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Sample records for spacecraft cells initial

  1. Guaranteed initialization of distributed spacecraft formations

    NASA Technical Reports Server (NTRS)

    Scharf, Daniel P.; Ploen, Scott R.; Hadaegh, Fred Y.; Keim, Jason A.; Phan, Linh H.

    2003-01-01

    In this paper we present a solution to the formation initialization (FI) problem for N distributed spacecraft located in deep space. Our solution to the FI problem is based on a three-stage sky search procedure that reduces the FI problem for N spacecraft to the simpler problem of initializing a set of sub-formations.

  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. Guaranteed spatial initialization of distributed spacecraft formations

    NASA Technical Reports Server (NTRS)

    Scharf, Daniel P.; Ploen, Scott R.; Hadaegh, Fred Y.; Sohl, Garett A.

    2004-01-01

    In a precious paper the authors developed a formation initialization (FI) algorithm for a deep space, N-spacecraft formation. It was demonstrated analytically that this FI contribution of this paper is to extend this planar guarantee to deep space formations with arbitrary initial conditions. As part of the guarantee of initialization, a bound on the time-to-initialize is obtained. The guaranteed FI algorithm is then demonstrated for a two-spacecraft formation with realistic deep space mission constraints (e.g. limited field-of-view relative sensors and attitude constraints). The two-spacecraft scenario is challenging in that it has the least relative sensor field-of-view overlap. Finally, for this scenario, the distribution of time-to-initialize is characterized through a 150,000-case Monte Carlo analysis.

  4. 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.

  5. 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.

  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. Initialization of distributed spacecraft for precision formation flying

    NASA Technical Reports Server (NTRS)

    Hadaegh, F. Y.; Scharf, D. P.; Ploen, S. R.

    2003-01-01

    In this paper we present a solution to the formation initialization problem for N distributed spacecraft located in deep space. Our solution to the FI problem is based on a three-stage sky search procedure that reduces the FI problem for N spacecraft to the simpler problem of initializing a set of sub-formations. We demonstrate our FI algorithm in simulation using NASA's five spacecraft Terrestrial Planet Finder mission as an example.

  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. AIAA spacecraft GN&C interface standards initiative: Overview

    NASA Technical Reports Server (NTRS)

    Challoner, A. Dorian

    1995-01-01

    The American Institute of Aeronautics and Astronautics (AIAA) has undertaken an important standards initiative in the area of spacecraft guidance, navigation, and control (GN&C) subsystem interfaces. The objective of this effort is to establish standards that will promote interchangeability of major GN&C components, thus enabling substantially lower spacecraft development costs. Although initiated by developers of conventional spacecraft GN&C, it is anticipated that interface standards will also be of value in reducing the development costs of micro-engineered spacecraft. The standardization targets are specifically limited to interfaces only, including information (i.e. data and signal), power, mechanical, thermal, and environmental interfaces between various GN&C components and between GN&C subsystems and other subsystems. The current emphasis is on information interfaces between various hardware elements (e.g., between star trackers and flight computers). The poster presentation will briefly describe the program, including the mechanics and schedule, and will publicize the technical products as they exist at the time of the conference. In particular, the rationale for the adoption of the AS1773 fiber-optic serial data bus and the status of data interface standards at the application layer will be presented.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  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. Voyager spacecraft radio observations of Jupiter - Initial cruise results

    NASA Technical Reports Server (NTRS)

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

    1979-01-01

    Low frequency (below 1326 kHz) observations of Jupiter obtained from November, 1977 through June, 1978 by the radio astronomy receivers carried by the two Voyager spacecraft are reported and compared with a large body of higher-frequency ground-based observations. Although the morphology of hectometric wavelength (HOM) emissions strongly resembles that of decametric (DAM) wavelength radio noise, they display opposite polarization. DAM emissions are strongly modulated by Io, whereas HOM emissions exhibit little or no influence from any satellite and appear to be modulated by the rotation phase of the planet. Several single-source models could possibly account for these results, including a model assuming emission at two well-separated frequencies above and below the local electron plasma frequency and the model proposed by Barbosa (1976) in which electrostatic waves at twice the upper hybrid frequency couple to both the ordinary and extraordinary electromagnetic modes. However, neither of these is entirely satisfactory.

  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: 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Active ion emission onboard the Double Star TC-1 spacecraft - results from initial science operations

    NASA Astrophysics Data System (ADS)

    Torkar, K.; Steiger, W.; Narheim, B. T.; Svenes, K.; Fehringer, M.; Escoubet, C. P.; Fazakerley, A. N.; Zhao, H.

    An ion emitter instrument ASPOC (Active Spacecraft Potential Control) belongs to the payload of the Chinese-European Double Star mission (TC-1) launched in December 2003. The instrument is a further development to the ones flown in the Cluster mission. Its objective is a reduction of the spacecraft potential in order to minimise the perturbations to the plasma measurements on board. The operation of the scientific payload began after commissioning in February 2004. Comparisons to Cluster are being made based on data from the first half year of the Double Star mission. The enhanced capabilities of the instrument allow to achieve even lower potentials than on Cluster. Differences to Cluster can also be expected because of the plasma environment at the equatorial orbit of TC-1. The effects of spacecraft potential control on the electron measurements by the instrument PEACE as observed during the first months of science operations are discussed.

  15. 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.

  16. 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.

  17. 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.

  18. Magnetospheric plasma analyzer - Initial three-spacecraft observations from geosynchronous orbit

    NASA Astrophysics Data System (ADS)

    McComas, D. J.; Bame, S. J.; Barraclough, B. L.; Donart, J. R.; Elphic, R. C.; Gosling, J. T.; Moldwin, M. B.; Moore, K. R.; Thomsen, M. F.

    1993-08-01

    A synoptic view of the morphology of the magnetosphere at geosynchronous orbit over a 6-wk interval in early 1992 is synthesized on the basis of simultaneous observations from three longitudinally separated spacecraft. Seven regions with characteristic plasma populations were discovered during this period. It is found that at geomagnetically quiet times geosynchronous orbit can lie entirely within the plasmasphere, while at more active times only the afternoon to evening portions of the orbit are typically within the plasmasphere. The plasma convection inside the plasmasphere is found to be generally sunward in the corotating reference frame, independent of activity level, in contrast to previous studies. Simultaneous prenoon and postnoon observations show that the magnetopause shape can be highly asymmetric about the earth-sun line.

  19. 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

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

    NASA Astrophysics Data System (ADS)

    Collier, M. R.; Rowland, D. E.; Keller, J. W.; Chornay, D. J.; Khazanov, G. V.; Herrero, F.; Moore, T. E.; Kujawski, J. T.; Casas, J. C.; Wilson, G. R.

    2011-12-01

    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 Experiments 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 (PI: Douglas Rowland).

  1. A simple attitude data filter for three-axis attitude initialization for autonomous ascent of Shuttle-launched spacecraft

    NASA Technical Reports Server (NTRS)

    Joshi, R. T.; Swale, J. F.

    1981-01-01

    A method for accurately initializing spacecraft attitude after release from the Orbiter is described. It is noted that the method is suitable for an autonomous ascent to mission orbit. Test results are given from a FORTRAN simulation of the estimation algorithm using measurement data from a detailed spacecraft dynamics simulation program. The technique here is orbital yaw-gyrocompassing. Attitude is estimated through a Kalman filter, using pitch and roll measurements from an earth sensor, while gyro data provide the system dynamics information. In the tests described, gyro and earth sensor data are generated by an existing control system simulation of earth-search and yaw-gyrocompassing attitude dynamics; they include realistic errors such as delays, random noise and quantization effects. The estimated attitude history is compared with the true attitude history from the simulation program to assess the accuracy and convergence of the filter in the presence of noisy measurements and disturbances, including thruster firings for momentum control. It is noted that since the earth sensor provides direct measurements of pitch and roll, the main criterion of filter performance is yaw accuracy.

  2. 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.

  3. 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.

  4. 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.

  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. Particle-In-Cell Analysis of an Electric Antenna for the BepiColombo/MMO spacecraft

    NASA Astrophysics Data System (ADS)

    Miyake, Yohei; Usui, Hideyuki; Kojima, Hirotsugu

    The BepiColombo/MMO spacecraft is planned to provide a first electric field measurement in Mercury's magnetosphere by mounting two types of the electric antennas: WPT and MEFISTO. The sophisticated calibration of such measurements should be performed based on precise knowledge of the antenna characteristics in space plasma. However, it is difficult to know prac-tical antenna characteristics considering the plasma kinetics and spacecraft-plasma interactions by means of theoretical approaches. Furthermore, some modern antenna designing techniques such as a "hockey puck" principle is applied to MEFISTO, which introduces much complexity in its overall configuration. Thus a strong demand arises regarding the establishment of a nu-merical method that can solve the complex configuration and plasma dynamics for evaluating the electric properties of the modern instrument. For the self-consistent antenna analysis, we have developed a particle simulation code named EMSES based on the particle-in-cell technique including a treatment antenna conductive sur-faces. In this paper, we mainly focus on electrostatic (ES) features and photoelectron distri-bution in the vicinity of MEFISTO. Our simulation model includes (1) a photoelectron guard electrode, (2) a bias current provided from the spacecraft body to the sensing element, (3) a floating potential treatment for the spacecraft body, and (4) photoelectron emission from sunlit surfaces of the conductive bodies. Of these, the photoelectron guard electrode is a key technol-ogy for producing an optimal condition of plasma environment around MEFISTO. Specifically, we introduced a pre-amplifier housing called puck located between the conductive boom and the sensor wire. The photoelectron guard is then simulated by forcibly fixing the potential difference between the puck surface and the spacecraft body. For the modeling, we use the Capacity Matrix technique in order to assure the conservation condition of total charge owned by the

  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. 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.

  9. [Cancer initiating cell theory: popularity and controversies].

    PubMed

    Chen, Hua; Huang, Qiang; Dong, Jun; Lan, Qing

    2006-06-01

    The cancer stem cell model proposes that most tumors are derived from a single cell that is transformed into a cancer-initiating cell (cancer stem cell). Cancer stem cells have the capacity to proliferate, differentiate, and form tumors in vivo. However, the origin of cancer stem cells remains controversial. Normal stem cells are regarded as an ideal candidate for the origin of cancer stem cells when take similar characters and signaling pathways between them into consideration. In addition,cell fusion is an important physiologic process during development and tissue repair,and is closely related to several fundamental features of tumors,and thus could be involved in the development of cancer stem cells.

  10. Identification of cells initiating human melanomas

    PubMed Central

    Schatton, Tobias; Murphy, George F.; Frank, Natasha Y.; Yamaura, Kazuhiro; Waaga-Gasser, Ana Maria; Gasser, Martin; Zhan, Qian; Jordan, Stefan; Duncan, Lyn M.; Weishaupt, Carsten; Fuhlbrigge, Robert C.; Kupper, Thomas S.; Sayegh, Mohamed H.; Frank, Markus H.

    2012-01-01

    Tumour-initiating cells capable of self-renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies1,2 and solid cancers3–6. If such minority populations are associated with tumour progression in human patients, specific targeting of tumour-initiating cells could be a strategy to eradicate cancers currently resistant to systemic therapy. Here we identify a subpopulation enriched for human malignant-melanoma-initiating cells (MMIC) defined by expression of the chemoresistance mediator ABCB5 (refs 7, 8) and show that specific targeting of this tumorigenic minority population inhibits tumour growth. ABCB5+ tumour cells detected in human melanoma patients show a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human-to-mouse xenotransplantation experiments, ABCB5+ melanoma cells possess greater tumorigenic capacity than ABCB5− bulk populations and re-establish clinical tumour heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5+ sub-populations for self-renewal and differentiation, because ABCB5+ cancer cells generate both ABCB5+ and ABCB5− progeny, whereas ABCB5− tumour populations give rise, at lower rates, exclusively to ABCB5− cells. In an initial proof-of-principle analysis, designed to test the hypothesis that MMIC are also required for growth of established tumours, systemic administration of a monoclonal antibody directed at ABCB5, shown to be capable of inducing antibody-dependent cell-mediated cytotoxicity in ABCB5+ MMIC, exerted tumour-inhibitory effects. Identification of tumour-initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting through a defining chemoresistance determinant has important implications for cancer therapy. PMID:18202660

  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. 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).

  13. 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.

  14. Adaptive immune cells temper initial innate responses

    PubMed Central

    Kim, Kwang Dong; Zhao, Jie; Auh, Sogyong; Yang, Xuanming; Du, Peishuang; Tang, Hong; Fu, Yang-Xin

    2008-01-01

    Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells1–4. Lymphocytedeficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4+ and CD8+ cells in wild-type mice and the transfer of T lymphocytes into Rag-1–deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4+CD25−Foxp3− or CD8+ T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses. PMID:17891146

  15. Adaptive immune cells temper initial innate responses.

    PubMed

    Kim, Kwang Dong; Zhao, Jie; Auh, Sogyong; Yang, Xuanming; Du, Peishuang; Tang, Hong; Fu, Yang-Xin

    2007-10-01

    Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells. Lymphocyte-deficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4+ and CD8+ cells in wild-type mice and the transfer of T lymphocytes into Rag-1-deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4+CD25-Foxp3- or CD8+ T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses.

  16. The potential origin of glioblastoma initiating cells

    PubMed Central

    Chesler, David A.; Berger, Mitchell S.; Quinones-Hinojosa, Alfredo

    2013-01-01

    Despite intensive clinical and laboratory research and effort, Glioblastoma remains the most common and invariably lethal primary cancer of the central nervous system. The identification of stem cell and lineage-restricted progenitor cell populations within the adult human brain in conjunction with the discovery of stem-like cells derived from gliomas which are themselves tumorigenic and have been shown to have properties of self-renewal and multipotency, has led to the hypothesis that this population of cells may represent glioma initiating cells. Extensive research characterizing the anatomic distribution and phenotype of neural stem cells in the adult brain, and the genetic underpinnings needed for malignant transformation may ultimately lead to the identification of the cellular origin for glioblastoma. Defining the cellular origin of this lethal disease may ultimately provide new therapeutic targets and modalities finally altering an otherwise bleak outcome for patients with glioblastoma. PMID:22202053

  17. 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

  18. Distinctive properties of metastasis-initiating cells

    PubMed Central

    Celià-Terrassa, Toni; Kang, Yibin

    2016-01-01

    Primary tumors are known to constantly shed a large number of cancer cells into systemic dissemination, yet only a tiny fraction of these cells is capable of forming overt metastases. The tremendous rate of attrition during the process of metastasis implicates the existence of a rare and unique population of metastasis-initiating cells (MICs). MICs possess advantageous traits that may originate in the primary tumor but continue to evolve during dissemination and colonization, including cellular plasticity, metabolic reprogramming, the ability to enter and exit dormancy, resistance to apoptosis, immune evasion, and co-option of other tumor and stromal cells. Better understanding of the molecular and cellular hallmarks of MICs will facilitate the development and deployment of novel therapeutic strategies. PMID:27083997

  19. Ionizing Radiation in Glioblastoma Initiating Cells

    PubMed Central

    Rivera, Maricruz; Sukhdeo, Kumar; Yu, Jennifer

    2013-01-01

    Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with a median survival of 12–15 months with treatment consisting of surgical resection followed by ionizing radiation (IR) and chemotherapy. Even aggressive treatment is often palliative due to near universal recurrence. Therapeutic resistance has been linked to a subpopulation of GBM cells with stem cell-like properties termed GBM initiating cells (GICs). Recent efforts have focused on elucidating resistance mechanisms activated in GICs in response to IR. Among these, GICs preferentially activate the DNA damage response (DDR) to result in a faster rate of double-strand break (DSB) repair induced by IR as compared to the bulk tumor cells. IR also activates NOTCH and the hepatic growth factor (HGF) receptor, c-MET, signaling cascades that play critical roles in promoting proliferation, invasion, and resistance to apoptosis. These pathways are preferentially activated in GICs and represent targets for pharmacologic intervention. While IR provides the benefit of improved survival, it paradoxically promotes selection of more malignant cellular phenotypes of GBM. As reviewed here, finding effective combinations of radiation and molecular inhibitors to target GICs and non-GICs is essential for the development of more effective therapies. PMID:23579692

  20. Particle-in-cell modeling of spacecraft-plasma interaction effects on double-probe electric field measurements

    NASA Astrophysics Data System (ADS)

    Miyake, Y.; Usui, H.

    2016-12-01

    The double-probe technique, commonly used for electric field measurements in magnetospheric plasmas, is susceptible to environmental perturbations caused by spacecraft-plasma interactions. To better model the interactions, we have extended the existing particle-in-cell simulation technique so that it accepts very small spacecraft structures, such as thin wire booms, by incorporating an accurate potential field solution calculated based on the boundary element method. This immersed boundary element approach is effective for quantifying the impact of geometrically small but electrically large spacecraft elements on the formation of sheaths or wakes. The developed model is applied to the wake environment near a Cluster satellite for three distinctive plasma conditions: the solar wind, the tail lobe, and just outside the plasmapause. The simulations predict the magnitudes and waveforms of wake-derived spurious electric fields, and these are in good agreement with in situ observations. The results also reveal the detailed structure of potential around the double probes. It shows that any probes hardly experience a negative wake potential in their orbit, and instead, they experience an unbalanced drop rate of a large potential hill that is created by the spacecraft and boom bodies. As a by-product of the simulations, we also found a photoelectron short-circuiting effect that is analogous to the well-known short-circuiting effect due to the booms of a double-probe instrument. The effect is sustained by asymmetric photoelectron distributions that cancel out the external electric field.

  1. 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.

