a 60 percent increase in specific energy at the battery level compared to current IPV Ni-H2 technology.

  8. A Scattered Light Correction to Color Images Taken of Europa by the Galileo Spacecraft: Initial Results

    NASA Astrophysics Data System (ADS)

    Phillips, C. B.; Valenti, M.

    2009-12-01

    interfaces of lenses. Because of the wavelength dependence of this effect, a scattered light correction must be performed on any SSI multispectral dataset before quantitative spectral analysis can be done. The process involves using a point-spread function for each filter that helps determine the amount of scattered light expected for a given pixel based on its location and the model attenuation factor for that pixel. To remove scattered light for a particular image taken through a particular filter, the Fourier transform of the attenuation function, which is the point spread function for that filter, is convolved with the Fourier transform of the image at the same wavelength. The result is then filtered for noise in the frequency domain, and then transformed back to the spatial domain. This results in a version of the original image that would have been taken without the scattered light contribution. We will report on our initial results from this calibration.

  9. CPIC: A Parallel Particle-In-Cell Code for Studying Spacecraft Charging

    NASA Astrophysics Data System (ADS)

    Meierbachtol, Collin; Delzanno, Gian Luca; Moulton, David; Vernon, Louis

    2015-11-01

    CPIC is a three-dimensional electrostatic particle-in-cell code designed for use with curvilinear meshes. One of its primary objectives is to aid in studying spacecraft charging in the magnetosphere. CPIC maintains near-optimal computational performance and scaling thanks to a mapped logical mesh field solver, and a hybrid physical-logical space particle mover (avoiding the need to track particles). CPIC is written for parallel execution, utilizing a combination of both OpenMP threading and MPI distributed memory. New capabilities are being actively developed and added to CPIC, including the ability to handle multi-block curvilinear mesh structures. Verification results comparing CPIC to analytic test problems will be provided. Particular emphasis will be placed on the charging and shielding of a sphere-in-plasma system. Simulated charging results of representative spacecraft geometries will also be presented. Finally, its performance capabilities will be demonstrated through parallel scaling data.

  10. Tumor initiating cells in malignant gliomas

    PubMed Central

    Hadjipanayis, Costas G.; Van Meir, Erwin G.

    2009-01-01

    A rare subpopulation of cells within malignant gliomas, which shares canonical properties with neural stem cells (NSCs), may be integral to glial tumor development and perpetuation. These cells, also known as tumor initiating cells (TICs), have the ability to self-renew, develop into any cell in the overall tumor population (multipotency), and proliferate. A defining property of TICs is their ability to initiate new tumors in immunocompromised mice with high efficiency. Mounting evidence suggests that TICs originate from the transformation of NSCs and their progenitors. New findings show that TICs may be more resistant to chemotherapy and radiation than the bulk of tumor cells, thereby permitting recurrent tumor formation and accounting for the failure of conventional therapies. The development of new therapeutic strategies selectively targeting TICs while sparing NSCs may provide for more effective treatment of malignant gliomas. PMID:19189072

  11. Advanced Dependent Pressure Vessel (DPV) nickel-hydrogen spacecraft cell and battery design

    NASA Technical Reports Server (NTRS)

    Coates, Dwaine; Wright, Doug; Repplinger, Ron

    1995-01-01

    The dependent pressure vessel (DPV) nickel-hydrogen (NiH2) battery is being developed as a potential spacecraft battery design for both military and commercial satellites. Individual pressure vessel (IPV) NiH2 batteries are currently flying on more than 70 Earth orbital satellites and have accumulated more than 140,000,000 cell-hours in actual spacecraft operation. The limitations of standard NiH2 IPV flight battery technology are primarily related to the internal cell design and the battery packaging issues associated with grouping multiple cylindrical cells. The DPV cell design offers higher specific energy and reduced cost, while retaining the established IPV NiH2 technology flight heritage and database. The advanced cell design offers a more efficient mechanical, electrical and thermal cell configuration and a reduced parts count. The internal electrode stack is a prismatic flat-plate arrangement. The flat individual cell pressure vessel provides a maximum direct thermal path for removing heat from the electrode stack. The cell geometry also minimizes multiple-cell battery packaging constraints by using an established end-plateltie-rod battery design. A major design advantage is that the battery support structure is efficiently required to restrain only the force applied to a portion of the end cell. As the cells are stacked in series to achieve the desired system voltage, this increment of the total battery weight becomes small. The geometry of the DPV cell promotes compact, minimum volume packaging and places all cell terminals along the length of the battery. The resulting ability to minimize intercell wiring offers additional design simplicity and significant weight savings. The DPV battery design offers significant cost and weight savings advantages while providing minimal design risks. Cell and battery level design issues will be addressed including mechanical, electrical and thermal design aspects. A design performance analysis will be presented at both

  12. Advanced Dependent Pressure Vessel (DPV) nickel-hydrogen spacecraft cell and battery design

    NASA Astrophysics Data System (ADS)

    Coates, Dwaine; Wright, Doug; Repplinger, Ron

    1995-04-01

    The dependent pressure vessel (DPV) nickel-hydrogen (NiH2) battery is being developed as a potential spacecraft battery design for both military and commercial satellites. Individual pressure vessel (IPV) NiH2 batteries are currently flying on more than 70 Earth orbital satellites and have accumulated more than 140,000,000 cell-hours in actual spacecraft operation. The limitations of standard NiH2 IPV flight battery technology are primarily related to the internal cell design and the battery packaging issues associated with grouping multiple cylindrical cells. The DPV cell design offers higher specific energy and reduced cost, while retaining the established IPV NiH2 technology flight heritage and database. The advanced cell design offers a more efficient mechanical, electrical and thermal cell configuration and a reduced parts count. The internal electrode stack is a prismatic flat-plate arrangement. The flat individual cell pressure vessel provides a maximum direct thermal path for removing heat from the electrode stack. The cell geometry also minimizes multiple-cell battery packaging constraints by using an established end-plateltie-rod battery design. A major design advantage is that the battery support structure is efficiently required to restrain only the force applied to a portion of the end cell. As the cells are stacked in series to achieve the desired system voltage, this increment of the total battery weight becomes small. The geometry of the DPV cell promotes compact, minimum volume packaging and places all cell terminals along the length of the battery. The resulting ability to minimize intercell wiring offers additional design simplicity and significant weight savings. The DPV battery design offers significant cost and weight savings advantages while providing minimal design risks. Cell and battery level design issues will be addressed including mechanical, electrical and thermal design aspects. A design performance analysis will be presented at both

  13. 270V Battery Using COTS NiCd Cells For Manned Spacecraft

    NASA Technical Reports Server (NTRS)

    Darcy, Eric; Davies,Frank; Hummer, Leigh; Strangways, Brad

    2002-01-01

    A high power (>35 kW at 215V), low capacity (5.2 Ah), and compact (45L) NiCd battery was developed for the X-38 Crew Return Vehicle (CRV), which is an experimental version of the lifeboat for the International Space Station (ISS). A simple design and innovative approach using a commercial-off-the-shelf (COTS) NiCd cell design enabled the design, qualification, and production of 4 flight units of this highly reliable and safe spacecraft battery to be achieved rapidly (2 years) and cheaply ($13M).

  14. An Experiment To Demonstrate Spacecraft Power Beaming and Solar Cell Annealing Using High-Energy Lasers

    NASA Astrophysics Data System (ADS)

    Luce, Richard; Michael, Sherif

    2003-05-01

    Satellite lifetime is often limited by degradation of the electrical power subsystem, e.g. radiation-damaged solar arrays or failed batteries. Being able to beam power from terrestrial sites could alleviate this limitation, extending the lifetime of billions of dollars of satellite assets, as well as providing additional energy for electric propulsion that can be used for stationkeeping and orbital changes. In addition, laboratory research at the Naval Postgraduate School (NPS) has shown the potential to anneal damaged solar cells using lasers. This paper describes that research and a proposed Maui experiment to demonstrate the relevant concepts by lasing PANSAT, an NPS-built and operated spacecraft.

  15. Infrared Studies of the Reflective Properties of Solar Cells and the HS376 Spacecraft

    NASA Technical Reports Server (NTRS)

    Frith, James; Reyes, Jacqueline; Cowardin, Heather; Anz-Meador, Phillip; Buckalew, Brent; Lederer, Susan

    2016-01-01

    In 2015, a selection of HS-376 buses were observed photometrically with the United Kingdom Infrared Telescope (UKIRT) to explore relationships between time-on-orbit and Near Infrared (NIR) color. These buses were chosen because of their relatively simple shape, for the abundance of similar observable targets, and their surface material being primarily covered by solar cells. While the HS-376 spacecraft were all very similar in design, differences in the specific solar cells used in the construction of each model proved to be an unconstrained variable that could affect the observed reflective properties. In 2016, samples of the solar cells used on various models of HS-376 spacecraft were obtained from Boeing and were analyzed in the Optical Measurements Center at the Johnson Space Center using a visible-near infrared field spectrometer. The laboratory-based spectra are convolved to match the photometric bands previously obtained using UKIRT and compared with the on-orbit photometry. The results and future work are discussed here.

  16. Apoptotic Cells Initiate Endothelial Cell Sprouting via Electrostatic Signaling

    PubMed Central

    Weihua, Zhang; Tsan, Rachel; Schroit, Alan J.; Fidler, Isaiah J.

    2006-01-01

    Angiogenesis, the development of new blood vessels from preexisting vessels, is crucial to tissue growth, repair, and maintenance. This process begins with the formation of endothelial cell sprouts followed by the proliferation and migration of neighboring endothelial cells along the pre-formed extensions. The initiating event and mechanism of sprouting is not known. We demonstrate that the phenotypic expression of negative-charged membrane surface in apoptotic cells initiates the formation of directional endothelial cell sprouts that extend toward the dying cells by a mechanism that involves endothelial cell membrane hyperpolarization and cytoskeleton reorganization but is independent of diffusible molecules. PMID:16357162

  17. Signaling to stomatal initiation and cell division

    PubMed Central

    Le, Jie; Zou, Junjie; Yang, Kezhen; Wang, Ming

    2014-01-01

    Stomata are two-celled valves that control epidermal pores whose opening and spacing optimizes shoot-atmosphere gas exchange. Arabidopsis stomatal formation involves at least one asymmetric division and one symmetric division. Stomatal formation and patterning are regulated by the frequency and placement of asymmetric divisions. This model system has already led to significant advances in developmental biology, such as the regulation of cell fate, division, differentiation, and patterning. Over the last 30 years, stomatal development has been found to be controlled by numerous intrinsic genetic and environmental factors. This mini review focuses on the signaling involved in stomatal initiation and in divisions in the cell lineage. PMID:25002867

  18. Signaling to stomatal initiation and cell division.

    PubMed

    Le, Jie; Zou, Junjie; Yang, Kezhen; Wang, Ming

    2014-01-01

    Stomata are two-celled valves that control epidermal pores whose opening and spacing optimizes shoot-atmosphere gas exchange. Arabidopsis stomatal formation involves at least one asymmetric division and one symmetric division. Stomatal formation and patterning are regulated by the frequency and placement of asymmetric divisions. This model system has already led to significant advances in developmental biology, such as the regulation of cell fate, division, differentiation, and patterning. Over the last 30 years, stomatal development has been found to be controlled by numerous intrinsic genetic and environmental factors. This mini review focuses on the signaling involved in stomatal initiation and in divisions in the cell lineage. PMID:25002867

  19. International Low-Earth-Orbit Spacecraft Materials Test Program Initiated for Better Prediction of Durability and Performance

    NASA Technical Reports Server (NTRS)

    Rutledge, Sharon K.

    1999-01-01

    Spacecraft in low Earth orbit (LEO) are subjected to many components of the environment, which can cause them to degrade much more rapidly than intended and greatly shorten their functional life. The atomic oxygen, ultraviolet radiation, and cross contamination present in LEO can affect sensitive surfaces such as thermal control paints, multilayer insulation, solar array surfaces, and optical surfaces. The LEO Spacecraft Materials Test (LEO-SMT) program is being conducted to assess the effects of simulated LEO exposure on current spacecraft materials to increase understanding of LEO degradation processes as well as to enable the prediction of in-space performance and durability. Using ground-based simulation facilities to test the durability of materials currently flying in LEO will allow researchers to compare the degradation evidenced in the ground-based facilities with that evidenced on orbit. This will allow refinement of ground laboratory test systems and the development of algorithms to predict the durability and performance of new materials in LEO from ground test results. Accurate predictions based on ground tests could reduce development costs and increase reliability. The wide variety of national and international materials being tested represent materials being functionally used on spacecraft in LEO. The more varied the types of materials tested, the greater the probability that researchers will develop and validate predictive models for spacecraft long-term performance and durability. Organizations that are currently participating in the program are ITT Research Institute (USA), Lockheed Martin (USA), MAP (France), SOREQ Nuclear Research Center (Israel), TNO Institute of Applied Physics (The Netherlands), and UBE Industries, Ltd. (Japan). These represent some of the major suppliers of thermal control and sensor materials currently flying in LEO. The participants provide materials that are exposed to selected levels of atomic oxygen, vacuum ultraviolet

  20. CDC20 maintains tumor initiating cells

    PubMed Central

    Xie, Qi; Wu, Qiulian; Mack, Stephen C.; Yang, Kailin; Kim, Leo; Hubert, Christopher G.; Flavahan, William A.; Chu, Chengwei; Bao, Shideng; Rich, Jeremy N.

    2015-01-01

    Glioblastoma is the most prevalent and lethal primary intrinsic brain tumor. Glioblastoma displays hierarchical arrangement with a population of self-renewing and tumorigenic glioma tumor initiating cells (TICs), or cancer stem cells. While non-neoplastic neural stem cells are generally quiescent, glioblastoma TICs are often proliferative with mitotic control offering a potential point of fragility. Here, we interrogate the role of cell-division cycle protein 20 (CDC20), an essential activator of anaphase-promoting complex (APC) E3 ubiquitination ligase, in the maintenance of TICs. By chromatin analysis and immunoblotting, CDC20 was preferentially expressed in TICs relative to matched non-TICs. Targeting CDC20 expression by RNA interference attenuated TIC proliferation, self-renewal and in vivo tumor growth. CDC20 disruption mediated its effects through induction of apoptosis and inhibition of cell cycle progression. CDC20 maintains TICs through degradation of p21CIP1/WAF1, a critical negative regulator of TICs. Inhibiting CDC20 stabilized p21CIP1/WAF1, resulting in repression of several genes critical to tumor growth and survival, including CDC25C, c-Myc and Survivin. Transcriptional control of CDC20 is mediated by FOXM1, a central transcription factor in TICs. These results suggest CDC20 is a critical regulator of TIC proliferation and survival, linking two key TIC nodes – FOXM1 and p21CIP1/WAF1 — elucidating a potential point for therapeutic intervention. PMID:25938542

  1. Particle-in-cell simulation of spacecraft/plasma interactions in the vicinity of Enceladus

    NASA Astrophysics Data System (ADS)

    Yaroshenko, V. V.; Miloch, W. J.; Lühr, H.

    2015-09-01

    The Cassini Langmuir Probe of the Radio and Plasma Wave Science instrument has measured an electron depletion in a region extending at least 50 satellite radii away from Saturn's small but geologically active icy moon Enceladus. The maximal imbalance between the electron and ion densities was observed in the dust loaded plume and to date is attributed to the electron attachment to abundant dust grains. We report the results from a three dimensional particle-in-cell simulation of a plasma structure formed around a charged spacecraft in the conditions relevant inside the Enceladus torus and in the moon's plume. In addition to the plasma population the plume simulation includes singly charged nanograins detected by the Cassini Plasma Spectrometer. The accompanied spacecraft plasma perturbations can significantly modify an ambient plasma at the Cassini Langmuir probe positions and thus impact the plasma measurements. Our modeling reveals a domination of water group ions over the electron population due to the formation of a conventional plasma sheath at the ram-oriented probe positions in the Enceladus torus and in the plume regions with low dust density (nd0 ne0) the plasma perturbations are strongly reduced in the ram direction but can significantly compromise the probe measurements in the orbiter wake. Simulation results can qualitatively explain the long profiles of the electron-ion imbalance registered by the Cassini Langmuir probe during the flybys E2, E3 and E5. In either case, the plasma perturbations associated with the moving Cassini orbiter appear to be important for reliable interpretations of the Langmuir probe measurements.

  2. An initial investigation of the long-term trends in the fluxgate magnetometer (FGM) calibration parameters on the four Cluster spacecraft

    NASA Astrophysics Data System (ADS)

    Alconcel, L. N. S.; Fox, P.; Brown, P.; Oddy, T. M.; Lucek, E. L.; Carr, C. M.

    2014-07-01

    Over the course of more than 10 years in operation, the calibration parameters of the outboard fluxgate magnetometer (FGM) sensors on the four Cluster spacecraft are shown to be remarkably stable. The parameters are refined on the ground during the rigorous FGM calibration process performed for the Cluster Active Archive (CAA). Fluctuations in some parameters show some correlation with trends in the sensor temperature (orbit position). The parameters, particularly the offsets, of the spacecraft 1 (C1) sensor have undergone more long-term drift than those of the other spacecraft (C2, C3 and C4) sensors. Some potentially anomalous calibration parameters have been identified and will require further investigation in future. However, the observed long-term stability demonstrated in this initial study gives confidence in the accuracy of the Cluster magnetic field data. For the most sensitive ranges of the FGM instrument, the offset drift is typically 0.2 nT per year in each sensor on C1 and negligible on C2, C3 and C4.

  3. An initial investigation of the long-term trends in the fluxgate magnetometer (FGM) calibration parameters on the four Cluster spacecraft

    NASA Astrophysics Data System (ADS)

    Alconcel, L. N. S.; Fox, P.; Brown, P.; Oddy, T. M.; Lucek, E. L.; Carr, C. M.

    2014-01-01

    Over the course of more than ten years in operation, the calibration parameters of the outboard fluxgate magnetometer (FGM) sensors on the four Cluster spacecraft are shown to be remarkably stable. The parameters are refined on the ground during the rigorous FGM calibration process performed for the Cluster Active Archive (CAA). Fluctuations in some parameters show some correlation with trends in the sensor temperature (orbit position). The parameters, particularly the offsets, of the Spacecraft1 (C1) sensor have undergone more long-term drift than those of the other spacecraft (C2, C3 and C4) sensors. Some potentially anomalous calibration parameters have been identified and will require further investigation in future. However, the observed long-term stability demonstrated in this initial study gives confidence in the relative accuracy of the Cluster magnetic field data. For the most sensitive ranges of the FGM instrument, the offset drift is typically 0.2 nT yr-1 in each sensor on C1 and negligible on C2, C3 and C4.

  4. Tumor-Initiating Cells and Methods of Use

    NASA Technical Reports Server (NTRS)

    Hlatky, Lynn (Inventor)

    2014-01-01

    Provided herein are an isolated or enriched population of tumor initiating cells derived from normal cells, cells susceptible to neoplasia, or neoplastic cells. Methods of use of the cells for screening for anti-hyperproliferative agents, and use of the cells for animal models of hyperproliferative disorders including metastatic cancer, diagnostic methods, and therapeutic methods are provided.

  5. Evaluation Program for Secondary Spacecraft Cells: Synchronous Orbit Testing of Sealed Nickel Cadmium Cells

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1977-01-01

    Performance data concerning sealed nickel-cadmium cells operating under a synchronous orbit regime are presented. A space satellite maintaining a position over a fixed point on earth as the earth rotates on its axis and revolves about the sun was simulated. Results include: (1) exposure to synchronous orbit testing at a temperature of 40 C yields less than 6 years of life; (2) performance at -20 C presents a low capacity problem; (3) the capacity check, performed at the middle of each show period, provides a temporary red reconditioning effect on the cells in that the end-of-discharge voltages are higher, for approximately 7 to 10 days, following the capacity check than they were 7 to 10 days prior to the capacity check; (4) all the test packs at -20 C and 40 C have either failed or were discontinued because of low capacity; and (5) test packs at temperatures of 0 C and 10 C have delivered the best capacity during life and packs tested at 20 C showed better life capability than packs tested at -20 C and 40 C.

  6. Spacecraft 2000

    NASA Technical Reports Server (NTRS)

    1986-01-01

    The objective of the Workshop was to focus on the key technology area for 21st century spacecraft and the programs needed to facilitate technology development and validation. Topics addressed include: spacecraft systems; system development; structures and materials; thermal control; electrical power; telemetry, tracking, and control; data management; propulsion; and attitude control.

  7. The Development of Fuel Cell Technology for Electric Power Generation - From Spacecraft Applications to the Hydrogen Economy

    NASA Technical Reports Server (NTRS)

    Scott, John H.

    2005-01-01

    The fuel cell uses a catalyzed reaction between a fuel and an oxidizer to directly produce electricity. Its high theoretical efficiency and low temperature operation made it a subject of much study upon its invention ca. 1900, but its relatively high life cycle costs kept it as "solution in search of a problem" for its first half century. The first problem for which fuel cells presented a cost effective solution was, starting in the 1960's that of a power source for NASA's manned spacecraft. NASA thus invested, and continues to invest, in the development of fuel cell power plants for this application. However, starting in the mid-1990's, prospective environmental regulations have driven increased governmental and industrial interest in "green power" and the "Hydrogen Economy." This has in turn stimulated greatly increased investment in fuel cell development for a variety of terrestrial applications. This investment is bringing about notable advances in fuel cell technology, but these advances are often in directions quite different from those needed for NASA spacecraft applications. This environment thus presents both opportunities and challenges for NASA's manned space program.

  8. Photovoltaic concentrator initiative: Concentrator cell development

    SciTech Connect

    Wohlgemuth, J.H.; Narayanan, S.

    1993-05-01

    This project involves the development of a large-area, low-cost, high-efficiency concentrator solar cell for use in the Entech 22-sun linear-focus Fresnel lens concentrator system. The buried contact solar cell developed at the University of New South Wales was selected for this project. Both Entech and the University of New South Wales are subcontractors. This annual report presents the program efforts from November 1990 through December 1991, including the design of the cell, development of a baseline cell process, and presentation of the results of preliminary cell processing. Important results include a cell designed for operation in a real concentrator system and substitution of mechanical grooving for the previously utilized laser scribing.

  9. Internet Access to Spacecraft

    NASA Technical Reports Server (NTRS)

    Rash, James; Parise, Ron; Hogie, Keith; Criscuolo, Ed; Langston, Jim; Jackson, Chris; Price, Harold; Powers, Edward I. (Technical Monitor)

    2000-01-01

    The Operating Missions as Nodes on the Internet (OMNI) project at NASA's Goddard Space flight Center (GSFC), is demonstrating the use of standard Internet protocols for spacecraft communication systems. This year, demonstrations of Internet access to a flying spacecraft have been performed with the UoSAT-12 spacecraft owned and operated by Surrey Satellite Technology Ltd. (SSTL). Previously, demonstrations were performed using a ground satellite simulator and NASA's Tracking and Data Relay Satellite System (TDRSS). These activities are part of NASA's Space Operations Management Office (SOMO) Technology Program, The work is focused on defining the communication architecture for future NASA missions to support both NASA's "faster, better, cheaper" concept and to enable new types of collaborative science. The use of standard Internet communication technology for spacecraft simplifies design, supports initial integration and test across an IP based network, and enables direct communication between scientists and instruments as well as between different spacecraft, The most recent demonstrations consisted of uploading an Internet Protocol (IP) software stack to the UoSAT- 12 spacecraft, simple modifications to the SSTL ground station, and a series of tests to measure performance of various Internet applications. The spacecraft was reconfigured on orbit at very low cost. The total period between concept and the first tests was only 3 months. The tests included basic network connectivity (PING), automated clock synchronization (NTP), and reliable file transfers (FTP). Future tests are planned to include additional protocols such as Mobile IP, e-mail, and virtual private networks (VPN) to enable automated, operational spacecraft communication networks. The work performed and results of the initial phase of tests are summarized in this paper. This work is funded and directed by NASA/GSFC with technical leadership by CSC in arrangement with SSTL, and Vytek Wireless.

  10. Initial TMX central-cell ICRH experiments

    SciTech Connect

    Molvik, A.W.; Coffield, F.E.; Falabella, S.; Griffin, D.; McVey, B.; Pickles, W.; Poulsen, P.; Simonen, T.C.; Yugo, J.

    1980-12-09

    Four topics are discussed in this report: the feasibility of applying ion cyclotron resonance heating (ICRH) in the TMX central cell, some applications of heating, the results of preliminary experiments, and plans for further ICRH experiments.

  11. Microfold Cells Actively Translocate Mycobacterium tuberculosis to Initiate Infection.

    PubMed

    Nair, Vidhya R; Franco, Luis H; Zacharia, Vineetha M; Khan, Haaris S; Stamm, Chelsea E; You, Wu; Marciano, Denise K; Yagita, Hideo; Levine, Beth; Shiloh, Michael U

    2016-08-01

    The prevailing paradigm is that tuberculosis infection is initiated when patrolling alveolar macrophages and dendritic cells within the terminal alveolus ingest inhaled Mycobacterium tuberculosis (Mtb). However, definitive data for this model are lacking. Among the epithelial cells of the upper airway, a specialized epithelial cell known as a microfold cell (M cell) overlies various components of mucosa-associated lymphatic tissue. Here, using multiple mouse models, we show that Mtb invades via M cells to initiate infection. Intranasal Mtb infection in mice lacking M cells either genetically or by antibody depletion resulted in reduced invasion and dissemination to draining lymph nodes. M cell-depleted mice infected via aerosol also had delayed dissemination to lymph nodes and reduced mortality. Translocation of Mtb across two M cell transwell models was rapid and transcellular. Thus, M cell translocation is a vital entry mechanism that contributes to the pathogenesis of Mtb. PMID:27452467

  12. The role of initial cells in maize anther morphogenesis.

    PubMed

    Dawe, R K; Freeling, M

    1992-12-01

    The near absence of cell movement in plants makes clonal analysis a particularly informative method for reconstructing the early events of organ formation. We traced the patterns of cell division during maize anther development by inducing sector boundaries that preceded the earliest events of anther initiation. In doing this, we were able to estimate the smallest number of cells that are fated to form an anther, characteristic cell division patterns that occur during anther morphogenesis, and the relationship between the pre-existing symmetry of the initial cells and the final symmetry of the mature anther. Four general conclusions are made: (1) anthers are initiated from small groups of 12 or fewer cells in each of two floral meristematic layers; (2) the early growth of the anther is more like a shoot than a glume or leaf; (3) cell ancestry does not dictate basic structure and (4) the orientation of initial cells predicts the orientation of the four pollen-containing microsporangia, which define the axes of symmetry on the mature anther. The final point is discussed with other data, and an explanation involving a 'structural template' is invoked. The idea is that the orientation of initial cells within the floral meristem establishes an architectural pattern into which anther cells are recruited without regard to their cellular lineages. The structural template hypothesis may prove to be generally applicable to problems of pattern formation in plants. PMID:1295730

  13. Cassini Spacecraft

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Jet Propulsion Research Lab (JPL) workers use a borescope to verify the pressure relief device bellow's integrity on a radioisotope thermoelectric generator (RTG) that has been installed on the Cassini spacecraft in the Payload Hazardous Servicing Facility. The activity is part of the mechanical and electrical verification testing of RTGs during prelaunch processing. RTGs use heat from the natural decay of plutonium to generate electrical power. The three RTGs on Cassini will enable the spacecraft to operate far from the Sun where solar power systems are not feasible. They will provide electrical power to Cassini on it seven year trip to the Saturnian system and during its four year mission at Saturn.

  14. Spacecraft sterilization.

    NASA Technical Reports Server (NTRS)

    Kalfayan, S. H.

    1972-01-01

    Spacecraft sterilization is a vital factor in projects for the successful biological exploration of other planets. The microorganisms of major concern are the fungi and bacteria. Sterilization procedures are oriented toward the destruction of bacterial spores. Gaseous sterilants are examined, giving attention to formaldehyde, beta-propiolactone, ethylene oxide, and the chemistry of the bactericidal action of sterilants. Radiation has been seriously considered as another method for spacecraft sterilization. Dry heat sterilization is discussed together with the effects of ethylene oxide decontamination and dry heat sterilization on materials.

  15. Spacecraft architecture

    NASA Technical Reports Server (NTRS)

    Zefeld, V. V.

    1986-01-01

    Three requirements for a spacecraft interior are considered. Adequate motor activity in the anatomical-physiological sense results from attention to the anthropometric characteristics of humans. Analysis of work requirements is a prerequisite for the planning of adequate performance space. The requirements for cognitive activity are also elucidated. The importance of a well-designed interior during a long space flight is discussed.

  16. Internet Technology on Spacecraft

    NASA Technical Reports Server (NTRS)

    Rash, James; Parise, Ron; Hogie, Keith; Criscuolo, Ed; Langston, Jim; Powers, Edward I. (Technical Monitor)

    2000-01-01

    The Operating Missions as Nodes on the Internet (OMNI) project has shown that Internet technology works in space missions through a demonstration using the UoSAT-12 spacecraft. An Internet Protocol (IP) stack was installed on the orbiting UoSAT-12 spacecraft and tests were run to demonstrate Internet connectivity and measure performance. This also forms the basis for demonstrating subsequent scenarios. This approach provides capabilities heretofore either too expensive or simply not feasible such as reconfiguration on orbit. The OMNI project recognized the need to reduce the risk perceived by mission managers and did this with a multi-phase strategy. In the initial phase, the concepts were implemented in a prototype system that includes space similar components communicating over the TDRS (space network) and the terrestrial Internet. The demonstration system includes a simulated spacecraft with sample instruments. Over 25 demonstrations have been given to mission and project managers, National Aeronautics and Space Administration (NASA), Department of Defense (DoD), contractor technologists and other decisions makers, This initial phase reached a high point with an OMNI demonstration given from a booth at the Johnson Space Center (JSC) Inspection Day 99 exhibition. The proof to mission managers is provided during this second phase with year 2000 accomplishments: testing the use of Internet technologies onboard an actual spacecraft. This was done with a series of tests performed using the UoSAT-12 spacecraft. This spacecraft was reconfigured on orbit at very low cost. The total period between concept and the first tests was only 6 months! On board software was modified to add an IP stack to support basic IP communications. Also added was support for ping, traceroute and network timing protocol (NTP) tests. These tests show that basic Internet functionality can be used onboard spacecraft. The performance of data was measured to show no degradation from current

  17. The New Horizons Spacecraft

    NASA Astrophysics Data System (ADS)

    Fountain, Glen H.; Kusnierkiewicz, David Y.; Hersman, Christopher B.; Herder, Timothy S.; Coughlin, Thomas B.; Gibson, William C.; Clancy, Deborah A.; Deboy, Christopher C.; Hill, T. Adrian; Kinnison, James D.; Mehoke, Douglas S.; Ottman, Geffrey K.; Rogers, Gabe D.; Stern, S. Alan; Stratton, James M.; Vernon, Steven R.; Williams, Stephen P.

    2008-10-01

    The New Horizons spacecraft was launched on 19 January 2006. The spacecraft was designed to provide a platform for seven instruments designated by the science team to collect and return data from Pluto in 2015. The design meets the requirements established by the National Aeronautics and Space Administration (NASA) Announcement of Opportunity AO-OSS-01. The design drew on heritage from previous missions developed at The Johns Hopkins University Applied Physics Laboratory (APL) and other missions such as Ulysses. The trajectory design imposed constraints on mass and structural strength to meet the high launch acceleration consistent with meeting the AO requirement of returning data prior to the year 2020. The spacecraft subsystems were designed to meet tight resource allocations (mass and power) yet provide the necessary control and data handling finesse to support data collection and return when the one-way light time during the Pluto fly-by is 4.5 hours. Missions to the outer regions of the solar system (where the solar irradiance is 1/1000 of the level near the Earth) require a radioisotope thermoelectric generator (RTG) to supply electrical power. One RTG was available for use by New Horizons. To accommodate this constraint, the spacecraft electronics were designed to operate on approximately 200 W. The travel time to Pluto put additional demands on system reliability. Only after a flight time of approximately 10 years would the desired data be collected and returned to Earth. This represents the longest flight duration prior to the return of primary science data for any mission by NASA. The spacecraft system architecture provides sufficient redundancy to meet this requirement with a probability of mission success of greater than 0.85. The spacecraft is now on its way to Pluto, with an arrival date of 14 July 2015. Initial in-flight tests have verified that the spacecraft will meet the design requirements.

  18. Docking mechanism for spacecraft

    NASA Technical Reports Server (NTRS)

    Lange, Gregory A. (Inventor); Mcmanamen, John P. (Inventor); Schliesing, John A. (Inventor)

    1989-01-01

    A system is presented for docking a space vehicle to a space station where a connecting tunnel for in-flight transfer of personnel is required. Cooperable coupling mechanisms include docking rings on the space vehicle and space station. The space station is provided with a tunnel structure, a retraction mechanism, and a docking ring. The vehicle coupling mechanism is designed to capture the station coupling mechanism, arrest relative spacecraft motions while limiting loads to acceptable levels, and then realign the spacecraft for final docking and tunnel interconnection. The docking ring of the space vehicle coupling mechanism is supported by linear attentuator actuator devices, each of which is controlled by a control system which receives loading information signals and attenuator stroke information signals from each device and supplies output signals for controlling its linear actuation to attenuate impact loading or to realign the spacecraft for final docking and tunnel interconnection. The retraction mechanism is used to draw the spacecraft together after initial contact and coupling. Tunnel trunnions, cooperative with the latches on the space vehicle constitute the primary structural tie between the spacecraft in final docked configuration.

  19. Mitochondria: An intriguing target for killing tumour-initiating cells.

    PubMed

    Yan, Bing; Dong, Lanfeng; Neuzil, Jiri

    2016-01-01

    Tumour-initiating cells (TICs) play a pivotal role in cancer initiation, metastasis and recurrence, as well as in resistance to therapy. Therefore, development of drugs targeting TICs has become a focus of contemporary research. Mitochondria have emerged as a promising target of anti-cancer therapies due to their specific role in cancer metabolism and modulation of apoptotic pathways. Mitochondria of TICs possess special characteristics, some of which can be utilised to design drugs specifically targeting these cells. In this paper, we will review recent research on TICs and their mitochondria, and introduce drugs that kill these cells by way of mitochondrial targeting. PMID:26702582

  20. Multiple Subsets of Brain Tumor Initiating Cells Coexist in Glioblastoma.

    PubMed

    Rennert, Robert C; Achrol, Achal S; Januszyk, Michael; Kahn, Suzana A; Liu, Tiffany T; Liu, Yi; Sahoo, Debashis; Rodrigues, Melanie; Maan, Zeshaan N; Wong, Victor W; Cheshier, Samuel H; Chang, Steven D; Steinberg, Gary K; Harsh, Griffith R; Gurtner, Geoffrey C

    2016-06-01

    Brain tumor-initiating cells (BTICs) are self-renewing multipotent cells critical for tumor maintenance and growth. Using single-cell microfluidic profiling, we identified multiple subpopulations of BTICs coexisting in human glioblastoma, characterized by distinct surface marker expression and single-cell molecular profiles relating to divergent bulk tissue molecular subtypes. These data suggest BTIC subpopulation heterogeneity as an underlying source of intra-tumoral bulk tissue molecular heterogeneity, and will support future studies into BTIC subpopulation-specific therapies. Stem Cells 2016;34:1702-1707. PMID:26991945

  1. Molecular Pathogenesis of Sporadic Melanoma and Melanoma-Initiating Cells

    PubMed Central

    Kong, Yunyi; Kumar, Suresh M.; Xu, Xiaowei

    2014-01-01

    Recent advances in molecular genetics and cancer stem cell biology have shed some light on the molecular basis of melanomagenesis. In this review, we will focus on major genetic alterations in the melanoma, particularly pathways involved in cell proliferation, apoptosis, and tumor suppression. The potential role of melanoma-initiating cells during melanomagenesis and progression will also be discussed. Understanding pathogenesis of melanoma may uncover new diagnostic clues and therapeutic targets for this increasingly prevalent disease. PMID:21128770

  2. CD271 is an imperfect marker for melanoma initiating cells

    PubMed Central

    Cheli, Yann; Bonnazi, Vanessa F.; Jacquel, Arnaud; Allegra, Maryline; Donatis, Gian Marco De; Bahadoran, Philippe; Bertolotto, Corine; Ballotti, Robert

    2014-01-01

    Understanding the molecular and cellular processes underlying melanoma plasticity and heterogeneity is of paramount importance to improve the efficiency of current treatment and to overcome resistance to chemotherapy drugs. The notion of plasticity and heterogeneity implies the existence of melanoma cell populations with different phenotypic and tumorigenic properties. Using melanoma cell lines and melanoma cells freshly isolated from patient biopsies, we investigated the relationship between ABCB5+, CD271+ and low-MITF, expressing populations that were reported to display melanoma initiating cell properties. Here, we showed that ABCB5+ and CD271+ populations poorly overlap. However, we found that the CD271+ population is enriched in low-MITF cells and expresses a higher level of stemness genes, such as OCT4, NANOG and NES. These features could explain the increased tumorigenicity of the CD271+ cells. The rapid conversion of CD271+ to CD271− cells in vitro demonstrates the plasticity ability of melanoma cells. Finally, we observed that the transient slow-growing population contains only CD271+ cells that are highly tumorigenic. However, the fast growing/CD271+ population exhibits a poor tumorigenic ability. Taking together, our data show that CD271 is an imperfect marker for melanoma initiating cells, but may be useful to identify melanoma cells with an increased stemness and tumorigenic potential. PMID:25105565

  3. In vitro Enrichment of Ovarian Cancer Tumor-initiating Cells

    PubMed Central

    House, Carrie D.; Hernandez, Lidia; Annunziata, Christina M.

    2015-01-01

    Evidence suggests that small subpopulations of tumor cells maintain a unique self-renewing and differentiation capacity and may be responsible for tumor initiation and/or relapse. Clarifying the mechanisms by which these tumor-initiating cells (TICs) support tumor formation and progression could lead to the development of clinically favorable therapies. Ovarian cancer is a heterogeneous and highly recurrent disease. Recent studies suggest TICs may play an important role in disease biology. We have identified culture conditions that enrich for TICs from ovarian cancer cell lines. Growing either adherent cells or non-adherent ‘floater’ cells in a low attachment plate with serum free media in the presence of growth factors supports the propagation of ovarian cancer TICs with stem cell markers (CD133 and ALDH activity) and increased tumorigenicity without the need to physically separate the TICs from other cell types within the culture. Although the presence of floater cells is not common for all cell lines, this population of cells with innate low adherence may have high tumorigenic potential.Compared to adherent cells grown in the presence of serum, TICs readily form spheres, are significantly more tumorigenic in mice, and express putative stem cell markers. The conditions are easy to establish in a timely manner and can be used to study signaling pathways important for maintaining stem characteristics, and to identify drugs or combinations of drugs targeting TICs. The culture conditions described herein are applicable for a variety of ovarian cancer cells of epithelial origin and will be critical in providing new information about the role of TICs in tumor initiation, progression, and relapse. PMID:25742116

  4. Evaluation program for secondary spacecraft cells: Seventeenth annual report of cycle life test

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1981-01-01

    Acceptance tests were conducted on nickel cadmium, silver cadmium, and silver zinc cells to insure that all cells put into the life cycle program meet the specifications outlined in the respective purchase contracts. Statistical information is presented on cell performance characteristics and limitations. Weaknesses discovered in cell design are reported and aid in research and development efforts toward improving the reliability of space batteries. Battery weaknesses encountered in satellite programs such as IMP, NIMBUS, OGO, OAO, SAS, and TETR were studied and remedied through special tests.

  5. The California stem cell initiative: persuasion, politics, and public science.

    PubMed

    Adelson, Joel W; Weinberg, Joanna K

    2010-03-01

    The California Institute for Regenerative Medicine (CIRM) was created by a California ballot initiative to make stem cell research a constitutional right, in response to Bush administration restrictions on stem cell research. The initiative created a taxpayer-funded, multibillion-dollar institution, intended to advance public health by developing cures and treatments for diabetes, cancer, paralysis, and other conditions. The initiative has been highly controversial among stakeholders and watchdog groups concerned with organizational transparency, accountability, and the ethics of stem cell research. We interviewed major stakeholders-both supporters and opponents-and analyzed documents and meeting notes. We found that the CIRM has overcome start-up challenges, been selectively influenced by criticism, and adhered to its core mission. PMID:20075315

  6. The California Stem Cell Initiative: Persuasion, Politics, and Public Science

    PubMed Central

    Weinberg, Joanna K.

    2010-01-01

    The California Institute for Regenerative Medicine (CIRM) was created by a California ballot initiative to make stem cell research a constitutional right, in response to Bush administration restrictions on stem cell research. The initiative created a taxpayer-funded, multibillion-dollar institution, intended to advance public health by developing cures and treatments for diabetes, cancer, paralysis, and other conditions. The initiative has been highly controversial among stakeholders and watchdog groups concerned with organizational transparency, accountability, and the ethics of stem cell research. We interviewed major stakeholders—both supporters and opponents—and analyzed documents and meeting notes. We found that the CIRM has overcome start-up challenges, been selectively influenced by criticism, and adhered to its core mission. PMID:20075315

  7. Brain Metastasis-Initiating Cells: Survival of the Fittest

    PubMed Central

    Singh, Mohini; Manoranjan, Branavan; Mahendram, Sujeivan; McFarlane, Nicole; Venugopal, Chitra; Singh, Sheila K.

    2014-01-01

    Brain metastases (BMs) are the most common brain tumor in adults, developing in about 10% of adult cancer patients. It is not the incidence of BM that is alarming, but the poor patient prognosis. Even with aggressive treatments, median patient survival is only months. Despite the high rate of BM-associated mortality, very little research is conducted in this area. Lack of research and staggeringly low patient survival is indicative that a novel approach to BMs and their treatment is needed. The ability of a small subset of primary tumor cells to produce macrometastases is reminiscent of brain tumor-initiating cells (BTICs) or cancer stem cells (CSCs) hypothesized to form primary brain tumors. BTICs are considered stem cell-like due to their self-renewal and differentiation properties. Similar to the subset of cells forming metastases, BTICs are most often a rare subpopulation. Based on the functional definition of a TIC, cells capable of forming a BM could be considered to be brain metastasis-initiating cells (BMICs). These putative BMICs would not only have the ability to initiate tumor growth in a secondary niche, but also the machinery to escape the primary tumor, migrate through the circulation, and invade the neural niche. PMID:24857921

  8. Spacecraft Antennas

    NASA Technical Reports Server (NTRS)

    Jamnejad, Vahraz; Manshadi, Farzin; Rahmat-Samii, Yahya; Cramer, Paul

    1990-01-01

    Some of the various categories of issues that must be considered in the selection and design of spacecraft antennas for a Personal Access Satellite System (PASS) are addressed, and parametric studies for some of the antenna concepts to help the system designer in making the most appropriate antenna choice with regards to weight, size, and complexity, etc. are provided. The question of appropriate polarization for the spacecraft as well as for the User Terminal Antenna required particular attention and was studied in some depth. Circular polarization seems to be the favored outcome of this study. Another problem that has generally been a complicating factor in designing the multiple beam reflector antennas, is the type of feeds (single vs. multiple element and overlapping vs. non-overlapping clusters) needed for generating the beams. This choice is dependent on certain system design factors, such as the required frequency reuse, acceptable interbeam isolation, antenna efficiency, number of beams scanned, and beam-forming network (BFN) complexity. This issue is partially addressed, but is not completely resolved. Indications are that it may be possible to use relatively simple non-overlapping clusters of only a few elements, unless a large frequency reuse and very stringent isolation levels are required.

  9. Targeting Cancer-initiating Cells With Oncolytic Viruses

    PubMed Central

    Cripe, Timothy P; Wang, Pin-Yi; Marcato, Paola; Mahller, Yonatan Y; Lee, Patrick WK

    2009-01-01

    Recent studies in a variety of leukemias and solid tumors indicate that there is significant heterogeneity with respect to tumor-forming ability within a given population of tumor cells, suggesting that only a subpopulation of cells is responsible for tumorigenesis. These cells have been commonly referred to as cancer stem cells (CSCs) or cancer-initiating cells (CICs). CICs have been shown to be relatively resistant to conventional anticancer therapies and are thus thought to be responsible for disease relapse. As such, they represent a potentially critical therapeutic target. Oncolytic viruses are in clinical trials for cancer and kill cells through mechanisms different from conventional therapeutics. Because these viruses are not susceptible to the same pathways of drug or radiation resistance, it is important to learn whether CICs are susceptible to oncolytic virus infection. Here we review the available data regarding the ability of several different oncolytic virus types to target CICs for destruction. PMID:19672244

  10. A study of degradation of plates for nickel-cadmium spacecraft cells. [feasibility of coining

    NASA Technical Reports Server (NTRS)

    Scott, W. R.

    1973-01-01

    The relative merits of coining and not coining of sintered nickel-oxide and cadmium plates was investigated. A survey of the industry including cell manufactures and users was made and results summarized. Sample plate materials from most commercial cell suppliers were obtained and characterized for properties that may correlate with the tendency toward physical disintegration during handling and over long periods of time in the cell. Special test methods were developed to obtain comparative data in a short time. A wide range of physical properties and coining thicknesses was observed, resulting in a range of responses. The stronger, less brittle materials resisted loss of sinter better than weaker materials whether or not coined. Coining improved handling and resistance to electrochemical cycling in all materials tested. An apparent exception was found to be due to improper coining of a tapered edge.

  11. A study of short test and charge retention test methods for nickel-cadmium spacecraft cells

    NASA Technical Reports Server (NTRS)

    Scott, W. R.

    1975-01-01

    Methods for testing nickel-cadmium cells for internal shorts and charge retention were studied. Included were (a) open circuit voltage decay after a brief charge, (b) open circuit voltage recovery after shorting, and (c) open circuit voltage decay and capacity loss after a full charge. The investigation included consideration of the effects of prior history, of conditioning cells prior to testing, and of various test method variables on the results of the tests. Sensitivity of the tests was calibrated in terms of equivalent external resistance. The results were correlated. It was shown that a large number of variables may affect the results of these tests. It is concluded that the voltage decay after a brief charge and the voltage recovery methods are more sensitive than the charged stand method, and can detect an internal short equivalent to a resistance of about (10,000/C)ohms where "C' is the numerical value of the capacity of the cell in ampere hours.

  12. Self-discharge characteristics of spacecraft nickel-cadmium cells at elevated temperatures

    NASA Technical Reports Server (NTRS)

    Donley, S. W.; Matsumoto, J. H.; Hwang, W. C.

    1986-01-01

    The effects of heat generation were determined in NiCd cells during high temperature storage on open circuits. The testing was designed to determine the extent to which thermal stability is a valid concern, at temperature of exposure (externally effected) between 40 and 120 C.

  13. Review of thin film solar cell technology and applications for ultra-light spacecraft solar arrays

    NASA Technical Reports Server (NTRS)

    Landis, Geoffrey A.

    1991-01-01

    Developments in thin-film amorphous and polycrystalline photovoltaic cells are reviewed and discussed with a view to potential applications in space. Two important figures of merit are discussed: efficiency (i.e., what fraction of the incident solar energy is converted to electricity), and specific power (power to weight ratio).

  14. Development of a lightweight, light-trapped, thin GaAs solar cell for spacecraft applications

    NASA Technical Reports Server (NTRS)

    Hannon, Margaret H.; Dinetta, Louis C.; Dashiell, Michael W.; Cummings, John R.; Barnett, Allen M.

    1994-01-01

    This paper describes ultra-lightweight, high performance, thin, light trapping GaAs solar cells for advanced space power systems. The device designs can achieve 24.5 percent efficiency at AMO and 1X conditions, corresponding to a power density of 330 W/m2. A significant breakthrough lies in the potential for a specific power of 2906 W/kg because the entire device is less than 1.5 microns thick. This represents a 440 percent improvement over conventional 4-mil silicon solar cells. In addition to being lightweight, this thin device design can result in increased radiation tolerance. The attachment of the cover glass support to the front surface has been demonstrated by both silicone and electrostatic bonding techniques. Device parameters of 1.002 volts open-circuit voltage, 80 percent fill factor, and a short-circuit current of 24.3 mA/sq cm have been obtained. This demonstrates a conversion efficiency of 14.4 percent resulting in a specific power of 2240 W/kg. Additionally, this new technology offers an alternative approach for enabling multi-bandgap solar cells and high output space solar power devices. The thin device structure can be applied to any 3-5 based solar cell application, yielding both an increase in specific power and radiation tolerance.

  15. Culture and Isolation of Brain Tumor Initiating Cells.

    PubMed

    Vora, Parvez; Venugopal, Chitra; McFarlane, Nicole; Singh, Sheila K

    2015-01-01

    Brain tumors are typically composed of heterogeneous cells that exhibit distinct phenotypic characteristics and proliferative potentials. Only a relatively small fraction of cells in the tumor with stem cell properties, termed brain tumor initiating cells (BTICs), possess an ability to differentiate along multiple lineages, self-renew, and initiate tumors in vivo. This unit describes protocols for the culture and isolation BTICs. We applied culture conditions and assays originally used for normal neural stem cells (NSCs) in vitro to a variety of brain tumors. Using fluorescence-activated cell sorting for the neural precursor cell surface marker CD133/CD15, BTICs can be isolated and studied prospectively. Isolation of BTICs from GBM bulk tumor will enable examination of dissimilar morphologies, self-renewal capacities, tumorigenicity, and therapeutic sensitivities. As cancer is also considered a disease of unregulated self-renewal and differentiation, an understanding of BTICs is fundamental to understanding tumor growth. Ultimately, it will lead to novel drug discovery approaches that strategically target the functionally relevant BTIC population. PMID:26237571

  16. Mechanics of motility initiation and motility arrest in crawling cells

    NASA Astrophysics Data System (ADS)

    Recho, Pierre; Putelat, Thibaut; Truskinovsky, Lev

    2015-11-01

    Motility initiation in crawling cells requires transformation of a symmetric state into a polarized state. In contrast, motility arrest is associated with re-symmetrization of the internal configuration of a cell. Experiments on keratocytes suggest that polarization is triggered by the increased contractility of motor proteins but the conditions of re-symmetrization remain unknown. In this paper we show that if adhesion with the extra-cellular substrate is sufficiently low, the progressive intensification of motor-induced contraction may be responsible for both transitions: from static (symmetric) to motile (polarized) at a lower contractility threshold and from motile (polarized) back to static (symmetric) at a higher contractility threshold. Our model of lamellipodial cell motility is based on a 1D projection of the complex intra-cellular dynamics on the direction of locomotion. In the interest of analytical transparency we also neglect active protrusion and view adhesion as passive. Despite the unavoidable oversimplifications associated with these assumptions, the model reproduces quantitatively the motility initiation pattern in fish keratocytes and reveals a crucial role played in cell motility by the nonlocal feedback between the mechanics and the transport of active agents. A prediction of the model that a crawling cell can stop and re-symmetrize when contractility increases sufficiently far beyond the motility initiation threshold still awaits experimental verification.

  17. A study of degradation of plates for nickel-cadmium spacecraft cells

    NASA Technical Reports Server (NTRS)

    Scott, W. R.

    1974-01-01

    The relative merits of coining and not coining of sintered nickel oxide and cadmium plates was investigated. Sample plate materials from most commercial cell suppliers were obtained and characterized for properties that may correlate with the tendency toward physical disintegration during handling and over long periods of time in the cell. Special test methods were developed to obtain comparative data in a short time. A wide range of physical properties and coining thickness was observed, resulting in a range of responses. The stronger materials resisted loss of sinter better than weaker materials whether or not coined. Coining improved handling and resistance to electrochemical cycling of weaker materials. The mechanism of break-down of positive plate edges under cycling appears to be the same as that of thickening and blistering. Brittle, nonadherent sinter, resulting from certain impregnation processes, is the most vulnerable to degradation. It is concluded that the latter type of materials should be coined, but coining of strong materials is optional.

  18. Communications spacecraft

    NASA Astrophysics Data System (ADS)

    Fordyce, Samuel W.

    Progress in the designs and performance capabilities of communications satellites is traced from the Echo 1 Al-coated mylar balloon in 1960 to systems planned for the 1990s and beyond. The services allowed with the passive balloon concept were too limited and led to Telstar spacecraft, with 600 voice channels, being placed in elliptical orbits. Geosynchronous communications began in 1963 with the Syncom satellite, which also carried television signals. The evolution of subsequent Intelsat and ANIK satellites is described, as are features of the Marisat, Marecs, and the DBS systems. The near-term capabilities for DBS, advanced communications satellites using TDMA techniques, and mobile communications systems are summarized, along with the NASA ACTS and MSAT-X satellites for exploring the necessary technologies. The roles the Space Station and unmanned GEO platforms will play in future satellite communications are discussed.

  19. C/EBPalpha initiates primitive myelopoiesis in pluripotent embryonic cells.

    PubMed

    Chen, Yaoyao; Costa, Ricardo M B; Love, Nick R; Soto, Ximena; Roth, Martin; Paredes, Roberto; Amaya, Enrique

    2009-07-01

    The molecular mechanisms that underlie the development of primitive myeloid cells in vertebrate embryos are not well understood. Here we characterize the role of cebpa during primitive myeloid cell development in Xenopus. We show that cebpa is one of the first known hematopoietic genes expressed in the embryo. Loss- and gain-of-function studies show that it is both necessary and sufficient for the development of functional myeloid cells. In addition, we show that cebpa misexpression leads to the precocious induction of myeloid cell markers in pluripotent prospective ectodermal cells, without the cells transitioning through a general mesodermal state. Finally, we use live imaging to show that cebpa-expressing cells exhibit many attributes of terminally differentiated myeloid cells, such as highly active migratory behavior, the ability to quickly and efficiently migrate toward wounds and phagocytose bacteria, and the ability to enter the circulation. Thus, C/EPBalpha is the first known single factor capable of initiating an entire myelopoiesis pathway in pluripotent cells in the embryo. PMID:19420355

  20. Spacecraft Charging Technology, 1980

    NASA Technical Reports Server (NTRS)

    1981-01-01

    The third Spacecraft Charging Technology Conference proceedings contain 66 papers on the geosynchronous plasma environment, spacecraft modeling, charged particle environment interactions with spacecraft, spacecraft materials characterization, and satellite design and testing. The proceedings is a compilation of the state of the art of spacecraft charging and environmental interaction phenomena.

  1. Programmed Cell Death Initiation and Execution in Budding Yeast

    PubMed Central

    Strich, Randy

    2015-01-01

    Apoptosis or programmed cell death (PCD) was initially described in metazoans as a genetically controlled process leading to intracellular breakdown and engulfment by a neighboring cell . This process was distinguished from other forms of cell death like necrosis by maintenance of plasma membrane integrity prior to engulfment and the well-defined genetic system controlling this process. Apoptosis was originally described as a mechanism to reshape tissues during development. Given this context, the assumption was made that this process would not be found in simpler eukaryotes such as budding yeast. Although basic components of the apoptotic pathway were identified in yeast, initial observations suggested that it was devoid of prosurvival and prodeath regulatory proteins identified in mammalian cells. However, as apoptosis became extensively linked to the elimination of damaged cells, key PCD regulatory proteins were identified in yeast that play similar roles in mammals. This review highlights recent discoveries that have permitted information regarding PCD regulation in yeast to now inform experiments in animals. PMID:26272996

  2. Xenia Spacecraft Study Addendum: Spacecraft Cost Estimate

    NASA Technical Reports Server (NTRS)

    Hill, Spencer; Hopkins, Randall

    2009-01-01

    This slide presentation reviews the Xenia spacecraft cost estimates as an addendum for the Xenia Spacecraft study. The NASA/Air Force Cost model (NAFCPOM) was used to derive the cost estimates that are expressed in 2009 dollars.

  3. Initial adherence of EPEC, EHEC and VTEC to host cells

    PubMed Central

    Bardiau, Marjorie; Szalo, Mihai; Mainil, Jacques G.

    2010-01-01

    Initial adherence to host cells is the first step of the infection of enteropathogenic Escherichia coli (EPEC), enterohaemorrhagic Escherichia coli (EHEC) and verotoxigenic Escherichia coli (VTEC) strains. The importance of this step in the infection resides in the fact that (1) adherence is the first contact between bacteria and intestinal cells without which the other steps cannot occur and (2) adherence is the basis of host specificity for a lot of pathogens. This review describes the initial adhesins of the EPEC, EHEC and VTEC strains. During the last few years, several new adhesins and putative colonisation factors have been described, especially in EHEC strains. Only a few adhesins (BfpA, AF/R1, AF/R2, Ral, F18 adhesins) appear to be host and pathotype specific. The others are found in more than one species and/or pathotype (EPEC, EHEC, VTEC). Initial adherence of EPEC, EHEC and VTEC strains to host cells is probably mediated by multiple mechanisms. PMID:20423697

  4. Nonlinear spacecraft`s gyromoment attitude control

    SciTech Connect

    Somov, Y.I.

    1994-12-31

    Nonlinear methods of attitude control for spacecraft`s spatial rotation maneuvers through the use of gyrodynes - single gimbal control moment gyroscopes - are developed. We present new results on optimizing and dynamic synthesis of the nonlinear gyromoment attitude control system for a fast-manoeuvring spacecraft with a minimum-excessive scheme of gyrodynes.

  5. Analysis of Initial Cell Spreading Using Mechanistic Contact Formulations for a Deformable Cell Model

    PubMed Central

    Odenthal, Tim; Smeets, Bart; Van Liedekerke, Paul; Tijskens, Engelbert; Van Oosterwyck, Hans; Ramon, Herman

    2013-01-01

    Adhesion governs to a large extent the mechanical interaction between a cell and its microenvironment. As initial cell spreading is purely adhesion driven, understanding this phenomenon leads to profound insight in both cell adhesion and cell-substrate interaction. It has been found that across a wide variety of cell types, initial spreading behavior universally follows the same power laws. The simplest cell type providing this scaling of the radius of the spreading area with time are modified red blood cells (RBCs), whose elastic responses are well characterized. Using a mechanistic description of the contact interaction between a cell and its substrate in combination with a deformable RBC model, we are now able to investigate in detail the mechanisms behind this universal power law. The presented model suggests that the initial slope of the spreading curve with time results from a purely geometrical effect facilitated mainly by dissipation upon contact. Later on, the spreading rate decreases due to increasing tension and dissipation in the cell's cortex as the cell spreads more and more. To reproduce this observed initial spreading, no irreversible deformations are required. Since the model created in this effort is extensible to more complex cell types and can cope with arbitrarily shaped, smooth mechanical microenvironments of the cells, it can be useful for a wide range of investigations where forces at the cell boundary play a decisive role. PMID:24146605

  6. Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

    SciTech Connect

    Ge, Yuqing; Zhou, Fengbiao; Chen, Hong; Cui, Chunhong; Liu, Dan; Li, Qiuping; Yang, Zhiyuan; Wu, Guoqiang; Sun, Shuhui; Gu, Jianxin; Wei, Yuanyan; Jiang, Jianhai

    2010-07-09

    Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.

  7. Ovarian tumor-initiating cells display a flexible metabolism

    SciTech Connect

    Anderson, Angela S.; Roberts, Paul C.; Frisard, Madlyn I.; Hulver, Matthew W.; Schmelz, Eva M.

    2014-10-15

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

  8. Understanding the initiation of B cell signaling through live cell imaging

    PubMed Central

    Pierce, Susan K.

    2013-01-01

    Antibody responses are initiated by the binding of antigens to clonally distributed cell surface B cell receptors (BCRs) that trigger signaling cascades resulting in B cell activation. Using conventional biochemical approaches, the components of the downstream BCR signaling pathways have been described in considerable detail. However, far less is known about the early molecular events by which the binding of antigens to the BCRs initiates BCR signaling. With the recent advent of high-resolution, high-speed, live-cell and single-molecule imaging technologies, these events are just beginning to be elucidated. Understanding the molecular mechanisms underlying the initiation of BCR signaling may provide new targets for therapeutics to block dysregulated BCR signaling in systemic autoimmune diseases and in B cell tumors and to aid in the design of protein subunit vaccines. In this chapter we describe the general procedures for using these new imaging techniques to investigate the early events in the initiation of BCR signaling. PMID:22341229

  9. Spacecraft Shielding: An Experimental Comparison Between Open Cell Aluminium Foam Core Sandwich Panel Structures and Whipple Shielding.

    NASA Astrophysics Data System (ADS)

    Pasini, D. L. S.; Price, M. C.; Burchell, M. J.; Cole, M. J.

    2013-09-01

    Spacecraft shielding is generally provided by metallic plates in a Whipple shield type configuration [1] where possible. However, mission restrictions such as spacecraft payload mass, can prevent the inclusion of a dedicated protective structure for prevention against impact damage from micrometeoroids. Due to this, often the spacecraft's primary structure will act as the de facto shield. This is commonly an aluminium honeycomb backed with either glass fibre reinforced plastic (GFRP) or aluminium faceplates [2]. Such materials are strong, lightweight and relatively cheap due to their abundance used within the aerospace industry. However, these materials do not offer the best protection (per unit weight) against hypervelocity impact damage. A new material for shielding (porous aluminium foam [3]) is suggested for low risk space missions. Previous studies by NASA [4] have been performed to test this new material against hypervelocity impacts using spherical aluminium projectiles. This showed its potential for protection for satellites in Earth orbit, against metallic space debris. Here we demonstrate the material's protective capabilities against micrometeoroids, using soda-lime glass spheres as projectiles to accurately gauge its potential with relation to silicatious materials, such as micrometeoroids and natural solar system debris. This is useful for spacecraft missions beyond Earth orbit where solar system materials are the dominant threat (via hypervelocity impacts) to the spacecraft, rather than manmade debris.

  10. Mesenchymal stem cells secretomes' affect multiple myeloma translation initiation.

    PubMed

    Marcus, H; Attar-Schneider, O; Dabbah, M; Zismanov, V; Tartakover-Matalon, S; Lishner, M; Drucker, L

    2016-06-01

    Bone marrow mesenchymal stem cells' (BM-MSCs) role in multiple myeloma (MM) pathogenesis is recognized. Recently, we have published that co-culture of MM cell lines with BM-MSCs results in mutual modulation of phenotype and proteome (via translation initiation (TI) factors eIF4E/eIF4GI) and that there are differences between normal donor BM-MSCs (ND-MSCs) and MM BM-MSCs (MM-MSCs) in this crosstalk. Here, we aimed to assess the involvement of soluble BM-MSCs' (ND, MM) components, more easily targeted, in manipulation of MM cell lines phenotype and TI with specific focus on microvesicles (MVs) capable of transferring critical biological material. We applied ND and MM-MSCs 72h secretomes to MM cell lines (U266 and ARP-1) for 12-72h and then assayed the cells' (viability, cell count, cell death, proliferation, cell cycle, autophagy) and TI (factors: eIF4E, teIF4GI; regulators: mTOR, MNK1/2, 4EBP; targets: cyclin D1, NFκB, SMAD5, cMyc, HIF1α). Furthermore, we dissected the secretome into >100kDa and <100kDa fractions and repeated the experiments. Finally, MVs were isolated from the ND and MM-MSCs secretomes and applied to MM cell lines. Phenotype and TI were assessed. Secretomes of BM-MSCs (ND, MM) significantly stimulated MM cell lines' TI, autophagy and proliferation. The dissected secretome yielded different effects on MM cell lines phenotype and TI according to fraction (>100kDa- repressed; <100kDa- stimulated) but with no association to source (ND, MM). Finally, in analyses of MVs extracted from BM-MSCs (ND, MM) we witnessed differences in accordance with source: ND-MSCs MVs inhibited proliferation, autophagy and TI whereas MM-MSCs MVs stimulated them. These observations highlight the very complex communication between MM and BM-MSCs and underscore its significance to major processes in the malignant cells. Studies into the influential MVs cargo are underway and expected to uncover targetable signals in the regulation of the TI/proliferation/autophagy cascade

  11. Spacecraft radiator systems

    NASA Technical Reports Server (NTRS)

    Anderson, Grant A. (Inventor)

    2012-01-01

    A spacecraft radiator system designed to provide structural support to the spacecraft. Structural support is provided by the geometric "crescent" form of the panels of the spacecraft radiator. This integration of radiator and structural support provides spacecraft with a semi-monocoque design.

  12. International Ultraviolet Explorer (IUE) spacecraft battery performance update

    NASA Technical Reports Server (NTRS)

    Tiller, Smith E.

    1987-01-01

    January 26, 1987 marks the ninth inflight aniversary of the IUE spacecraft, launched into an eccentric synchronous orbit. The orbital path has subjected the spacecraft to 18 solar eclipse seasons since launch. Nine years of inflight operations culminate a major milestone for battery support to a spacecraft, which is well in excess of the initial 3 year design life. A brief outline of events, power system characteristics, and papers presented a previous battery workshops are provided. The IUE battery cell performance is excellent with the exception of the third electrode anomaly and temperature delta between batteries. Data indicates that battery depth-of-discharge (DOD) may be more critical to extend battery life than small operational temperature deltas between batteries. It is predicted that several additional years of battery life may be obtained by a reduction in operational battery DOD.

  13. Spacecraft Charging and the Microwave Anisotropy Probe Spacecraft

    NASA Technical Reports Server (NTRS)

    Timothy, VanSant J.; Neergaard, Linda F.

    1998-01-01

    The Microwave Anisotropy Probe (MAP), a MIDEX mission built in partnership between Princeton University and the NASA Goddard Space Flight Center (GSFC), will study the cosmic microwave background. It will be inserted into a highly elliptical earth orbit for several weeks and then use a lunar gravity assist to orbit around the second Lagrangian point (L2), 1.5 million kilometers, anti-sunward from the earth. The charging environment for the phasing loops and at L2 was evaluated. There is a limited set of data for L2; the GEOTAIL spacecraft measured relatively low spacecraft potentials (approx. 50 V maximum) near L2. The main area of concern for charging on the MAP spacecraft is the well-established threat posed by the "geosynchronous region" between 6-10 Re. The launch in the autumn of 2000 will coincide with the falling of the solar maximum, a period when the likelihood of a substorm is higher than usual. The likelihood of a substorm at that time has been roughly estimated to be on the order of 20% for a typical MAP mission profile. Because of the possibility of spacecraft charging, a requirement for conductive spacecraft surfaces was established early in the program. Subsequent NASCAP/GEO analyses for the MAP spacecraft demonstrated that a significant portion of the sunlit surface (solar cell cover glass and sunshade) could have nonconductive surfaces without significantly raising differential charging. The need for conductive materials on surfaces continually in eclipse has also been reinforced by NASCAP analyses.