  2. Particle-In-Cell Modeling and Analysis of an Electric Antenna for the BepiColombo/MMO spacecraft

    NASA Astrophysics Data System (ADS)

    Miyake, Yohei; Usui, Hideyuki; Kojima, Hirotsugu

    2010-05-01

    The sophisticated calibration of a space-based electric antenna should be performed based on precise knowledge of electric antenna characteristics in space plasma environment. However, it is often difficult to know practical antenna characteristics considering the effects of plasma kinetics and spacecraft-plasma interactions by means of only theoretical approaches. Furthermore, some modern electric field instruments, such as the Cluster EFW instrument and MEFISTO for the BepiColombo/MMO spacecraft, are designed based on a ``hockey puck'' principle, which introduces much complexity in their overall configurations. Thus a strong demand arises regarding the establishment of a numerical method that can solve the complex configuration and plasma dynamics for evaluating the electric properties of such modern instruments. For the self-consistent antenna analysis, we have newly developed an electromagnetic (EM) particle simulation code named EMSES. The code is based on the particle-in-cell technique and also supports a treatment of inner boundaries describing spacecraft conductive surfaces. This enables us to naturally include the effects of the inhomogeneous plasma environment such as a plasma and photoelectron sheaths created around the antenna. The support of the full EM treatment is also important to apply our tool to antenna properties for not only electrostatic (ES) but also EM plasma waves. In the current study, we mainly focus on ES features and photoelectron distribution in the vicinity of the electric field instrument MEFISTO. Our simulation model includes (1) a photoelectron guard electrode, (2) a bias current provided from the spacecraft body to the sensing element, (3) a floating potential treatment for the spacecraft body, and (4) photoelectron emission from sunlit surfaces of the conductive bodies. Of these, the photoelectron guard electrode is a key technology for producing an optimal condition of plasma environment around MEFISTO. Specifically, we

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  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. Immunological Targeting of Tumor Initiating Prostate Cancer Cells

    DTIC Science & Technology

    2014-10-01

    AD Award Number: W81XWH-13-1-0369 TITLE: Immunological Targeting of Tumor Initiating Prostate Cancer Cells PRINCIPAL...5a. CONTRACT NUMBER Immunological Targeting of Tumor Initiating Prostate Cancer Cells 5b. GRANT NUMBER W81XWH13-1-0369 5c... prostate cancer . In two specific aims, we proposed to first identify novel antigenic targets on these castrate resistant luminal epithelial cells (CRLEC

  9. 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.

  10. Combined energy production and waste management in manned spacecraft utilizing on-demand hydrogen production and fuel cells

    NASA Astrophysics Data System (ADS)

    Elitzur, Shani; Rosenband, Valery; Gany, Alon

    2016-11-01

    Energy supply and waste management are among the most significant challenges in human spacecraft. Great efforts are invested in managing solid waste, recycling grey water and urine, cleaning the atmosphere, removing CO2, generating and saving energy, and making further use of components and products. This paper describes and investigates a concept for managing waste water and urine to simultaneously produce electric and heat energies as well as fresh water. It utilizes an original technique for aluminum activation to react spontaneously with water at room temperature to produce hydrogen on-site and on-demand. This reaction has further been proven to be effective also when using waste water and urine. Applying the hydrogen produced in a fuel cell, one obtains electric energy as well as fresh (drinking) water. The method was compared to the traditional energy production technology of the Space Shuttle, which is based on storing the fuel cell reactants, hydrogen and oxygen, in cryogenic tanks. It is shown that the alternative concept presented here may provide improved safety, compactness (reduction of more than one half of the volume of the hydrogen storage system), and management of waste liquids for energy generation and drinking water production. Nevertheless, it adds mass compared to the cryogenic hydrogen technology. It is concluded that the proposed method may be used as an emergency and backup power system as well as an additional hydrogen source for extended missions in human spacecraft.

  11. 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

  12. 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.

  13. 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.

  14. Pericycle cell proliferation and lateral root initiation in Arabidopsis.

    PubMed

    Dubrovsky, J G; Doerner, P W; Colón-Carmona, A; Rost, T L

    2000-12-01

    In contrast with other cells generated by the root apical meristem in Arabidopsis, pericycle cells adjacent to the protoxylem poles of the vascular cylinder continue to cycle without interruption during passage through the elongation and differentiation zones. However, only some of the dividing pericycle cells are committed to the asymmetric, formative divisions that give rise to lateral root primordia (LRPs). This was demonstrated by direct observation and mapping of mitotic figures, cell-length measurements, and the histochemical analysis of a cyclin-GUS fusion protein in pericycle cells. The estimated duration of a pericycle cell cycle in the root apical meristem was similar to the interval between cell displacement from the meristem and the initiation of LRP formation. Developmentally controlled LRP initiation occurs early, 3 to 8 mm from the root tip. Thus the first growth control point in lateral root formation is defined by the initiation of primordia in stochastic patterns by cells passing through the elongation and young differentiation zones, up to where lateral roots begin to emerge from the primary root. Therefore, the first growth control point is not restricted to a narrow developmental window. We propose that late LRP initiation is developmentally unrelated to the root apical meristem and is operated by a second growth control point that can be activated by environmental cues. The observation that pericycle cells divide and lateral root primordia form without intervening mitotic quiescence suggests that lateral organ formation in roots and shoots might not be as fundamentally different as previously thought.

  15. 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.

  16. 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.

  17. 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

  18. Bone marrow-derived stem cells initiate pancreatic regeneration.

    PubMed

    Hess, David; Li, Li; Martin, Matthew; Sakano, Seiji; Hill, David; Strutt, Brenda; Thyssen, Sandra; Gray, Douglas A; Bhatia, Mickie

    2003-07-01

    We show that transplantation of adult bone marrow-derived cells expressing c-kit reduces hyperglycemia in mice with streptozotocin-induced pancreatic damage. Although quantitative analysis of the pancreas revealed a low frequency of donor insulin-positive cells, these cells were not present at the onset of blood glucose reduction. Instead, the majority of transplanted cells were localized to ductal and islet structures, and their presence was accompanied by a proliferation of recipient pancreatic cells that resulted in insulin production. The capacity of transplanted bone marrow-derived stem cells to initiate endogenous pancreatic tissue regeneration represents a previously unrecognized means by which these cells can contribute to the restoration of organ function.

  19. 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.

  20. On the nature of the tumor-initiating cell.

    PubMed

    Lara-Padilla, Eleazar; Caceres-Cortes, Julio Roberto

    2012-01-01

    Certain aspects of tumors that may influence areas of basic biology and medicine are reviewed. The hypothesis that malignant stem cells evolve from normal stem cells, is considered. Information is being accumulated on the possibility that certain cell populations that can be propagated as cell lines in vitro can produce cells with features of differentiated cells in addition to others that maintain the line and, in some cases may also initiate tumor formation in vivo. Up to the present time, there is evidence to show that cancer stem cells persist in many cell lines. Tyrosine kinase inhibition produces combinations of autophagy and apoptosis in the human erythroleukemia cell line TF-1 hinting at a heterotypic aggregation of cells containing cancer stem cells. Finally, the mechanisms of cancer development, invasion and metastasis are operatively defined. The purpose of this paper is to review some of the salient features of cancer stem cells in support of the proposal that research in neoplasia be increased. Rather than presenting details of various studies, we have attempted to indicate general areas in which work has been done or is in progress. It is hoped that this survey of the subject will demonstrate a variety of opportunities for additional research in human neoplasia.

  1. Long life and low weight Ni/Cd cells for spacecraft

    SciTech Connect

    Lim, H.S.; Knechtli, R.C.; Margerum, J.D.; Pickett, D.F.; Rogers, M.M.; Verzwyvelt, S.A.

    1984-08-01

    Nickel-cadmium cells of various designs, containing polymer reinforced inorganic separators and either chemically deposited or electrochemically deposited nickel and cadmium electrodes, have been studied for their cycle life performance. The performance goal of these Ni/Cd cells is more than 10 years of cycle life at 80% depth of discharge operation in a geosynchronous orbit. Three alternate cycle regimes, including one with a high rate (0.4C) charging (HGEO regime), were used to test the cells. In all cycle regimes, the performance goal appears to be feasible with selected cell designs. The cycle life, in general, was longer in the HGEO cycling regime. However, in practice this HGEO cycling requires a sequential charging system which results in a tradeoff to a standard low rate charge for GEO cycling because of the extra charge control equipment needed for an HGEO regime.

  2. Aging affects initiation and continuation of T cell proliferation.

    PubMed

    Jiang, Jiu; Gross, Diara; Elbaum, Philip; Murasko, Donna M

    2007-04-01

    Aging is associated with a decline in immune responses, particularly within the T cell compartment. While the expansion of specific T cells in response to virus infections is consistently decreased in aged mice, the differences in T cell activation between young and aged mice as demonstrated in each round of proliferation remain poorly defined. In the present study, we utilized the T cell mitogen, ConA, to explore if fewer T cells of aged mice initiate proliferation upon mitogen stimulation or if similar numbers of T cells of aged mice begin proliferation but undergo fewer rounds of division. We also examined whether these age-associated changes in proliferation are reflected by differences in T cell activation by comparing activation markers (CD25, CD69, CD44, and CD62L) on T cells of young and aged mice at each round of proliferation. Not only was the kinetics of the expression of these markers greatly different between young and aged mice on the entire CD8 T cell population, but also at each round of proliferation. Our results demonstrate that a larger percentage of CD8 T cells of aged mice do not proliferate at all upon stimulation. Of the CD8 T cells of aged mice that do proliferate, a larger percentage start later and stop sooner. These results suggest that multiple levels of alteration may need to be considered when trying to maximize the immune response of aged individuals.

  3. TERRA Spacecraft

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Earth Observing System (EOS) is managed by NASA's Goddard Space Flight Center (GSFC), Greenbelt, MD, is the centerpiece of the Earth Science Enterprise (formerly called 'Mission to Planet Earth'), a long-term coordinated research effort to study the Earth as a global system. Terra was launched on December 18, 1999 aboard an ATLAS-IIAS launch vehicle from Vandenberg Air Force Base, CA. Terra is a near-polar orbiting spacecraft that will cross the equator at 10:30 am local time. Terra will collect data simultaneously from a complement of five instruments: CERES, MISR, and MODIS are proved by the US; MOPITT by Canada; and ASTER by Japan. Researchers around the world will use data from these instruments to study how the atmosphere, land, ocean, and life interact with each other on a global scale.

  4. 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.

  5. 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.

  6. 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.

  7. Culture and Isolation of Brain Tumor Initiating Cells.

    PubMed

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

    2015-08-03

    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.

  8. Resveratrol sensitizes glioblastoma-initiating cells to temozolomide by inducing cell apoptosis and promoting differentiation.

    PubMed

    Li, Hao; Liu, Yaodong; Jiao, Yumin; Guo, Anchen; Xu, Xiaoxue; Qu, Xianjun; Wang, Shuo; Zhao, Jizong; Li, Ye; Cao, Yong

    2016-01-01

    Glioblastoma-initiating cells play crucial roles in the origin, growth, and recurrence of glioblastoma multiforme. The elimination of glioblastoma-initiating cells is believed to be a key strategy for achieving long-term survival of glioblastoma patients due to the highly resistant property of glioblastoma-initiating cells to temozolomide. Resveratrol, a naturally occurring polyphenol, has been widely studied as a promising candidate for cancer prevention and treatment. Whether resveratrol could enhance the sensitivity of glioblastoma-initiating cells to temozolomide therapy has not yet been reported. Here, using patient-derived glioblastoma-initiating cell lines, we found that resveratrol sensitized glioblastoma-initiating cells to temozolomide both in vitro and in vivo. Furthermore, we showed that resveratrol enhanced glioblastoma-initiating cells to temozolomide-induced apoptosis through DNA double-stranded breaks/pATM/pATR/p53 pathway activation, and promoted glioblastoma-initiating cell differentiation involving p-STAT3 inactivation. Our results propose that temozolomide and resveratrol combination strategy may be effective in the management of glioblastoma patients, particularly for those patients who have been present with a high abundance of glioblastoma-initiating cells in their tumors and show slight responsiveness to temozolomide.

  9. 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.

  10. 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.

  11. 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).

  12. 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.

  13. Ovarian tumor-initiating cells display a flexible metabolism

    PubMed Central

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

    2014-01-01

    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-LFFLv (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. PMID:25172556

  14. C/EBPα initiates primitive myelopoiesis in pluripotent embryonic cells

    PubMed Central

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

    2013-01-01

    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/EPBα is the first known single factor capable of initiating an entire myelopoeisis pathway in pluripotent cells in the embryo. PMID:19420355

  15. TERRA Spacecraft

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Earth Observing System (EOS), managed by NASA's Goddard Space Flight Center (GSFC), Greenbelt, Maryland, is the centerpiece of the Earth Science Enterprise (formerly called "Mission to Planet Earth"), a long-term coordinated research effort to study the Earth as a global system. Terra was launched on December 18, 1999 aboard an ATLAS-IIAS launch vehicle from Vandenberg Air Force Base, California. Terra is a near-polar orbiting spacecraft that will cross the equator at 10:30 AM local time. Terra will collect data simultaneously from a complement of five instruments: CERES (Clouds and the Earth's Radiant Energy System), MISR (Multi-angle Imaging SpectroRadiometer) and MODIS (Moderate-resolution Imaging Spectroradiometer) are provided by the United States; MOPITT (Measurements Of Pollution In The Troposphere) by Canada; and ASTER (Advanced Spaceborne Thermal Emission and Reflection radiometer) by Japan. Researchers around the world will use data from these instruments to study how the atmosphere, land, ocean, and life interact with each other on a global scale. This interactive CD introduces Terra's overall objectives and its instruments, the new technologies developed for Terra, the launch of Terra, and its flight dynamics.

  16. 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

  17. Spacecraft -- Capsule Separation (Animation)

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Click on the image for Spacecraft -- Capsule Separation animation

    This animation shows the return capsule separating from the Stardust spacecraft.

  18. Mesenchymal stem cell-like properties of CD133+ glioblastoma initiating cells

    PubMed Central

    Pavon, Lorena Favaro; Sibov, Tatiana Tais; de Oliveira, Daniela Mara; Marti, Luciana C.; Cabral, Francisco Romero; de Souza, Jean Gabriel; Boufleur, Pamela; Malheiros, Suzana M.F.; de Paiva Neto, Manuel A.; da Cruz, Edgard Ferreira; Chudzinski-Tavassi, Ana Marisa; Cavalheiro, Sérgio

    2016-01-01

    Glioblastoma is composed of dividing tumor cells, stromal cells and tumor initiating CD133+ cells. Recent reports have discussed the origin of the glioblastoma CD133+ cells and their function in the tumor microenvironment. The present work sought to investigate the multipotent and mesenchymal properties of primary highly purified human CD133+ glioblastoma-initiating cells. To accomplish this aim, we used the following approaches: i) generation of tumor subspheres of CD133+ selected cells from primary cell cultures of glioblastoma; ii) analysis of the expression of pluripotency stem cell markers and mesenchymal stem cell (MSC) markers in the CD133+ glioblastoma-initiating cells; iii) side-by-side ultrastructural characterization of the CD133+ glioblastoma cells, MSC and CD133+ hematopoietic stem cells isolated from human umbilical cord blood (UCB); iv) assessment of adipogenic differentiation of CD133+ glioblastoma cells to test their MSC-like in vitro differentiation ability; and v) use of an orthotopic glioblastoma xenograft model in the absence of immune suppression. We found that the CD133+ glioblastoma cells expressed both the pluripotency stem cell markers (Nanog, Mush-1 and SSEA-3) and MSC markers. In addition, the CD133+ cells were able to differentiate into adipocyte-like cells. Transmission electron microscopy (TEM) demonstrated that the CD133+ glioblastoma-initiating cells had ultrastructural features similar to those of undifferentiated MSCs. In addition, when administered in vivo to non-immunocompromised animals, the CD133+ cells were also able to mimic the phenotype of the original patient's tumor. In summary, we showed that the CD133+ glioblastoma cells express molecular signatures of MSCs, neural stem cells and pluripotent stem cells, thus possibly enabling differentiation into both neural and mesodermal cell types. PMID:27244897

  19. Kinetics of MDR Transport in Tumor-Initiating Cells

    PubMed Central

    Koshkin, Vasilij; Yang, Burton B.; Krylov, Sergey N.

    2013-01-01

    Multidrug resistance (MDR) driven by ABC (ATP binding cassette) membrane transporters is one of the major causes of treatment failure in human malignancy. MDR capacity is thought to be unevenly distributed among tumor cells, with higher capacity residing in tumor-initiating cells (TIC) (though opposite finding are occasionally reported). Functional evidence for enhanced MDR of TICs was previously provided using a “side population” assay. This assay estimates MDR capacity by a single parameter - cell’s ability to retain fluorescent MDR substrate, so that cells with high MDR capacity (“side population”) demonstrate low substrate retention. In the present work MDR in TICs was investigated in greater detail using a kinetic approach, which monitors MDR efflux from single cells. Analysis of kinetic traces obtained allowed for the estimation of both the velocity (Vmax) and affinity (KM) of MDR transport in single cells. In this way it was shown that activation of MDR in TICs occurs in two ways: through the increase of Vmax in one fraction of cells, and through decrease of KM in another fraction. In addition, kinetic data showed that heterogeneity of MDR parameters in TICs significantly exceeds that of bulk cells. Potential consequences of these findings for chemotherapy are discussed. PMID:24223908

  20. 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.

  1. Tumor-Initiating Cells: Emerging Biophysical Methods of Isolation

    PubMed Central

    Cermeño, Efraín A.; García, Andrés J.