  14. Implications of arcing due to spacecraft charging on spacecraft EMI margins of immunity

    NASA Technical Reports Server (NTRS)

    Inouye, G. T.

    1981-01-01

    Arcing due to spacecraft charging on spacecraft EMI margins of immunity was determined. The configuration of the P78-2 spacecraft of the SCATHA program was analyzed. A brushfire arc discharge model was developed, and a technique for initiating discharges with a spark plug trigger was for data configuration. A set of best estimate arc discharge parameters was defined. The effects of spacecraft potentials in limiting the discharge current blowout component are included. Arc discharge source models were incorporated into a SEMCAP EMI coupling analysis code for the DSP spacecraft. It is shown that with no mission critical circuits will be affected.

  15. Long-lived intestinal tuft cells serve as colon cancer–initiating cells

    PubMed Central

    Westphalen, C. Benedikt; Asfaha, Samuel; Hayakawa, Yoku; Takemoto, Yoshihiro; Lukin, Dana J.; Nuber, Andreas H.; Brandtner, Anna; Setlik, Wanda; Remotti, Helen; Muley, Ashlesha; Chen, Xiaowei; May, Randal; Houchen, Courtney W.; Fox, James G.; Gershon, Michael D.; Quante, Michael; Wang, Timothy C.

    2014-01-01

    Doublecortin-like kinase 1 protein (DCLK1) is a gastrointestinal tuft cell marker that has been proposed to identify quiescent and tumor growth–sustaining stem cells. DCLK1+ tuft cells are increased in inflammation-induced carcinogenesis; however, the role of these cells within the gastrointestinal epithelium and their potential as cancer-initiating cells are poorly understood. Here, using a BAC-CreERT–dependent genetic lineage–tracing strategy, we determined that a subpopulation of DCLK1+ cells is extremely long lived and possesses rare stem cell abilities. Moreover, genetic ablation of Dclk1 revealed that DCLK1+ tuft cells contribute to recovery following intestinal and colonic injury. Surprisingly, conditional knockdown of the Wnt regulator APC in DCLK1+ cells was not sufficient to drive colonic carcinogenesis under normal conditions; however, dextran sodium sulfate–induced (DSS-induced) colitis promoted the development of poorly differentiated colonic adenocarcinoma in mice lacking APC in DCLK1+ cells. Importantly, colonic tumor formation occurred even when colitis onset was delayed for up to 3 months after induced APC loss in DCLK1+ cells. Thus, our data define an intestinal DCLK1+ tuft cell population that is long lived, quiescent, and important for intestinal homeostasis and regeneration. Long-lived DCLK1+ cells maintain quiescence even following oncogenic mutation, but are activated by tissue injury and can serve to initiate colon cancer. PMID:24487592

  16. A method for determining the drift velocity of plasma depletions in the equatorial ionosphere using far-ultraviolet spacecraft observations: initial results

    NASA Astrophysics Data System (ADS)

    England, S. L.; Immel, T. J.; Park, S. H.; Frey, H. U.; Mende, S. B.

    2007-12-01

    The Far-Ultraviolet Imager (IMAGE-FUV) on-board the NASA IMAGE satellite has been used to observe plasma depletions in the nightside equatorial ionosphere. Observations from periods around spacecraft apogee, during which equatorial regions are visible for several hours, have allowed the velocity of these plasma depletions to be determined. A new method for determining the velocity of these depletions using an image analysis technique, Tracking Of Airglow Depletions (TOAD), has been developed. TOAD allows the objective identification and tracking of depletions. The automation of this process has also allowed for the tracking of a greater number of depletions than previously achieved without requiring any human input, which shows that TOAD is suitable for use with large data sets and for future routine monitoring of the ionosphere from space. Furthermore, this allows the drift velocities of each depletion to be determined as a function of magnetic latitude as well as local time. Previous ground-based airglow observations from a small number of locations have indicated that the drift velocities of depletions may vary rapidly with magnetic latitude. Here we shall present the first results from TOAD of this shear in drift velocities from our global sample of depletion drift velocities.

  17. Positive correlation between size at initiation of chromosome replication in Escherichia coli and size at initiation of cell constriction.

    PubMed Central

    Koppes, L J; Nanninga, N

    1980-01-01

    The variability of (i) the length (size) at which cells initiate chromosome replication, (ii) the length at which they initiate cell constriction, and (iii) the time interval between these events has been estimated for Escherichia coli B/r K at two different slow growth rates. Steady-state cultures were pulse-labeled with [3H]thymidine and, after fixation, analyzed by electron microscopic radioautography. The coefficient of variation of length at initiation of chromosome replication was found to be 15 to 22%, the coefficient of variation of length at initiation of cell constriction was 10%, and the coefficient of variation of the time interval between both events was 25%. With the help of these values we calculated a high positive coefficient of correlation (rho) between the length at which a round of chromosome replication is initiated and that at which the onset of cell constriction occurs. At both growth rates rho has a value of 0.6 to 1.0. This correlation excludes a model in which chromosome initiation and cell constriction are independently triggered by some aspects of cell growth. It favors a model in which an event before or at chromosome initiation triggers both. PMID:6995452

  18. Cellular microenvironment modulates the galvanotaxis of brain tumor initiating cells

    PubMed Central

    Huang, Yu-Ja; Hoffmann, Gwendolyn; Wheeler, Benjamin; Schiapparelli, Paula; Quinones-Hinojosa, Alfredo; Searson, Peter

    2016-01-01

    Galvanotaxis is a complex process that represents the collective outcome of various contributing mechanisms, including asymmetric ion influxes, preferential activation of voltage-gated channels, and electrophoretic redistribution of membrane components. While a large number of studies have focused on various up- and downstream signaling pathways, little is known about how the surrounding microenvironment may interact and contribute to the directional response. Using a customized galvanotaxis chip capable of carrying out experiments in both two- and three-dimensional microenvironments, we show that cell-extracellular matrix (ECM) interactions modulate the galvanotaxis of brain tumor initiating cells (BTICs). Five different BTICs across three different glioblastoma subtypes were examined and shown to all migrate toward the anode in the presence of a direct-current electric field (dcEF) when cultured on a poly-L-ornithine/laminin coated surface, while the fetal-derived neural progenitor cells (fNPCs) migrated toward the cathode. Interestingly, when embedded in a 3D ECM composed of hyaluronic acid and collagen, BTICs exhibited opposite directional response and migrated toward the cathode. Pharmacological inhibition against a panel of key molecules involved in galvanotaxis further revealed the mechanistic differences between 2- and 3D galvanotaxis in BTICs. Both myosin II and phosphoinositide 3-kinase (PI3K) were found to hold strikingly different roles in different microenvironments. PMID:26898606

  19. Optimizing Spacecraft Placement for Liaison Constellations

    NASA Technical Reports Server (NTRS)

    Chow, C. Channing; Villac, Benjamin F.; Lo, Martin W.

    2011-01-01

    A navigation and communications network is proposed to support an anticipated need for infrastructure in the Earth-Moon system. Periodic orbits will host the constellations while a novel, autonomous navigation strategy will guide the spacecraft along their path strictly based on satellite-to-satellite telemetry. In particular, this paper investigates the second stage of a larger constellation optimization scheme for multi-spacecraft systems. That is, following an initial orbit down-selection process, this analysis provides insights into the ancillary problem of spacecraft placement. Two case studies are presented that consider configurations of up to four spacecraft for a halo orbit and a cycler trajectory.

  20. A global spacecraft control network for spacecraft autonomy research

    NASA Technical Reports Server (NTRS)

    Kitts, Christopher A.

    1996-01-01

    The development and implementation of the Automated Space System Experimental Testbed (ASSET) space operations and control network, is reported on. This network will serve as a command and control architecture for spacecraft operations and will offer a real testbed for the application and validation of advanced autonomous spacecraft operations strategies. The proposed network will initially consist of globally distributed amateur radio ground stations at locations throughout North America and Europe. These stations will be linked via Internet to various control centers. The Stanford (CA) control center will be capable of human and computer based decision making for the coordination of user experiments, resource scheduling and fault management. The project's system architecture is described together with its proposed use as a command and control system, its value as a testbed for spacecraft autonomy research, and its current implementation.

  1. Apoptosis and cell-cycle arrest in human and murine tumor cells are initiated by isoprenoids.

    PubMed

    Mo, H; Elson, C E

    1999-04-01

    Diverse classes of phytochemicals initiate biological responses that effectively lower cancer risk. One class of phytochemicals, broadly defined as pure and mixed isoprenoids, encompasses an estimated 22,000 individual components. A representative mixed isoprenoid, gamma-tocotrienol, suppresses the growth of murine B16(F10) melanoma cells, and with greater potency, the growth of human breast adenocarcinoma (MCF-7) and human leukemic (HL-60) cells. beta-Ionone, a pure isoprenoid, suppresses the growth of B16 cells and with greater potency, the growth of MCF-7, HL-60 and human colon adenocarcinoma (Caco-2) cells. Results obtained with diverse cell lines differing in ras and p53 status showed that the isoprenoid-mediated suppression of growth is independent of mutated ras and p53 functions. beta-Ionone suppressed the growth of human colon fibroblasts (CCD-18Co) but only when present at three-fold the concentration required to suppress the growth of Caco-2 cells. The isoprenoids initiated apoptosis and, concomitantly arrested cells in the G1 phase of the cell cycle. Both suppress 3-hydroxy-3-methylglutaryl CoA reductase activity. beta-Ionone and lovastatin interfered with the posttranslational processing of lamin B, an activity essential to assembly of daughter nuclei. This interference, we postulate, renders neosynthesized DNA available to the endonuclease activities leading to apoptotic cell death. Lovastatin-imposed mevalonate starvation suppressed the glycosylation and translocation of growth factor receptors to the cell surface. As a consequence, cells were arrested in the G1 phase of the cell cycle. This rationale may apply to the isoprenoid-mediated G1-phase arrest of tumor cells. The additive and potentially synergistic actions of these isoprenoids in the suppression of tumor cell proliferation and initiation of apoptosis coupled with the mass action of the diverse isoprenoid constituents of plant products may explain, in part, the impact of fruit, vegetable

  2. B-1 B cell IgM antibody initiates T cell elicitation of contact sensitivity.

    PubMed

    Askenase, P W; Tsuji, R F

    2000-01-01

    Although B-1 B cells have received considerable attention, their actual role in the normal functioning of the immune system is unclear. The hypothesized role of B-1 cell IgM in natural protective immunity is just being established. We have uncovered a separate and novel role for B-1 cell IgM in initiating the elicitation of acquired T cell-dependent contact sensitivity (CS), the prototype of in vivo T cell immunity, early after immunization (within 4 days). The recent recognition of a similarly unanticipated role of B cells in a variety of T cell responses, may indicate that B-1 cell IgM has a broader role in immunity than thought previously. We showed that 24 hr CS responses, and rises in local IFN-gamma levels at 24 hrs later after antigen (Ag) challenge the ears, were absent in pan B cell and antibody deficient mice. The mechanism of B cell involvement in CS-initiation is via local C5a generation early (1-2 hrs) after antigen (Ag) challenge of the ears, in 4 day contact sensitized mice. C5a activates local mast cells to release serotonin (5-HT) and TNF alpha to induce endothelial ICAM-1 and VCAM-1, leading to T cell recruitment. We hypothesized that C5a was generated via complement activation due to antibodies forming local AgAb complexes, and that B-1 cell IgM was involved because isotype switching of B-2 cells to produce C-activating IgG isotypes, could not occur as early as day 4. Indeed, B-1 cell deficient CBA/N-xid mice lacked C5a in 2 hr ear extracts, and had impaired CS ear swelling and elaboration of IFN-gamma at 24 hrs. Importantly, adoptive transfer of purified normal peritoneal B-1 cells, or just i.v. injection of Ag-specific IgM monoclonal antibodies in sensitized xid, restored deficient early C5a and late 24 hr ear swelling. These results suggest that early after Ag challenge, specific B-1 cell IgM, produced at distant sites by prior sensitization, forms AgAb complexes that trigger elaboration of C5a, to activate mast cell release of vasoactive TNF

  3. Mitochondrial Control by DRP1 in Brain Tumor Initiating Cells

    PubMed Central

    Xie, Qi; Wu, Qiulian; Horbinski, Craig M.; Flavahan, William A.; Yang, Kailin; Zhou, Wenchao; Dombrowski, Stephen M.; Huang, Zhi; Fang, Xiaoguang; Shi, Yu; Ferguson, Ashley N.; Kashatus, David F.; Bao, Shideng; Rich, Jeremy N.

    2015-01-01

    Brain tumor initiating cells (BTICs) coopt the neuronal high affinity GLUT3 glucose transporter to withstand metabolic stress. Here, we investigated another mechanism critical to brain metabolism, mitochondrial morphology. BTICs displayed mitochondrial fragmentation relative to non-BTICs, suggesting that BTICs have increased mitochondrial fission. The essential mediator of mitochondrial fission, dynamin-related protein 1 (DRP1), was activated in BTICs and inhibited in non-BTICs. Targeting DRP1 using RNA interference or pharmacologic inhibition induced BTIC apoptosis and inhibited tumor growth. Downstream, DRP1 activity regulated the essential metabolic stress sensor, AMP-activated protein kinase (AMPK), and AMPK targeting rescued the effects of DRP1 disruption. Cyclin-dependent kinase 5 (CDK5) phosphorylated DRP1 to increase its activity in BTICs, whereas Ca2+–calmodulin-dependent protein kinase 2 (CAMK2) inhibited DRP1 in non-BTICs, suggesting tumor cell differentiation induces a regulatory switch in mitochondrial morphology. DRP1 activation correlates with poor prognosis in glioblastoma, suggesting mitochondrial dynamics may represent a therapeutic target for BTICs. PMID:25730670

  4. Differential remodeling of extracellular matrices by breast cancer initiating cells.

    PubMed

    Raja, Anju M; Xu, Shuoyu; Zhuo, Shuangmu; Tai, Dean C S; Sun, Wanxin; So, Peter T C; Welsch, Roy E; Chen, Chien-Shing; Yu, Hanry

    2015-10-01

    Cancer initiating cells (CICs) have been the focus of recent anti-cancer therapies, exhibiting strong invasion capability via potentially enhanced ability to remodel extracellular matrices (ECM). We have identified CICs in a human breast cancer cell line, MX-1, and developed a xenograft model in SCID mice. We investigated the CICs' matrix-remodeling effects using Second Harmonic Generation (SHG) microscopy to identify potential phenotypic signatures of the CIC-rich tumors. The isolated CICs exhibit higher proliferation, drug efflux and drug resistant properties in vitro; were more tumorigenic than non-CICs, resulting in more and larger tumors in the xenograft model. The CIC-rich tumors have less collagen in the tumor interior than in the CIC-poor tumors supporting the idea that the CICs can remodel the collagen more effectively. The collagen fibers were preferentially aligned perpendicular to the CIC-rich tumor boundary while parallel to the CIC-poor tumor boundary suggesting more invasive behavior of the CIC-rich tumors. These findings would provide potential translational values in quantifying and monitoring CIC-rich tumors in future anti-cancer therapies. CIC-rich tumors remodel the collagen matrix more than CIC-poor tumors. PMID:25597396

  5. Initial activation of EpCAM cleavage via cell-to-cell contact

    PubMed Central

    2009-01-01

    Background Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein, which is frequently over-expressed in simple epithelia, progenitors, embryonic and tissue stem cells, carcinoma and cancer-initiating cells. Besides functioning as a homophilic adhesion protein, EpCAM is an oncogenic receptor that requires regulated intramembrane proteolysis for activation of its signal transduction capacity. Upon cleavage, the extracellular domain EpEX is released as a soluble ligand while the intracellular domain EpICD translocates into the cytoplasm and eventually into the nucleus in combination with four-and-a-half LIM domains protein 2 (FHL2) and β-catenin, and drives cell proliferation. Methods EpCAM cleavage, induction of the target genes, and transmission of proliferation signals were investigated under varying density conditions using confocal laser scanning microscopy, immunoblotting, cell counting, and conditional cell systems. Results EpCAM cleavage, induction of the target genes, and transmission of proliferation signals were dependent on adequate cell-to-cell contact. If cell-to-cell contact was prohibited EpCAM did not provide growth advantages. If cells were allowed to undergo contact to each other, EpCAM transmitted proliferation signals based on signal transduction-related cleavage processes. Accordingly, the pre-cleaved version EpICD was not dependent on cell-to-cell contact in order to induce c-myc and cell proliferation, but necessitated nuclear translocation. For the case of contact-inhibited cells, although cleavage of EpCAM occurred, nuclear translocation of EpICD was reduced, as were EpCAM effects. Conclusion Activation of EpCAM's cleavage and oncogenic capacity is dependent on cellular interaction (juxtacrine) to provide for initial signals of regulated intramembrane proteolysis, which then support signalling via soluble EpEX (paracrine). PMID:19925656

  6. Tumour-initiating cells vs. cancer 'stem' cells and CD133: What's in the name?

    SciTech Connect

    Neuzil, Jiri; E-mail: j.neuzil@griffith.edu.au; Stantic, Marina; Zobalova, Renata; Chladova, Jaromira; Wang, Xiufang; Prochazka, Lubomir; Dong, Lanfeng; Andera, Ladislav; Ralph, Stephen J.

    2007-04-20

    Recent evidence suggests that a subset of cells within a tumour have 'stem-like' characteristics. These tumour-initiating cells, distinct from non-malignant stem cells, show low proliferative rates, high self-renewing capacity, propensity to differentiate into actively proliferating tumour cells, resistance to chemotherapy or radiation, and they are often characterised by elevated expression of the stem cell surface marker CD133. Understanding the molecular biology of the CD133{sup +} cancer cells is now essential for developing more effective cancer treatments. These may include drugs targeting organelles, such as mitochondria or lysosomes, using highly efficient and selective inducers of apoptosis. Alternatively, agents or treatment regimens that enhance sensitivity of these therapy-resistant 'tumour stem cells' to the current or emerging anti-tumour drugs would be of interest as well.

  7. Curvelet initialized level set cell segmentation for touching cells in low contrast images.

    PubMed

    Kaur, Sarabpreet; Sahambi, J S

    2016-04-01

    Cell segmentation is an important element of automatic cell analysis. This paper proposes a method to extract the cell nuclei and the cell boundaries of touching cells in low contrast images. First, the contrast of the low contrast cell images is improved by a combination of multiscale top hat filter and h-maxima. Then, a curvelet initialized level set method has been proposed to detect the cell nuclei and the boundaries. The image enhancement results have been verified using PSNR (Peak Signal to noise ratio) and the segmentation results have been verified using accuracy, sensitivity and precision metrics. The results show improved values of the performance metrics with the proposed method. PMID:26922612

  8. Computer simulation of spacecraft/environment interaction.

    PubMed

    Krupnikov, K K; Makletsov, A A; Mileev, V N; Novikov, L S; Sinolits, V V

    1999-10-01

    This report presents some examples of a computer simulation of spacecraft interaction with space environment. We analysed a set data on electron and ion fluxes measured in 1991 1994 on geostationary satellite GORIZONT-35. The influence of spacecraft eclipse and device eclipse by solar-cell panel on spacecraft charging was investigated. A simple method was developed for an estimation of spacecraft potentials in LEO. Effects of various particle flux impact and spacecraft orientation are discussed. A computer engineering model for a calculation of space radiation is presented. This model is used as a client/server model with WWW interface, including spacecraft model description and results representation based on the virtual reality markup language. PMID:11542669

  9. Modeling of spacecraft charging

    NASA Technical Reports Server (NTRS)

    Whipple, E. C., Jr.

    1977-01-01

    Three types of modeling of spacecraft charging are discussed: statistical models, parametric models, and physical models. Local time dependence of circuit upset for DoD and communication satellites, and electron current to a sphere with an assumed Debye potential distribution are presented. Four regions were involved in spacecraft charging: (1) undisturbed plasma, (2) plasma sheath region, (3) spacecraft surface, and (4) spacecraft equivalent circuit.

  10. CD44, Hyaluronan, the Hematopoietic Stem Cell, and Leukemia-Initiating Cells

    PubMed Central

    Zöller, Margot

    2015-01-01

    CD44 is an adhesion molecule that varies in size due to glycosylation and insertion of so-called variant exon products. The CD44 standard isoform (CD44s) is highly expressed in many cells and most abundantly in cells of the hematopoietic system, whereas expression of CD44 variant isoforms (CD44v) is more restricted. CD44s and CD44v are known as stem cell markers, first described for hematopoietic stem cells and later on confirmed for cancer- and leukemia-initiating cells. Importantly, both abundantly expressed CD44s as well as CD44v actively contribute to the maintenance of stem cell features, like generating and embedding in a niche, homing into the niche, maintenance of quiescence, and relative apoptosis resistance. This is surprising, as CD44 is not a master stem cell gene. I here will discuss that the functional contribution of CD44 relies on its particular communication skills with neighboring molecules, adjacent cells and, last not least, the surrounding matrix. In fact, it is the interaction of the hyaluronan receptor CD44 with its prime ligand, which strongly assists stem cells to fulfill their special and demanding tasks. Recent fundamental progress in support of this “old” hypothesis, which may soon pave the way for most promising new therapeutics, is presented for both hematopoietic stem cell and leukemia-initiating cell. The contribution of CD44 to the generation of a stem cell niche, to homing of stem cells in their niche, to stem cell quiescence and apoptosis resistance will be in focus. PMID:26074915

  11. Initial evaluation tests of General Electric Company 12.0 ampere hour nickel cadmium spacecraft cells with design variables

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1979-01-01

    All evaluation tests were performed at room ambient pressure and temperature, with discharges at a 2 hour rate. Tests consisted of phenolphthalein leak tests, three capacity tests, an auxiliary electrode test, a charge retention test, an internal short test, a charge efficiency test, overcharge tests, and a pressure versus capacity test. Results of the tests and recommendations for improvements in manufacturing are presented.

  12. Targeting ALDHbright human carcinoma initiating cells with ALDH1A1- specific CD8+ T cells

    PubMed Central

    Visus, Carmen; Wang, Yangyang; Lozano-Leon, Antonio; Ferris, Robert L.; Silver, Susan; Szczepanski, Miroslaw J.; Brand, Randall E.; Ferrone, Cristina R.; Whiteside, Theresa L.; Ferrone, Soldano; DeLeo, Albert B.; Wang, Xinhui

    2011-01-01

    Purpose Tumor cells expressing elevated aldehyde dehydrogenase (ALDH) activity attributed to ALDH1/3 isoforms have been identified as ALDHbright cells and have the properties attributed to cancer initiating cells (CIC). CIC represent the subpopulation of tumor cells that are resistant to conventional cancer treatments and highly tumorigenic in immunodeficient mice. They are considered to be responsible for tumor recurrence and metastasis. The ALDH1A1 isoform was previously identified as a tumor antigen recognized by CD8+ T cells. This study examines the ability of ALDH1A1-specific CD8+ T cells to eliminate ALDHbright cells and control tumor growth and metastases. Experimental Design ALDHbright cells were isolated by flow cytometry from HLA-A2+ human head and neck, breast and pancreas carcinoma cell lines using ALDEFLUOR® and tested for their tumorigenicity in immunodeficient mice. ALDH1A1-specific CD8+ T cells were generated in vitro and tested for their ability to eliminate CIC in vitro and in vivo by adoptive transfer to immunodeficient mice bearing human tumor xenografts. Results ALDHbright cells isolated by flow cytometry from HLA-A2+ breast, head and neck and pancreas carcinoma cell lines at low numbers (500 cells) were tumorigenic in immunodeficient mice. ALDHbright cells present in these cell lines, xenografts or surgically removed lesions were recognized by ALDH1A1-specific CD8+ T cells in vitro. Adoptive therapy with ALDH1A1-specific CD8+ T cells eliminated ALDHbright cells, inhibited tumor growth, metastases or prolonged survival of xenograft-bearing immunodeficient mice. Conclusions The results of this translational study strongly support the potential of ALDH1A1-based immunotherapy to selectively target CIC in human cancer. PMID:21856769

  13. Spacecraft Charging Technology, 1978

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The interaction of the aerospace environment with spacecraft surfaces and onboard, high voltage spacecraft systems operating over a wide range of altitudes from low Earth orbit to geosynchronous orbit is considered. Emphasis is placed on control of spacecraft electric potential. Electron and ion beams, plasma neutralizers material selection, and magnetic shielding are among the topics discussed.

  14. Tissue-Specific Stem Cells in the Myometrium and Tumor-Initiating Cells in Leiomyoma1

    PubMed Central

    Ono, Masanori; Bulun, Serdar E.; Maruyama, Tetsuo

    2014-01-01

    ABSTRACT Tissue-specific (or somatic) stem cells constitute a subset of cells residing in normal adult tissues. By undergoing asymmetric division, they retain their ability to self-renew while producing daughter cells that go on to differentiate and play a role in tissue regeneration and repair. The human uterus consists primarily of endometrium and myometrium (the smooth muscle layer) that rapidly enlarges through its tremendous regenerative and remodeling capacity to accommodate the developing fetus. Such uterine enlargement and remodeling can take place repeatedly and cyclically over the course of a woman's reproductive life. These unique properties of the uterus suggest the existence of endometrial and myometrial stem cell systems. In addition, like somatic cells, tumor stem cells or tumor-initiating cells, a subset of cells within a tumor, retain the ability to reconstitute tumors. Uterine smooth muscle cells are thought to be the origin of leiomyomas that are the most common type of gynecologic tumor. Recent work has identified, isolated, and characterized putative stem/progenitor cells in the myometrium and in leiomyomas. Here, we review current studies of myometrial and leiomyoma stem/progenitor cells and provide a new paradigm for understanding myometrial physiology and pathology and how these cells might contribute to uterine remodeling during pregnancy and the formation of leiomyomas. The role of the WNT/CTNNB1 pathway in the pathogenesis of leiomyoma is also discussed. PMID:25376230

  15. Long-lived intestinal tuft cells serve as colon cancer-initiating cells.

    PubMed

    Westphalen, C Benedikt; Asfaha, Samuel; Hayakawa, Yoku; Takemoto, Yoshihiro; Lukin, Dana J; Nuber, Andreas H; Brandtner, Anna; Setlik, Wanda; Remotti, Helen; Muley, Ashlesha; Chen, Xiaowei; May, Randal; Houchen, Courtney W; Fox, James G; Gershon, Michael D; Quante, Michael; Wang, Timothy C

    2014-03-01

    Doublecortin-like kinase 1 protein (DCLK1) is a gastrointestinal tuft cell marker that has been proposed to identify quiescent and tumor growth-sustaining stem cells. DCLK1⁺ tuft cells are increased in inflammation-induced carcinogenesis; however, the role of these cells within the gastrointestinal epithelium and their potential as cancer-initiating cells are poorly understood. Here, using a BAC-CreERT-dependent genetic lineage-tracing strategy, we determined that a subpopulation of DCLK1⁺ cells is extremely long lived and possesses rare stem cell abilities. Moreover, genetic ablation of Dclk1 revealed that DCLK1⁺ tuft cells contribute to recovery following intestinal and colonic injury. Surprisingly, conditional knockdown of the Wnt regulator APC in DCLK1⁺ cells was not sufficient to drive colonic carcinogenesis under normal conditions; however, dextran sodium sulfate-induced (DSS-induced) colitis promoted the development of poorly differentiated colonic adenocarcinoma in mice lacking APC in DCLK1⁺ cells. Importantly, colonic tumor formation occurred even when colitis onset was delayed for up to 3 months after induced APC loss in DCLK1⁺ cells. Thus, our data define an intestinal DCLK1⁺ tuft cell population that is long lived, quiescent, and important for intestinal homeostasis and regeneration. Long-lived DCLK1⁺ cells maintain quiescence even following oncogenic mutation, but are activated by tissue injury and can serve to initiate colon cancer. PMID:24487592

  16. Lean spacecraft avionics trade study

    NASA Technical Reports Server (NTRS)

    Main, John A.

    1994-01-01

    Spacecraft design is generally an exercise in design trade-offs: fuel vs. weight, power vs. solar cell area, radiation exposure vs. shield weight, etc. Proper analysis of these trades is critical in the development of lightweight, efficient, 'lean' satellites. The modification of the launch plans for the Magnetosphere Imager (MI) to a Taurus launcher from the much more powerful Delta has forced a reduction in spacecraft weight availability into the mission orbit from 1300 kg to less than 500 kg. With weight now a driving factor it is imperative that the satellite design be extremely efficient and lean. The accuracy of engineering trades now takes on an added importance. An understanding of spacecraft subsystem interactions is critical in the development of a good spacecraft design, yet it is a challenge to define these interactions while the design is immature. This is currently an issue in the development of the preliminary design of the MI. The interaction and interfaces between this spacecraft and the instruments it carries are currently unclear since the mission instruments are still under development. It is imperative, however, to define these interfaces so that avionics requirements ideally suited to the mission's needs can be determined.

  17. Autonomy Architectures for a Constellation of Spacecraft

    NASA Technical Reports Server (NTRS)

    Barrett, Anthony

    2000-01-01

    Until the past few years, missions typically involved fairly large expensive spacecraft. Such missions have primarily favored using older proven technologies over more recently developed ones, and humans controlled spacecraft by manually generating detailed command sequences with low-level tools and then transmitting the sequences for subsequent execution on a spacecraft controller. This approach toward controlling a spacecraft has worked spectacularly on previous missions, but it has limitations deriving from communications restrictions - scheduling time to communicate with a particular spacecraft involves competing with other projects due to the limited number of deep space network antennae. This implies that a spacecraft can spend a long time just waiting whenever a command sequence fails. This is one reason why the New Millennium program has an objective to migrate parts of mission control tasks onboard a spacecraft to reduce wait time by making spacecraft more robust. The migrated software is called a "remote agent" and has 4 components: a mission manager to generate the high level goals, a planner/scheduler to turn goals into activities while reasoning about future expected situations, an executive/diagnostics engine to initiate and maintain activities while interpreting sensed events by reasoning about past and present situations, and a conventional real-time subsystem to interface with the spacecraft to implement an activity's primitive actions. In addition to needing remote planning and execution for isolated spacecraft, a trend toward multiple-spacecraft missions points to the need for remote distributed planning and execution. The past few years have seen missions with growing numbers of probes. Pathfinder has its rover (Sojourner), Cassini has its lander (Huygens), and the New Millenium Deep Space 3 (DS3) proposal involves a constellation of 3 spacecraft for interferometric mapping. This trend is expected to continue to progressively larger fleets. For

  18. The Effect of Initial Cell Concentration on Xylose Fermentation by Pichia stipitis

    NASA Astrophysics Data System (ADS)

    Agbogbo, Frank K.; Coward-Kelly, Guillermo; Torry-Smith, Mads; Wenger, Kevin; Jeffries, Thomas W.

    Xylose was fermented using Pichia stipitis CBS 6054 at different initial cell concentrations. A high initial cell concentration increased the rate of xylose utilization, ethanol formation, and the ethanol yield. The highest ethanol concentration of 41.0 g/L and a yield of 0.38 g/g was obtained using an initial cell concentration of 6.5 g/L. Even though more xylitol was produced when the initial cell concentrations were high, cell density had no effect on the final ethanol yield. A two-parameter mathematical model was used to predict the cell population dynamics at the different initial cell concentrations. The model parameters, a and b correlate with the initial cell concentrations used with an R 2 of 0.99.

  19. The ISO Spacecraft

    NASA Astrophysics Data System (ADS)

    Ximenez de Ferrin, S.

    1995-11-01

    ESA's Infrared Space Observatory (ISO) consists of two modules: the Payload module, which includes the telescope and the scientific instruments, and the Service Module, which houses the instruments electronics, the hydrazine propellant tank and all other classical spacecraft subsystems. To ensure that the telescope is kept near absolute zero and thus is the least disturbed by the effects of the infrared emissions from other elements of the system, the telescope is enclosed in a helium-cooled cryostat. The cryostat in turn is shaded by a Sun-shield to protect it from the heat of the direct Sun. The shield has a covering of solar cells that provide the electrical power needed for the mission.

  20. Spacecraft Dynamics and Control Program at AFRPL

    NASA Technical Reports Server (NTRS)

    Das, A.; Slimak, L. K. S.; Schloegel, W. T.

    1986-01-01

    A number of future DOD and NASA spacecraft such as the space based radar will be not only an order of magnitude larger in dimension than the current spacecraft, but will exhibit extreme structural flexibility with very low structural vibration frequencies. Another class of spacecraft (such as the space defense platforms) will combine large physical size with extremely precise pointing requirement. Such problems require a total departure from the traditional methods of modeling and control system design of spacecraft where structural flexibility is treated as a secondary effect. With these problems in mind, the Air Force Rocket Propulsion Laboratory (AFRPL) initiated research to develop dynamics and control technology so as to enable the future large space structures (LSS). AFRPL's effort in this area can be subdivided into the following three overlapping areas: (1) ground experiments, (2) spacecraft modeling and control, and (3) sensors and actuators. Both the in-house and contractual efforts of the AFRPL in LSS are summarized.

  1. Distinct EMT programs control normal mammary stem cells and tumour-initiating cells.

    PubMed

    Ye, Xin; Tam, Wai Leong; Shibue, Tsukasa; Kaygusuz, Yasemin; Reinhardt, Ferenc; Ng Eaton, Elinor; Weinberg, Robert A

    2015-09-10

    Tumour-initiating cells (TICs) are responsible for metastatic dissemination and clinical relapse in a variety of cancers. Analogies between TICs and normal tissue stem cells have led to the proposal that activation of the normal stem-cell program within a tissue serves as the major mechanism for generating TICs. Supporting this notion, we and others previously established that the Slug epithelial-to-mesenchymal transition-inducing transcription factor (EMT-TF), a member of the Snail family, serves as a master regulator of the gland-reconstituting activity of normal mammary stem cells, and that forced expression of Slug in collaboration with Sox9 in breast cancer cells can efficiently induce entrance into the TIC state. However, these earlier studies focused on xenograft models with cultured cell lines and involved ectopic expression of EMT-TFs, often at non-physiological levels. Using genetically engineered knock-in reporter mouse lines, here we show that normal gland-reconstituting mammary stem cells residing in the basal layer of the mammary epithelium and breast TICs originating in the luminal layer exploit the paralogous EMT-TFs Slug and Snail, respectively, which induce distinct EMT programs. Broadly, our findings suggest that the seemingly similar stem-cell programs operating in TICs and normal stem cells of the corresponding normal tissue are likely to differ significantly in their details. PMID:26331542

  2. Endothelial cell-initiated signaling promotes the survival and self-renewal of cancer stem cells

    PubMed Central

    Krishnamurthy, Sudha; Dong, Zhihong; Vodopyanov, Dmitry; Imai, Atsushi; Helman, Joseph I.; Prince, Mark E.; Wicha, Max S.; Nör, Jacques E.

    2010-01-01

    Recent studies have demonstrated that cancer stem cells play an important role in the pathobiology of head and neck squamous cell carcinomas (HNSCC). However, little is known about functional interactions between head and neck cancer stem-like cells (CSC) and surrounding stromal cells. Here, we used Aldehyde Dehydrogenase activity and CD44 expression to sort putative stem cells from primary human HNSCC. Implantation of 1,000 CSC (ALDH+CD44+Lin−) led to tumors in 13 (out of 15) mice, while 10,000 non-cancer stem cells (NCSC; ALDH−CD44−Lin−) resulted in 2 tumors in 15 mice. These data demonstrated that ALDH and CD44 select a sub-population of cells that are highly tumorigenic. The ability to self-renew was confirmed by the observation that ALDH+CD44+Lin− cells sorted from human HNSCC formed more spheroids (orospheres) in 3-D agarose matrices or ultra-low attachment plates than controls and were serially passaged in vivo. We observed that approximately 80% of the CSC were located in close proximity (within 100-µm radius) of blood vessels in human tumors, suggesting the existence of perivascular niches in HNSCC. In vitro studies demonstrated that endothelial cell-secreted factors promoted self-renewal of CSC, as demonstrated by the upregulation of Bmi-1 expression and the increase in the number of orospheres as compared to controls. Notably, selective ablation of tumor-associated endothelial cells stably transduced with a caspase-based artificial death switch (iCaspase-9) caused a marked reduction in the fraction of CSC in xenograft tumors. Collectively, these findings indicate that endothelial cell-initiated signaling can enhance the survival and self-renewal of head and neck cancer stem cells. PMID:21098716

  3. Hydrodynamics of cell-cell mechanical signaling in the initial stages of aggregation.

    PubMed

    Bouffanais, Roland; Yue, Dick K P

    2010-04-01

    Mechanotactic cell motility has recently been shown to be a key player in the initial aggregation of crawling cells such as leukocytes and amoebae. The effects of mechanotactic signaling in the early aggregation of amoeboid cells are here investigated using a general mathematical model based on known biological evidence. We elucidate the hydrodynamic fundamentals of the direct guiding of a cell through mechanotaxis in the case where one cell transmits a mechanotactic signal through the fluid flow by changing its shape. It is found that any mechanosensing cells placed in the stimulus field of mechanical stress are able to determine the signal transmission direction with a certain angular dispersion which does not preclude the aggregation from happening. The ubiquitous presence of noise is accounted for by the model. Finally, the mesoscopic pattern of aggregation is obtained which constitutes the bridge between, on one hand, the microscopic world where the changes in the cell shape occur and, on the other hand, the cooperative behavior of the cells at the mesoscopic scale. PMID:20481766

  4. RIPK3 Restricts Myeloid Leukemogenesis by Promoting Cell Death and Differentiation of Leukemia Initiating Cells.

    PubMed

    Höckendorf, Ulrike; Yabal, Monica; Herold, Tobias; Munkhbaatar, Enkhtsetseg; Rott, Stephanie; Jilg, Stefanie; Kauschinger, Johanna; Magnani, Giovanni; Reisinger, Florian; Heuser, Michael; Kreipe, Hans; Sotlar, Karl; Engleitner, Thomas; Rad, Roland; Weichert, Wilko; Peschel, Christian; Ruland, Jürgen; Heikenwalder, Mathias; Spiekermann, Karsten; Slotta-Huspenina, Julia; Groß, Olaf; Jost, Philipp J

    2016-07-11

    Since acute myeloid leukemia (AML) is characterized by the blockade of hematopoietic differentiation and cell death, we interrogated RIPK3 signaling in AML development. Genetic loss of Ripk3 converted murine FLT3-ITD-driven myeloproliferation into an overt AML by enhancing the accumulation of leukemia-initiating cells (LIC). Failed inflammasome activation and cell death mediated by tumor necrosis factor receptor caused this accumulation of LIC exemplified by accelerated leukemia onset in Il1r1(-/-), Pycard(-/-), and Tnfr1/2(-/-) mice. RIPK3 signaling was partly mediated by mixed lineage kinase domain-like. This link between suppression of RIPK3, failed interleukin-1β release, and blocked cell death was supported by significantly reduced RIPK3 in primary AML patient cohorts. Our data identify RIPK3 and the inflammasome as key tumor suppressors in AML. PMID:27411587

  5. Initial Comparisons between the Advanced Technology Development Gen 2 Baseline Cells and Variant C Cells

    SciTech Connect

    Christophersen, Jon Petter; Motloch, Chester George; Wright, Randy Ben; Murphy, Timothy Collins; Belt, Jeffrey R; Ho, Chinh Dac; Bloom, Ira D.; Jones, S. A.; Battaglia, Vincent S.; Jungst, Rudy G.; Case, Herb L.; Sutula, Raymond A.; Barnes, James A.; Duong, Tien Q.

    2002-06-01

    The Advanced Technology Development Program is testing a second generation of lithium-ion cells, consisting of a baseline and three variant chemistries. The cathode composition of the Variant C chemistry was altered with an increase to the aluminum dopant and a decrease to the cobalt dopant to explore the impact on performance. However, it resulted in a 20% drop in rated capacity. Also, the Variant C average power fade is higher, but capacity fade is higher for the Baseline cell chemistry. Initial results indicate that the Variant C chemistry will reach end of life sooner than the Baseline chemistry.

  6. Implicit Spacecraft Gyro Calibration

    NASA Technical Reports Server (NTRS)

    Harman, Richard; Bar-Itzhack, Itzhack Y.

    2003-01-01

    This paper presents an implicit algorithm for spacecraft onboard instrument calibration, particularly to onboard gyro calibration. This work is an extension of previous work that was done where an explicit gyro calibration algorithm was applied to the AQUA spacecraft gyros. The algorithm presented in this paper was tested using simulated data and real data that were downloaded from the Microwave Anisotropy Probe (MAP) spacecraft. The calibration tests gave very good results. A comparison between the use of the implicit calibration algorithm used here with the explicit algorithm used for AQUA spacecraft indicates that both provide an excellent estimation of the gyro calibration parameters with similar accuracies.

  7. Spacecraft camera image registration

    NASA Technical Reports Server (NTRS)

    Kamel, Ahmed A. (Inventor); Graul, Donald W. (Inventor); Chan, Fred N. T. (Inventor); Gamble, Donald W. (Inventor)

    1987-01-01

    A system for achieving spacecraft camera (1, 2) image registration comprises a portion external to the spacecraft and an image motion compensation system (IMCS) portion onboard the spacecraft. Within the IMCS, a computer (38) calculates an image registration compensation signal (60) which is sent to the scan control loops (84, 88, 94, 98) of the onboard cameras (1, 2). At the location external to the spacecraft, the long-term orbital and attitude perturbations on the spacecraft are modeled. Coefficients (K, A) from this model are periodically sent to the onboard computer (38) by means of a command unit (39). The coefficients (K, A) take into account observations of stars and landmarks made by the spacecraft cameras (1, 2) themselves. The computer (38) takes as inputs the updated coefficients (K, A) plus synchronization information indicating the mirror position (AZ, EL) of each of the spacecraft cameras (1, 2), operating mode, and starting and stopping status of the scan lines generated by these cameras (1, 2), and generates in response thereto the image registration compensation signal (60). The sources of periodic thermal errors on the spacecraft are discussed. The system is checked by calculating measurement residuals, the difference between the landmark and star locations predicted at the external location and the landmark and star locations as measured by the spacecraft cameras (1, 2).

  8. Reactor power system/spacecraft integration

    NASA Technical Reports Server (NTRS)

    Elms, R. V.

    1985-01-01

    The new national initiative in space reactor technology evaluation and development is strongly tied to mission applications and to spacecraft and space transportation system (STS) compatibility. This paper discusses the power system integration interfaces with potential using spacecraft and the STS, and the impact of these requirements on the design. The integration areas of interest are mechanical, thermal, electrical, attitude control, and mission environments. The mission environments include space vacuum, solar input, heat sink, space radiation, weapons effects, and reactor power system radiation environments. The natural, reactor, and weapons effects radiation must be evaluated and combined to define the design requirements for spacecraft electronic equipment.

  9. Development of cancer-initiating cells and immortalized cells with genomic instability.

    PubMed

    Yoshioka, Ken-Ichi; Atsumi, Yuko; Nakagama, Hitoshi; Teraoka, Hirobumi

    2015-03-26

    Cancers that develop after middle age usually exhibit genomic instability and multiple mutations. This is in direct contrast to pediatric tumors that usually develop as a result of specific chromosomal translocations and epigenetic aberrations. The development of genomic instability is associated with mutations that contribute to cellular immortalization and transformation. Cancer occurs when cancer-initiating cells (CICs), also called cancer stem cells, develop as a result of these mutations. In this paper, we explore how CICs develop as a result of genomic instability, including looking at which cancer suppression mechanisms are abrogated. A recent in vitro study revealed the existence of a CIC induction pathway in differentiating stem cells. Under aberrant differentiation conditions, cells become senescent and develop genomic instabilities that lead to the development of CICs. The resulting CICs contain a mutation in the alternative reading frame of CDKN2A (ARF)/p53 module, i.e., in either ARF or p53. We summarize recently established knowledge of CIC development and cellular immortality, explore the role of the ARF/p53 module in protecting cells from transformation, and describe a risk factor for genomic destabilization that increases during the process of normal cell growth and differentiation and is associated with the downregulation of histone H2AX to levels representative of growth arrest in normal cells. PMID:25815132

  10. Development of cancer-initiating cells and immortalized cells with genomic instability

    PubMed Central

    Yoshioka, Ken-ichi; Atsumi, Yuko; Nakagama, Hitoshi; Teraoka, Hirobumi

    2015-01-01

    Cancers that develop after middle age usually exhibit genomic instability and multiple mutations. This is in direct contrast to pediatric tumors that usually develop as a result of specific chromosomal translocations and epigenetic aberrations. The development of genomic instability is associated with mutations that contribute to cellular immortalization and transformation. Cancer occurs when cancer-initiating cells (CICs), also called cancer stem cells, develop as a result of these mutations. In this paper, we explore how CICs develop as a result of genomic instability, including looking at which cancer suppression mechanisms are abrogated. A recent in vitro study revealed the existence of a CIC induction pathway in differentiating stem cells. Under aberrant differentiation conditions, cells become senescent and develop genomic instabilities that lead to the development of CICs. The resulting CICs contain a mutation in the alternative reading frame of CDKN2A (ARF)/p53 module, i.e., in either ARF or p53. We summarize recently established knowledge of CIC development and cellular immortality, explore the role of the ARF/p53 module in protecting cells from transformation, and describe a risk factor for genomic destabilization that increases during the process of normal cell growth and differentiation and is associated with the downregulation of histone H2AX to levels representative of growth arrest in normal cells. PMID:25815132

  11. Tumor-initiating label-retaining cancer cells in human gastrointestinal cancers undergo asymmetric cell division.

    PubMed

    Xin, Hong-Wu; Hari, Danielle M; Mullinax, John E; Ambe, Chenwi M; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J; Wiegand, Gordon W; Garfield, Susan H; Thorgeirsson, Snorri S; Avital, Itzhak

    2012-04-01

    Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. PMID:22331764

  12. Discussion meeting on Gossamer spacecraft (ultralightweight spacecraft)

    NASA Technical Reports Server (NTRS)

    Brereton, R. G. (Editor)

    1980-01-01

    Concepts, technology, and application of ultralightweight structures in space are examined. Gossamer spacecraft represented a generic class of space vehicles or structures characterized by a low mass per unit area (approximately 50g/m2). Gossamer concepts include the solar sail, the space tether, and various two and three dimensional large lightweight structures that were deployed or assembled in space. The Gossamer Spacecraft had a high potential for use as a transportation device (solar sail), as a science instrument (reflecting or occulting antenna), or as a large structural component for an enclosure, manned platform, or other human habitats. Inflatable structures were one possible building element for large ultralightweight structures in space.

  13. Tumor-initiating and -propagating cells: cells that we would like to identify and control.

    PubMed

    Tysnes, Berit Bølge

    2010-07-01

    Identification of the cell types capable of initiating and sustaining growth of the neoplastic clone in vivo is a fundamental problem in cancer research. It is likely that tumor growth can be sustained both by rare cancer stem-like cells and selected aggressive clones and that the nature of the mutations, the cell of origin, and its environment will contribute to tumor propagation. Genomic instability, suggested as a driving force in tumorigenesis, may be induced by genetic and epigenetic changes. The feature of self-renewal in stem cells is shared with tumor cells, and deviant function of the stem cell regulatory networks may, in complex ways, contribute to malignant transformation and the establishment of a cancer stem cell-like phenotype. Understanding the nature of the more quiescent cancer stem-like cells and their niches has the potential to develop novel cancer therapeutic protocols including pharmacological targeting of self-renewal pathways. Drugs that target cancer-related inflammation may have the potential to reeducate a tumor-promoting microenvironment. Because most epigenetic modifications may be reversible, DNA methylation and histone deacetylase inhibitors can be used to induce reexpression of genes that have been silenced epigenetically. Design of therapies that eliminate cancer stem-like cells without eliminating normal stem cells will be important. Further insight into the mechanisms by which pluripotency transcription factors (e.g., OCT4, SOX2, and Nanog), polycomb repressive complexes and microRNA balance selfrenewal and differentiation will be essential for our understanding of both embryonic differentiation and human carcinogenesis and for the development of new treatment strategies. PMID:20651980

  14. Tumor-Initiating and -Propagating Cells: Cells That We Would Like to Identify and Control1

    PubMed Central

    Tysnes, Berit Bølge

    2010-01-01

    Identification of the cell types capable of initiating and sustaining growth of the neoplastic clone in vivo is a fundamental problem in cancer research. It is likely that tumor growth can be sustained both by rare cancer stem-like cells and selected aggressive clones and that the nature of the mutations, the cell of origin, and its environment will contribute to tumor propagation. Genomic instability, suggested as a driving force in tumorigenesis, may be induced by genetic and epigenetic changes. The feature of self-renewal in stem cells is shared with tumor cells, and deviant function of the stem cell regulatory networks may, in complex ways, contribute to malignant transformation and the establishment of a cancer stem cell-like phenotype. Understanding the nature of the more quiescent cancer stem-like cells and their niches has the potential to develop novel cancer therapeutic protocols including pharmacological targeting of self-renewal pathways. Drugs that target cancer-related inflammation may have the potential to reeducate a tumor-promoting microenvironment. Because most epigenetic modifications may be reversible, DNA methylation and histone deacetylase inhibitors can be used to induce reexpression of genes that have been silenced epigenetically. Design of therapies that eliminate cancer stem-like cells without eliminating normal stem cells will be important. Further insight into the mechanisms by which pluripotency transcription factors (e.g., OCT4, SOX2, and Nanog), polycomb repressive complexes and microRNA balance selfrenewal and differentiation will be essential for our understanding of both embryonic differentiation and human carcinogenesis and for the development of new treatment strategies. PMID:20651980

  15. Spacecraft 2000: The challenge of the future

    NASA Technical Reports Server (NTRS)

    Brandhorst, Henry W., Jr.; Faymon, Karl A.; Bercaw, Robert W.

    1987-01-01

    Considerable opportunity exists to improve the systems, subsystems, components, etc., included in the space station bus, the non-payload portion of the spacecraft. The steps followed to date, the challenges being faced by industry, and the progress toward establishing a new NASA initiative which will identify the technologies required to build spacecraft of the 21st century and which will implement the technology development/validation programs necessary are described.

  16. Micro-Inspector Spacecraft: An Overview

    NASA Technical Reports Server (NTRS)

    Goldberg, Hannah; Mueller, Juergen; Alkalai, Leon

    2006-01-01

    JPL has developed a small(<5 kg) spacecraft capable of visual inspection of a host vehicle with support from NASA's Exploration Systems Mission Directorate (ESMD). This paper describes the multi-mission utility of the Micro-Inspector and presents an overview of the spacecraft system and subsystem designs, description of a typical inspection mission scenario, and initial hardware demonstrations of key subsystems, partially integrated with each other in a Micro-Inspector testbed at JPL.

  17. Beam experiments in space: how do we take the charge off the spacecraft?

    NASA Astrophysics Data System (ADS)

    Delzanno, G. L.; Borovsky, J.; Thomsen, M. F.; Moulton, J. D.; MacDonald, E.

    2014-12-01

    The idea of using a high intensity electron beam to actively probe magnetic field line connectivity in space has been discussed since the 1970's. However, its experimental realization onboard a magnetospheric spacecraft has never been accomplished because of serious spacecraft charging concerns. Unlike the case of beam experiments in the ionosphere, the tenuous magnetospheric plasma cannot provide the return current necessary to keep the spacecraft charging under control and alternative pathways must therefore be sought. One such pathway is the concept in which a high density contactor plasma emitted prior to the electron beam is used to aid beam emission. In this work, we perform Particle-In-Cell simulations to investigate the conditions under which a high intensity electron beam can be emitted from a magnetospheric spacecraft. First, we show that the electron beam cannot simply be compensated for by an ion beam of equal current, because the Child-Langmuir law is easily violated under conditions of interest. Second, we study the release of a contactor neutral plasma before beam emission and show that the presence of the contactor plasma allows beam emission for longer times. This is consistent with a simple picture where the capacitance of the system consisting of the spacecraft and the ion contactor cloud is increased, as is the time necessary for the spacecraft to charge to the beam kinetic energy and call the beam back. Last, we perform simulations where both the electron beam and the contactor plasma are emitted simultaneously. We show that, after an initial transient controlled by the size of the initial contactor cloud, where the spacecraft potential rises, the spacecraft potential can settle into conditions that allow for electron beam emission. A physical explanation of this result is presented and its implications for beam experiments in space are discussed.

  18. Cancer stem cells, cancer-initiating cells and methods for their detection.

    PubMed

    Akbari-Birgani, Shiva; Paranjothy, Ted; Zuse, Anna; Janikowski, Tomasz; Cieślar-Pobuda, Artur; Likus, Wirginia; Urasińska, Elżbieta; Schweizer, Frank; Ghavami, Saeid; Klonisch, Thomas; Łos, Marek J

    2016-05-01

    The cancer stem cell (CSC) hypothesis considers CSCs as the main culprits of tumor initiation, propagation, metastasis and therapy failure. CSCs represent a minority subpopulation of cells within a tumor. Their detection, characterization and monitoring are crucial steps toward a better understanding of the biological roles of these special cells in the development and propagation of tumors which, in turn, improves clinical reasoning and treatment options. Nowadays, in vitro and in vivo assays are available that address the self-renewal and differentiation potential of CSCs, and advanced in vivo molecular imaging technology facilitates the detection and provides an unprecedented in vivo observation platform to study the behavior of CSCs in their natural environment. Here, we provide a brief overview of CSCs and describe modern cellular models and labeling techniques to study and trace CSCs. PMID:26976692

  19. Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves

    PubMed Central

    Gomez-Sanchez, Jose A.; Carty, Lucy; Iruarrizaga-Lejarreta, Marta; Palomo-Irigoyen, Marta; Varela-Rey, Marta; Griffith, Megan; Hantke, Janina; Macias-Camara, Nuria; Azkargorta, Mikel; Aurrekoetxea, Igor; De Juan, Virginia Gutiérrez; Jefferies, Harold B.J.; Aspichueta, Patricia; Elortza, Félix; Aransay, Ana M.; Martínez-Chantar, María L.; Baas, Frank; Mato, José M.; Mirsky, Rhona

    2015-01-01

    Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell–mediated myelin digestion possible have not been established. We report that Schwann cells degrade myelin after injury by a novel form of selective autophagy, myelinophagy. Autophagy was up-regulated by myelinating Schwann cells after nerve injury, myelin debris was present in autophagosomes, and pharmacological and genetic inhibition of autophagy impaired myelin clearance. Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury. We also present evidence that myelinophagy is defective in the injured central nervous system. These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease. PMID:26150392

  20. Timing of initiation of chromosome replication in individual Escherichia coli cells.

    PubMed Central

    Skarstad, K; Boye, E; Steen, H B

    1986-01-01

    The synchrony of initiation of chromosome replication at multiple origins within individual Escherichia coli cells was studied by a novel method. Initiation of replication was inhibited with rifampicin or chloramphenicol and after completion of ongoing rounds of replication the numbers of fully replicated chromosomes in individual cells were measured by flow cytometry. In rapidly growing cultures, with parallel replication of several chromosomes, cells will end up with 2n (n = 1, 2, 3) chromosomes if initiation occurs simultaneously at all origins. A culture with asynchronous initiation may in addition contain cells with irregular numbers (not equal to 2n) of chromosomes. The frequency of cells with irregular numbers of chromosomes is a measure of the degree of asynchrony of initiation. After inhibition of initiation and run-out of replication in rapidly growing B/r A and K-12 cultures, a small fraction of the cells (2-7%) contained 3, 5, 6 or 7 chromosomes. From these measurements it was calculated that initiation at four origins in a single cell occurred within a small fraction, 0.1, of the doubling time (tau). A dnaA(Ts) mutant strain grown at permissive temperature exhibited a very large fraction of cells with irregular numbers of chromosomes after drug treatment demonstrating virtually random timing of initiation. A similar pattern of chromosome number per cell was found after treatment of a recA strain. PMID:3527695

  1. Small Spacecraft Technology

    NASA Technical Reports Server (NTRS)

    Shope, R.

    1995-01-01

    Aerospace designers are aggressively pursuing new ideas in advanced technology for smaller spacecraft. NASA's 'faster, better, cheaper' philosophy is the driving force to accomplish higher level scientific exploration more efficiently. More memory and higher performance is packed into computer hardware that takes up a fraction of the space of earlier generation spacecraft. Current technology is described.

  2. Toxicology of spacecraft materials

    NASA Technical Reports Server (NTRS)

    Harris, E. S.

    1971-01-01

    The procedures for determining the toxicity of products outgassed from spacecraft structures are discussed. The test equipment involved in the tests and the criteria for acceptability are described. The use of animals as the final step in determining toxicity of a spacecraft environment is explained.

  3. Docking system for spacecraft

    NASA Technical Reports Server (NTRS)

    Kahn, Jon B. (Inventor)

    1988-01-01

    A mechanism is disclosed for the docking of a spacecraft to a space station where a connection for transfer of personnel and equipment is desired. The invention comprises an active docking structure on a spacecraft and a passive docking structure on the station. The passive structure includes a docking ring mounted on a tunnel structure fixed to the space station. The active structure includes a docking ring carried by an actuator-attenuator devices, each attached at one end to the ring and at its other end in the spacecraft payload bay. The devices respond to command signals for moving the docking ring between a stowed position in the spacecraft to a deployed position suitable for engagement with the docking ring. The devices comprise means responsive to signals of sensed loadings to absorb impact energy and retraction means for drawing the coupled spacecraft and station into final docked configuration and moving the tunnel structure to a berthed position in the spacecraft. Latches couple the spacecraft and space station upon contact of the docking rings and latches establish a structural tie between the spacecraft when retracted.

  4. Spacecraft thermal control

    NASA Technical Reports Server (NTRS)

    1973-01-01

    Guidance for the assessment and control of spacecraft temperatures is provided with emphasis on unmanned spacecraft in the space environment. The heat balance, elements of thermal design, and thermal control are discussed along with thermal testing, design criteria, and recommended practices.

  5. The electrification of spacecraft

    NASA Technical Reports Server (NTRS)

    Akishin, A. I.; Novikov, L. S.

    1985-01-01

    Physical and applied aspects of the electrification of space vehicles and natural celestial objects are discussed, the factors resulting in electrification of spacecraft are analyzed, and methods of investigating various phenomena associated with this electrification and ways of protecting spacecraft against the influence of static electricity are described. The booklet is intended for the general reader interested in present day questions of space technology.

  6. Spacecraft Thermal Control

    NASA Technical Reports Server (NTRS)

    Birur, Gajanana C.; Siebes, Georg; Swanson, Theodore D.; Powers, Edward I. (Technical Monitor)

    2001-01-01

    Thermal control of the spacecraft is typically achieved by removing heat from the spacecraft parts that tend to overheat and adding heat to the parts that tend get too cold. The equipment on the spacecraft can get very hot if it is exposed to the sun or have internal heat generation. The pans also can get very cold if they are exposed to the cold of deep space. The spacecraft and instruments must be designed to achieve proper thermal balance. The combination of the spacecraft's external thermal environment, its internal heat generation (i.e., waste heat from the operation of electrical equipment), and radiative heat rejection will determine this thermal balance. It should also be noted that this is seldom a static situation, external environmental influences and internal heat generation are normally dynamic variables which change with time. Topics discussed include thermal control system components, spacecraft mission categories, spacecraft thermal requirements, space thermal environments, thermal control hardware, launch and flight operations, advanced technologies for future spacecraft,

  7. NAC, Tiron and Trolox Impair Survival of Cell Cultures Containing Glioblastoma Tumorigenic Initiating Cells by Inhibition of Cell Cycle Progression

    PubMed Central

    Stigliani, Sara; Carra, Elisa; Monteghirfo, Stefano; Longo, Luca; Daga, Antonio; Dono, Mariella; Zupo, Simona; Giaretti, Walter; Castagnola, Patrizio

    2014-01-01

    Reactive oxygen species (ROS) are metabolism by-products that may act as signaling molecules to sustain tumor growth. Antioxidants have been used to impair cancer cell survival. Our goal was to determine the mechanisms involved in the response to antioxidants of a human cell culture (PT4) containing glioblastoma (GBM) tumorigenic initiating cells (TICs). ROS production in the absence or presence of N-acetyl-L-cysteine (NAC), tiron, and trolox was evaluated by flow cytometry (FCM). The effects of these antioxidants on cell survival and apoptosis were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) and FCM. The biological processes modulated by these drugs were determined by oligonucleotide microarray gene expression profiling. Our results showed that NAC, tiron and trolox impaired PT4 cell survival, had minor effects on ROS levels and caused wide deregulation of cell cycle genes. Furthermore, tiron and trolox caused inhibition of cell survival in two additional cell cultures containing TICs, FO-1 and MM1, established from a melanoma and a mesothelioma patient, respectively. NAC, instead, impaired survival of the MM1 cells but not of the FO-1 cells. However, when used in combination, NAC enhanced the inhibitory effect of PLX4032 (BRAF V600E inhibitor) and Gefitinib (EGFR inhibitor), on FO-1 and PT4 cell survival. Collectively, NAC, tiron and trolox modulated gene expression and impaired the growth of cultures containing TICs primarily by inhibiting cell cycle progression. PMID:24587218

  8. Miniature Robotic Spacecraft for Inspecting Other Spacecraft

    NASA Technical Reports Server (NTRS)

    Fredrickson, Steven; Abbott, Larry; Duran, Steve; Goode, Robert; Howard, Nathan; Jochim, David; Rickman, Steve; Straube, Tim; Studak, Bill; Wagenknecht, Jennifer; Lemke, Matthew; Wade, Randall; Wheeler, Scott; Baggerman, Clinton

    2004-01-01

    A report discusses the Miniature Autonomous Extravehicular Robotic Camera (Mini AERCam)-- a compact robotic spacecraft intended to be released from a larger spacecraft for exterior visual inspection of the larger spacecraft. The Mini AERCam is a successor to the AERCam Sprint -- a prior miniature robotic inspection spacecraft that was demonstrated in a space-shuttle flight experiment in 1997. The prototype of the Mini AERCam is a demonstration unit having approximately the form and function of a flight system. The Mini AERCam is approximately spherical with a diameter of about 7.5 in. (.19 cm) and a weight of about 10 lb (.4.5 kg), yet it has significant additional capabilities, relative to the 14-in. (36-cm), 35-lb (16-kg) AERCam Sprint. The Mini AERCam includes miniaturized avionics, instrumentation, communications, navigation, imaging, power, and propulsion subsystems, including two digital video cameras and a high-resolution still camera. The Mini AERCam is designed for either remote piloting or supervised autonomous operations, including station keeping and point-to-point maneuvering. The prototype has been tested on an air-bearing table and in a hardware-in-the-loop orbital simulation of the dynamics of maneuvering in proximity to the International Space Station.

  9. Technology for small spacecraft

    NASA Technical Reports Server (NTRS)

    1994-01-01

    This report gives the results of a study by the National Research Council's Panel on Small Spacecraft Technology that reviewed NASA's technology development program for small spacecraft and assessed technology within the U.S. government and industry that is applicable to small spacecraft. The panel found that there is a considerable body of advanced technology currently available for application by NASA and the small spacecraft industry that could provide substantial improvement in capability and cost over those technologies used for current NASA small spacecraft. These technologies are the result of developments by commercial companies, Department of Defense agencies, and to a lesser degree NASA. The panel also found that additional technologies are being developed by these same entities that could provide additional substantial improvement if development is successfully completed. Recommendations for future technology development efforts by NASA across a broad technological spectrum are made.

  10. Surviving Atmospheric Spacecraft Breakup

    NASA Technical Reports Server (NTRS)

    Szewczyk, Nathaniel J.; Conley, Catharine A.

    2003-01-01

    In essence, to survival a spacecraft breakup an animal must not experience a lethal event. Much as with surviving aircraft breakup, dissipation of lethal forces via breakup of the craft around the organism is likely to greatly increase the odds of survival. As spacecraft can travel higher and faster than aircraft, it is often assumed that spacecraft breakup is not a survivable event. Similarly, the belief that aircraft breakup or crashes are not survivable events is still prevalent in the general population. As those of us involved in search and rescue know, it is possible to survive both aircraft breakup and crashes. Here we make the first report of an animal, C. elegans, surviving atmospheric breakup of the spacecraft supporting it and discuss both the lethal events these animals had to escape and the implications implied for search and rescue following spacecraft breakup.

  11. Current LISA Spacecraft Design

    NASA Technical Reports Server (NTRS)

    Merkowitz, Stephen

    2008-01-01

    The Laser Interferometer Space Antenna (LISA) mission, a space based gravitational wave detector, uses laser metrology to measure distance fluctuations between proof masses aboard three spacecraft. LISA is unique from a mission design perspective in that three spacecraft and their associated operations form one distributed science instrument, unlike more conventional missions where an instrument is a component of an individual spacecraft. The design of the LiSA spacecraft is also tightly coupled to the design and requirements of the scientific payload; for this reason it is often referred to as a "sciencecraft." A detailed discussion will be presented that describes the current spacecraft design and mission architecture needed to meet the LISA science requirements.

  12. Current LISA Spacecraft Design

    NASA Technical Reports Server (NTRS)

    Merkowitz, S. M.; Castellucci, K. E.; Depalo, S. V.; Generie, J. A.; Maghami, P. G.; Peabody, H. L.

    2009-01-01

    The Laser Interferometer Space Antenna (LISA) mission. a space based gravitational wave detector. uses laser metrology to measure distance fluctuations between proof masses aboard three spacecraft. LISA is unique from a mission design perspective in that the three spacecraft and their associated operations form one distributed science instrument. unlike more conventional missions where an instrument is a component of an individual spacecraft. The design of the LISA spacecraft is also tightly coupled to the design and requirements of the scientific payload; for this reason it is often referred to as a "sciencecraft." Here we describe some of the unique features of the LISA spacecraft design that help create the quiet environment necessary for gravitational wave observations.

  13. Bactericidal effect of hydrogen peroxide on spacecraft isolates

    NASA Technical Reports Server (NTRS)

    Wardle, M. D.; Renninger, G. M.

    1975-01-01

    Results are presented for an experimental study designed to assess the effect of hydrogen peroxide on both sporeforming and nonsporeforming spacecraft isolates as an initial step in determining its suitability for microbiological decontamination of certain United States spacecraft. Survivor data were obtained for eight bacterial isolates (six sporeformers and two nonsporeformers) recovered before launch Mariner 9 and exposed to concentrations of 3, 10, and 15% hydrogen peroxide. The effects of various concentrations of hydrogen peroxide on the spores are presented in tabular form, along with the percentage of survival of nonsporeformers exposed to hydrogen peroxide. No viable vegetative cells were recovered after a 10-min exposure time to any of the three concentration of hydrogen peroxide.