    2016-01-01

    The discovery and subsequent isolation of tumor-initiating cells (TICs), a small population of highly tumorigenic and drug-resistant cancer cells also called cancer stem cells (CSCs), have revolutionized our understanding of cancer. TICs are isolated using various methodologies, including selection of surface marker expression, ALDH activity, suspension culture, and chemotherapy/drug resistance. These methods have several drawbacks, including their variability, lack of robustness and scalability, and low specificity. Alternative methods of purification take advantage of biophysical properties of TICs including their adhesion and stiffness. This review will provide a brief overview of TIC biology as well as review the most important methods of TIC isolation with a focus on biophysical methods of TIC purification. PMID:27141429

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Tumor-initiating cell frequency is relevant for glioblastoma aggressiveness

    PubMed Central

    Richichi, Cristina; Osti, Daniela; Del Bene, Massimiliano; Fornasari, Lorenzo; Patanè, Monica; Pollo, Bianca; DiMeco, Francesco; Pelicci, Giuliana

    2016-01-01

    Glioblastoma (GBM) is maintained by a small subpopulation of tumor-initiating cells (TICs). The arduous assessment of TIC frequencies challenges the prognostic role of TICs in predicting the clinical outcome in GBM patients. We estimated the TIC frequency in human GBM injecting intracerebrally in mice dissociated cells without any passage in culture. All GBMs contained rare TICsand were tumorigenic in vivo but only 54% of them grew in vitro as neurospheres. We demonstrated that neurosphere formation in vitro did not foretell tumorigenic ability in vivo and frequencies calculated in vitro overestimated the TIC content. Our findings assert the pathological significance of GBM TICs. TIC number correlated positively with tumor incidence and inversely with survival of tumor-bearing mice. Stratification of GBM patients according to TIC content revealed that patients with low TIC frequency experienced a trend towards a longer progression free survival. The expression of either putative stem-cell markers or markers associated with different GBM molecular subtypes did not associate with either TIC content or neurosphere formation underlying the limitations of TIC identification based on the expression of some putative stem cell-markers. PMID:27582543

  10. Two distinct cytokinesis pathways drive trypanosome cell division initiation from opposite cell ends

    PubMed Central

    Zhou, Qing; Gu, Jianhua; Lun, Zhao-Rong; Ayala, Francisco J.; Li, Ziyin

    2016-01-01

    Cytokinesis in Trypanosoma brucei, an early branching protozoan, occurs along its longitudinal axis uni-directionally from the anterior tip of the new flagellum attachment zone filament toward the cell’s posterior end. However, the underlying mechanisms remain elusive. Here we report that cytokinesis in T. brucei is regulated by a concerted action of Polo-like kinase, Aurora B kinase, and a trypanosome-specific protein CIF1. Phosphorylation of CIF1 by Polo-like kinase targets it to the anterior tip of the new flagellum attachment zone filament, where it subsequently recruits Aurora B kinase to initiate cytokinesis. Consistent with its role, CIF1 depletion inhibits cytokinesis initiation from the anterior end of the cell, but, surprisingly, triggers cytokinesis initiation from the posterior end of the cell, suggesting the activation of an alternative cytokinesis from the opposite cell end. Our results reveal the mechanistic roles of CIF1 and Polo-like kinase in cytokinesis initiation and elucidate the mechanism underlying the recruitment of Aurora B kinase to the cytokinesis initiation site at late anaphase. These findings also delineate a signaling cascade controlling cytokinesis initiation from the anterior end of the cell and uncover a backup cytokinesis that is initiated from the posterior end of the cell when the typical anterior-to-posterior cytokinesis is compromised. PMID:26929336

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

    PubMed

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

    2016-02-22

    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.

  12. Salinomycin inhibits the tumor growth of glioma stem cells by selectively suppressing glioma-initiating cells.

    PubMed

    Chen, Tunan; Yi, Liang; Li, Fei; Hu, Rong; Hu, Shengli; Yin, Yi; Lan, Chuan; Li, Zhao; Fu, Chuhua; Cao, Liu; Chen, Zhi; Xian, Jishu; Feng, Hua

    2015-04-01

    Glioma‑initiating cells are a small population of cells that have the ability to undergo self‑renewal and initiate tumorigenesis. In the present study, the potential role of salinomycin, a polyether antibiotic, on the suppression of glioma cell growth was investigated. GL261 glioma cells were maintained in a stem‑cell‑like status [GL261 neurospheres (GL261‑NS)] or induced for differentiation [GL261 adherent cells (GL261‑AC)]. It was demonstrated that salinomycin significantly reduced the cell viability of GL261‑NS and GL261‑AC cells in a dose‑dependent manner, with a more substantial inhibition of GL261‑NS proliferation (P<0.05). The inhibitory effect of salinomycin on cell growth was more effective than that of 1‑(4‑amino‑2‑methyl‑5‑pyrimid l)‑methyl‑3‑(2‑chloroethyl)‑3‑nitrosourea hydrochloride and vincristine (P<0.05). Salinomycin depleted GL261‑NS from tumorspheres and induced cell apoptosis. In addition, salinomycin prolonged the median survival time of glioma‑bearing mice (P<0.05). Therefore, the present study indicated that salinomycin may preferentially inhibit glioma‑initiated cell growth by inducing apoptosis, suggesting that salinomycin may provide a valuable therapeutic strategy for the treatment of malignant glioma.

  13. Spacecraft propulsion: new methods.

    PubMed

    Alfvén, H

    1972-04-14

    Cosmic plasmas contain energy which may be tapped and used for spacecraft propulsion. The energy needed for launching a spacecraft could be supplied to it from the ground through a plasma channel in the atmosphere.

  14. 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

  15. Replication initiation patterns in the beta-globin loci of totipotent and differentiated murine cells: evidence for multiple initiation regions.

    PubMed

    Aladjem, Mirit I; Rodewald, Luo Wei; Lin, Chii Mai; Bowman, Sarah; Cimbora, Daniel M; Brody, Linnea L; Epner, Elliot M; Groudine, Mark; Wahl, Geoffrey M

    2002-01-01

    The replication initiation pattern of the murine beta-globin locus was analyzed in totipotent embryonic stem cells and in differentiated cell lines. Initiation events in the murine beta-globin locus were detected in a region extending from the embryonic Ey gene to the adult betaminor gene, unlike the restricted initiation observed in the human locus. Totipotent and differentiated cells exhibited similar initiation patterns. Deletion of the region between the adult globin genes did not prevent initiation in the remainder of the locus, suggesting that the potential to initiate DNA replication was not contained exclusively within the primary sequence of the deleted region. In addition, a deletion encompassing the six identified 5' hypersensitive sites in the mouse locus control region had no effect on initiation from within the locus. As this deletion also did not affect the chromatin structure of the locus, we propose that the sequences determining both chromatin structure and replication initiation lie outside the hypersensitive sites removed by the deletion.

  16. Gata6 potently initiates reprograming of pluripotent and differentiated cells to extraembryonic endoderm stem cells

    PubMed Central

    Wamaitha, Sissy E.; del Valle, Ignacio; Cho, Lily T.Y.; Wei, Yingying; Fogarty, Norah M.E.; Blakeley, Paul; Sherwood, Richard I.; Ji, Hongkai; Niakan, Kathy K.

    2015-01-01

    Transcription factor-mediated reprograming is a powerful method to study cell fate changes. In this study, we demonstrate that the transcription factor Gata6 can initiate reprograming of multiple cell types to induced extraembryonic endoderm stem (iXEN) cells. Intriguingly, Gata6 is sufficient to drive iXEN cells from mouse pluripotent cells and differentiated neural cells. Furthermore, GATA6 induction in human embryonic stem (hES) cells also down-regulates pluripotency gene expression and up-regulates extraembryonic endoderm (ExEn) genes, revealing a conserved function in mediating this cell fate switch. Profiling transcriptional changes following Gata6 induction in mES cells reveals step-wise pluripotency factor disengagement, with initial repression of Nanog and Esrrb, then Sox2, and finally Oct4, alongside step-wise activation of ExEn genes. Chromatin immunoprecipitation and subsequent high-throughput sequencing analysis shows Gata6 enrichment near pluripotency and endoderm genes, suggesting that Gata6 functions as both a direct repressor and activator. Together, this demonstrates that Gata6 is a versatile and potent reprograming factor that can act alone to drive a cell fate switch from diverse cell types. PMID:26109048

  17. LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer.

    PubMed

    Amsterdam, Abraham; Raanan, Calanit; Schreiber, Letizia; Polin, Nava; Givol, David

    2013-04-05

    Pancreas cancer, is the fourth leading cause of cancer death but its cell of origin is controversial. We compared the localization of stem cells in normal and cancerous pancreas using antibodies to the stem cell markers Nanog and LGR5. Here we show, for the first time, that LGR5 is expressed in normal pancreas, exclusively in the islets of Langerhans and it is co-localized, surprisingly, with Nanog and insulin in clusters of beta cells. In cancerous pancreas Nanog and LGR5 are expressed in the remaining islets and in all ductal cancer cells. We observed insulin staining among the ductal cancer cells, but not in metastases. This indicates that the islet's beta cells, expressing LGR5 and Nanog markers are the initiating cells of pancreas cancer, which migrated from the islets to form the ductal cancerous tissue, probably after mutation and de-differentiation. This discovery may facilitate treatment of this devastating cancer.

  18. 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.

  19. 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

  20. 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.

  1. Vessel wall-embedded dendritic cells induce T-cell autoreactivity and initiate vascular inflammation.

    PubMed

    Han, Ji W; Shimada, Kazunori; Ma-Krupa, Wei; Johnson, Tiffany L; Nerem, Robert M; Goronzy, Jörg J; Weyand, Cornelia M

    2008-03-14

    Human medium-sized and large arteries are targeted by inflammation with innate and adaptive immune responses occurring within the unique microspace of the vessel wall. How 3D spatial arrangements influence immune recognition and cellular response thresholds and which cell populations sense immunoactivating ligands and function as antigen-presenting cells are incompletely understood. To mimic the 3D context of human arteries, bioartificial arteries were engineered from collagen type I matrix, human vascular smooth muscle cells (VSMCs), and human endothelial cells and populated with cells implicated in antigen presentation and T-cell stimulation, including monocytes, macrophages, and myeloid dendritic cells (DCs). Responsiveness of wall-embedded antigen-presenting cells was probed with the Toll-like receptor ligand lipopolysaccharide, and inflammation was initiated by adding autologous CD4(+) T cells. DCs colonized the outermost VSMC layer, recapitulating their positioning at the media-adventitia border of normal arteries. Wall-embedded DCs responded to the microbial product lipopolysaccharide by entering the maturation program and upregulating the costimulatory ligand CD86. Activated DCs effectively stimulated autologous CD4 T cells, which produced the proinflammatory cytokine interferon-gamma and infiltrated deeply into the VSMC layer, causing matrix damage. Lipopolysaccharide-triggered macrophages were significantly less efficacious in recruiting T cells and promoting T-cell stimulation. CD14(+) monocytes, even when preactivated, failed to support initial steps of vascular wall inflammation. Innate immune cells, including monocytes, macrophages, and DCs, display differential functions in the vessel wall. DCs are superior in sensing pathogen-derived motifs and are highly efficient in breaking T-cell tolerance, guiding T cells toward proinflammatory and tissue-invasive behavior.

  2. Docking structure for spacecraft

    NASA Technical Reports Server (NTRS)

    Belew, R. R. (Inventor)

    1973-01-01

    A docking structure for a pair of spacecraft is described comprising a conical receptacle on the docking end of a first spacecraft that receives a mating conical projection on the docking end of the second spacecraft. The conical receptacle of the first spacecraft constitutes an exterior portion of a sealed gas-tight compartment. Pressurization of the sealed compartment causes the conical receptacle to extend toward the incoming conical projection of the second spacecraft. When the mating conical portions are latched together, the docking energy is absorbed by the compressed gas in the sealed compartment. Rebound forces are countered by a plurality of actuator cylinders supporting the conical receptacle.

  3. 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.

  4. β-escin selectively targets the glioblastoma-initiating cell population and reduces cell viability

    PubMed Central

    Harford-Wright, Elizabeth; Bidère, Nicolas; Gavard, Julie

    2016-01-01

    Glioblastoma multiforme (GBM) is a highly aggressive tumour of the central nervous system and is associated with an extremely poor prognosis. Within GBM exists a subpopulation of cells, glioblastoma-initiating cells (GIC), which possess the characteristics of progenitor cells, have the ability to initiate tumour growth and resist to current treatment strategies. We aimed at identifying novel specific inhibitors of GIC expansion through use of a large-scale chemical screen of approved small molecules. Here, we report the identification of the natural compound β-escin as a selective inhibitor of GIC viability. Indeed, β-escin was significantly cytotoxic in nine patient-derived GIC, whilst exhibiting no substantial effect on the other human cancer or control cell lines tested. In addition, β-escin was more effective at reducing GIC growth than current clinically used cytotoxic agents. We further show that β-escin triggers caspase-dependent cell death combined with a loss of stemness properties. However, blocking apoptosis could not rescue the β-escin-induced reduction in sphere formation or stemness marker activity, indicating that β-escin directly modifies the stem identity of GIC, independent of the induction of cell death. Thus, this study has repositioned β-escin as a promising potential candidate to selectively target the aggressive population of initiating cells within GBM. PMID:27589691

  5. 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

  6. CD200-expressing human basal cell carcinoma cells initiate tumor growth.

    PubMed

    Colmont, Chantal S; Benketah, Antisar; Reed, Simon H; Hawk, Nga V; Telford, William G; Ohyama, Manabu; Udey, Mark C; Yee, Carole L; Vogel, Jonathan C; Patel, Girish K

    2013-01-22

    Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC.

  7. Sphere Culture of Murine Lung Cancer Cell Lines Are Enriched with Cancer Initiating Cells

    PubMed Central

    Morrison, Brian J.

    2012-01-01

    Cancer initiating cells (CICs) represent a unique cell population essential for the maintenance and growth of tumors. Most in vivo studies of CICs utilize human tumor xenografts in immunodeficient mice. These models provide limited information on the interaction of CICs with the host immune system and are of limited value in assessing therapies targeting CICs, especially immune-based therapies. To assess this, a syngeneic cancer model is needed. We examined the sphere-forming capacity of thirteen murine lung cancer cell lines and identified TC-1 and a metastatic subclone of Lewis lung carcinoma (HM-LLC) as cell lines that readily formed and maintained spheres over multiple passages. TC-1 tumorspheres were not enriched for expression of CD133 or CD44, putative CIC markers, nor did they demonstrate Hoechst 33342 side population staining or Aldefluor activity compared to adherent TC-1 cells. However, in tumorsphere culture, these cells exhibited self-renewal and long-term symmetric division capacity and expressed more Oct-4 compared to adherent cells. HM-LLC sphere-derived cells exhibited increased Oct-4, CD133, and CD44 expression, demonstrated a Hoechst 33342 side population and Aldefluor activity compared to adherent cells or a low metastatic subclone of LLC (LM-LLC). In syngeneic mice, HM-LLC sphere-derived cells required fewer cells to initiate tumorigenesis compared to adherent or LM-LLC cells. Similarly TC-1 sphere-derived cells were more tumorigenic than adherent cells in syngeneic mice. In contrast, in immunocompromised mice, less than 500 sphere or adherent TC-1 cells and less than 1,000 sphere or adherent LLC cells were required to initiate a tumor. We suggest that no single phenotypic marker can identify CICs in murine lung cancer cell lines. Tumorsphere culture may provide an alternative approach to identify and enrich for murine lung CICs. Furthermore, we propose that assessing tumorigenicity of murine lung CICs in syngeneic mice better models the

  8. Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation.

    PubMed

    Youssef, Khalil Kass; Lapouge, Gaëlle; Bouvrée, Karine; Rorive, Sandrine; Brohée, Sylvain; Appelstein, Ornella; Larsimont, Jean-Christophe; Sukumaran, Vijayakumar; Van de Sande, Bram; Pucci, Doriana; Dekoninck, Sophie; Berthe, Jean-Valery; Aerts, Stein; Salmon, Isabelle; del Marmol, Véronique; Blanpain, Cédric

    2012-12-01

    Basal cell carcinoma, the most frequent human skin cancer, arises from activating hedgehog (HH) pathway mutations; however, little is known about the temporal changes that occur in tumour-initiating cells from the first oncogenic hit to the development of invasive cancer. Using an inducible mouse model enabling the expression of a constitutively active Smoothened mutant (SmoM2) in the adult epidermis, we carried out transcriptional profiling of SmoM2-expressing cells at different times during cancer initiation. We found that tumour-initiating cells are massively reprogrammed into a fate resembling that of embryonic hair follicle progenitors (EHFPs). Wnt/ β-catenin signalling was very rapidly activated following SmoM2 expression in adult epidermis and coincided with the expression of EHFP markers. Deletion of β-catenin in adult SmoM2-expressing cells prevents EHFP reprogramming and tumour initiation. Finally, human basal cell carcinomas also express genes of the Wnt signalling and EHFP signatures.

  9. 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.

  10. 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.

  11. Persistence of biomarker ATP and ATP-generating capability in bacterial cells and spores contaminating spacecraft materials under earth conditions and in a simulated martian environment.

    PubMed

    Fajardo-Cavazos, Patricia; Schuerger, Andrew C; Nicholson, Wayne L

    2008-08-01

    Most planetary protection research has concentrated on characterizing viable bioloads on spacecraft surfaces, developing techniques for bioload reduction prior to launch, and studying the effects of simulated martian environments on microbial survival. Little research has examined the persistence of biogenic signature molecules on spacecraft materials under simulated martian surface conditions. This study examined how endogenous adenosine-5'-triphosphate (ATP) would persist on aluminum coupons under simulated martian conditions of 7.1 mbar, full-spectrum simulated martian radiation calibrated to 4 W m(-2) of UV-C (200 to 280 nm), -10 degrees C, and a Mars gas mix of CO(2) (95.54%), N(2) (2.7%), Ar (1.6%), O(2) (0.13%), and H(2)O (0.03%). Cell or spore viabilities of Acinetobacter radioresistens, Bacillus pumilus, and B. subtilis were measured in minutes to hours, while high levels of endogenous ATP were recovered after exposures of up to 21 days. The dominant factor responsible for temporal reductions in viability and loss of ATP was the simulated Mars surface radiation; low pressure, low temperature, and the Mars gas composition exhibited only slight effects. The normal burst of endogenous ATP detected during spore germination in B. pumilus and B. subtilis was reduced by 1 or 2 orders of magnitude following, respectively, 8- or 30-min exposures to simulated martian conditions. The results support the conclusion that endogenous ATP will persist for time periods that are likely to extend beyond the nominal lengths of most surface missions on Mars, and planetary protection protocols prior to launch may require additional rigor to further reduce the presence and abundance of biosignature molecules on spacecraft surfaces.