  14. Spectra and spacecraft

    NASA Astrophysics Data System (ADS)

    Moroz, V. I.

    2001-02-01

    In June 1999, Dr. Regis Courtin, Associate Editor of PSS, suggested that I write an article for the new section of this journal: "Planetary Pioneers". I hesitated , but decided to try. One of the reasons for my doubts was my primitive English, so I owe the reader an apology for this in advance. Writing took me much more time than I supposed initially, I have stopped and again returned to manuscript many times. My professional life may be divided into three main phases: pioneering work in ground-based IR astronomy with an emphasis on planetary spectroscopy (1955-1970), studies of the planets with spacecraft (1970-1989), and attempts to proceed with this work in difficult times. I moved ahead using the known method of trials and errors as most of us do. In fact, only a small percentage of efforts led to some important results, a sort of dry residue. I will try to describe below how has it been in my case: what may be estimated as the most important, how I came to this, what was around, etc.

  15. Mechanics of Bacterial Cells and Initial Surface Colonisation.

    PubMed

    Aguayo, Sebastian; Bozec, Laurent

    2016-01-01

    The mechanical properties of bacterial cells play an important role in crucial bacterial processes such as cell growth, colonisation and biofilm formation. Recent developments in the field of nanotechnology and atomic force microscopy (AFM) have made it possible to observe, characterise and understand the nanomechanic behaviour of live bacterial cells as never before. Unlike traditional techniques, AFM makes it possible to employ living bacteria in their physiological environment with minimal or no sample preparation. The technique of AFM nanoindentation opens new possibilities to study bacterial cell wall stiffness under different mechanical and buffer conditions. Also, by attaching bacterial cells to functionalised AFM cantilevers, single-cell force spectroscopy (SCFS) can be used to measure the adhesion of bacteria to biological and non-biological substrates at the nano-newton and pico-newton scale, and provide specific information on receptor-ligand interactions. By studying the biophysics of the bacterial-surface interaction with the abovementioned techniques, it has been possible to gain new insight on the early stages of bacterial colonisation and biofilm formation. PMID:27193547

  16. Targeting breast cancer-initiating/stem cells with melanoma differentiation-associated gene-7/interleukin-24.

    PubMed

    Bhutia, Sujit K; Das, Swadesh K; Azab, Belal; Menezes, Mitchell E; Dent, Paul; Wang, Xiang-Yang; Sarkar, Devanand; Fisher, Paul B

    2013-12-01

    Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) displays a broad range of antitumor properties including cancer-specific induction of apoptosis, inhibition of tumor angiogenesis and modulation of antitumor immune responses. In our study, we elucidated the role of MDA-7/IL-24 in inhibiting growth of breast cancer-initiating/stem cells. Ad.mda-7 infection decreased proliferation of breast cancer-initiating/stem cells without affecting normal breast stem cells. Ad.mda-7 induced apoptosis and endoplasmic reticulum stress in breast cancer-initiating/stem cells similar to unsorted breast cancer cells and inhibited the self-renewal property of breast cancer-initiating/stem cells by suppressing Wnt/β-catenin signaling. Prevention of inhibition of Wnt signaling by LiCl increased cell survival upon Ad.mda-7 treatment, suggesting that Wnt signaling inhibition might play a key role in MDA-7/IL-24-mediated death of breast cancer-initiating/stem cells. In a nude mouse subcutaneous xenograft model, Ad.mda-7 injection profoundly inhibited growth of tumors generated from breast cancer-initiating/stem cells and also exerted a potent "bystander" activity inhibiting growth of distant uninjected tumors. Further studies revealed that tumor growth inhibition by Ad.mda-7 was associated with a decrease in proliferation and angiogenesis, two intrinsic features of MDA-7/IL-24, and a reduction in vivo in the percentage of breast cancer-initiating/stem cells. Our findings demonstrate that MDA-7/IL-24 is not only nontoxic to normal cells and normal stem cells but also can kill both unsorted cancer cells and enriched populations of cancer-initiating/stem cells, providing further documentation that MDA-7/IL-24 might be a safe and effective way to eradicate cancers and also potentially establish disease-free survival. PMID:23720015

  17. Regulation of Ovarian Cancer Stem Cells or Tumor-Initiating Cells

    PubMed Central

    Kwon, Mi Jeong; Shin, Young Kee

    2013-01-01

    Cancer stem cells or tumor-initiating cells (CSC/TICs), which can undergo self-renewal and differentiation, are thought to play critical roles in tumorigenesis, therapy resistance, tumor recurrence and metastasis. Tumor recurrence and chemoresistance are major causes of poor survival rates of ovarian cancer patients, which may be due in part to the existence of CSC/TICs. Therefore, elucidating the molecular mechanisms responsible for the ovarian CSC/TICs is required to develop a cure for this malignancy. Recent studies have indicated that the properties of CSC/TICs can be regulated by microRNAs, genes and signaling pathways which also function in normal stem cells. Moreover, emerging evidence suggests that the tumor microenvironments surrounding CSC/TICs are crucial for the maintenance of these cells. Similarly, efforts are now being made to unravel the mechanism involved in the regulation of ovarian CSC/TICs, although much work is still needed. This review considers recent advances in identifying the genes and pathways involved in the regulation of ovarian CSC/TICs. Furthermore, current approaches targeting ovarian CSC/TICs are described. Targeting both CSC/TICs and bulk tumor cells is suggested as a more effective approach to eliminating ovarian tumors. Better understanding of the regulation of ovarian CSC/TICs might facilitate the development of improved therapeutic strategies for recurrent ovarian cancer. PMID:23528891

  18. Failure Modes Experienced on Spacecraft Nicd Batteries

    NASA Technical Reports Server (NTRS)

    Gross, S.

    1985-01-01

    A review was made of failures and irregularities experienced on nickel cadmium batteries for 31 spacecraft. Only rarely did batteries fail completely. In many cases, poorly performing batteries were compensated for by a reduction in loads or by continuing to operate in spite of out-of-voltage conditions. Low discharge voltage was the most common problem observed in flight spacecraft (42%). Spacecraft batteries are often designed to protect against cell shorts, but cell shorts accounted for only 16% of the failures. Other causes of problems were high charge voltage (16%), battery problems caused by other elements of the spacecraft (10%), and open circuit failures (6%). Problems of miscellaneous or unknown causes occurred in 10% of the cases.

  19. EpCAM-positive hepatocellular carcinoma cells are tumor initiating cells with stem/progenitor cell features

    PubMed Central

    Yamashita, Taro; Ji, Junfang; Budhu, Anuradha; Forgues, Marshonna; Yang, Wen; Wang, Hong-Yang; Jia, Huliang; Ye, Qinghai; Qin, Lun-Xiu; Wauthier, Elaine; Reid, Lola M.; Minato, Hiroshi; Honda, Masao; Kaneko, Shuichi; Tang, Zhao-You; Wei Wang, Xin

    2009-01-01

    Background & Aims Cancer progression/metastases and embryonic development share many properties including cellular plasticity, dynamic cell motility, and integral interaction with the microenvironment. We hypothesized that the heterogeneous nature of hepatocellular carcinoma (HCC) may be, in part, due to the presence of hepatic cancer cells with stem/progenitor features. Methods Gene expression profiling and immunohistochemistry analyses were used to analyze 235 tumor specimens derived from two recently identified HCC subtypes (EpCAM+ AFP+ HCC and EpCAM− AFP− HCC). These subtypes differed in their expression of alpha-fetoprotein (AFP), a molecule produced in the developing embryo, and EpCAM, a cell surface hepatic stem cell marker. Fluorescence-activated cell sorting (FACS) was used to isolate EpCAM+ HCC cells, which were tested for hepatic stem/progenitor cell properties. Results Gene expression and pathway analyses revealed that the EpCAM+ AFP+ HCC subtype had features of hepatic stem/progenitor cells. Indeed, the FACS-isolated EpCAM+ HCC cells displayed hepatic cancer stem cell-like traits including the abilities to self-renew and differentiate. Moreover, these cells were capable of initiating highly invasive HCC in NOD/SCID mice. Activation of Wnt/β-catenin signaling enriched the EpCAM+ cell population, while RNA interference-based blockage of EpCAM, a Wnt/β-catenin signaling target, attenuated the activities of these cells. Conclusions Taken together, our results suggest that HCC growth and invasiveness is dictated by a subset of EpCAM+ cells, opening a new avenue for HCC cancer cell eradication by targeting Wnt/β-catenin signaling components such as EpCAM. PMID:19150350

  20. Initial results for the silicon monolithically interconnected solar cell product

    NASA Astrophysics Data System (ADS)

    Dinetta, L. C.; Shreve, K. P.; Cotter, J. E.; Barnett, A. M.

    1995-10-01

    This proprietary technology is based on AstroPower's electrostatic bonding and innovative silicon solar cell processing techniques. Electrostatic bonding allows silicon wafers to be permanently attached to a thermally matched glass superstrate and then thinned to final thicknesses less than 25 micron. These devices are based on the features of a thin, light-trapping silicon solar cell: high voltage, high current, light weight (high specific power) and high radiation resistance. Monolithic interconnection allows the fabrication costs on a per watt basis to be roughly independent of the array size, power or voltage, therefore, the cost effectiveness to manufacture solar cell arrays with output powers ranging from milliwatts up to four watts and output voltages ranging from 5 to 500 volts will be similar. This compares favorably to conventionally manufactured, commercial solar cell arrays, where handling of small parts is very labor intensive and costly. In this way, a wide variety of product specifications can be met using the same fabrication techniques. Prototype solar cells have demonstrated efficiencies greater than 11%. An open-circuit voltage of 5.4 volts, fill factor of 65%, and short-circuit current density of 28 mA/sq cm at AM1.5 illumination are typical. Future efforts are being directed to optimization of the solar cell operating characteristics as well as production processing. The monolithic approach has a number of inherent advantages, including reduced cost per interconnect and increased reliability of array connections. These features make this proprietary technology an excellent candidate for a large number of consumer products.

  1. Initial results for the silicon monolithically interconnected solar cell product

    NASA Technical Reports Server (NTRS)

    Dinetta, L. C.; Shreve, K. P.; Cotter, J. E.; Barnett, A. M.

    1995-01-01

    This proprietary technology is based on AstroPower's electrostatic bonding and innovative silicon solar cell processing techniques. Electrostatic bonding allows silicon wafers to be permanently attached to a thermally matched glass superstrate and then thinned to final thicknesses less than 25 micron. These devices are based on the features of a thin, light-trapping silicon solar cell: high voltage, high current, light weight (high specific power) and high radiation resistance. Monolithic interconnection allows the fabrication costs on a per watt basis to be roughly independent of the array size, power or voltage, therefore, the cost effectiveness to manufacture solar cell arrays with output powers ranging from milliwatts up to four watts and output voltages ranging from 5 to 500 volts will be similar. This compares favorably to conventionally manufactured, commercial solar cell arrays, where handling of small parts is very labor intensive and costly. In this way, a wide variety of product specifications can be met using the same fabrication techniques. Prototype solar cells have demonstrated efficiencies greater than 11%. An open-circuit voltage of 5.4 volts, fill factor of 65%, and short-circuit current density of 28 mA/sq cm at AM1.5 illumination are typical. Future efforts are being directed to optimization of the solar cell operating characteristics as well as production processing. The monolithic approach has a number of inherent advantages, including reduced cost per interconnect and increased reliability of array connections. These features make this proprietary technology an excellent candidate for a large number of consumer products.

  2. YAP/TEAD Co-Activator Regulated Pluripotency and Chemoresistance in Ovarian Cancer Initiated Cells

    PubMed Central

    Yu, Chao; Chang, Ting; Fan, Heng-Yu

    2014-01-01

    Recent evidence suggests that some solid tumors, including ovarian cancer, contain distinct populations of stem cells that are responsible for tumor initiation, growth, chemo-resistance, and recurrence. The Hippo pathway has attracted considerable attention and some investigators have focused on YAP functions for maintaining stemness and cell differentiation. In this study, we successfully isolated the ovarian cancer initiating cells (OCICs) and demonstrated YAP promoted self-renewal of ovarian cancer initiated cell (OCIC) through its downstream co-activator TEAD. YAP and TEAD families were required for maintaining the expression of specific genes that may be involved in OCICs' stemness and chemoresistance. Taken together, our data first indicate that YAP/TEAD co-activator regulated ovarian cancer initiated cell pluripotency and chemo-resistance. It proposed a new mechanism on the drug resistance in cancer stem cell that Hippo-YAP signal pathway might serve as therapeutic targets for ovarian cancer treatment in clinical. PMID:25369529

  3. Hydraulic conductivity of endothelial cell-initiated arterial cocultures.

    PubMed

    Mathura, Rishi A; Russell-Puleri, Sparkle; Cancel, Limary M; Tarbell, John M

    2014-04-01

    This study describes cocultures of arterial smooth muscle cells (SMCs) and endothelial cells (ECs) and the influences of their heterotypic interactions on hydraulic conductivity (L p ), an important transport property. A unique feature of these cocultures is that ECs were first grown to confluence and then SMCs were inoculated. Bovine aortic smooth muscle cells and bovine aortic endothelial cells (BAECs) were cocultured on Transwell Permeable Supports, and then exposed to a pressure-driven transmural flow. L p across each culture was measured using a bubble tracking apparatus that determined water flux (J v ). Our results indicate that arterial L p is significantly modulated by EC-SMC proximity, and serum content in culture. The L p of cocultures was also compared to the predictions of a resistances-in-series model to distinguish the contributions of heterotypic interactions between SMCs and ECs. Conditions that lead to significantly reduced coculture L p , compared to BAEC monoculture controls, have been uncovered and the lowest L p in the literature for an in vitro system are reported. In addition, VE-cadherin immunostaining of intact BAEC monolayers in each culture configuration reveals that EC-SMC proximity on a porous membrane has a dramatic influence on EC morphology patterns. The cocultures with the lowest L p have ECs with significantly elongated morphology. Confocal imaging indicates that there are no direct EC-SMC contacts in coculture. PMID:24264601

  4. Spacecraft Docking System

    NASA Technical Reports Server (NTRS)

    Ghofranian, Siamak (Inventor); Chuang, Li-Ping Christopher (Inventor); Motaghedi, Pejmun (Inventor)

    2016-01-01

    A method and apparatus for docking a spacecraft. The apparatus comprises elongate members, movement systems, and force management systems. The elongate members are associated with a docking structure for a spacecraft. The movement systems are configured to move the elongate members axially such that the docking structure for the spacecraft moves. Each of the elongate members is configured to move independently. The force management systems connect the movement systems to the elongate members and are configured to limit a force applied by the each of the elongate members to a desired threshold during movement of the elongate members.

  5. What cell biologists should know about the National Institutes of Health BRAIN Initiative

    PubMed Central

    Insel, Thomas R.; Koroshetz, Walter

    2015-01-01

    The BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative is an ambitious project to develop innovative tools for a deeper understanding of how the brain functions in health and disease. Early programs in the National Institutes of Health BRAIN Initiative focus on tools for next-generation imaging and recording, studies of cell diversity and cell census, and integrative approaches to circuit function. In all of these efforts, cell biologists can play a leading role. PMID:26668172

  6. Spacecraft dielectric material properties and spacecraft charging

    NASA Technical Reports Server (NTRS)

    Frederickson, A. R.; Wall, J. A.; Cotts, D. B.; Bouquet, F. L.

    1986-01-01

    The physics of spacecraft charging is reviewed, and criteria for selecting and testing semiinsulating polymers (SIPs) to avoid charging are discussed and illustrated. Chapters are devoted to the required properties of dielectric materials, the charging process, discharge-pulse phenomena, design for minimum pulse size, design to prevent pulses, conduction in polymers, evaluation of SIPs that might prevent spacecraft charging, and the general response of dielectrics to space radiation. SIPs characterized include polyimides, fluorocarbons, thermoplastic polyesters, poly(alkanes), vinyl polymers and acrylates, polymers containing phthalocyanine, polyacene quinones, coordination polymers containing metal ions, conjugated-backbone polymers, and 'metallic' conducting polymers. Tables summarizing the results of SIP radiation tests (such as those performed for the NASA Galileo Project) are included.

  7. Changes in inositol phosphates in wild carrot cells upon initiation of cell wall digestion

    SciTech Connect

    Rincon, M.; Boss, W.F.

    1987-04-01

    Previous studies have shown that inositol trisphosphate (IP/sub 3/) stimulated /sup 45/Ca/sup +2/ efflux from fusogenic carrot protoplasts and it was suggested that IP/sub 3/ may serve as a second messenger for the mobilization of intracellular Ca/sup +2/ in higher plant cells. To determine whether or not inositol phosphate metabolism changes in response to external stimuli, the cells were labeled with myo-(2-/sup 3/H) inositol for 18 h and exposed to cell wall digestion enzymes, Driselase. The inositol phosphates were extracted with ice cold 10% TCA and separated by anion exchange chromatography. The radioactivity of the fraction that contained IP/sub 3/ increased 2-3.8 fold and that which contained inositol bisphosphate increased 1.9-2.6 fold within 1.5 min of exposure to Driselase. After 6 min, the radioactivity of both fractions increased 6-7.7 fold and an increase in inositol monophosphate was observed. These data indicate that inositol phosphate metabolism is stimulated by Driselase and suggest polyphosphoinositide hydrolysis occurs upon initiation of cell wall digestion.

  8. A Comparative Systematic Review of the Optimal CD4 Cell Count Threshold for HIV Treatment Initiation

    PubMed Central

    Mitchell-Fearon, Kathryn

    2014-01-01

    HIV infection is no longer characterized by high morbidity, rapid progression to AIDS, and death as when the infection was first identified. While anti-retroviral drugs have improved the outcome of AIDS patients, clinical research on the appropriate time to initiate therapy continues to evolve. Optimal therapy initiation would maximize the benefits of these drugs, while minimizing side effects and drug resistance. Recent 2013 WHO guidelines changed HIV therapy initiation from 350 cells/μL to 500 cells/μL. This systematic review provides an evidence-based comparison of starting treatment at >500 cells/μL with starting treatment at the range between 350 cells/μL and 500 cells/μL. An 11% increase in risk was detected from initiation therapy at the 350–500 cells/μL range (0.37 [0.26, 0.53]), when compared with starting treatment before 500 cells/μL (0.33 [0.22, 0.48]). Most individual study comparisons showed a benefit for starting treatment at 500 cells/μL in comparison with starting at the 350–500 cells/μL range with risks ranging from 19% to 300%, though a number of comparisons were not statistically significant. Overall, the study provides evidence based support for initiating anti retroviral therapy at cell counts >500 cells/μL wherever possible to prevent AIDS mortality and morbidity. PMID:24778646

  9. Advanced nickel-hydrogen spacecraft battery development

    NASA Astrophysics Data System (ADS)

    Coates, Dwaine K.; Fox, Chris L.; Standlee, D. J.; Grindstaff, B. K.

    1994-02-01

    Eagle-Picher currently has several advanced nickel-hydrogen (NiH2) cell component and battery designs under development including common pressure vessel (CPV), single pressure vessel (SPV), and dependent pressure vessel (DPV) designs. A CPV NiH2 battery, utilizing low-cost 64 mm (2.5 in.) cell diameter technology, has been designed and built for multiple smallsat programs, including the TUBSAT B spacecraft which is currently scheduled (24 Nov. 93) for launch aboard a Russian Proton rocket. An advanced 90 mm (3.5 in.) NiH2 cell design is currently being manufactured for the Space Station Freedom program. Prototype 254 mm (10 in.) diameter SPV batteries are currently under construction and initial boilerplate testing has shown excellent results. NiH2 cycle life testing is being continued at Eagle-Picher and IPV cells have currently completed more than 89,000 accelerated LEO cycles at 15% DOD, 49,000 real-time LEO cycles at 30 percent DOD, 37,800 cycles under a real-time LEO profile, 30 eclipse seasons in accelerated GEO, and 6 eclipse seasons in real-time GEO testing at 75 percent DOD maximum. Nickel-metal hydride battery development is continuing for both aerospace and electric vehicle applications. Eagle-Picher has also developed an extensive range of battery evaluation, test, and analysis (BETA) measurement and control equipment and software, based on Hewlett-Packard computerized data acquisition/control hardware.

  10. Advanced nickel-hydrogen spacecraft battery development

    NASA Technical Reports Server (NTRS)

    Coates, Dwaine K.; Fox, Chris L.; Standlee, D. J.; Grindstaff, B. K.

    1994-01-01

    Eagle-Picher currently has several advanced nickel-hydrogen (NiH2) cell component and battery designs under development including common pressure vessel (CPV), single pressure vessel (SPV), and dependent pressure vessel (DPV) designs. A CPV NiH2 battery, utilizing low-cost 64 mm (2.5 in.) cell diameter technology, has been designed and built for multiple smallsat programs, including the TUBSAT B spacecraft which is currently scheduled (24 Nov. 93) for launch aboard a Russian Proton rocket. An advanced 90 mm (3.5 in.) NiH2 cell design is currently being manufactured for the Space Station Freedom program. Prototype 254 mm (10 in.) diameter SPV batteries are currently under construction and initial boilerplate testing has shown excellent results. NiH2 cycle life testing is being continued at Eagle-Picher and IPV cells have currently completed more than 89,000 accelerated LEO cycles at 15% DOD, 49,000 real-time LEO cycles at 30 percent DOD, 37,800 cycles under a real-time LEO profile, 30 eclipse seasons in accelerated GEO, and 6 eclipse seasons in real-time GEO testing at 75 percent DOD maximum. Nickel-metal hydride battery development is continuing for both aerospace and electric vehicle applications. Eagle-Picher has also developed an extensive range of battery evaluation, test, and analysis (BETA) measurement and control equipment and software, based on Hewlett-Packard computerized data acquisition/control hardware.

  11. Unusual spacecraft materials

    NASA Technical Reports Server (NTRS)

    Post, Jonathan V.

    1990-01-01

    For particularly innovative space exploration missions, unusual requirements are levied on the structural components of the spacecraft. In many cases, the preferred solution is the utilization of unusual materials. This trend is forecast to continue. Several hypothetic examples are discussed.

  12. Surviving atmospheric spacecraft breakup

    NASA Technical Reports Server (NTRS)

    Szewczyk, Nathaniel J.; McLamb, William

    2005-01-01

    Spacecraft travel higher and faster than aircraft, making breakup potentially less survivable. As with aircraft breakup, the dissipation of lethal forces via spacecraft breakup around an organism is likely to greatly increase the odds of survival. By employing a knowledge of space and aviation physiology, comparative physiology, and search-and-rescue techniques, we were able to correctly predict and execute the recovery of live animals following the breakup of the space shuttle Columbia. In this study, we make what is, to our knowledge, the first report of an animal, Caenorhabditis elegans, surviving the atmospheric breakup of the spacecraft that was supporting it and discuss both the lethal events these animals had to escape and the implications for search and rescue following spacecraft breakup.

  13. Quick spacecraft charging primer

    SciTech Connect

    Larsen, Brian Arthur

    2014-03-12

    This is a presentation in PDF format which is a quick spacecraft charging primer, meant to be used for program training. It goes into detail about charging physics, RBSP examples, and how to identify charging.

  14. Spacecraft Fire Safety

    NASA Technical Reports Server (NTRS)

    Margle, Janice M. (Editor)

    1987-01-01

    Fire detection, fire standards and testing, fire extinguishment, inerting and atmospheres, fire-related medical science, aircraft fire safety, Space Station safety concerns, microgravity combustion, spacecraft material flammability testing, and metal combustion are among the topics considered.

  15. Viking lander spacecraft battery

    NASA Technical Reports Server (NTRS)

    Newell, D. R.

    1976-01-01

    The Viking Lander was the first spacecraft to fly a sterilized nickel-cadmium battery on a mission to explore the surface of a planet. The significant results of the battery development program from its inception through the design, manufacture, and test of the flight batteries which were flown on the two Lander spacecraft are documented. The flight performance during the early phase of the mission is also presented.

  16. NASA spacecraft propulsion activities

    NASA Technical Reports Server (NTRS)

    Curran, Francis M.; Tyburski, Timothy E.; Sankovic, John M.; Jankovsky, Robert S.; Reed, Brian D.; Schneider, Steven J.; Hamley, John A.; Patterson, Michael J.; Sovey, James S.

    1997-01-01

    The NASA's activities in the development of spacecraft propulsion systems are reviewed, with emphasis on program directions and recent progress made in this domain. The recent trends towards the use of smaller spacecraft and launch vehicles call for new onboard propulsion systems. The NASA's efforts are conducted within the framework of the onboard propulsion program. The research and development work carried out in relation to the different propulsion system technologies are considered: electromagnetic systems; electrostatic systems; electrothermal systems; bipropellant systems; and monopropellant systems.

  17. Orbital spacecraft resupply technology

    NASA Technical Reports Server (NTRS)

    Eberhardt, R. N.; Tracey, T. R.; Bailey, W. J.

    1986-01-01

    The resupplying of orbital spacecraft using the Space Shuttle, Orbital Maneuvering Vehicle, Orbital Transfer Vehicle or a depot supply at a Space Station is studied. The governing factor in fluid resupply designs is the system size with respect to fluid resupply quantities. Spacecraft propellant management for tankage via diaphragm or surface tension configurations is examined. The capabilities, operation, and application of adiabatic ullage compression, ullage exchange, vent/fill/repressurize, and drain/vent/no-vent fill/repressurize, which are proposed transfer methods for spacecraft utilizing tankage configurations, are described. Selection of the appropriate resupply method is dependent on the spacecraft design features. Hydrazine adiabatic compression/detonation, liquid-free vapor venting to prevent freezing, and a method for no-vent liquid filling are analyzed. Various procedures for accurate measurements of propellant mass in low gravity are evaluated; a system of flowmeters with a PVT system was selected as the pressurant solubility and quantity gaging technique. Monopropellant and bipropellant orbital spacecraft consumable resupply system tanks which resupply 3000 lb of hydrazine and 7000 lb of MMH/NTO to spacecraft on orbit are presented.

  18. Pulmonary langerhans cell histiocytosis: PET/CT for initial workup and treatment response evaluation.

    PubMed

    Hansen, Neil J; Hankins, Jordan H

    2015-02-01

    A 40-year-old man underwent pan-endoscopy owing to abdominal pain. Biopsies of the gastrointestinal tract demonstrated diffuse Langerhans cell histiocytosis. PET/CT was done, with CT demonstrating classic pulmonary manifestations of Langerhans cell histiocytosis that had association with intense FDG uptake on PET. Bowel appeared normal. Treatment was initiated with smoking cessation and 6 cycles of cytarabine. Follow-up PET/CT after initial treatment demonstrated improvement of parenchymal abnormalities seen on CT, with resolution of hypermetabolic activity. Maintenance chemotherapy was initiated. PET/CT is increasingly being used for initial staging and treatment response assessment in this rare disorder. PMID:24999688

  19. Hydraulic Conductivity of Smooth Muscle Cell-Initiated Arterial Cocultures.

    PubMed

    Mathura, Rishi A; Russell-Puleri, Sparkle; Cancel, Limary M; Tarbell, John M

    2016-05-01

    The purpose of the study was to examine the effects of arterial coculture conditions on the transport properties of several in vitro endothelial cell (EC)-smooth muscle cell (SMC)-porous filter constructs in which SMC were grown to confluence first and then EC were inoculated. This order of culturing simulates the environment of a blood vessel wall after endothelial layer damage due to stenting, vascular grafting or other vascular wall insult. For all coculture configurations examined, we observed that hydraulic conductivity (L p) values were significantly higher than predicted by a resistances-in-series (RIS) model accounting for the L p of EC and SMC measured separately. The greatest increases were observed when EC were plated directly on top of a confluent SMC layer without an intervening filter, presumably mediated by direct EC-SMC contacts that were observed under confocal microscopy. The results are the opposite of a previous study that showed L p was significantly reduced compared to an RIS model when EC were grown to confluency first. The physiological, pathophysiological and tissue engineering implications of these results are discussed. PMID:26265460

  20. Spacecraft Attitude Maneuver Planning Using Genetic Algorithms

    NASA Technical Reports Server (NTRS)

    Kornfeld, Richard P.

    2004-01-01

    A key enabling technology that leads to greater spacecraft autonomy is the capability to autonomously and optimally slew the spacecraft from and to different attitudes while operating under a number of celestial and dynamic constraints. The task of finding an attitude trajectory that meets all the constraints is a formidable one, in particular for orbiting or fly-by spacecraft where the constraints and initial and final conditions are of time-varying nature. This approach for attitude path planning makes full use of a priori constraint knowledge and is computationally tractable enough to be executed onboard a spacecraft. The approach is based on incorporating the constraints into a cost function and using a Genetic Algorithm to iteratively search for and optimize the solution. This results in a directed random search that explores a large part of the solution space while maintaining the knowledge of good solutions from iteration to iteration. A solution obtained this way may be used as is or as an initial solution to initialize additional deterministic optimization algorithms. A number of representative case examples for time-fixed and time-varying conditions yielded search times that are typically on the order of minutes, thus demonstrating the viability of this method. This approach is applicable to all deep space and planet Earth missions requiring greater spacecraft autonomy, and greatly facilitates navigation and science observation planning.

  1. Future beam experiments in the magnetosphere with plasma contactors: How do we get the charge off the spacecraft?

    NASA Astrophysics Data System (ADS)

    Delzanno, G. L.; Borovsky, J. E.; Thomsen, M. F.; Moulton, J. D.; MacDonald, E. A.

    2015-05-01

    The idea of using a high-voltage electron beam with substantial current to actively probe magnetic field line connectivity in space has been discussed since the 1970s. However, its experimental realization onboard a magnetospheric spacecraft has never been accomplished because the tenuous magnetospheric plasma cannot provide the return current necessary to keep spacecraft charging under control. In this work, we perform Particle-In-Cell simulations to investigate the conditions under which a high-voltage electron beam can be emitted from a spacecraft and explore solutions that can mitigate spacecraft charging. The electron beam cannot simply be compensated for by an ion beam of equal current, because the Child-Langmuir space charge limit is violated under conditions of interest. On the other hand, releasing a high-density neutral contactor plasma prior and during beam emission is critical in aiding beam emission. We show that after an initial transient controlled by the size of the contactor cloud where the spacecraft potential rises, the spacecraft potential can settle into conditions that allow for electron beam emission. A physical explanation of this result in terms of ion emission into spherical geometry from the surface of the plasma cloud is presented, together with scaling laws of the peak spacecraft potential varying the ion mass and beam current. These results suggest that a strategy where the contactor plasma and the electron beam operate simultaneously might offer a pathway to perform beam experiments in the magnetosphere.

  2. Electrostatic charging of spacecraft in geosynchronous orbit

    NASA Astrophysics Data System (ADS)

    Sims, Andrew J.

    1992-12-01

    This Memorandum is a study of the spacecraft charging phenomenon applicable to satellites in geosynchronous orbit. Differential charging of spacecraft surfaces can induce electrostatic discharges which may manifest themselves as 'operational anomalies' or permanent damage to surface features such as solar cells and thermal control surfaces. Understanding of the problem is achieved via laboratory experiments, analysis of data from spacecraft instrumentation, and by numerical simulation. Long-term statistical studies are presented for the location of plasma boundaries at geostationary altitude and for the occurrence frequency and intensity of geomagnetic substorms which permit the probability of severe charging conditions to be predicted for future missions. Laboratory experiments are used to demonstrate the importance of bulk and surface conductivity of dielectric materials to the charging process and a sensitivity analysis is employed to investigate the detailed interaction between the plasma environment and spacecraft surface materials. Finally, a study and simulation of charging events observed in geosynchronous orbit is presented.

  3. Electrolysis Propulsion for Spacecraft Applications

    NASA Technical Reports Server (NTRS)

    deGroot, Wim A.; Arrington, Lynn A.; McElroy, James F.; Mitlitsky, Fred; Weisberg, Andrew H.; Carter, Preston H., II; Myers, Blake; Reed, Brian D.

    1997-01-01

    Electrolysis propulsion has been recognized over the last several decades as a viable option to meet many satellite and spacecraft propulsion requirements. This technology, however, was never used for in-space missions. In the same time frame, water based fuel cells have flown in a number of missions. These systems have many components similar to electrolysis propulsion systems. Recent advances in component technology include: lightweight tankage, water vapor feed electrolysis, fuel cell technology, and thrust chamber materials for propulsion. Taken together, these developments make propulsion and/or power using electrolysis/fuel cell technology very attractive as separate or integrated systems. A water electrolysis propulsion testbed was constructed and tested in a joint NASA/Hamilton Standard/Lawrence Livermore National Laboratories program to demonstrate these technology developments for propulsion. The results from these testbed experiments using a I-N thruster are presented. A concept to integrate a propulsion system and a fuel cell system into a unitized spacecraft propulsion and power system is outlined.

  4. Embedded Thermal Control for Spacecraft Subsystems Miniaturization

    NASA Technical Reports Server (NTRS)

    Didion, Jeffrey R.

    2014-01-01

    Optimization of spacecraft size, weight and power (SWaP) resources is an explicit technical priority at Goddard Space Flight Center. Embedded Thermal Control Subsystems are a promising technology with many cross cutting NSAA, DoD and commercial applications: 1.) CubeSatSmallSat spacecraft architecture, 2.) high performance computing, 3.) On-board spacecraft electronics, 4.) Power electronics and RF arrays. The Embedded Thermal Control Subsystem technology development efforts focus on component, board and enclosure level devices that will ultimately include intelligent capabilities. The presentation will discuss electric, capillary and hybrid based hardware research and development efforts at Goddard Space Flight Center. The Embedded Thermal Control Subsystem development program consists of interrelated sub-initiatives, e.g., chip component level thermal control devices, self-sensing thermal management, advanced manufactured structures. This presentation includes technical status and progress on each of these investigations. Future sub-initiatives, technical milestones and program goals will be presented.

  5. Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation.

    PubMed

    Marhavý, Peter; Montesinos, Juan Carlos; Abuzeineh, Anas; Van Damme, Daniel; Vermeer, Joop E M; Duclercq, Jerôme; Rakusová, Hana; Nováková, Petra; Friml, Jiři; Geldner, Niko; Benková, Eva

    2016-02-15

    To sustain a lifelong ability to initiate organs, plants retain pools of undifferentiated cells with a preserved proliferation capacity. The root pericycle represents a unique tissue with conditional meristematic activity, and its tight control determines initiation of lateral organs. Here we show that the meristematic activity of the pericycle is constrained by the interaction with the adjacent endodermis. Release of these restraints by elimination of endodermal cells by single-cell ablation triggers the pericycle to re-enter the cell cycle. We found that endodermis removal substitutes for the phytohormone auxin-dependent initiation of the pericycle meristematic activity. However, auxin is indispensable to steer the cell division plane orientation of new organ-defining divisions. We propose a dual, spatiotemporally distinct role for auxin during lateral root initiation. In the endodermis, auxin releases constraints arising from cell-to-cell interactions that compromise the pericycle meristematic activity, whereas, in the pericycle, auxin defines the orientation of the cell division plane to initiate lateral roots. PMID:26883363

  6. Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation

    PubMed Central

    Marhavý, Peter; Montesinos, Juan Carlos; Abuzeineh, Anas; Van Damme, Daniel; Vermeer, Joop E.M.; Duclercq, Jerôme; Rakusová, Hana; Nováková, Petra; Friml, Jiři; Geldner, Niko; Benková, Eva

    2016-01-01

    To sustain a lifelong ability to initiate organs, plants retain pools of undifferentiated cells with a preserved proliferation capacity. The root pericycle represents a unique tissue with conditional meristematic activity, and its tight control determines initiation of lateral organs. Here we show that the meristematic activity of the pericycle is constrained by the interaction with the adjacent endodermis. Release of these restraints by elimination of endodermal cells by single-cell ablation triggers the pericycle to re-enter the cell cycle. We found that endodermis removal substitutes for the phytohormone auxin-dependent initiation of the pericycle meristematic activity. However, auxin is indispensable to steer the cell division plane orientation of new organ-defining divisions. We propose a dual, spatiotemporally distinct role for auxin during lateral root initiation. In the endodermis, auxin releases constraints arising from cell-to-cell interactions that compromise the pericycle meristematic activity, whereas, in the pericycle, auxin defines the orientation of the cell division plane to initiate lateral roots. PMID:26883363

  7. Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis

    PubMed Central

    Rodríguez-Fraticelli, Alejo E.; Auzan, Muriel; Alonso, Miguel A.; Bornens, Michel

    2012-01-01

    Epithelial organ morphogenesis involves sequential acquisition of apicobasal polarity by epithelial cells and development of a functional lumen. In vivo, cells perceive signals from components of the extracellular matrix (ECM), such as laminin and collagens, as well as sense physical conditions, such as matrix stiffness and cell confinement. Alteration of the mechanical properties of the ECM has been shown to promote cell migration and invasion in cancer cells, but the effects on epithelial morphogenesis have not been characterized. We analyzed the effects of cell confinement on lumen morphogenesis using a novel, micropatterned, three-dimensional (3D) Madin-Darby canine kidney cell culture method. We show that cell confinement, by controlling cell spreading, limits peripheral actin contractility and promotes centrosome positioning and lumen initiation after the first cell division. In addition, peripheral actin contractility is mediated by master kinase Par-4/LKB1 via the RhoA–Rho kinase–myosin II pathway, and inhibition of this pathway restores lumen initiation in minimally confined cells. We conclude that cell confinement controls nuclear–centrosomal orientation and lumen initiation during 3D epithelial morphogenesis. PMID:22965908

  8. Taurus Lightweight Manned Spacecraft Earth orbiting vehicle

    NASA Technical Reports Server (NTRS)

    Bosset, M.

    1991-01-01

    The Taurus Lightweight Manned Spacecraft (LMS) was developed by students of the University of Maryland's Aerospace Engineering course in Space Vehicle Design. That course required students to design an Alternative Manned Spacecraft (AMS) to augment or replace the Space Transportation System and meet the following design requirements: (1) launch on the Taurus Booster being developed by Orbital Sciences Corporation; (2) 99.9 percent assured crew survival rate; (3) technology cutoff date of 1 Jan. 1991; (4) compatibility with current space administration infrastructure; and (5) first flight by May 1995. The Taurus LMS design meets the above requirements and represents an initial step toward larger and more complex spacecraft. The Taurus LMS has a very limited application when compared to the space shuttle, but it demonstrates that the U.S. can have a safe, reliable, and low-cost space system. The Taurus LMS is a short mission duration spacecraft designed to place one man into low Earth orbit (LEO). The driving factor for this design was the low payload carrying capabilities of the Taurus Booster - 1300 kg to a 300-km orbit. The Taurus LMS design is divided into six major design sections. The Human Factors section deals with the problems of life support and spacecraft cooling. The Propulsion section contains the Abort System, the Orbital Maneuvering System (OMS), the Reaction Control System (RCS), and Power Generation. The thermal protection systems and spacecraft structure are contained in the Structures section. The Avionics section includes Navigation, Attitude Determination, Data Processing, Communication systems, and Sensors. The Mission Analysis section was responsible for ground processing and spacecraft astrodynamics. The Systems Integration Section pulled the above sections together into one spacecraft, and addressed costing and reliability.

  9. Taurus Lightweight Manned Spacecraft Earth orbiting vehicle

    NASA Astrophysics Data System (ADS)

    Bosset, M.

    The Taurus Lightweight Manned Spacecraft (LMS) was developed by students of the University of Maryland's Aerospace Engineering course in Space Vehicle Design. That course required students to design an Alternative Manned Spacecraft (AMS) to augment or replace the Space Transportation System and meet the following design requirements: (1) launch on the Taurus Booster being developed by Orbital Sciences Corporation; (2) 99.9 percent assured crew survival rate; (3) technology cutoff date of 1 Jan. 1991; (4) compatibility with current space administration infrastructure; and (5) first flight by May 1995. The Taurus LMS design meets the above requirements and represents an initial step toward larger and more complex spacecraft. The Taurus LMS has a very limited application when compared to the space shuttle, but it demonstrates that the U.S. can have a safe, reliable, and low-cost space system. The Taurus LMS is a short mission duration spacecraft designed to place one man into low Earth orbit (LEO). The driving factor for this design was the low payload carrying capabilities of the Taurus Booster - 1300 kg to a 300-km orbit. The Taurus LMS design is divided into six major design sections. The Human Factors section deals with the problems of life support and spacecraft cooling. The Propulsion section contains the Abort System, the Orbital Maneuvering System (OMS), the Reaction Control System (RCS), and Power Generation. The thermal protection systems and spacecraft structure are contained in the Structures section. The Avionics section includes Navigation, Attitude Determination, Data Processing, Communication systems, and Sensors. The Mission Analysis section was responsible for ground processing and spacecraft astrodynamics. The Systems Integration Section pulled the above sections together into one spacecraft, and addressed costing and reliability.

  10. Taurus lightweight manned spacecraft Earth orbiting vehicle

    NASA Technical Reports Server (NTRS)

    Chase, Kevin A.; Vandersall, Eric J.; Plotkin, Jennifer; Travisano, Jeffrey J.; Loveless, Dennis; Kaczmarek, Michael; White, Anthony G.; Est, Andy; Bulla, Gregory; Henry, Chris

    1991-01-01

    The Taurus Lightweight Manned Spacecraft (LMS) was developed by students of the University of Maryland's Aerospace Engineering course in Space Vehicle Design. That course required students to design an Alternative Manned Spacecraft (AMS) to augment or replace the Space Transportation System and meet the following design requirements: (1) launch on the Taurus Booster being developed by Orbital Sciences Corporation; (2) 99.9 percent assured crew survival rate; (3) technology cutoff data of 1 Jan. 1991; (4) compatibility with current space administration infrastructure; and (5) first flight by May 1995. The Taurus LMS design meets the above requirements and represents an initial step towards larger and more complex spacecraft. The Taurus LMS has a very limited application when compared to the Space Shuttle, but it demonstrates that the U.S. can have a safe, reliable, and low cost space system. The Taurus LMS is a short mission duration spacecraft designed to place one man into low earth orbit (LEO). The driving factor for this design was the low payload carrying capabilities of the Taurus Booster--1300 kg to a 300 km orbit. The Taurus LMS design is divided into six major design sections. The human factors system deals with the problems of life support and spacecraft cooling. The propulsion section contains the abort system, the Orbital Maneuvering System (OMS), the Reaction Control System (RCS), and power generation. The thermal protection systems and spacecraft structure are contained in the structures section. The avionics section includes navigation, attitude determination, data processing, communication systems, and sensors. The mission analysis section was responsible for ground processing and spacecraft astrodynamics. The systems integration section pulled the above sections together into one spacecraft and addressed costing and reliability.

  11. Fibroblasts—a key host cell type in tumor initiation, progression, and metastasis

    PubMed Central

    Strell, Carina; Rundqvist, Helene

    2012-01-01

    Tumor initiation, growth, invasion, and metastasis occur as a consequence of a complex interplay between the host environment and cancer cells. Fibroblasts are now recognized as a key host cell type involved in host–cancer signaling. This review discusses some recent studies that highlight the roles of fibroblasts in tumor initiation, early progression, invasion, and metastasis. Some clinical studies describing the prognostic significance of fibroblast-derived markers and signatures are also discussed. PMID:22509805

  12. Spacecraft Environment Interactions

    NASA Technical Reports Server (NTRS)

    Garrett, Henry B.; Jun, Insoo

    2011-01-01

    As electronic components have grown smaller in size and power and have increased in complexity, their enhanced sensitivity to the space radiation environment and its effects has become a major source of concern for the spacecraft engineer. As a result, the description of the sources of space radiation, the determination of how that radiation propagates through material, and, ultimately, how radiation affects specific circuit components are primary considerations in the design of modern spacecraft. The objective of this paper will be to address the first 2 aspects of the radiation problem. This will be accomplished by first reviewing the natural and man-made space radiation environments. These environments include both the particulate and, where applicable, the electromagnetic (i.e., photon) environment. As the "ambient" environment is typically only relevant to the outer surface of a space vehicle, it will be necessary to treat the propagation of the external environment through the complex surrounding structures to the point inside the spacecraft where knowledge of the internal radiation environment is required. While it will not be possible to treat in detail all aspects of the problem of the radiation environment within a spacecraft, by dividing the problem into these parts-external environment, propagation, and internal environment-a basis for understanding the practical process of protecting a spacecraft from radiation will be established. The consequences of this environment will be discussed by the other presenters at this seminar.

  13. Modeling the Initiation of Ewing Sarcoma Tumorigenesis in Differentiating Human Embryonic Stem Cells

    PubMed Central

    Gordon, David J.; Motwani, Mona; Pellman, David

    2015-01-01

    Oncogenic transformation in Ewing sarcoma tumors is driven by the fusion oncogene EWS-FLI1. However, despite the well-established role of EWS-FLI1 in tumor initiation, the development of models of Ewing sarcoma in human cells with defined genetic elements has been challenging. Here, we report a novel approach to model the initiation of Ewing sarcoma tumorigenesis that exploits the developmental and pluripotent potential of human embryonic stem cells. The inducible expression of EWS-FLI1 in embryoid bodies, or collections of differentiating stem cells, generates cells with properties of Ewing sarcoma tumors, including characteristics of transformation. These cell lines exhibit anchorage-independent growth, a lack of contact inhibition and a strong Ewing sarcoma gene expression signature. Furthermore, these cells also demonstrate a requirement for the persistent expression of EWS-FLI1 for cell survival and growth, which is a hallmark Ewing sarcoma tumors. PMID:26455317

  14. Identification and analysis of CXCR4-positive synovial sarcoma-initiating cells.

    PubMed

    Kimura, T; Wang, L; Tabu, K; Tsuda, M; Tanino, M; Maekawa, A; Nishihara, H; Hiraga, H; Taga, T; Oda, Y; Tanaka, S

    2016-07-28

    Synovial sarcoma accounts for almost 10% of all soft tissue sarcomas, and its prognosis is poor with 5-year survival rates at 36%. Thus, new treatments and therapeutic targets for synovial sarcoma are required. Tumor-initiating cells have been defined by the ability for self-renewal and multipotent differentiation, and they exhibit higher tumorigenic capacity, chemoresistance and radiation resistance, expecting to be a new therapeutic target. In synovial sarcoma, the presence of such stemness remains largely unclear; thus, we analyzed whether synovial sarcoma possessed tumor-initiating cells and explored specific markers, and we discovered that synovial sarcoma cell lines possessed heterogeneity by way of containing a sphere-forming subpopulation highly expressing NANOG, OCT4 and SOX2. By expression microarray analysis, CXCR4 was identified to be highly expressed in the sphere subpopulation and correlated with stem-cell-associated markers. Inhibition of CXCR4 suppressed the cell proliferation of synovial sarcoma cell lines in vitro. The tumor-initiating ability of CXCR4-positive cells was demonstrated by xenograft propagation assay. CXCR4-positive cells showed higher tumorigenicity than negative ones and possessed both self-renewal and multipotent differentiation ability. Immunohistochemical analysis of 39 specimens of synovial sarcoma patients revealed that CXCR4 strongly correlated with poor prognosis of synovial sarcoma. Thus, we conclude that CXCR4 is the marker of synovial sarcoma-initiating cells, a new biomarker for prognosis and a new potential therapeutic target. PMID:26640147

  15. Induction of cytotoxic T lymphocytes against ovarian cancer-initiating cells.

    PubMed

    Weng, Desheng; Song, Baizheng; Durfee, John; Sugiyama, Valerie; Wu, Zhengrong; Koido, Shigeo; Calderwood, Stuart K; Gong, Jianlin

    2011-10-15

    The majority of patients with stage III/IV ovarian carcinoma that respond initially to standard therapies ultimately undergo relapse due to the survival of small populations of cells with tumor-initiating potential. These ovarian cancer (OVCA)-initiating cells (OCIC) are sometimes called cancer stem cells (CSC) because they express stem cell markers, and can survive conventional therapies such as chemotherapy, which usually target rapidly replicating tumor cells, and give rise to recurrent tumors that are more chemo-resistant and more aggressive. Thus, it would be desirable to develop a therapy that could selectively target OCIC and be used to complement the conventional therapies. In this study, we isolated a subset of OVCA cells with a CD44(+) phenotype in samples from patients with OVCA that possess CSC properties including the formation of spheroids in culture, self-renewal and the ability to be engrafted in immune-compromised mice. We next explored the use of immunotherapy using fusions of dendritic cells and OCIC to specifically target the OCIC subpopulations. Fusion cells (FCs) prepared in this way activated T cells to express elevated levels of IFN-γ with enhanced killing of CD44(+) OVCA cells. We envision a combined approach where conventional therapies such as chemotherapy kill the bulk of tumor cells, whereas OCIC-reactive cytotoxic T lymphocytes target the resistant OCIC fraction. A combined therapy such as this may represent a promising approach for the treatment of OVCA. PMID:21154809

  16. Actin–myosin network reorganization breaks symmetry at the cell rear to spontaneously initiate polarized cell motility

    PubMed Central

    Yam, Patricia T.; Wilson, Cyrus A.; Ji, Lin; Hebert, Benedict; Barnhart, Erin L.; Dye, Natalie A.; Wiseman, Paul W.; Danuser, Gaudenz; Theriot, Julie A.

    2007-01-01

    We have analyzed the spontaneous symmetry breaking and initiation of actin-based motility in keratocytes (fish epithelial cells). In stationary keratocytes, the actin network flow was inwards and radially symmetric. Immediately before motility initiation, the actin network flow increased at the prospective cell rear and reoriented in the perinuclear region, aligning with the prospective axis of movement. Changes in actin network flow at the cell front were detectable only after cell polarization. Inhibition of myosin II or Rho kinase disrupted actin network organization and flow in the perinuclear region and decreased the motility initiation frequency, whereas increasing myosin II activity with calyculin A increased the motility initiation frequency. Local stimulation of myosin activity in stationary cells by the local application of calyculin A induced directed motility initiation away from the site of stimulation. Together, these results indicate that large-scale actin–myosin network reorganization and contractility at the cell rear initiate spontaneous symmetry breaking and polarized motility of keratocytes. PMID:17893245

  17. Degradation of Spacecraft Materials

    NASA Technical Reports Server (NTRS)

    Dever, Joyce; Banks, Bruce; deGroh, Kim; Miller, Sharon

    2004-01-01

    This chapter includes descriptions of specific space environmental threats to exterior spacecraft materials. The scope will be confined to effects on exterior spacecraft surfaces, and will not, therefore, address environmental effects on interior spacecraft systems, such as electronics. Space exposure studies and laboratory simulations of individual and combined space environemntal threats will be summarized. A significant emphasis is placed on effects of Earth orbit environments, because the majority of space missions have been flown in Earth orbits which have provided a significant amount of data on materials effects. Issues associated with interpreting materials degradation results will be discussed, and deficiencies of ground testing will be identified. Recommendations are provided on reducing or preventing space environmental degradation through appropriate materials selection.

  18. Spacecraft servicing demonstration plan

    NASA Technical Reports Server (NTRS)

    Bergonz, F. H.; Bulboaca, M. A.; Derocher, W. L., Jr.

    1984-01-01

    A preliminary spacecraft servicing demonstration plan is prepared which leads to a fully verified operational on-orbit servicing system based on the module exchange, refueling, and resupply technologies. The resulting system can be applied at the space station, in low Earth orbit with an orbital maneuvering vehicle (OMV), or be carried with an OMV to geosynchronous orbit by an orbital transfer vehicle. The three phase plan includes ground demonstrations, cargo bay demonstrations, and free flight verifications. The plan emphasizes the exchange of multimission modular spacecraft (MMS) modules which involves space repairable satellites. Three servicer mechanism configurations are the engineering test unit, a protoflight quality unit, and two fully operational units that have been qualified and documented for use in free flight verification activity. The plan balances costs and risks by overlapping study phases, utilizing existing equipment for ground demonstrations, maximizing use of existing MMS equipment, and rental of a spacecraft bus.

  19. Multipurpose hardened spacecraft insulation

    NASA Technical Reports Server (NTRS)

    Steimer, Carlos H.

    1990-01-01

    A Multipurpose Hardened Spacecraft Multilayer Insulation (MLI) system was developed and implemented to meet diverse survivability and performance requirements. Within the definition and confines of a MLI assembly (blanket), the design: (1) provides environmental protection from natural and induced nuclear, thermal, and electromagnetic radiation; (2) provides adequate electrostatic discharge protection for a geosynchronous satellite; (3) provides adequate shielding to meet radiated emission needs; and (4) will survive ascent differential pressure loads between enclosed volume and space. The MLI design is described which meets these requirements and design evolution and verification is discussed. The application is for MLI blankets which closeout the area between the laser crosslink subsystem (LCS) equipment and the DSP spacecraft cabin. Ancillary needs were implemented to ease installation at launch facility and to survive ascent acoustic and vibration loads. Directional venting accommodations were also incorporated to avoid contamination of LCS telescope, spacecraft sensors, and second surface mirrors (SSMs).

  20. Maneuver analysis for spinning thrusting spacecraft and spinning tethered spacecraft

    NASA Astrophysics Data System (ADS)

    Martin, Kaela M.

    During axial thrusting of a spin-stabilized spacecraft undergoing orbital injections or control maneuvers, misalignments and center-of-mass offset create undesired body-fixed torques. The effects of the body-fixed torques, which in turn cause velocity pointing errors, can be reduced by ramping up (and then ramping down) the thruster. The first topic discussed in this thesis derives closed-form solutions for the angular velocity, Euler angles, inertial velocity, and inertial displacement solutions with nonzero initial conditions. Using the closed-form solutions, the effect of variations in the spin-axis moment of inertia and spin-rate on the spacecraft velocity pointing error are shown. The analytical solutions closely match numerical simulations. The next topic considers various ramp-up profiles (including parabolic, cosine, logarithmic, exponential, and cubic) to heuristically find a suboptimal solution to reduce the velocity pointing error. Some of the considered cosine, logarithmic, exponential, parabolic, and cubic profiles drive the velocity pointing error to nearly zero and hence qualify as effective solutions. The third topic examines a large tethered spacecraft that produces artificial gravity with the propulsion system on one end of the tether. Instead of thrusting through the center of mass, the offset thrust occurs at an angle to the tether which is held in the desired direction by changing the spin rate to compensate for decreasing propellant mass. The dynamics and control laws of the system are derived for constant, time-varying, planar, and non-planar thrust as well as spin-up maneuvers. The final topic discusses how the Bodewadt solution of a self-excited rigid body is unable to accurately predict the motion compared to a numerical integration of the equations of motion.

  1. Autonomy Architectures for a Constellation of Spacecraft

    NASA Technical Reports Server (NTRS)

    Barrett, Anthony

    2000-01-01

    Until the past few years, missions typically involved fairly large expensive spacecraft. Such missions have primarily favored using older proven technologies over more recently developed ones, and humans controlled spacecraft by manually generating detailed command sequences with low-level tools and then transmitting the sequences for subsequent execution on a spacecraft controller. This approach toward controlling a spacecraft has worked spectacularly on previous missions, but it has limitations deriving from communications restrictions - scheduling time to communicate with a particular spacecraft involves competing with other projects due to the limited number of deep space network antennae. This implies that a spacecraft can spend a long time just waiting whenever a command sequence fails. This is one reason why the New Millennium program has an objective to migrate parts of mission control tasks onboard a spacecraft to reduce wait time by making spacecraft more robust. The migrated software is called a "remote agent" and has 4 components: a mission manager to generate the high level goals, a planner/scheduler to turn goals into activities while reasoning about future expected situations, an executive/diagnostics engine to initiate and maintain activities while interpreting sensed events by reasoning about past and present situations, and a conventional real-time subsystem to interface with the spacecraft to implement an activity's primitive actions. In addition to needing remote planning and execution for isolated spacecraft, a trend toward multiple-spacecraft missions points to the need for remote distributed planning and execution. The past few years have seen missions with growing numbers of probes. Pathfinder has its rover (Sojourner), Cassini has its lander (Huygens), and the New Millenium Deep Space 3 (DS3) proposal involves a constellation of 3 spacecraft for interferometric mapping. This trend is expected to continue to progressively larger fleets. For

  2. Spacecraft Attitude Determination Methods

    NASA Technical Reports Server (NTRS)

    Markley, F. Landis; Bauer, Frank H. (Technical Monitor)

    2000-01-01

    This document is presentation in viewgraph form, which outlines the methods of determining spacecraft attitude. The presentation reviews several parameterizations relating to spacecraft attitude, such as Euler's Theorem, Rodriques parameters, and Euler-Rodriques parameters or Quaternion. Onboard attitude determination is the norm, using either single frame or filtering methods. The presentation reviews several mathematical representations of attitude. The mechanisms for determining attitude on board the Hubble Space Telescope, the Tropical Rainfall and Measuring Mission and the Solar Anomalous and Magnetospheric Particle Explorer are reviewed. Wahba's problem, Procrustes Problem, and some solutions are also summarized.

  3. Revamping Spacecraft Operational Intelligence

    NASA Technical Reports Server (NTRS)

    Hwang, Victor

    2012-01-01

    The EPOXI flight mission has been testing a new commercial system, Splunk, which employs data mining techniques to organize and present spacecraft telemetry data in a high-level manner. By abstracting away data-source specific details, Splunk unifies arbitrary data formats into one uniform system. This not only reduces the time and effort for retrieving relevant data, but it also increases operational visibility by allowing a spacecraft team to correlate data across many different sources. Splunk's scalable architecture coupled with its graphing modules also provide a solid toolset for generating data visualizations and building real-time applications such as browser-based telemetry displays.

  4. Spacecraft Radiation Analysis

    NASA Technical Reports Server (NTRS)

    Harris, D. W.

    1972-01-01

    The radiation interface in spacecrafts using radioisotope thermoelectric generators is studied. A Monte Carlo analysis of the radiation field that includes scattered radiation effects, produced neutron and gamma photon isoflux contours as functions of distance from the RTG center line. It is shown that the photon flux is significantly depressed in the RTG axial direction because of selfshielding. Total flux values are determined by converting the uncollided flux values into an equivalent RTG surface source and then performing a Monte Carlo analysis for each specific dose point. Energy distributions of the particle spectra completely define the radiation interface for a spacecraft model.

  5. Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation

    PubMed Central

    Le Rolle, Anne-France; Chiu, Thang K.; Zeng, Zhaoshi; Shia, Jinru; Weiser, Martin R.; Paty, Philip B.; Chiu, Vi K.

    2016-01-01

    Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer initiation by performing gene set enrichment analysis on gene expression from human colon tissues. We find that KRASmut imposes the embryonic stem cell-like program during human colon cancer initiation from colon adenoma to stage I carcinoma. Expression of miR145, an embryonic SC program inhibitor, promotes cell lineage differentiation marker expression in KRASmut colon cancer cells and significantly suppresses their tumorigenicity. Our data support an in vivo plasticity model of human colon cancer initiation that merges the intrinsic stem cell properties of aberrant colon stem cells with the embryonic stem cell-like program induced by KRASmut to optimize malignant transformation. Inhibition of the embryonic SC-like program in KRASmut colon cancer cells reveals a novel therapeutic strategy to programmatically inhibit KRASmut tumors and prevent colon cancer. PMID:26744320

  6. Characterisation of Mesothelioma-Initiating Cells and Their Susceptibility to Anti-Cancer Agents

    PubMed Central

    Pasdar, Elham Alizadeh; Smits, Michael; Stapelberg, Michael; Bajzikova, Martina; Stantic, Marina; Goodwin, Jacob; Yan, Bing; Stursa, Jan; Kovarova, Jaromira; Sachaphibulkij, Karishma; Bezawork-Geleta, Ayenachew; Sobol, Margaryta; Filimonenko, Anatoly; Tomasetti, Marco; Zobalova, Renata; Hozak, Pavel; Dong, Lan-Feng; Neuzil, Jiri

    2015-01-01

    Malignant mesothelioma (MM) is an aggressive type of tumour causing high mortality. One reason for this paradigm may be the existence of a subpopulation of tumour-initiating cells (TICs) that endow MM with drug resistance and recurrence. The objective of this study was to identify and characterise a TIC subpopulation in MM cells, using spheroid cultures, mesospheres, as a model of MM TICs. Mesospheres, typified by the stemness markers CD24, ABCG2 and OCT4, initiated tumours in immunodeficient mice more efficiently than adherent cells. CD24 knock-down cells lost the sphere-forming capacity and featured lower tumorigenicity. Upon serial transplantation, mesospheres were gradually more efficiently tumrigenic with increased level of stem cell markers. We also show that mesospheres feature mitochondrial and metabolic properties similar to those of normal and cancer stem cells. Finally, we show that mesothelioma-initiating cells are highly susceptible to mitochondrially targeted vitamin E succinate. This study documents that mesospheres can be used as a plausible model of mesothelioma-initiating cells and that they can be utilised in the search for efficient agents against MM. PMID:25932953

  7. IGFC response to initial fuel cell load for various syngas compositions

    SciTech Connect

    Tucker, David; Hughes, Dimitri O.; Haynes, Comas L.

    2012-01-01

    The system response to an initial electric load of the fuel cell during the startup of a direct-fired fuel cell turbine power system was studied using the Hybrid Performance (Hyper) project hardware-based simulation facility at the U.S. Department of Energy, National Energy Technology Laboratory for a range of input fuel compositions. The facility was brought to a steady condition at a temperature deemed adequate to minimize stress on the fuel cell during the initial load transient. A 1D distributed fuel cell model operating in real-time was used to produce individual cell transient temperature profiles during the course of the load change. The process was conducted with humidified hydrogen, and then repeated with various syngas compositions representative of different gasifier technologies. The results provide insight into control strategy requirements for mitigation of expected fuel cell failure modes relevant to available gasifier technology.

  8. Evaluation program for secondary spacecraft cells: Acceptance test of Eagle-Picher 100 ampere-hour nickel-cadmium cells with auxiliary electrodes

    NASA Technical Reports Server (NTRS)

    Christy, D. E.

    1972-01-01

    Tests were conducted on a group of 29 cells for the purpose of removing from the life cycle program all cells found to have electrolyte leakage, internal shorts, low capacity, or inability to recover open circuit voltage above 1.150 volts after the cell short test. The test findings include the following: (1) All the cells exceeded the rated capacity of 103.5 to 119.0 ampere-hours on all three capacity checks. (2) All cells recovered above the 1.150 volt requirement after the cell short test. (3) The cells cannot be overcharged at the c/10 rate without exceeding 1.500 volts after approximately 12 to 13 hours of charge. (4) The resistance value necessary to provide maximum signal power across the auxiliary electrode was found to be 10 ohms. (5) One cell revealed a definite leak at the negative terminal.

  9. Evaluation program for secondary spacecraft cells: Acceptance tests of Eagle-Picher 20.0 ampere-hour nickel-cadmium cells with auxiliary electrodes

    NASA Technical Reports Server (NTRS)

    Christy, D. E.

    1972-01-01

    A group of 29 cells with capacities ranging from 21.7 to 28.8 ampere-hours were tested. A summary of the results indicates: (1) All cells exceeded the rated capacity on all three capacity checks. (2) Five cells failed to recover to 1.150 volts. (3) During the overcharge tests, 15 of the 29 cells had to be removed from charge before completion of the respective tests due to high pressure.

  10. Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein

    SciTech Connect

    Lu, Na; Chen, Yan; Wang, Zhengmin; Chen, Guoling; Lin, Qin; Chen, Zheng-Yi; Li, Huawei

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer Shh activation in neonatal cochleae enhances sensory cell proliferation. Black-Right-Pointing-Pointer Proliferating supporting cells can transdifferentiate into hair cells. Black-Right-Pointing-Pointer Shh promotes proliferation by transiently modulating pRb activity. Black-Right-Pointing-Pointer Shh inhibits pRb by inhibiting transcription and increasing phosphorylation of pRb. -- Abstract: Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration.

  11. Adoptive cell transfer of contact sensitivity-initiation mediated by nonimmune cells sensitized with monoclonal IgE antibodies. Dependence on host skin mast cells.

    PubMed

    Matsuda, H; Ushio, H; Paliwal, V; Ptak, W; Askenase, P W

    1995-05-15

    A role for mast cell release of serotonin (5-HT), via Ag-specific factors derived from Thy-1+ B220+ lymphoid cells in the initiation of murine contact sensitivity (CS) has been suggested. However, because CS in mast cell-deficient mice was intact, a role for mast cells in CS initiation was unclear. Therefore, we examined whether CS could be initiated by i.v. injection of nonimmune mixed lymphoid cells that were sensitized in vitro with IgE. When naive mice received IgE-sensitized nonimmune spleen or lymph node cells, or IgE-sensitized purified mast cells, together with immune CS-effector B220- T cells, which therefore were depleted of CS-initiating, Thy-1+, B220+ cells, which could not transfer CS, then reconstitution of CS occurred. Mast cell-deficient W/Wv mice could not elicit this IgE-dependent CS ear swelling, but when mast cell deficiency was reversed by ear injection of normal bone marrow-derived cultured mast cells, then CS was restored. In vitro pretreatment with irrelevant monoclonal anti-OVA IgE prevented CS initiation mediated by Ag-specific, IgE mAb-sensitized cells, presumably by blocking sensitization with IgE. Thus Fc epsilon R on the normal lymphoid cells were involved. When ketanserin, a 5-HT2 receptor antagonist, was injected i.v. before cell transfer, CS initiation via IgE-sensitized cells and CS were no longer elicited. Thus, in this system, IgE Abs bound to circulating IgE Fc epsilon R bearing lymphoid cells sensitized in vitro (most likely basophils), probably mediated early activation of these circulating basophils to release mediators, causing 5-HT release from cutaneous mast cells, to mediate CS initiation. PMID:7730614

  12. Evaluation program for secondary spacecraft cells: Acceptance tests of Eagle-Picher 12.0 ampere-hour nickel-cadmium cells with auxiliary electrodes

    NASA Technical Reports Server (NTRS)

    Christy, D. E.