  12. Persistence of Biomarker ATP and ATP-Generating Capability in Bacterial Cells and Spores Contaminating Spacecraft Materials under Earth Conditions and in a Simulated Martian Environment▿

    PubMed Central

    Fajardo-Cavazos, Patricia; Schuerger, Andrew C.; Nicholson, Wayne L.

    2008-01-01

    Most planetary protection research has concentrated on characterizing viable bioloads on spacecraft surfaces, developing techniques for bioload reduction prior to launch, and studying the effects of simulated martian environments on microbial survival. Little research has examined the persistence of biogenic signature molecules on spacecraft materials under simulated martian surface conditions. This study examined how endogenous adenosine-5′-triphosphate (ATP) would persist on aluminum coupons under simulated martian conditions of 7.1 mbar, full-spectrum simulated martian radiation calibrated to 4 W m−2 of UV-C (200 to 280 nm), −10°C, and a Mars gas mix of CO2 (95.54%), N2 (2.7%), Ar (1.6%), O2 (0.13%), and H2O (0.03%). Cell or spore viabilities of Acinetobacter radioresistens, Bacillus pumilus, and B. subtilis were measured in minutes to hours, while high levels of endogenous ATP were recovered after exposures of up to 21 days. The dominant factor responsible for temporal reductions in viability and loss of ATP was the simulated Mars surface radiation; low pressure, low temperature, and the Mars gas composition exhibited only slight effects. The normal burst of endogenous ATP detected during spore germination in B. pumilus and B. subtilis was reduced by 1 or 2 orders of magnitude following, respectively, 8- or 30-min exposures to simulated martian conditions. The results support the conclusion that endogenous ATP will persist for time periods that are likely to extend beyond the nominal lengths of most surface missions on Mars, and planetary protection protocols prior to launch may require additional rigor to further reduce the presence and abundance of biosignature molecules on spacecraft surfaces. PMID:18567687

  13. Isolation of canine mammary cells with stem cell properties and tumour-initiating potential.

    PubMed

    Cocola, C; Anastasi, P; Astigiano, S; Piscitelli, E; Pelucchi, P; Vilardo, L; Bertoli, G; Beccaglia, M; Veronesi, M C; Sanzone, S; Barbieri, O; Reinbold, R A; Luvoni, G C; Zucchi, I

    2009-07-01

    Recent data suggest that mammary carcinogenesis may be driven by cancer stem cells (CSCs) derived from mutated adult stem cells, which have acquired aberrant cell self-renewal or by progenitor cells that have acquired the capacity for cell self-renewal. Spontaneous mammary cancers in cats and dogs are important models for the understanding of human breast cancer and may represent alternative species model systems that can significantly contribute to the study of human oncogenesis. With the goal of identifying markers for isolating human breast CSCs, we have generated a canine model system to isolate and characterize normal and CSCs from dog mammary gland. Insight into the hierarchical organization of canine tumours may contribute to the development of universal concepts in oncogenesis by CSCs. Cells with stem cell properties were isolated from normal and tumoural canine breast tissue and propagated as mammospheres and tumourspheres in long-term non-adherent culture conditions. We showed that cells obtained from spheres that display self-renewing properties, have multi-lineage differentiation potential, could generate complex branched tubular structures in vitro and form tumours in NOD/SCID mice. We analysed these cells for the expression of human stem and CSC markers and are currently investigating the tumour-initiating properties of these cells and the hierarchical organization of normal and neoplastic canine mammary tissue.

  14. 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.

  15. 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).

  16. Reprogramming bladder cancer cells for studying cancer initiation and progression.

    PubMed

    Iskender, Banu; Izgi, Kenan; Canatan, Halit

    2016-10-01

    The induced pluripotent stem cell (iPSC) technology is the forced expression of specific transcription factors in somatic cells resulting in transformation into self-renewing, pluripotent cells which possess the ability to differentiate into any type of cells in the human body. While malignant cells could also be reprogrammed into iPSC-like cells with lower efficiency due to the genetic and epigenetic barriers in cancer cells, only a limited number of cancer cell types could be successfully reprogrammed until today. In the present study, we aimed at reprogramming two bladder cancer cell lines HTB-9 and T24 using a non-integrating Sendai virus (SeV) system. We have generated six sub-clones using distinct combinations of four factors-OCT4, SOX2, KLF4 and c-MYC-in two bladder cancer cell lines. Only a single sub-clone, T24 transduced with 4Fs, gave rise to iPSC-like cells. Bladder cancer cell-derived T24 4F cells represent unique features of pluripotent cells such as epithelial-like morphology, colony-forming ability, expression of pluripotency-associated markers and bearing the ability to differentiate in vitro. This is the first study focusing on the reprogramming susceptibility of two different bladder cancer cell lines to nuclear reprogramming. Further molecular characterisation of T24 4F cells could provide a better insight for biomarker research in bladder carcinogenesis and could offer a valuable tool for the development of novel therapeutic approaches in bladder carcinoma.

  17. Effect of initial carbon sources on the performance of microbial fuel cells containing Proteus vulgaris.

    PubMed

    Kim, N; Choi, Y; Jung, S; Kim, S

    2000-10-05

    Mediator-coupled microbial fuel cells containing Proteus vulgaris were constructed and the cell performance was tested. Fuel cell efficiency depended on the carbon source in the initial medium of the microorganism. Maltose and trehalose were not utilized substantially by P. vulgaris; however, their presence in the initial medium resulted in enhanced cell performance. In particular, galactose showed 63% coulombic efficiency in a biofuel cell after P. vulgaris was cultured in a trehalose-containing medium. This work demonstrates that optimum utilization of carbon sources by microorganisms, which leads to the maximization of fuel cell performance, is possible simply by adjusting initial carbon sources.

  18. 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.

  19. Heterogeneity of tumor cells in terms of cancer-initiating cells

    PubMed Central

    Morii, Eiichi

    2016-01-01

    Tumors derive from a single cell clone but consist of heterogeneous cell subpopulations with diverse features and functions. A limited number of subclones with a selective advantage can initiate tumors when inoculated into immunocompromised mice, and are called cancer-initiating cells (CICs). CICs can be isolated from the bulk of tumors on the basis of their characteristics, such as high reagent efflux, degradation of reactive oxygen species, and aldehyde dehydrogenase (ALDH) activity. Under normal conditions, new CICs are produced by existing CICs rather than non-CICs. However, under stress conditions, non-CICs can occasionally produce CICs, a phenomenon known as plasticity. The dynamic exchange between CICs and non-CICs may enable tumors to survive under unfavorable conditions. CICs are located in a small portion of tumors. This suggests that microenvironmental factors induce or inhibit the CIC phenotype, which might be regulated by intercellular signaling between tumor cells. This review describes isolation of CICs from tumor cell populations and the microenvironmental factors that regulate CIC phenotypes in uterine cancer and lymphoma. PMID:28190919

  20. 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,

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells

    PubMed Central

    Corsaro, Alessandro; Bajetto, Adriana; Thellung, Stefano; Begani, Giulia; Villa, Valentina; Nizzari, Mario; Pattarozzi, Alessandra; Solari, Agnese; Gatti, Monica; Pagano, Aldo; Würth, Roberto; Daga, Antonio; Barbieri, Federica; Florio, Tullio

    2016-01-01

    Prion protein (PrPC) is a cell surface glycoprotein whose misfolding is responsible for prion diseases. Although its physiological role is not completely defined, several lines of evidence propose that PrPC is involved in self-renewal, pluripotency gene expression, proliferation and differentiation of neural stem cells. Moreover, PrPC regulates different biological functions in human tumors, including glioblastoma (GBM). We analyzed the role of PrPC in GBM cell pathogenicity focusing on tumor-initiating cells (TICs, or cancer stem cells, CSCs), the subpopulation responsible for development, progression and recurrence of most malignancies. Analyzing four GBM CSC-enriched cultures, we show that PrPC expression is directly correlated with the proliferation rate of the cells. To better define its role in CSC biology, we knocked-down PrPC expression in two of these GBM-derived CSC cultures by specific lentiviral-delivered shRNAs. We provide evidence that CSC proliferation rate, spherogenesis and in vivo tumorigenicity are significantly inhibited in PrPC down-regulated cells. Moreover, PrPC down-regulation caused loss of expression of the stemness and self-renewal markers (NANOG, Sox2) and the activation of differentiation pathways (i.e. increased GFAP expression). Our results suggest that PrPC controls the stemness properties of human GBM CSCs and that its down-regulation induces the acquisition of a more differentiated and less oncogenic phenotype. PMID:27229535

  11. 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

  12. Printed Spacecraft Separation System

    SciTech Connect

    Holmans, Walter; Dehoff, Ryan

    2016-10-01

    In this project Planetary Systems Corporation proposed utilizing additive manufacturing (3D printing) to manufacture a titanium spacecraft separation system for commercial and US government customers to realize a 90% reduction in the cost and energy. These savings were demonstrated via “printing-in” many of the parts and sub-assemblies into one part, thus greatly reducing the labor associated with design, procurement, assembly and calibration of mechanisms. Planetary Systems Corporation redesigned several of the components of the separation system based on additive manufacturing principles including geometric flexibility and the ability to fabricate complex designs, ability to combine multiple parts of an assembly into a single component, and the ability to optimize design for specific mechanical property targets. Shock absorption was specifically targeted and requirements were established to attenuate damage to the Lightband system from shock of initiation. Planetary Systems Corporation redesigned components based on these requirements and sent the designs to Oak Ridge National Laboratory to be printed. ORNL printed the parts using the Arcam electron beam melting technology based on the desire for the parts to be fabricated from Ti-6Al-4V based on the weight and mechanical performance of the material. A second set of components was fabricated from stainless steel material on the Renishaw laser powder bed technology due to the improved geometric accuracy, surface finish, and wear resistance of the material. Planetary Systems Corporation evaluated these components and determined that 3D printing is potentially a viable method for achieving significant cost and savings metrics.

  13. 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.

  14. Modeling Laser Effects on Multi-Junction Solar Cells Using Silvaco ATLAS Software for Spacecraft Power Beaming Applications

    DTIC Science & Technology

    2010-06-01

    devised was meant to achieve the highest efficiency of the solar cell while maintaining the same power output. In a perfect world the system would...CHAMPION CELL - 36.28% Efficiency !! #This model is an explicit InGaP/ GaAs /Ge Triple Junction solar cell with Tunnel Junction KATO OPTM 0.82InGaP...the same output of the cell as experienced under solar illumination, thereby replacing the sun. The original cell boasted 36.29% efficiency under

  15. 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.

  16. Cytokinin-mediated cell cycling arrest of pericycle founder cells in lateral root initiation of Arabidopsis.

    PubMed

    Li, Xiang; Mo, Xiaorong; Shou, Huixia; Wu, Ping

    2006-08-01

    In Arabidopsis, lateral root formation is a post-embryonic developmental event, which is regulated by hormones and environmental signals. In this study, via analyzing the expression of cyclin genes during lateral root (LR) formation, we report that cytokinins (CTKs) inhibit the initiation of LR through blocking the pericycle founder cells cycling at the G(2) to M transition phase, while the promotion by CTK of LR elongation is due to the stimulation of the G(1) to S transition. No significant difference was detected in the inhibitory effect of CTK on LR formation between wild-type plants and mutants defective in auxin response or transport. In addition, exogenously applied auxin at different concentrations could not rescue the CTK-mediated inhibition of LR initiation. Our data suggest that CTK and auxin might control LR initiation through two separate signaling pathways in Arabidopsis. The CTK-mediated repression of LR initiation is transmitted through the two-component signal system and mediated by the receptor CRE1.

  17. SHARP: Automated monitoring of spacecraft health and status

    NASA Technical Reports Server (NTRS)

    Atkinson, David J.; James, Mark L.; Martin, R. Gaius

    1991-01-01

    Briefly discussed here are the spacecraft and ground systems monitoring process at the Jet Propulsion Laboratory (JPL). Some of the difficulties associated with the existing technology used in mission operations are highlighted. A new automated system based on artificial intelligence technology is described which seeks to overcome many of these limitations. The system, called the Spacecraft Health Automated Reasoning Prototype (SHARP), is designed to automate health and status analysis for multi-mission spacecraft and ground data systems operations. The system has proved to be effective for detecting and analyzing potential spacecraft and ground systems problems by performing real-time analysis of spacecraft and ground data systems engineering telemetry. Telecommunications link analysis of the Voyager 2 spacecraft was the initial focus for evaluation of the system in real-time operations during the Voyager spacecraft encounter with Neptune in August 1989.

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

    PubMed Central

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

    2015-01-01

    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

  19. Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production.

    PubMed

    Nestle, Frank O; Conrad, Curdin; Tun-Kyi, Adrian; Homey, Bernhard; Gombert, Michael; Boyman, Onur; Burg, Günter; Liu, Yong-Jun; Gilliet, Michel

    2005-07-04

    Psoriasis is one of the most common T cell-mediated autoimmune diseases in humans. Although a role for the innate immune system in driving the autoimmune T cell cascade has been proposed, its nature remains elusive. We show that plasmacytoid predendritic cells (PDCs), the natural interferon (IFN)-alpha-producing cells, infiltrate the skin of psoriatic patients and become activated to produce IFN-alpha early during disease formation. In a xenograft model of human psoriasis, we demonstrate that blocking IFN-alpha signaling or inhibiting the ability of PDCs to produce IFN-alpha prevented the T cell-dependent development of psoriasis. Furthermore, IFN-alpha reconstitution experiments demonstrated that PDC-derived IFN-alpha is essential to drive the development of psoriasis in vivo. These findings uncover a novel innate immune pathway for triggering a common human autoimmune disease and suggest that PDCs and PDC-derived IFN-alpha represent potential early targets for the treatment of psoriasis.

  20. 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.

  1. Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition.

    PubMed

    Latil, Mathilde; Nassar, Dany; Beck, Benjamin; Boumahdi, Soufiane; Wang, Li; Brisebarre, Audrey; Dubois, Christine; Nkusi, Erwin; Lenglez, Sandrine; Checinska, Agnieszka; Vercauteren Drubbel, Alizée; Devos, Michael; Declercq, Wim; Yi, Rui; Blanpain, Cédric

    2017-02-02

    Epithelial to mesenchymal transition (EMT) in cancer cells has been associated with metastasis, stemness, and resistance to therapy. Some tumors undergo EMT while others do not, which may reflect intrinsic properties of their cell of origin. However, this possibility is largely unexplored. By targeting the same oncogenic mutations to discrete skin compartments, we show that cell-type-specific chromatin and transcriptional states differentially prime tumors to EMT. Squamous cell carcinomas (SCCs) derived from interfollicular epidermis (IFE) are generally well differentiated, while hair follicle (HF) stem cell-derived SCCs frequently exhibit EMT, efficiently form secondary tumors, and possess increased metastatic potential. Transcriptional and epigenomic profiling revealed that IFE and HF tumor-initiating cells possess distinct chromatin landscapes and gene regulatory networks associated with tumorigenesis and EMT that correlate with accessibility of key epithelial and EMT transcription factor binding sites. These findings highlight the importance of chromatin states and transcriptional priming in dictating tumor phenotypes and EMT.

  2. Flywheel energy storage for spacecraft

    NASA Technical Reports Server (NTRS)

    Gross, S.

    1984-01-01

    Flywheel energy storage systems have been studied to determine their potential for use in spacecraft. This system was found to be superior to alkaline secondary batteries and regenerative fuel cells in most of the areas that are important in spacecraft applications. Of special importance, relative to batteries, are lighter weight, longer cycle and operating life, and high efficiency which minimizes solar array size and the amount of orbital makeup fuel required. In addition, flywheel systems have a long shelf life, give a precise state of charge indication, have modest thermal control needs, are capable of multiple discharges per orbit, have simple ground handling needs, and have the capability of generating extremely high power for short durations.

  3. 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.

  4. The phytoalexin resveratrol regulates the initiation of hypersensitive cell death in Vitis cell.

    PubMed

    Chang, Xiaoli; Heene, Ernst; Qiao, Fei; Nick, Peter

    2011-01-01

    Resveratrol is a major phytoalexin produced by plants in response to various stresses and promotes disease resistance. The resistance of North American grapevine Vitis rupestris is correlated with a hypersensitive reaction (HR), while susceptible European Vitis vinifera cv. 'Pinot Noir' does not exhibit HR, but expresses basal defence. We have shown previously that in cell lines derived from the two Vitis species, the bacterial effector Harpin induced a rapid and sensitive accumulation of stilbene synthase (StSy) transcripts, followed by massive cell death in V. rupestris. In the present work, we analysed the function of the phytoalexin resveratrol, the product of StSy. We found that cv. 'Pinot Noir' accumulated low resveratrol and its glycoside trans-piceid, whereas V. rupestris produced massive trans-resveratrol and the toxic oxidative δ-viniferin, indicating that the preferred metabolitism of resveratrol plays role in Vitis resistance. Cellular responses to resveratrol included rapid alkalinisation, accumulation of pathogenesis-related protein 5 (PR5) transcripts, oxidative burst, actin bundling, and cell death. Microtubule disruption and induction of StSy were triggered by Harpin, but not by resveratrol. Whereas most responses proceeded with different amplitude for the two cell lines, the accumulation of resveratrol, and the competence for resveratrol-induced oxidative burst differed in quality. The data lead to a model, where resveratrol, in addition to its classical role as antimicrobial phytoalexin, represents an important regulator for initiation of HR-related cell death.

  5. 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.

  6. Concept of Operations for the Dust Dispenser Spacecraft for Active Orbital Debris Removal

    DTIC Science & Technology

    2014-03-25

    spacecraft systems. For the dispenser spacecraft , power will likely be generated by solar cells and storage within batteries. From these sources...exterior components such as the sensors and solar panels. Upon launch vehicle and fairing geometry selection, the dispenser spacecraft configuration...occur. Thermal Control System This system maintains temperature of all spacecraft components within design limits throughout the mission lifetime

  7. Lightweight, light-trapped, thin GaAs solar cell for spacecraft applications: Progress and results update

    NASA Technical Reports Server (NTRS)

    Hannon, M. H.; Dashiell, M. W.; Dinetta, L. C.; Barnett, A. M.