    1971-01-01

    An acceptance test program was conducted on 24 cells to insure that all cells put into the life cycle program were of high quality by the removal of cells found to have electrolyte leakage, internal shorts, low capacity, or inability of any cell to recover its open circuit voltage above 1.150 volts after the cell short test. The cells were rated at 12.0 ampere-hours and equipped with auxiliary electrodes. Test results were: (1) The capacity of the 24 cells ranged from 14.6 to 16.8 ah. All the cells exceeded the rated capacity on all three capacity checks. (2) One cell failed to recover to 1.150 volts after the cell short test. (3) During the overcharge tests, all cells but one failed the test at the c/10 rate after the first minute. (4) A special resistance test was conducted on the auxiliary electrodes of these cells to establish the resistance value necessary which would provide maximum signal power across the auxiliary electrode. The resistance value established was 10 ohms. (5) No electrolyte leakage was observed.

  13. CCD architecture for spacecraft SAR image processing

    NASA Technical Reports Server (NTRS)

    Arens, W. E.

    1977-01-01

    A real-time synthetic aperture radar (SAR) image processing architecture amenable to future on-board spacecraft applications is currently under development. Using state-of-the-art charge-coupled device (CCD) technology, low cost and power are inherent features. Other characteristics include the ability to reprogram correlation reference functions, correct for range migration, and compensate for antenna beam pointing errors on the spacecraft in real time. The first spaceborne demonstration is scheduled to be flown as an experiment on a 1982 Shuttle imaging radar mission (SIR-B). This paper describes the architecture and implementation characteristics of this initial spaceborne CCD SAR image processor.

  14. Comet explorer spacecraft design project

    NASA Technical Reports Server (NTRS)

    1987-01-01

    The small, chemically primitive objects of the solar system, comets and asteroids, are one of the most important frontiers remaining for future planetary exploration. So stated the Solar System Exploration Committee of the NASA Advisory Council in its 1986 report 'Planetary Exploration Through the Year 2000.' The Halley's comet flyby missions completed last spring raised more questions than were answered about the nature of comets. The next mission to a comet must be able to explore some of these questions. In the late 1990's, a spacecraft might be built to explore the hazardous area surrounding a comet nucleus. Rigorous pointing requirements for remote sensing instruments will place a considerable burden on their attendant control systems. To meet these requirements we have pursued the initial design and analysis of a multi-bodied comet explorer spacecraft. Sized so as to be built on-orbit after the space station is operational, the spacecraft is comprised of Orbit Replaceable Unit (ORU) subsystems, packaged into two major components: a three-axis controlled instrument platform and a spinning, detached comet dust shield. Such a configuration decouples the dynamics of dust impaction from the stringent pointing out requirements of the imaging experiments. At the same time, it offers an abundance of simple analysis problems that may be carried out by undergraduates. These problems include the following: Selection of subsystem components, sizing trade studies, investigation of three-axis and simple spin dynamics, design of simple control systems, orbit determination, and intercept trajectory generation. Additionally, such topics as proposal writing project management, human interfacing, and costing have been covered. A new approach to design teaching has been taken, whereby students will 'learn by teaching.' They are asked to decompose trade options into a set of 'if-then' rules, which then 'instruct' the Mechanically Intelligent Designer (MIND) expert design system

  15. Comparison of picornaviral IRES-driven internal initiation of translation in cultured cells of different origins.

    PubMed Central

    Borman, A M; Le Mercier, P; Girard, M; Kean, K M

    1997-01-01

    We recently compared the efficiency of six picornaviral internal ribosome entry segments (IRESes) and the hepatitis C virus (HCV) IRES for their ability to drive internal initiation of translationin vitro. Here we present the results of a similar comparison performed in six different cultured cell lines infected with a recombinant vaccinia virus expressing the T7 polymerase and transfected with dicistronic plasmids. The IRESes could be divided into three groups: (i) the cardiovirus and aphthovirus IRESes (and the HCV element) direct internal initiation efficiently in all cell lines tested; (ii) the enterovirus and rhinovirus IRESes are at least equally efficient in several cell lines, but are extremely inefficient in certain cell types; and (iii) the hepatitis A virus IRES is incapable of directing efficient internal initiation in any of the cell lines used (including human hepatocytes). These are the same three groups found when IRESes were classified according to their activitiesin vitro, or according to sequence homologies. In a mouse neuronal cell line, the poliovirus and other type I IRESes were not functional in an artificial bicistronic context. However, infectious poliovirions were produced efficiently after transfection of these cells with a genomic length RNA. Furthermore, activity of the type I IRESes was dramatically increased upon co-expression of the poliovirus 2A proteinase, demonstrating that while IRES efficiency may vary considerably from one cell type to another, at least in some cases viral proteins are capable of overcoming cell-specific translational defects. PMID:9023100

  16. Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites.

    PubMed

    Gerbe, François; Sidot, Emmanuelle; Smyth, Danielle J; Ohmoto, Makoto; Matsumoto, Ichiro; Dardalhon, Valérie; Cesses, Pierre; Garnier, Laure; Pouzolles, Marie; Brulin, Bénédicte; Bruschi, Marco; Harcus, Yvonne; Zimmermann, Valérie S; Taylor, Naomi; Maizels, Rick M; Jay, Philippe

    2016-01-14

    Helminth parasitic infections are a major global health and social burden. The host defence against helminths such as Nippostrongylus brasiliensis is orchestrated by type 2 cell-mediated immunity. Induction of type 2 cytokines, including interleukins (IL) IL-4 and IL-13, induce goblet cell hyperplasia with mucus production, ultimately resulting in worm expulsion. However, the mechanisms underlying the initiation of type 2 responses remain incompletely understood. Here we show that tuft cells, a rare epithelial cell type in the steady-state intestinal epithelium, are responsible for initiating type 2 responses to parasites by a cytokine-mediated cellular relay. Tuft cells have a Th2-related gene expression signature and we demonstrate that they undergo a rapid and extensive IL-4Rα-dependent amplification following infection with helminth parasites, owing to direct differentiation of epithelial crypt progenitor cells. We find that the Pou2f3 gene is essential for tuft cell specification. Pou2f3(-/-) mice lack intestinal tuft cells and have defective mucosal type 2 responses to helminth infection; goblet cell hyperplasia is abrogated and worm expulsion is compromised. Notably, IL-4Rα signalling is sufficient to induce expansion of the tuft cell lineage, and ectopic stimulation of this signalling cascade obviates the need for tuft cells in the epithelial cell remodelling of the intestine. Moreover, tuft cells secrete IL-25, thereby regulating type 2 immune responses. Our data reveal a novel function of intestinal epithelial tuft cells and demonstrate a cellular relay required for initiating mucosal type 2 immunity to helminth infection. PMID:26762460

  17. Analysis of spacecraft data

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Support was provided for the maintenance and modifications of software for the production and detailed analysis of data from the DE-A spacecraft and new software developed for this end. Software for the analysis of the data from the Spacelab Experimental Particle Accelerator (SEPAC) was also developed.

  18. Microbial contamination of spacecraft

    NASA Technical Reports Server (NTRS)

    Pierson, D. L.

    2001-01-01

    Spacecraft and space habitats supporting human exploration contain a diverse population of microorganisms. Microorganisms may threaten human habitation in many ways that directly or indirectly impact the health, safety, or performance of astronauts. The ability to produce and maintain spacecraft and space stations with environments suitable for human habitation has been established over 40 years of human space flight. An extensive database of environmental microbiological parameters has been provided for short-term (< 20 days) space flight by more than 100 missions aboard the Space Shuttle. The NASA Mir Program provided similar data for long-duration missions. Interestingly, the major bacterial and fungal species found in the Space Shuttle are similar to those encountered in the nearly 15-year-old Mir. Lessons learned from both the US and Russian space programs have been incorporated into the habitability plan for the International Space Station. The focus is on preventive measures developed for spacecraft, cargo, and crews. On-orbit regular housekeeping practices complete with visual inspections are essential, along with microbiological monitoring. Risks associated with extended stays on the Moon or a Mars exploration mission will be much greater than previous experiences because of additional unknown variables. The current knowledge base is insufficient for exploration missions, and research is essential to understand the effects of space flight on biological functions and population dynamics of microorganisms in spacecraft. Equally important is a better understanding of the immune response and of human-microorganism-environment interactions during long-term space habitation.

  19. Multifunctional Tanks for Spacecraft

    NASA Technical Reports Server (NTRS)

    Collins, David H.; Lewis, Joseph C.; MacNeal, Paul D.

    2006-01-01

    A document discusses multifunctional tanks as means to integrate additional structural and functional efficiencies into designs of spacecraft. Whereas spacecraft tanks are traditionally designed primarily to store fluids and only secondarily to provide other benefits, multifunctional tanks are designed to simultaneously provide multiple primary benefits. In addition to one or more chamber(s) for storage of fluids, a multifunctional tank could provide any or all of the following: a) Passageways for transferring the fluids; b) Part or all of the primary structure of a spacecraft; c) All or part of an enclosure; d) Mechanical interfaces to components, subsystems, and/or systems; e) Paths and surfaces for transferring heat; f)Shielding against space radiation; j) Shielding against electromagnetic interference; h) Electrically conductive paths and surfaces; and i) Shades and baffles to protect against sunlight and/or other undesired light. Many different multifunctional-tank designs are conceivable. The design of a particular tank can be tailored to the requirements for the spacecraft in which the tank is to be installed. For example, the walls of the tank can be flat or curved or have more complicated shapes, and the tank can include an internal structure for strengthening the tank and/or other uses.

  20. Unmanned spacecraft for research

    NASA Technical Reports Server (NTRS)

    Graves, C. D.

    1972-01-01

    The applications of unmanned spacecraft for research purposes are discussed. Specific applications of the Communication and Navigation satellites and the Earth Observations satellites are described. Diagrams of communications on world-wide basis using synchronous satellites are developed. Photographs of earth resources and geology obtained from space vehicles are included.

  1. Microbial contamination of spacecraft.

    PubMed

    Pierson, D L

    2001-06-01

    Spacecraft and space habitats supporting human exploration contain a diverse population of microorganisms. Microorganisms may threaten human habitation in many ways that directly or indirectly impact the health, safety, or performance of astronauts. The ability to produce and maintain spacecraft and space stations with environments suitable for human habitation has been established over 40 years of human space flight. An extensive database of environmental microbiological parameters has been provided for short-term (< 20 days) space flight by more than 100 missions aboard the Space Shuttle. The NASA Mir Program provided similar data for long-duration missions. Interestingly, the major bacterial and fungal species found in the Space Shuttle are similar to those encountered in the nearly 15-year-old Mir. Lessons learned from both the US and Russian space programs have been incorporated into the habitability plan for the International Space Station. The focus is on preventive measures developed for spacecraft, cargo, and crews. On-orbit regular housekeeping practices complete with visual inspections are essential, along with microbiological monitoring. Risks associated with extended stays on the Moon or a Mars exploration mission will be much greater than previous experiences because of additional unknown variables. The current knowledge base is insufficient for exploration missions, and research is essential to understand the effects of space flight on biological functions and population dynamics of microorganisms in spacecraft. Equally important is a better understanding of the immune response and of human-microorganism-environment interactions during long-term space habitation. PMID:11865864

  2. Submarines, spacecraft and exhaled breath.

    PubMed

    Pleil, Joachim D; Hansel, Armin

    2012-03-01

    important concern is a suite of products from chemical reactions among oxidizing compounds with biological chemicals such as amines, thiols and carbonyls. SAMAP Meeting We (Armin and Joachim) attended the 2011 SAMAP conference in Taranto, Italy (10-14 October), which occurred just a few weeks after the IABR meeting in Parma, Italy (11-15 September 2011). It was held at the Officers' Club of the Taranto Naval Base under the patronage of the Italian navy; the local host was Lucio Ricciardi of the University of Insubria, Varese, Italy. At the 2011 SAMAP meeting, the theme was air-independent propulsion (AIP), meaning the capability of recharging the main batteries of the submarine without the need to surface. Only a few navies (e.g. US, UK, France, Russia, China) have historically had this capability using nuclear-powered submarines that can function underwater for extended periods of time (months). Most navies operate submarines with conventional diesel-electric propulsion, wherein diesel-powered generators charge battery banks which then drive an electric motor connected to the propeller. The batteries are charged while the boat is on the surface or during snorkelling, when the boat is submerged a few meters below the surface and a snorkel tube is extended to the surface. The period between battery charges can vary from several hours to one or two days depending on the power requirements and the nature of the mission. The process is necessary for breathing air revitalization (flushing out accumulated contaminants) and for the operation of the diesel engines. However, during this period the submarine is vulnerable to detection. Since the 1940s there have been various attempts to develop a power generation system that is independent of external air (AIP). To this end hydrogen peroxide was initially used and later liquid oxygen (LOX). Currently, most AIP submarines use fuel cell technology (LOX and hydrogen) to supplement the conventional diesel-electric system in order to

  3. Aberrant cell cycle regulation in rat liver cells induced by post-initiation treatment with hepatocarcinogens/hepatocarcinogenic tumor promoters.

    PubMed

    Kimura, Masayuki; Mizukami, Sayaka; Watanabe, Yousuke; Onda, Nobuhiko; Yoshida, Toshinori; Shibutani, Makoto

    2016-08-01

    The present study aimed to determine the onset time of hepatocarcinogen/hepatocarcinogenic tumor promoter-specific cell proliferation, apoptosis and aberrant cell cycle regulation after post-initiation treatment. Six-week-old rats were treated with the genotoxic hepatocarcinogen, carbadox (CRB), the marginally hepatocarcinogenic leucomalachite green (LMG), the tumor promoter, β-naphthoflavone (BNF) or the non-carcinogenic hepatotoxicant, acetaminophen, for 2, 4 or 6 weeks during the post-initiation phase using a medium-term liver bioassay. Cell proliferation activity, expression of G2 to M phase- and spindle checkpoint-related molecules, and apoptosis were immunohistochemically analyzed at week 2 and 4, and tumor promotion activity was assessed at week 6. At week 2, hepatocarcinogen/tumor promoter-specific aberrant cell cycle regulation was not observed. At week 4, BNF and LMG increased cell proliferation together with hepatotoxicity, while CRB did not. Additionally, BNF and CRB reduced the number of cells expressing phosphorylated-histone H3 in both ubiquitin D (UBD)(+) cells and Ki-67(+) proliferating cells, suggesting development of spindle checkpoint dysfunction, regardless of cell proliferation activity. At week 6, examined hepatocarcinogens/tumor promoters increased preneoplastic hepatic foci expressing glutathione S-transferase placental form. These results suggest that some hepatocarcinogens/tumor promoters increase their toxicity after post-initiation treatment, causing regenerative cell proliferation. In contrast, some genotoxic hepatocarcinogens may disrupt the spindle checkpoint without facilitating cell proliferation at the early stage of tumor promotion. This suggests that facilitation of cell proliferation and disruption of spindle checkpoint function are induced by different mechanisms during hepatocarcinogenesis. Four weeks of post-initiation treatment may be sufficient to induce hepatocarcinogen/tumor promoter-specific cellular responses. PMID

  4. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    SciTech Connect

    Kim, Yoo-Shin; Lee, Tae Hoon; O'Neill, Brian E.

    2015-08-14

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

  5. Murine complement receptor 1 is required for germinal center B cell maintenance but not initiation

    PubMed Central

    Donius, Luke R.; Weis, Janis J.; Weis, John H.

    2014-01-01

    Germinal centers are the anatomic sites for the generation of high affinity immunoglobulin expressing plasma cells and memory B cells. The germinal center B cells that are precursors of these cells circulate between the light zone B cell population that interact with antigen laden follicular dendritic cells (FDC) and the proliferative dark zone B cell population. Antigen retention by follicular dendritic cells is dependent on Fc receptors and complement receptors, and complement receptor 1 (Cr1) is the predominant complement receptor expressed by FDC. The newly created Cr1KO mouse was used to test the effect of Cr1-deficiency on the kinetics of the germinal center reaction and the generation of IgM and switched memory B cell formation. Immunization of Cr1KO mice with a T cell-dependent antigen resulted in the normal initial expansion of B cells with a germinal center phenotype however these cells were preferentially lost in the Cr1KO animal over time (days). Bone marrow chimera animals documented the surprising finding that the loss of germinal center B cell maintenance was linked to the expression of Cr1 on B cells, not the FDC. Cr1-deficiency further resulted in antigen-specific IgM titer and IgM memory B cell reductions, but not antigen-specific IgG after 35-37 days. Investigations of nitrophenyl (NP)-specific IgG demonstrated that Cr1 is not necessary for affinity maturation during the response to particulate antigen. These data, along with those generated in our initial description of the Cr1KO animal describe unique functions of Cr1 on the surface of both B cells and FDC. PMID:24636730

  6. Apoptotic cells trigger a membrane-initiated pathway to increase ABCA1.

    PubMed

    Fond, Aaron M; Lee, Chang Sup; Schulman, Ira G; Kiss, Robert S; Ravichandran, Kodi S

    2015-07-01

    Macrophages clear millions of apoptotic cells daily and, during this process, take up large quantities of cholesterol. The membrane transporter ABCA1 is a key player in cholesterol efflux from macrophages and has been shown via human genetic studies to provide protection against cardiovascular disease. How the apoptotic cell clearance process is linked to macrophage ABCA1 expression is not known. Here, we identified a plasma membrane-initiated signaling pathway that drives a rapid upregulation of ABCA1 mRNA and protein. This pathway involves the phagocytic receptor brain-specific angiogenesis inhibitor 1 (BAI1), which recognizes phosphatidylserine on apoptotic cells, and the intracellular signaling intermediates engulfment cell motility 1 (ELMO1) and Rac1, as ABCA1 induction was attenuated in primary macrophages from mice lacking these molecules. Moreover, this apoptotic cell-initiated pathway functioned independently of the liver X receptor (LXR) sterol-sensing machinery that is known to regulate ABCA1 expression and cholesterol efflux. When placed on a high-fat diet, mice lacking BAI1 had increased numbers of apoptotic cells in their aortic roots, which correlated with altered lipid profiles. In contrast, macrophages from engineered mice with transgenic BAI1 overexpression showed greater ABCA1 induction in response to apoptotic cells compared with those from control animals. Collectively, these data identify a membrane-initiated pathway that is triggered by apoptotic cells to enhance ABCA1 within engulfing phagocytes and with functional consequences in vivo. PMID:26075824

  7. Spacecraft Images Comet Target's Jets

    NASA Video Gallery

    The Deep Impact spacecraft's High- and Medium-Resolution Imagers (HRI and MRI) have captured multiple jets turning on and off while the spacecraft is 8 million kilometers (5 million miles) away fro...

  8. NASA Now: EPOXI Flyby Spacecraft

    NASA Video Gallery

    Close Encounters of the Comet Kind: In this installment of NASA Now, you’ll meet spacecraft pilot and engineer Steven Wissler, who talks about the challenges of flying a spacecraft remotely from ...

  9. Method for deploying multiple spacecraft

    NASA Technical Reports Server (NTRS)

    Sharer, Peter J. (Inventor)

    2007-01-01

    A method for deploying multiple spacecraft is disclosed. The method can be used in a situation where a first celestial body is being orbited by a second celestial body. The spacecraft are loaded onto a single spaceship that contains the multiple spacecraft and the spacecraft is launched from the second celestial body towards a third celestial body. The spacecraft are separated from each other while in route to the third celestial body. Each of the spacecraft is then subjected to the gravitational field of the third celestial body and each of the spacecraft assumes a different, independent orbit about the first celestial body. In those situations where the spacecraft are launched from Earth, the Sun can act as the first celestial body, the Earth can act as the second celestial body and the Moon can act as the third celestial body.

  10. Stereotyped initiation of retinal waves by bipolar cells via presynaptic NMDA autoreceptors.

    PubMed

    Zhang, Rong-Wei; Li, Xiao-Quan; Kawakami, Koichi; Du, Jiu-Lin

    2016-01-01

    Glutamatergic retinal waves, the spontaneous patterned neural activities propagating among developing retinal ganglion cells (RGCs), instruct the activity-dependent refinement of visuotopic maps. However, its initiation and underlying mechanism remain largely elusive. Here using larval zebrafish and multiple in vivo approaches, we discover that bipolar cells (BCs) are responsible for the generation of glutamatergic retinal waves. The wave originates from BC axon terminals (ATs) and propagates laterally to nearby BCs and vertically to downstream RGCs and the optic tectum. Its initiation is triggered by the activation of and consequent glutamate release from BC ATs, and is mediated by the N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) expressed at these ATs. Intercellular asymmetry of NMDAR expression at BC ATs enables the preferential initiation of waves at the temporal retina, where BC ATs express more NMDARs. Thus, our findings indicate that glutamatergic retinal waves are initiated by BCs through a presynaptic NMDA autoreceptor-dependent process. PMID:27586999

  11. Initial conditioning of polymer eelectrolyte membrane fuel cell by temperature and potential cycling.

    PubMed

    Bezmalinović, Dario; Radošević, Jagoda; Barbir, Frano

    2015-01-01

    Polymer electrolyte membrane fuel cells need initial conditioning, activation or break-in the first time they are operated after being assembled. During this period performance of the fuel cell improves until it reaches its nominal performance. The exact mechanism of this initial conditioning is not completely understood, but it is assumed that during the conditioning process the polymer membrane, as well as the polymer in the catalyst layer, get humidified, and the number of active catalyst sites increases. Activation procedure proposed here consists of temperature and potential cycling. Temperature cycling is a new approach for the conditioning and the idea is to rapidly cool the running cell at some point to allow the membrane to equilibrate with condensed water which should result in higher intake of water within the membrane. The results show that proposed procedure is better or at least comparable to some conventional procedures for the initial conditioning. PMID:25830963

  12. FSD- FLEXIBLE SPACECRAFT DYNAMICS

    NASA Technical Reports Server (NTRS)

    Fedor, J. V.

    1994-01-01

    The Flexible Spacecraft Dynamics and Control program (FSD) was developed to aid in the simulation of a large class of flexible and rigid spacecraft. FSD is extremely versatile and can be used in attitude dynamics and control analysis as well as in-orbit support of deployment and control of spacecraft. FSD has been used to analyze the in-orbit attitude performance and antenna deployment of the RAE and IMP class satellites, and the HAWKEYE, SCATHA, EXOS-B, and Dynamics Explorer flight programs. FSD is applicable to inertially-oriented spinning, earth oriented, or gravity gradient stabilized spacecraft. The spacecraft flexibility is treated in a continuous manner (instead of finite element) by employing a series of shape functions for the flexible elements. Torsion, bending, and three flexible modes can be simulated for every flexible element. FSD can handle up to ten tubular elements in an arbitrary orientation. FSD is appropriate for studies involving the active control of pointed instruments, with options for digital PID (proportional, integral, derivative) error feedback controllers and control actuators such as thrusters and momentum wheels. The input to FSD is in four parts: 1) Orbit Construction FSD calculates a Keplerian orbit with environmental effects such as drag, magnetic torque, solar pressure, thermal effects, and thruster adjustments; or the user can supply a GTDS format orbit tape for a particular satellite/time-span; 2) Control words - for options such as gravity gradient effects, control torques, and integration ranges; 3) Mathematical descriptions of spacecraft, appendages, and control systems- including element geometry, properties, attitudes, libration damping, tip mass inertia, thermal expansion, magnetic tracking, and gimbal simulation options; and 4) Desired state variables to output, i.e., geometries, bending moments, fast Fourier transform plots, gimbal rotation, filter vectors, etc. All FSD input is of free format, namelist construction. FSD

  13. Initiation of antiretroviral therapy at high CD4+ cell counts is associated with positive treatment outcomes

    PubMed Central

    Lima, Viviane D.; Reuter, Anja; Harrigan, P. Richard; Lourenço, Lillian; Chau, William; Hull, Mark; Mackenzie, Lauren; Guillemi, Silvia; Hogg, Robert S.; Barrios, Rolando; Montaner, Julio S.G.

    2015-01-01

    Objective There is limited research investigating the possible mechanisms of how starting combination antiretroviral therapy (cART) at a higher CD4+ cell count decreases mortality. This study investigated the association between initiating cART with short-term and long-term achievement of viral suppression; emergence of any drug resistance and of an AIDS-defining illness (ADI); long-term treatment adherence; and all-cause mortality. Methods This retrospective cohort study included 4120 naive patients who initiated cART between 2000 and 2012. Patients were followed until 2013, death or until the last contact date (varied by outcome). The main exposure was the interaction between period of cART initiation (2000–2006 and 2007–2012) and CD4+ cell count at cART initiation (<500 versus ≥500 cells/μl). We considered both baseline and longitudinal covariates. We fitted different multivariable models using cross-sectional and longitudinal statistical methods, depending on the outcome. Results Patients who initiated cART with a CD4+ cell count at least 500 cells/μl in 2007–2012 had an increased likelihood of achieving viral suppression at 9 months and of maintaining an adherence level of at least 95% over time, and the lowest probability of developing any resistance and an ADI during follow-up. These patients were not the ones with the highest likelihood of maintaining viral suppression over time, most likely due to viral load blips experienced during the follow-up. Conclusion The outcomes in this study likely play an important role in explaining the positive impact of early cART initiation on mortality. These results should alleviate some of the concerns clinicians may have when initiating cART in patients with high CD4+s as recommended by current treatment guidelines. PMID:26165354

  14. Specific initiation by RNA polymerase I in a whole-cell extract from yeast.

    PubMed Central

    Schultz, M C; Choe, S Y; Reeder, R H

    1991-01-01

    A protocol is described for making a soluble whole-cell extract from yeast (Saccharomyces cerevisiae) that supports active and specific transcription initiation by RNA polymerases I, II, and III. Specific initiation by polymerase I decreases in high-density cultures, paralleling the decrease in abundance of the endogenous 35S rRNA precursor. This extract should be useful for studying the molecular mechanisms that regulate rRNA transcription in yeast. Images PMID:1992452

  15. Ultrastructural analyses of somatic embryo initiation, development and polarity establishment from mesophyll cells of Dactylis glomerata

    NASA Technical Reports Server (NTRS)

    Vasilenko, A.; McDaniel, J. K.; Conger, B. V.

    2000-01-01

    Somatic embryos initiate and develop directly from single mesophyll cells in in vitro-cultured leaf segments of orchardgrass (Dactylis glomerata L.). Embryogenic cells establish themselves in the predivision stage by formation of thicker cell walls and dense cytoplasm. Electron microscopy observations for embryos ranging from the pre-cell-division stage to 20-cell proembryos confirm previous light microscopy studies showing a single cell origin. They also confirm that the first division is predominantly periclinal and that this division plane is important in establishing embryo polarity and in determining the embryo axis. If the first division is anticlinal or if divisions are in random planes after the first division, divisions may not continue to produce an embryo. This result may produce an embryogenic cell mass, callus formation, or no structure at all. Grant numbers: NAGW-3141, NAG10-0221.

  16. Effects of arcing due to spacecraft charging on spacecraft survival

    NASA Technical Reports Server (NTRS)

    Rosen, A.; Sanders, N. L.; Ellen, J. M., Jr.; Inouye, G. T.

    1978-01-01

    A quantitative assessment of the hazard associated with spacecraft charging and arcing on spacecraft systems is presented. A literature survey on arc discharge thresholds and characteristics was done and gaps in the data and requirements for additional experiments were identified. Calculations of coupling of arc discharges into typical spacecraft systems were made and the susceptibility of typical spacecraft to disruption by arc discharges was investigated. Design guidelines and recommended practices to reduce or eliminate the threat of malfunction and failures due to spacecraft charging/arcing were summarized.

  17. Apoptotic cells trigger a membrane-initiated pathway to increase ABCA1

    PubMed Central

    Fond, Aaron M.; Lee, Chang Sup; Schulman, Ira G.; Kiss, Robert S.; Ravichandran, Kodi S.

    2015-01-01

    Macrophages clear millions of apoptotic cells daily and, during this process, take up large quantities of cholesterol. The membrane transporter ABCA1 is a key player in cholesterol efflux from macrophages and has been shown via human genetic studies to provide protection against cardiovascular disease. How the apoptotic cell clearance process is linked to macrophage ABCA1 expression is not known. Here, we identified a plasma membrane–initiated signaling pathway that drives a rapid upregulation of ABCA1 mRNA and protein. This pathway involves the phagocytic receptor brain-specific angiogenesis inhibitor 1 (BAI1), which recognizes phosphatidylserine on apoptotic cells, and the intracellular signaling intermediates engulfment cell motility 1 (ELMO1) and Rac1, as ABCA1 induction was attenuated in primary macrophages from mice lacking these molecules. Moreover, this apoptotic cell–initiated pathway functioned independently of the liver X receptor (LXR) sterol–sensing machinery that is known to regulate ABCA1 expression and cholesterol efflux. When placed on a high-fat diet, mice lacking BAI1 had increased numbers of apoptotic cells in their aortic roots, which correlated with altered lipid profiles. In contrast, macrophages from engineered mice with transgenic BAI1 overexpression showed greater ABCA1 induction in response to apoptotic cells compared with those from control animals. Collectively, these data identify a membrane-initiated pathway that is triggered by apoptotic cells to enhance ABCA1 within engulfing phagocytes and with functional consequences in vivo. PMID:26075824

  18. The electrical power subsystem design for the high energy solar physics spacecraft concepts

    NASA Technical Reports Server (NTRS)

    Kulkarni, Milind

    1993-01-01

    This paper discusses the Electrical Power Subsystem (EPS) requirements, architecture, design description, performance analysis, and heritage of the components for two spacecraft concepts for the High Energy Solar Physics (HESP) Mission. It summarizes the mission requirements and the spacecraft subsystems and instrument power requirements, and it describes the EPS architecture for both options. A trade study performed on the selection of the solar cells - body mounted versus deployed panels - and the optimum number of panels is also presented. Solar cell manufacturing losses, array manufacturing losses, and the radiation and temperature effects on the GaAs/Ge and Si solar cells were considered part of the trade study and are included in this paper. Solar cell characteristics, cell circuit description, and the solar array area design are presented, as is battery sizing analysis performed based on the power requirements during launch and initial spacecraft operations. This paper discusses Earth occultation periods and the battery power requirements during this period as well as shunt control, battery conditioning, and bus regulation schemes. Design margins, redundancy philosophy, and predicted on-orbit battery and solar cell performance are summarized. Finally, the heritage of the components and technology risk assessment are provided.

  19. The epigenetics of tumour initiation: cancer stem cells and their chromatin.

    PubMed

    Avgustinova, Alexandra; Benitah, Salvador Aznar

    2016-02-01

    Cancer stem cells (CSCs) have been identified in various tumours and are defined by their potential to initiate tumours upon transplantation, self-renew and reconstitute tumour heterogeneity. Modifications of the epigenome can favour tumour initiation by affecting genome integrity, DNA repair and tumour cell plasticity. Importantly, an in-depth understanding of the epigenomic alterations underlying neoplastic transformation may open new avenues for chromatin-targeted cancer treatment, as these epigenetic changes could be inherently more amenable to inhibition and reversal than hard-wired genomic alterations. Here we discuss how CSC function is affected by chromatin state and epigenomic instability. PMID:26874045

  20. Putative CD133+ melanoma cancer stem cells induce initial angiogenesis in vivo.

    PubMed

    Zimmerer, Rüdiger M; Matthiesen, Peter; Kreher, Fritjof; Kampmann, Andreas; Spalthoff, Simon; Jehn, Philipp; Bittermann, Gido; Gellrich, Nils-Claudius; Tavassol, Frank

    2016-03-01

    Tumor angiogenesis is essential for tumor growth and metastasis, and is regulated by a complex network of various types of cells, chemokines, and stimulating factors. In contrast to sprouting angiogenesis, tumor angiogenesis is also influenced by hypoxia, inflammation, and the attraction of bone-marrow-derived cells. Recently, cancer stem cells have been reported to mimic vascularization by differentiating into endothelial cells and inducing vessel formation. In this study, the influence of cancer stem cells on initial angiogenesis was evaluated for the metastatic melanoma cell line D10. Following flow cytometry, CD133+ and CD133- cells were isolated using magnetic cell separation and different cell fractions were transferred to porcine gelatin sponges, which were implanted into the dorsal skinfold chamber of immunocompromised mice. Angiogenesis was analyzed based on microvessel density over a 10-day period using in vivo fluorescence microscopy, and the results were verified using immunohistology. CD133+ D10 cells showed a significant induction of early angiogenesis in vivo, contrary to CD133- D10 cells, unsorted D10 cells, and negative control. Neovascularization was confirmed by visualizing endothelial cells by immunohistology using an anti-CD31 antibody. Because CD133+ cells are rare in clinical specimens and hardly amenable to functional assays, the D10 cell line provides a suitable model to study the angiogenic potential of putative cancer stem cells and the leukocyte-endothelial cell interaction in the dorsal skinfold chamber in vivo. This cancer stem cell model might be useful in the development and evaluation of therapeutic agents targeting tumors. PMID:26656667

  1. Habitability design for spacecraft

    NASA Technical Reports Server (NTRS)

    Franklin, G. C.

    1978-01-01

    Habitability is understood to mean those spacecraft design elements that involve a degree of comfort, quality or necessities to support man in space. These elements are environment, architecture, mobility, clothing, housekeeping, food and drink, personal hygiene, off-duty activities, each of which plays a substantial part in the success of a mission. Habitability design for past space flights is discussed relative to the Mercury, Gemini, Apollo, and Skylab spacecraft, with special emphasis on an examination of the Shuttle Orbiter cabin design from a habitability standpoint. Future projects must consider the duration and mission objectives to meet their habitability requirements. Larger ward rooms, improved sleeping quarters and more complete hygiene facilities must be provided for future prolonged space flights

  2. LEO Spacecraft Charging Guidelines

    NASA Technical Reports Server (NTRS)

    Hillard, G. B.; Ferguson, D. C.

    2002-01-01

    Over the past decade, Low Earth Orbiting (LEO) spacecraft have gradually required ever-increasing power levels. As a rule, this has been accomplished through the use of high voltage systems. Recent failures and anomalies on such spacecraft have been traced to various design practices and materials choices related to the high voltage solar arrays. NASA Glenn has studied these anomalies including plasma chamber testing on arrays similar to those that experienced difficulties on orbit. Many others in the community have been involved in a comprehensive effort to understand the problems and to develop practices to avoid them. The NASA Space Environments and Effects program, recognizing the timeliness of this effort, has commissioned and funded a design guidelines document intended to capture the current state of understanding. We present here an overview of this document, which is now nearing completion.

  3. Flexible spacecraft simulator

    NASA Technical Reports Server (NTRS)

    1987-01-01

    Verification of control algorithms for flexible spacecraft can be done only through simulation and test; these are necessary to understand control/structure interaction (C/SI) sufficiently to design robust controllers for future spacecraft. The objective persued is to develop a low-cost facility which simulates the fundamental problem of C/SI; and to provide accessibility for designs so that experience can be gained in applying various multivariable control design methods to an actual structure. A test facility is being constructed with test elements that provide 3 rigid body and 6 flexible modes, all in the horizontal plane, with frequencies below 2.5 Hz. The control force actuator are on/off air jets with sensing by optical displacement sensors. Loop closure is provided by a digital computer with control algorithms designed using the IAC and MATRIX-X.

  4. Radiation Environment Inside Spacecraft

    NASA Technical Reports Server (NTRS)

    O'Neill, Patrick

    2015-01-01

    Dr. Patrick O'Neill, NASA Johnson Space Center, will present a detailed description of the radiation environment inside spacecraft. The free space (outside) solar and galactic cosmic ray and trapped Van Allen belt proton spectra are significantly modified as these ions propagate through various thicknesses of spacecraft structure and shielding material. In addition to energy loss, secondary ions are created as the ions interact with the structure materials. Nuclear interaction codes (FLUKA, GEANT4, HZTRAN, MCNPX, CEM03, and PHITS) transport free space spectra through different thicknesses of various materials. These "inside" energy spectra are then converted to Linear Energy Transfer (LET) spectra and dose rate - that's what's needed by electronics systems designers. Model predictions are compared to radiation measurements made by instruments such as the Intra-Vehicular Charged Particle Directional Spectrometer (IV-CPDS) used inside the Space Station, Orion, and Space Shuttle.

  5. Spacecraft drag modelling

    NASA Astrophysics Data System (ADS)

    Mostaza Prieto, David; Graziano, Benjamin P.; Roberts, Peter C. E.

    2014-01-01

    This paper reviews currently available methods to calculate drag coefficients of spacecraft traveling in low Earth orbits (LEO). Aerodynamic analysis of satellites is necessary to predict the drag force perturbation to their orbital trajectory, which for LEO orbits is the second in magnitude after the gravitational disturbance due to the Earth's oblateness. Historically, accurate determination of the spacecraft drag coefficient (CD) was rarely required. This fact was justified by the low fidelity of upper atmospheric models together with the lack of experimental validation of the theory. Therefore, the calculation effort was a priori not justified. However, advances on the field, such as new atmospheric models of improved precision, have allowed for a better characterization of the drag force. They have also addressed the importance of using physically consistent drag coefficients when performing aerodynamic calculations to improve analysis and validate theories. We review the most common approaches to predict these coefficients.

  6. MIF Maintains the Tumorigenic Capacity of Brain Tumor-Initiating Cells by Directly Inhibiting p53.

    PubMed

    Fukaya, Raita; Ohta, Shigeki; Yaguchi, Tomonori; Matsuzaki, Yumi; Sugihara, Eiji; Okano, Hideyuki; Saya, Hideyuki; Kawakami, Yutaka; Kawase, Takeshi; Yoshida, Kazunari; Toda, Masahiro

    2016-05-01

    Tumor-initiating cells thought to drive brain cancer are embedded in a complex heterogeneous histology. In this study, we isolated primary cells from 21 human brain tumor specimens to establish cell lines with high tumorigenic potential and to identify the molecules enabling this capability. The morphology, sphere-forming ability upon expansion, and differentiation potential of all cell lines were indistinguishable in vitro However, testing for tumorigenicity revealed two distinct cell types, brain tumor-initiating cells (BTIC) and non-BTIC. We found that macrophage migration inhibitory factor (MIF) was highly expressed in BTIC compared with non-BTIC. MIF bound directly to both wild-type and mutant p53 but regulated p53-dependent cell growth by different mechanisms, depending on glioma cell line and p53 status. MIF physically interacted with wild-type p53 in the nucleus and inhibited its transcription-dependent functions. In contrast, MIF bound to mutant p53 in the cytoplasm and abrogated transcription-independent induction of apoptosis. Furthermore, MIF knockdown inhibited BTIC-induced tumor formation in a mouse xenograft model, leading to increased overall survival. Collectively, our findings suggest that MIF regulates BTIC function through direct, intracellular inhibition of p53, shedding light on the molecular mechanisms underlying the tumorigenicity of certain malignant brain cells. Cancer Res; 76(9); 2813-23. ©2016 AACR. PMID:26980763

  7. Spacecraft transmitter reliability

    NASA Technical Reports Server (NTRS)

    1980-01-01

    A workshop on spacecraft transmitter reliability was held at the NASA Lewis Research Center on September 25 and 26, 1979, to discuss present knowledge and to plan future research areas. Since formal papers were not submitted, this synopsis was derived from audio tapes of the workshop. The following subjects were covered: users' experience with space transmitters; cathodes; power supplies and interfaces; and specifications and quality assurance. A panel discussion ended the workshop.

  8. Spacecraft Thermal Management

    NASA Technical Reports Server (NTRS)

    Hurlbert, Kathryn Miller

    2009-01-01

    In the 21st century, the National Aeronautics and Space Administration (NASA), the Russian Federal Space Agency, the National Space Agency of Ukraine, the China National Space Administration, and many other organizations representing spacefaring nations shall continue or newly implement robust space programs. Additionally, business corporations are pursuing commercialization of space for enabling space tourism and capital business ventures. Future space missions are likely to include orbiting satellites, orbiting platforms, space stations, interplanetary vehicles, planetary surface missions, and planetary research probes. Many of these missions will include humans to conduct research for scientific and terrestrial benefits and for space tourism, and this century will therefore establish a permanent human presence beyond Earth s confines. Other missions will not include humans, but will be autonomous (e.g., satellites, robotic exploration), and will also serve to support the goals of exploring space and providing benefits to Earth s populace. This section focuses on thermal management systems for human space exploration, although the guiding principles can be applied to unmanned space vehicles as well. All spacecraft require a thermal management system to maintain a tolerable thermal environment for the spacecraft crew and/or equipment. The requirements for human rating and the specified controlled temperature range (approximately 275 K - 310 K) for crewed spacecraft are unique, and key design criteria stem from overall vehicle and operational/programatic considerations. These criteria include high reliability, low mass, minimal power requirements, low development and operational costs, and high confidence for mission success and safety. This section describes the four major subsystems for crewed spacecraft thermal management systems, and design considerations for each. Additionally, some examples of specialized or advanced thermal system technologies are presented

  9. Very Small Interstellar Spacecraft

    NASA Astrophysics Data System (ADS)

    Peck, Mason A.

    2007-02-01

    This paper considers lower limits of length scale in spacecraft: interstellar vehicles consisting of little more material than found in a typical integrated-circuit chip. Some fundamental scaling principles are introduced to show how the dynamics of the very small can be used to realize interstellar travel with minimal advancements in technology. Our recent study for the NASA Institute for Advanced Concepts provides an example: the use of the Lorentz force that acts on electrically charged spacecraft traveling through planetary and stellar magnetospheres. Schaffer and Burns, among others, have used Cassini and Voyager imagery to show that this interaction is responsible for some of the resonances in the orbital dynamics of dust in Jupiter's and Saturn's rings. The Lorentz force turns out to vary in inverse proportion to the square of this characteristic length scale, making it a more effective means of propelling tiny spacecraft than solar sailing. Performance estimates, some insight into plasma interactions, and some hardware concepts are offered. The mission architectures considered here involve the use of these propellantless propulsion techniques for acceleration within our solar system and deceleration near the destination. Performance estimates, some insight into plasma interactions, and some hardware concepts are offered. The mission architectures considered here involve the use of these propellantless propulsion techniques for acceleration within our solar system and deceleration near the destination. We might envision a large number of such satellites with intermittent, bursty communications set up as a one-dimensional network to relay signals across great distances using only the power likely from such small spacecraft. Conveying imagery in this fashion may require a long time because of limited power, but the prospect of imaging another star system close-up ought to be worth the wait.

  10. Spacecraft sanitation agent development

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The development of an effective sanitizing agent that is compatible with the spacecraft environment and the human occupant is discussed. Experimental results show that two sanitation agents must be used to satisfy mission requirements: one agent for personal hygiene and one for equipment maintenance. It was also recommended that a water rinse be used with the agents for best results, and that consideration be given to using the agents pressure packed or in aerosol formulations.

  11. Clonal Analysis Provides Evidence for Transient Initial Cells in Shoot Apical Meristems of Seed Plants.

    PubMed

    Zagórska-Marek; Turzańska

    2000-03-01

    Drift of mutated sectors in sectorial or mericlinal plant chimeras has been interpreted as indirect evidence of initial impermanence at the apex. However, the same effect may result from mutation in noninitial cells positioned close to the vertex of the apical dome. Clonal analysis of the cell packets present in the superficial layer of spruce and magnolia apices provided the library of patterns suggesting that the position and the number of initial cells, and in some cases also the meristem axis inclination, may change over time. Multicellular clones originating from a single cell have been found in the geometric center of some apices, whereas in other apices the cellular center (where three or four clonal borders meet) did not correspond to the geome PMID:11010992

  12. Dynamic competition between transcription initiation and repression: Role of nonequilibrium steps in cell-to-cell heterogeneity.

    PubMed

    Mitarai, Namiko; Semsey, Szabolcs; Sneppen, Kim

    2015-08-01

    Transcriptional repression may cause transcriptional noise by a competition between repressor and RNA polymerase binding. Although promoter activity is often governed by a single limiting step, we argue here that the size of the noise strongly depends on whether this step is the initial equilibrium binding or one of the subsequent unidirectional steps. Overall, we show that nonequilibrium steps of transcription initiation systematically increase the cell-to-cell heterogeneity in bacterial populations. In particular, this allows also weak promoters to give substantial transcriptional noise. PMID:26382435

  13. Gaia Spacecraft Mechanical Development

    NASA Astrophysics Data System (ADS)

    Lebranchu, C.; Blender, F.; Touzeau, S.; Escolar, D.

    2012-07-01

    Gaia is the European Space Agency's cornerstone mission for global space astrometry. Its goal is to make the largest, most precise three-dimensional map of our Galaxy by surveying an unprecedented number of stars. This paper gives an overview of the mechanical system engineering and verification of the spacecraft. This development includes several technical challenges. First of all, the very high stability performance as required for the mission is a key driver for the design; which incurs a high degree of stability. This is achieved through decoupling between payload and service module, and the use of high-performance engineering tools and of Silicon Carbide (Boostec® SiC) for the Payload. Compliance of spacecraft mass and volume with launcher capability is another key challenge, as well as the development of the 10.3 meter diameter deployable sunshield. The spacecraft mechanical verification follows an innovative approach, with direct testing on the flight model, without dedicated structural model. Gaia mechanical development is the fruit of a successful international cooperation.

  14. Mechanism of initial attachment of corneal epithelial cells to polymeric surfaces.

    PubMed

    Steele, J G; Johnson, G; Griesser, H J; Underwood, P A

    1997-12-01

    The initial attachment of cultured bovine corneal epithelial cells and stromal fibroblasts to two oxygen-containing synthetic polymers was studied. Cultured epithelial cells and stromal fibroblasts were seeded onto two oxygen-containing surfaces: 'tissue culture' polystyrene (TCPS) and a polymer film deposited by RF plasma deposition using a methylmethacrylate monomer (MMA/FEP). To establish the mechanism of cell attachment, the effect of the selective removal of the vitronectin and fibronectin from the serum used in the culture medium was tested. The attachment of cultured epithelial cells during the first 90 min of culture was reduced by 40% (TCPS)-80% (MMA/FEP) as a result of removing vitronectin from the medium. Attachment of these cells to TCPS was reduced by 85-95% when the serum was depleted of both fibronectin and vitronectin. However, depletion of fibronectin reduced cell attachment to TCPS by 20%, whilst on MMA/FEP cell attachment was equivalent, or higher, than that for intact serum. The attachment of cultured corneal stromal fibroblasts was similarly dependent on vitronectin but less dependent on fibronectin. Therefore, for the attachment of both cultured epithelial cells and fibroblasts to oxygen-containing surfaces in the presence of serum, there is a high requirement for serum vitronectin but a lesser requirement for fibronectin. The effects of the establishment of corneal epithelial cells in culture and the site of origin of the cells, were determined. Primary isolates of epithelial cells isolated from the limbal, central or peripheral regions of the cornea were less dependent on vitronectin for initial attachment to TCPS than were these cells after several passages in culture. Furthermore, the primary isolates were dramatically less responsive to vitronectin than the cultured cells. These results indicate that the mechanism of attachment of corneal epithelial cells to TCPS varies with the culture experience of the cells. Cells that are culture

  15. Addressing EO-1 Spacecraft Pulsed Plasma Thruster EMI Concerns

    NASA Technical Reports Server (NTRS)

    Zakrzwski, C. M.; Davis, Mitch; Sarmiento, Charles; Bauer, Frank H. (Technical Monitor)

    2001-01-01

    The Pulsed Plasma Thruster (PPT) Experiment on the Earth Observing One (EO-1) spacecraft has been designed to demonstrate the capability of a new generation PPT to perform spacecraft attitude control. Results from PPT unit level radiated electromagnetic interference (EMI) tests led to concerns about potential interference problems with other spacecraft subsystems. Initial plans to address these concerns included firing the PPT at the spacecraft level both in atmosphere, with special ground support equipment. and in vacuum. During the spacecraft level tests, additional concerns where raised about potential harm to the Advanced Land Imager (ALI). The inadequacy of standard radiated emission test protocol to address pulsed electromagnetic discharges and the lack of resources required to perform compatibility tests between the PPT and an ALI test unit led to changes in the spacecraft level validation plan. An EMI shield box for the PPT was constructed and validated for spacecraft level ambient testing. Spacecraft level vacuum tests of the PPT were deleted. Implementation of the shield box allowed for successful spacecraft level testing of the PPT while eliminating any risk to the ALI. The ALI demonstration will precede the PPT demonstration to eliminate any possible risk of damage of ALI from PPT operation.

  16. Effect of Initial Seeding Density on Human Umbilical Cord Mesenchymal Stromal Cells for Fibrocartilage Tissue Engineering

    PubMed Central

    Wang, Limin; Seshareddy, Kiran; Weiss, Mark L.

    2009-01-01

    Cells derived from Wharton's jelly from human umbilical cords (called umbilical cord mesenchymal stromal cells herein) are a novel cell source for musculoskeletal tissue engineering. In this study, we examined the effects of different seeding densities on seeding efficiency, cell proliferation, biosynthesis, mechanical integrity, and chondrogenic differentiation. Cells were seeded on non-woven polyglycolic acid (PGA) meshes in an orbital shaker at densities of 5, 25, or 50 million cells/mL and then statically cultured for 4 weeks in chondrogenic medium. At week 0, initial seeding density did not affect seeding efficiency. Throughout the 4-week culture period, absolute cell numbers of the 25 and 50 million-cells/mL (higher density) groups were significantly larger than in the 5 million-cells/mL (lower density) group. The presence of collagen types I and II and aggrecan was confirmed using immunohistochemical staining. Glycosaminoglycan and collagen contents per construct in the higher-density groups were significantly greater than in the lower-density group. Constructs in the high-density groups maintained their mechanical integrity, which was confirmed using unconfined compression testing. In conclusion, human umbilical cord cells demonstrated the potential for chondrogenic differentiation in three-dimensional tissue engineering, and higher seeding densities better promoted biosynthesis and mechanical integrity, and thus a seeding density of at least 25 million cells/mL is recommended for fibrocartilage tissue engineering with umbilical cord mesenchymal stromal cells. PMID:18759671

  17. CD271 is a functional and targetable marker of tumor-initiating cells in head and neck squamous cell carcinoma

    PubMed Central

    Murillo-Sauca, Oihana; Chung, Man Ki; Shin, June Ho; Karamboulas, Christina; Kwok, Shirley; Jung, Young Ho; Oakley, Richard; Tysome, James R.; Farnebo, Lovisa O.; Kaplan, Michael J.; Sirjani, Davud; Divi, Vasu; Holsinger, F. Christopher; Tomeh, Chafeek; Nichols, Anthony; Le, Quynh T.; Colevas, A. A. Dimitrios; Kong, Christina S.; Uppaluri, Ravindra; Lewis, James S.; Ailles, Laurie E.; Sunwoo, John B.

    2014-01-01

    Tumor-initiating cells (TICs) in squamous cell carcinoma of the head and neck (SCCHN) are best characterized by their surface expression of CD44. Although there is great interest in identifying strategies to target this population, no marker of these cells has been found to be functionally active. Here, we examined the expression of the purported marker of normal human oral epithelial stem cells, CD271. We show that CD271 expression is restricted to a subset of the CD44+ cells. Using xenograft assays, we show that the CD44+CD271+ subpopulation contains the most tumorigenic cells. Loss of CD271 function results in a block in the G2-M phase of the cell cycle and a profound negative impact on the capacity of these cells to initiate tumor formation in vivo. Incubation with recombinant NGF results in enhanced phosphorylation of Erk, providing additional evidence that CD271 is functionally active. Finally, incubation of SCCHN cells with antibody to CD271 results in decreased Erk phosphorylation and decreased tumor formation in vivo. Thus, our data are the first to demonstrate that CD271 more specifically identifies the TIC subpopulation within the CD44+ compartment in SCCHN and that this receptor is a functionally active and targetable molecule. PMID:25149537

  18. Acoustic sensing of the initial adhesion of chemokine-stimulated cancer cells.

    PubMed

    Wei, Xiao-Lan; Zhang, Jing; Zhao, Na

    2013-11-01

    Chemokines together with their receptors play important roles in tumor metastasis. Intracellular signals stimulated by chemokines regulate the initial adhesion of cancer cells, which controls the subsequent cell spreading and migration. Until now, the nature of initial cell adhesion has been understood very poorly, since conventional assays are static and could not provide dynamic information. In order to address this issue, we adopt an acoustic sensor, quartz crystal microbalance (QCM), to monitor the attachment of chemokine-stimulated cancer cells in real-time. As a model, the chemokine CXCL12 was used to stimulate three human breast cancer cell lines expressing different levels of its receptor CXCR4, which triggers intracellular signaling pathways that activate integrins across cell membrane. Interaction between cellular integrins and adhesion molecules (CAMs) pre-coated on sensor surfaces were in situ monitored by QCM of which the frequency was sensitive to the mechanical connection of cells to the sensor surface. The ratio of frequency shift under stimulation to that without stimulation indicated the number and strength of integrin-CAM binding stimulated by the chemokine. The cell-surface binding was found to be enhanced by CXCL12, which depends on the CAM type and levels of chemokine and receptor, and was significantly inhibited by a blocker of the chemokine pathway. The binding of integrin with intercellular adhesion molecule was also found to be strong and in good correlated with the chemotactic indexes obtained by the classical Boyden chamber assay. This research suggests that acoustic sensing of initial cell adhesion could provide a dynamic insight into cell interfacial phenomena. PMID:23911626

  19. Multiple myeloma and bone marrow mesenchymal stem cells' crosstalk: Effect on translation initiation.

    PubMed

    Attar-Schneider, Oshrat; Zismanov, Victoria; Dabbah, Mahmoud; Tartakover-Matalon, Shelly; Drucker, Liat; Lishner, Michael

    2016-09-01

    Multiple myeloma (MM) malignant plasma cells reside in the bone marrow (BM) and convert it into a specialized pre-neoplastic niche that promotes the proliferation and survival of the cancer cells. BM resident mesenchymal stem cells (BM-MSCs) are altered in MM and in vitro studies indicate their transformation by MM proximity is within hours. The response time frame suggested that protein translation may be implicated. Thus, we assembled a co-culture model of MM cell lines with MSCs from normal donors (ND) and MM patients to test our hypothesis. The cell lines (U266, ARP-1) and BM-MSCs (ND, MM) were harvested separately after 72 h of co-culture and assayed for proliferation, death, levels of major translation initiation factors (eIF4E, eIF4GI), their targets, and regulators. Significant changes were observed: BM-MSCs (ND and MM) co-cultured with MM cell lines displayed elevated proliferation and death as well as increased expression/activity of eIF4E/eIF4GI; MM cell lines co-cultured with MM-MSCs also displayed higher proliferation and death rates coupled with augmented translation initiation factors; in contrast, MM cell lines co-cultured with ND-MSCs did not display elevated proliferation only death and had no changes in eIF4GI levels/activity. eIF4E expression was increased in one of the cell lines. Our study demonstrates that there is direct dialogue between the MM and BM-MSCs populations that includes translation initiation manipulation and critically affects cell fate. Future research should be aimed at identifying therapeutic targets that may be used to minimize the collateral damage to the cancer microenvironment and limit its recruitment into the malignant process. © 2015 Wiley Periodicals, Inc. PMID:26293751

  20. JNK Signaling in the Control of the Tumor-Initiating Capacity Associated with Cancer Stem Cells

    PubMed Central

    Sato, Atsushi; Okada, Masashi

    2013-01-01

    Deregulation of c-Jun NH2-terminal kinase (JNK) signaling occurs frequently in a variety of human cancers, yet the exact role(s) of JNK deregulation in cancer cell biology remains to be fully elucidated. Our recent demonstration that the activity of JNK is required not only for self-renewal of glioma stem cells but also for their tumor initiation has, however, identified a new role for JNK in the control of the stemness and tumor-initiating capacity of cancer cells. Significantly, transient JNK inhibition was sufficient to cause sustained loss of the tumor-initiating capacity of glioma stem cells, suggesting that the phenotype of “lost tumor-initiating capacity” may be as stable as the differentiated state and that the tumor-initiating capacity might therefore be under the control of JNK through an epigenetic mechanism that also governs stemness and differentiation. Here, in this article, we review the role and mechanism of JNK in the control of this “stemness-associated tumor-initiating capacity” (STATIC), a new hypothetical concept we introduce in this review article. Since the idea of STATIC is essentially applicable to both cancer types that do and do not follow the cancer stem cell hypothesis, we also give consideration to the possible involvement of JNK-mediated control of STATIC in a wide range of human cancers in which JNK is aberrantly activated. Theoretically, successful targeting of STATIC through JNK could contribute to long-term control of cancer. Issues to be considered before clinical application of therapies targeting this JNK-STATIC axis are also discussed. PMID:24349636

  1. Positive mRNA Translational Control in Germ Cells by Initiation Factor Selectivity

    PubMed Central

    Friday, Andrew J.; Keiper, Brett D.

    2015-01-01

    Ultimately, the production of new proteins in undetermined cells pushes them to new fates. Other proteins hold a stem cell in a mode of self-renewal. In germ cells, these decision-making proteins are produced largely from translational control of preexisting mRNAs. To date, all of the regulation has been attributed to RNA binding proteins (RBPs) that repress mRNAs in many models of germ cell development (Drosophila, mouse, C. elegans, and Xenopus). In this review, we focus on the selective, positive function of translation initiation factors eIF4E and eIF4G, which recruit mRNAs to ribosomes upon derepression. Evidence now shows that the two events are not separate but rather are coordinated through composite complexes of repressors and germ cell isoforms of eIF4 factors. Strikingly, the initiation factor isoforms are themselves mRNA selective. The mRNP complexes of translation factors and RBPs are built on specific populations of mRNAs to prime them for subsequent translation initiation. Simple rearrangement of the partners causes a dormant mRNP to become synthetically active in germ cells when and where they are required to support gametogenesis. PMID:26357652

  2. MicroRNA-203 represses selection and expansion of oncogenic Hras transformed tumor initiating cells

    PubMed Central

    Riemondy, Kent; Wang, Xiao-jing; Torchia, Enrique C; Roop, Dennis R; Yi, Rui

    2015-01-01

    In many mouse models of skin cancer, only a few tumors typically form even though many cells competent for tumorigenesis receive the same oncogenic stimuli. These observations suggest an active selection process for tumor-initiating cells. Here, we use quantitative mRNA- and miR-Seq to determine the impact of HrasG12V on the transcriptome of keratinocytes. We discover that microRNA-203 is downregulated by HrasG12V. Using a knockout mouse model, we demonstrate that loss of microRNA-203 promotes selection and expansion of tumor-initiating cells. Conversely, restoration of microRNA-203 using an inducible model potently inhibits proliferation of these cells. We comprehensively identify microRNA-203 targets required for Hras-initiated tumorigenesis. These targets include critical regulators of the Ras pathway and essential genes required for cell division. This study establishes a role for the loss of microRNA-203 in promoting selection and expansion of Hras mutated cells and identifies a mechanism through which microRNA-203 antagonizes Hras-mediated tumorigenesis. DOI: http://dx.doi.org/10.7554/eLife.07004.001 PMID:26203562

  3. Tumour promoting functions of TGF-β in CML-initiating cells.

    PubMed

    Miyazono, Kohei

    2012-11-01

    Recent data have shown that transforming growth factor-β (TGF-β) plays bi-directional roles in the maintenance of cancer stem cells in a cell-type and context-dependent manner. Zhu et al. (TGF-β1-induced PI3K/Akt/NF-κB/MMP9 signalling pathway is activated in Philadelphia chromosome-positive chronic myeloid leukaemia hemangioblasts. J. Biochem. 2011;149:405-414) studied the functions of TGF-β in hemangioblasts from patients with chronic myeloid leukemia (CML), which displayed properties of leukemia-initiating cells. They have shown that the BCR/ABL oncoprotein induced the production of TGF-β in the CML hemangioblasts, and that TGF-β activated the phosphoinositide 3-kinase-Akt-NF-κB pathway in these cells. Activation of this pathway enhanced the production of matrix metalloproteinase-9 leading to increased synthesis of soluble Kit ligand and intercellular adhesion molecule-1. TGF-β is known to maintain the CML-initiating cells through the Akt-FoxO pathway. Together, these findings suggest that TGF-β may exhibit multiple functions in progression of CML through acting on leukemia-initiating cells. PMID:22989931

  4. Solar array/spacecraft biasing

    NASA Technical Reports Server (NTRS)

    Fitzgerald, D. J.

    1981-01-01

    Biasing techniques and their application to the control of spacecraft potential is discussed. Normally when a spacecraft is operated with ion thrusters, the spacecraft will be 10-20 volts negative of the surrounding plasma. This will affect scientific measurements and will allow ions from the charge-exchange plasma to bombard the spacecraft surfaces with a few tens of volts of energy. This condition may not be tolerable. A proper bias system is described that can bring the spacecraft to or near the potential of the surrounding plasma.

  5. Upsets related to spacecraft charging

    SciTech Connect

    Frederickson, A.R.

    1996-04-01

    The charging of spacecraft components by high energy radiation can result in spontaneous pulsed discharges. The pulses can interrupt normal operations of spacecraft electronics. The 20-year history of ground studies and spacecraft studies of this phenomenon are reviewed. The data from space are not sufficient to unambiguously point to a few specific solutions. The ground based data continue to find more problem areas the longer one looks. As spacecraft become more complex and carry less radiation shielding, the charging and discharging of insulators is becoming a more critical problem area. Ground experiments indicate that solutions for spacecraft are multiple and diverse, and many technical details are reviewed or introduced here.

  6. Initiation of oncogenic transformation in human mammary epithelial cells by charged particles

    NASA Technical Reports Server (NTRS)

    Yang, T. C.; Georgy, K. A.; Craise, L. M.; Durante, M.

    1997-01-01

    Experimental studies have shown that high linear-energy transfer (LET) charged particles can be more effective than x-rays and gamma-rays in inducing oncogenic transformation in cultured cells and tumors in animals. Based on these results, experiments were designed and performed with an immortal human mammary epithelial cell line (H184B5), and several clones transformed by heavy ions were obtained. Cell fusion experiments were subsequently done, and results indicate that the transforming gene(s) is recessive. Chromosome analysis with fluorescence in situ hybridization (FISH) techniques also showed additional translocations in transformed human mammary epithelial cells. In addition, studies with these cell lines indicate that heavy ions can effectively induce deletion, break, and dicentrics. Deletion of tumor suppressor gene(s) and/or formation of translocation through DNA double strand breaks is a likely mechanism for the initiation of oncogenic transformation in human mammary epithelial cells.

  7. Increased initial levels of chromosome damage and heterogeneous chromosome repair in ataxia telangiectasia heterozygote cells.

    PubMed

    Pandita, T K; Hittelman, W N

    1994-10-01

    Individuals heterozygous for ataxia telangiectasia (AT) appear clinically normal but have a 2-3-fold overall excess risk of cancer. Various approaches have been used to identify AT heterozygotes, however, the results are ambiguous. We recently reported that AT homozygotes exhibit more initial chromosome damage after irradiation than normal cells despite identical levels of DNA double strand breaks (DSBs) as well as a reduced fast repair component at both the DNA and chromosome levels. To determine whether AT heterozygotes exhibit the AT or normal cellular phenotype, we compared four AT heterozygote lymphoblastoid cell lines with normal control and AT homozygote lymphoblastoid cells with regard to cell survival, initial levels of damage, and repair at the DNA and chromosome levels after gamma-irradiation in G1, S, and G2 phase (estimated by neutral DNA filter elution and premature chromosome condensation). There was no significant difference in survival, induction and repair of DNA DSBs, or chromosome repair between AT heterozygote and normal cells. In contrast, all four AT heterozygote cell lines showed increased levels of chromosome damage; G1 phase cells showed intermediate levels and G2 phase cells showed levels equivalent to the AT homozygote phenotype. These results suggest that premature chromosome condensation may be useful for detecting AT heterozygotes. PMID:7523872

  8. Proceedings of the Spacecraft Charging Technology Conference

    NASA Technical Reports Server (NTRS)

    Pike, C. P. (Editor); Lovell, R. R. (Editor)

    1977-01-01

    Over 50 papers from the spacecraft charging conference are included on subjects such as: (1) geosynchronous plasma environment, (2) spacecraft modeling, (3) spacecraft materials characterization, (4) spacecraft materials development, and (5) satellite design and test.

  9. A Role for OCT4 in Tumor Initiation of Drug-Resistant Prostate Cancer Cells

    PubMed Central

    Linn, Douglas E.; Yang, Xi; Sun, Feng; Xie, Yingqiu; Chen, Hege; Jiang, Richeng; Chen, Hegang; Chumsri, Saranya; Burger, Angelika M.; Qiu, Yun

    2010-01-01

    Drug resistance remains a clinical challenge in cancer treatment due to poor understanding of underlying mechanisms. We have established several drug-resistant prostate cancer cell lines by long-term culture in medium containing chemotherapeutic drugs. These resistant lines displayed a significant increase in side population cells due to overexpression of drug efflux pumps including ABCG2/BCRP and MDR1/Pgp. To uncover potential mechanisms underlying drug resistance, we performed microarray analysis to identify differentially expressed genes in 2 drug-resistant lines. We observed that POU5F1/OCT4, a transcription factor key to regulating pluripotency in embryonic stem cells, was upregulated in drug-resistant lines and accompanied by transcriptional activation of a set of its known target genes. Upregulation of OCT4 in drug-resistant cells was validated by RT-PCR and sequencing of PCR products as well as confirmation by Western blot and specific shRNA knockdown. Analysis of the regulatory region of POU5F1/OCT4 revealed a reduction of methylation in drug-resistant cell lines. Furthermore, these drug-resistant cells exhibited a significant increase in tumorigenicity in vivo. Subcutaneous inoculation of as few as 10 drug-resistant cells could initiate tumor formation in SCID mice, whereas no detectable tumors were observed from the parental line under similar conditions, suggesting that these drug-resistant cells may be enriched for tumor-initiating cells. Knocking down OCT4 expression by specific shRNAs attenuated growth of drug-resistant cells. Our data suggest that OCT4 re-expression in cancer cells may play an important role in carcinogenesis and provide one possible mechanism by which cancer cells acquire/maintain a drug-resistant phenotype. PMID:21779471

  10. Spacecraft Modularity for Serviceable Satellites

    NASA Technical Reports Server (NTRS)

    Rossetti, Dino; Keer, Beth; Panek, John; Ritter, Bob; Reed, Benjamin; Cepollina, Frank

    2015-01-01

    Spacecraft modularity has been a topic of interest at NASA since the 1970s, when the Multi-­-Mission Modular Spacecraft (MMS) was developed at the Goddard Space Flight Center. Since then, modular concepts have been employed for a variety of spacecraft and, as in the case of the Hubble Space Telescope (HST) and the International Space Station (ISS), have been critical to the success of on-­- orbit servicing. Modularity is even more important for future robotic servicing. Robotic satellite servicing technologies under development by NASA can extend mission life and reduce lifecycle cost and risk. These are optimized when the target spacecraft is designed for servicing, including advanced modularity. This paper will explore how spacecraft design, as demonstrated by the Reconfigurable Operational spacecraft for Science and Exploration (ROSE) spacecraft architecture, and servicing technologies can be developed in parallel to fully take advantage of the promise of both.