    1995-01-01

    Progress is reported with respect to the development of ultra-lightweight, high performance, thin, light trapped GaAs solar cells for advanced space power systems. Conversion efficiencies of over 17.7% have been demonstrated for a 3 micron thick, 1 sq cm silicone bonded solar cell. This results in a specific power of over 1020 W/kg. Device parameters were 1.011 V open circuit voltage, 80% fill factor, and a short-circuit current density of 29.5 mA/sq cm . In addition to silicone bonding, the use of electrostatic bonding to attach the coverglass support to the front surface enables an ultra-thin, all back contact design that survives processing temperatures greater than 750 C. This also results in a 10% reduction of the cell weight for a potential specific power of 1270 W/kg. All back contact, ultra-thin, electrostatically bonded GaAs solar cell prototypes have been completed demonstrating an open circuit voltage of 1 volt for a cell base thickness of 1 micron with a 0.5 micron emitter. This technology will result in a revolutionary improvement in survivability, performance, and manufacturability of lightweight GaAs solar cell products for future Earth-orbiting science and space exploration missions. The thin, electrostatically bonded, all back contact GaAs device technology has multiple uses for specialty high performance solar cells and other optoelectronic devices.

  8. Lightweight, light-trapped, thin GaAs solar cell for spacecraft applications: Progress and results update

    NASA Astrophysics Data System (ADS)

    Hannon, M. H.; Dashiell, M. W.; Dinetta, L. C.; Barnett, A. M.

    1995-10-01

    Progress is reported with respect to the development of ultra-lightweight, high performance, thin, light trapped GaAs solar cells for advanced space power systems. Conversion efficiencies of over 17.7% have been demonstrated for a 3 micron thick, 1 sq cm silicone bonded solar cell. This results in a specific power of over 1020 W/kg. Device parameters were 1.011 V open circuit voltage, 80% fill factor, and a short-circuit current density of 29.5 mA/sq cm . In addition to silicone bonding, the use of electrostatic bonding to attach the coverglass support to the front surface enables an ultra-thin, all back contact design that survives processing temperatures greater than 750 C. This also results in a 10% reduction of the cell weight for a potential specific power of 1270 W/kg. All back contact, ultra-thin, electrostatically bonded GaAs solar cell prototypes have been completed demonstrating an open circuit voltage of 1 volt for a cell base thickness of 1 micron with a 0.5 micron emitter. This technology will result in a revolutionary improvement in survivability, performance, and manufacturability of lightweight GaAs solar cell products for future Earth-orbiting science and space exploration missions. The thin, electrostatically bonded, all back contact GaAs device technology has multiple uses for specialty high performance solar cells and other optoelectronic devices.

  9. 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.

  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. 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.

  13. 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.

  14. 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.

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

    PubMed

    Insel, Thomas R; Koroshetz, Walter

    2015-12-15

    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.

  16. 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.

  17. Spacecraft Charge as a Source of Electrical Power for Spacecraft

    DTIC Science & Technology

    1988-11-01

    Progress in Astronautics and Aeronautics.47: Spacecraft Charging by3Maanetospheric Plasmas : 15-30, 1976. Nicholson, Dwight R...34 Spacecraft Charging Investigation: A Joint Research and Technology Program," Progress in Astronautics and Astronautics . 47: Spacecraft Charging by... Magnetospheric Plasmas : 3-14, 1976. l Massaro, N.J. and others. "A Charging Model for Three-Axis Stabilized Spacecraft ,"

  18. 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.

  19. Physiological responses to acid stress by Saccharomyces cerevisiae when applying high initial cell density

    PubMed Central

    Guo, Zhong-peng; Olsson, Lisbeth

    2016-01-01

    High initial cell density is used to increase volumetric productivity and shorten production time in lignocellulosic hydrolysate fermentation. Comparison of physiological parameters in high initial cell density cultivation of Saccharomyces cerevisiae in the presence of acetic, formic, levulinic and cinnamic acids demonstrated general and acid-specific responses of cells. All the acids studied impaired growth and inhibited glycolytic flux, and caused oxidative stress and accumulation of trehalose. However, trehalose may play a role other than protecting yeast cells from acid-induced oxidative stress. Unlike the other acids, cinnamic acid did not cause depletion of cellular ATP, but abolished the growth of yeast on ethanol. Compared with low initial cell density, increasing initial cell density reduced the lag phase and improved the bioconversion yield of cinnamic acid during acid adaptation. In addition, yeast cells were able to grow at elevated concentrations of acid, probable due to the increase in phenotypic cell-to-cell heterogeneity in large inoculum size. Furthermore, the specific growth rate and the specific rates of glucose consumption and metabolite production were significantly lower than at low initial cell density, which was a result of the accumulation of a large fraction of cells that persisted in a viable but non-proliferating state. PMID:27620460

  20. Linking genomic reorganization to tumor initiation via the giant cell cycle

    PubMed Central

    Niu, N; Zhang, J; Zhang, N; Mercado-Uribe, I; Tao, F; Han, Z; Pathak, S; Multani, A S; Kuang, J; Yao, J; Bast, R C; Sood, A K; Hung, M-C; Liu, J

    2016-01-01

    To investigate the mechanisms underlying our recent paradoxical finding that mitotically incapacitated and genomically unstable polyploid giant cancer cells (PGCCs) are capable of tumor initiation, we labeled ovarian cancer cells with α-tubulin fused to green fluorescent protein, histone-2B fused to red fluorescent protein and FUCCI (fluorescent ubiquitination cell cycle indicator), and tracked the spatial and time-dependent change in spindle and chromosomal dynamics of PGCCs using live-cell fluorescence time-lapse recording. We found that single-dose (500 nm) treatment with paclitaxel paradoxically initiated endoreplication to form PGCCs after massive cell death. The resulting PGCCs continued self-renewal via endoreplication and further divided by nuclear budding or fragmentation; the small daughter nuclei then acquired cytoplasm, split off from the giant mother cells and acquired competency in mitosis. FUCCI showed that PGCCs divided via truncated endoreplication cell cycle (endocycle or endomitosis). Confocal microscopy showed that PGCCs had pronounced nuclear fragmentation and lacked expression of key mitotic proteins. PGCC-derived daughter cells were capable of long-term proliferation and acquired numerous new genome/chromosome alterations demonstrated by spectral karyotyping. These data prompt us to conceptualize a giant cell cycle composed of four distinct but overlapping phases, initiation, self-renewal, termination and stability. The giant cell cycle may represent a fundamental cellular mechanism to initiate genomic reorganization to generate new tumor-initiating cells in response to chemotherapy-induced stress and contributes to disease relapse. PMID:27991913

  1. 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.

  2. 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.

  3. 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.

  4. Selection of brain metastasis-initiating breast cancer cells determined by growth on hard agar.

    PubMed

    Guo, Lixia; Fan, Dominic; Zhang, Fahao; Price, Janet E; Lee, Ju-Seog; Marchetti, Dario; Fidler, Isaiah J; Langley, Robert R

    2011-05-01

    An approach that facilitates rapid isolation and characterization of tumor cells with enhanced metastatic potential is highly desirable. Here, we demonstrate that plating GI-101A human breast cancer cells on hard (0.9%) agar selects for the subpopulation of metastasis-initiating cells. The agar-selected cells, designated GI-AGR, were homogeneous for CD44(+) and CD133(+) and five times more invasive than the parental GI-101A cells. Moreover, mice injected with GI-AGR cells had significantly more experimental brain metastases and shorter overall survival than did mice injected with GI-101A cells. Comparative gene expression analysis revealed that GI-AGR cells were markedly distinct from the parental cells but shared an overlapping pattern of gene expression with the GI-101A subline GI-BRN, which was generated by repeated in vivo recycling of GI-101A cells in an experimental brain metastasis model. Data mining on 216 genes shared between GI-AGR and GI-BRN breast cancer cells suggested that the molecular phenotype of these cells is consistent with that of cancer stem cells and the aggressive basal subtype of breast cancer. Collectively, these results demonstrate that analysis of cell growth in a hard agar assay is a powerful tool for selecting metastasis-initiating cells in a heterogeneous population of breast cancer cells, and that such selected cells have properties similar to those of tumor cells that are selected based on their potential to form metastases in mice.

  5. RNA processing body (P-body) dynamics in mesophyll protoplasts re-initiating cell division.

    PubMed

    Bhullar, Dilbag S; Sheahan, Michael B; Rose, Ray J

    2016-12-07

    The ability of plants to regenerate lies in the capacity of differentiated cells to reprogram and re-enter the cell cycle. Reprogramming of cells requires changes in chromatin organisation and gene expression. However, there has been less focus on changes at the post transcription level. We have investigated P-bodies, sites of post transcriptional gene regulation, in plant cell reprogramming in cultured mesophyll protoplasts; by using a YFP-VARICOSE (YFP-VCSc) translational fusion. We showed an early increase in P-body number and volume, followed by a decline, then a subsequent continued increase in P-body number and volume as cell division was initiated and cell proliferation continued. We infer that plant P-bodies have a role to play in reprogramming the mature cell and re-initiating the cell division cycle. The timing of the first phase is consistent with the degredation of messages no longer required, as the cell transits to the division state, and may also be linked to the stress response associated with division induction in cultured cells. The subsequent increase in P-body formation, with partitioning to the daughter cells during the division process, suggests a role in the cell cycle and its re-initiation in daughter cells. P-bodies were shown to be mobile in the cytoplasm and show actin-based motility which facilitates their post-transcriptional role and partitioning to daughter cells.

  6. 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.

  7. 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.

  8. Thyroid metastasis as initial presentation of clear cell renal carcinoma

    PubMed Central

    Ramírez-Plaza, César Pablo; Domínguez-López, Marta Elena; Blanco-Reina, Francisco

    2015-01-01

    Introduction Metastatic tumors account for 1.4–2.5% of thyroid malignancies. About 25–30% of patients with clear cell renal carcinoma (CCRC) have distant metastasis at the time of diagnosis, being the thyroid gland a rare localization [5%]. Presentation of the case A 62-year woman who underwent a cervical ultrasonography and a PAAF biopsy reporting atypical follicular proliferation with a few intranuclear vacuoles “suggestive” of thyroid papillary cancer in the context of a multinodular goiter was reported. A total thyroidectomy was performed and the histology of a clear cell renal carcinoma (CCRC) was described in four nodules of the thyroid gland. A CT scan was performed and a renal giant right tumor was found. The patient underwent an eventful radical right nephrectomy and the diagnosis of CCRC was confirmed. Discussion Thyroid metastasis (TM) from CCRC are usually apparent in a metachronic context during the follow-up of a treated primary (even many years after) but may sometimes be present at the same time than the primary renal tumor. Our case is exceptional because the TM was the first evidence of the CCRC, which was subsequently diagnosed and treated. Conclusion The possibility of finding of an incidental metastatic tumor in the thyroid gland from a previous unknown and non-diganosed primary (as CCRC in our case was) is rare and account only for less than 1% of malignancies. Nonetheless, the thyroid gland is a frequent site of metastasis and the presence of “de novo” thyroid nodules in oncologic patients must be always considered and studied. PMID:25827295

  9. 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.

  10. YAP/TAZ initiate and maintain Schwann cell myelination

    PubMed Central

    Grove, Matthew; Kim, Hyukmin; Santerre, Maryline; Krupka, Alexander J; Han, Seung Baek; Zhai, Jinbin; Cho, Jennifer Y; Park, Raehee; Harris, Michele; Kim, Seonhee; Sawaya, Bassel E; Kang, Shin H; Barbe, Mary F; Cho, Seo-Hee; Lemay, Michel A; Son, Young-Jin

    2017-01-01

    Nuclear exclusion of the transcriptional regulators and potent oncoproteins, YAP/TAZ, is considered necessary for adult tissue homeostasis. Here we show that nuclear YAP/TAZ are essential regulators of peripheral nerve development and myelin maintenance. To proliferate, developing Schwann cells (SCs) require YAP/TAZ to enter S-phase and, without them, fail to generate sufficient SCs for timely axon sorting. To differentiate, SCs require YAP/TAZ to upregulate Krox20 and, without them, completely fail to myelinate, resulting in severe peripheral neuropathy. Remarkably, in adulthood, nuclear YAP/TAZ are selectively expressed by myelinating SCs, and conditional ablation results in severe peripheral demyelination and mouse death. YAP/TAZ regulate both developmental and adult myelination by driving TEAD1 to activate Krox20. Therefore, YAP/TAZ are crucial for SCs to myelinate developing nerve and to maintain myelinated nerve in adulthood. Our study also provides a new insight into the role of nuclear YAP/TAZ in homeostatic maintenance of an adult tissue. DOI: http://dx.doi.org/10.7554/eLife.20982.001 PMID:28124973

  11. Tobacco and e-cigarette products initiate Kupffer cell inflammatory responses.

    PubMed

    Rubenstein, David A; Hom, Sarah; Ghebrehiwet, Berhane; Yin, Wei

    2015-10-01

    Kupffer cells are liver resident macrophages that are responsible for screening and clearing blood of pathogens and foreign particles. It has recently been shown that Kupffer cells interact with platelets, through an adhesion based mechanism, to aid in pathogen clearance and then these platelets re-enter the general systemic circulation. Thus, a mechanism has been identified that relates liver inflammation to possible changes in the systemic circulation. However, the role that Kupffer cells play in cardiovascular disease initiation/progression has not been elucidated. Thus, our objective was to determine whether or not Kupffer cells are responsive to a classical cardiovascular risk factor and if these changes can be transmitted into the general systemic circulation. If Kupffer cells initiate inflammatory responses after exposure to classical cardiovascular risk factors, then this provides a potential alternative/synergistic pathway for cardiovascular disease initiation. We aimed to elucidate the prevalence of this potential pathway. We hypothesized that Kupffer cells would initiate a robust inflammatory response after exposure to tobacco cigarette or e-cigarette products and that the inflammatory response would have the potential to antagonize other salient cells for cardiovascular disease progression. To test this, Kupffer cells were incubated with tobacco smoke extracts, e-cigarette vapor extracts or pure nicotine. Complement deposition onto Kupffer cells, Kupffer cell complement receptor expression, oxidative stress production, cytokine release and viability and density were assessed after the exposure. We observed a robust inflammatory response, oxidative stress production and cytokine release after Kupffer cells were exposed to tobacco or e-cigarette extracts. We also observed a marginal decrease in cell viability coupled with a significant decrease in cell density. In general, this was not a function of the extract formulation (e.g. tobacco vs. e

  12. Mechanical Design of Spacecraft

    NASA Technical Reports Server (NTRS)

    1962-01-01

    In the spring of 1962, engineers from the Engineering Mechanics Division of the Jet Propulsion Laboratory gave a series of lectures on spacecraft design at the Engineering Design seminars conducted at the California Institute of Technology. Several of these lectures were subsequently given at Stanford University as part of the Space Technology seminar series sponsored by the Department of Aeronautics and Astronautics. Presented here are notes taken from these lectures. The lectures were conceived with the intent of providing the audience with a glimpse of the activities of a few mechanical engineers who are involved in designing, building, and testing spacecraft. Engineering courses generally consist of heavily idealized problems in order to allow the more efficient teaching of mathematical technique. Students, therefore, receive a somewhat limited exposure to actual engineering problems, which are typified by more unknowns than equations. For this reason it was considered valuable to demonstrate some of the problems faced by spacecraft designers, the processes used to arrive at solutions, and the interactions between the engineer and the remainder of the organization in which he is constrained to operate. These lecture notes are not so much a compilation of sophisticated techniques of analysis as they are a collection of examples of spacecraft hardware and associated problems. They will be of interest not so much to the experienced spacecraft designer as to those who wonder what part the mechanical engineer plays in an effort such as the exploration of space.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. Standardized Spacecraft Onboard Interfaces

    NASA Technical Reports Server (NTRS)

    Smith, Joseph F.; Plummer, Chris; Plancke, Patrick

    2003-01-01

    The Consultative Committee for Space Data Systems (CCSDS), an international organization of national space agencies, is branching out to provide new standards to enhanced reuse of onboard spacecraft equipment and software. These Spacecraft Onboard Interface (SOIF) standards will be, in part, based on the well-known Internet protocols. This paper will provide a description of the SOIF work by describing three orthogonal views: the Services View that describes data communications services, the Interoperability view shows how to exchange data and messages between different spacecraft elements, and the Protocol view, that describes the SOIF protocols and services. We will also provide a description of the present state of the services that will be provided to SOIF users, and are the basis of the utility of these standards.

  19. 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.

  20. Initiate Tumors with Single Cell Spheres Formed in Serum-Containing Medium

    PubMed Central

    Zhang, Guozhou; Xiong, Kun; Ma, Weiwei; Xu, Wei; Zeng, Huihui

    2015-01-01

    Background: It is difficult to prospectively identify and maintain putative tumor-initiating cells (TICs). Spheres that formed in serum-free media contained more TICs while spheres formed in serum-containing media were not used in tumor-initiating. Methods: Soft-agar was used to isolate colonies. A continuous, static suspension culture using serum-containing media was modified from liquid overlay technique and tumor cell spheres could be maintained by this method for >90 days. Tumor-initiating capacity of these spheres was tested in nude mice. The nuclear staining of OCT4 in sphere cells and the expression profile of hepatic cell lineage related genes were examined. Results: Soft-agar derived HepG2 colonies indicated different properties from their parental cells. The suspension cells of A549 and MCF7 could initiate tumors at 104 cells level. The growth proportions of individual A549, MCF7 and HepG2 spheres with diameter of 101-150 µm were significantly higher than smaller spheres. After suspension culture for 15-27 days, HepG2 and MCF7 spheres could initiate tumors with diameter up to 200 µm; the estimated TIC frequency was 1/1500-1/400. The HepG2 and MCF7 spheres retain tumor-initiating potential for at least 52 days. Conclusion: After 15 days' serum-containing suspension culture small HepG2 and MCF7 cell spheres (diameter ~200 µm) could initiate tumors in nude mice. PMID:26284142

  1. DNA Replication Origin Interference Increases the Spacing between Initiation Events in Human Cells

    PubMed Central

    Lebofsky, Ronald; Heilig, Roland; Sonnleitner, Max; Weissenbach, Jean

    2006-01-01

    Mammalian DNA replication origins localize to sites that range from base pairs to tens of kilobases. A regular distribution of initiations in individual cell cycles suggests that only a limited number of these numerous potential start sites are converted into activated origins. Origin interference can silence redundant origins; however, it is currently unknown whether interference participates in spacing functional human initiation events. By using a novel hybridization strategy, genomic Morse code, on single combed DNA molecules from primary keratinocytes, we report the initiation sites present on 1.5 Mb of human chromosome 14q11.2. We confirm that initiation zones are widespread in human cells, map to intergenic regions, and contain sequence motifs found at other mammalian initiation zones. Origins used per cell cycle are less abundant than the potential sites of initiation, and their limited use increases the spacing between initiation events. Between-zone interference decreases in proportion to the distance from the active origin, whereas within-zone interference is 100% efficient. These results identify a hierarchical organization of origin activity in human cells. Functional origins govern the probability that nearby origins will fire in the context of multiple potential start sites of DNA replication, and this is mediated by origin interference. PMID:17005913

  2. 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

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

    PubMed

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

    2016-01-19

    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.