  11. Spacecraft Modularity for Serviceable Satellites

    NASA Technical Reports Server (NTRS)

    Reed, Benjamin B.; Rossetti, Dino; Keer, Beth; Panek, John; Cepollina, Frank; Ritter, Robert

    2015-01-01

    Spacecraft modularity has been a topic of interest at NASA since the 1970s, when the Multi-Mission Modular Spacecraft (MMS) was developed at the Goddard Space Flight Center. Since then, modular concepts have been employed for a variety of spacecraft and, as in the case of the Hubble Space Telescope (HST) and the International Space Station (ISS), have been critical to the success of on-orbit servicing. Modularity is even more important for future robotic servicing. Robotic satellite servicing technologies under development by NASA can extend mission life and reduce life-cycle cost and risk. These are optimized when the target spacecraft is designed for servicing, including advanced modularity. This paper will explore how spacecraft design, as demonstrated by the Reconfigurable Operational spacecraft for Science and Exploration (ROSE) spacecraft architecture, and servicing technologies can be developed in parallel to fully take advantage of the promise of both.

  12. Automating Trend Analysis for Spacecraft Constellations

    NASA Technical Reports Server (NTRS)

    Davis, George; Cooter, Miranda; Updike, Clark; Carey, Everett; Mackey, Jennifer; Rykowski, Timothy; Powers, Edward I. (Technical Monitor)

    2001-01-01

    missions such as DRACO with the intent that mission operations costs be significantly reduced. The goal of the Constellation Spacecraft Trend Analysis Toolkit (CSTAT) project is to serve as the pathfinder for a fully automated trending system to support spacecraft constellations. The development approach to be taken is evolutionary. In the first year of the project, the intent is to significantly advance the state of the art in current trending systems through improved functionality and increased automation. In the second year, the intent is to add an expert system shell, likely through the adaptation of an existing commercial-off-the-shelf (COTS) or government-off-the-shelf (GOTS) tool to implement some level of the trending intelligence that humans currently provide in manual operations. In the third year, the intent is to infuse the resulting technology into a near-term constellation or formation-flying mission to test it and gain experience in automated trending. The lessons learned from the real missions operations experience will then be used to improve the system, and to ultimately incorporate it into a fully autonomous, closed-loop mission operations system that is truly capable of supporting large constellations. In this paper, the process of automating trend analysis for spacecraft constellations will be addressed. First, the results of a survey on automation in spacecraft mission operations in general, and in trending systems in particular will be presented to provide an overview of the current state of the art. Next, a rule-based model for implementing intelligent spacecraft subsystem trending will be then presented, followed by a survey of existing COTS/GOTS tools that could be adapted for implementing such a model. The baseline design and architecture of the CSTAT system will be presented. Finally, some results obtained from initial software tests and demonstrations will be presented.

  13. miR-17 inhibition enhances the formation of kidney cancer spheres with stem cell/tumor initiating cell properties

    PubMed Central

    Lichner, Zsuzsanna; Saleh, Carol; Subramaniam, Venkateswaran; Seivwright, Annetta; Prud'homme, Gerald Joseph; Yousef, George Makram

    2015-01-01

    Renal cell carcinoma (RCC) is an aggressive disease, with 35% chance of metastasis. The ‘cancer stem cell’ hypothesis suggests that a subset of cancer cells possess stem cell properties and is crucial in tumor initiation, metastasis and treatment resistance. We isolated RCC spheres and showed that they exhibit cancer stem cell/tumor initiating cell-like properties including the formation of self-renewing spheres, high tumorigenicity and the ability to differentiate to cell types of the original tumor. Spheres showed increased expression of stem cell-related transcription factors and mesenchymal markers.  miRNAs were differentially expressed between RCC spheres and their parental cells. Inhibition of miR-17 accelerated the formation of RCC spheres which shared molecular characteristics with the spontaneous RCC spheres. Target prediction pointed out TGFβ pathway activation as a possible mechanism to drive RCC sphere formation. We demonstrate that miR-17 overexpression interferes with the TGFβ-EMT axis and hinders RCC sphere formation; and validated TGFBR2 as a direct and biologically relevant target during this process. Thus, a single miRNA may have an impact on the formation of highly tumorigenic cancer spheres of kidney cancer. PMID:25011053

  14. Mesenchymal stem cells expressing GD2 and CD271 correlate with breast cancer-initiating cells in bone marrow

    PubMed Central

    Cohen, Evan N; Gao, Hui; Mego, Michal; Lee, Bang-Ning; Lodhi, Ashutosh; Cristofanilli, Massimo; Lucci, Anthony

    2011-01-01

    Purpose The bone marrow microenvironment is considered a critical component in the dissemination and fate of cancer cells in the metastatic process. We explored the possible correlation between bone marrow mesenchymal stem cells (BM-MSC) and disseminated breast cancer-initiating cells (BCIC) in primary breast cancer patients. Results The percentages of BCIC (Aldefluor+CD326+CD44+CD24−) correlated with the percentages of BM-MSC, either CD45−GD2+CD200+CD271+ (Kedall's τ = 0.684, p = 0.004) or CD45−GD2+CD271+ in the bone marrow (Kedall's τ = 0.464, p = 0.042). Experimental Design Bone marrow mononuclear cells (BM-MNC) were collected at the time of primary surgery in 12 breast cancer patients. BM-MNC was immunophenotyped and BCIC was defined as epithelial cells (CD326+CD45−) with a “stem-like” phenotype (CD44+CD24low/−, ALDH activity). BM-MSC was defined as CD34−CD45− cells that co-expressed GD2, CD271 and/or CD200 within CD326-depleted BM-MNC. Conclusions There was a positive correlation between mesenchymal stem cells expressing GD2 and CD271 and breast cancer-initiating cells in BM of patients with primary breast cancer. PMID:21358274

  15. Single Unpurified Breast Tumor-Initiating Cells from Multiple Mouse Models Efficiently Elicit Tumors in Immune-Competent Hosts

    PubMed Central

    Kurpios, Natasza A.; Girgis-Gabardo, Adele; Hallett, Robin M.; Rogers, Stephen; Gludish, David W.; Kockeritz, Lisa; Woodgett, James; Cardiff, Robert; Hassell, John A.

    2013-01-01

    The tumor-initiating cell (TIC) frequency of bulk tumor cell populations is one of the criteria used to distinguish malignancies that follow the cancer stem cell model from those that do not. However, tumor-initiating cell frequencies may be influenced by experimental conditions and the extent to which tumors have progressed, parameters that are not always addressed in studies of these cells. We employed limiting dilution cell transplantation of minimally manipulated tumor cells from mammary tumors of several transgenic mouse models to determine their tumor-initiating cell frequency. We determined whether the tumors that formed following tumor cell transplantation phenocopied the primary tumors from which they were isolated and whether they could be serially transplanted. Finally we investigated whether propagating primary tumor cells in different tissue culture conditions affected their resident tumor-initiating cell frequency. We found that tumor-initiating cells comprised between 15% and 50% of the bulk tumor cell population in multiple independent mammary tumors from three different transgenic mouse models of breast cancer. Culture of primary mammary tumor cells in chemically-defined, serum-free medium as non-adherent tumorspheres preserved TIC frequency to levels similar to that of the primary tumors from which they were established. By contrast, propagating the primary tumor cells in serum-containing medium as adherent populations resulted in a several thousand-fold reduction in their tumor-initiating cell fraction. Our findings suggest that experimental conditions, including the sensitivity of the transplantation assay, can dramatically affect estimates of tumor initiating cell frequency. Moreover, conditional on cell culture conditions, the tumor-initiating cell fraction of bulk mouse mammary tumor cell preparations can either be maintained at high or low frequency in vitro thus permitting comparative studies of tumorigenic and non-tumorigenic cancer cells

  16. Long life nickel electrodes for a nickel-hydrogen cell. I Initial performance

    NASA Technical Reports Server (NTRS)

    Lim, H. S.; Verzwyvelt, S. A.; Blaser, C.; Keener, K. M.

    1983-01-01

    In order to develop a long life nickel electrode for a Ni/H2 cell, an investigation was begun to study the effects of sinter structure and active material loading level on the long life performance of nickel electrodes. This paper is a report on the initial performance of these electrodes as a part of an accelerated life test program. Seven different types of nickel plaques were made which included three levels of both their mechanical strength and median pore size. These plaques were impregnated with three levels of active material loading. The resultant electrodes were tested by a 200-cycle stress test which was conducted in flooded electrolyte, and also for initial performance in a Ni/H2 boiler plate cell. An interesting and unexpected observation was that an increased initial utilization of the active material was due more to its complete discharge to the lower average oxidation state than its increased charge acceptance in the charged state.

  17. Radiation-resistant B-1 cells: A possible initiating cells of neoplastic transformation.

    PubMed

    Guimarães-Cunha, Caroline Ferreira; Alvares-Saraiva, Anuska Marcelino; de Souza Apostolico, Juliana; Popi, Ana Flavia

    2016-07-01

    The role of B-1 cells in the hyperproliferative hematologic disease has been described. Several reports bring evidences that B-1 cells are the main cell population in the chronic lymphatic leukemia. It is also described that these cells have an important involvement in the lupus erythematous systemic. The murine model used to investigate both disease models is NZB/NZW. Data from literature point that mutation in micro-RNA 15a and 16 are the responsible for the B-1 hyperplasia in these mice. Interestingly, it was demonstrated that NZB/NZW B-1 cells are radioresistant, contrariwise to observe in other mouse lineage derived B-1 cells and B-2 cells. However, some reports bring evidences that a small percentage of B-1 cells in healthy mice are also able to survive to irradiation. Herein, we aim to investigate the malignant potential of ionizing-radiation resistant B-1 cells in vitro. Our main goal is to establish a model that mimics the neoplastic transformation originate to a damage exposure of DNA, and not only related to intrinsic mutations. Data shown here demonstrated that radiation-resistant B-1 cells were able to survive long periods in culture. Further, these cells show proliferation index increase in relation to non-irradiated B-1 cells. In addition, radiation resistant B-1 cells showed hyperploid, morphologic alterations, increased induction of apoptosis after anti-IgM stimulation. Based on these results, we could suggest that radiation resistant B-1 cells showed some modifications in that could be related to induction of malignant potential. PMID:26898918

  18. The emerging roles of Oct4 in tumor-initiating cells.

    PubMed

    Wang, Ying-Jie; Herlyn, Meenhard

    2015-12-01

    Octamer-binding transcription factor 4 (Oct4), a homeodomain transcription factor, is well established as a master factor controlling the self-renewal and pluripotency of pluripotent stem cells. Also, a large body of research has documented the detection of Oct4 in tumor cells and tissues and has indicated its enrichment in a subpopulation of undifferentiated tumor-initiating cells (TICs) that critically account for tumor initiation, metastasis, and resistance to anticancer therapies. There is circumstantial evidence for low-level expression of Oct4 in cancer cells and TICs, and the participation of Oct4 in various TIC functions such as its self-renewal and survival, epithelial-mesenchymal transition (EMT) and metastasis, and drug resistance development is implicated from considerable Oct4 knockdown and overexpression-based studies. In a few studies, efforts have been made to identify Oct4 target genes in TICs of different sources. Based on such information, Oct4 in TICs appears to act via mechanisms quite distinct from those in pluripotent stem cells, and a main challenge for future studies is to unravel the molecular mechanisms of action of Oct4, particularly to address the question on how such low levels of Oct4 may exert its functions in TICs. Acquiring cells from their native microenvironment that are of high enough quantity and purity is the key to reliably analyze Oct4 functions and its target genes in TICs, and the information gained may greatly facilitate targeting and eradicating those cells. PMID:26447206

  19. Initiation of DNA Interstrand Cross-link Repair in Mammalian Cells

    PubMed Central

    Hlavin, Erica M.; Smeaton, Michael B.; Miller, Paul S.

    2010-01-01

    Interstrand cross-links (ICLs) are among the most cytotoxic DNA lesions to cells because they prevent the two DNA strands from separating, thereby precluding replication and transcription. Even though chemotherapeutic cross-linking agents are well established in clinical use, and numerous repair proteins have been implicated in the initial events of mammalian ICL repair, the precise mechanistic details of these events remain to be elucidated. This review will summarize our current understanding of how ICL repair is initiated with an emphasis on the context (replicating, transcribed or quiescent DNA) in which the ICL is recognized, and how the chemical and physical properties of ICLs influence repair. Although most studies have focused on replication-dependent repair because of the relation to highly replicative tumor cells, replication-independent ICL repair is likely to be important in the circumvention of cross-link cytotoxicity in non-dividing, terminally differentiated cells that may be challenged with exogenous or endogenous sources of ICLs. Consequently, the ICL repair pathway that should be considered ‘dominant’ appears to depend on the cell type and the DNA context in which the ICL is encountered. The ability to define and inhibit distinct pathways of ICL repair in different cell cycle phases may help in developing methods that increase cytotoxicity to cancer cells while reducing side-effects in non-dividing normal cells. This may also lead to a better understanding of pathways that protect against malignancy and aging. PMID:20658650

  20. The organoid-initiating cells in mouse pancreas and liver are phenotypically and functionally similar

    PubMed Central

    Dorrell, Craig; Tarlow, Branden; Wang, Yuhan; Canaday, Pamela S; Haft, Annelise; Schug, Jonathan; Streeter, Philip R; Finegold, Milton J; Shenje, Lincoln T; Kaestner, Klaus H; Grompe, Markus

    2014-01-01

    Pancreatic Lgr5 expression has been associated with organoid-forming epithelial progenitor populations but the identity of the organoid-initiating epithelial cell subpopulation has remained elusive. Injury causes the emergence of an Lgr5+ organoid-forming epithelial progenitor population in the adult mouse liver and pancreas. Here, we define the origin of organoid-initiating cells from mouse pancreas and liver prior to Lgr5 activation. This clonogenic population was defined as MIC1-1C3+/CD133+/CD26− in both tissues and the frequency of organoid initiation within this population was approximately 5% in each case. The transcriptomes of these populations overlapped extensively and showed enrichment of epithelial progenitor-associated regulatory genes such as Sox9 and FoxJ1. Surprisingly, pancreatic organoid cells also had the capacity to generate hepatocyte-like cells upon transplantation to Fah-/- mice, indicating a differentiation capacity similar to hepatic organoids. Although spontaneous endocrine differentiation of pancreatic progenitors was not observed in culture, adenoviral delivery of fate-specifying factors Pdx1, Neurog3 and MafA induced insulin expression without glucagon or somatostatin. Pancreatic organoid cultures therefore preserve many key attributes of progenitor cells while allowing unlimited expansion, facilitating the study of fate determination. PMID:25151611

  1. The organoid-initiating cells in mouse pancreas and liver are phenotypically and functionally similar.

    PubMed

    Dorrell, Craig; Tarlow, Branden; Wang, Yuhan; Canaday, Pamela S; Haft, Annelise; Schug, Jonathan; Streeter, Philip R; Finegold, Milton J; Shenje, Lincoln T; Kaestner, Klaus H; Grompe, Markus

    2014-09-01

    Pancreatic Lgr5 expression has been associated with organoid-forming epithelial progenitor populations but the identity of the organoid-initiating epithelial cell subpopulation has remained elusive. Injury causes the emergence of an Lgr5(+) organoid-forming epithelial progenitor population in the adult mouse liver and pancreas. Here, we define the origin of organoid-initiating cells from mouse pancreas and liver prior to Lgr5 activation. This clonogenic population was defined as MIC1-1C3(+)/CD133(+)/CD26(-) in both tissues and the frequency of organoid initiation within this population was approximately 5% in each case. The transcriptomes of these populations overlapped extensively and showed enrichment of epithelial progenitor-associated regulatory genes such as Sox9 and FoxJ1. Surprisingly, pancreatic organoid cells also had the capacity to generate hepatocyte-like cells upon transplantation to Fah(-/-) mice, indicating a differentiation capacity similar to hepatic organoids. Although spontaneous endocrine differentiation of pancreatic progenitors was not observed in culture, adenoviral delivery of fate-specifying factors Pdx1, Neurog3 and MafA induced insulin expression without glucagon or somatostatin. Pancreatic organoid cultures therefore preserve many key attributes of progenitor cells while allowing unlimited expansion, facilitating the study of fate determination. PMID:25151611

  2. Decitabine Treatment of Glioma-Initiating Cells Enhances Immune Recognition and Killing.

    PubMed

    Riccadonna, Cristina; Yacoub Maroun, Céline; Vuillefroy de Silly, Romain; Boehler, Margaux; Calvo Tardón, Marta; Jueliger, Simone; Taverna, Pietro; Barba, Leticia; Marinari, Eliana; Pellegatta, Serena; Bassoy, Esen Yonca; Martinvalet, Denis; Dietrich, Pierre-Yves; Walker, Paul R

    2016-01-01

    Malignant gliomas are aggressive brain tumours with very poor prognosis. The majority of glioma cells are differentiated (glioma-differentiated cells: GDCs), whereas the smaller population (glioma-initiating cells, GICs) is undifferentiated and resistant to conventional therapies. Therefore, to better target this pool of heterogeneous cells, a combination of diverse therapeutic approaches is envisaged. Here we investigated whether the immunosensitising properties of the hypomethylating agent decitabine can be extended to GICs. Using the murine GL261 cell line, we demonstrate that decitabine augments the expression of the death receptor FAS both on GDCs and GICs. Interestingly, it had a higher impact on GICs and correlated with an enhanced sensitivity to FASL-mediated cell death. Moreover, the expression of other critical molecules involved in cognate recognition by cytotoxic T lymphocytes, MHCI and ICAM-1, was upregulated by decitabine treatment. Consequently, T-cell mediated killing of both GDCs and GICs was enhanced, as was T cell proliferation after reactivation. Overall, although GICs are described to resist classical therapies, our study shows that hypomethylating agents have the potential to enhance glioma cell recognition and subsequent destruction by immune cells, regardless of their differentiation status. These results support the development of combinatorial treatment modalities including epigenetic modulation together with immunotherapy in order to treat heterogenous malignancies such as glioblastoma. PMID:27579489

  3. Thyroid tumor-initiating cells: Increasing evidence and opportunities for anticancer therapy (Review)

    PubMed Central

    GAO, YONG-JU; LI, BO; WU, XIN-YU; CUI, JING; HAN, JIAN-KUI

    2014-01-01

    Accumulating evidence supports the notion that thyroid cancer is initiated by tumor-initiating cells (TICs) (commonly known as cancer stem cells), which are thought to play a crucial role in malignant progression, therapeutic resistance and recurrence. Thyroid TICs have been isolated and identified using specific biomarkers (such as CD133), the side population, sphere formation and aldehyde dehydrogenase activity assays. Although their characteristics remain largely unknown, TICs provide an attractive cellular mechanism to explain therapeutic refractoriness. Efforts are currently being directed toward the identification of therapeutic strategies that could target these cells. The present review discusses the cellular origins of TICs and the main approaches used to isolate and identify thyroid TICs, with a focus on the remaining challenges and opportunities for anticancer therapy. PMID:24424445

  4. Inhibition of replicon initiation in human cells following stabilization of topoisomerase-DNA cleavable complexes.

    PubMed Central

    Kaufmann, W K; Boyer, J C; Estabrooks, L L; Wilson, S J

    1991-01-01

    Diploid human fibroblast strains were treated for 10 min with inhibitors of type I and type II DNA topoisomerases, and after removal of the inhibitors, the rate of initiation of DNA synthesis at replicon origins was determined. By alkaline elution chromatography, 4'-(9-acridinylamino)methanesulfon-m-anisidide (amsacrine), an inhibitor of DNA topoisomerase II, was shown to produce DNA strand breaks. These strand breaks are thought to reflect drug-induced stabilization of topoisomerase-DNA cleavable complexes. Removal of the drug led to a rapid resealing of the strand breaks by dissociation of the complexes. Velocity sedimentation analysis was used to quantify the effects of amsacrine treatment on DNA replication. It was demonstrated that transient exposure to low concentrations of amsacrine inhibited replicon initiation but did not substantially affect DNA chainelongation within operating replicons. Maximal inhibition of replicon initiation occurred 20 to 30 min after drug treatment, and the initiation rate recovered 30 to 90 min later. Ataxia telangiectasia cells displayed normal levels of amsacrine-induced DNA strand breaks during stabilization of cleavable complexes but failed to downregulate replicon initiation after exposure to the topoisomerase inhibitor. Thus, inhibition of replicon initiation in response to DNA damage appears to be an active process which requires a gene product which is defective or missing in ataxia telangiectasia cells. In normal human fibroblasts, the inhibition of DNA topoisomerase I by camptothecin produced reversible DNA strand breaks. Transient exposure to this drug also inhibited replicon initiation. These results suggest that the cellular response pathway which downregulates replicon initiation following genotoxic damage may respond to perturbations of chromatin structure which accompany stabilization of topoisomerase-DNA cleavable complexes. PMID:1646393

  5. Orion Spacecraft MMOD Protection Design and Assessment

    NASA Technical Reports Server (NTRS)

    Bohl, W.; Miller, J.; Deighton, K.; Yasensky, J.; Foreman C.; Christiansen, Eric; Hyde, J.; Nahra, H.

    2010-01-01

    The Orion spacecraft will replace the Space Shuttle Orbiter for American and international partner access to the International Space Station by 2015 and, afterwards, for access to the moon for initial sorties and later for extended outpost visits as part of the Constellation Exploration Initiative. This work describes some of the efforts being undertaken to ensure that the Constellation Program, Orion Crew Exploration Vehicle design will meet or exceed the stringent micrometeoroid and orbital debris (MMOD) requirements set out by NASA when exposed to the environments encountered with these missions. This paper will provide a brief overview of the approaches being used to provide MMOD protection to the Orion vehicle and to assess the spacecraft for compliance to the Constellation Program s MMOD requirements.

  6. Orion Spacecraft MMOD Protection Design and Assessment

    NASA Technical Reports Server (NTRS)

    Bohl, William; Miller, Joshua; Deighton, Kevin; Foreman, Cory; Yasensky, John; Christiansen, Eric; Hyde, James; Nahra, Henry

    2009-01-01

    The Orion spacecraft will replace the Space Shuttle Orbiter for American and international partner access to the International Space Station by 2015 and, afterwards, for access to the moon for initial sorties and later for extend outpost visits as part of the Constellation Exploration Initiative. This work describes some of the efforts being undertaken to ensure that Orion design will meet or exceed the stringent MicroMeteoroid and Orbital Debris (MMOD) requirements set out by NASA when exposed to the environments encountered with these missions. This paper will provide a brief overview of the approaches being used to provide MMOD protection to the Orion vehicle and to assess the spacecraft for compliance to the Constellation Program s MMOD requirements.

  7. Spacecraft Electrostatic Radiation Shielding

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This project analyzed the feasibility of placing an electrostatic field around a spacecraft to provide a shield against radiation. The concept was originally proposed in the 1960s and tested on a spacecraft by the Soviet Union in the 1970s. Such tests and analyses showed that this concept is not only feasible but operational. The problem though is that most of this work was aimed at protection from 10- to 100-MeV radiation. We now appreciate that the real problem is 1- to 2-GeV radiation. So, the question is one of scaling, in both energy and size. Can electrostatic shielding be made to work at these high energy levels and can it protect an entire vehicle? After significant analysis and consideration, an electrostatic shield configuration was proposed. The selected architecture was a torus, charged to a high negative voltage, surrounding the vehicle, and a set of positively charged spheres. Van de Graaff generators were proposed as the mechanism to move charge from the vehicle to the torus to generate the fields necessary to protect the spacecraft. This design minimized complexity, residual charge, and structural forces and resolved several concerns raised during the internal critical review. But, it still is not clear if such a system is costeffective or feasible, even though several studies have indicated usefulness for radiation protection at energies lower than that of the galactic cosmic rays. Constructing such a system will require power supplies that can generate voltages 10 times that of the state of the art. Of more concern is the difficulty of maintaining the proper net charge on the entire structure and ensuring that its interaction with solar wind will not cause rapid discharge. Yet, if these concerns can be resolved, such a scheme may provide significant radiation shielding to future vehicles, without the excessive weight or complexity of other active shielding techniques.

  8. Differential spacecraft charging on the geostationary operational environmental satellites

    NASA Technical Reports Server (NTRS)

    Farthing, W. H.; Brown, J. P.; Bryant, W. C.

    1982-01-01

    Subsystems aboard the Geostationary Operational Environmental Satellites 4 and 5 showed instances of anomalous changes in state corresponding to false commands. Evidence linking the anomalous changes to geomagnetic activity, and presumably static discharges generated by spacecraft differential charging induced by substorm particle injection events is presented. The anomalies are shown to be correlated with individual substorms as monitored by stations of the North American Magnetometer Chain. The relative frequency of the anomalies is shown to be a function of geomagnetic activity. Finally a least squares fit to the time delay between substorm initiation and spacecraft anomaly as a function of spacecraft local time is shown to be consistent with injected electron populations with energy in the range 10 keV to 15 keV, in agreement with present understanding of the spacecraft charging mechanism. The spacecraft elements responsible for the differential charging were not satisfactorily identified. That question is currently under investigation.

  9. Spacecraft ceramic protective shield

    NASA Technical Reports Server (NTRS)

    Larriva, Rene F. (Inventor); Nelson, Anne (M.); Czechanski, James G. (Inventor); Poff, Ray E. (Inventor)

    1995-01-01

    A low areal density protective shield apparatus, and method for making same, for protecting spacecraft structures from impact with hypervelocity objects, including a bumper member comprising a bumper ceramic layer, a bumper shock attenuator layer, and a bumper confining layer. The bumper ceramic layer can be SiC or B.sub.4 C; the bumper shock attenuator layer can be zirconia felt; and the bumper confining layer can be aluminum. A base armor member can be spaced from the bumper member and a ceramic fiber-based curtain can be positioned between the bumper and base armor members.

  10. Xenia Spacecraft Study

    NASA Technical Reports Server (NTRS)

    Hopkins, Randy

    2009-01-01

    This slide presentation reviews the proposed design for the Xenia mission spacecraft. The goal of this study is to perform a mission concept study for the mission. Included in this study are: the overall ground rules and assumptions (GR&A), a mission analysis, the configuration, the mass properties, the guidance, Navigation and control, the proposed avionics, the power system, the thermal protection system, the propulsion system, and the proposed structures. Conclusions from the study indicate that the observatory fits within the Falcon 9 mass and volume envelope for launching from Omelek, the pointing, slow slewing, and fast slewing requirements and the thermal requirements are met.

  11. Gimballing Spacecraft Thruster

    NASA Technical Reports Server (NTRS)

    Pickens, Tim; Bossard, John

    2010-01-01

    A gimballing spacecraft reaction-control-system thruster was developed that consists of a small hydrogen/oxygen-burning rocket engine integrated with a Canfield joint. (Named after its inventor, a Canfield joint is a special gimbal mount that is strong and stable yet allows a wide range of motion.) One especially notable aspect of the design of this thruster is integration, into both the stationary legs and the moving arms of the Canfield joint, of the passages through which the hydrogen and oxygen flow to the engine. The thruster was assembled and subjected to tests in which the engine was successfully fired both with and without motion in the Canfield joint.

  12. Toward autonomous spacecraft

    NASA Technical Reports Server (NTRS)

    Fogel, L. J.; Calabrese, P. G.; Walsh, M. J.; Owens, A. J.

    1982-01-01

    Ways in which autonomous behavior of spacecraft can be extended to treat situations wherein a closed loop control by a human may not be appropriate or even possible are explored. Predictive models that minimize mean least squared error and arbitrary cost functions are discussed. A methodology for extracting cyclic components for an arbitrary environment with respect to usual and arbitrary criteria is developed. An approach to prediction and control based on evolutionary programming is outlined. A computer program capable of predicting time series is presented. A design of a control system for a robotic dense with partially unknown physical properties is presented.

  13. Furlable spacecraft antenna development

    NASA Technical Reports Server (NTRS)

    Oliver, R. E.; Wilson, A. H.

    1972-01-01

    The development of large furlable spacecraft antennas using conical main reflectors is described. Two basic antenna configurations which utilize conical main reflectors have been conceived and are under development. In the conical-Gregorian configuration each ray experiences two reflections in traveling from the feed center to the aperture plane. In the Quadreflex (four reflection) configuration, each ray experiences four reflections, one at each of two subreflector surfaces and two at the main conical reflector surface. The RF gain measurements obtained from 6-ft and 30-in. models of the conical-Gregorian and Quadreflex concepts respectively were sufficiently encouraging to warrant further development of the concepts.

  14. Analysis of spacecraft anomalies

    NASA Technical Reports Server (NTRS)

    Bloomquist, C. E.; Graham, W. C.

    1976-01-01

    The anomalies from 316 spacecraft covering the entire U.S. space program were analyzed to determine if there were any experimental or technological programs which could be implemented to remove the anomalies from future space activity. Thirty specific categories of anomalies were found to cover nearly 85 percent of all observed anomalies. Thirteen experiments were defined to deal with 17 of these categories; nine additional experiments were identified to deal with other classes of observed and anticipated anomalies. Preliminary analyses indicate that all 22 experimental programs are both technically feasible and economically viable.

  15. Cluster Inter-Spacecraft Communications

    NASA Technical Reports Server (NTRS)

    Cox, Brian

    2008-01-01

    A document describes a radio communication system being developed for exchanging data and sharing data-processing capabilities among spacecraft flying in formation. The system would establish a high-speed, low-latency, deterministic loop communication path connecting all the spacecraft in a cluster. The system would be a wireless version of a ring bus that complies with the Institute of Electrical and Electronics Engineers (IEEE) standard 1393 (which pertains to a spaceborne fiber-optic data bus enhancement to the IEEE standard developed at NASA's Jet Propulsion Laboratory). Every spacecraft in the cluster would be equipped with a ring-bus radio transceiver. The identity of a spacecraft would be established upon connection into the ring bus, and the spacecraft could be at any location in the ring communication sequence. In the event of failure of a spacecraft, the ring bus would reconfigure itself, bypassing a failed spacecraft. Similarly, the ring bus would reconfigure itself to accommodate a spacecraft newly added to the cluster or newly enabled or re-enabled. Thus, the ring bus would be scalable and robust. Reliability could be increased by launching, into the cluster, spare spacecraft to be activated in the event of failure of other spacecraft.

  16. IMP-I spacecraft final magnetic tests

    NASA Technical Reports Server (NTRS)

    Harris, C. A.

    1972-01-01

    The increased IMP-I spacecraft spin axis moment resulting from excessive field exposures during environmental testing substantiated the need for a final pre-launch magnetic deperm and measurement. By performing a dc rotation deperm it was possible to reduce this moment below the previous initial test post deperm magnitude. In addition, the magnetic field disturbance at the flight magnetometer diminished to below 0.1 nanotesla (gamma) in all directions.

  17. Actinomyces naeslundii GroEL-dependent initial attachment and biofilm formation in a flow cell system.

    PubMed

    Arai, Toshiaki; Ochiai, Kuniyasu; Senpuku, Hidenobu

    2015-02-01

    Actinomyces naeslundii is an early colonizer with important roles in the development of the oral biofilm. The effects of butyric acid, one of short chain fatty acids in A. naeslundii biofilm formation was observed using a flow cell system with Tryptic soy broth without dextrose and with 0.25% sucrose (TSB sucrose). Significant biofilms were established involving live and dead cells in TSB sucrose with 60mM butyric acid but not in concentrations of 6, 30, 40, and 50mM. Biofilm formation failed in 60mM sodium butyrate but biofilm level in 60mM sodium butyrate (pH4.7) adjusted with hydrochloric acid as 60mM butyric media (pH4.7) was similar to biofilm levels in 60mM butyric acid. Therefore, butyric acid and low pH are required for significant biofilm formation in the flow cell. To determine the mechanism of biofilm formation, we investigated initial A. naeslundii colonization in various conditions and effects of anti-GroEL antibody. The initial colonization was observed in the 60mM butyric acid condition and anti-GroEL antibody inhibited the initial colonization. In conclusion, we established a new biofilm formation model in which butyric acid induces GroEL-dependent initial colonization of A. naeslundii resulting in significant biofilm formation in a flow system. PMID:25555820

  18. Oncolytic herpes simplex virus kills stem-like tumor-initiating colon cancer cells

    PubMed Central

    Warner, Susanne G; Haddad, Dana; Au, Joyce; Carson, Joshua S; O’Leary, Michael P; Lewis, Christina; Monette, Sebastien; Fong, Yuman

    2016-01-01

    Stem-like tumor-initiating cells (TICs) are implicated in cancer progression and recurrence, and can be identified by sphere-formation and tumorigenicity assays. Oncolytic viruses infect, replicate in, and kill a variety of cancer cells. In this study, we seek proof of principle that TICs are susceptible to viral infection. HCT8 human colon cancer cells were subjected to serum-free culture to generate TIC tumorspheres. Parent cells and TICs were infected with HSV-1 subtype NV1066. Cytotoxicity, viral replication, and Akt1 expression were assessed. TIC tumorigenicity was confirmed and NV1066 efficacy was assessed in vivo. NV1066 infection was highly cytotoxic to both parent HCT8 cells and TICs. In both populations, cell-kill of >80% was achieved within 3 days of infection at a multiplicity of infection (MOI) of 1.0. However, the parent cells required 2-log greater viral replication to achieve the same cytotoxicity. TICs overexpressed Akt1 in vitro and formed flank tumors from as little as 100 cells, growing earlier, faster, larger, and with greater histologic atypia than tumors from parent cells. Treatment of TIC-induced tumors with NV1066 yielded tumor regression and slowed tumor growth. We conclude that colon TICs are selected for by serum-free culture, overexpress Akt1, and are susceptible to oncolytic viral infection. PMID:27347556

  19. The Role of Surface Receptor Density in Surface-Initiated Polymerizations for Cancer Cell Isolation.

    PubMed

    Lilly, Jacob L; Berron, Brad J

    2016-06-01

    Fluid biopsies potentially offer a minimally invasive alternative to traditional tissue biopsies for the continual monitoring of metastatic cancer. Current established technologies for isolating circulating tumor cells (CTCs) suffer from poor purity and yield and require fixatives that preclude the collection of viable cells for longitudinal analyses of biological function. Antigen specific lysis (ASL) is a rapid, high-purity method of cell isolation based on targeted protective coatings on antigen-presenting cells and lysis depletion of unprotected antigen-negative cells. In ASL, photoinitiators are specifically labeled on cell surfaces that enable subsequent surface-initiated polymerization. Critically, the significant determinants of process yield have yet to be investigated for this emerging technology. In this work, we show that the labeling density of photoinitiators is strongly correlated with the yield of intact cells during ASL by flow cytometry analysis. Results suggest ASL is capable of delivering ∼25% of targeted cells after isolation using traditional antibody labeling approaches. Monomer formulations of two molecular weights of PEG-diacrylate (Mn ∼ 575 and 3500) are examined. The gelation response during ASL polymerization is also investigated via protein microarray analogues on planar glass. Finally, a density threshold of photoinitiator labeling required for protection during lysis is determined for both monomer formulations. These results indicate ASL is a promising technology for high yield CTC isolation for rare-cell function assays and fluid biopsies. PMID:27206735

  20. Oncolytic herpes simplex virus kills stem-like tumor-initiating colon cancer cells.

    PubMed

    Warner, Susanne G; Haddad, Dana; Au, Joyce; Carson, Joshua S; O'Leary, Michael P; Lewis, Christina; Monette, Sebastien; Fong, Yuman

    2016-01-01

    Stem-like tumor-initiating cells (TICs) are implicated in cancer progression and recurrence, and can be identified by sphere-formation and tumorigenicity assays. Oncolytic viruses infect, replicate in, and kill a variety of cancer cells. In this study, we seek proof of principle that TICs are susceptible to viral infection. HCT8 human colon cancer cells were subjected to serum-free culture to generate TIC tumorspheres. Parent cells and TICs were infected with HSV-1 subtype NV1066. Cytotoxicity, viral replication, and Akt1 expression were assessed. TIC tumorigenicity was confirmed and NV1066 efficacy was assessed in vivo. NV1066 infection was highly cytotoxic to both parent HCT8 cells and TICs. In both populations, cell-kill of >80% was achieved within 3 days of infection at a multiplicity of infection (MOI) of 1.0. However, the parent cells required 2-log greater viral replication to achieve the same cytotoxicity. TICs overexpressed Akt1 in vitro and formed flank tumors from as little as 100 cells, growing earlier, faster, larger, and with greater histologic atypia than tumors from parent cells. Treatment of TIC-induced tumors with NV1066 yielded tumor regression and slowed tumor growth. We conclude that colon TICs are selected for by serum-free culture, overexpress Akt1, and are susceptible to oncolytic viral infection. PMID:27347556

  1. Cryptotanshinone targets tumor-initiating cells through down-regulation of stemness genes expression

    PubMed Central

    ZHANG, YING; CABARCAS, STEPHANIE M.; ZHENG, JI; SUN, LEI; MATHEWS, LESLEY A.; ZHANG, XIAOHU; LIN, HONGSHENG; FARRAR, WILLIAM L.

    2016-01-01

    Recent evidence indicates that tumor-initiating cells (TICs), also called cancer stem cells (CSCs), are responsible for tumor initiation and progression, therefore representing an important cell population that may be used as a target for the development of future anticancer therapies. In the present study, Cryptotanshinone (CT), a traditional Chinese herbal medicine, was demonstrated to regulate the behaviors of LNCaP prostate cells and prostate LNCaP TICs. The results demonstrate that treatment with CT alters cellular proliferation, cell cycle status, migration, viability, colony formation and notably, sphere formation and down-regulation of stemness genes (Nanog, OCT4, SOX2, β-catenin, CXCR4) in TICs. The present study demonstrates that CT targets the LNCaP CD44+CD24- population that is representative of prostate TICs and also affects total LNCaP cells as well via down-regulation of stemness genes. The strong effect with which CT has on prostate TICs suggests that CT may potentially function as a novel natural anticancer agent that specifically targets TICs. PMID:27313698

  2. The neurite-initiating effect of microbial extracellular glycolipids in PC12 cells.

    PubMed

    Isoda, H; Shinmoto, H; Matsumura, M; Nakahara, T

    1999-09-01

    The effects of several kinds of microbial extracellular glycolipids on neurite initiation in PC12 cells were examined. Addition of mannosylerythritol lipid-A (MEL-A), MEL-B, and sophorose lipid (SL) to PC12 cells caused significant neurite outgrowth. Other glycolipids, such as polyol lipid (PL), rhamnose lipid (RL), succinoyl trehalose lipid-A (STL-A) and STL-B caused no neurite-initiation. MEL-A increased acetylcholine esterase (AChE) activity to an extent similar to nerve growth factor (NGF). However, MEL-A induced one or two long neurites from the cell body, while NGF induced many neurites. In addition, MEL-A-induced differentiation was transient, and after 48 h, percentage of cells with neurites started to decrease in contrast to neurons induced by NGF, which occurred in a time-dependent manner. MEL-A could induce neurite outgrowth after treatment of PC12 cells with an anti-NGF receptor antibody that obstructed NGF action. These results indicate that MEL-A and NGF induce differentiation of PC12 cells through different mechanisms. PMID:19003137

  3. Regulation of leukemia-initiating cell activity by the ubiquitin ligase FBXW7

    PubMed Central

    King, Bryan; Trimarchi, Thomas; Reavie, Linsey; Xu, Luyao; Mullenders, Jasper; Ntziachristos, Panagiotis; Aranda-Orgilles, Beatriz; Perez-Garcia, Arianne; Shi, Junwei; Vakoc, Christopher; Sandy, Peter; Shen, Steven S.; Ferrando, Adolfo; Aifantis, Iannis

    2013-01-01

    SUMMARY Sequencing efforts led to the identification of somatic mutations that could affect self-renewal and differentiation of cancer-initiating cells. One such recurrent mutation targets the binding pocket of the ubiquitin ligase FBXW7. Missense FBXW7 mutations are prevalent in various tumors, including T-cell acute lymphoblastic leukemia (T-ALL). To study the effects of such lesions, we generated animals carrying regulatable Fbxw7 mutant alleles. We show here that these mutations specifically bolster cancer-initiating cell activity in collaboration with Notch1 oncogenes, but spare normal hematopoietic stem cell function. We were also able to show that FBXW7 mutations specifically affect the ubiquitylation and half-life of c-Myc protein, a key T-ALL oncogene. Using animals carrying c-Myc fusion alleles, we connected Fbxw7 function to c-Myc abundance and correlated c-Myc expression to leukemia-initiating activity. Finally, we demonstrated that small molecule-mediated suppression of MYC activity leads to T-ALL remission, suggesting a novel effective therapeutic strategy. PMID:23791182

  4. Electromagnetic propulsion for spacecraft

    NASA Astrophysics Data System (ADS)

    Myers, Roger M.

    1993-09-01

    Three electromagnetic propulsion technologies, solid propellant pulsed plasma thrusters (PPT), magnetoplasmadynamic (MPD) thrusters, and pulsed inductive thrusters (PIT), were developed for application to auxiliary and primary spacecraft propulsion. Both the PPT and MPD thrusters were flown in space, though only PPT's were used on operational satellites. The performance of operational PPT's is quite poor, providing only approximately 8 percent efficiency at approximately 1000 s specific impulse. However, laboratory PPT's yielding 34 percent efficiency at 2000 s specific impulse were extensively tested, and peak performance levels of 53 percent efficiency at 5170 s specific impulse were demonstrated. MPD thrusters were flown as experiments on the Japanese MS-T4 spacecraft and the Space Shuttle and were qualified for a flight in 1994. The flight MPD thrusters were pulsed, with a peak performance of 22 percent efficiency at 2500 s specific impulse using ammonia propellant. Laboratory MPD thrusters were demonstrated with up to 70 percent efficiency and 700 s specific impulse using lithium propellant. While the PIT thruster has never been flown, recent performance measurements using ammonia and hydrazine propellants are extremely encouraging, reaching 50 percent efficiency for specific impulses between 4000 to 8000 s. The fundamental operating principles, performance measurements, and system level design for the three types of electromagnetic thrusters are reviewed, and available data on flight tests are discussed for the PPT and MPD thrusters.

  5. Electromagnetic propulsion for spacecraft

    NASA Technical Reports Server (NTRS)

    Myers, Roger M.

    1993-01-01

    Three electromagnetic propulsion technologies, solid propellant pulsed plasma thrusters (PPT), magnetoplasmadynamic (MPD) thrusters, and pulsed inductive thrusters (PIT), were developed for application to auxiliary and primary spacecraft propulsion. Both the PPT and MPD thrusters were flown in space, though only PPT's were used on operational satellites. The performance of operational PPT's is quite poor, providing only approximately 8 percent efficiency at approximately 1000 s specific impulse. However, laboratory PPT's yielding 34 percent efficiency at 2000 s specific impulse were extensively tested, and peak performance levels of 53 percent efficiency at 5170 s specific impulse were demonstrated. MPD thrusters were flown as experiments on the Japanese MS-T4 spacecraft and the Space Shuttle and were qualified for a flight in 1994. The flight MPD thrusters were pulsed, with a peak performance of 22 percent efficiency at 2500 s specific impulse using ammonia propellant. Laboratory MPD thrusters were demonstrated with up to 70 percent efficiency and 700 s specific impulse using lithium propellant. While the PIT thruster has never been flown, recent performance measurements using ammonia and hydrazine propellants are extremely encouraging, reaching 50 percent efficiency for specific impulses between 4000 to 8000 s. The fundamental operating principles, performance measurements, and system level design for the three types of electromagnetic thrusters are reviewed, and available data on flight tests are discussed for the PPT and MPD thrusters.

  6. Spacecraft Compartment Venting

    NASA Technical Reports Server (NTRS)

    Scialdone, John J.

    1998-01-01

    At various time concerns have been expressed that rapid decompressions of compartments of gas pockets and thermal blankets during spacecraft launches may have caused pressure differentials across their walls sufficient to cause minor structural failures, separations of adhesively-joined parts, ballooning, and flapping of blankets. This paper presents a close form equation expressing the expected pressure differentials across the walls of a compartment as a function of the external to the volume pressure drops, the pressure at which the rates occur and the vent capability of the compartment. The pressure profiles measured inside the shrouds of several spacecraft propelled by several vehicles and some profiles obtained from ground vacuum systems have been included. The equation can be used to design the appropriate vent, which will preclude excessive pressure differentials. Precautions and needed approaches for the evaluations of the expected pressures have been indicated. Methods to make a rapid assessment of the response of the compartment to rapid external pressure drops have been discussed. These are based on the evaluation of the compartment vent flow conductance, the volume and the length of time during which the rapid pressure drop occurs.

  7. NASA's spacecraft data system

    NASA Technical Reports Server (NTRS)

    Cudmore, Alan; Flanegan, Mark

    1993-01-01

    The NASA Small Explorer Data System (SEDS), a space flight data system developed to support the Small Explorer (SMEX) project, is addressed. The system was flown on the Solar Anomalous Magnetospheric Particle Explorer (SAMPEX) SMEX mission, and with reconfiguration for different requirements will fly on the X-ray Timing Explorer (XTE) and the Tropical Rainfall Measuring Mission (TRMM). SEDS is also foreseen for the Hubble repair mission. Its name was changed to Spacecraft Data System (SDS) in view of expansions. Objectives, SDS hardware, and software are described. Each SDS box contains two computers, data storage memory, uplink (command) reception circuitry, downlink (telemetry) encoding circuitry, Instrument Telemetry Controller (ITC), and spacecraft timing circuitry. The SDS communicates with other subsystems over the MIL-STD-1773 data bus. The SDS software uses a real time Operating System (OS) and the C language. The OS layer, communications and scheduling layer, application task layer, and diagnostic software, are described. Decisions on the use of advanced technologies, such as ASIC's (Application Specific Integrated Circuits) and fiber optics, led to technical improvements, such as lower power and weight, without increasing the risk associated with the data system. The result was a successful SAMPEX development, integration and test, and mission using SEDS, and the upgrading of that system to SDS for TRMM and XTE.

  8. Mechanistic aspects of initiation and promotion in C3H/10T1/2 cells.

    PubMed

    Boreiko, C J

    1985-01-01

    The transformation of C3H/10T1/2 cells can be made to proceed through discrete stages of initiation and promotion. Studies of the effect of cell density upon focus formation in cultures treated with MNNG and TPA suggest that initiation by MNNG is due to a relatively infrequent, irreversible event induced by a single carcinogen treatment. In contrast, promotion appears to be a reversible process requiring multiple treatments with TPA over a protracted period of time. Some evidence suggests that promotion may entail the induction of phenotypic changes which impart a growth advantage to phenotypically unstable "initiated" cell populations. The actual cellular mechanism(s) for most of the phenomena observed in C3H/10T1/2 cultures have eluded precise definition and widely divergent hypotheses have been advanced to explain transformation, initiation, and promotion. Conceivably there are multiple mechanisms responsible for each of these phenomenon. Some agents may transform by a multistage mechanism whereas others may exert their effects in a more direct fashion. Some of the foci produced by promotion may be the result of simple selective processes, others the product of more complex inductive events. Variations would thus be expected between laboratories working with different protocols and agents. As demonstrated by the possible involvement of an MCA residue in transformation, it is also apparent that fundamental technical aspects of this conceptually simple cell transformation system are poorly understood. While it is natural to develop mechanistic models based on quantitative observations of transformation, a limited understanding of the basic cell culture variables which modulate both the induction and expression of transformation dictate that caution be exercised in extrapolating the significance of such models to in vivo carcinogenesis. PMID:4053071

  9. Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation

    SciTech Connect

    Meeran, Syed M.; Katiyar, Suchitra; Katiyar, Santosh K.

    2008-05-15

    Phytochemicals show promise as potential chemopreventive or chemotherapeutic agents against various cancers. Here we report the chemotherapeutic effects of berberine, a phytochemical, on human prostate cancer cells. The treatment of human prostate cancer cells (PC-3) with berberine induced dose-dependent apoptosis but this effect of berberine was not seen in non-neoplastic human prostate epithelial cells (PWR-1E). Berberine-induced apoptosis was associated with the disruption of the mitochondrial membrane potential, release of apoptogenic molecules (cytochrome c and Smac/DIABLO) from mitochondria and cleavage of caspase-9,-3 and PARP proteins. This effect of berberine on prostate cancer cells was initiated by the generation of reactive oxygen species (ROS) irrespective of their androgen responsiveness, and the generation of ROS was through the increased induction of xanthine oxidase. Treatment of cells with allopurinol, an inhibitor of xanthine oxidase, inhibited berberine-induced oxidative stress in cancer cells. Berberine-induced apoptosis was blocked in the presence of antioxidant, N-acetylcysteine, through the prevention of disruption of mitochondrial membrane potential and subsequently release of cytochrome c and Smac/DIABLO. In conclusion, the present study reveals that the berberine-mediated cell death of human prostate cancer cells is regulated by reactive oxygen species, and therefore suggests that berberine may be considered for further studies as a promising therapeutic candidate for prostate cancer.

  10. Oncolytic adenoviruses kill breast cancer initiating CD44+CD24-/low cells.

    PubMed

    Eriksson, Minna; Guse, Kilian; Bauerschmitz, Gerd; Virkkunen, Pekka; Tarkkanen, Maija; Tanner, Minna; Hakkarainen, Tanja; Kanerva, Anna; Desmond, Renee A; Pesonen, Sari; Hemminki, Akseli

    2007-12-01

    Cancer stem cells have been indicated in the initiation of tumors and are even found to be responsible for relapses after apparently curative therapies have been undertaken. In breast cancer, they may reside in the CD44(+)CD24(-/low) population. The use of oncolytic adenoviruses presents an attractive anti-tumor approach for eradication of these cells because their entry occurs through infection and they are, therefore, not susceptible to those mechanisms that commonly render stem cells resistant to many drugs. We isolated CD44(+)CD24(-/low) cells from patient pleural effusions and confirmed stem cell-like features including oct4 and sox2 expression and Hoechst 33342 exclusion. CD44(+)CD24(-/low) cells, including the Hoechst excluding subpopulation, could be effectively killed by oncolytic adenoviruses Ad5/3-Delta24 and Ad5.pk7-Delta24. In mice, CD44(+)CD24(-/low) cells formed orthotopic breast tumors but virus infection prevented tumor formation. Ad5/3-Delta24 and Ad5.pk7-Delta24 were effective against advanced orthotopic CD44(+)CD24(-/low)-derived tumors. In summary, Ad5/3-Delta24 and Ad5.pk7-Delta24 can kill CD44(+)CD24(-/low), and also committed breast cancer cells, making them promising agents for treatment of breast cancer. PMID:17848962

  11. CK2 phosphorylation of eukaryotic translation initiation factor 5 potentiates cell cycle progression

    PubMed Central

    Homma, Miwako Kato; Wada, Ikuo; Suzuki, Toshiyuki; Yamaki, Junko; Krebs, Edwin G.; Homma, Yoshimi

    2005-01-01

    Casein kinase 2 (CK2) is a ubiquitous eukaryotic Ser/Thr protein kinase that plays an important role in cell cycle progression. Although its function in this process remains unclear, it is known to be required for the G1 and G2/M phase transitions in yeast. Here, we show that CK2 activity changes notably during cell cycle progression and is increased within 3 h of serum stimulation of quiescent cells. During the time period in which it exhibits high enzymatic activity, CK2 associates with and phosphorylates a key molecule for translation initiation, eukaryotic translation initiation factor (eIF) 5. Using MS, we show that Ser-389 and -390 of eIF5 are major sites of phosphorylation by CK2. This is confirmed using eIF5 mutants that lack CK2 sites; the phosphorylation levels of mutant eIF5 proteins are significantly reduced, relative to WT eIF5, both in vitro and in vivo. Expression of these mutants reveals that they have a dominant-negative effect on phosphorylation of endogenous eIF5, and that they perturb synchronous progression of cells through S to M phase, resulting in a significant reduction in growth rate. Furthermore, the formation of mature eIF5/eIF2/eIF3 complex is reduced in these cells, and, in fact, restricted diffusional motion of WT eIF5 was almost abolished in a GFP-tagged eIF5 mutant lacking CK2 phosphorylation sites, as measured by fluorescence correlation spectroscopy. These results suggest that CK2 may be involved in the regulation of cell cycle progression by associating with and phosphorylating a key molecule for translation initiation. PMID:16227438

  12. Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells.

    PubMed

    Dowling, Ryan J O; Zakikhani, Mahvash; Fantus, I George; Pollak, Michael; Sonenberg, Nahum

    2007-11-15

    Metformin is used for the treatment of type 2 diabetes because of its ability to lower blood glucose. The effects of metformin are explained by the activation of AMP-activated protein kinase (AMPK), which regulates cellular energy metabolism. Recently, we showed that metformin inhibits the growth of breast cancer cells through the activation of AMPK. Here, we show that metformin inhibits translation initiation. In MCF-7 breast cancer cells, metformin treatment led to a 30% decrease in global protein synthesis. Metformin caused a dose-dependent specific decrease in cap-dependent translation, with a maximal inhibition of 40%. Polysome profile analysis showed an inhibition of translation initiation as metformin treatment of MCF-7 cells led to a shift of mRNAs from heavy to light polysomes and a concomitant increase in the amount of 80S ribosomes. The decrease in translation caused by metformin was associated with mammalian target of rapamycin (mTOR) inhibition, and a decrease in the phosphorylation of S6 kinase, ribosomal protein S6, and eIF4E-binding protein 1. The effects of metformin on translation were mediated by AMPK, as treatment of cells with the AMPK inhibitor compound C prevented the inhibition of translation. Furthermore, translation in MDA-MB-231 cells, which lack the AMPK kinase LKB1, and in tuberous sclerosis complex 2 null (TSC2(-/-)) mouse embryonic fibroblasts was unaffected by metformin, indicating that LKB1 and TSC2 are involved in the mechanism of action of metformin. These results show that metformin-mediated AMPK activation leads to inhibition of mTOR and a reduction in translation initiation, thus providing a possible mechanism of action of metformin in the inhibition of cancer cell growth. PMID:18006825

  13. Flagellin modulates IgE expression in B cells to initiate food allergy in mice

    PubMed Central

    Li, Lin-Jing; Ma, Na; Zeng, Lu; Mo, Li-Hua; Li, Xiao-Xi; Xu, Ling-Zhi; Yang, Bo; Liu, Zhi-Gang; Feng, Bai-Sui; Zheng, Peng-Yuan; Zhang, Huan-Ping; Yang, Ping-Chang

    2016-01-01

    The initiation mechanism of IgE expression has not been fully understood. Flagellin (FGN) is an important microbial factor in the regulation of immune responses in the intestine. This study tests a hypothesis that FGN plays a crucial role in the isotype switching of IgE in B cells and the initiation of food allergy. In this study, the expression of IgE in B cells was analyzed by real time RT-PCR, Western blotting and chromatin immunoprecipitation. A mouse model was developed to assess the role of Toll like receptor-5 in the development of IgE-mediated allergic reaction in the intestinal mucosa. The results showed that exposure to FGN suppressed the expression of Bcl6 in B cells via increasing the levels of histone deacetylase (HDAC) 7; the latter up regulated the levels of methylated H3K9 and H3K27, down regulated RNA polymerase II and STAT3 (signal transducer and activator of transcription 3) at the Bcl6 promoter locus. Exposure to FGN and IL-4 markedly increased the expression of IgE in B cells via activating p300, H3K4, Pol II and STAT6 at the IgE promoter locus. As compared with the sensitized wild mice, the sensitized TLR5-deficient mice showed no detectable OVA-specific IgE in the serum; mast cells in the intestinal mucosa were not activated, no apparent allergic symptoms were evoked after the specific antigen challenge. In conclusion, FGN facilitates the initiation of food allergy in mice by triggering IgE transcription in B cells in a Th2 polarization environment via activating HDAC7 and suppressing Bcl6 expression. PMID:27398157

  14. Graphical Planning Of Spacecraft Missions

    NASA Technical Reports Server (NTRS)

    Jeletic, J. F.; Ruley, L. T.

    1991-01-01

    Mission Planning Graphical Tool (MPGT) computer program provides analysts with graphical representations of spacecraft and environmental data used in planning missions. Designed to be generic software tool configured to analyze any specified Earth-orbiting spacecraft mission. Data presented as series of overlays on top of two-dimensional or three-dimensional projection of Earth. Includes spacecraft-orbit tracks, ground-station-antenna masks, solar and lunar ephemerides, and coverage by Tracking Data and Relay Satellite System (TDRSS). From graphical representations, analyst determines such spacecraft-related constraints as communication coverage, infringement upon zones of interference, availability of sunlight, and visibility of targets to instruments.

  15. Spacecraft telecommunications system mass estimates

    NASA Technical Reports Server (NTRS)

    Yuen, J. H.; Sakamoto, L. L.

    1988-01-01

    Mass is the most important limiting parameter for present-day planetary spacecraft design, In fact, the entire design can be characterized by mass. The more efficient the design of the spacecraft, the less mass will be required. The communications system is an essential and integral part of planetary spacecraft. A study is presented of the mass attributable to the communications system for spacecraft designs used in recent missions in an attempt to help guide future design considerations and research and development efforts. The basic approach is to examine the spacecraft by subsystem and allocate a portion of each subsystem to telecommunications. Conceptually, this is to divide the spacecraft into two parts, telecommunications and nontelecommunications. In this way, it is clear what the mass attributable to the communications system is. The percentage of mass is calculated using the actual masses of the spacecraft parts, except in the case of CRAF. In that case, estimated masses are used since the spacecraft was not yet built. The results show that the portion of the spacecraft attributable to telecommunications is substantial. The mass fraction for Voyager, Galileo, and CRAF (Mariner Mark 2) is 34, 19, and 18 percent, respectively. The large reduction of telecommunications mass from Voyager to Galileo is mainly due to the use of a deployable antenna instead of the solid antenna on Voyager.

  16. Hertwig's epithelial root sheath cell behavior during initial acellular cementogenesis in rat molars.

    PubMed

    Yamamoto, Tsuneyuki; Yamamoto, Tomomaya; Yamada, Tamaki; Hasegawa, Tomoka; Hongo, Hiromi; Oda, Kimimitsu; Amizuka, Norio

    2014-11-01

    This study was designed to examine developing acellular cementum in rat molars by immunohistochemistry, to elucidate (1) how Hertwig's epithelial root sheath disintegrates and (2) whether epithelial sheath cells transform into cementoblasts through epithelial-mesenchymal transition (EMT). Initial acellular cementogenesis was divided into three developmental stages, which can be seen in three different portions of the root: portion 1, where the epithelial sheath is intact; portion 2, where the epithelial sheath becomes fragmented; and portion 3, where acellular cementogenesis begins. Antibodies against three kinds of matrix proteinases, which degrade epithelial sheath-maintaining factors, including basement membrane and desmosomes, were used to investigate proteolytic activity of the epithelial sheath. Tissue non-specific alkaline phosphatase (TNALP) and keratin were used to investigate EMT. Epithelial sheath cells showed immunoreactivity for all three enzymes at fragmentation, which suggests that epithelial sheath disintegration is enzymatically mediated. Dental follicle cells and cementoblasts showed intense immunoreactivity for TNALP, and from portion 1 through to 3, the reaction extended from the alveolar bone-related zone to the root-related zone. Cells possessing keratin/TNALP double immunoreactivity were virtually absent. Keratin-positive epithelial sheath cells showed negligible immunoreactivity for TNALP, and epithelial cells did not appear to migrate to the dental follicle. Together, these findings suggest that a transition phenotype between epithelial cells and cementoblasts does not exist in the developing dental follicle and hence that epithelial sheath cells do not undergo EMT during initial acellular cementogenesis. In brief, this study supports the notion that cementoblasts derive from the dental follicle. PMID:24859538

  17. Glycometabolic reprogramming associated with the initiation of human dental pulp stem cell differentiation.

    PubMed

    Wang, Linyan; Cheng, Li; Wang, Huning; Pan, Hongying; Yang, Hui; Shao, Meiying; Hu, Tao

    2016-03-01

    Glycometabolism, particularly mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis, plays a central role in cell life activities. Glycometabolism can be reprogrammed to maintain the stemness or to induce the differentiation of stem cells, thereby regulating tissue repair and regeneration. However, research on the glycometabolism of human dental pulp stem cells (hDPSCs) remains scarce. Here, we investigated the relationship between glycometabolic reprogramming and initiation of hDPSC differentiation. We found the differentiation of hDPSCs commenced on day 3 when cells were cultured in mineralized medium. When cell differentiation commenced, mitochondria became elongated with well-developed cristae, and the oxygen consumption rate of mitochondria was enhanced, manifested as an increase in basal respiration, mitochondrial ATP production, and maximal respiration. Interestingly, glycolytic enzyme activities, glycolysis capacity, and glycolysis reserve were also upregulated at this time to match the powerful bioenergetic demands. More importantly, hDPSCs derived from different donors or cultured in various oxygen environments showed similar glycometabolic changes when they began to differentiate. Thus, glycometabolic reprogramming accompanies initiation of hDPSC differentiation and could potentially play a role in the regulation of dental pulp repair. PMID:26634800

  18. Red blood cells initiate leukocyte rolling in postcapillary expansions: a lattice Boltzmann analysis.

    PubMed

    Sun, Chenghai; Migliorini, Cristiano; Munn, Lance L

    2003-07-01

    Leukocyte rolling on the vascular endothelium requires initial contact between leukocytes circulating in the blood and the vessel wall. Although specific adhesion mechanisms are involved in leukocyte-endothelium interactions, adhesion patterns in vivo suggest other rheological mechanisms also play a role. Previous studies have proposed that the abundance of leukocyte rolling in postcapillary venules is due to interactions between red blood cells (RBCs) and leukocytes as they enter postcapillary expansions, but the details of the fluid dynamics have not been elucidated. We have analyzed the interactions of red and white blood cells as they flow from a capillary into a postcapillary venule using a lattice Boltzmann approach. This technique provides the complete solution of the flow field and quantification of the particle-particle forces in a relevant geometry. Our results show that capillary-postcapillary venule diameter ratio, RBC configuration, and RBC shape are critical determinants of the initiation of cell rolling in postcapillary venules. The model predicts that an optimal configuration of the trailing red blood cells is required to drive the white blood cell to the wall. PMID:12829477

  19. Red Blood Cells Initiate Leukocyte Rolling in Postcapillary Expansions: A Lattice Boltzmann Analysis

    PubMed Central

    Sun, Chenghai; Migliorini, Cristiano; Munn, Lance L.

    2003-01-01

    Leukocyte rolling on the vascular endothelium requires initial contact between leukocytes circulating in the blood and the vessel wall. Although specific adhesion mechanisms are involved in leukocyte-endothelium interactions, adhesion patterns in vivo suggest other rheological mechanisms also play a role. Previous studies have proposed that the abundance of leukocyte rolling in postcapillary venules is due to interactions between red blood cells (RBCs) and leukocytes as they enter postcapillary expansions, but the details of the fluid dynamics have not been elucidated. We have analyzed the interactions of red and white blood cells as they flow from a capillary into a postcapillary venule using a lattice Boltzmann approach. This technique provides the complete solution of the flow field and quantification of the particle-particle forces in a relevant geometry. Our results show that capillary-postcapillary venule diameter ratio, RBC configuration, and RBC shape are critical determinants of the initiation of cell rolling in postcapillary venules. The model predicts that an optimal configuration of the trailing red blood cells is required to drive the white blood cell to the wall. PMID:12829477

  20. Crack Initiation and Growth in Rigid Polymeric Closed-Cell Foam Cryogenic Applications

    NASA Technical Reports Server (NTRS)

    Sayyah, Tarek; Steeve, Brian; Wells, Doug

    2006-01-01

    Cryogenic vessels, such as the Space Shuttle External Tank, are often insulated with closed-cell foam because of its low thermal conductivity. The coefficient of thermal expansion mismatch between the foam and metallic substrate places the foam under a biaxial tension gradient through the foam thickness. The total foam thickness affects the slope of the stress gradient and is considered a significant contributor to the initiation of subsurface cracks. Rigid polymeric foams are brittle in nature and any subsurface cracks tend to propagate a finite distance toward the surface. This presentation investigates the relationship between foam thickness and crack initiation and subsequent crack growth, using linear elastic fracture mechanics, in a rigid polymeric closed-cell foam through analysis and comparison with experimental results.

  1. Targeting Tumor Initiating Cells through Inhibition of Cancer Testis Antigens and Notch Signaling: A Hypothesis.

    PubMed

    Colombo, Michela; Mirandola, Leonardo; Reidy, Adair; Suvorava, Natallia; Konala, Venu; Chiaramonte, Raffaella; Grizzi, Fabio; Rahman, Rakhshanda Layeequr; Jenkins, Marjorie R; Nugyen, Diane D; Dalhbeck, Scott; Cobos, Everardo; Figueroa, Jose A; Chiriva-Internati, Maurizio

    2015-03-01

    Tumor initiating cells (TICs) differ from normal stem cells (SCs) in their ability to initiate tumorigenesis, invasive growth, metastasis and the acquisition of chemo and/or radio-resistance. Over the past years, several studies have indicated the potential role of the Notch system as a key regulator of cellular stemness and tumor development. Furthermore, the expression of cancer testis antigens (CTA) in TICs, and their role in SC differentiation and biology, has become an important area of investigation. Here, we propose a model in which CTA expression and Notch signaling interacts to maintain the sustainability of self-replicating tumor populations, ultimately leading to the development of metastasis, drug resistance and cancer progression. We hypothesize that Notch-CTA interactions in TICs offer a novel opportunity for meaningful therapeutic interventions in cancer. PMID:25901861

  2. Basal cell carcinoma: clues to its presence in histologic sections when the initial slide is nondiagnostic.

    PubMed

    Haupt, H M; Stern, J B; Dilaimy, M S

    2000-09-01

    Initial sections of skin biopsies may not be diagnostic of basal cell carcinoma (BCC). Are there histologic predictors of BCC that should prompt deeper sections? Ninety-four cases in which the clinical diagnosis was BCC or "rule-out BCC," and the initial histologic slides were nondiagnostic, were submitted for deeper sections on three additional slides. Of the 94 cases, 50 (53%) demonstrated BCC on deeper sections. This relatively high incidence suggests that deeper sections should be taken in all cases of clinically suspected BCCs unless alternate histologic findings adequately account for the clinical lesion. The results of this study suggest that additional sections are more likely to yield BCC when the initial nondiagnostic slide demonstrates focal epidermal atypia, equivocal adnexae, stromal fibrosis, empty dermal space, and microcalcifications, criteria which may be useful in determining the need to do deeper sections in cases in which BCC is not clinically suspected. PMID:10976705

  3. Effect of initial salt concentrations on cell performance and distribution of internal resistance in microbial desalination cells.

    PubMed

    Yang, Euntae; Choi, Mi-Jin; Kim, Kyoung-Yeol; Chae, Kyu-Jung; Kim, In S

    2015-01-01

    Microbial desalination cells (MDCs) are modified microbial fuel cells (MFCs) that concurrently produce electricity and desalinate seawater, but adding a desalination compartment and an ion-exchange membrane may increase the internal resistance (Ri), which can limit the cell performance. However, the effects of a desalination chamber and initial NaCl concentrations on the internal resistances and the cell performances (i.e. Coulombic efficiency (CE), current and power density) of MDCs have yet to be thoroughly explored; thus, the cell performance and Ri distributions of MDCs having different initial concentrations and an MFC having no desalination chamber were compared. In the MDCs, the current and power density generation increased from 2.82 mA and 158.2 mW/m2 to 3.17 mA and 204.5 mW/m2 when the initial NaCl concentrations were increased from 5 to 30 g/L, as a consequence of the internal resistances decreasing from 2432.0 to 2328.4 Ω. And even though the MFC has a lower Ri than the MDCs, lower cell performances (current: 2.59 mA; power density: 141.6 mW/m2 and CE: 62.1%) were observed; there was no effect of improved junction potential in the MFC. Thus, in the MDCs, the higher internal resistances due to the addition of a desalination compartment can be offset by reducing the electrolyte resistance and improving the junction potential at higher NaCl concentrations. PMID:25212471

  4. Electromagnetic propulsion for spacecraft

    NASA Technical Reports Server (NTRS)

    Myers, Roger M.

    1993-01-01

    Three electromagnetic propulsion technologies, solid propellant pulsed plasma thrusters (PPT), magnetoplasmadynamic (MPD) thrusters, and pulsed inductive thrusters (PIT) have been developed for application to auxiliary and primary spacecraft propulsion. Both the PPT and MPD thrusters have been flown in space, though only PPTs have been used on operational satellites. The performance of operational PPTs is quite poor, providing only about 8 percent efficiency at about 1000 sec specific impulse. Laboratory PPTs yielding 34 percent efficiency at 5170 sec specific impulse have been demonstrated. Laboratory MPD thrusters have been demonstrated with up to 70 percent efficiency and 7000 sec specific impulse. Recent PIT performance measurements using ammonia and hydrazine propellants are extremely encouraging, reaching 50 percent efficiency for specific impulses between 4000 and 8000 sec.

  5. Spacecraft Attitude Representations

    NASA Technical Reports Server (NTRS)

    Markley, F. Landis

    1999-01-01

    The direction cosine matrix or attitude matrix is the most fundamental representation of the attitude, but it is very inefficient: It has six redundant parameters, it is difficult to enforce the six (orthogonality) constraints. the four-component quaternion representation is very convenient: it has only one redundant parameter, it is easy to enforce the normalization constraint, the attitude matrix is a homogeneous quadratic function of q, quaternion kinematics are bilinear in q and m. Euler angles are extensively used: they often have a physical interpretation, they provide a natural description of some spacecraft motions (COBE, MAP), but kinematics and attitude matrix involve trigonometric functions, "gimbal lock" for certain values of the angles. Other minimum (three-parameter) representations: Gibbs vector is infinite for 180 deg rotations, but useful for analysis, Modified Rodrigues Parameters are nonsingular, no trig functions, Rotation vector phi is nonsingular, but requires trig functions.

  6. Spacecraft stability and control

    NASA Technical Reports Server (NTRS)

    Barret, Chris

    1992-01-01

    The Earth's first artificial satellite, Sputnik 1, slowly tumbled in orbit. The first U.S. satellite, Explorer 1, also tumbled out of control. Today, satellite stability and control has become a higher priority. For a satellite design that is to have a life expectancy of 14 years, appropriate spacecraft flight control systems will be reviewed, stability requirements investigated, and an appropriate flight control system recommended in order to see the design process. Disturbance torques, including aerodynamic, magnetic, gravity gradient, solar, micrometeorite, debris, collision, and internal torques, will be assessed to quantify the disturbance environment so that the required compensating torques can be determined. The control torques, including passive versus active, momentum control, bias momentum, spin stabilization, dual spin, gravity gradient, magnetic, reaction wheels, control moment gyros, inertia augmentation techniques, three-axis control, and reaction control systems (RCSs), will be considered. Conditions for stability will also be considered.

  7. Magnetic bearings for spacecraft

    NASA Technical Reports Server (NTRS)

    Studer, P. A.

    1972-01-01

    Magnetic bearings have been successfully applied to motorized rotor systems in the multi-kilogram range, at speeds up to 1200 radians per second. These engineering models also indicated the need for continued development in specific areas to make them feasible for spacecraft applications. Significant power reductions have recently been attained. A unique magnetic circuit, combining permanent magnets with electromagnetic control, has a bidirectional forcing capability with improved current sensitivity. The multi-dimensional nature of contact-free rotor support is discussed. Stable continuous radial suspension is provided by a rotationally symmetric permanent magnet circuit. Two bearings, on a common shaft, counteract the normal instability perpendicular to the rotational axis. The axial direction is servoed to prevent contact. A new bearing technology and a new field of application for magnetics is foreseen.

  8. Self-Organizing Properties of Mouse Pluripotent Cells Initiate Morphogenesis upon Implantation

    PubMed Central

    Bedzhov, Ivan; Zernicka-Goetz, Magdalena

    2014-01-01

    Summary Transformation of pluripotent epiblast cells into a cup-shaped epithelium as the mouse blastocyst implants is a poorly understood and yet key developmental step. Studies of morphogenesis in embryoid bodies led to the current belief that it is programmed cell death that shapes the epiblast. However, by following embryos developing in vivo and in vitro, we demonstrate that not cell death but a previously unknown morphogenetic event transforms the amorphous epiblast into a rosette of polarized cells. This transformation requires basal membrane-stimulated integrin signaling that coordinates polarization of epiblast cells and their apical constriction, a prerequisite for lumenogenesis. We show that basal membrane function can be substituted in vitro by extracellular matrix (ECM) proteins and that ES cells can be induced to form similar polarized rosettes that initiate lumenogenesis. Together, these findings lead to a completely revised model for peri-implantation morphogenesis in which ECM triggers the self-organization of the embryo’s stem cells. PMID:24529478

  9. Rapid Reprogramming of Primary Human Astrocytes into Potent Tumor-Initiating Cells with Defined Genetic Factors.

    PubMed

    Li, Fang; Liu, Xinjian; Sampson, John H; Bigner, Darell D; Li, Chuan-Yuan

    2016-09-01

    Cancer stem-like cells (CSC) are thought to drive brain cancer, but their cellular and molecular origins remain uncertain. Here, we report the successful generation of induced CSC (iCSC) from primary human astrocytes through the expression of defined genetic factors. Combined transduction of four factors, Myc, Oct-4, p53DD, and Ras, induced efficient transformation of primary human astrocytes into malignant cells with powerful tumor-initiating capabilities. Notably, transplantation of 100 transduced cells into nude mice was sufficient for tumor formation. The cells showed unlimited self-renewal ability with robust telomerase activities. In addition, they expressed typical glioma stem-like cell markers, such as CD133, CD15, and CD90. Moreover, these cells could form spheres in culture and differentiate into neuron-like, astrocyte-like, and oligodendrocyte-like cells. Finally, they also displayed resistance to the widely used brain cancer drug temozolomide. These iCSCs could provide important tools for studies of glioma biology and therapeutics development. Cancer Res; 76(17); 5143-50. ©2016 AACR. PMID:27364552

  10. Microbiological Contamination of Spacecraft

    NASA Technical Reports Server (NTRS)

    Pierson, D. L.; Bruce, R. J.; Groves, T. O.; Novikova, N. D.; Viktorov, A. N.

    2000-01-01

    The International Space Station (ISS) Phase1 Program resulted in seven US astronauts residing aboard the Russian Space Station Mir between March 1995 and May 1998. Collaboration between U.S. and Russian scientists consisted of collection and analyses of samples from the crewmembers and the Mir and Shuttle environments before, during, and after missions that lasted from 75 to 209 days in duration. The effects of long-duration space flight on the microbial characteristics of closed life support systems and the interactions of microbes with the spacecraft environment and crewmembers were investigated. Air samples were collected using a Russian or U.S.-supplied sampler (SAS, RCS, or Burkard,) while surface samples were collected using contact slides (Hycon) or swabs. Mir recycled condensate and stored potable water sources were analyzed using the U.S.-supplied Water Experiment Kit. In-flight analysis consisted of enumeration of levels of bacteria and fungi. Amounts of microorganisms seen in the air and on surfaces were mostly within acceptability lin1its; observed temporal fluctuations in levels of microbes probably reflect changes in environmental conditions (e.g., humidity). All Mir galley hot water samples were within the standards set for Mir and the ISS. Microbial isolates were returned to Earth for identification of bacterial and fungal isolates. Crew samples (nose, throat, skin, urine, and feces) were analyzed using methods approved for the medical evaluations of Shuttle flight crews. No significant changes in crew microbiota were found during space flight or upon return relative to preflight results. Dissemination of microbes between the crew and environment was demonstrated by D A fingerprinting. Some biodegradation of spacecraft materials was observed. Accumulation of condensate allowed for the recovery of a wide range of bacteria and fungi as well as some protozoa and dust mites.

  11. Improvements in Modeling Thruster Plume Erosion Damage to Spacecraft Surfaces

    NASA Technical Reports Server (NTRS)

    Soares, Carlos; Olsen, Randy; Steagall, Courtney; Huang, Alvin; Mikatarian, Ron; Myers, Brandon; Koontz, Steven; Worthy, Erica

    2015-01-01

    Spacecraft bipropellant thrusters impact spacecraft surfaces with high speed droplets of unburned and partially burned propellant. These impacts can produce erosion damage to optically sensitive hardware and systems (e.g., windows, camera lenses, solar cells and protective coatings). On the International Space Station (ISS), operational constraints are levied on the position and orientation of the solar arrays to mitigate erosion effects during thruster operations. In 2007, the ISS Program requested evaluation of erosion constraint relief to alleviate operational impacts due to an impaired Solar Alpha Rotary Joint (SARJ). Boeing Space Environments initiated an activity to identify and remove sources of conservatism in the plume induced erosion model to support an expanded range of acceptable solar array positions ? The original plume erosion model over-predicted plume erosion and was adjusted to better correlate with flight experiment results. This paper discusses findings from flight experiments and the methodology employed in modifying the original plume erosion model for better correlation of predictions with flight experiment data. The updated model has been successful employed in reducing conservatism and allowing for enhanced flexibility in ISS solar array operations.

  12. Cross talk Initiated by Endothelial Cells Enhances Migration and Inhibits Anoikis of Squamous Cell Carcinoma Cells through STAT3/Akt/ERK Signaling12

    PubMed Central

    Neiva, Kathleen G; Zhang, Zhaocheng; Miyazawa, Marta; Warner, Kristy A; Karl, Elisabeta; Nör, Jacques E

    2009-01-01

    It is well known that cancer cells secrete angiogenic factors to recruit and sustain tumor vascular networks. However, little is known about the effect of endothelial cell-secreted factors on the phenotype and behavior of tumor cells. The hypothesis underlying this study is that endothelial cells initiate signaling pathways that enhance tumor cell survival and migration. Here, we observed that soluble mediators from primary human dermal microvascular endothelial cells induce phosphorylation of signal transducer and activator of transcription 3 (STAT3), Akt, and extracellular signal-regulated kinase (ERK) in a panel of head and neck squamous cell carcinoma (HNSCC) cells (OSCC-3, UM-SCC-1, UM-SCC-17B, UM-SCC-74A). Gene expression analysis demonstrated that interleukin-6 (IL- 6), interleukin-8 (CXCL8), and epidermal growth factor (EGF) are upregulated in endothelial cells cocultured with HNSCC. Blockade of endothelial cell-derived IL-6, CXCL8, or EGF by gene silencing or neutralizing antibodies inhibited phosphorylation of STAT3, Akt, and ERK in tumor cells, respectively. Notably, activation of STAT3, Akt, and ERK by endothelial cells enhanced migration and inhibited anoikis of tumor cells. We have previously demonstrated that Bcl-2 is upregulated in tumor microvessels in patients with HNSCC. Here, we observed that Bcl-2 signaling induces expression of IL-6, CXCL8, and EGF, providing a mechanism for the upregulation of these cytokines in tumor-associated endothelial cells. This study expands the contribution of endothelial cells to the pathobiology of tumor cells. It unveils a new mechanism in which endothelial cells function as initiators of molecular crosstalks that enhance survival and migration of tumor cells. PMID:19484147

  13. Estimating the Reliability of a Crewed Spacecraft

    NASA Astrophysics Data System (ADS)

    Lutomski, M. G.; Garza, J.

    2012-01-01

    Now that the Space Shuttle Program has been retired, the Russian Soyuz Launcher and Soyuz Spacecraft are the only means for crew transportation to and from the International Space Station (ISS). Are the astronauts and cosmonauts safer on the Soyuz than the Space Shuttle system? How do you estimate the reliability of such a crewed spacecraft? The recent loss of the 44 Progress resupply flight to the ISS has put these questions front and center. The Soyuz launcher has been in operation for over 40 years. There have been only two Loss of Crew (LOC) incidents and two Loss of Mission (LOM) incidents involving crew missions. Given that the most recent crewed Soyuz launcher incident took place in 1983, how do we determine current reliability of such a system? How do all of the failures of unmanned Soyuz family launchers such as the 44P impact the reliability of the currently operational crewed launcher? Does the Soyuz exhibit characteristics that demonstrate reliability growth and how would that be reflected in future estimates of success? In addition NASA has begun development of the Orion or Multi-Purpose Crewed Vehicle as well as started an initiative to purchase Commercial Crew services from private firms. The reliability targets are currently several times higher than the last Shuttle reliability estimate. Can these targets be compared to the reliability of the Soyuz arguably the highest reliable crewed spacecraft and launcher in the world to determine whether they are realistic and achievable? To help answer these questions this paper will explore how to estimate the reliability of the Soyuz launcher/spacecraft system over its mission to give a benchmark for other human spaceflight vehicles and their missions. Specifically this paper will look at estimating the Loss of Mission (LOM) and Loss of Crew (LOC) probability for an ISS crewed Soyuz launcher/spacecraft mission using historical data, reliability growth, and Probabilistic Risk Assessment (PRA) techniques.

  14. The Akt1/IL-6/STAT3 pathway regulates growth of lung tumor initiating cells.

    PubMed

    Malanga, Donatella; De Marco, Carmela; Guerriero, Ilaria; Colelli, Fabiana; Rinaldo, Nicola; Scrima, Marianna; Mirante, Teresa; De Vitis, Claudia; Zoppoli, Pietro; Ceccarelli, Michele; Riccardi, Miriam; Ravo, Maria; Weisz, Alessandro; Federico, Antonella; Franco, Renato; Rocco, Gaetano; Mancini, Rita; Rizzuto, Antonia; Gulletta, Elio; Ciliberto, Gennaro; Viglietto, Giuseppe

    2015-12-15

    Here we report that the PI3K/Akt1/IL-6/STAT3 signalling pathway regulates generation and stem cell-like properties of Non-Small Cell Lung Cancer (NSCLC) tumor initiating cells (TICs). Mutant Akt1, mutant PIK3CA or PTEN loss enhances formation of lung cancer spheroids (LCS), self-renewal, expression of stemness markers and tumorigenic potential of human immortalized bronchial cells (BEAS-2B) whereas Akt inhibition suppresses these activities in established (NCI-H460) and primary NSCLC cells. Matched microarray analysis of Akt1-interfered cells and LCSs identified IL-6 as a critical target of Akt signalling in NSCLC TICs. Accordingly, suppression of Akt in NSCLC cells decreases IL-6 levels, phosphorylation of IkK and IkB, NF-kB transcriptional activity, phosphorylation and transcriptional activity of STAT3 whereas active Akt1 up-regulates them. Exposure of LCSs isolated from NSCLC cells to blocking anti-IL-6 mAbs, shRNA to IL-6 receptor or to STAT3 markedly reduces the capability to generate LCSs, to self-renew and to form tumors, whereas administration of IL-6 to Akt-interfered cells restores the capability to generate LCSs. Finally, immunohistochemical studies in NSCLC patients demonstrated a positive correlative trend between activated Akt, IL-6 expression and STAT3 phosphorylation (n = 94; p < 0.05). In conclusion, our data indicate that aberrant Akt signalling contributes to maintaining stemness in lung cancer TICs through a NF-kB/IL-6/STAT3 pathway and provide novel potential therapeutic targets for eliminating these malignant cells in NSCLC. PMID:26486080

  15. The Akt1/IL-6/STAT3 pathway regulates growth of lung tumor initiating cells

    PubMed Central

    Malanga, Donatella; De Marco, Carmela; Guerriero, Ilaria; Colelli, Fabiana; Rinaldo, Nicola; Scrima, Marianna; Mirante, Teresa; De Vitis, Claudia; Zoppoli, Pietro; Ceccarelli, Michele; Riccardi, Miriam; Ravo, Maria; Weisz, Alessandro; Federico, Antonella; Franco, Renato; Rocco, Gaetano; Mancini, Rita; Rizzuto, Antonia; Gulletta, Elio; Ciliberto, Gennaro; Viglietto, Giuseppe

    2015-01-01

    Here we report that the PI3K/Akt1/IL-6/STAT3 signalling pathway regulates generation and stem cell-like properties of Non-Small Cell Lung Cancer (NSCLC) tumor initiating cells (TICs). Mutant Akt1, mutant PIK3CA or PTEN loss enhances formation of lung cancer spheroids (LCS), self-renewal, expression of stemness markers and tumorigenic potential of human immortalized bronchial cells (BEAS-2B) whereas Akt inhibition suppresses these activities in established (NCI-H460) and primary NSCLC cells. Matched microarray analysis of Akt1-interfered cells and LCSs identified IL-6 as a critical target of Akt signalling in NSCLC TICs. Accordingly, suppression of Akt in NSCLC cells decreases IL-6 levels, phosphorylation of IkK and IkB, NF-kB transcriptional activity, phosphorylation and transcriptional activity of STAT3 whereas active Akt1 up-regulates them. Exposure of LCSs isolated from NSCLC cells to blocking anti-IL-6 mAbs, shRNA to IL-6 receptor or to STAT3 markedly reduces the capability to generate LCSs, to self-renew and to form tumors, whereas administration of IL-6 to Akt-interfered cells restores the capability to generate LCSs. Finally, immunohistochemical studies in NSCLC patients demonstrated a positive correlative trend between activated Akt, IL-6 expression and STAT3 phosphorylation (n = 94; p < 0.05). In conclusion, our data indicate that aberrant Akt signalling contributes to maintaining stemness in lung cancer TICs through a NF-kB/IL-6/STAT3 pathway and provide novel potential therapeutic targets for eliminating these malignant cells in NSCLC. PMID:26486080

  16. IMP1 promotes tumor growth, dissemination and a tumor-initiating cell phenotype in colorectal cancer cell xenografts

    PubMed Central

    Hamilton, Kathryn E.; Noubissi, Felicite K.; Rustgi, Anil K.

    2013-01-01

    Igf2 mRNA binding protein 1 (IMP1, CRD-BP, ZBP-1) is a messenger RNA binding protein that we have shown previously to regulate colorectal cancer (CRC) cell growth in vitro. Furthermore, increased IMP1 expression correlates with enhanced metastasis and poor prognosis in CRC patients. In the current study, we sought to elucidate IMP1-mediated functions in CRC pathogenesis in vivo. Using CRC cell xenografts, we demonstrate that IMP1 overexpression promotes xenograft tumor growth and dissemination into the blood. Furthermore, intestine-specific knockdown of Imp1 dramatically reduces tumor number in the Apc Min/+ mouse model of intestinal tumorigenesis. In addition, IMP1 knockdown xenografts exhibit a reduced number of tumor cells entering the circulation, suggesting that IMP1 may directly modulate this early metastatic event. We further demonstrate that IMP1 overexpression decreases E-cadherin expression, promotes survival of single tumor cell-derived colonospheres and promotes enrichment and maintenance of a population of CD24+CD44+ cells, signifying that IMP1 overexpressing cells display evidence of loss of epithelial identity and enhancement of a tumor-initiating cell phenotype. Taken together, these findings implicate IMP1 as a modulator of tumor growth and provide evidence for a novel role of IMP1 in early events in CRC metastasis. PMID:23764754

  17. Suppression of cancer-initiating cells and selection of adipose-derived stem cells cultured on biomaterials having specific nanosegments.

    PubMed

    Kao, Ta-Chun; Lee, Henry Hsin-Chung; Higuchi, Akon; Ling, Qing-Dong; Yu, Wan-Chun; Chou, Yu-Hsuan; Wang, Pin-Yu; Suresh Kumar, S; Chang, Yu; Hung Chen, Yung; Chang, Yung; Chen, Da-Chung; Hsu, Shih-Tien

    2014-04-01

    Cancer-initiating cells [cancer stem cells (CSCs)] in colon cancer cells can be selectively suppressed when they are cultured on Pluronic (nanosegment)-grafted dishes, whereas CSCs are maintained on conventional tissue culture dishes and extracellular matrix-coated dishes. CSCs persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumorigenic clones. The purification or depletion (suppression) of CSCs should be useful for analyzing CSC characteristics and for clinical application. CSCs can be selectively suppressed from colon cancer cells containing adipose-derived stem cells (ADSCs) on Pluronic-grafted dishes, while ADSCs remain on the dishes. ADSCs on Pluronic-grafted dishes after the suppression of the CSCs can differentiate into osteoblasts, chondrocytes, adipocytes, cardiomyocytes, and neuronal cells. The CSCs and ADSCs exhibited different characteristics. The selection of ADSCs was possible on Pluronic-grafted dishes that suppressed the CSCs from the fat tissues of cancer patients (i.e., cell-sorting dishes), which was explained by specific biomedical characteristics of Pluronic. PMID:24039170

  18. N° 28-1998: SOHO spacecraft contacted

    NASA Astrophysics Data System (ADS)

    Contact has been re-established with the ESA/NASA Solar and Heliospheric Observatory (SOHO) following six weeks of silence. Signals sent yesterday through the NASA Deep Space Network (DSN) station at Canberra, Australia, were answered at 22:51 GMT in the form of bursts of signal lasting from 2 to 10 seconds. These signals were recorded both by the NASA DSN station and the ESA Perth station. Contact is being maintained through the NASA DSN stations at Goldstone (California), Canberra and Madrid (Spain). Although the signals are intermittent and do not contain any data information, they show that the spacecraft is still capable of receiving and responding to ground commands. The slow process of regaining control of the spacecraft and restoring it to an operational attitude will commence immediately, with attempts to initiate data transmissions in order to perform an initial assessment of the spacecraft on-board conditions. Radio contact with SOHO, a joint mission of the European Space Agency and NASA, was interrupted on 25 June (see ESA press releases N°24,25 and 26-98). More information on SOHO, including mission status reports is available on the Internet at http://sohowww.estec.esa.nl or via the new ESA science website: http://sci.esa.int

  19. IKKβ in intestinal mesenchymal cells promotes initiation of colitis-associated cancer

    PubMed Central

    Pasparakis, Manolis

    2015-01-01

    The importance of mesenchymal cells in inflammation and/or neoplastic transformation is well recognized, but their role in the initiation of these processes, particularly in the intestine, remains elusive. Using mouse models of colorectal cancer, we show that IKKβ in intestinal mesenchymal cells (IMCs) is critically involved in colitis-associated, but not spontaneous tumorigenesis. We further demonstrate that IMC-specific IKKβ is involved in the initiation of colitis-associated cancer (CAC), as in its absence mice develop reduced immune cell infiltration, epithelial cell proliferation, and dysplasia at the early stages of the disease. At the molecular level, these effects are associated with decreased early production of proinflammatory and protumorigenic mediators, including IL-6, and reduced STAT3 activation. Ex vivo IKKβ-deficient IMCs show defective responses to innate immune stimuli such as LPS, as shown by decreased NF-κB signaling and reduced expression of important NF-κB target genes. Collectively, our results reveal a hitherto unknown role of mesenchymal IKKβ in driving inflammation and enabling carcinogenesis in the intestine. PMID:26621453

  20. IKKβ in intestinal mesenchymal cells promotes initiation of colitis-associated cancer.

    PubMed

    Koliaraki, Vasiliki; Pasparakis, Manolis; Kollias, George

    2015-12-14

    The importance of mesenchymal cells in inflammation and/or neoplastic transformation is well recognized, but their role in the initiation of these processes, particularly in the intestine, remains elusive. Using mouse models of colorectal cancer, we show that IKKβ in intestinal mesenchymal cells (IMCs) is critically involved in colitis-associated, but not spontaneous tumorigenesis. We further demonstrate that IMC-specific IKKβ is involved in the initiation of colitis-associated cancer (CAC), as in its absence mice develop reduced immune cell infiltration, epithelial cell proliferation, and dysplasia at the early stages of the disease. At the molecular level, these effects are associated with decreased early production of proinflammatory and protumorigenic mediators, including IL-6, and reduced STAT3 activation. Ex vivo IKKβ-deficient IMCs show defective responses to innate immune stimuli such as LPS, as shown by decreased NF-κB signaling and reduced expression of important NF-κB target genes. Collectively, our results reveal a hitherto unknown role of mesenchymal IKKβ in driving inflammation and enabling carcinogenesis in the intestine. PMID:26621453

  1. Role of initial cell density of algal bioassay of toxic chemicals.

    PubMed

    Singh, Prashant Kumar; Shrivastava, Alok Kumar

    2016-07-01

    A variety of toxicants such as, metal ions, pesticides, dyes, etc. are continuously being introduced anthropogenically in the environment and adversely affect to the biotic component of the ecosystem. Therefore, the assessment of negative effects of these toxicants is required. However, toxicity assessment anticipated by chemical analysis are extremely poor, therefore the application of the living systems for the same is an excellent approach. Concentration of toxicant as well as cell density both influenced the result of the algal toxicity assay. Here, Scenedesmus sp, a very fast growing green microalgae was selected for study the effects of initial cell densities on the toxicity of Cu(II), Cd(II), Zn(II), paraquat and 2,4-D. Results demonstrated concentration dependent decrease in biomass and specific growth rate of Scenedesmus sp. on exposure of abovesaid toxicants. Paraquat and 2,4-D emerged as extremely toxic to the test alga which reflected from the lowest EC value and very steep decline in biomass was evident with increasing concentration of paraquat and 2,4-D in the medium. Result also demonstrated that initial cell density is a very important parameter than specific growth rate for algal bioassay of various toxicants. Present study clearly illustrated that the use of smaller cell density is always recommended for assaying toxicity of chemicals in algal assays. PMID:26593761

  2. MicroRNA Regulation of Brain Tumour Initiating Cells in Central Nervous System Tumours

    PubMed Central

    Vijayakumar, Thusyanth; Bakhshinyan, David; Venugopal, Chitra; Singh, Sheila K.

    2015-01-01

    CNS tumours occur in both pediatric and adult patients and many of these tumours are associated with poor clinical outcome. Due to a paradigm shift in thinking for the last several years, these tumours are now considered to originate from a small population of stem-like cells within the bulk tumour tissue. These cells, termed as brain tumour initiating cells (BTICs), are perceived to be regulated by microRNAs at the posttranscriptional/translational levels. Proliferation, stemness, differentiation, invasion, angiogenesis, metastasis, apoptosis, and cell cycle constitute some of the significant processes modulated by microRNAs in cancer initiation and progression. Characterization and functional studies on oncogenic or tumour suppressive microRNAs are made possible because of developments in sequencing and microarray techniques. In the current review, we bring recent knowledge of the role of microRNAs in BTIC formation and therapy. Special attention is paid to two highly aggressive and well-characterized brain tumours: gliomas and medulloblastoma. As microRNA seems to be altered in the pathogenesis of many human diseases, “microRNA therapy” may now have potential to improve outcomes for brain tumour patients. In this rapidly evolving field, further understanding of miRNA biology and its contribution towards cancer can be mined for new therapeutic tools. PMID:26064134

  3. Solving a Spacecraft Design Problem

    NASA Technical Reports Server (NTRS)

    Fisher, D. K.

    1998-01-01

    We have probably all been amazed at the ingenuity of spacecraft engineers when we see some of the solutions they invent for such problems as landing a roving vehicle on Mars-as engineers at the Jet Propulsion Laboratory did for NASA's Mars Pathfinder project-without using retro-rockets or even putting a spacecraft in orbit first.

  4. The Galeleo spacecraft magnetometer boom

    NASA Technical Reports Server (NTRS)

    Packard, D. T.; Benton, M. D.

    1985-01-01

    The Galileo spacecraft utilizes a deployable lattice boom to position three science instruments at remote distances from the spacecraft body. An improved structure and mechanism to precisely control deployment of the boom, and the unique deployment of an outer protective cover are described.

  5. Spacecraft detumbling through energy dissipation

    NASA Technical Reports Server (NTRS)

    Fitz-Coy, Norman; Chatterjee, Anindya

    1993-01-01

    The attitude motion of a tumbling, rigid, axisymmetric spacecraft is considered. A methodology for detumbling the spacecraft through energy dissipation is presented. The differential equations governing this motion are stiff, and therefore an approximate solution, based on the variation of constants method, is developed and utilized in the analysis of the detumbling strategy. Stability of the detumbling process is also addressed.

  6. Active Spacecraft Potential Control Investigation

    NASA Astrophysics Data System (ADS)

    Torkar, K.; Nakamura, R.; Tajmar, M.; Scharlemann, C.; Jeszenszky, H.; Laky, G.; Fremuth, G.; Escoubet, C. P.; Svenes, K.

    2016-03-01

    In tenuous plasma the floating potential of sunlit spacecraft reaches tens of volts, positive. The corresponding field disturbs measurements of the ambient plasma by electron and ion sensors and can reduce micro-channel plate lifetime in electron detectors owing to large fluxes of attracted photoelectrons. Also the accuracy of electric field measurements may suffer from a high spacecraft potential. The Active Spacecraft Potential Control (ASPOC) neutralizes the spacecraft potential by releasing positive charge produced by indium ion emitters. The method has been successfully applied on other spacecraft such as Cluster and Double Star. Two ASPOC units are present on each spacecraft. Each unit contains four ion emitters, whereby one emitter per instrument is operated at a time. ASPOC for the Magnetospheric Multiscale (MMS) mission includes new developments in the design of the emitters and the electronics. New features include the use of capillaries instead of needles, new materials for the emitters and their internal thermal insulators, an extended voltage and current range of the electronics, both for ion emission and heating purposes, and a more capable control software. This enables lower spacecraft potentials, higher reliability, and a more uniform potential structure in the spacecraft's sheath compared to previous missions. Results from on-ground testing demonstrate compliance with requirements. Model calculations confirm the findings from previous applications that the plasma measurements will not be affected by the beam's space charge. Finally, the various operating modes to adapt to changing boundary conditions are described along with the main data products.

  7. Tumor Initiating Cells and Chemoresistance: Which Is the Best Strategy to Target Colon Cancer Stem Cells?

    PubMed Central

    Paldino, Emanuela; Tesori, Valentina; Casalbore, Patrizia; Gasbarrini, Antonio

    2014-01-01

    There is an emerging body of evidence that chemoresistance and minimal residual disease result from selective resistance of a cell subpopulation from the original tumor that is molecularly and phenotypically distinct. These cells are called “cancer stem cells” (CSCs). In this review, we analyze the potential targeting strategies for eradicating CSCs specifically in order to develop more effective therapeutic strategies for metastatic colon cancer. These include induction of terminal epithelial differentiation of CSCs or targeting some genes expressed only in CSCs and involved in self-renewal and chemoresistance. Ideal targets could be cell regulators that simultaneously control the stemness and the resistance of CSCs. Another important aspect of cancer biology, which can also be harnessed to create novel broad-spectrum anticancer agents, is the Warburg effect, also known as aerobic glycolysis. Actually, little is yet known with regard to the metabolism of CSCs population, leaving an exciting unstudied avenue in the dawn of the emerging field of metabolomics. PMID:24527460

  8. Scalable Production of Glioblastoma Tumor-initiating Cells in 3 Dimension Thermoreversible Hydrogels

    PubMed Central

    Li, Qiang; Lin, Haishuang; Wang, Ou; Qiu, Xuefeng; Kidambi, Srivatsan; Deleyrolle, Loic P.; Reynolds, Brent A.; Lei, Yuguo

    2016-01-01

    There is growing interest in developing drugs that specifically target glioblastoma tumor-initiating cells (TICs). Current cell culture methods, however, cannot cost-effectively produce the large numbers of glioblastoma TICs required for drug discovery and development. In this paper we report a new method that encapsulates patient-derived primary glioblastoma TICs and grows them in 3 dimension thermoreversible hydrogels. Our method allows long-term culture (~50 days, 10 passages tested, accumulative ~>1010-fold expansion) with both high growth rate (~20-fold expansion/7 days) and high volumetric yield (~2.0 × 107 cells/ml) without the loss of stemness. The scalable method can be used to produce sufficient, affordable glioblastoma TICs for drug discovery. PMID:27549983

  9. Integrin-fibronectin interactions at the cell-material interface: initial integrin binding and signaling.

    PubMed

    García, A J; Boettiger, D

    1999-12-01

    Integrin receptors mediate cell adhesion to extracellular matrices and provide signals that direct proliferation and differentiation. Integrin binding involves receptor-ligand interactions at the cell-substrate interface and assembly and reorganization of structural and signaling elements at the cytoplasmic face. Using a cross-linking/extraction/reversal method to quantify bound integrins, we demonstrate that the density of alpha5beta1 integrin-fibronectin bonds increases linearly with ligand density, as predicted by simple receptor-ligand equilibrium. This linear relationship is consistent with linear increases in cell adhesion strength with receptor and ligand surface densities. Furthermore, we show that phosphorylation of FAK, a tyrosine kinase involved in early integrin-mediated signaling, increases linearly with the number of integrin-Fn bonds. These linear relationships suggest the absence of cooperative effects in the initial stages of mechanical coupling and adhesion-mediated signaling. PMID:10614947

  10. Scalable Production of Glioblastoma Tumor-initiating Cells in 3 Dimension Thermoreversible Hydrogels.

    PubMed

    Li, Qiang; Lin, Haishuang; Wang, Ou; Qiu, Xuefeng; Kidambi, Srivatsan; Deleyrolle, Loic P; Reynolds, Brent A; Lei, Yuguo

    2016-01-01

    There is growing interest in developing drugs that specifically target glioblastoma tumor-initiating cells (TICs). Current cell culture methods, however, cannot cost-effectively produce the large numbers of glioblastoma TICs required for drug discovery and development. In this paper we report a new method that encapsulates patient-derived primary glioblastoma TICs and grows them in 3 dimension thermoreversible hydrogels. Our method allows long-term culture (~50 days, 10 passages tested, accumulative ~>10(10)-fold expansion) with both high growth rate (~20-fold expansion/7 days) and high volumetric yield (~2.0 × 10(7) cells/ml) without the loss of stemness. The scalable method can be used to produce sufficient, affordable glioblastoma TICs for drug discovery. PMID:27549983

  11. Conditions for initiating Lake Victoria haplochromine (Oreochromis esculentus) primary cell cultures from caudal fin biopsies.

    PubMed

    Filice, Melissa; Lee, C; Mastromonaco, Gabriela F

    2014-10-01

    The global decline of freshwater fishes has created a need to cryopreserve biological materials from endangered species in an effort to conserve the biodiversity within this taxon. Since maternal gametes and embryos from fish are difficult to cryopreserve, somatic cells obtained from caudal fins have become an increasingly popular resource as they contain both maternal and paternal DNA ensuring valuable traits are not lost from the population. Somatic cells stored in cryobanks can be used to supplement endangered populations with genetically valuable offspring with the use of assisted reproductive technologies. However, initiating primary cell cultures from caudal fin biopsies of endangered species can be challenging as standardized protocols have not yet been developed. The objective of this study was to identify culture conditions, including antibiotic supplementation, biopsy size, and culture temperature, suitable for establishing primary cell cultures of ngege (Oreochromis esculentus), a critically endangered African cichlid. Six-millimeter caudal fin biopsies provided sufficient material to develop a primary cell culture when incubated at 25°C using standard fish cell culture medium containing 1× Primocin. Further investigation and application of these culture conditions for other endangered freshwater fishes is necessary. PMID:24985486

  12. Comparative Analysis of Media and Supplements on Initiation and Expansion of Adipose-Derived Stem Cells.

    PubMed

    Riis, Simone; Nielsen, Frederik Mølgaard; Pennisi, Cristian Pablo; Zachar, Vladimir; Fink, Trine

    2016-03-01

    Adipose-derived stem cells (ASCs) are being tested in clinical trials related to cell-based regenerative therapies. Although most of the current expansion protocols for ASCs use fetal calf serum (FCS), xenogeneic-free medium supplements are greatly desired. This study aims to compare the effect of FCS, human platelet lysate (hPL), and a fully defined medium on the initiation and maintenance of ASC cultures. ASCs obtained from five donors were cultured in five different media: StemPro, Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% hPL, or α-minimum essential medium (A-MEM) supplemented with 5% hPL, 10% hPL, or 10% FCS. The effect of media on proliferation, colony-forming units (CFUs), attachment, and morphology was assessed along with cell size, granularity, and immunophenotype. StemPro greatly compromised the initiation of ASC cultures, which could not survive more than a few passages. Cells cultured in A-MEM proliferated at a faster rate than in DMEM, and hPL significantly enhanced cell size, granularity, and proliferation compared with FCS. All media except StemPro supported CFUs equally well. Analysis of surface markers revealed higher levels of CD73 and CD105 in FCS-cultured ASCs, whereas increased levels of CD146 were found in hPL-cultured cells. Multiparametric flow cytometric analysis performed after seven passages revealed the existence of four distinct ASC subpopulations, all positive for CD73, CD90, and CD105, which mainly differed by their expression of CD146 and CD271. Analysis of the different subpopulations might represent an important biological measure when assessing different medium formulations for a particular clinical application. PMID:26838270

  13. The matricellular protein CCN6 (WISP3) decreases Notch1 and suppresses breast cancer initiating cells.

    PubMed

    Huang, Wei; Martin, Emily E; Burman, Boris; Gonzalez, Maria E; Kleer, Celina G

    2016-05-01

    Increasing evidence supports that the epithelial to mesenchymal transition (EMT) in breast cancer cells generates tumor initiating cells (TICs) but the contribution of the tumor microenvironment to these programs needs further elucidation. CCN6 (WISP3) is a secreted matrix-associated protein (36.9 kDa) of the CCN family (named after CTGF, Cyr61 and Nov) that is reduced or lost in invasive carcinomas of the breast with lymph node metastasis and in inflammatory breast cancer. CCN6 exerts breast cancer growth and invasion inhibitory functions, but the mechanisms remain to be defined. In the present study we discovered that ectopic CCN6 overexpression in triple negative (TN) breast cancer cells and in cells derived from patients is sufficient to induce a mesenchymal to epithelial transition (MET) and to reduce TICs. In vivo, CCN6 overexpression in the TIC population of MDA-MB-231 cells delayed tumor initiation, reduced tumor volume, and inhibited the development of metastasis. Our studies reveal a novel CCN6/Slug signaling axis that regulates Notch1 signaling activation, epithelial cell phenotype and breast TICs, which requires the conserved thrombospondin type 1 (TSP1) motif of CCN6. The relevance of these data to human breast cancer is highlighted by the finding that CCN6 protein levels are inversely correlated with Notch1 intracellular activated form (NICD1) in 69.5% of invasive breast carcinomas. These results demonstrate that CCN6 regulates epithelial and mesenchymal states transition and TIC programs, and pinpoint one responsible mechanism. PMID:26933820

  14. On-orbit spacecraft reliability

    NASA Technical Reports Server (NTRS)

    Bloomquist, C.; Demars, D.; Graham, W.; Henmi, P.

    1978-01-01

    Operational and historic data for 350 spacecraft from 52 U.S. space programs were analyzed for on-orbit reliability. Failure rates estimates are made for on-orbit operation of spacecraft subsystems, components, and piece parts, as well as estimates of failure probability for the same elements during launch. Confidence intervals for both parameters are also given. The results indicate that: (1) the success of spacecraft operation is only slightly affected by most reported incidents of anomalous behavior; (2) the occurrence of the majority of anomalous incidents could have been prevented piror to launch; (3) no detrimental effect of spacecraft dormancy is evident; (4) cycled components in general are not demonstrably less reliable than uncycled components; and (5) application of product assurance elements is conductive to spacecraft success.

  15. NOTCH Signaling Regulates Asymmetric Cell Fate of Fast- and Slow-Cycling Colon Cancer-Initiating Cells.

    PubMed

    Srinivasan, Tara; Walters, Jewell; Bu, Pengcheng; Than, Elaine Bich; Tung, Kuei-Ling; Chen, Kai-Yuan; Panarelli, Nicole; Milsom, Jeff; Augenlicht, Leonard; Lipkin, Steven M; Shen, Xiling

    2016-06-01

    Colorectal cancer cells with stem-like properties, referred to as colon cancer-initiating cells (CCIC), have high tumorigenic potential. While CCIC can differentiate to promote cellular heterogeneity, it remains unclear whether CCIC within a tumor contain distinct subpopulations. Here, we describe the co-existence of fast- and slow-cycling CCIC, which can undergo asymmetric division to generate each other, highlighting CCIC plasticity and interconvertibility. Fast-cycling CCIC express markers, such as LGR5 and CD133, rely on MYC for their proliferation, whereas slow-cycling CCIC express markers, such as BMI1 and hTERT, are independent of MYC. NOTCH signaling promotes asymmetric cell fate, regulating the balance between these two populations. Overall, our results illuminate the basis for CCIC heterogeneity and plasticity by defining a direct interconversion mechanism between slow- and fast-cycling CCIC. Cancer Res; 76(11); 3411-21. ©2016 AACR. PMID:27197180

  16. Fault tolerant control of spacecraft

    NASA Astrophysics Data System (ADS)

    Godard

    Autonomous multiple spacecraft formation flying space missions demand the development of reliable control systems to ensure rapid, accurate, and effective response to various attitude and formation reconfiguration commands. Keeping in mind the complexities involved in the technology development to enable spacecraft formation flying, this thesis presents the development and validation of a fault tolerant control algorithm that augments the AOCS on-board a spacecraft to ensure that these challenging formation flying missions will fly successfully. Taking inspiration from the existing theory of nonlinear control, a fault-tolerant control system for the RyePicoSat missions is designed to cope with actuator faults whilst maintaining the desirable degree of overall stability and performance. Autonomous fault tolerant adaptive control scheme for spacecraft equipped with redundant actuators and robust control of spacecraft in underactuated configuration, represent the two central themes of this thesis. The developed algorithms are validated using a hardware-in-the-loop simulation. A reaction wheel testbed is used to validate the proposed fault tolerant attitude control scheme. A spacecraft formation flying experimental testbed is used to verify the performance of the proposed robust control scheme for underactuated spacecraft configurations. The proposed underactuated formation flying concept leads to more than 60% savings in fuel consumption when compared to a fully actuated spacecraft formation configuration. We also developed a novel attitude control methodology that requires only a single thruster to stabilize three axis attitude and angular velocity components of a spacecraft. Numerical simulations and hardware-in-the-loop experimental results along with rigorous analytical stability analysis shows that the proposed methodology will greatly enhance the reliability of the spacecraft, while allowing for potentially significant overall mission cost reduction.

  17. Novel Material for Future Spacecrafts

    NASA Technical Reports Server (NTRS)

    Sen, Subbayu; Cothran, Ernestine

    2005-01-01

    Outside earth's protective magnetosphere crew members and sensitive equipment need to be protected against two primary radiation sources, namely Galactic Cosmic Rays (GCR) and Solar Energetic Particles (SEP). For planetary missions, this combination of radiation particles could result in doses that are higher than the allowable level currently permitted for low-earth orbit manned missions. This SBIR project aims to develop a multifunctional and lightweight composite material that not only provides sufficient radiation shielding but also provides sufficient structural integrity to be considered as a spacecraft material. This presentation will discuss the deep space radiation problem and the material based solutions being proposed by BAE SYS scientists to overcome this problem. The presentation will focus on the initiative taken by BAE SYS scientists to proactively engage and team with experts at NASA, small business, and other federal laboratories to develop and test a dual phase composite material. The presentation will also highlight the potential benefits to our customer, NASA and also to BAE SYS.

  18. Low-Temperature Spacecraft: Challenges/Opportunities

    NASA Astrophysics Data System (ADS)

    Dickman, J. E.; Patterson, R. L.; Overton, E.; Hammoud, A. N.; Gerber, S. S.

    2001-01-01

    Imagine sending a spacecraft into deep space that operates at the ambient temperature of its environment rather than hundreds of degrees Kelvin warmer. The average temperature of a spacecraft warmed only by the sun drops from 279 K near the Earth's orbit to 90 K near the orbit of Saturn, and to 44 K near Pluto's orbit. At present, deep space probes struggle to maintain an operating temperature near 300 K for the onboard electronics. To warm the electronics without consuming vast amounts of electrical energy, radioisotope heater units (RHUs) are used in vast numbers. Unfortunately, since RHU are always 'on', an active thermal management system is required to reject the excess heat. A spacecraft designed to operate at cryogenic temperatures and shielded from the sun by a large communication dish or solar cell array could be less complex, lighter, and cheaper than current deep space probes. Before a complete low-temperature spacecraft becomes a reality, there are several challenges to be met. Reliable cryogenic power electronics is one of the major challenges. The Low-Temperature Power Electronics Research Group at NASA Glenn Research Center (GRC) has demonstrated the ability of some commercial off the shelf power electronic components to operate at temperatures approaching that of liquid nitrogen (77 K). Below 77 K, there exists an opportunity for the development of reliable semiconductor power switching technologies other than bulk silicon CMOS. This paper will report on the results of NASA GRC's Low-Temperature Power Electronics Program and discuss the challenges to (opportunities for) the creation of a low-temperature spacecraft.

  19. Spatial-Temporal Patterns of Viral Amplification and Interference Initiated by a Single Infected Cell

    PubMed Central

    Akpinar, Fulya; Inankur, Bahar

    2016-01-01

    ABSTRACT When viruses infect their host cells, they can make defective virus-like particles along with intact virus. Cells coinfected with virus and defective particles often exhibit interference with virus growth caused by the competition for resources by defective genomes. Recent reports of the coexistence and cotransmission of such defective interfering particles (DIPs) in vivo, across epidemiological length and time scales, suggest a role in viral pathogenesis, but it is not known how DIPs impact infection spread, even under controlled culture conditions. Using fluorescence microscopy, we quantified coinfections of vesicular stomatitis virus (VSV) expressing a fluorescent reporter protein and its DIPs on BHK-21 host cell monolayers. We found that viral gene expression was more delayed, infections spread more slowly, and patterns of spread became more “patchy” with higher DIP inputs to the initial cell. To examine how infection spread might depend on the behavior of the initial coinfected cell, we built a computational model, adapting a cellular automaton (CA) approach to incorporate kinetic data on virus growth for the first time. Specifically, changes in observed patterns of infection spread could be directly linked to previous high-throughput single-cell measures of virus-DIP coinfection. The CA model also provided testable hypotheses on the spatial-temporal distribution of the DIPs, which remain governed by their predator-prey interaction. More generally, this work offers a data-driven computational modeling approach for better understanding of how single infected cells impact the multiround spread of virus infections across cell populations. IMPORTANCE Defective interfering particles (DIPs) compete with intact virus, depleting host cell resources that are essential for virus growth and infection spread. However, it is not known how such competition, strong or weak, ultimately affects the way in which infections spread and cause disease. In this study

  20. Cobblestone-Area Forming Cells Derived from Patients with Mantle Cell Lymphoma Are Enriched for CD133+ Tumor-Initiating Cells

    PubMed Central

    Medina, Daniel J.; Abass-Shereef, Jeneba; Walton, Kelly; Goodell, Lauri; Aviv, Hana; Strair, Roger K.; Budak-Alpdogan, Tulin

    2014-01-01

    Mantle cell lymphoma (MCL) is associated with a significant risk of therapeutic failure and disease relapse, but the biological origin of relapse is poorly understood. Here, we prospectively identify subpopulations of primary MCL cells with different biologic and immunophenotypic features. Using a simple culture system, we demonstrate that a subset of primary MCL cells co-cultured with either primary human mesenchymal stromal cells (hMSC) or murine MS-5 cells form in cobblestone-areas consisting of cells with a primitive immunophenotype (CD19−CD133+) containing the chromosomal translocation t (11;14)(q13;q32) characteristic of MCL. Limiting dilution serial transplantation experiments utilizing immunodeficient mice revealed that primary MCL engraftment was only observed when either unsorted or CD19−CD133+ cells were utilized. No engraftment was seen using the CD19+CD133− subpopulation. Our results establish that primary CD19−CD133+ MCL cells are a functionally distinct subpopulation of primary MCL cells enriched for MCL-initiating activity in immunodeficient mice. This rare subpopulation of MCL-initiating cells may play an important role in the pathogenesis of MCL. PMID:24722054

  1. Inter-polysomal coupling of termination and initiation during translation in eukaryotic cell-free system

    PubMed Central

    Sogorin, Evgeny A.; Agalarov, Sultan Ch.; Spirin, Alexander S.

    2016-01-01

    The recording of the luciferase-generated luminescence in the eukaryotic cell-free translation system programmed with mRNA encoding firefly luciferase (Luc-mRNA) showed that the addition of free exogenous mRNAs into the translation reactor induces the immediate release of the functionally active protein from the polyribosomes of the translation system. The phenomenon did not depend on the coding specificity of the added free mRNA. At the same time it depended on the “initiation potential” of the added mRNA (including the features that ensure the successful initiation of translation, such as the presence of the cap structure and the sufficient concentration of the added mRNA in the translation mixture). The phenomenon also strictly depended on the presence of the stop codon in the translated mRNA. As the above-mentioned features of the added mRNA imply its activity in initiation of a new translation, the experimental data are found in agreement with the scenario where the molecules of the added mRNA interact by their 5′-ends with terminating and recycling ribosomes, stimulating the release of the complete polypeptides and providing for the initiation of a new translation. PMID:27075299

  2. Inter-polysomal coupling of termination and initiation during translation in eukaryotic cell-free system.

    PubMed

    Sogorin, Evgeny A; Agalarov, Sultan Ch; Spirin, Alexander S

    2016-01-01

    The recording of the luciferase-generated luminescence in the eukaryotic cell-free translation system programmed with mRNA encoding firefly luciferase (Luc-mRNA) showed that the addition of free exogenous mRNAs into the translation reactor induces the immediate release of the functionally active protein from the polyribosomes of the translation system. The phenomenon did not depend on the coding specificity of the added free mRNA. At the same time it depended on the "initiation potential" of the added mRNA (including the features that ensure the successful initiation of translation, such as the presence of the cap structure and the sufficient concentration of the added mRNA in the translation mixture). The phenomenon also strictly depended on the presence of the stop codon in the translated mRNA. As the above-mentioned features of the added mRNA imply its activity in initiation of a new translation, the experimental data are found in agreement with the scenario where the molecules of the added mRNA interact by their 5'-ends with terminating and recycling ribosomes, stimulating the release of the complete polypeptides and providing for the initiation of a new translation. PMID:27075299

  3. Multi-Spacecraft Modeling of the Topological Evolution of ICMEs

    NASA Astrophysics Data System (ADS)

    Liu, Y.; Richardson, J. D.; Kasper, J. C.; Belcher, J. W.; Hu, Q.

    2005-12-01

    Plasma and magnetic field data from the Helios and Voyager spacecraft are used to investigate the 3D structure of ICMEs. Helios 1 and 2 remained fairly near to each other in the inner heliosphere between 1978 and 1982, while Voyagers 1 and 2 followed each other through the heliosphere out to 10 AU. This period was active in terms of ICME frequency, with about 50 ICMEs observed by the Helios spacecraft and 70 by the Voyagers. If both spacecraft observe the same ICME, we can set lower limits to the longitudinal and azimuthal extents of the event; upper limits can be obtained if an ICME is seen at one spacecraft but missed at the other. The radial variations and sizes of ICMEs can also be obtained as ICMEs pass the spacecraft radially. On a statistical basis, we determine the longitudinal separation and the cross section (radial width plus perpendicular size) of ICMEs. The cross section of the ICMEs deduced above is compared to the numerical solution of the Grad-Shafranov equation fed with 1D observations of the plasma and magnetic field as spatial initial values. The Grad-Shafranov reconstruction of the cross section is tested using multi-spacecraft data since two spacecraft give radial profiles through different parts of an ICME. The association between shock waves and sheath regions of ICMEs will be also investigated.

  4. Phosphoproteome of Human Glioblastoma Initiating Cells Reveals Novel Signaling Regulators Encoded by the Transcriptome

    PubMed Central

    Kozuka-Hata, Hiroko; Nasu-Nishimura, Yukiko; Koyama-Nasu, Ryo; Ao-Kondo, Hiroko; Tsumoto, Kouhei; Akiyama, Tetsu; Oyama, Masaaki

    2012-01-01

    Background Glioblastoma is one of the most aggressive tumors with poor prognosis. Although various studies have been performed so far, there are not effective treatments for patients with glioblastoma. Methodology/Principal Findings In order to systematically elucidate the aberrant signaling machinery activated in this malignant brain tumor, we investigated phosphoproteome dynamics of glioblastoma initiating cells using high-resolution nanoflow LC-MS/MS system in combination with SILAC technology. Through phosphopeptide enrichment by titanium dioxide beads, a total of 6,073 phosphopeptides from 2,282 phosphorylated proteins were identified based on the two peptide fragmentation methodologies of collision induced dissociation and higher-energy C-trap dissociation. The SILAC-based quantification described 516 up-regulated and 275 down-regulated phosphorylation sites upon epidermal growth factor stimulation, including the comprehensive status of the phosphorylation sites on stem cell markers such as nestin. Very intriguingly, our in-depth phosphoproteome analysis led to identification of novel phosphorylated molecules encoded by the undefined sequence regions of the human transcripts, one of which was regulated upon external stimulation in human glioblastoma initiating cells. Conclusions/Significance Our result unveils an expanded diversity of the regulatory phosphoproteome defined by the human transcriptome. PMID:22912867

  5. Microtubule plus end–associated CLIP-170 initiates HSV-1 retrograde transport in primary human cells

    PubMed Central

    Jovasevic, Vladimir

    2015-01-01

    Dynamic microtubules (MTs) continuously explore the intracellular environment and, through specialized plus end–tracking proteins (+TIPs), engage a variety of targets. However, the nature of cargoes that require +TIP-mediated capture for their movement on MTs remains poorly understood. Using RNA interference and dominant-negative approaches, combined with live cell imaging, we show that herpes simplex virus particles that have entered primary human cells exploit a +TIP complex comprising end-binding protein 1 (EB1), cytoplasmic linker protein 170 (CLIP-170), and dynactin-1 (DCTN1) to initiate retrograde transport. Depletion of these +TIPs completely blocked post-entry long-range transport of virus particles and suppressed infection ∼5,000-fold, whereas transferrin uptake, early endosome organization, and dynein-dependent movement of lysosomes and mitochondria remained unaffected. These findings provide the first insights into the earliest stages of viral engagement of MTs through specific +TIPs, akin to receptors, with therapeutic implications, and identify herpesvirus particles as one of a very limited number of cargoes absolutely dependent on CLIP-170–mediated capture to initiate transport in primary human cells. PMID:26504169

  6. Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion

    PubMed Central

    Yamamoto, Yusuke; Wang, Xia; Bertrand, Denis; Kern, Florian; Zhang, Ting; Duleba, Marcin; Srivastava, Supriya; Khor, Chiea Chuen; Hu, Yuanyu; Wilson, Lane H.; Blaszyk, Hagen; Rolshud, Daniil; Teh, Ming; Liu, Jianjun; Howitt, Brooke E.; Vincent, Matthew; Crum, Christopher P.; Nagarajan, Niranjan; Ho, Khek Yu; McKeon, Frank; Xian, Wa

    2016-01-01

    The precancerous lesion known as Barrett's oesophagus can evolve to oesophageal adenocarcinoma in decades-long processes of regenerative growth. Here we report the isolation and propagation of distinct, patient-matched stem cells of Barrett's, gastric and oesophageal epithelia that yield divergent tumour types following in vitro transformation and xenografting. Genomic analyses reveal a broad mutational spectrum unique to Barrett's stem cells that likely reflects their risk for oncogenesis. Remarkably, 25% of cases show no cancer-related genomic changes, suggesting that Barrett's initiates without driver mutations. Most cases, however, sustain patterns of deletions almost identical to adenocarcinoma though tumour-associated gene amplifications were absent. Notably, those suspected of low-grade dysplasia have p53 mutations or undergo amplifications of proto-oncogenes and receptor tyrosine kinases, implicating these events in lethal transitions. Our findings suggest paths for the initiation and progression of Barrett's and define a discrete stem cell underlying its regenerative growth whose eradication could prevent oesophageal adenocarcinoma. PMID:26783136

  7. Constraints on plate tectonics initiation from scaling laws for single-cell convection

    NASA Astrophysics Data System (ADS)

    Wong, Teresa; Solomatov, Viatcheslav S.

    2016-08-01

    The Earth is the only planet known to have plate tectonics, while other planets are covered with a stagnant lid. On the Earth, the initiation of subduction, which is thought to be the fundamental process for plate tectonics initiation, is caused not only by the negative buoyancy of the lithosphere but also by the forces from plate motions. However, for planets which do not have plate tectonics, the very first episode of lithospheric failure has to be caused by forces other than plate motions. Sublithospheric convection has been proposed as a possible mechanism that provides lithospheric instability through inducing stresses in the lithosphere, and lithospheric failure can occur when the yield stress is below a critical value. We test the applicability of scaling laws for the critical yield stress obtained in single-cell convection simulations to strongly time-dependent multi-cell systems. We show that with an appropriate choice of characteristic aspect ratio for the convective system, the scaling laws from single-cell simulations can be used to evaluate the conditions on the terrestrial planets in the inner Solar System for plate tectonics to exist. In agreement with previous studies, the estimated values for critical yield stress and coefficient of friction are much lower than the expected values for the Earth's lithosphere.

  8. N-Acetylcysteine blocks formation of cancer-initiating estrogen-DNA adducts in cells

    PubMed Central

    Zahid, Muhammad; Saeed, Muhammad; Ali, Mohammed F.; Rogan, Eleanor G.; Cavalieri, Ercole L.

    2010-01-01

    Catechol estrogens, especially 4-hydroxylated metabolites of 17β-estradiol (E2), are responsible for estrogen-induced carcinogenesis. 4-Hydroxyestradiol (4-OHE2), a major metabolite of E2 formed preferentially by cytochrome P-450 1B1, is oxidized to E2-3,4-quinone, which can react with DNA to yield the depurinating adducts 4-OHE2-1-N3Ade and 4-OHE2-1-N7Gua. The apurinic sites generated by the loss of these depurinating adducts induce mutations that could lead to cancer initiation. In the present study, we have evaluated the effects of N-acetycysteine (NAcCys) on the metabolism of two cell lines, MCF-10F (a normal human breast epithelial cell line) and E6 (a normal mouse mammary epithelial cell line), treated with 4-OHE2 or its reactive metabolite, E2-3,4-quinone. Extensive HPLC with electrochemical detection and UPLC-MS/MS analyses of the cell media demonstrated that the presence of NAcCys very efficiently shifted the estrogen metabolism towards protective methoxylation and conjugation pathways in multiple ways, while formation of depurinating DNA adducts was inhibited. Protection by NAcCys appears to be similar in both cell lines irrespective of their origin (human or mouse) or the presence of estrogen receptor-alpha. This finding suggests that NAcCys, a common dietary supplement, could be used as a potential chemopreventive agent to block the initial step in the genotoxicity caused by catechol estrogen quinones. PMID:20472053

  9. The Hughes HS601HP spacecraft power subsystem

    SciTech Connect

    Krummann, W.; Ayvazian, H.

    1998-07-01

    The introduction of the Hughes HS 601HP (high power) spacecraft product line continuous the highly successful HS601 three axis stabilized geosynchronus spacecraft with increased power capabilities for larger payload applications. The enhanced power capabilities of the HS 601HP are built upon the heritage of 29 HS601 spacecraft presently in operation. The HS 601HP accommodates payload power ranges of 3 to 7 kilowatts and provides a smooth transition from the lower power HS 601 spacecraft to the HS 702 spacecraft, which has a payload capability up to 13 kilowatts. The HS 601HP spacecraft is designed for a 15 year life with minimal operator interaction. The HS 601HP power subsystem provides a regulated power bus with a voltage range of 52 to 53 volts during all operational phases. The power subsystem is tailored to the specific needs of the spacecraft by selecting standard products from the HS 601HP power catalog. The solar arrays, battery, power control electronics and power distribution electronics are all modular and configurable to the requirements of the spacecraft. The HS 601HP solar array is the primary power source for the spacecraft. The solar array is comprised of two sets of planar solar panels (solar wings) which track the sun in a single spacecraft axis. The solar cells are selected from three different types based upon the spacecraft power generation requirements; silicon, single junction gallium arsenide or dual junction gallium arsenide. The maximum power capability at end of life (15 years, summer solstice) ranges from 4 to 7.7 kilowatts for the three types of solar cells. The HS 601HP battery is the power source for the spacecraft during eclipse and peak sunlight power periods. The battery is comprised of four individual battery packs connected in series to produce a single battery. Each battery pack can accommodate a maximum of eight battery cells with a capacity of 350 ampere-hours. The battery pack also provides for mounting of all electronics

  10. Plasma Cell Neoplasm Manifesting Initially as a Sub-Cutaneous Supra-Orbital Swelling.

    PubMed

    Jaiswal, Riddhi; Agarwal, Garima; Singh, Sudhir

    2016-01-01

    Multiple myeloma is a plasma cell neoplasm seen usually in patients over 50 years of age. Some cases may be asymptomatic initially and are detected during a routine test like complete blood count. They only require a close follow-up and monitoring. However, around 1% of these monoclonal gammopathy of undetermined significance progress to multiple myeloma every year and then they need to be taken care of by chemotherapy, targeted therapy, bisphosphonates and 6 monthly urine and bone examinations. Here, we present a case of 35-year-old female with an initial symptom of a vague backache along with a left subcutaneous supra-orbital swelling which was diagnosed as multiple myeloma by aspiration cytology and confirmed by ancillary tests. She has since been on treatment with bortezomib and prednisone and is responding well. PMID:26955130

  11. Plasma Cell Neoplasm Manifesting Initially as a Sub-Cutaneous Supra-Orbital Swelling

    PubMed Central

    Jaiswal, Riddhi; Agarwal, Garima; Singh, Sudhir

    2016-01-01

    Multiple myeloma is a plasma cell neoplasm seen usually in patients over 50 years of age. Some cases may be asymptomatic initially and are detected during a routine test like complete blood count. They only require a close follow-up and monitoring. However, around 1% of these monoclonal gammopathy of undetermined significance progress to multiple myeloma every year and then they need to be taken care of by chemotherapy, targeted therapy, bisphosphonates and 6 monthly urine and bone examinations. Here, we present a case of 35-year-old female with an initial symptom of a vague backache along with a left subcutaneous supra-orbital swelling which was diagnosed as multiple myeloma by aspiration cytology and confirmed by ancillary tests. She has since been on treatment with bortezomib and prednisone and is responding well. PMID:26955130

  12. Substrate-Initiated Synthesis of Cell-Penetrating Poly(disulfide)s

    PubMed Central

    Molinard, Guillaume; Roux, Aurélien; Sakai, Naomi; Matile, Stefan

    2015-01-01

    Lessons from surface-initiated polymerization are applied to grow cell-penetrating poly(disulfide)s directly on substrates of free choice. Reductive depolymerization after cellular uptake should then release the native substrates and minimize toxicity. In the presence of thiolated substrates, propagators containing a strained disulfide from asparagusic or, preferably, lipoic acid and a guanidinium cation polymerize into poly(disulfide)s in less than 5 min at room temperature at pH 7. Substrate-initiated polymerization of cationic poly(disulfide)s and their depolymerization with dithiothreitol causes the appearance and disappearance of transport activity in fluorogenic vesicles. The same process is further characterized by gel-permeation chromatography and fluorescence resonance energy transfer. PMID:23363440

  13. Obstructive jaundice at the initial presentation in small-cell lung cancer

    PubMed Central

    Ochi, Nobuaki; Takigawa, Nagio; Yasugi, Masayuki; Ishida, Etsuji; Kawamoto, Hirofumi; Taniguchi, Akihiko; Harada, Daijiro; Hayashi, Eiko; Toda, Hiroko; Yanai, Hiroyuki; Tanimoto, Mitsune; Kiura, Katsuyuki

    2010-01-01

    Obstructive jaundice sometimes may develop in association with advanced small-cell lung cancer (SCLC); however, SCLC initially presenting with obstructive jaundice is rare. This report presents the cases of two SCLC patients with obstructive jaundice at the initial diagnosis. A 64-year-old male presented with obstructive jaundice due to a tumor at the head of the pancreas. He was diagnosed with SCLC by transbronchial biopsy from a lung tumor in the left upper lobe. Another 74-year-old male was admitted with jaundice due to a tumor in the porta hepatis. He was also diagnosed with SCLC by a fine-needle aspiration biopsy of a lung tumor in the left lower lobe. Both cases were successfully treated with systemic chemotherapy after endoscopic retrograde biliary drainage. PMID:23754881

  14. Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells

    PubMed Central

    Celià-Terrassa, Toni; Meca-Cortés, Óscar; Mateo, Francesca; Martínez de Paz, Alexia; Rubio, Nuria; Arnal-Estapé, Anna; Ell, Brian J.; Bermudo, Raquel; Díaz, Alba; Guerra-Rebollo, Marta; Lozano, Juan José; Estarás, Conchi; Ulloa, Catalina; ρlvarez-Simón, Daniel; Milà, Jordi; Vilella, Ramón; Paciucci, Rosanna; Martínez-Balbás, Marian; García de Herreros, Antonio; Gomis, Roger R.; Kang, Yibin; Blanco, Jerónimo; Fernández, Pedro L.; Thomson, Timothy M.