  4. Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance

    PubMed Central

    2012-01-01

    Background Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I). Methods Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. Results CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 103 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 105 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR). Conclusions We characterized a self-renewing subpopulation of CICs found among four well known human

  5. Does physiological beta cell turnover initiate autoimmune diabetes in the regional lymph nodes?

    PubMed

    Pearl-Yafe, Michal; Iskovich, Svetlana; Kaminitz, Ayelet; Stein, Jerry; Yaniv, Isaac; Askenasy, Nadir

    2006-05-01

    The initial immune process that triggers autoimmune beta cell destruction in type 1 diabetes is not fully understood. In early infancy there is an increased beta cell turnover. Recurrent exposure of tissue-specific antigens could lead to primary sensitization of immune cells in the draining lymph nodes of the pancreas. An initial immune injury to the beta cells can be inflicted by several cell types, primarily macrophages and T cells. Subsequently, infiltrating macrophages transfer antigens exposed by apoptotic beta cells to the draining lymph nodes, where antigen presenting cells process and amplify a secondary immune reaction. Antigen presenting cells evolve as dual players in the activation and suppression of the autoimmune reaction in the draining lymph nodes. We propose a scenario where destructive insulitis is caused by recurrent exposure of specific antigens due to the physiological turnover of beta cells. This sensitization initiates the evolution of reactive clones that remain silent in the regional lymph nodes, where they succeed to evade regulatory clonal deletion.

  6. 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.

  7. Spacecraft Environmental Anomalies Handbook

    DTIC Science & Technology

    1989-08-01

    engineering solutions for mitigating the effects of environmental anomalies have been developed. Among the causes o, spacecraft anomalies are surface...have been discovered after years of investig!:tion, and engineering solutions for mitigating the effccts of environmental anomalies have been developed...23 * 6.4.3 Fauth Tolerant Solutions .............................................................................. 23 6.4.4. Methods

  8. 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.

  9. 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.

  10. Spacecraft attitude sensor

    NASA Technical Reports Server (NTRS)

    Davidson, A. C.; Grant, M. M. (Inventor)

    1973-01-01

    A system for sensing the attitude of a spacecraft includes a pair of optical scanners having a relatively narrow field of view rotating about the spacecraft x-y plane. The spacecraft rotates about its z axis at a relatively high angular velocity while one scanner rotates at low velocity, whereby a panoramic sweep of the entire celestial sphere is derived from the scanner. In the alternative, the scanner rotates at a relatively high angular velocity about the x-y plane while the spacecraft rotates at an extremely low rate or at zero angular velocity relative to its z axis to provide a rotating horizon scan. The positions of the scanners about the x-y plane are read out to assist in a determination of attitude. While the satellite is spinning at a relatively high angular velocity, the angular positions of the bodies detected by the scanners are determined relative to the sun by providing a sun detector having a field of view different from the scanners.

  11. 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

  12. Human immunodeficiency virus 1 envelope-initiated G2-phase programmed cell death.

    PubMed Central

    Kolesnitchenko, V; Wahl, L M; Tian, H; Sunila, I; Tani, Y; Hartmann, D P; Cossman, J; Raffeld, M; Orenstein, J; Samelson, L E

    1995-01-01

    Despite intensive investigation, no clearly defined mechanism explaining human immunodeficiency virus (HIV)-induced cell killing has emerged. HIV-1 infection is initiated through a high-affinity interaction between the HIV-1 external envelope glycoprotein (gp120) and the CD4 receptor on T cells. Cell killing is a later event intimately linked by in vitro genetic analyses with the fusogenic properties of the HIV envelope glycoprotein gp120 and transmembrane glycoprotein gp41. In this report, we describe aberrancies in cell cycle regulatory proteins initiated by cell-cell contact between T cells expressing HIV-1 envelope glycoproteins and other T cells expressing CD4 receptors. Cells rapidly accumulate cyclin B protein and tyrosine-hyperphosphorylated p34cdc2 (cdk1) kinase, indicative of cell cycle arrest at G2 phase. Moreover, these cells continue to synthesize cyclin B protein, enlarge and display an abnormal ballooned morphology, and disappear from the cultures in a pattern previously described for cytotoxicity induced by DNA synthesis (S phase) inhibitors. Similar changes are observed in peripheral blood mononuclear cells infected in vitro with pathogenic primary isolates of HIV-1. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:8524869

  13. 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.

  14. Biased inheritance of the protein PatN frees vegetative cells to initiate patterned heterocyst differentiation.

    PubMed

    Risser, Douglas D; Wong, Francis C Y; Meeks, John C

    2012-09-18

    Heterocysts, cells specialized for nitrogen fixation in certain filamentous cyanobacteria, appear singly in a nonrandom spacing pattern along the chain of vegetative cells. A two-stage, biased initiation and competitive resolution model has been proposed to explain the establishment of this spacing pattern. There is substantial evidence that competitive resolution of a subset of cells initiating differentiation occurs by interactions between a self-enhancing activator protein, HetR, and a diffusible pentapeptide inhibitor PatS-5 (RGSGR). Results presented here show that the absence of a unique membrane protein, PatN, in Nostoc punctiforme strain ATCC 29133 leads to a threefold increase in heterocyst frequency and a fourfold decrease in the vegetative cell interval between heterocysts. A PatN-GFP translational fusion shows a pattern of biased inheritance in daughter vegetative cells of ammonium-grown cultures. Inactivation of another heterocyst patterning gene, patA, is epistatic to inactivation of patN, and transcription of patA increases in a patN-deletion strain, implying that patN may function by modulating levels of patA. The presence of PatN is hypothesized to decrease the competency of a vegetative cell to initiate heterocyst differentiation, and the cellular concentration of PatN is dependent on cell division that results in cells transiently depleted of PatN. We suggest that biased inheritance of cell-fate determinants is a phylogenetic domain-spanning paradigm in the development of biological patterns.

  15. On the prenatal initiation of T cell development in the opossum Monodelphis domestica.

    PubMed

    Hansen, Victoria L; Miller, Robert D

    2017-04-01

    Thymus-dependent lymphocytes (T cells) are a critical cell lineage in the adaptive immune system of all jawed vertebrates. In eutherian mammals the initiation of T cell development takes place prenatally and the offspring of many species are born relatively immuno-competent. Marsupials, in contrast, are born in a comparatively altricial state and with a less well developed immune system. As such, marsupials are valuable models for studying the peri- and postnatal initiation of immune system development in mammals. Previous results supported a lack of prenatal T cell development in a variety of marsupial species. In the gray short-tailed opossum, Monodelphis domestica, however, there was evidence that αβT cells were present on postnatal day 1 and likely initiated development prenatally. Demonstrated here is the presence of CD3ε(+) lymphocytes in late-stage embryos at a site in the upper thoracic cavity, the site of an early developing thymus. CD3ε(+) cells were evident as early as 48 h prior to parturition. In day 14 embryos, where there is clear organogenesis, CD3ε(+) cells were only found at the site of the early thymus, consistent with no extra-thymic sites of T cell development in the opossum. These observations are the first evidence of prenatal T cell lineage commitment in any marsupial.

  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.

  17. Cell cycle regulated phosphorylation of RPA-32 occurs within the replication initiation complex.

    PubMed Central

    Fotedar, R; Roberts, J M

    1992-01-01

    The transition from G1 to S phase of the cell cycle may be regulated by modification of proteins which are essential for initiating DNA replication. One of the first events during initiation is to unwind the origin DNA and this requires a single-stranded DNA binding protein. RPA, a highly conserved multi-subunit single-stranded DNA binding protein, was first identified as a cellular protein necessary for the initiation of SV40 DNA replication. The 32 kDa subunit of RPA has been shown to be phosphorylated at the start of S phase. Using SV40 replication as a model, we have reproduced in vitro the S phase-dependent phosphorylation of RPA-32 and show that it occurs specifically within the replication initiation complex. Phosphorylated RPA-32 is predominantly associated with DNA. Phosphorylation is not a pre-requisite for association with DNA, but occurs after RPA binds to single-stranded DNA formed at the origin during the initiation phase. The protein kinase(s) which phosphorylates RPA-32 is present at all stages of the cell cycle but RPA-32 does not bind to the SV40 origin or become phosphorylated in extracts from G1 cells. Therefore, the cell cycle-dependent phosphorylation of RPA-32 may be regulated by its binding to single-stranded origin DNA during replication initiation. Images PMID:1318194

  18. 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.

  19. 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 ...

  20. 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...

  1. Targeting metastasis-initiating cells through the fatty acid receptor CD36.

    PubMed

    Pascual, Gloria; Avgustinova, Alexandra; Mejetta, Stefania; Martín, Mercè; Castellanos, Andrés; Attolini, Camille Stephan-Otto; Berenguer, Antoni; Prats, Neus; Toll, Agustí; Hueto, Juan Antonio; Bescós, Coro; Di Croce, Luciano; Benitah, Salvador Aznar

    2017-01-05

    The fact that the identity of the cells that initiate metastasis in most human cancers is unknown hampers the development of antimetastatic therapies. Here we describe a subpopulation of CD44(bright) cells in human oral carcinomas that do not overexpress mesenchymal genes, are slow-cycling, express high levels of the fatty acid receptor CD36 and lipid metabolism genes, and are unique in their ability to initiate metastasis. Palmitic acid or a high-fat diet specifically boosts the metastatic potential of CD36(+) metastasis-initiating cells in a CD36-dependent manner. The use of neutralizing antibodies to block CD36 causes almost complete inhibition of metastasis in immunodeficient or immunocompetent orthotopic mouse models of human oral cancer, with no side effects. Clinically, the presence of CD36(+) metastasis-initiating cells correlates with a poor prognosis for numerous types of carcinomas, and inhibition of CD36 also impairs metastasis, at least in human melanoma- and breast cancer-derived tumours. Together, our results indicate that metastasis-initiating cells particularly rely on dietary lipids to promote metastasis.

  2. Fine Pointing of Military Spacecraft

    DTIC Science & Technology

    2007-03-01

    better spacecraft control . In the early 1990s, researchers introduced nonlinear adaptive control techniques to estimate on- orbit spacecraft inertia...general form, the resulting regression model used in the control signal requires several pages to express for three-dimensional spacecraft rotational...a reference trajectory that addresses system lead/lag when applying the assumed control to a spacecraft with modeling errors, disturbances and

  3. Towards a Mathematical Formalism for Semi-stochastic Cell-Level Computational Modeling of Tumor Initiation.

    PubMed

    Vermolen, F J; Meijden, R P van der; Es, M van; Gefen, A; Weihs, D

    2015-07-01

    A phenomenological model is formulated to model the early stages of tumor formation. The model is based on a cell-based formalism, where each cell is represented as a circle or sphere in two-and three dimensional simulations, respectively. The model takes into account constituent cells, such as epithelial cells, tumor cells, and T-cells that chase the tumor cells and engulf them. Fundamental biological processes such as random walk, haptotaxis/chemotaxis, contact mechanics, cell proliferation and death, as well as secretion of chemokines are taken into account. The developed formalism is based on the representation of partial differential equations in terms of fundamental solutions, as well as on stochastic processes and stochastic differential equations. We also take into account the likelihood of seeding of tumors. The model shows the initiation of tumors and allows to study a quantification of the impact of various subprocesses and possibly even of various treatments.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

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

    PubMed

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

    2014-06-01

    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.

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

    PubMed Central

    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

  12. 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.

  13. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy

    PubMed Central

    Aggerholm-Pedersen, Ninna; Demuth, Christina; Meldgaard, Peter; Kassem, Moustapha; Sandahl Sorensen, Boe

    2016-01-01

    Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI) treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8. However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin. PMID:26788073

  14. 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

  15. 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.

  16. [Effect of the initial anode potential on electricity generation in microbial fuel cell].

    PubMed

    Fan, Ming-Zhi; Liang, Peng; Cao, Xiao-Xin; Huang, Xia

    2008-01-01

    The initial anode potential of the microbial fuel cell (MFC) was changed by additional circuit in the anode chamber, and the influence of the initial anode potential on the electricigens was studied. When the initial anode potential was 350 mV (vs Hg/Hg2 Cl2), the growth of microorganisms was much slower than that of the microorganisms which grew on the anode with an initial potential of -200 mV or 200 mV (vs Hg/Hg2 Cl2). After stable electricity generation, the anode resistances of the three MFCs, which had initial anode potentials of 350 mV, 200 mV and -200 mV respectively, were 71 Omega, 43 Omega and 80 Omega. The community structures in MFCs, before and after the electricity generation, were also studied by denaturing gradient gel electrophoresis (DGGE). Clostridium sticklandii, Pseudomonas mendocina and Paenibacillus taejonensis were the three most enriched strains on the anode.

  17. Autonomous spacecraft design methodology

    SciTech Connect

    Divita, E.L.; Turner, P.R.

    1984-08-01

    A methodology for autonomous spacecraft design blends autonomy requirements with traditional mission requirements and assesses the impact of autonomy upon the total system resources available to support faulttolerance and automation. A baseline functional design can be examined for autonomy implementation impacts, and the costs, risk, and benefits of various options can be assessed. The result of the process is a baseline design that includes autonomous control functions.

  18. 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.

  19. 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.

  20. 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

  1. The influence of artificial-thunderstorm cell polarity on discharge initiation by model hydrometeor arrays

    NASA Astrophysics Data System (ADS)

    Temnikov, A. G.; Chernenskii, L. L.; Orlov, A. V.; Lysov, N. Yu.; Belova, O. S.; Kalugina, I. E.; Gerastenok, T. K.; Zhuravkova, D. S.

    2017-02-01

    The initiation of discharge by model hydrometeors between an artificial-thunderstorm cell (aerosol cloud) of negative or positive polarity and ground has been experimentally studied. It is established for the first time that the conditions of cloud-ground spark discharge initiation by hydrometeors, as well as the characteristics of discharge significantly depend on the polarity of charged cloud. The effect of hydrometeor arrays can be manifested by the cloud-ground lightning initiated in a thundercloud and used for developing scientific principles of artificial lightning discharge.

  2. 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.

  3. SPASIM: A Spacecraft Simulator

    NASA Technical Reports Server (NTRS)

    Liceaga, Carlos A.

    1997-01-01

    The SPAcecraft SIMulator (SPASIM) simulates the functions and resources of a spacecraft to quickly perform conceptual design (Phase A) trade-off and sensitivity analyses and uncover any operational bottlenecks during any part of the mission. Failure modes and operational contingencies can be evaluated allowing operational planning (what-if scenarios) and optimization for a range of mission scenarios. The payloads and subsystems are simulated, using a hierarchy of graphical models, in terms of how their functions affect resources such as propellant, power, and data. Any of the inputs and outputs of the payloads and subsystems can be plotted during the simulation or stored in a file so they can be used by other programs. Most trade-off analyses, including those that compare current versus advanced technology, can be performed by changing values in the parameter menus. However, when a component is replaced by one with a different functional architecture, its graphical model can also be modified or replaced by drawing from a component library. SPASIM has been validated using several spacecraft designs that were at least at the Critical Design Review level. The user and programmer guide, including figures, is available on line as a hypertext document. This is an easy-to-use and expandable tool which is based on MATLAB(R) and SIMULINK(R). It runs on Silicon Graphics Inc. workstations and personal computers with Windows 95(TM) or NT(TM).

  4. 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.

  5. Isolation of prostate tumor initiating cells (TICs) through their dielectrophoretic signature.

    PubMed

    Salmanzadeh, Alireza; Romero, Lina; Shafiee, Hadi; Gallo-Villanueva, Roberto C; Stremler, Mark A; Cramer, Scott D; Davalos, Rafael V

    2012-01-07

    In this study, the dielectrophoretic response of prostate tumor initiating cells (TICs) was investigated in a microfluidic system utilizing contactless dielectrophoresis (cDEP). The dielectrophoretic response of prostate TICs was observed to be distinctively different than that for non-TICs, enabling them to be sorted using cDEP. Culturing the sorted TICs generated spheroids, indicating that they were indeed initiating cells. This study presents the first marker-free TIC separation from non-TICs utilizing their electrical fingerprints through dielectrophoresis.

  6. Expression and initial promoter characterization of PCAN1 in retinal tissue and prostate cell lines.

    PubMed

    Cross, D; Reding, D J; Salzman, S A; Zhang, K Q; Catalona, W J; Burke, J; Burmester, J K

    2004-01-01

    Prostate cancer is the most frequently diagnosed neoplasia in men and one of the leading causes of cancer-related deaths in men over 60. In an effort to understand the molecular events leading to prostate cancer, we have identified PCAN1 (prostate cancer gene 1) (also known as GDEP), a gene that is highly expressed in prostate epithelial tissue and frequently mutated in prostate tumors. Here we demonstrate its expression in neural retina, and retinoblastoma cell culture but not retinal pigment epithelial cell culture. We further characterize PCAN1 expression in the prostate cell lines RWPE1, RWPE2, and LnCAP FGC. We demonstrate an increase in expression when the cells are grown in the presence of Matrigel, an artificial extracellular basement membrane. Expression was time dependent, with expression observed on d 6 and little or no expression on d 12. Testosterone was not found to increase PCAN1 expression in this culture system. In addition, normal prostate epithelial cells co-cultured with normal prostate stromal cells did not exhibit PCAN1 expression at any time. To definitively locate the transcription initiation sites, we performed restriction-ligase-mediated 5' RACE, to selectively amplify only mRNA with a 5' cap. An initial characterization of the sequence upstream of the initiation sites determined six possible binding sites for the prostate specific regulatory protein NKX3.1 and four potential binding sites for the PPAR/RXR heterodimer that is involved in the control of cell differentiation and apoptosis.