    2012-01-01

    Malignant progression in cancer requires populations of tumor-initiating cells (TICs) endowed with unlimited self renewal, survival under stress, and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by epithelial-mesenchymal transition (EMT) is critical for the evolution of neoplastic cells into fully metastatic populations. Here, we characterize 2 human cellular models derived from prostate and bladder cancer cell lines to better understand the relationship between TIC and EMT programs in local invasiveness and distant metastasis. The model tumor subpopulations that expressed a strong epithelial gene program were enriched in highly metastatic TICs, while a second subpopulation with stable mesenchymal traits was impoverished in TICs. Constitutive overexpression of the transcription factor Snai1 in the epithelial/TIC-enriched populations engaged a mesenchymal gene program and suppressed their self renewal and metastatic phenotypes. Conversely, knockdown of EMT factors in the mesenchymal-like prostate cancer cell subpopulation caused a gain in epithelial features and properties of TICs. Both tumor cell subpopulations cooperated so that the nonmetastatic mesenchymal-like prostate cancer subpopulation enhanced the in vitro invasiveness of the metastatic epithelial subpopulation and, in vivo, promoted the escape of the latter from primary implantation sites and accelerated their metastatic colonization. Our models provide new insights into how dynamic interactions among epithelial, self-renewal, and mesenchymal gene programs determine the plasticity of epithelial TICs. PMID:22505459

  15. The effects of telomerase inhibition on prostate tumor-initiating cells.

    PubMed

    Marian, Calin O; Wright, Woodring E; Shay, Jerry W

    2010-07-15

    Prostate cancer is the most common malignancy in men, and patients with metastatic disease have poor outcome even with the most advanced therapeutic approaches. Most cancer therapies target the bulk tumor cells, but may leave intact a small population of tumor-initiating cells (TICs), which are believed to be responsible for the subsequent relapse and metastasis. Using specific surface markers (CD44, integrin alpha(2)beta(1) and CD133), Hoechst 33342 dye exclusion, and holoclone formation, we isolated TICs from a panel of prostate cancer cell lines (DU145, C4-2 and LNCaP). We have found that prostate TICs have significant telomerase activity which is inhibited by imetelstat sodium (GRN163L), a new telomerase antagonist that is currently in Phase I/II clinical trials for several hematological and solid tumor malignancies. Prostate TICs telomeres were of similar average length to the telomeres of the main population of cells and significant telomere shortening was detected in prostate TICs as a result of imetelstat treatment. These findings suggest that telomerase inhibition therapy may be able to efficiently target the prostate TICs in addition to the bulk tumor cells, providing new opportunities for combination therapies. PMID:19908230

  16. Accurate initiation by RNA polymerase II in a whole cell extract from Saccharomyces cerevisiae.

    PubMed

    Woontner, M; Jaehning, J A

    1990-06-01

    We have developed a simple procedure for isolating a transcriptional extract from whole yeast cells which obviates the requirement for nuclear isolation. Detection of accurate mRNA initiation by RNA polymerase II in the extract requires the use of a sensitive assay, recently described by Kornberg and co-workers (Lue, N. F., Flanagan, P. M., Sugimoto, K., and Kornberg, R. D. (1989) Science 246, 661-664) that involves activation by a GAL4-VP16 fusion protein and a template lacking guanosine residues in the coding strand. The extract is prepared from fresh or frozen yeast cells by disruption with glass beads and fractionation of proteins by ammonium sulfate precipitation. The alpha-amanitin-sensitive transcripts synthesized in the assay were identical to those produced in a parallel assay using a yeast nuclear extract. The activity of the whole cell extract is lower per mg of protein than a nuclear extract but proportional to the volume of the nucleus relative to the whole cell. The optimal ranges for several reaction components including template, mono- and divalent cations, and nucleotide substrate concentration were determined. Under optimal conditions the whole cell extract produced a maximum of approximately 1 X 10(-2) transcripts/template molecule in 30 min. PMID:2188968

  17. Stress-associated erythropoiesis initiation is regulated by type 1 conventional dendritic cells.

    PubMed

    Kim, Taeg S; Hanak, Mark; Trampont, Paul C; Braciale, Thomas J

    2015-10-01

    Erythropoiesis is an important response to certain types of stress, including hypoxia, hemorrhage, bone marrow suppression, and anemia, that result in inadequate tissue oxygenation. This stress-induced erythropoiesis is distinct from basal red blood cell generation; however, neither the cellular nor the molecular factors that regulate this process are fully understood. Here, we report that type 1 conventional dendritic cells (cDC1s), which are defined by expression of CD8α in the mouse and XCR1 and CLEC9 in humans, are critical for induction of erythropoiesis in response to stress. Specifically, using murine models, we determined that engagement of a stress sensor, CD24, on cDC1s upregulates expression of the Kit ligand stem cell factor on these cells. The increased expression of stem cell factor resulted in Kit-mediated proliferative expansion of early erythroid progenitors and, ultimately, transient reticulocytosis in the circulation. Moreover, this stress response was triggered in part by alarmin recognition and was blunted in CD24 sensor- and CD8α+ DC-deficient animals. The contribution of the cDC1 subset to the initiation of stress erythropoiesis was distinct from the well-recognized role of macrophages in supporting late erythroid maturation. Together, these findings offer insight into the mechanism of stress erythropoiesis and into disorders of erythrocyte generation associated with stress. PMID:26389678

  18. Chemical Screening Identifies EUrd as a Novel Inhibitor Against Temozolomide-Resistant Glioblastoma-Initiating Cells.

    PubMed

    Tsukamoto, Yoshihiro; Ohtsu, Naoki; Echizenya, Smile; Otsuguro, Satoko; Ogura, Ryosuke; Natsumeda, Manabu; Isogawa, Mizuho; Aoki, Hiroshi; Ichikawa, Satoshi; Sakaitani, Masahiro; Matsuda, Akira; Maenaka, Katsumi; Fujii, Yukihiko; Kondo, Toru

    2016-08-01

    Glioblastoma (GBM), one of the most malignant human cancers, frequently recurs despite multimodal treatment with surgery and chemo/radiotherapies. GBM-initiating cells (GICs) are the likely cell-of-origin in recurrences, as they proliferate indefinitely, form tumors in vivo, and are resistant to chemo/radiotherapies. It is therefore crucial to find chemicals that specifically kill GICs. We established temozolomide (the standard medicine for GBM)-resistant GICs (GICRs) and used the cells for chemical screening. Here, we identified 1-(3-C-ethynyl-β-d-ribopentofuranosyl) uracil (EUrd) as a selective drug for targeting GICRs. EUrd induced the death in GICRs more effectively than their parental GICs, while it was less toxic to normal neural stem cells. We demonstrate that the cytotoxic effect of EUrd on GICRs partly depended on the increased expression of uridine-cytidine kinase-like 1 (UCKL1) and the decreased one of 5'-nucleotidase cytosolic III (NT5C3), which regulate uridine-monophosphate synthesis positively and negatively respectively. Together, these findings suggest that EUrd can be used as a new therapeutic drug for GBM with the expression of surrogate markers UCKL1 and NT5C3. Stem Cells 2016;34:2016-2025. PMID:27090194

  19. Nanoporous metals for biodegradable implants: Initial bone mesenchymal stem cell adhesion and degradation behavior.

    PubMed

    Heiden, Michael; Huang, Sabrina; Nauman, Eric; Johnson, David; Stanciu, Lia

    2016-07-01

    Nanostructured Fe-Mn and Fe-Mn-Zn metal scaffolds were generated through a well-controlled selective leaching process in order to fulfill the growing demand for adjustable degradation rates and improved cellular response of resorbable materials. Mouse bone marrow mesenchymal stem cells (D1 ORL UVA) were seeded onto eleven, carefully chosen nanoporous surfaces for 24 h in vitro. Using a combination of fluorescence microscopy, scanning electron microscopy (SEM), and an MTS assay, it was discovered that scaffolds with nanoscale roughened surfaces had increased cell attachment by up to 123% compared to polished smooth Fe-Mn surfaces. Significant cell spreading and construction of cell multilayers were also apparent after 24 h, suggesting better adhesion. Additionally, static electrochemical polarization experiments revealed an improvement of up to 26% in the actual rate of biodegradation for Fe-Mn surface-modified materials. However, any residual concentration of zinc after leaching was shown to slightly increase corrosion resistance. The results demonstrate that selectively leached, nanostructured Fe-Mn surfaces have the potential of being tailored to a diverse set of transient implant scenarios, while also effectively boosting overall biocompatibility, initial cell attachment, and degradation rate. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1747-1758, 2016. PMID:26990484

  20. [Effect of lidamycin on mitochondria initiated apoptotic pathway in human cancer cells].

    PubMed

    Qiu, Qiang; Wang, Zhen; Jiang, Jian-ming; Li, Dian-dong

    2007-02-01

    Although enediyne antibiotic lidamycin ( LDM) is a potent inducer of apoptosis, the underlying mechanisms of its apoptotic functions remain to be explored. Here, we aim to elucidate its possible mechanisms in mitochondria initiated apoptotic pathway involved in human BEL-7402 and MCF-7 cells. Cytochrome c released from mitchondria to cytosol fraction was detected by Western blotting. p53 and Bax, Bcl-2 expressions were detected by Western blotting and RT-PCR. MTT assay was used to detect cytotoxicity of LDM with or without caspase inhibitor z-VAD-fmk. After the BEL-7402 cells were exposed to 0. 1 micromol x L(-1) LDM within 6 h, the increase of cytochrome c in the cytosol and decrease in the mitochondria were observed when compared with untreated cells. The expression of Bax, an important proapoptotic member of the Bcl-2 family, increased gradually in the BEL-7402 cells after exposure to LDM of 0. 1 micromol x L (-1) for 2, 6, and 9 h, separately, while Bcl-2 increased at 2 and 6 h, and decreased at 9 h after LDM treatment. Enhanced protein expressions were parallel with respective increased mRNA level for Bax only, but not p53. Caspase inhibitor may inhibit partially the killing effects induced by LDM. Therefore we conclude that the rapid activation of mitochondrial pathway induced by LDM in tumor cells might contribute to its highly potent cytotoxicities. PMID:17518039

  1. A Cell-Autonomous Molecular Cascade Initiated by AMP-Activated Protein Kinase Represses Steroidogenesis

    PubMed Central

    Abdou, Houssein S.; Bergeron, Francis

    2014-01-01

    Steroid hormones regulate essential physiological processes, and inadequate levels are associated with various pathological conditions. In testosterone-producing Leydig cells, steroidogenesis is strongly stimulated by luteinizing hormone (LH) via its receptor leading to increased cyclic AMP (cAMP) production and expression of the steroidogenic acute regulatory (STAR) protein, which is essential for the initiation of steroidogenesis. Steroidogenesis then passively decreases with the degradation of cAMP into AMP by phosphodiesterases. In this study, we show that AMP-activated protein kinase (AMPK) is activated following cAMP-to-AMP breakdown in MA-10 and MLTC-1 Leydig cells. Activated AMPK then actively inhibits cAMP-induced steroidogenesis by repressing the expression of key regulators of steroidogenesis, including Star and Nr4a1. Similar results were obtained in Y-1 adrenal cells and in the constitutively steroidogenic R2C cells. We have also determined that maximum AMPK activation following stimulation of steroidogenesis in MA-10 Leydig cells occurs when steroid hormone production has reached a plateau. Our data identify AMPK as a molecular rheostat that actively represses steroid hormone biosynthesis to preserve cellular energy homeostasis and prevent excess steroid production. PMID:25225331

  2. Stress-associated erythropoiesis initiation is regulated by type 1 conventional dendritic cells

    PubMed Central

    Kim, Taeg S.; Hanak, Mark; Trampont, Paul C.; Braciale, Thomas J.

    2015-01-01

    Erythropoiesis is an important response to certain types of stress, including hypoxia, hemorrhage, bone marrow suppression, and anemia, that result in inadequate tissue oxygenation. This stress-induced erythropoiesis is distinct from basal red blood cell generation; however, neither the cellular nor the molecular factors that regulate this process are fully understood. Here, we report that type 1 conventional dendritic cells (cDC1s), which are defined by expression of CD8α in the mouse and XCR1 and CLEC9 in humans, are critical for induction of erythropoiesis in response to stress. Specifically, using murine models, we determined that engagement of a stress sensor, CD24, on cDC1s upregulates expression of the Kit ligand stem cell factor on these cells. The increased expression of stem cell factor resulted in Kit-mediated proliferative expansion of early erythroid progenitors and, ultimately, transient reticulocytosis in the circulation. Moreover, this stress response was triggered in part by alarmin recognition and was blunted in CD24 sensor– and CD8α+ DC-deficient animals. The contribution of the cDC1 subset to the initiation of stress erythropoiesis was distinct from the well-recognized role of macrophages in supporting late erythroid maturation. Together, these findings offer insight into the mechanism of stress erythropoiesis and into disorders of erythrocyte generation associated with stress. PMID:26389678

  3. GLAS Spacecraft Pointing Study

    NASA Technical Reports Server (NTRS)

    Born, George H.; Gold, Kenn; Ondrey, Michael; Kubitschek, Dan; Axelrad, Penina; Komjathy, Attila

    1998-01-01

    Science requirements for the GLAS mission demand that the laser altimeter be pointed to within 50 m of the location of the previous repeat ground track. The satellite will be flown in a repeat orbit of 182 days. Operationally, the required pointing information will be determined on the ground using the nominal ground track, to which pointing is desired, and the current propagated orbit of the satellite as inputs to the roll computation algorithm developed by CCAR. The roll profile will be used to generate a set of fit coefficients which can be uploaded on a daily basis and used by the on-board attitude control system. In addition, an algorithm has been developed for computation of the associated command quaternions which will be necessary when pointing at targets of opportunity. It may be desirable in the future to perform the roll calculation in an autonomous real-time mode on-board the spacecraft. GPS can provide near real-time tracking of the satellite, and the nominal ground track can be stored in the on-board computer. It will be necessary to choose the spacing of this nominal ground track to meet storage requirements in the on-board environment. Several methods for generating the roll profile from a sparse reference ground track are presented.

  4. Hydrazine monitoring in spacecraft

    NASA Technical Reports Server (NTRS)

    Cross, J. H.; Beck, S. W.; Limero, T. F.; James, J. T.

    1992-01-01

    Hydrazine (HZ) and monomethyl hydrazine (MMH) are highly toxic compounds used as fuels in the Space Shuttle Orbiter Main Engines and in its maneuvering and reaction control system. Satellite refueling during a mission may also result in release of hydrazines. During extravehicular activities, the potential exists for hydrazines to contaminate the suit and to be brought into the internal atmosphere inadvertantly. Because of the high toxicity of hydrazines, a very sensitive, reliable, interference-free, and real-time method of measurement is required. A portable ion mobility spectrometer (IMS) has exhibited a low ppb detection limit for hydrazines suggesting a promising technology for the detection of hydrazines in spacecraft air. The Hydrazine Monitor is a modified airborne vapor monitor (AVM) with a custom-built datalogger. This off-the-shelf IMS was developed for the detection of chemical warfare agents on the battlefield. After early evaluations of the AVM for hydrazine measurements showed a serious interference from ammonia, the AVM was modified to measure HZ and MMH in the ppb concentration range without interference from ammonia in the low ppm range. A description of the Hydrazine Monitor and how it functions is presented.

  5. Spacecraft Escape Capsule

    NASA Technical Reports Server (NTRS)

    Robertson, Edward A.; Charles, Dingell W.; Bufkin, Ann L.; Rodriggs, Liana M.; Peterson, Wayne; Cuthbert, Peter; Lee, David E.; Westhelle, Carlos

    2006-01-01

    A report discusses the Gumdrop capsule a conceptual spacecraft that would enable the crew to escape safely in the event of a major equipment failure at any time from launch through atmospheric re-entry. The scaleable Gumdrop capsule would comprise a command module (CM), a service module (SM), and a crew escape system (CES). The CM would contain a pressurized crew environment that would include avionic, life-support, thermal control, propulsive attitude control, and recovery systems. The SM would provide the primary propulsion and would also supply electrical power, life-support resources, and active thermal control to the CM. The CES would include a solid rocket motor, embedded within the SM, for pushing the CM away from the SM in the event of a critical thermal-protection-system failure or loss of control. The CM and SM would normally remain integrated with each other from launch through recovery, but could be separated using the CES, if necessary, to enable the safe recovery of the crew in the CM. The crew escape motor could be used, alternatively, as a redundant means of de-orbit propulsion for the CM in the event of a major system failure in the SM.

  6. Analyzing Spacecraft Telecommunication Systems

    NASA Technical Reports Server (NTRS)

    Kordon, Mark; Hanks, David; Gladden, Roy; Wood, Eric

    2004-01-01

    Multi-Mission Telecom Analysis Tool (MMTAT) is a C-language computer program for analyzing proposed spacecraft telecommunication systems. MMTAT utilizes parameterized input and computational models that can be run on standard desktop computers to perform fast and accurate analyses of telecommunication links. MMTAT is easy to use and can easily be integrated with other software applications and run as part of almost any computational simulation. It is distributed as either a stand-alone application program with a graphical user interface or a linkable library with a well-defined set of application programming interface (API) calls. As a stand-alone program, MMTAT provides both textual and graphical output. The graphs make it possible to understand, quickly and easily, how telecommunication performance varies with variations in input parameters. A delimited text file that can be read by any spreadsheet program is generated at the end of each run. The API in the linkable-library form of MMTAT enables the user to control simulation software and to change parameters during a simulation run. Results can be retrieved either at the end of a run or by use of a function call at any time step.

  7. Docking system for spacecraft

    NASA Technical Reports Server (NTRS)

    Kahn, Jon B. (Inventor)

    1990-01-01

    A mechanism for the docking of a space vehicle to a space station where a connection for transfer of personnel and equipment is desired. The invention comprises an active docking structure on a space vehicle 10 and a passive docking structure on a station 11. The passive structure includes a docking ring 50 mounted on a tunnel structure 35 fixed to the space station. The active structure including a docking ring 18 carried by actuator-attenuator devices 20, each attached at one end to the ring 18 and at its other end in the vehicle's payload bay 12. The devices 20 respond to command signals for moving the docking ring 18 between a stowed position in the space vehicle to a deployed position suitable for engagement with the docking ring 50. The devices 20 comprise means responsive to signals of sensed loadings to absorb impact energy and retraction means for drawing the coupled space vehicle and station into final docked configuration and moving the tunnel structure to a berthed position in the space vehicle 10. Latches 60 couple the space vehicle and space station upon contact of docking rings 18 and 50 and latches 41-48 establish a structural tie between the spacecraft when retracted.

  8. Putative cancer-initiating stem cells in cell culture models for molecular subtypes of clinical breast cancer

    PubMed Central

    TELANG, NITIN

    2015-01-01

    Cancer-initiating stem cells (CISC) represent a minor subpopulation of heterogeneous breast cancer. CISC are responsible for the acquired resistance to conventional chemoendocrine therapy and eventual relapse observed in patients with breast cancer. Certain molecular subtypes of clinical breast cancer that exhibit differential expression of genes coding for hormone and growth factor receptors differ in their response to conventional chemoendocrine therapy and targeted therapeutic inhibitors. Thus, the development of reliable cell culture models for CISC may provide a valuable experimental approach for the study of stem cell-targeted therapy for the treatment of breast cancer. The present study utilized optimized cell culture systems as experimental models for different molecular subtypes of clinical breast cancer, including luminal A, human epidermal growth factor receptor (HER)-2-enriched and triple negative breast cancer. Biomarker end points, including control of homeostatic growth, cancer risk and drug resistance, were quantitatively analyzed in the selected models. The results of the analyses indicated that, compared with the non-tumorigenic controls, the cell models representing the aforementioned molecular subtypes of clinical breast cancer exhibited aberrant cell cycle progression, downregulated cellular apoptosis and loss of control of homeostatic growth, as evidenced by hyperproliferation. Additionally, these models displayed persistent cancer risk, as indicated by their high incidence and frequency of anchorage-independent (AI) colony formation in vitro and their tumor development capacity in vivo. Furthermore, in the presence of maximum cytostatic drug concentrations, the drug-resistant phenotypes isolated from the parental drug-sensitive cell lines representing luminal A, HER-2-enriched and triple negative breast cancer exhibited an 11.5, 5.0 and 6.2 fold increase in cell growth, and a 5.6, 5.4 and 4.4 fold increase in the number of AI colonies

  9. Robust control of initiation of prokaryotic chromosome replication: essential considerations for a minimal cell.

    PubMed

    Browning, Samuel T; Castellanos, Mariajosé; Shuler, Michael L

    2004-12-01

    A genomically and chemically detailed mathematical model of a "minimal cell" would be useful to understand better the "design logic" of cellular regulation. A "minimal cell" will be a prokaryote with the minimum number of genes necessary for growth and replication in an ideal environment (i.e., preformed precursors, constant temperature, etc.). The Cornell single-cell model of Escherichia coli serves as the basic framework upon which a minimal cell model can be constructed. A critical issue for any cell model is to describe a mechanism for control of initiation of chromosome replication. There is strong evidence that the essence of chromosome replication control is highly conserved in eubacteria and even extends to the archae. A generalized mechanism is possible based on binding of the protein DnaA-ATP to the origin of replication (oriC) as a primary control. Other features, such as regulatory inactivation of DnaA (RIDA) by conversion of DnaA-ATP to DnaA-ADP and titration of DnaA by binding to other DnaA boxes on the chromosome, have emerged as critical elements in obtaining a functional system to control initiation of chromosome synthesis. We describe a biologically realistic model of chromosome replication initiation control embedded in a complete whole-cell model that explicitly links the external environment to the mechanism of replication control. The base model is deterministic and then modified to include stochastic variation in the components for replication control. The stochastic model allows evaluation of the model's robustness, employing a low standard deviation of interinitiation time as a measure of robustness. Four factors were examined: DnaA synthesis rate; DnaA-ATP binding sites at oriC; the binding rate of DnaA-ATP to the nonfunctional DnaA boxes; and the effect of changing the number of nonfunctional binding sites. The observed DnaA synthesis rate (2000 molecules/cell) and the number of DnaA binding sites per origin (30) are close to the values

  10. Inhibition of Phosphatidylcholine-Specific Phospholipase C Interferes with Proliferation and Survival of Tumor Initiating Cells in Squamous Cell Carcinoma

    PubMed Central

    Ferri, Renata; Mercurio, Laura; Canevari, Silvana; Podo, Franca; Miotti, Silvia; Iorio, Egidio

    2015-01-01

    Purpose The role of phosphatidylcholine-specific phospholipase C (PC-PLC), the enzyme involved in cell differentiation and proliferation, has not yet been explored in tumor initiating cells (TICs). We investigated PC-PLC expression and effects of PC-PLC inhibition in two adherent (AD) squamous carcinoma cell lines (A431 and CaSki), with different proliferative and stemness potential, and in TIC-enriched floating spheres (SPH) originated from them. Results Compared with immortalized non-tumoral keratinocytes (HaCaT) A431-AD cells showed 2.5-fold higher PC-PLC activity, nuclear localization of a 66-kDa PC-PLC isoform, but a similar distribution of the enzyme on plasma membrane and in cytoplasmic compartments. Compared with A431-AD, A431-SPH cells showed about 2.8-fold lower PC-PLC protein and activity levels, but similar nuclear content. Exposure of adherent cells to the PC-PLC inhibitor D609 (48h) induced a 50% reduction of cell proliferation at doses comprised between 33 and 50 μg/ml, without inducing any relevant cytotoxic effect (cell viability 95±5%). In A431-SPH and CaSki-SPH D609 induced both cytostatic and cytotoxic effects at about 20 to 30-fold lower doses (IC50 ranging between 1.2 and 1.6 μg/ml). Furthermore, D609 treatment of A431-AD and CaSki-AD cells affected the sphere-forming efficiency, which dropped in both cells, and induced down-modulation of stem-related markers mRNA levels (Oct4, Nestin, Nanog and ALDH1 in A431; Nestin and ALDH1 in CaSki cells). Conclusions These data suggest that the inhibition of PC-PLC activity may represent a new therapeutic approach to selectively target the most aggressive and tumor promoting sub-population of floating spheres originated from squamous cancer cells possessing different proliferative and stemness potential. PMID:26402860

  11. Safety aspects of spacecraft commanding

    NASA Technical Reports Server (NTRS)

    Peccia, N.

    1994-01-01

    The commanding of spacecraft is a potentially hazardous activity for the safety of the spacecraft. Present day control systems contain safety features in their commanding subsystem and in addition, strict procedures are also followed by operations staff. However, problems have occurred on a number of missions as a result of erroneous commanding leading in some cases to spacecraft contingencies and even to near loss of the spacecraft. The problems of checking commands in advance are increased by the tendency in modern spacecraft to use blocked/time-tagged commands and the increased usage of on-board computers, for which commands changing on-board software tables can radically change spacecraft or subsystem behavior. This paper reports on an on-going study. The study aims to improve the approach to safety of spacecraft commanding. It will show how ensuring 'safe' commanding can be carried out more efficiently, and with greater reliability, with the help of knowledge based systems and/or fast simulators. The whole concept will be developed based on the Object-Oriented approach.

  12. SF3B1 mutant MDS-initiating cells may arise from the haematopoietic stem cell compartment

    PubMed Central

    Mian, Syed A.; Rouault-Pierre, Kevin; Smith, Alexander E.; Seidl, Thomas; Pizzitola, Irene; Kizilors, Aytug; Kulasekararaj, Austin G.; Bonnet, Dominique; Mufti, Ghulam J.

    2015-01-01

    Despite the recent evidence of the existence of myelodysplastic syndrome (MDS) stem cells in 5q-MDS patients, it is unclear whether haematopoietic stem cells (HSCs) could also be the initiating cells in other MDS subgroups. Here we demonstrate that SF3B1 mutation(s) in our cohort of MDS patients with ring sideroblasts can arise from CD34+CD38−CD45RA−CD90+CD49f+ HSCs and is an initiating event in disease pathogenesis. Xenotransplantation of SF3B1 mutant HSCs leads to persistent long-term engraftment restricted to myeloid lineage. Moreover, genetically diverse evolving subclones of mutant SF3B1 exist in mice, indicating a branching multi-clonal as well as ancestral evolutionary paradigm. Subclonal evolution in mice is also seen in the clinical evolution in patients. Sequential sample analysis shows clonal evolution and selection of the malignant driving clone leading to AML transformation. In conclusion, our data show SF3B1 mutations can propagate from HSCs to myeloid progeny, therefore providing a therapeutic target. PMID:26643973

  13. Co-Transcriptomes of Initial Interactions In Vitro between Streptococcus Pneumoniae and Human Pleural Mesothelial Cells

    PubMed Central

    Heath, Claire J.; del Mar Cendra, Maria; Watson, Alastair; Auger, Jean-Philippe; Pandey, Anish; Tighe, Paddy; Christodoulides, Myron

    2015-01-01

    Streptococcus pneumoniae (Spn) is a major causative organism of empyema, an inflammatory condition occurring in the pleural sac. In this study, we used human and Spn cDNA microarrays to characterize the transcriptional responses occurring during initial contact between Spn and a human pleural mesothelial cell line (PMC) in vitro. Using stringent filtering criteria, 42 and 23 Spn genes were up-and down-regulated respectively. In particular, genes encoding factors potentially involved in metabolic processes and Spn adherence to eukaryotic cells were up-regulated e.g. glnQ, glnA, aliA, psaB, lytB and nox. After Spn initial contact, 870 human genes were differentially regulated and the largest numbers of significant gene expression changes were found in canonical pathways for eukaryotic initiation factor 2 signaling (60 genes out of 171), oxidative phosphorylation (32/103), mitochondrial dysfunction (37/164), eIF4 and p70S6K signaling (28/142), mTOR signaling (27/182), NRF2-mediated oxidative stress response (20/177), epithelial adherens junction remodeling (11/66) and ubiquitination (22/254). The cellular response appeared to be directed towards host cell survival and defense. Spn did not activate NF-kB or phosphorylate p38 MAPK or induce cytokine production from PMC. Moreover, Spn infection of TNF-α pre-stimulated PMC inhibited production of IL-6 and IL-8 secretion by >50% (p<0.01). In summary, this descriptive study provides datasets and a platform for examining further the molecular mechanisms underlying the pathogenesis of empyema. PMID:26566142

  14. STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity

    PubMed Central

    Demaria, Olivier; De Gassart, Aude; Coso, Sanja; Gestermann, Nicolas; Di Domizio, Jeremy; Flatz, Lukas; Gaide, Olivier; Michielin, Olivier; Hwu, Patrick; Petrova, Tatiana V.; Martinon, Fabio; Modlin, Robert L.; Speiser, Daniel E.; Gilliet, Michel

    2015-01-01

    Spontaneous CD8 T-cell responses occur in growing tumors but are usually poorly effective. Understanding the molecular and cellular mechanisms that drive these responses is of major interest as they could be exploited to generate a more efficacious antitumor immunity. As such, stimulator of IFN genes (STING), an adaptor molecule involved in cytosolic DNA sensing, is required for the induction of antitumor CD8 T responses in mouse models of cancer. Here, we find that enforced activation of STING by intratumoral injection of cyclic dinucleotide GMP-AMP (cGAMP), potently enhanced antitumor CD8 T responses leading to growth control of injected and contralateral tumors in mouse models of melanoma and colon cancer. The ability of cGAMP to trigger antitumor immunity was further enhanced by the blockade of both PD1 and CTLA4. The STING-dependent antitumor immunity, either induced spontaneously in growing tumors or induced by intratumoral cGAMP injection was dependent on type I IFNs produced in the tumor microenvironment. In response to cGAMP injection, both in the mouse melanoma model and an ex vivo model of cultured human melanoma explants, the principal source of type I IFN was not dendritic cells, but instead endothelial cells. Similarly, endothelial cells but not dendritic cells were found to be the principal source of spontaneously induced type I IFNs in growing tumors. These data identify an unexpected role of the tumor vasculature in the initiation of CD8 T-cell antitumor immunity and demonstrate that tumor endothelial cells can be targeted for immunotherapy of melanoma. PMID:26607445

  15. Human blood cells at microgravity: the NASA Initial Blood Storage Experiment.

    PubMed

    Surgenor, D M; Kevy, S V; Chao, F C; Lionetti, F J; Kenney, D M; Jacobson, M S; Kim, B; Ausprunk, D H; Szymanski, I O; Button, L N

    1990-09-01

    The Initial Blood Storage Experiment (IBSE) probed the behavior of human red cells, white cells, and platelets during exposure to microgravity for 6 days and 2 hours on a National Aeronautics and Space Administration (NASA) shuttle mission, named STS 61-C, which was launched on January 12, 1986. IBSE involved carefully controlled comparisons between two identical sets of blood cells, one exposed to microgravity and the other held on the ground. Specially designed and fabricated, electrically powered environmental chambers provided appropriate environmental temperatures and air flow to support cell metabolism throughout the experiment. To circumvent the need for constant agitation of platelets during storage, a new thin-layer compression method for platelet preservation was developed. Blood cell samples were allocated to the two arms of the experiment, microgravity and earth gravity, by blind assignment. Moreover, to ensure unbiased assessment of the experiment's findings, postexperiment samples for measurement were identified by code. To optimize the chances of detecting possible gravitational effects, a wide array of measurements of cellular function, morphology, metabolism, and immunology were made. Analysis of variance was used in analyzing the data. The most striking finding was that platelets displayed markedly superior structural and functional integrity at microgravity. Granulocytes held on the ground were preserved slightly better than those that orbited in the shuttle, whereas red cells displayed few effects that were attributable to the gravitational variable. Polyvinylchloride-di-(2-ethylhexyl)phthalate (PVC-DEHP) was the plastic of choice for storage of red cells, while PVC-trioctyltrimellitate (TOTM) was superior to PVC-DEHP and polyolefin (PO) for platelets. PMID:2402774

  16. Decreased origin usage and initiation of DNA replication in haploinsufficient HCT116 Ku80+/- cells.

    PubMed

    Sibani, Sahar; Price, Gerald B; Zannis-Hadjopoulos, Maria

    2005-08-01

    One of the functions of the abundant heterodimeric nuclear protein, Ku (Ku70/Ku80), is its involvement in the initiation of DNA replication through its ability to bind to chromosomal replication origins in a sequence-specific and cell cycle dependent manner. Here, using HCT116 Ku80+/- cells, the effect of Ku80 deficiency on cell cycle progression and origin activation was examined. Western blot analyses revealed a 75% and 36% decrease in the nuclear expression of Ku80 and Ku70, respectively. This was concomitant with a 33% and 40% decrease in chromatin binding of both proteins, respectively. Cell cycle analysis of asynchronous and late G1 synchronized Ku80+/- cells revealed a prolonged G1 phase. Furthermore, these Ku-deficient cells had a 4.5-, 3.4- and 4.3-fold decrease in nascent strand DNA abundance at the lamin B2, beta-globin and c-myc replication origins, respectively. Chromatin immunoprecipitation (ChIP) assays showed that the association of Ku80 with the lamin B2, beta-globin and c-myc origins was decreased by 1.5-, 2.3- and 2.5-fold, respectively, whereas that of Ku70 was similarly decreased (by 2.1-, 1.5- and 1.7-fold, respectively) in Ku80+/- cells. The results indicate that a deficiency of Ku80 resulted in a prolonged G1 phase, as well as decreased Ku binding to and activation of origins of DNA replication. PMID:16014376

  17. Bone scintigraphy in the initial staging of patients with renal-cell carcinoma: concise communication

    SciTech Connect

    Rosen, P.R.; Murphy, K.G.

    1984-03-01

    The records of 40 consecutive patients who received bone scintigraphy in conjunction with the initial evaluation and staging of renal-cell carcinoma were reviewed to determine the role of bone imaging in this clinical context. Bone scintigrams were positive in three out of 40 patients at the time of diagnosis. In view of the low yield of bone imaging, it appears that routine scintigraphy is unwarranted in the absence of skeletal symptoms before the diagnosis of renal lesions. The presence of a positive bone image did not alter the indication for nephrectomy.

  18. Initial Design and Construction of a Mobil Regenerative Fuel Cell System

    NASA Technical Reports Server (NTRS)

    Colozza, Anthony J.; Maloney, Thomas; Hoberecht, Mark (Technical Monitor)

    2003-01-01

    The design and initial construction of a mobile regenerative power system is described. The main components of the power system consists of a photovoltaic array, regenerative fuel cell and electrolyzer. The system is mounted on a modified landscape trailer and is completely self contained. An operational analysis is also presented that shows predicted performance for the system at various times of the year. The operational analysis consists of performing an energy balance on the system based on array output and total desired operational time.

  19. Synchronous Diagnosis of Multiple Myeloma, Breast Cancer, and Monoclonal B-Cell Lymphocytosis on Initial Presentation

    PubMed Central

    Vennepureddy, A.; Motilal Nehru, V.; Liu, Y.; Mohammad, F.; Atallah, J. P.

    2016-01-01

    The cooccurrence of more than one oncologic illness in a patient can present a diagnostic challenge. Here we report an unusual case of concomitant existence of multiple myeloma, breast cancer, and monoclonal B-cell lymphocytosis on initial presentation. The challenge was to accurately diagnose each disease and stage in order to maximize the therapeutic regimen to achieve cure/remission. Successful management of the patient and increased life expectancy can be achieved by multidisciplinary management and patient-oriented approach in multiple primary malignant synchronous tumors. PMID:27247815

  20. POWOW: A Modular, High Power Spacecraft Concept

    NASA Technical Reports Server (NTRS)

    Brandhorst, Henry W., Jr.

    2000-01-01

    A robust space infrastructure encompasses a broad range of mission needs along with an imperative to reduce costs of satellites meeting those needs. A critical commodity for science, commercial and civil satellites is power at an affordable cost. The POWOW (POwer WithOut Wires) spacecraft concept was created to provide, at one end of the scale, multi-megawatts of power yet also be composed of modules that can meet spacecraft needs in the kilowatt range. With support from the NASA-sponsored Space Solar Power Exploratory Research and Technology Program, the POWOW spacecraft concept was designed to meet Mars mission needs - while at the same time having elements applicable to a range of other missions. At Mars, the vehicle would reside in an aerosynchronous orbit and beam power to a variety of locations on the surface. It is the purpose of this paper to present the latest concept design results. The Space Power Institute along with four companies: Able Engineering, Inc., Entech, Inc., Primex Aerospace Co., and TECSTAR have produced a modular, power-rich electrically propelled spacecraft design that meets these requirements. In addition, it also meets a range of civil and commercial needs. The spacecraft design is based on multijunction Ill-V solar cells, the new Stretched Lens Aurora (SLA) module, a lightweight array design based on a multiplicity of 8 kW end-of-life subarrays and electric thrusters. The solar cells have excellent radiation resistance and efficiencies above 30%. The SLA has a concentration ratio up to 15x while maintaining an operating temperature of 80 C. The design of the 8 kW array building block will be presented and its applicability to commercial and government missions will be discussed. Electric propulsion options include Hall, MPD and ion thrusters of various power levels and trade studies have been conducted to define the most advantageous options. The present baseline spacecraft design providing 900 kW using technologies expected to be

  1. Spacecraft power system architecture to mitigate spacecraft charging effects

    NASA Technical Reports Server (NTRS)

    Manner, David B. (Inventor)

    1997-01-01

    A power system architecture for a spacecraft and a method of a power supply for a spacecraft are presented which take advantage of the reduced plasma interaction associated with positive ground high voltage photovoltaic arrays and provide a negative ground power supply for electrical loads of the spacecraft. They efficiently convert and regulate power to the load bus and reduce power system mass and complexity. The system and method ground the positive terminal of the solar arrays to the spacecraft hull, and using a power converter to invert the electric sign, permit a negative ground for the electrical distribution bus and electrical components. A number of variations including a load management system and a battery management system having charging and recharging devices are presented.

  2. Automated techniques for spacecraft monitoring

    NASA Technical Reports Server (NTRS)

    Segnar, H. R.

    1972-01-01

    The feasibility of implementing automated spacecraft monitoring depends on four factors: sufficient computer resources, suitable monitoring function definitions, adequate spacecraft data, and effective and economical test systems. The advantages of automated monitoring lie in the decision-making speed of the computer and the continuous monitoring coverage provided by an automated monitoring program. Use of these advantages introduces a new concept of spacecraft monitoring in which system specialists, ground based or onboard, freed from routine and tedious monitoring, could devote their expertise to unprogrammed or contingency situations.

  3. Spacecraft cryogenic gas storage systems

    NASA Technical Reports Server (NTRS)

    Rysavy, G.

    1971-01-01

    Cryogenic gas storage systems were developed for the liquid storage of oxygen, hydrogen, nitrogen, and helium. Cryogenic storage is attractive because of the high liquid density and low storage pressure of cryogens. This situation results in smaller container sizes, reduced container-strength levels, and lower tankage weights. The Gemini and Apollo spacecraft used cryogenic gas storage systems as standard spacecraft equipment. In addition to the Gemini and Apollo cryogenic gas storage systems, other systems were developed and tested in the course of advancing the state of the art. All of the cryogenic storage systems used, developed, and tested to date for manned-spacecraft applications are described.

  4. Evaluation of Ultrafiltration for Spacecraft Water Reuse

    NASA Technical Reports Server (NTRS)

    Pickering, Karen D.; Wiesner, Mark R.

    2001-01-01

    Ultrafiltration is examined for use as the first stage of a primary treatment process for spacecraft wastewater. It is hypothesized that ultrafiltration can effectively serve as pretreatment for a reverse osmosis system, removing the majority of organic material in a spacecraft wastewater. However, it is believed that the interaction between the membrane material and the surfactant found in the wastewater will have a significant impact on the fouling of the ultrafiltration membrane. In this study, five different ultrafiltration membrane materials are examined for the filtration of wastewater typical of that expected to be produced onboard the International Space Station. Membranes are used in an unstirred batch cell. Flux, organic carbon rejection, and recovery from fouling are measured. The results of this evaluation will be used to select the most promising membranes for further study.

  5. An expert system concept for autonomous spacecraft energy management

    SciTech Connect

    Imamura, M.S.; Dietrich, E.

    1983-08-01

    This paper presents a concept for an on-board spacecraft energy management system utilizing an expert systems approach. The energy management system continuously monitors and predicts the power capability of the spacecraft power subsystem, determines the overall electrical load profile, defines necessary changes to the initial equipment timeline, and implements new mission timeline and electrical load sequencing activities with little or no ground intervention. The system is intended to not only permit continued spacecraft operation in a degraded power subsystem state due to internal or external causes, but also to significantly optimize mission operation via maximum utilization of available power. The paper discusses the present state of the art of artificial intelligence technology and why the expert system is an attractive option to automate the energy management system for high power spacecraft.

  6. The Multimission Modular Spacecraft for the 80's

    NASA Technical Reports Server (NTRS)

    Bartlett, R. O.; Cepollina, F. J.

    1975-01-01

    The challenge to NASA is to prepare for the missions of tomorrow with manpower and funding constraints of today. The Goddard Space Flight Center has met this challenge with the Multimission Modular Spacecraft (MMS). This spacecraft design has evolved over the past six years while studying various potential missions. The key to the concept of the MMS is modularity and flexibility to accept mission unique hardware with minimum impact on the basic spacecraft bus. Beyond this, it was imperative that this multiple mission bus be cost effective even though it would not be of an optimum design for many missions having minimum performance requirements. The MMS performance and cost will capture 34 of the 43 potential spacecraft missions which have been initially studied. Gamma Ray Explorer (GRE) will be the first mission to utilize the MMS.

  7. Kick-starting the cell cycle: From growth-factor stimulation to initiation of DNA replication

    NASA Astrophysics Data System (ADS)

    Aguda, Baltazar D.

    2001-03-01

    The essential genes, proteins and associated regulatory networks involved in the entry into the mammalian cell cycle are identified, from activation of growth-factor receptors to intracellular signal transduction pathways that impinge on the cell cycle machinery and ultimately on the initiation of DNA replication. Signaling pathways mediated by the oncoproteins Ras and Myc induce the activation of cyclin-dependent kinases CDK4 and CDK2, and the assembly and firing of pre-replication complexes require a collaboration among E2F, CDK2, and Cdc7 kinase. A proposed core mechanism of the restriction point, the major checkpoint prior to commitment to DNA synthesis, involves cyclin E/CDK2, the phosphatase Cdc25A, and the CDK inhibitor p27Kip1.

  8. Initial presentation of CNS-restricted acute lymphoblastic B cell leukaemia as peripheral polyneuropathy.

    PubMed

    Piovezani Ramos, Guilherme; Villasboas Bisneto, Jose C; Chen, Dong; Pardanani, Animesh

    2016-01-01

    We report a case of a 58-year-old woman who presented with a 1-month course of progressive lower and upper extremity weakness in addition to binocular diplopia. Diagnostic lumbar puncture revealed atypical lymphoid cells with 28% blasts. Immunophenotype was consistent with B cell acute lymphoblastic leukaemia (B-ALL). Further work up showed no systemic involvement but extensive thoracolumbar-sacral leptomeningeal disease. The patient was treated with several courses of intrathecal and systemic chemotherapy followed by craniospinal irradiation for consolidation. There was initial steady improvement in neurological symptoms and leptomeningeal disease, the latter being ascertained through radiological studies and cerebrospinal fluid examination. After 10 months of response, the patient relapsed with central nervous system (CNS) and systemic disease. B-ALL is a rare precursor lymphoid neoplasm that generally presents with systemic disease. While CNS involvement is not uncommon, isolated involvement of this compartment without systemic disease is exceedingly rare. PMID:27095809

  9. Brain Tumor Initiating Cells Adapt to Restricted Nutrition through Preferential Glucose Uptake

    PubMed Central

    Flavahan, William A.; Wu, Qiulian; Hitomi, Masahiro; Rahim, Nasiha; Kim, Youngmi; Sloan, Andrew E.; Weil, Robert J.; Nakano, Ichiro; Sarkaria, Jann N.; Stringer, Brett W.; Day, Bryan W.; Li, Meizhang; Lathia, Justin D.; Rich, Jeremy N.; Hjelmeland, Anita B.

    2013-01-01

    Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) due to preferential BTIC survival and adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3 and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, TICs may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may instruct the tumor hierarchy and portend poor prognosis. PMID:23995067

  10. Chromium(VI) stimulates Fyn to initiate innate immune gene induction in human airway epithelial cells

    PubMed Central

    Nemec, Antonia A.; Zubritsky, Lindsey M.; Barchowsky, Aaron

    2009-01-01

    Mechanisms for pathogenic metal signaling in airway injury or disease promotion are poorly understood. It is widely believed that one mechanism for pathogenic and possible carcinogenic effects of inhaled chromium (Cr(VI)) is inhibition of inducible gene transactivation. However, we recently reported that Cr(VI) inhibition of Sp1-dependent transactivation required signal transducer and activator of transcription 1 (STAT1)-dependent expression of an inhibitory protein in airway epithelium. Thus, Cr(VI) exposures can induce genes and we hypothesized this induction resulted from Cr(VI) signaling through an innate immune-like STAT1-dependent pathway initiated by Fyn. Exposure of human airway epithelial (BEAS-2B) cells to Cr(VI) selectively transactivated STAT-responsive interferon-stimulated response element (ISRE) and induced ISRE-driven transactivation of interferon regulatory factor 7 (IRF7), without affecting the gamma interferon-activated site (GAS)-driven IRF1 expression. Cr(VI)-induced IRF7 was absent or greatly reduced in cells that lacked STAT1, were treated with the Src family kinase inhibitor, PP2, or lacked Fyn. Expressing Fyn, but not Src, in mouse embryonic fibroblasts cells null for Src, Yes, and Fyn restored Cr(VI)-stimulated STAT1 tyrosine phosphorylation and IRF7 expression. Finally, shRNA knockdown of Fyn in BEAS-2B cells prevented Cr(VI)-activated STAT1 transactivation of IRF7. These data support a novel mechanism through which Cr(VI) stimulates Fyn to initiate interferon-like signaling for STAT1-dependent gene transactivation. PMID:19994902

  11. Using Drained Spacecraft Propellant Tanks for Habitation

    NASA Technical Reports Server (NTRS)

    Thomas, Andrew S. W.

    2009-01-01

    A document proposes that future spacecraft for planetary and space exploration be designed to enable reuse of drained propellant tanks for occupancy by humans. This proposal would enable utilization of volume and mass that would otherwise be unavailable and, in some cases, discarded. Such utilization could enable reductions in cost, initial launch mass, and number of launches needed to build up a habitable outpost in orbit about, or on the surface of, a planet or moon. According to the proposal, the large propellant tanks of a spacecraft would be configured to enable crews to gain access to their interiors. The spacecraft would incorporate hatchways, between a tank and the crew volume, that would remain sealed while the tank contained propellant and could be opened after the tank was purged by venting to outer space and then refilled with air. The interior of the tank would be pre-fitted with some habitation fixtures that were compatible with the propellant environment. Electrical feed-throughs, used originally for gauging propellants, could be reused to supply electric power to equipment installed in the newly occupied space. After a small amount of work, the tank would be ready for long-term use as a habitation module.

  12. Spacecraft contamination prediction and testing techniques

    NASA Technical Reports Server (NTRS)

    Jeffery, J. A.; Maag, C. R.; Morelli, F. A.

    1981-01-01

    Techniques used in the prediction of spacecraft contamination for the Galileo Jupiter Orbiter and in the determination of the effects of such contamination are presented. Following a quick-look assessment of the contributions of ground-based initial contaminant loading, launch vehicle interface effects, vacuum-exposed outgassing deposition and attitude control thruster impingement and venting to the spacecraft contamination burden, the evaluations centered on the effects of the attitude control thruster on the scan platform optics, including calculations of thruster flowfields and a high-fidelity computer simulation of contaminant distribution. The evaluations revealed a considerable problem with thruster contamination, which could be solved by the use of a thrust shield and the avoidance of thruster operation at certain scan platform orientations. The effects of the various possible contaminants on spacecraft thermal and optical system performances were also investigated in studies of the optical transmittance of deposited monomethyl hydrazine nitrate, vacuum optical degradation due to contaminant outgassing and re-emission outgassing, and an operational satellite contaminant monitor on the NOAA-C satellite. It is concluded that with a good evaluation and testing program, contamination control may become a necessary portion of system design procedures, and recommendations for the implementation of various practices and tests to minimize contamination effects are presented.

  13. Delamination Assessment Tool for Spacecraft Composite Structures

    NASA Astrophysics Data System (ADS)

    Portela, Pedro; Preller, Fabian; Wittke, Henrik; Sinnema, Gerben; Camanho, Pedro; Turon, Albert

    2012-07-01

    Fortunately only few cases are known where failure of spacecraft structures due to undetected damage has resulted in a loss of spacecraft and launcher mission. However, several problems related to damage tolerance and in particular delamination of composite materials have been encountered during structure development of various ESA projects and qualification testing. To avoid such costly failures during development, launch or service of spacecraft, launcher and reusable launch vehicles structures a comprehensive damage tolerance verification approach is needed. In 2009, the European Space Agency (ESA) initiated an activity called “Delamination Assessment Tool” which is led by the Portuguese company HPS Lda and includes academic and industrial partners. The goal of this study is the development of a comprehensive damage tolerance verification approach for launcher and reusable launch vehicles (RLV) structures, addressing analytical and numerical methodologies, material-, subcomponent- and component testing, as well as non-destructive inspection. The study includes a comprehensive review of current industrial damage tolerance practice resulting from ECSS and NASA standards, the development of new Best Practice Guidelines for analysis, test and inspection methods and the validation of these with a real industrial case study. The paper describes the main findings of this activity so far and presents a first iteration of a Damage Tolerance Verification Approach, which includes the introduction of novel analytical and numerical tools at an industrial level. This new approach is being put to the test using real industrial case studies provided by the industrial partners, MT Aerospace, RUAG Space and INVENT GmbH

  14. Heterogeneity of leukemia-initiating capacity of chronic myelogenous leukemia stem cells

    PubMed Central

    Zhang, Bin; Li, Ling; Ho, Yinwei; Li, Min; Marcucci, Guido

    2016-01-01

    Chronic myelogenous leukemia (CML) results from transformation of a long-term hematopoietic stem cell (LTHSC) by expression of the BCR-ABL fusion gene. However, BCR-ABL–expressing LTHSCs are heterogeneous in their capacity as leukemic stem cells (LSCs). Although discrepancies in proliferative, self-renewal, and differentiation properties of normal LTHSCs are being increasingly recognized, the mechanisms underlying heterogeneity of leukemic LTHSCs are poorly understood. Using a CML mouse model, we identified gene expression differences between leukemic and nonleukemic LTHSCs. Expression of the thrombopoietin (THPO) receptor MPL was elevated in leukemic LTHSC populations. Compared with LTHSCs with low MPL expression, LTHSCs with high MPL expression showed enhanced JAK/STAT signaling and proliferation in response to THPO in vitro and increased leukemogenic capacity in vivo. Although both G0 and S phase subpopulations were increased in LTHSCs with high MPL expression, LSC capacity was restricted to quiescent cells. Inhibition of MPL expression in CML LTHSCs reduced THPO-induced JAK/STAT signaling and leukemogenic potential. These same phenotypes were also present in LTHSCs from patients with CML, and patient LTHSCs with high MPL expression had reduced sensitivity to BCR-ABL tyrosine kinase inhibitor treatment but increased sensitivity to JAK inhibitors. Together, our studies identify MPL expression levels as a key determinant of heterogeneous leukemia-initiating capacity and drug sensitivity of CML LTHSCs and suggest that high MPL–expressing CML stem cells are potential targets for therapy. PMID:26878174

  15. Neutrophils support lung colonization of metastasis-initiating breast cancer cells.

    PubMed

    Wculek, Stefanie K; Malanchi, Ilaria

    2015-12-17

    Despite progress in the development of drugs that efficiently target cancer cells, treatments for metastatic tumours are often ineffective. The now well-established dependency of cancer cells on their microenvironment suggests that targeting the non-cancer-cell component of the tumour might form a basis for the development of novel therapeutic approaches. However, the as-yet poorly characterized contribution of host responses during tumour growth and metastatic progression represents a limitation to exploiting this approach. Here we identify neutrophils as the main component and driver of metastatic establishment within the (pre-)metastatic lung microenvironment in mouse breast cancer models. Neutrophils have a fundamental role in inflammatory responses and their contribution to tumorigenesis is still controversial. Using various strategies to block neutrophil recruitment to the pre-metastatic site, we demonstrate that neutrophils specifically support metastatic initiation. Importantly, we find that neutrophil-derived leukotrienes aid the colonization of distant tissues by selectively expanding the sub-pool of cancer cells that retain high tumorigenic potential. Genetic or pharmacological inhibition of the leukotriene-generating enzyme arachidonate 5-lipoxygenase (Alox5) abrogates neutrophil pro-metastatic activity and consequently reduces metastasis. Our results reveal the efficacy of using targeted therapy against a specific tumour microenvironment component and indicate that neutrophil Alox5 inhibition may limit metastatic progression. PMID:26649828

  16. Erythropoietin promotes breast tumorigenesis through tumor-initiating cell self-renewal

    PubMed Central

    Zhou, Bing; Damrauer, Jeffrey S.; Bailey, Sean T.; Hadzic, Tanja; Jeong, Youngtae; Clark, Kelly; Fan, Cheng; Murphy, Laura; Lee, Cleo Y.; Troester, Melissa A.; Miller, C. Ryan; Jin, Jian; Darr, David; Perou, Charles M.; Levine, Ross L.; Diehn, Maximilian; Kim, William Y.

    2014-01-01

    Erythropoietin (EPO) is a hormone that induces red blood cell production. In its recombinant form, EPO is the one of most prescribed drugs to treat anemia, including that arising in cancer patients. In randomized trials, EPO administration to cancer patients has been associated with decreased survival. Here, we investigated the impact of EPO modulation on tumorigenesis. Using genetically engineered mouse models of breast cancer, we found that EPO promoted tumorigenesis by activating JAK/STAT signaling in breast tumor-initiating cells (TICs) and promoted TIC self renewal. We determined that EPO was induced by hypoxia in breast cancer cell lines, but not in human mammary epithelial cells. Additionally, we demonstrated that high levels of endogenous EPO gene expression correlated with shortened relapse-free survival and that pharmacologic JAK2 inhibition was synergistic with chemotherapy for tumor growth inhibition in vivo. These data define an active role for endogenous EPO in breast cancer progression and breast TIC self-renewal and reveal a potential application of EPO pathway inhibition in breast cancer therapy. PMID:24435044

  17. Erythropoietin promotes breast tumorigenesis through tumor-initiating cell self-renewal.

    PubMed

    Zhou, Bing; Damrauer, Jeffrey S; Bailey, Sean T; Hadzic, Tanja; Jeong, Youngtae; Clark, Kelly; Fan, Cheng; Murphy, Laura; Lee, Cleo Y; Troester, Melissa A; Miller, C Ryan; Jin, Jian; Darr, David; Perou, Charles M; Levine, Ross L; Diehn, Maximilian; Kim, William Y

    2014-02-01

    Erythropoietin (EPO) is a hormone that induces red blood cell production. In its recombinant form, EPO is the one of most prescribed drugs to treat anemia, including that arising in cancer patients. In randomized trials, EPO administration to cancer patients has been associated with decreased survival. Here, we investigated the impact of EPO modulation on tumorigenesis. Using genetically engineered mouse models of breast cancer, we found that EPO promoted tumorigenesis by activating JAK/STAT signaling in breast tumor-initiating cells (TICs) and promoted TIC self renewal. We determined that EPO was induced by hypoxia in breast cancer cell lines, but not in human mammary epithelial cells. Additionally, we demonstrated that high levels of endogenous EPO gene expression correlated with shortened relapse-free survival and that pharmacologic JAK2 inhibition was synergistic with chemotherapy for tumor growth inhibition in vivo. These data define an active role for endogenous EPO in breast cancer progression and breast TIC self-renewal and reveal a potential application of EPO pathway inhibition in breast cancer therapy. PMID:24435044

  18. Heterogeneity of leukemia-initiating capacity of chronic myelogenous leukemia stem cells.

    PubMed

    Zhang, Bin; Li, Ling; Ho, Yinwei; Li, Min; Marcucci, Guido; Tong, Wei; Bhatia, Ravi

    2016-03-01

    Chronic myelogenous leukemia (CML) results from transformation of a long-term hematopoietic stem cell (LTHSC) by expression of the BCR-ABL fusion gene. However, BCR-ABL-expressing LTHSCs are heterogeneous in their capacity as leukemic stem cells (LSCs). Although discrepancies in proliferative, self-renewal, and differentiation properties of normal LTHSCs are being increasingly recognized, the mechanisms underlying heterogeneity of leukemic LTHSCs are poorly understood. Using a CML mouse model, we identified gene expression differences between leukemic and nonleukemic LTHSCs. Expression of the thrombopoietin (THPO) receptor MPL was elevated in leukemic LTHSC populations. Compared with LTHSCs with low MPL expression, LTHSCs with high MPL expression showed enhanced JAK/STAT signaling and proliferation in response to THPO in vitro and increased leukemogenic capacity in vivo. Although both G0 and S phase subpopulations were increased in LTHSCs with high MPL expression, LSC capacity was restricted to quiescent cells. Inhibition of MPL expression in CML LTHSCs reduced THPO-induced JAK/STAT signaling and leukemogenic potential. These same phenotypes were also present in LTHSCs from patients with CML, and patient LTHSCs with high MPL expression had reduced sensitivity to BCR-ABL tyrosine kinase inhibitor treatment but increased sensitivity to JAK inhibitors. Together, our studies identify MPL expression levels as a key determinant of heterogeneous leukemia-initiating capacity and drug sensitivity of CML LTHSCs and suggest that high MPL-expressing CML stem cells are potential targets for therapy. PMID:26878174

  19. Oncogenic mTOR signalling recruits myeloid-derived suppressor cells to promote tumour initiation.

    PubMed

    Welte, Thomas; Kim, Ik Sun; Tian, Lin; Gao, Xia; Wang, Hai; Li, June; Holdman, Xue B; Herschkowitz, Jason I; Pond, Adam; Xie, Guorui; Kurley, Sarah; Nguyen, Tuan; Liao, Lan; Dobrolecki, Lacey E; Pang, Lan; Mo, Qianxing; Edwards, Dean P; Huang, Shixia; Xin, Li; Xu, Jianming; Li, Yi; Lewis, Michael T; Wang, Tian; Westbrook, Thomas F; Rosen, Jeffrey M; Zhang, Xiang H-F

    2016-06-01

    Myeloid-derived suppressor cells (MDSCs) play critical roles in primary and metastatic cancer progression. MDSC regulation is widely variable even among patients harbouring the same type of malignancy, and the mechanisms governing such heterogeneity are largely unknown. Here, integrating human tumour genomics and syngeneic mammary tumour models, we demonstrate that mTOR signalling in cancer cells dictates a mammary tumour's ability to stimulate MDSC accumulation through regulating G-CSF. Inhibiting this pathway or its activators (for example, FGFR) impairs tumour progression, which is partially rescued by restoring MDSCs or G-CSF. Tumour-initiating cells (TICs) exhibit elevated G-CSF. MDSCs reciprocally increase TIC frequency through activating Notch in tumour cells, forming a feedforward loop. Analyses of primary breast cancers and patient-derived xenografts corroborate these mechanisms in patients. These findings establish a non-canonical oncogenic role of mTOR signalling in recruiting pro-tumorigenic MDSCs and show how defined cancer subsets may evolve to promote and depend on a distinct immune microenvironment. PMID:27183469

  20. A Sertoli Cell-Specific Knockout of Connexin43 Prevents Initiation of Spermatogenesis

    PubMed Central

    Brehm, Ralph; Zeiler, Martina; Rüttinger, Christina; Herde, Katja; Kibschull, Mark; Winterhager, Elke; Willecke, Klaus; Guillou, Florian; Lécureuil, Charlotte; Steger, Klaus; Konrad, Lutz; Biermann, Katharina; Failing, Klaus; Bergmann, Martin

    2007-01-01

    The predominant testicular gap junctional protein connexin43 (cx43) is located between neighboring Sertoli cells (SCs) and between SCs and germ cells. It is assumed to be involved in testicular development, cell differentiation, initiation, and maintenance of spermatogenesis with alterations of its expression being correlated with various testicular disorders. Because total disruption of the cx43 gene leads to perinatal death, we generated a conditional cx43 knockout (KO) mouse using the Cre/loxP recombination system, which lacks the cx43 gene solely in SCs (SCCx43KO), to evaluate the SC-specific functions of cx43 on spermatogenesis in vivo. Adult SCCx43KO−/− mice showed normal testis descent and development of the urogenital tract, but testis size and weight were drastically lower compared with heterozygous and wild-type littermates. Histological analysis and quantitation of mRNA expression of germ cell-specific marker genes revealed a significant reduction in the number of spermatogonia but increased SC numbers/tubule with only a few tubules left showing normal spermatogenesis. Thus, SC-specific deletion of cx43 mostly resulted in an arrest of spermatogenesis at the level of spermatogonia or SC-only syndrome and in intratubular SC clusters. Our data demonstrate for the first time that cx43 expression in SCs is an absolute requirement for normal testicular development and spermatogenesis. PMID:17591950

  1. Sunsynchronous low Earth orbit spacecraft concepts and technology requirements for global change monitoring

    NASA Technical Reports Server (NTRS)

    Garrett, L. Bernard; Butterfield, Ansel J.; Taback, Israel; Garn, Paul A.; Burrowbridge, Donald R., Jr.

    1991-01-01

    The Global Change Technology Initiative listing of instruments for operation in low Earth, sunsynchronous orbits contain 21 entries, of which 20 are carried aboard multi-instrument spacecraft. This list identifies the temporal requirements for repetition of measurements and also includes groups of instruments that make complementing measurements. Definitions for individual spacecraft follows the temporal and grouping requirements to establish constellations which will provide the measurement data. The definitions of constellations for multi-instrument spacecraft show two alternatives: a constellation of 10 spacecraft, each compatible with launch by a Delta booster; a constellation of 4 spacecraft, each requiring a Titan booster. Operating subsystems for the individual spacecraft can use modular concepts that are adaptations based upon current plans for improving the performance of the NASA-Goddard Multimission Modular units. The descriptions of the spacecraft and constellations begins with a compilation of instrument related requirements that define the principal system performance parameters and operating capabilities.

  2. IDENTIFYING AND TARGETING TUMOR-INITIATING CELLS IN THE TREATMENT OF BREAST CANCER

    PubMed Central

    Wei, Wei; Lewis, Michael T.

    2015-01-01

    Breast cancer is the most common cancer in women (exclusive of skin cancer), and is the second leading cause of cancer-related deaths. Although conventional and targeted therapies have improved survival rates, there are still considerable challenges in treating breast cancer, including treatment resistance, disease recurrence, and metastasis. Treatment resistance can be either de novo - due to traits that tumor cells possess prior to treatment, or acquired, - due to traits that tumor cells gain in response to treatment. A recently proposed mechanism of de novo resistance invokes existence of a specialized subset of cancer cells defined as tumor-initiating cells (TICs), or cancer stem cells (CSC). TICs have the capacity to self-renew and regenerate new tumors that consist of all clonally-derived cell types present in the parental tumor. There are data to suggest that TICs are resistant to many conventional cancer therapies, and survive treatment in spite of dramatic shrinkage of the tumor. Residual TICs can then eventually regrow resulting in disease relapse. It is also hypothesized that TIC may be responsible for metastatic disease. If these hypotheses are correct, targeting TICs may be imperative to achieve cure. In this review, we discuss evidence for breast TICs and their apparent resistance to conventional chemotherapy and radiotherapy, as well as to various targeted therapies. We also address the potential impact of breast TIC plasticity and metastatic potential on therapeutic strategies. Finally, we describe several genes and signaling pathways that appear important for TIC function that may represent promising therapeutic targets. PMID:25876646

  3. Advanced Solar-propelled Cargo Spacecraft for Mars Missions

    NASA Technical Reports Server (NTRS)

    Auziasdeturenne, Jacqueline; Beall, Mark; Burianek, Joseph; Cinniger, Anna; Dunmire, Barbrina; Haberman, Eric; Iwamoto, James; Johnson, Stephen; Mccracken, Shawn; Miller, Melanie

    1989-01-01

    Three concepts for an unmanned, solar powered, cargo spacecraft for Mars support missions were investigated. These spacecraft are designed to carry a 50,000 kg payload from a low Earth orbit to a low Mars orbit. Each design uses a distinctly different propulsion system: A Solar Radiation Absorption (SRA) system, a Solar-Pumped Laser (SPL) system and a solar powered magnetoplasmadynamic (MPD) arc system. The SRA directly converts solar energy to thermal energy in the propellant through a novel process. In the SPL system, a pair of solar-pumped, multi-megawatt, CO2 lasers in sunsynchronous Earth orbit converts solar energy to laser energy. The MPD system used indium phosphide solar cells to convert sunlight to electricity, which powers the propulsion system. Various orbital transfer options are examined for these concepts. In the SRA system, the mother ship transfers the payload into a very high Earth orbit and a small auxiliary propulsion system boosts the payload into a Hohmann transfer to Mars. The SPL spacecraft and the SPL powered spacecraft return to Earth for subsequent missions. The MPD propelled spacecraft, however, remains at Mars as an orbiting space station. A patched conic approximation was used to determine a heliocentric interplanetary transfer orbit for the MPD propelled spacecraft. All three solar-powered spacecraft use an aerobrake procedure to place the payload into a low Mars parking orbit. The payload delivery times range from 160 days to 873 days (2.39 years).

  4. Targeting pancreatitis blocks tumor-initiating stem cells and pancreatic cancer progression.

    PubMed

    Mohammed, Altaf; Janakiram, Naveena B; Madka, Venkateshwar; Brewer, Misty; Ritchie, Rebekah L; Lightfoot, Stan; Kumar, Gaurav; Sadeghi, Michael; Patlolla, Jagan Mohan R; Yamada, Hiroshi Y; Cruz-Monserrate, Zobeida; May, Randal; Houchen, Courtney W; Steele, Vernon E; Rao, Chinthalapally V

    2015-06-20

    Recent development of genetically engineered mouse models (GEMs) for pancreatic cancer (PC) that recapitulates human disease progression has helped to identify new strategies to delay/inhibit PC development. We first found that expression of the pancreatic tumor-initiating/cancer stem cells (CSC) marker DclK1 occurs in early stage PC and in both early and late pancreatic intraepithelial neoplasia (PanIN) and that it increases as disease progresses in GEM and also in human PC. Genome-wide next generation sequencing of pancreatic ductal adenocarcinoma (PDAC) from GEM mice revealed significantly increased DclK1 along with inflammatory genes. Genetic ablation of cyclo-oxygenase-2 (COX-2) decreased DclK1 in GEM. Induction of inflammation/pancreatitis with cerulein in GEM mice increased DclK1, and the novel dual COX/5-lipoxygenase (5-LOX) inhibitor licofelone reduced it. Dietary licofelone significantly inhibited the incidence of PDAC and carcinoma in situ with significant inhibition of pancreatic CSCs. Licofelone suppressed pancreatic tumor COX-2 and 5-LOX activities and modulated miRNAs characteristic of CSC and inflammation in correlation with PDAC inhibition. These results offer a preclinical proof of concept to target the inflammation initiation to inhibit cancer stem cells early for improving the treatment of pancreatic cancers, with immediate clinical implications for repositioning dual COX/5-LOX inhibitors in human trials for high risk patients. PMID:25906749

  5. Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells

    PubMed Central

    Yang, Chi-Chun; Suzuki, Masahiro; Yamakawa, Shiori; Uno, Syuzi; Ishii, Ai; Yamazaki, Satoshi; Fukatsu, Rino; Fujisawa, Ryo; Sakimura, Kenji; Tsurimoto, Toshiki; Masai, Hisao

    2016-01-01

    Claspin transmits replication stress signal from ATR to Chk1 effector kinase as a mediator. It also plays a role in efficient replication fork progression during normal growth. Here we have generated conditional knockout of Claspin and show that Claspin knockout mice are dead by E12.5 and Claspin knockout mouse embryonic fibroblast (MEF) cells show defect in S phase. Using the mutant cell lines, we report the crucial roles of the acidic patch (AP) near the C terminus of Claspin in initiation of DNA replication. Cdc7 kinase binds to AP and this binding is required for phosphorylation of Mcm. AP is involved also in intramolecular interaction with a N-terminal segment, masking the DNA-binding domain and a newly identified PIP motif, and Cdc7-mediated phosphorylation reduces the intramolecular interaction. Our results suggest a new role of Claspin in initiation of DNA replication during normal S phase through the recruitment of Cdc7 that facilitates phosphorylation of Mcm proteins. PMID:27401717

  6. Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells.

    PubMed

    Yang, Chi-Chun; Suzuki, Masahiro; Yamakawa, Shiori; Uno, Syuzi; Ishii, Ai; Yamazaki, Satoshi; Fukatsu, Rino; Fujisawa, Ryo; Sakimura, Kenji; Tsurimoto, Toshiki; Masai, Hisao

    2016-01-01

    Claspin transmits replication stress signal from ATR to Chk1 effector kinase as a mediator. It also plays a role in efficient replication fork progression during normal growth. Here we have generated conditional knockout of Claspin and show that Claspin knockout mice are dead by E12.5 and Claspin knockout mouse embryonic fibroblast (MEF) cells show defect in S phase. Using the mutant cell lines, we report the crucial roles of the acidic patch (AP) near the C terminus of Claspin in initiation of DNA replication. Cdc7 kinase binds to AP and this binding is required for phosphorylation of Mcm. AP is involved also in intramolecular interaction with a N-terminal segment, masking the DNA-binding domain and a newly identified PIP motif, and Cdc7-mediated phosphorylation reduces the intramolecular interaction. Our results suggest a new role of Claspin in initiation of DNA replication during normal S phase through the recruitment of Cdc7 that facilitates phosphorylation of Mcm proteins. PMID:27401717

  7. Degradation mechanism of alkyl carbonate solvents used in lithium-ion cells during initial charging

    NASA Astrophysics Data System (ADS)

    Yoshida, H.; Fukunaga, T.; Hazama, T.; Terasaki, M.; Mizutani, M.; Yamachi, M.

    The degradation mechanism of electrolytes in the lithium-ion cell with LiCoO 2 and graphite electrodes was investigated by analyzing: (i) the composition of generated gases; (ii) thin films formed on the electrode, and (iii) the compositional change of the electrolyte during the initial charging. The solvents in this work were ethylene carbonate (EC), dimethyl carbonate (DMC), ethylmethyl carbonate (EMC) and diethyl carbonate (DEC). LiPF 6 was used as a salt. In the one- to three-component systems containing EC, carbon monoxide and ethane were detected, whereas Li 2CO 3, RCOOLi and (CH 2OLi) 2 were the main components of the surface film on the negative electrode. From these results, it can be assumed that the decomposition of the systems was mainly due to the reductive reaction of EC at the initial charging. Through the additional analysis of the electrolyte composition, it was confirmed that the dialkyl-2,5-dioxahexane carboxylate was produced in the electrolyte after initial charging. This suggests the occurrence of trans-esterification.

  8. Initiation of programmed cell death in the suspensor is predominantly regulated maternally in a tobacco hybrid

    PubMed Central

    Luo, An; Zhao, Peng; Zhang, Li-Yao; Sun, Meng-Xiang

    2016-01-01

    Maternal gene products deposited in the egg regulate early embryogenesis before activation of the embryonic genome in animals. While in higher plants, it is believed that genes of parental origin contribute to early embryogenesis. However, little is known regarding the particular processes in which genes of parental origin are involved during early embryogenesis. Previously, we found that the initiation of programmed cell death (PCD) in the suspensor of the embryo is regulated by the cystatin, NtCYS. Here, we confirmed that both parental transcripts contribute to PCD, but the relative expression level of the maternal NtCYS allele was much higher than that of the paternal allele in early embryos of tobacco interspecific hybrids. The expression level of the maternal NtCYS allele was decreased markedly, which was necessary for the initiation of PCD, while the paternal allele didn’t change. Interestingly, the pattern of PCD in the hybrid suspensor and the morphology of the hybrid suspensor were similar to those of the maternal parent. Our results suggest that NtCYS-mediated PCD initiation in the hybrid suspensor is likely controlled in a maternal dominant manner. This finding represents an example of the involvement of parental transcripts in a specific developmental event during early embryogenesis. PMID:27432530

  9. Characterizing IGR IRES-mediated translation initiation for use in yeast cell-free protein synthesis.

    PubMed

    Hodgman, C Eric; Jewett, Michael C

    2014-09-25

    Eukaryotic cell-free protein synthesis (CFPS) systems are limited, in part, by inefficient translation initiation. Here, we report three internal ribosome entry site (IRES) sequences from the Dicistroviridae family that are highly active in yeast CFPS. These include the intergenic region (IGR) IRES from cricket paralysis virus (CrPV), plautia stali intestine virus (PSIV) and Solenopsis invicta virus 1 (SINV1). Optimization of combined transcription and translation (Tx/Tl) CFPS reactions primed with linear DNA containing the CrPV IGR IRES resulted in batch synthesis yields of 0.92 ± 0.17 μg/mL luciferase. Further template engineering, such as including the first 12 nt of native CrPV gene, increased yields to 2.33 ± 0.11 μg/mL. We next observed that the inclusion of a 50 nt poly(A) to the 3' end of the IGR IRES-mediated message increased yields an additional 81% to 4.33 ± 0.37 μg/mL, without any effect on mRNA stability or copy number. This was surprising because the CrPV IGR IRES requires no known translation initiation factors. Lastly, we investigated a method to inhibit background expression through competitive inhibition by supplying the reaction with 5' cap structure analog. This study highlights the crucial role translation initiation plays in yeast CFPS and offers a simple platform to study IRES sequences. PMID:25017988

  10. Gravity Probe B spacecraft description

    NASA Astrophysics Data System (ADS)

    Bennett, Norman R.; Burns, Kevin; Katz, Russell; Kirschenbaum, Jon; Mason, Gary; Shehata, Shawky

    2015-11-01

    The Gravity Probe B spacecraft, developed, integrated, and tested by Lockheed Missiles & Space Company and later Lockheed Martin Corporation, consisted of structures, mechanisms, command and data handling, attitude and translation control, electrical power, thermal control, flight software, and communications. When integrated with the payload elements, the integrated system became the space vehicle. Key requirements shaping the design of the spacecraft were: (1) the tight mission timeline (17 months, 9 days of on-orbit operation), (2) precise attitude and translational control, (3) thermal protection of science hardware, (4) minimizing aerodynamic, magnetic, and eddy current effects, and (5) the need to provide a robust, low risk spacecraft. The spacecraft met all mission requirements, as demonstrated by dewar lifetime meeting specification, positive power and thermal margins, precision attitude control and drag-free performance, reliable communications, and the collection of more than 97% of the available science data.

  11. Gemini 9 spacecraft recovery operations

    NASA Technical Reports Server (NTRS)

    1966-01-01

    The Gemini 9-A spacecraft, with Astronauts Thomas Stafford and Eugene Cernan still inside, in water as the aircraft carrier U.S.S. Wasp, the recovery ship, comes alongside to recover the astronauts and their spaceship.

  12. ISS Update: Dream Chaser Spacecraft

    NASA Video Gallery

    NASA Public Affairs Officer Michael Curie talks with Cheryl McPhillips, Commercial Crew Program Partner Manager for the Sierra Nevada Corporation, the company developing the Dream Chaser spacecraft...

  13. Thermoelectric Outer Planets Spacecraft (TOPS)

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The research and advanced development work is reported on a ballistic-mode, outer planet spacecraft using radioisotope thermoelectric generator (RTG) power. The Thermoelectric Outer Planet Spacecraft (TOPS) project was established to provide the advanced systems technology that would allow the realistic estimates of performance, cost, reliability, and scheduling that are required for an actual flight mission. A system design of the complete RTG-powered outer planet spacecraft was made; major technical innovations of certain hardware elements were designed, developed, and tested; and reliability and quality assurance concepts were developed for long-life requirements. At the conclusion of its active phase, the TOPS Project reached its principal objectives: a development and experience base was established for project definition, and for estimating cost, performance, and reliability; an understanding of system and subsystem capabilities for successful outer planets missions was achieved. The system design answered long-life requirements with massive redundancy, controlled by on-board analysis of spacecraft performance data.

  14. Autonomous spacecraft maintenance study group

    NASA Technical Reports Server (NTRS)

    Marshall, M. H.; Low, G. D.

    1981-01-01

    A plan to incorporate autonomous spacecraft maintenance (ASM) capabilities into Air Force spacecraft by 1989 is outlined. It includes the successful operation of the spacecraft without ground operator intervention for extended periods of time. Mechanisms, along with a fault tolerant data processing system (including a nonvolatile backup memory) and an autonomous navigation capability, are needed to replace the routine servicing that is presently performed by the ground system. The state of the art fault handling capabilities of various spacecraft and computers are described, and a set conceptual design requirements needed to achieve ASM is established. Implementations for near term technology development needed for an ASM proof of concept demonstration by 1985, and a research agenda addressing long range academic research for an advanced ASM system for 1990s are established.

  15. Spacecraft Environmental Interactions Technology, 1983

    NASA Technical Reports Server (NTRS)

    1985-01-01

    State of the art of environment interactions dealing with low-Earth-orbit plasmas; high-voltage systems; spacecraft charging; materials effects; and direction of future programs are contained in over 50 papers.

  16. Nitric Oxide Inhibits Hetero-adhesion of Cancer Cells to Endothelial Cells: Restraining Circulating Tumor Cells from Initiating Metastatic Cascade

    NASA Astrophysics Data System (ADS)

    Lu, Yusheng; Yu, Ting; Liang, Haiyan; Wang, Jichuang; Xie, Jingjing; Shao, Jingwei; Gao, Yu; Yu, Suhong; Chen, Shuming; Wang, Lie; Jia, Lee

    2014-03-01

    Adhesion of circulating tumor cells (CTCs) to vascular endothelial bed becomes a crucial starting point in metastatic cascade. We hypothesized that nitric oxide (NO) may prevent cancer metastasis from happening by its direct vasodilation and inhibition of cell adhesion molecules (CAMs). Here we show that S-nitrosocaptopril (CAP-NO, a typical NO donor) produced direct vasorelaxation that can be antagonized by typical NO scavenger hemoglobin and guanylate cyclase inhibitor. Cytokines significantly stimulated production of typical CAMs by the highly-purified human umbilical vein endothelial cells (HUVECs). CAP-NO inhibited expression of the stimulated CAMs (particularly VCAM-1) and the resultant hetero-adhesion of human colorectal cancer cells HT-29 to the HUVECs in a concentration-dependent manner. The same concentration of CAP-NO, however, did not significantly affect cell viability, cell cycle and mitochondrial membrane potential of HT-29, thus excluding the possibility that inhibition of the hetero-adhesion was caused by cytotoxicity by CAP-NO on HT-29. Hemoglobin reversed the inhibition of CAP-NO on both the hetero-adhesion between HT-29 and HUVECs and VCAM-1 expression. These data demonstrate that CAP-NO, by directly releasing NO, produces vasorelaxation and interferes with hetero-adhesion of cancer cells to vascular endothelium via down-regulating expression of CAMs. The study highlights the importance of NO in cancer metastatic prevention.

  17. A critical role for AID in the initiation of reprogramming to induced pluripotent stem cells

    PubMed Central

    Bhutani, Nidhi; Decker, Matthew N.; Brady, Jennifer J.; Bussat, Rose T.; Burns, David M.; Corbel, Stephane Y.; Blau, Helen M.

    2013-01-01

    Mechanistic insights into the reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) are limited, particularly for early acting molecular regulators. Here we use an acute loss of function approach to demonstrate that activation-induced deaminase (AID) activity is necessary for the initiation of reprogramming to iPSCs. While AID is well known for antibody diversification, it has also recently been shown to have a role in active DNA demethylation in reprogramming toward pluripotency and development. These findings suggested a potential role for AID in iPSC generation, yet, iPSC yield from AID-knockout mouse fibroblasts was similar to that of wild-type (WT) fibroblasts. We reasoned that an acute loss of AID function might reveal effects masked by compensatory mechanisms during development, as reported for other proteins. Accordingly, we induced an acute reduction (>50%) in AID levels using 4 different shRNAs and determined that reprogramming to iPSCs was significantly impaired by 79 ± 7%. The deaminase activity of AID was critical, as coexpression of WT but not a catalytic mutant AID rescued reprogramming. Notably, AID was required only during a 72-h time window at the onset of iPSC reprogramming. Our findings show a critical role for AID activity in the initiation of reprogramming to iPSCs.—Bhutani, N., Decker, M. N., Brady, J. J., Bussat, R. T., Burns, D. M., Corbel, S. Y., Blau, H. M. A critical role for AID in the initiation of reprogramming to induced pluripotent stem cells. PMID:23212122

  18. Artist's drawing of Viking spacecraft

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The National Aeronautics and Space Administration is developing an unmanned spacecraft called Viking to continue the exploration of Mars in the mid-1970s. Two Viking spacecraft, each including an orbiter and a lander will be launched by TitanIII/Centaur launch vehicles in August and September 1975 from Cape Kennedy to reach Mars in mid-1976. They will perform scientific investigations both from orbit and on the surface of Mars, including a search for life form on the planet.

  19. Spacecraft Thermal Control Coatings References

    NASA Technical Reports Server (NTRS)

    Kauder, Lonny

    2005-01-01

    The successful thermal design of spacecraft depends in part on a knowledge of the solar absorption and hemispherical emittance of the thermal control coatings used in and on the spacecraft. Goddard Space Flight Center has had since its beginning a group whose mission has been to provide thermal/optical properties data of thermal control coatings to thermal engineers. This handbook represents a summary of the data and knowledge accumulated over many years at GSFC.

  20. Small Spacecraft for Planetary Science

    NASA Astrophysics Data System (ADS)

    Baker, John; Castillo-Rogez, Julie; Bousquet, Pierre-W.; Vane, Gregg; Komarek, Tomas; Klesh, Andrew

    2016-07-01

    As planetary science continues to explore new and remote regions of the Solar system with comprehensive and more sophisticated payloads, small spacecraft offer the possibility for focused and more affordable science investigations. These small spacecraft or micro spacecraft (< 100 kg) can be used in a variety of architectures consisting of orbiters, landers, rovers, atmospheric probes, and penetrators. A few such vehicles have been flown in the past as technology demonstrations. However, technologies such as new miniaturized science-grade sensors and electronics, advanced manufacturing for lightweight structures, and innovative propulsion are making it possible to fly much more capable micro spacecraft for planetary exploration. While micro spacecraft, such as CubeSats, offer significant cost reductions with added capability from advancing technologies, the technical challenges for deep space missions are very different than for missions conducted in low Earth orbit. Micro spacecraft must be able to sustain a broad range of planetary environments (i.e., radiations, temperatures, limited power generation) and offer long-range telecommunication performance on a par with science needs. Other capabilities needed for planetary missions, such as fine attitude control and determination, capable computer and data handling, and navigation are being met by technologies currently under development to be flown on CubeSats within the next five years. This paper will discuss how micro spacecraft offer an attractive alternative to accomplish specific science and technology goals and what relevant technologies are needed for these these types of spacecraft. Acknowledgements: Part of this work is being carried out at the Jet Propulsion Laboratory, California Institute of Technology under contract to NASA. Government sponsorship acknowledged.

  1. The Atmosphere Explorer spacecraft system.

    NASA Technical Reports Server (NTRS)

    Spencer, N. W.; Brace, L. H.; Grimes, D. W.

    1973-01-01

    Brief description of the design goals, spacecraft, data system, and data analysis concept for the Atmosphere Explorer (AE) mission. The AE mission is shown to have been conceived and to be implemented for making possible a variety of studies of the lower thermosphere. The spacecraft support system, including an onboard propulsion system, will enable investigations to be carried out deep in the thermosphere and at all points of aeronomic significance about the earth.

  2. Spacecraft external molecular contamination analysis

    NASA Technical Reports Server (NTRS)

    Ehlers, H. K. F.

    1990-01-01

    Control of contamination on and around spacecraft is required to avoid adverse effects on the performance of instruments and spacecraft systems. Recent work in this area is reviewed and discussed. Specific issues and limitations to be considered as part of the effort to predict contamination effects using modeling techniques are addressed. Significant results of Space Shuttle missions in the field of molecule/surface interactions as well as their implications for space station design and operation are reviewed.

  3. Spacecraft design applications of QUICK

    NASA Technical Reports Server (NTRS)

    Skinner, David L.

    1992-01-01

    The interactive space mission trajectory design environment software QUICK, which is currently available on 14 different machine architectures, furnishes a programmable FORTRAN-like interface for a wide range of both built-in and user-defined functions. Since its inception at JPL in 1971, QUICK has evolved from a specialized calculator into a general-purpose engineering tool which also facilitates spacecraft conceptual design by treating spacecraft as collections of data records describing individual components of instruments.

  4. TLR4-dependent tumor-initiating stem cell-like cells (TICs) in alcohol-associated hepatocellular carcinogenesis.

    PubMed

    Machida, Keigo; Feldman, Douglas E; Tsukamoto, Hidekazu

    2015-01-01

    Alcohol abuse predisposes individuals to the development of hepatocellular carcinoma (HCC) and synergistically heightens the HCC risk in patients infected with hepatitis C virus (HCV). The mechanisms of this synergism have been elusive until our recent demonstration of the obligatory role of ectopically expressed TLR4 in liver tumorigenesis in alcohol-fed HCV Ns5a or Core transgenic mice. CD133+/CD49f+ tumor-initiating stem cell-like cells (TICs) isolated from these models are tumorigenic in a manner dependent on TLR4 and NANOG. TICs' tumor-initiating activity and chemoresistance are causally associated with inhibition of TGF-β tumor suppressor pathway due to NANOG-mediated expression of IGF2BP3 and YAP1. TLR4/NANOG activation causes p53 degradation via phosphorylation of the protective protein NUMB and its dissociation from p53 by the oncoprotein TBC1D15. Nutrient deprivation reduces overexpressed TBC1D15 in TICs via autophagy-mediated degradation, suggesting a possible role of this oncoprotein in linking metabolic reprogramming and self-renewal. PMID:25427905

  5. Development of orbital debris spacecraft breakup models

    NASA Astrophysics Data System (ADS)

    Tedeschi, William J.; Connell, John C.; McKnight, Darren S.

    1991-08-01

    The Defense Nuclear Agency has initiated an Orbital Debris Spacecraft Breakup Modeling Program to improve the accuracy and usefulness of satellite breakup models with an emphasis on collision-induced events. Empirical, semianalytic, and complex approaches are used in the modeling. Current results from the modeling effort are presented and discussed along with data from associated hypervelocity impact test programs. It is shown that major improvements in modeling have been made but that milestones must be achieved before the models will routinely provide accurate predictions for a wide range of collision scenarios.

  6. Software for Autonomous Spacecraft Maneuvers

    NASA Technical Reports Server (NTRS)

    Bristow, John; Folta, Dave; Hawkins, Al; Dell, Greg

    2004-01-01

    The AutoCon computer programs facilitate and accelerate the planning and execution of orbital control maneuvers of spacecraft while analyzing and resolving mission constraints. AutoCon-F is executed aboard spacecraft, enabling the spacecraft to plan and execute maneuvers autonomously; AutoCon-G is designed for use on the ground. The AutoCon programs utilize advanced techniques of artificial intelligence, including those of fuzzy logic and natural-language scripting, to resolve multiple conflicting constraints and automatically plan maneuvers. These programs can be used to satisfy requirements for missions that involve orbits around the Earth, the Moon, or any planet, and are especially useful for missions in which there are requirements for frequent maneuvers and for resolution of complex conflicting constraints. During operations, the software targets new trajectories, places and sizes maneuvers, and controls spacecraft burns. AutoCon-G provides a userfriendly graphical interface, and can be used effectively by an analyst with minimal training. AutoCon-F reduces latency and supports multiple-spacecraft and formation-flying missions. The AutoCon architecture supports distributive processing, which can be critical for formation- control missions. AutoCon is completely object-oriented and can easily be enhanced by adding new objects and events. AutoCon-F was flight demonstrated onboard GSFC's EO-1 spacecraft flying in formation with Landsat-7.

  7. Examination of physical processes of convective cell evolved from a MCS - using a different model initialization

    NASA Astrophysics Data System (ADS)

    Spiridonov, Vlado; Ćurić, Mladjen

    2016-06-01

    The present study is focused on examination of the physical processes of convective cell evolved from a MCS occurred on 4 November 2011 over Genoa, Italy. The Quantitative Precipitation Forecasts (QPF) have been performed using WRF v3.6 model under different configurations and cloud permitting simulations. The results indicate underestimation of the amount of precipitation and spatial displacement of the area with a peak 24-h accumulated rainfall in (mm). Our main objective in the research is to test the cloud model ability and performance in simulation of this particular case. For that purpose a set of sensitivity experiments under different model initializations and initial data have been conducted. The results also indicate that the merging process apparently alters the physical processes through low- and middle-level forcing, increasing cloud depth, and enhancing convection. The examination of the microphysical process simulated by the model indicates that dominant production terms are the accretion of rain by graupel and snow, probabilistic freezing of rain to form graupel and dry and wet growth of graupel. Experiment under WRF v3.6 model initialization has shown some advantage in simulation of the physical processes responsible for production and initiation of heavy rainfall compared to other model runs. Most of the precipitation came from ice-phase particles-via accretion processes and the graupel melting at temperature T0 ≥ 0°C. The rainfall intensity and accumulated rainfall calculated by the model closely reflect the amount of rainfall recorded. Thus, the main benefit is to better resolve convective showers or storms which, in extreme cases, can give rise to major flooding events. In such a way, this model may become major contributor to improvements in weather analysis and small-scale atmospheric predictions and early warnings of such subscale processes.

  8. Inhibition of Mouse Breast Tumor-Initiating Cells by Calcitriol and Dietary Vitamin D.

    PubMed

    Jeong, Youngtae; Swami, Srilatha; Krishnan, Aruna V; Williams, Jasmaine D; Martin, Shanique; Horst, Ronald L; Albertelli, Megan A; Feldman, Brian J; Feldman, David; Diehn, Maximilian

    2015-08-01

    The anticancer actions of vitamin D and its hormonally active form, calcitriol, have been extensively documented in clinical and preclinical studies. However, the mechanisms underlying these actions have not been completely elucidated. Here, we examined the effect of dietary vitamin D and calcitriol on mouse breast tumor-initiating cells (TICs, also known as cancer stem cells). We focused on MMTV-Wnt1 mammary tumors, for which markers for isolating TICs have previously been validated. We confirmed that these tumors expressed functional vitamin D receptors and estrogen receptors (ER) and exhibited calcitriol-induced molecular responses including ER downregulation. Following orthotopic implantation of MMTV-Wnt1 mammary tumor cells into mice, calcitriol injections or a vitamin D-supplemented diet caused a striking delay in tumor appearance and growth, whereas a vitamin D-deficient diet accelerated tumor appearance and growth. Calcitriol inhibited TIC tumor spheroid formation in a dose-dependent manner in primary cultures and inhibited TIC self-renewal in secondary passages. A combination of calcitriol and ionizing radiation inhibited spheroid formation more than either treatment alone. Further, calcitriol significantly decreased TIC frequency as evaluated by in vivo limiting dilution analyses. Calcitriol inhibition of TIC spheroid formation could be overcome by the overexpression of β-catenin, suggesting that the inhibition of Wnt/β-catenin pathway is an important mechanism mediating the TIC inhibitory activity of calcitriol in this tumor model. Our findings indicate that vitamin D compounds target breast TICs reducing tumor-initiating activity. Our data also suggest that combining vitamin D compounds with standard therapies may enhance anticancer activity and improve therapeutic outcomes. PMID:25934710

  9. Intelligent spacecraft module

    NASA Astrophysics Data System (ADS)

    Oungrinis, Konstantinos-Alketas; Liapi, Marianthi; Kelesidi, Anna; Gargalis, Leonidas; Telo, Marinela; Ntzoufras, Sotiris; Paschidi, Mariana

    2014-12-01

    The paper presents the development of an on-going research project that focuses on a human-centered design approach to habitable spacecraft modules. It focuses on the technical requirements and proposes approaches on how to achieve a spatial arrangement of the interior that addresses sufficiently the functional, physiological and psychosocial needs of the people living and working in such confined spaces that entail long-term environmental threats to human health and performance. Since the research perspective examines the issue from a qualitative point of view, it is based on establishing specific relationships between the built environment and its users, targeting people's bodily and psychological comfort as a measure toward a successful mission. This research has two basic branches, one examining the context of the system's operation and behavior and the other in the direction of identifying, experimenting and formulating the environment that successfully performs according to the desired context. The latter aspect is researched upon the construction of a scaled-model on which we run series of tests to identify the materiality, the geometry and the electronic infrastructure required. Guided by the principles of sensponsive architecture, the ISM research project explores the application of the necessary spatial arrangement and behavior for a user-centered, functional interior where the appropriate intelligent systems are based upon the existing mechanical and chemical support ones featured on space today, and especially on the ISS. The problem is set according to the characteristics presented at the Mars500 project, regarding the living quarters of six crew-members, along with their hygiene, leisure and eating areas. Transformable design techniques introduce spatial economy, adjustable zoning and increased efficiency within the interior, securing at the same time precise spatial orientation and character at any given time. The sensponsive configuration is

  10. Myeloproliferative neoplasms can be initiated from a single hematopoietic stem cell expressing JAK2-V617F

    PubMed Central

    Lundberg, Pontus; Takizawa, Hitoshi; Kubovcakova, Lucia; Guo, Guoji; Hao-Shen, Hui; Dirnhofer, Stephan; Orkin, Stuart H.; Manz, Markus G.

    2014-01-01

    The majority of patients with myeloproliferative neoplasms (MPNs) carry a somatic JAK2-V617F mutation. Because additional mutations can precede JAK2-V617F, it is questioned whether JAK2-V617F alone can initiate MPN. Several mouse models have demonstrated that JAK2-V617F can cause MPN; however, in all these models disease was polyclonal. Conversely, cancer initiates at the single cell level, but attempts to recapitulate single-cell disease initiation in mice have thus far failed. We demonstrate by limiting dilution and single-cell transplantations that MPN disease, manifesting either as erythrocytosis or thrombocytosis, can be initiated clonally from a single cell carrying JAK2-V617F. However, only a subset of mice reconstituted from single hematopoietic stem cells (HSCs) displayed MPN phenotype. Expression of JAK2-V617F in HSCs promoted cell division and increased DNA damage. Higher JAK2-V617F expression correlated with a short-term HSC signature and increased myeloid bias in single-cell gene expression analyses. Lower JAK2-V617F expression in progenitor and stem cells was associated with the capacity to stably engraft in secondary recipients. Furthermore, long-term repopulating capacity was also present in a compartment with intermediate expression levels of lineage markers. Our studies demonstrate that MPN can be initiated from a single HSC and illustrate that JAK2-V617F has complex effects on HSC biology. PMID:25288396

  11. Expression of human eukaryotic initiation factor 3f oscillates with cell cycle in A549 cells and is essential for cell viability

    PubMed Central

    2010-01-01

    Background Transcriptional and postranslational regulation of the cell cycle has been widely studied. However, there is scarce knowledge concerning translational control of this process. Several mammalian eukaryotic initiation factors (eIFs) seem to be implicated in controlling cell proliferation. In this work, we investigated if the human eIF3f expression and function is cell cycle related. Results The human eIF3f expression has been found to be upregulated in growth-stimulated A549 cells and downregulated in G0. Western blot analysis and eIF3f promotor-luciferase fusions revealed that eIF3f expression peaks twice in the cell cycle: in the S and the M phases. Deregulation of eIF3f expression negatively affects cell viability and induces apoptosis. Conclusions The expression pattern of human eIF3f during the cell cycle confirms that this gene is cell division related. The fact that eIF3f expression peaks in two cell cycle phases raises the possibility that this gene may exert a differential function in the S and M phases. Our results strongly suggest that eIF3f is essential for cell proliferation. PMID:20462454

  12. Secretome of human bone marrow mesenchymal stem cells: an emerging player in lung cancer progression and mechanisms of translation initiation.

    PubMed

    Attar-Schneider, Oshrat; Zismanov, Victoria; Drucker, Liat; Gottfried, Maya

    2016-04-01

    Non-small cell lung cancer (NSCLC) remains the most common cause of cancer-related death worldwide. Patients presenting with advanced-stage NSCLC have poor prognosis, while metastatic spread accounts for >70 % of patient's deaths. The major advances in the treatment of lung cancer have brought only minor improvements in survival; therefore, novel strategic treatment approaches are urgently needed. Accumulating data allocate a central role for the cancer microenvironment including mesenchymal stem cells (MSCs) in acquisition of drug resistance and disease relapse. Furthermore, studies indicate that translation initiation factors are over expressed in NSCLC and negatively impact its prognosis. Importantly, translation initiation is highly modulated by microenvironmental cues. Therefore, we decided to examine the effect of bone marrow MSCs (BM-MSCs) from normal donors on NSCLC cell lines with special emphasis on translation initiation mechanism in the crosstalk. We cultured NSCLC cell lines with BM-MSC conditioned media (i.e., secretome) and showed deleterious effects on the cells' proliferation, viability, death, and migration. We also demonstrated reduced levels of translation initiation factors implicated in cancer progression [eukaryotic translation initiation factor 4E (eIF4E) and eukaryotic translation initiation factor 4GI (eIF4GI)], their targets, and regulators. Finally, we outlined a mechanism by which BM-MSCs' secretome affected NSCLC's mitogen-activated protein kinase (MAPK) signaling pathway, downregulated the cell migration, and diminished translation initiation factors' levels. Taken together, our study demonstrates that there is direct dialogue between the BM-MSCs' secretome and NSCLC cells that manipulates translation initiation and critically affects cell fate. We suggest that therapeutic approach that will sabotage this dialogue, especially in the BM microenvironment, may diminish lung cancer metastatic spread and morbidity and improve the patient

  13. Electrochemical deposition and surface-initiated RAFT polymerization: protein and cell-resistant PPEGMEMA polymer brushes.

    PubMed

    Tria, Maria Celeste R; Grande, Carlos David T; Ponnapati, Ramakrishna R; Advincula, Rigoberto C

    2010-12-13

    This paper introduces a novel and versatile method of grafting protein and cell-resistant poly(poly ethylene glycol methyl ether methacrylate) (PPEGMEMA) brushes on conducting Au surface. The process started with the electrochemical deposition and full characterization of an electro-active chain transfer agent (CTA) on the Au surface. The electrochemical behavior of the CTA was investigated by cyclic voltammetry (CV) while the deposition and stability of the CTA on the surface were confirmed by ellipsometry, contact angle, and X-ray photoelectron spectroscopy (XPS). The capability of the electrodeposited CTA to mediate surface-initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization on both the polymethyl methacrylate (PMMA; model polymer) and PPEGMEMA brushes was demonstrated by the increase in thicknesses of the films after polymerization. Contact angles also decreased with the incorporation of the more hydrophilic brushes. Significant changes in the morphologies of the films before and after polymerization were also observed with atomic force microscopy (AFM) analyses. Furthermore, XPS results showed an increase in the O 1s peak intensity relative to C 1s after polymerizations, which confirmed the grafting of polyethyleneglycol (PEG) bearing brushes. The ability of the PPEGMEMA-modified Au surface to resist nonspecific adhesion of proteins and cells was monitored and confirmed by XPS, ellipsometry, contact angle, AFM, and fluorescence imaging. The new method presented has potential application as robust protein and cell-resistant coatings for electrically conducting electrodes and biomedical devices. PMID:21028799

  14. Roles of signaling pathways in drug resistance, cancer initiating cells and cancer progression and metastasis.

    PubMed

    McCubrey, James A; Abrams, Stephen L; Fitzgerald, Timothy L; Cocco, Lucio; Martelli, Alberto M; Montalto, Giuseppe; Cervello, Melchiorre; Scalisi, Aurora; Candido, Saverio; Libra, Massimo; Steelman, Linda S

    2015-01-01

    The EGFR/PI3K/PTEN/Akt/mTORC pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance, cancer initiating cells (CICs) and metastasis. The expression of this pathway is frequently altered in breast and other cancers due to mutations at or aberrant expression of: HER2, EGFR1, PIK3CA, and PTEN as well as other oncogenes and tumor suppressor genes. miRs and epigenetic mechanisms of gene regulation are also important events which regulate this pathway. In some breast cancer cases, mutations at certain components of this pathway (e.g., PIK3CA) are associated with a better prognosis than breast cancers lacking these mutations. The expression of this pathway has been associated with CICs and in some cases resistance to therapeutics. We will review the effects of activation of the EGFR/PI3K/PTEN/Akt/mTORC pathway primarily in breast cancer and development of drug resistance. The targeting of this pathway and other interacting pathways will be discussed as well as clinical trials with novel small molecule inhibitors as well as established drugs that are used to treat other diseases. In this manuscript, we will discuss an inducible EGFR model (v-ERB-B:ER) and its effects on cell growth, cell cycle progression, activation of signal transduction pathways, prevention of apoptosis in hematopoietic, breast and prostate cancer models. PMID:25453219

  15. Implantable controlled release devices for BMP-7 delivery and suppression of glioblastoma initiating cells.

    PubMed

    Reguera-Nuñez, Elaine; Roca, Carlota; Hardy, Eugenio; de la Fuente, Maria; Csaba, Noemi; Garcia-Fuentes, Marcos

    2014-03-01

    Designing therapeutic devices capable of manipulating glioblastoma initiating cells (GICs) is critical to stop tumor recurrence and its associated mortality. Previous studies have indicated that bone morphogenetic protein-7 (BMP-7) acts as an endogenous suppressor of GICs, and thus, it could become a treatment for this cancer. In this work, we engineer an implantable microsphere system optimized for the controlled release of BMP-7 as a bioinspired therapeutic device against GICs. This microsphere delivery system is based on the formation of a heparin-BMP-7 nanocomplex, first coated with Tetronic(®) and further entrapped in a biodegradable polyester matrix. The obtained microspheres can efficiently encapsulate BMP-7, and release it in a controlled manner with minimum burst effect for over two months while maintaining protein bioactivity. Released BMP-7 showed a remarkable capacity to stop tumor formation in a GICs cell culture model, an effect that could be mediated by forced reprogramming of tumorigenic cells towards a non-tumorigenic astroglial lineage. PMID:24406213

  16. Lidamycin inhibits tumor initiating cells of hepatocellular carcinoma Huh7 through GSK3β/β-catenin pathway.

    PubMed

    Chen, Yi; Yu, Dongke; Zhang, Caixia; Shang, Boyang; He, Hongwei; Chen, Jinjing; Zhang, Hao; Zhao, Wuli; Wang, Zhen; Xu, Xiaoyu; Zhen, Yongsu; Shao, Rong-guang

    2015-01-01

    Recently, tumor initiating cells are considered as the central role of tumorigenicity in hepatocellular carcinoma. Enediyne anticancer antibiotic lidamycin with great potential antitumor activity is currently evaluated in Phase II clinical trials. In this study, we evaluated the effect of lidamycin on tumor initiating cells of hepatocellular carcinoma Huh7 and identified the potential mechanism. Flow cytometry analysis and sorting assay, surface marker assay, sphere formation assay, and aldefluor assay were used to evaluate the effect of lidamycin on Huh7 tumor initiating cells in vitro. To investigate the potential mechanism, the activity of GSK3β/β-catenin pathway was detected by Western blot and T cell factors transcriptional activity assay. Subcutaneous tumor model in nude mice was used to observe in vivo effect of lidamycin on Huh7 cells. Lidamycin decreased the proportion of EpCAM+ cells and the expression of EpCAM protein. Lidamycin inhibited sphere formation of sorted EpCAM+ cells in 7 d, and of parental cells in three serial passages. The population of aldehyde dehydrogenase-positive cells was reduced by lidamycin. In addition, lidamycin restrained tumor volume and incidence in vivo. Lidamycin activated GSK3β, and degraded the activity of β-catenin. Consequently, transcriptional activity of β-catenin/T cell factors was decreased. In brief, these results suggest that lidamycin suppressed Huh7 tumor initiating cells via GSK3β/β-catenin pathway. These findings reveal the potential mechanism of lidamycin on tumor initiating cells and the benefit for further clinical evaluation. PMID:23857500

  17. Carbon monoxide detector. [electrochemical gas detector for spacecraft use

    NASA Technical Reports Server (NTRS)

    Holleck, G. L.; Bradspies, J. L.; Brummer, S. B.; Nelsen, L. L.

    1973-01-01

    A sensitive carbon monoxide detector, developed specifically for spacecraft use, is described. An instrument range of 0 to 60 ppm CO in air was devised. The fuel cell type detector is used as a highly sensitive electrolysis cell for electrochemically detecting gases. The concept of an electrochemical CO detector is discussed and the CO oxidation behavior in phosphoric and sulfuric acid electrolytes is reported.

  18. Spacecraft Power. America in Space: The First Decade.

    ERIC Educational Resources Information Center

    Corliss, William R.

    The various electric power sources suitable for use aboard spacecraft are described in this booklet. These power sources include batteries, fuel cells, solar cells, RTGs (radioisotope thermoelectric generator), and nuclear fission power plants. The introductory sections include a discussion of power requirements and the anatomy of a space power…

  19. Increased sensitivity to ionizing radiation by targeting the homologous recombination pathway in glioma initiating cells.

    PubMed

    Lim, Yi Chieh; Roberts, Tara L; Day, Bryan W; Stringer, Brett W; Kozlov, Sergei; Fazry, Shazrul; Bruce, Zara C; Ensbey, Kathleen S; Walker, David G; Boyd, Andrew W; Lavin, Martin F

    2014-12-01

    Glioblastoma is deemed the most malignant form of brain tumour, particularly due to its resistance to conventional treatments. A small surviving group of aberrant stem cells termed glioma initiation cells (GICs) that escape surgical debulking are suggested to be the cause of this resistance. Relatively quiescent in nature, GICs are capable of driving tumour recurrence and undergo lineage differentiation. Most importantly, these GICs are resistant to radiotherapy, suggesting that radioresistance contribute to their survival. In a previous study, we demonstrated that GICs had a restricted double strand break (DSB) repair pathway involving predominantly homologous recombination (HR) associated with a lack of functional G1/S checkpoint arrest. This unusual behaviour led to less efficient non-homologous end joining (NHEJ) repair and overall slower DNA DSB repair kinetics. To determine whether specific targeting of the HR pathway with small molecule inhibitors could increase GIC radiosensitivity, we used the Ataxia-telangiectasia mutated inhibitor (ATMi) to ablate HR and the DNA-dependent protein kinase inhibitor (DNA-PKi) to inhibit NHEJ. Pre-treatment with ATMi prior to ionizing radiation (IR) exposure prevented HR-mediated DNA DSB repair as measured by Rad51 foci accumulation. Increased cell death in vitro and improved in vivo animal survival could be observed with combined ATMi and IR treatment. Conversely, DNA-PKi treatment had minimal impact on GICs ability to resolve DNA DSB after IR with only partial reduction in cell survival, confirming the major role of HR. These results provide a mechanistic insight into the predominant form of DNA DSB repair in GICs, which when targeted may be a potential translational approach to increase patient survival. PMID:25017126

  20. Lenalidomide plus Rituximab as Initial Treatment for Mantle-Cell Lymphoma

    PubMed Central

    Ruan, Jia; Martin, Peter; Shah, Bijal; Schuster, Stephen J.; Smith, Sonali M.; Furman, Richard R.; Christos, Paul; Rodriguez, Amelyn; Svoboda, Jakub; Lewis, Jessica; Katz, Orel; Coleman, Morton; Leonard, John P.

    2015-01-01

    BACKGROUND Mantle-cell lymphoma is generally incurable. Initial treatment is not standardized but usually includes cytotoxic chemotherapy. Lenalidomide, an immunomodulatory compound, and rituximab, an anti-CD20 antibody, are active in patients with recurrent mantle-cell lymphoma. We evaluated lenalidomide plus rituximab as a first-line therapy. METHODS We conducted a single-group, multicenter, phase 2 study with induction and maintenance phases. During the induction phase, lenalidomide was administered at a dose of 20 mg daily on days 1 through 21 of every 28-day cycle for 12 cycles; the dose was escalated to 25 mg daily after the first cycle if no dose-limiting adverse events occurred during the first cycle and was reduced to 15 mg daily during the maintenance phase. Rituximab was administered once weekly for the first 4 weeks and then once every other cycle until disease progression. The primary end point was the overall response rate. Secondary end points included outcomes related to safety, survival, and quality of life. RESULTS A total of 38 participants were enrolled at four centers from July 2011 through April 2014. The median age was 65 years. On the basis of the Mantle Cell Lymphoma International Prognostic Index scores, the proportions of participants with low-risk, intermediate-risk, and high-risk disease at baseline were similar (34%, 34%, and 32%, respectively). The most common grade 3 or 4 adverse events were neutropenia (in 50% of the patients), rash (in 29%), thrombocytopenia (in 13%), an inflammatory syndrome (“tumor flare”) (in 11%), anemia (in 11%), serum sickness (in 8%), and fatigue (in 8%). At the median follow-up of 30 months (through February 2015), the overall response rate among the participants who could be evaluated was 92% (95% confidence interval [CI], 78 to 98), and the complete response rate was 64% (95% CI, 46 to 79); median progression-free survival had not been reached. The 2-year progression-free survival was estimated to be

  1. RALFL34 regulates formative cell divisions in Arabidopsis pericycle during lateral root initiation.

    PubMed

    Murphy, Evan; Vu, Lam Dai; Van den Broeck, Lisa; Lin, Zhefeng; Ramakrishna, Priya; van de Cotte, Brigitte; Gaudinier, Allison; Goh, Tatsuaki; Slane, Daniel; Beeckman, Tom; Inzé, Dirk; Brady, Siobhan M; Fukaki, Hidehiro; De Smet, Ive

    2016-08-01

    In plants, many signalling molecules, such as phytohormones, miRNAs, transcription factors, and small signalling peptides, drive growth and development. However, very few small signalling peptides have been shown to be necessary for lateral root development. Here, we describe the role of the peptide RALFL34 during early events in lateral root development, and demonstrate its specific importance in orchestrating formative cell divisions in the pericycle. Our results further suggest that this small signalling peptide acts on the transcriptional cascade leading to a new lateral root upstream of GATA23, an important player in lateral root formation. In addition, we describe a role for ETHYLENE RESPONSE FACTORs (ERFs) in regulating RALFL34 expression. Taken together, we put forward RALFL34 as a new, important player in lateral root initiation. PMID:27521602

  2. RALFL34 regulates formative cell divisions in Arabidopsis pericycle during lateral root initiation

    PubMed Central

    Murphy, Evan; Vu, Lam Dai; Van den Broeck, Lisa; Lin, Zhefeng; Ramakrishna, Priya; van de Cotte, Brigitte; Gaudinier, Allison; Goh, Tatsuaki; Slane, Daniel; Beeckman, Tom; Inzé, Dirk; Brady, Siobhan M.; Fukaki, Hidehiro; De Smet, Ive

    2016-01-01

    In plants, many signalling molecules, such as phytohormones, miRNAs, transcription factors, and small signalling peptides, drive growth and development. However, very few small signalling peptides have been shown to be necessary for lateral root development. Here, we describe the role of the peptide RALFL34 during early events in lateral root development, and demonstrate its specific importance in orchestrating formative cell divisions in the pericycle. Our results further suggest that this small signalling peptide acts on the transcriptional cascade leading to a new lateral root upstream of GATA23, an important player in lateral root formation. In addition, we describe a role for ETHYLENE RESPONSE FACTORs (ERFs) in regulating RALFL34 expression. Taken together, we put forward RALFL34 as a new, important player in lateral root initiation. PMID:27521602

  3. A Case of Malignant Gastrointestinal Stromal Tumor Initially Misdiagnosed as Malignant B-Cell Lymphoma

    PubMed Central

    Suh, Byoung Jo

    2016-01-01

    Errors that occur in anatomic pathology influence the treatment strategy of patients with malignancy. There are four general types of error with three subtypes in the category of defective interpretation. The first subtype is a false-negative diagnosis or undercall of the extent or severity of the lesion, the second is a false-positive diagnosis, and the third is misclassification. We herein report a 65-year-old female patient with malignant gastrointestinal stromal tumor that was diagnosed after reevaluation of the lesion at our hospital – and treated with proximal gastrectomy – after initial diagnosis as malignant B-cell lymphoma on esophagogastroduodenoscopy biopsy of a small gastric fundic mass and subsequent treatment with six cycles of CHOP chemotherapy with aggravation of the mass at another hospital. PMID:27462236

  4. Space environmental interactions with spacecraft surfaces

    NASA Technical Reports Server (NTRS)

    Stevens, J. N.

    1979-01-01

    Environmental interactions are defined as the response of spacecraft surfaces to the charged-particle environment. These interactions are divided into two broad categories: spacecraft passive, in which the environment acts on the surfaces and spacecraft active, in which the spacecraft or a system on the spacecraft causes the interaction. The principal spacecraft passive interaction of concern is the spacecraft charging phenomenon. The spacecraft active category introduces the concept of interactions with the thermal plasma environment and Earth's magnetic fields, which are important at all altitudes and must be considered the designs of proposed large space structures and space power systems. The status of the spacecraft charging investigations is reviewed along with the spacecraft active interactions.

  5. Spacecraft oxygen recovery system

    NASA Technical Reports Server (NTRS)

    Quattrone, P. D.

    1974-01-01

    Recovery system is comprised of three integrated subsystems: electrochemical carbon dioxide concentrator which removes carbon dioxide from atmosphere, Sabatier reactor in which carbon dioxide is reduced with hydrogen to form methane and water, and static-feed water electrolysis cell to recover oxygen from water.

  6. ABCG2 is a potential marker of tumor-initiating cells in breast cancer.

    PubMed

    Sicchieri, Renata Danielle; da Silveira, Willian Abraham; Mandarano, Larissa Raquel Mouro; de Oliveira, Tatiane Mendes Gonçalves; Carrara, Hélio Humberto Angotti; Muglia, Valdair Francisco; de Andrade, Jurandyr Moreira; Tiezzi, Daniel Guimarães

    2015-12-01

    The existence of tumor-initiating cells (TICs) within solid tumors has been hypothesized to explain tumor heterogeneity and resistance to cancer therapy. In breast cancer, the expression of CD44 and CD24 and the activity of aldehyde dehydrogenase 1 (ALDH1) can be used to selectively isolate a cell population enriched in TICs. However, the ideal marker to identify TICs has not been established. The aim of this study was to evaluate the expression of novel potential markers for TIC in breast carcinoma. We prospectively analyzed the expression of CD44, CD24, ABCG2, and CXCR4, and the activity of ALDH1 by using flow cytometry in 48 invasive ductal carcinomas from locally advanced and metastatic breast cancer patients who were administered primary chemotherapy. A mammosphere assay was employed in 30 samples. The relationship among flow cytometric analyses, ABCG2 gene expression, and clinical and pathological responses to therapy was analyzed. The GSE32646 database was analyzed in silico to identify genes associated with tumors with low and high ABCG2 expression. We observed that the presence of ABCG2(+) cells within the primary tumor was the only marker to predict the formation of mammospheres in vitro (R (2) = 0.15, p = 0.029). Quantitative polymerase chain reaction (qPCR) revealed a positive correlation between ABCG2 expression and the presence of ABCG2(+) cells within the primary tumor. The expression of ABCG2 was predictive of the response to neoadjuvant chemotherapy in our experiments and in the GSE32646 dataset (p = 0.04 and p = 0.002, respectively). The in silico analysis demonstrated that ABCG2(Up) breast cancer samples have a slower cell cycle and a higher expression of membrane proteins but a greater potential for chromosomal instability, metastasis, immune evasion, and resistance to hypoxia. Such genetic characteristics are compatible with highly aggressive and resistant tumors. Our results support the hypothesis that the presence of ABCG2

  7. Analysis of spacecraft data

    NASA Technical Reports Server (NTRS)

    1984-01-01

    A software program for the production and analysis of data from the Dynamics Explorer-A (DE-A) satellite was maintained and modified and new software initiated. A capability was developed to process DE-A plasma-wave instrument mission analysis files on the Tektronic 4027 color CRT, for which two programs were written. The algorithm for the calibration lookup table for the plasma-wave instrument data was modified and verified, and a production program to generate color FR-80 spectrograms was written.

  8. Simulating Flexible-Spacecraft Dynamics and Control

    NASA Technical Reports Server (NTRS)

    Fedor, Joseph

    1987-01-01

    Versatile program applies to many types of spacecraft and dynamical problems. Flexible Spacecraft Dynamics and Control program (FSD) developed to aid in simulation of large class of flexible and rigid spacecraft. Extremely versatile and used in attitude dynamics and control analysis as well as in-orbit support of deployment and control of spacecraft. Applicable to inertially oriented spinning, Earth-oriented, or gravity-gradient-stabilized spacecraft. Written in FORTRAN 77.

  9. Magnetic shielding for interplanetary spacecraft

    SciTech Connect

    Herring, J.S.; Merrill, B.J.

    1991-12-01

    The protection of spacecraft crews from the radiation produced by high energy electrons, protons and heavier ions in the space environment is a major health concern on long duration missions. Conventional approaches to radiation shielding in space have relied on thicker spacecraft walls to stop the high energy charged particles and to absorb the resulting gamma and bremsstrahlung photons. The shielding concept described here uses superconducting magnets to deflect charged particles before they collide with the spacecraft, thus avoiding the production of secondary particles. A number of spacecraft configurations and sizes have been analyzed, ranging from a small ``storm cellar`` for use during solar flares to continuous shielding for space stations having a crew of 15--25. The effectiveness of the magnetic shielding has been analyzed using a Monte Carlo program with incident proton energies from 0.5 to 1000 MeV. Typically the shield deflects 35--99 percent of the incident particles, depending, of course on particle energy and magnetic field strength. Further evaluation studies have been performed to assess weight comparisons between magnetic and conventional shielding; to determine magnet current distributions which minimize the magnetic field within the spacecraft itself; and to assess the potential role of ceramic superconductors. 2 figs., 8 tabs.

  10. Magnetic shielding for interplanetary spacecraft

    SciTech Connect

    Herring, J.S.; Merrill, B.J.

    1991-01-01

    The protection of spacecraft crews from the radiation produced by high energy electrons, protons and heavier ions in the space environment is a major health concern on long duration missions. Conventional approaches to radiation shielding in space have relied on thicker spacecraft walls to stop the high energy charged particles and to absorb the resulting gamma and bremsstrahlung photons. The shielding concept described here uses superconducting magnets to deflect charged particles before they collide with the spacecraft, thus avoiding the production of secondary particles. A number of spacecraft configurations and sizes have been analyzed, ranging from a small storm cellar'' for use during solar flares to continuous shielding for space stations having a crew of 15--25. The effectiveness of the magnetic shielding has been analyzed using a Monte Carlo program with incident proton energies from 0.5 to 1000 MeV. Typically the shield deflects 35--99 percent of the incident particles, depending, of course on particle energy and magnetic field strength. Further evaluation studies have been performed to assess weight comparisons between magnetic and conventional shielding; to determine magnet current distributions which minimize the magnetic field within the spacecraft itself; and to assess the potential role of ceramic superconductors. 2 figs., 8 tabs.

  11. Cycle life test. Evaluation program for secondary spacecraft cells. [performance tests on silver zinc batteries, silver cadmium batteries, and nickel cadmium batteries

    NASA Technical Reports Server (NTRS)

    Harkness, J. D.

    1976-01-01

    Considerable research is being done to find more efficient and reliable means of starting electrical energy for orbiting satellites. Rechargeable cells offer one such means. A test program is described which has been established in order to further the evaluation of certain types of cells and to obtain performance and failure data as an aid to their continued improvement. The purpose of the program is to determine the cycling performance capabilities of packs of cells under different load and temperature conditions. The various kinds of cells tested were nickel-cadmium, silver-cadmium, and silver-zinc sealed cells. A summary of the results of the life cycling program is given in this report.

  12. Novel initiation genes in squamous cell carcinomagenesis: a role for substrate-specific ubiquitylation in the control of cell survival.

    PubMed

    Albor, Amador; Kulesz-Martin, Molly

    2007-08-01

    The study of experimental epidermal carcinogenesis offers several advantages over other epithelial carcinogenesis models, including easy accessibility and a database of research findings spanning over a century. Our studies make use of a clonal in vitro/in vivo keratinocyte carcinogenesis model with low frequency of ras mutation and derivative clonal-initiated lineages with distinct tumor fate. Analysis of this model has yielded candidate genes involved in the stages of initiation and tumorigenic progression, and has revealed novel roles for ubiquitylation in transcriptional control of survival and apoptotic pathways during the early stages of carcinogenesis. The expression of a recently described E3-ubiquitin ligase, Trim32, is elevated during initiation, and ectopic expression of Trim32 confers extended survival in response to terminal differentiation and ultraviolet light (UV) B/TNF-alpha death signals. Trim32 binds and ubiquitylates Piasy, controlling its stability and accumulation. Piasy is a SUMOylation factor involved in the control of apoptosis, senescence, and NF-kappaB activation. NF-kappaB is a survival factor for keratinocytes in response to UV irradiation, the main carcinogenic stimulus for the epidermis. Piasy inhibits NF-kappaB activity, and promotes keratinocyte apoptosis in response to UV and TNF-alpha. In human skin squamous cell carcinoma (SCC) samples, we found an inverse correlation between Trim32 and Piasy expression supporting a role for Trim32-Piasy interaction in human epidermal carcinogenesis. Our hypothesis is that increased expression of Trim32 may enhance epidermal carcinogenesis, by increasing the threshold of NF-kappaB activity through Piasy downmodulation. PMID:17626251

  13. Mechanisms of triplex DNA-mediated inhibition of transcription initiation in cells.

    PubMed

    Jain, Aklank; Magistri, Marco; Napoli, Sara; Carbone, Giuseppina M; Catapano, Carlo V

    2010-03-01

    Triplex-forming oligonucleotides (TFOs) are attractive tools to control gene expression at the transcriptional level. This anti-gene approach has proven to be successful in various experimental settings. However, the mechanisms leading to transcriptional repression in cells have not been fully investigated yet. Here, we examined the consequence of triplex DNA formation on the binding of transcriptional activators, co-activators and RNA Polymerase II to the ets2 gene promoter using chromatin immunoprecipitation assays. The triplex target sequence was located approximately 40-bp upstream of the transcription start site (TSS) and overlapped an Sp1 binding site relevant for ets2 transcription. We found that the ets2-TFO prevented binding of Sp1, TAF(II)130 and TAF(II)250 to the ets2 promoter, while binding of RNA polymerase II and TBP were not affected. The effects were both sequence and target specific, since the TFO had no effect on the c-myc promoter and a mutated ets2 promoter construct. Thus, triplex DNA formation near a TSS leads to formation of a non-functional pre-initiation complex (PIC) by blocking binding of transcriptional activators and co-activator molecules. This is the first direct demonstration of interference with PIC assembly at the TSS by oligonucleotide-triplex DNA formation in cells. PMID:20045441

  14. Effect of component compression on the initial performance of an IPV nickel-hydrogen cell

    NASA Technical Reports Server (NTRS)

    Gahn, Randall F.

    1987-01-01

    An experimental method was developed for evaluating the effect of component compression on the charge and discharge voltage characteristics of a 3 1/2 in. diameter boiler plate cell. A standard boiler plate pressure vessel was modified by the addition of a mechanical feedthrough on the bottom of the vessel which permitted different compressions to be applied to the components without disturbing the integrity of the stack. Compression loadings from 0.94 to 27.4 psi were applied by suspending weights from the feedthrough rod. Cell voltages were measured for 0.96-C, 55-min charge and for 1.37-C, 35-min and 2-C, 24-min discharges. An initial change in voltage performance on both charge and discharge as the loading increased was attributed to seating of the components. Subsequent variation of the compression from 2.97 to 27.4 psi caused only minor changes in either the charge or the discharge voltages. Several one month open-circuit voltage stands and 1100 cycles under LEO conditions at the maximum loading have produced no change in performance.

  15. Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans.

    PubMed

    Stapelberg, Michael; Zobalova, Renata; Nguyen, Maria Nga; Walker, Tom; Stantic, Marina; Goodwin, Jacob; Pasdar, Elham Alizadeh; Thai, Thuan; Prokopova, Katerina; Yan, Bing; Hall, Susan; de Pennington, Nicholas; Thomas, Shane R; Grant, Gary; Stursa, Jan; Bajzikova, Martina; Meedeniya, Adrian C B; Truksa, Jaroslav; Ralph, Stephen J; Ansorge, Olaf; Dong, Lan-Feng; Neuzil, Jiri

    2014-02-01

    Tumor-initiating cells (TICs) often survive therapy and give rise to second-line tumors. We tested the plausibility of sphere cultures as models of TICs. Microarray data and microRNA data analysis confirmed the validity of spheres as models of TICs for breast and prostate cancer as well as mesothelioma cell lines. Microarray data analysis revealed the Trp pathway as the only pathway upregulated significantly in all types of studied TICs, with increased levels of indoleamine-2,3-dioxygenase-1 (IDO1), the rate-limiting enzyme of Trp metabolism along the kynurenine pathway. All types of TICs also expressed higher levels of the Trp uptake system consisting of CD98 and LAT1 with functional consequences. IDO1 expression was regulated via both transcriptional and posttranscriptional mechanisms, depending on the cancer type. Serial transplantation of TICs in mice resulted in gradually increased IDO1. Mitocans, represented by α-tocopheryl succinate and mitochondrially targeted vitamin E succinate (MitoVES), suppressed IDO1 in TICs. MitoVES suppressed IDO1 in TICs with functional mitochondrial complex II, involving transcriptional and posttranscriptional mechanisms. IDO1 increase and its suppression by VE analogues were replicated in TICs from primary human glioblastomas. Our work indicates that IDO1 is increased in TICs and that mitocans suppress the protein. PMID:24145120

  16. CBP/catenin antagonist safely eliminates drug-resistant leukemia-initiating cells.

    PubMed

    Zhao, Y; Masiello, D; McMillian, M; Nguyen, C; Wu, Y; Melendez, E; Smbatyan, G; Kida, A; He, Y; Teo, J-L; Kahn, M

    2016-07-14

    CREB-binding protein (CBP) and p300 are highly homologous transcriptional coactivators with unique, non-redundant roles that bind a wide array of proteins, including catenins-β and γ. ICG-001 is a small-molecule inhibitor that specifically inhibits the CBP/catenin interaction. Importantly, ICG-001 does not inhibit the p300/catenin interaction. We demonstrate that specifically inhibiting the interaction between CBP and catenin with ICG-001 results in the differentiation of quiescent drug-resistant chronic myelogenous leukemia-initiating cells (CML LICs), thereby sensitizing them to BCR-ABL tyrosine kinase inhibitors, for example, Imatinib. Using ICG-001 in a NOD/SCID/IL2Rγ(-/-) mouse model of engrafted human chronic myelogenous leukemia, we now demonstrate the complete elimination of engrafted leukemia after only one course of combined chemotherapy. Combination-treated animals live as long as their non-engrafted littermates. Results from these studies demonstrate that specifically antagonizing the CBP/catenin interaction with ICG-001 can eliminate drug-resistant CML LICs without deleterious effects to the normal endogenous hematopoietic stem cell population. PMID:26657156

  17. Prostatic inflammation enhances basal-to-luminal differentiation and accelerates initiation of prostate cancer with a basal cell origin

    PubMed Central

    Kwon, Oh-Joon; Zhang, Li; Ittmann, Michael M.; Xin, Li

    2014-01-01

    Chronic inflammation has been shown to promote the initiation and progression of diverse malignancies by inducing genetic and epigenetic alterations. In this study, we investigate an alternative mechanism through which inflammation promotes the initiation of prostate cancer. Adult murine prostate epithelia are composed predominantly of basal and luminal cells. Previous studies revealed that the two lineages are largely self-sustained when residing in their native microenvironment. To interrogate whether tissue inflammation alters the differentiation program of basal cells, we conducted lineage tracing of basal cells using a K14-CreER;mTmG model in concert with a murine model of prostatitis induced by infection from the uropathogenic bacteria CP9. We show that acute prostatitis causes tissue damage and creates a tissue microenvironment that induces the differentiation of basal cells into luminal cells, an alteration that rarely occurs under normal physiological conditions. Previously we showed that a mouse model with prostate basal cell-specific deletion of Phosphatase and tensin homolog (K14-CreER;Ptenfl/fl) develops prostate cancer with a long latency, because disease initiation in this model requires and is limited by the differentiation of transformation-resistant basal cells into transformation-competent luminal cells. Here, we show that CP9-induced prostatitis significantly accelerates the initiation of prostatic intraepithelial neoplasia in this model. Our results demonstrate that inflammation results in a tissue microenvironment that alters the normal prostate epithelial cell differentiation program and that through this cellular process inflammation accelerates the initiation of prostate cancer with a basal cell origin. PMID:24367088

  18. Identification of a Novel Subpopulation of Tumor-Initiating Cells from Gemcitabine-Resistant Pancreatic Ductal Adenocarcinoma Patients

    PubMed Central

    Shimizu, Kazuya; Chiba, Sachie; Hori, Yuichi

    2013-01-01

    Pancreatic ductal adenocarcinoma is highly resistant to systemic chemotherapy. Although there are many reports using pancreatic cancer cells derived from patients who did not receive chemotherapy, characteristics of pancreatic cancer cells from chemotherapy-resistant patients remain unclear. In this study, we set out to establish a cancer cell line in disseminated cancer cells derived from gemcitabine-resistant pancreatic ductal adenocarcinoma patients. By use of in vitro co-culture system with stromal cells, we established a novel pancreatic tumor-initiating cell line. The cell line required its direct interaction with stromal cells for its in vitro clonogenic growth and passaging. Their direct interaction induced basal lamina-like extracellular matrix formation that maintained colony formation. The cell line expressed CD133 protein, which expression level changed autonomously and by culture conditions. These results demonstrated that there were novel pancreatic tumor-initiating cells that required direct interactions with stromal cells for their in vitro cultivation in gemcitabine-resistant pancreatic ductal adenocarcinoma. This cell line would help to develop novel therapies that enhance effects of gemcitabine or novel anti-cancer drugs. PMID:24278411

  19. Spacecraft Crew Cabin Condensation Control

    NASA Technical Reports Server (NTRS)

    Carrillo, Laurie Y.; Rickman, Steven L.; Ungar, Eugene K.

    2013-01-01

    A report discusses a new technique to prevent condensation on the cabin walls of manned spacecraft exposed to the cold environment of space, as such condensation could lead to free water in the cabin. This could facilitate the growth of mold and bacteria, and could lead to oxidation and weakening of the cabin wall. This condensation control technique employs a passive method that uses spacecraft waste heat as the primary wallheating mechanism. A network of heat pipes is bonded to the crew cabin pressure vessel, as well as the pipes to each other, in order to provide for efficient heat transfer to the cabin walls and from one heat pipe to another. When properly sized, the heat-pipe network can maintain the crew cabin walls at a nearly uniform temperature. It can also accept and distribute spacecraft waste heat to maintain the pressure vessel above dew point.

  20. Electromagnetic braking for Mars spacecraft

    NASA Technical Reports Server (NTRS)

    Holt, A. C.

    1986-01-01

    Aerobraking concepts are being studied to improve performance and cost effectiveness of propulsion systems for Mars landers and Mars interplanetary spacecraft. Access to megawatt power levels (nuclear power coupled to high-storage inductive or capacitive devices) on a manned Mars interplanetary spacecraft may make feasible electromagnetic braking and lift modulation techniques which were previously impractical. Using pulsed microwave and magnetic field technology, potential plasmadynamic braking and hydromagnetic lift modulation techniques have been identified. Entry corridor modulation to reduce loads and heating, to reduce vertical descent rates, and to expand horizontal and lateral landing ranges are possible benefits. In-depth studies are needed to identify specific design concepts for feasibility assessments. Standing wave/plasma sheath interaction techniques appear to be promising. The techniques may require some tailoring of spacecraft external structures and materials. In addition, rapid response guidance and control systems may require the use of structurally embedded sensors coupled to expert systems or to artificial intelligence systems.