  7. 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

  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. 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.

  10. Distinct and Overlapping Sarcoma Subtypes Initiated from Muscle Stem and Progenitor Cells

    PubMed Central

    Blum, Jordan M.; Añó, Leonor; Li, Zhizhong; Van Mater, David; Bennett, Brian D.; Sachdeva, Mohit; Lagutina, Irina; Zhang, Minsi; Mito, Jeffrey K.; Dodd, Leslie G.; Cardona, Diana M.; Dodd, Rebecca D.; Williams, Nerissa; Ma, Yan; Lepper, Christoph; Linardic, Corinne M.; Mukherjee, Sayan; Grosveld, Gerard C.; Fan, Chen-Ming; Kirsch, David G.

    2013-01-01

    SUMMARY Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, while undifferentiated pleomorphic sarcoma (UPS) is one of the most common soft tissue sarcomas diagnosed in adults. To investigate the myogenic cell(s) of origin of these sarcomas, we used Pax7-CreER and MyoD-CreER mice to transform Pax7+ and MyoD+ myogenic progenitors by expressing oncogenic KrasG12D and deleting p53 in vivo. Pax7-CreER mice developed RMS and UPS, while MyoD-CreER mice developed UPS. Using gene set enrichment analysis, RMS and UPS each clustered specifically within their human counterparts. These results suggest that RMS and UPS have distinct and overlapping cells of origin within the muscle lineage. Taken together, we have established novel mouse models of soft tissue sarcoma from muscle stem and progenitor cells. SIGNIFICANCE Although muscle stem cells have been presumed to be a cell of origin for RMS, studies with constitutive Cre drivers expressed in Myf6-expressing cells or adipocyte P2-expressing cells suggest that cells of origin for RMS can be differentiated myofibers or adipogenic precursors, respectively. However, recent studies have demonstrated that Myf6 is expressed in muscle stem cell precursors, revealing a potential limitation of utilizing constitutive Cre drivers for cell of origin studies. Here, using inducible CreER mice, we mutate genes relevant to human RMS specifically in Pax7-expressing or MyoD-expressing cells. Our results suggest that RMS can be initiated in muscle stem cells, while UPS can be initiated in activated (Pax7+MyoD+) satellite cells. PMID:24239359

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Gene Expression Correlates with the Number of Herpes Viral Genomes Initiating Infection in Single Cells

    PubMed Central

    Cohen, Efrat M.

    2016-01-01

    Viral gene expression varies significantly among genetically identical cells. The sources of these variations are not well understood and have been suggested to involve both deterministic host differences and stochastic viral host interactions. For herpesviruses, only a limited number of incoming viral genomes initiate expression and replication in each infected cell. To elucidate the effect of this limited number of productively infecting genomes on viral gene expression in single cells, we constructed a set of fluorescence-expressing genetically tagged herpes recombinants. The number of different barcodes originating from a single cell is a good representative of the number of incoming viral genomes replicating (NOIVGR) in that cell. We identified a positive correlation between the NOIVGR and viral gene expression, as measured by the fluorescent protein expressed from the viral genome. This correlation was identified in three distinct cell-types, although the average NOIVGR per cell differed among these cell-types. Among clonal single cells, high housekeeping gene expression levels are not supportive of high viral gene expression, suggesting specific host determinants effecting viral infection. We developed a model to predict NOIVGR from cellular parameters, which supports the notion that viral gene expression is tightly linked to the NOIVGR in single-cells. Our results support the hypothesis that the stochastic nature of viral infection and host cell determinants contribute together to the variability observed among infected cells. PMID:27923068

  17. Residual Tumor Cells That Drive Disease Relapse after Chemotherapy Do Not Have Enhanced Tumor Initiating Capacity

    PubMed Central

    Hegde, Ganapati V.; de la Cruz, Cecile; Eastham-Anderson, Jeffrey; Zheng, Yanyan; Sweet-Cordero, E. Alejandro; Jackson, Erica L.

    2012-01-01

    Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs) have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC) to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs). We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell’s ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell’s ability to drive disease recurrence. PMID:23115623

  18. 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.

  19. Nuclear-Shell Biopolymers Initiated by Telomere Elongation for Individual Cancer Cell Imaging and Drug Delivery.

    PubMed

    Zhang, Zhen; Jiao, Yuting; Zhu, Mengting; Zhang, Shusheng

    2017-04-04

    Here, we propose a strategy for unique nuclear-shell biopolymers initiated by telomere elongation for telomerase activity detection and precise drug delivery to individual cancer cells. Telomerase-triggered DNA rolling-circle amplification (RCA) is used to assemble nuclear-shell biopolymers with signal molecules for selective cancer cell recognition and efficient drug delivery to targeted individual cells. This strategy not only should allow the creation of clustered 5-carboxyfluorescein (FAM)-fluorescence spots in response to human-telomerase activity in individual cancer cells but also could efficiently deliver drugs to reduce the undesired death of healthy cells. These findings offer new opportunities to improve the efficacy of cancer cell imaging and therapy.

  20. 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.

  1. Effect of culture age, protectants, and initial cell concentration on viability of freeze-dried cells of Metschnikowia pulcherrima.

    PubMed

    Spadaro, Davide; Ciavorella, Annalisa Alessandra; Lopez-Reyes, Jorge Giovanny; Garibaldi, Angelo; Gullino, Maria Lodovica

    2010-10-01

    The effect of freeze-drying using different lyoprotectants at different concentrations on the viability and biocontrol efficacy of Metschnikowia pulcherrima was evaluated. The effects of initial yeast cell concentration and culture age on viability were also considered. Yeast cells grown for 36 h were more resistant to freeze-drying than were 48 h cells. An initial concentration of 10⁸ cells·mL⁻¹ favoured the highest survival after freeze-drying. When maltose (25%, m/v) was used as protectant, a high cell viability was obtained (64.2%). Cells maintained a high viability after 6 months of storage at 4 °C. The biocontrol efficacy of freeze-dried cells was similar to the activity of fresh cells on 'Gala' apples and was slightly lower on 'Golden Delicious' apples. After optimizing freeze-drying conditions, the viability of M. pulcherrima cells was similar to that obtained in other studies. The results constitute a first step towards the commercial development of M. pulcherrima as a biocontrol agent.

  2. RK2 plasmid dynamics in Caulobacter crescentus cells--two modes of DNA replication initiation.

    PubMed

    Wegrzyn, Katarzyna; Witosinska, Monika; Schweiger, Pawel; Bury, Katarzyna; Jenal, Urs; Konieczny, Igor

    2013-06-01

    Undisturbed plasmid dynamics is required for the stable maintenance of plasmid DNA in bacterial cells. In this work, we analysed subcellular localization, DNA synthesis and nucleoprotein complex formation of plasmid RK2 during the cell cycle of Caulobacter crescentus. Our microscopic observations showed asymmetrical distribution of plasmid RK2 foci between the two compartments of Caulobacter predivisional cells, resulting in asymmetrical allocation of plasmids to progeny cells. Moreover, using a quantitative PCR (qPCR) method, we estimated that multiple plasmid particles form a single fluorescent focus and that the number of plasmids per focus is approximately equal in both swarmer and predivisional Caulobacter cells. Analysis of the dynamics of TrfA-oriV complex formation during the Caulobacter cell cycle revealed that TrfA binds oriV primarily during the G1 phase, however, plasmid DNA synthesis occurs during the S and G2 phases of the Caulobacter cell cycle. Both in vitro and in vivo analysis of RK2 replication initiation in C. crescentus cells demonstrated that it is independent of the Caulobacter DnaA protein in the presence of the longer version of TrfA protein, TrfA-44. However, in vivo stability tests of plasmid RK2 derivatives suggested that a DnaA-dependent mode of plasmid replication initiation is also possible.

  3. 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.

  4. 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.

  5. Statistical analysis of the correlations between cell performance and its initial states in contact resistive random access memory cells

    NASA Astrophysics Data System (ADS)

    Kao, Yun Feng; Hsieh, Wei Ting; Che Chen, Chun; King, Ya-Chin; Lin, Chrong Jung

    2017-04-01

    Variability has been one of the critical challenges in the implementation of large resistive random access memory (RRAM) arrays. Wide variations in set/reset, read and cycling characteristics can significantly reduce the design margin and feasibility of a memory array. Predicting the characteristics of RRAM cells is constructive to provide insights and to adjust the memory operations accordingly. In this study, a strong correlation between the cell performance and its initial state is found in contact RRAM (CRRAM) cells by 28 nm CMOS logic technology. Furthermore, a verify-reset operation is proposed to identify the type of conductive filament (CF) in a cell. Distinctive CRRAM characteristics are found to be linked directly to initial CFs, enabling preliminary screening and adaptive resets to address the large variability problems in sizable CRRAM arrays.

  6. Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells

    PubMed Central

    Lee, Hsin-chung; Ling, Qing-Dong; Yu, Wan-Chun; Hung, Chunh-Ming; Kao, Ta-Chun; Huang, Yi-Wei; Higuchi, Akon

    2013-01-01

    Purpose We evaluated the higher levels of carcinoembryonic antigen (CEA) secreted by the LoVo human colon carcinoma cells in a medium containing anticancer drugs. Drug-resistant LoVo cells were analyzed by subcutaneously xenotransplanting them into mice. The aim of this study was to evaluate whether the drug-resistant cells isolated in this study were cancer-initiating cells, known also as cancer stem cells (CSCs). Methods The production of CEA was investigated in LoVo cells that were cultured with 0–10 mM of anticancer drugs, and we evaluated the increase in CEA production by the LoVo cells that were stimulated by anticancer drug treatment. The expression of several CSC markers in LoVo cells treated with anticancer drugs was also evaluated. Following anticancer drug treatment, LoVo cells were injected subcutaneously into the flanks of severe combined immunodeficiency mice in order to evaluate the CSC fraction. Results Production of CEA by LoVo cells was stimulated by the addition of anticancer drugs. Drug-resistant LoVo cells expressed lower levels of CSC markers, and LoVo cells treated with any of the anticancer drugs tested did not generate tumors within 8 weeks from when the cells were injected subcutaneously into severe combined immunodeficiency mice. These results suggest that the drug-resistant LoVo cells have a smaller population of CSCs than the untreated LoVo cells. Conclusion Production of CEA by LoVo cells can be stimulated by the addition of anticancer drugs. The drug-resistant subpopulation of LoVo colon cancer cells could stimulate the production of CEA, but these cells did not act as CSCs in in vivo tumor generation experiments. PMID:23818760

  7. Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cells

    PubMed Central

    Noto, A; Raffa, S; De Vitis, C; Roscilli, G; Malpicci, D; Coluccia, P; Di Napoli, A; Ricci, A; Giovagnoli, M R; Aurisicchio, L; Torrisi, M R; Ciliberto, G; Mancini, R

    2013-01-01

    In recent years, studies of cancer development and recurrence have been influenced by the cancer stem cells (CSCs)/cancer-initiating cells (CICs) hypothesis. According to this, cancer is sustained by highly positioned, chemoresistant cells with extensive capacity of self renewal, which are responsible for disease relapse after chemotherapy. Growth of cancer cells as three-dimensional non-adherent spheroids is regarded as a useful methodology to enrich for cells endowed with CSC-like features. We have recently reported that cell cultures derived from malignant pleural effusions (MPEs) of patients affected by adenocarcinoma of the lung are able to efficiently form spheroids in non-adherent conditions supplemented with growth factors. By expression profiling, we were able to identify a set of genes whose expression is significantly upregulated in lung tumor spheroids versus adherent cultures. One of the most strongly upregulated gene was stearoyl-CoA desaturase (SCD1), the main enzyme responsible for the conversion of saturated into monounsaturated fatty acids. In the present study, we show both by RNA interference and through the use of a small molecule inhibitor that SCD1 is required for lung cancer spheroids propagation both in stable cell lines and in MPE-derived primary tumor cultures. Morphological examination and image analysis of the tumor spheroids formed in the presence of SCD1 inhibitors showed a different pattern of growth characterized by irregular cell aggregates. Electron microscopy revealed that the treated spheroids displayed several features of cellular damage and immunofluorescence analysis on optical serial sections showed apoptotic cells positive for the M30 marker, most of them positive also for the stemness marker ALDH1A1, thus suggesting that the SCD1 inhibitor is selectively killing cells with stem-like properties. Furthermore, SCD1-inhibited lung cancer cells were strongly impaired in their in vivo tumorigenicity and ALDH1A1 expression. These

  8. CD44 and EpCAM: cancer-initiating cell markers.

    PubMed

    Marhaba, Rachid; Klingbeil, Pamela; Nuebel, Tobias; Nazarenko, Irina; Buechler, Markus W; Zoeller, Margot

    2008-12-01

    Embryonic stem cells are immortal, can self renew, and differentiate into all cells of the body. The adult organism maintains adult stem cells in regenerative organs that can differentiate into all cells of the respective organ. Virchow's hypothesis that cancer may arise from embryonic-like cells has received strong support, as it was demonstrated that tumors contain few cells, known as cancer stem or cancer-initiating cells (CIC), that account for primary and metastatic tumor growth. CIC are mostly defined by expression of CIC-markers that are associated and correlated with the potential of CIC to grow in xenogeneic mice. CIC marker profiles have been elaborated for many tumors, with several markers as CD24, CD44, CD133, CD166, EpCAM, and some integrins, being expressed by tumors of different histological type. Their function in promoting CIC maintenance and activity is largely unknown. The fate of stem cells, determined by their position, is minutely regulated by few adjacent cells creating a niche. CIC also require a niche, mostly for settlement and growth in distant organs. This so called pre-metastatic niche is initiated by the primary tumor before metastasizing cell arrival. How do CIC prepare the pre-metastatic niche? Cancer cells secrete a matrix that serves a cross-talk with surrounding tissues. Additionally, cancer cells can abundantly deliver exosomes, which function as long-distance intercellular communicators. Studies on a rat pancreatic adenocarcinoma support our hypothesis that tumor-derived matrix and exosomes are the main actors in forming the pre-metastatic niche with CIC markers being engaged in matrix preparation and/or exosome delivery.

  9. Maize germinal cell initials accommodate hypoxia and precociously express meiotic genes.

    PubMed

    Kelliher, Timothy; Walbot, Virginia

    2014-02-01

    In flowering plants, anthers are the site of de novo germinal cell specification, male meiosis, and pollen development. Atypically, anthers lack a meristem. Instead, both germinal and somatic cell types differentiate from floral stem cells packed into anther lobes. To better understand anther cell fate specification and to provide a resource for the reproductive biology community, we isolated cohorts of germinal and somatic initials from maize anthers within 36 h of fate acquisition, identifying 815 specific and 1714 significantly enriched germinal transcripts, plus 2439 specific and 2112 significantly enriched somatic transcripts. To clarify transcripts involved in cell differentiation, we contrasted these profiles to anther primordia prior to fate specification and to msca1 anthers arrested in the first step of fate specification and hence lacking normal cell types. The refined cell-specific profiles demonstrated that both germinal and somatic cell populations differentiate quickly and express unique transcription factor sets; a subset of transcript localizations was validated by in situ hybridization. Surprisingly, germinal initials starting 5 days of mitotic divisions were enriched significantly in >100 transcripts classified in meiotic processes that included recombination and synapsis, along with gene sets involved in RNA metabolism, redox homeostasis, and cytoplasmic ATP generation. Enrichment of meiotic-specific genes in germinal initials challenges current dogma that the mitotic to meiotic transition occurs later in development during pre-meiotic S phase. Expression of cytoplasmic energy generation genes suggests that male germinal cells accommodate hypoxia by diverting carbon away from mitochondrial respiration into alternative pathways that avoid producing reactive oxygen species (ROS).

  10. Proteolysis-a characteristic of tumor-initiating cells in murine metastatic breast cancer

    PubMed Central

    Hillebrand, Larissa E.; Bengsch, Fee; Hochrein, Jochen; Hülsdünker, Jan; Bender, Julia; Follo, Marie; Busch, Hauke; Boerries, Melanie; Reinheckel, Thomas

    2016-01-01

    Tumor initiating cells (TICs) have been identified and functionally characterized in hematological malignancies as well as in solid tumors such as breast cancer. In addition to their high tumor-initiating potential, TICs are founder cells for metastasis formation and are involved in chemotherapy resistance. In this study we explored molecular pathways which enable this tumor initiating potential for a cancer cell subset of the transgenic MMTV-PyMT mouse model for metastasizing breast cancer. The cell population, characterized by the marker profile CD24+CD90+CD45−, showed a high tumorigenicity compared to non-CD24+CD90+CD45− cancer cells in colony formation assays, as well as upon orthotopic transplantation into the mammary fat pad of mice. In addition, these orthotopically grown CD24+CD90+CD45− TICs metastasized to the lungs. The transcriptome of TICs freshly isolated from primary tumors by cell sorting was compared with that of sorted non-CD24+CD90+CD45− cancer cells by RNA-seq. In addition to more established TIC signatures, such as epithelial-to-mesenchymal transition or mitogen signaling, an upregulated gene set comprising several classes of proteolytic enzymes was uncovered in the TICs. Accordingly, TICs showed high intra- and extracellular proteolytic activity. Application of a broad range of protease inhibitors to TICs in a colony formation assay reduced anchorage independent growth and had an impact on colony morphology in 3D cell culture assays. We conclude that CD24+CD90+CD45− cells of the MMTV- PyMT mouse model possess an upregulated proteolytic signature which could very well represent a functional hallmark of metastatic TICs from mammary carcinomas. PMID:27542270

  11. Functional Sphere Profiling Reveals the Complexity of Neuroblastoma Tumor-Initiating Cell Model12

    PubMed Central

    Coulon, Aurélie; Flahaut, Marjorie; Mühlethaler-Mottet, Annick; Meier, Roland; Liberman, Julie; Balmas-Bourloud, Katia; Nardou, Katya; Yan, Pu; Tercier, Stéphane; Joseph, Jean-Marc; Sommer, Lukas; Gross, Nicole

    2011-01-01

    Neuroblastoma (NB) is a neural crest-derived childhood tumor characterized by a remarkable phenotypic diversity, ranging from spontaneous regression to fatal metastatic disease. Although the cancer stem cell (CSC) model provides a trail to characterize the cells responsible for tumor onset, the NB tumor-initiating cell (TIC) has not been identified. In this study, the relevance of the CSC model in NB was investigated by taking advantage of typical functional stem cell characteristics. A predictive association was established between self-renewal, as assessed by serial sphere formation, and clinical aggressiveness in primary tumors. Moreover, cell subsets gradually selected during serial sphere culture harbored increased in vivo tumorigenicity, only highlighted in an orthotopic microenvironment. A microarray time course analysis of serial spheres passages from metastatic cells allowed us to specifically “profile” the NB stem cell-like phenotype and to identify CD133, ABC transporter, and WNT and NOTCH genes as spheres markers. On the basis of combined sphere markers expression, at least two distinct tumorigenic cell subpopulations were identified, also shown to preexist in primary NB. However, sphere markers-mediated cell sorting of parental tumor failed to recapitulate the TIC phenotype in the orthotopic model, highlighting the complexity of the CSC model. Our data support the NB stem-like cells as a dynamic and heterogeneous cell population strongly dependent on microenvironmental signals and add novel candidate genes as potential therapeutic targets in the control of high-risk NB. PMID:22028624

  12. The Interaction of Relativistic Spacecrafts with the Interstellar Medium

    NASA Astrophysics Data System (ADS)

    Hoang, Thiem; Lazarian, A.; Burkhart, Blakesley; Loeb, Abraham

    2017-03-01

    The Breakthrough Starshot initiative aims to launch a gram-scale spacecraft to a speed of v ∼ 0.2c, capable of reaching the nearest star system, α Centauri, in about 20 years. However, a critical challenge for the initiative is the damage to the spacecraft by interstellar gas and dust during the journey. In this paper, we quantify the interaction of a relativistic spacecraft with gas and dust in the interstellar medium (ISM). For gas bombardment, we find that damage by track formation due to heavy elements is an important effect. We find that gas bombardment can potentially damage the surface of the spacecraft to a depth of ∼0.1 mm for quartz material after traversing a gas column of {N}{{H}}∼ 2× {10}18 {{cm}}-2 along the path to α Centauri, whereas the effect is much weaker for graphite material. The effect of dust bombardment erodes the spacecraft surface and produces numerous craters due to explosive evaporation of surface atoms. For a spacecraft speed v=0.2c, we find that dust bombardment can erode a surface layer of ∼0.5 mm thickness after the spacecraft has swept a column density of {N}{{H}}∼ 3× {10}17 {{cm}}-2, assuming the standard gas-to-dust ratio of the ISM. Dust bombardment also damages the spacecraft surface by modifying the material structure through melting. We calculate the equilibrium surface temperature due to collisional heating by gas atoms as well as the temperature profile as a function of depth into the spacecraft. Our quantitative results suggest methods for damage control, and we highlight possibilities for shielding strategies and protection of the spacecraft.

  13. 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

  14. Five-Membered Ring Peroxide Selectively Initiates Ferroptosis in Cancer Cells.

    PubMed

    Abrams, Rachel P; Carroll, William L; Woerpel, K A

    2016-05-20

    A 1,2-dioxolane (FINO2) was identified as a lead compound from a screen of organic peroxides. FINO2 does not induce apoptosis, but instead initiates ferroptosis, an iron-dependent, oxidative cell death pathway. Few compounds are known to induce primarily ferroptosis. In contrast to the perceived instability of peroxides, FINO2 was found to be thermally stable to at least 150 °C. FINO2 was more potent in cancer cells than nonmalignant cells of the same type. One of the enantiomers was found to be more responsible for the observed activity.

  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. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.

    PubMed

    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

    2013-10-01

    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) owing to preferential BTIC survival and to 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, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

  4. 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.

  5. In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells

    PubMed Central

    Leikam, C; Hufnagel, A L; Otto, C; Murphy, D J; Mühling, B; Kneitz, S; Nanda, I; Schmid, M; Wagner, T U; Haferkamp, S; Bröcker, E-B; Schartl, M; Meierjohann, S

    2015-01-01

    Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi- or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS61K in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation. PMID:25837487

  6. The EMT universe: space between cancer cell dissemination and metastasis initiation.

    PubMed

    Ombrato, Luigi; Malanchi, Ilaria

    2014-01-01

    Tumor metastasis, the cause of more than 90% of cancer cell mortality, is a multistep process by which tumor cells disseminate from their primary site via local invasion and intravasation into blood or lymphatic vessels and reach secondary distant sites, where they survive and reinitiate tumor growth. Activation of a developmental program called the epithelial-to-mesenchymal transition (EMT) has been shown to be a very efficient strategy adopted by epithelial cancer cells to promote local invasion and dissemination at distant organs. Remarkably, the activation of EMT programs in epithelial cells correlates with the appearance of stemness. This finding suggests that the EMT process also drives the initial cancer cell colonization at distant sites. However, recent studies support the concept that its reverse program, a mesenchymal-to-epithelial transition, is required for efficient metastatic colonization and that EMT is not necessarily associated with stemness. This review analyzes the conflicting experimental evidence linking epithelial plasticity to stemness in the light of an "EMT gradient model," according to which the outcome of EMT program activation in epithelial cells would be bimodal: coupled to stemness during initial activation, but when forced to reach an advanced mesenchymal status, it would become incompatible with stem cell abilities.

  7. Galileo spacecraft power management and distribution system

    NASA Technical Reports Server (NTRS)

    Detwiler, R. C.; Smith, R. L.

    1990-01-01

    The Galileo PMAD (power management and distribution system) is described, and the design drivers that established the final as-built hardware are discussed. The spacecraft is powered by two general-purpose heat-source-radioisotope thermoelectric generators. Power bus regulation is provided by a shunt regulator. Galileo PMAD distributes a 570-W beginning of mission (BOM) power source to a user complement of some 137 load elements. Extensive use of pyrotechnics requires two pyro switching subassemblies. They initiate 148 squibs which operate the 47 pyro devices on the spacecraft. Detection and correction of faults in the Galileo PMAD is an autonomous feature dictated by requirements for long life and reliability in the absence of ground-based support. Volatile computer memories in the spacecraft command and data system and attitude control system require a continuous source of backup power during all anticipated power bus fault scenarios. Power for the Jupiter Probe is conditioned, isolated, and controlled by a Probe interface subassembly. Flight performance of the spacecraft and the PMAD has been successful to date, with no major anomalies.

  8. Cofilin and Vangl2 cooperate in the initiation of planar cell polarity in the mouse embryo

    PubMed Central

    Mahaffey, James P.; Grego-Bessa, Joaquim; Liem, Karel F.; Anderson, Kathryn V.

    2013-01-01

    The planar cell polarity (PCP; non-canonical Wnt) pathway is required to orient the cells within the plane of an epithelium. Here, we show that cofilin 1 (Cfl1), an actin-severing protein, and Vangl2, a core PCP protein, cooperate to control PCP in the early mouse embryo. Two aspects of planar polarity can be analyzed quantitatively at cellular resolution in the mouse embryo: convergent extension of the axial midline; and posterior positioning of cilia on cells of the node. Analysis of the spatial distribution of brachyury+ midline cells shows that the Cfl1 mutant midline is normal, whereas Vangl2 mutants have a slightly wider midline. By contrast, midline convergent extension fails completely in Vangl2 Cfl1 double mutants. Planar polarity is required for the posterior positioning of cilia on cells in the mouse node, which is essential for the initiation of left-right asymmetry. Node cilia are correctly positioned in Cfl1 and Vangl2 single mutants, but cilia remain in the center of the cell in Vangl2 Cfl1 double mutants, leading to randomization of left-right asymmetry. In both the midline and node, the defect in planar polarity in the double mutants arises because PCP protein complexes fail to traffic to the apical cell membrane, although other aspects of apical-basal polarity are unaffected. Genetic and pharmacological experiments demonstrate that F-actin remodeling is essential for the initiation, but not maintenance, of PCP. We propose that Vangl2 and cofilin cooperate to target Rab11+ vesicles containing PCP proteins to the apical membrane during the initiation of planar cell polarity. PMID:23406901

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

    PubMed Central

    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

  10. NEAR spacecraft flight system performance

    NASA Astrophysics Data System (ADS)

    Santo, Andrew G.

    2002-01-01

    The Near Earth Asteroid Rendezvous (NEAR) spacecraft was built and launched in 29 months. After a 4-year cruise phase the spacecraft was in orbit about the asteroid Eros for 1 year, which enabled the science payload to return unprecedented scientific data. A summary of spacecraft in-flight-performance, including a discussion of the December 1998 aborted orbit insertion burn, is provided. Several minor hardware failures that occurred during the last few years of operations are described. Lessons learned during the cruise phase led to new features being incorporated into several in-flight software uploads. The added innovative features included the capability for the spacecraft to autonomously choose a spacecraft attitude that simultaneously kept the medium-gain antennas pointed at Earth while using solar pressure to control system momentum and a capability to combine a propulsive momentum dump with a trajectory correction maneuver. The spacecraft proved flexible, reliable, and resilient over the 5-year mission.

  11. Designing a micro-spacecraft

    NASA Technical Reports Server (NTRS)

    Burke, J. D.

    1985-01-01

    Planetary spacecraft design could move toward less complex probes which would cost less then previous highly instrumented missions. The goal then becomes to fly more frequent missions and use commercial, proven hardware to ameliorate development costs. A commonality would be kept in place from spacecraft to spacecraft, with upgrades being introduced only to meet specific objectives or take advantage of advances in commercial hardware. Mission costs are in large part determined by spacecraft mass, so instrumentation must be miniaturized, i.e., the concept of a micro-satellite. A design study for the Cosimi project, which would feature placing a spacecraft on the far side of the solar corona to broadcast radio signals to earth, demonstrates the feasibility of a 20 cm diam rocket and integrated instruments for performing low-cost solar physics experiments. It is concluded, however, that current program start-ups will continue to maximize the mass and instrumentation of spacecraft.

  12. In vivo behavior of murine epidermal cell lines derived from initiated and noninitiated skin.

    PubMed

    Conti, C J; Fries, J W; Viaje, A; Miller, D R; Morris, R; Slaga, T J

    1988-01-15

    The in vivo behavior of cell cultures derived from normal and carcinogen-treated mouse epidermis was studied by implanting the cultures in a s.c. vascularized bed protected by a silicone chamber. Cells derived from normal adult mouse epidermis as well as cells derived from tumor-promoter-treated skin were unable to grow in these systems. Conversely, cell lines derived from skin initiated with single doses of N-methyl-N'-nitro-N-nitrosoguanidine or 9,10-dimethyl-1,2-benzanthracene proliferated in these chambers, reforming an epithelial structure. The type of structure in the chambers varied, ranging from formation of almost normal epithelia to atypical invasive behavior. The variable in vivo behavior among the different cell lines may be attributed to the initiation agent, the number of passages of the cultures, random genetic events, the strain of mouse, or a combination of these factors. Most of the cell types used in this study and all the cell lines that were able to grow in these chambers were selected for resistance to Ca-induced terminal differentiation. However, resistance to terminal differentiation according to the Ca2+ switch does not always correlate with the ability to grow in the chambers, since cell lines derived from spontaneous foci of resistance failed to grow in this system. These studies showed some of the possibilities of the SC silicone chambers to study the histogenic potential of cell lines derived from carcinogen-treated epidermis. This system also appears suitable to study the complex relationship between epidermal cells and specialized (dermal) stroma.

  13. A model of membrane contraction predicting initiation and completion of bacterial cell division.

    PubMed

    Dow, Claire E; Rodger, Alison; Roper, David I; van den Berg, Hugo A

    2013-05-01

    Bacterial cell division involves a complex and dynamic sequence of events whereby polymers of the protein FtsZ assemble at the division plane and rearrange to achieve the goal of contracting the cell membrane at the site of cell division, thus dividing the parent cell into two daughter cells. We present a mathematical model (which we refer to as CAM-FF: Critical Accumulation of Membrane-bound FtsZ Fibres) of the assembly of the contractile ring in terms of the accumulation of short linear polymers of FtsZ that associate and dissociate from the cell membrane. In prokaryotes, the biochemical function of FtsZ is thought to underpin the assembly and at least the initial kinetic force of ring contraction. Our model extends earlier work of Surovtsev et al. [PLoS Comput. Biol., 2008, 4, e1000102] by adding (i) the kinetics of FtsZ accumulation on cell membrane anchor proteins and (ii) the physical forces required to deform the cell against its surface tension. Moreover, we provide a more rigorous treatment of intracellular diffusion and we revise some of the model parameter values in light of the experimental evidence now available. We derive a critical contraction parameter which links the chemical population dynamics of membrane-bound FtsZ molecules to the force of contraction. Using this parameter as a tool to predict the ability of the cell to initiate division, we are able to predict the division outcome in cells depleted of key FtsZ-binding proteins.

  14. 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.

  15. SOHO spacecraft observations interrupted

    NASA Astrophysics Data System (ADS)

    1998-06-01

    Efforts to re-establish nominal operations did not succeed and telemetry was lost. Subsequent attempts using the full NASA Deep Space Network capabilities have so far not been successful. ESA and NASA engineers are continuing with the task of re-establishing contact with the spacecraft. The SOHO mission is a joint undertaking of ESA and NASA. The spacecraft was launched aboard an Atlas II rocket from Florida on 2 December 1995 from the Cape Canaveral Air Station. Mission operations are directed from the control center at NASA Goddard Space Flight Center in Maryland, USA. In April 1998 SOHO successfully completed its nominal two-year mission to study the Sun's atmosphere, surface and interior. Major science highlights include the detection of rivers of plasma beneath the surface of the sun; the discovery of a magnetic "carpet" on the solar surface that seems to account for a substantial part of the energy that is needed to cause the very high temperatures of the corona, the Sun's outermost layer; the first detection of flare-induced solar quakes; the discovery of more than 50 sungrazing comets; the most detailed view to date of the solar atmosphere; and spectacular images and movies of Coronal Mass Ejections, which are being used to improve the ability to forecast space weather.

  16. 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.

  17. Electric propulsion for constellation deployment and spacecraft maneuvering

    NASA Technical Reports Server (NTRS)

    Deininger, W. D.; Vondra, R. J.

    1988-01-01

    This paper outlines the near-term (1990s) advantages of electric propulsion for two SDI missions: (1) the launch of a constellation of spacecraft, and (2) continual spacecraft defensive maneuvering. Ammonia arcjet and Xe-ion electric propulsion systems are compared to advanced chemical propulsion for each of these missions. The number of launch vehicles required for constellation deployment can be reduced by up to a factor of 2 when electric propulsion upper stages are used in place of advanced upper stages. Electric propulsion can provide significant benefits when used for continuous defensive maneuvering by enabling a large reduction in the initial spacecraft mass.

  18. A convenient and effective strategy for the enrichment of tumor-initiating cell properties in prostate cancer cells.

    PubMed

    Zhang, Yiming; Huang, Yiqiang; Jin, Zhong; Li, Xiezhao; Li, Bingkun; Xu, Peng; Huang, Peng; Liu, Chunxiao

    2016-09-01

    Stem-like prostate cancer (PrCa) cells, also called PrCa stem cells (PrCSCs) or PrCa tumor-initiating cells (PrTICs), are considered to be involved in the mediation of tumor metastasis and may be responsible for the poor prognosis of PrCa patients. Currently, the methods for PrTIC sorting are mainly based on cell surface marker or side population (SP). However, the rarity of these sorted cells limits the investigation of the molecular mechanisms and therapeutic strategies targeting PrTICs. For PrTIC enrichment, we induced cancer stem cell (CSC) properties in PrCa cells by transducing three defined factors (OCT3/4, SOX2, and KLF4), followed by culture with conventional serum-containing medium. The CSC properties in the transduced cells were evaluated by proliferation, cell cycle, SP assay, drug sensitivity technology, in vivo tumorigenicity, and molecular marker analysis of PrCSCs compared with parental cells and spheroids. After culture with serum-containing medium for 8 days, the PrCa cells transduced with the three factors showed significantly enhanced CSC properties in terms of marker gene expression, sphere formation, chemoresistance to docetaxel, and tumorigenicity. The percentage of CD133(+)/CD44(+) cells was ninefold higher in the transduced cell population than in the adherent PC3 cell population (2.25 ± 0.62 vs. 0.25 ± 0.12 %, respectively), and the SP increased to 1.22 ± 0.18 % in the transduced cell population, but was undetectable in the adherent population. This method can be used to obtain abundant PrTIC material and enables a complete understanding of PrTIC biology and development of novel therapeutic agents targeting PrTICs.

  19. Reactive Carbonyl Species Activate Caspase-3-Like Protease to Initiate Programmed Cell Death in Plants.

    PubMed

    Biswas, Md Sanaullah; Mano, Jun'ichi

    2016-07-01

    Reactive oxygen species (ROS)-triggered programmed cell death (PCD) is a typical plant response to biotic and abiotic stressors. We have recently shown that lipid peroxide-derived reactive carbonyl species (RCS), downstream products of ROS, mediate oxidative signal to initiate PCD. Here we investigated the mechanism by which RCS initiate PCD. Tobacco Bright Yellow-2 cultured cells were treated with acrolein, one of the most potent RCS. Acrolein at 0.2 mM caused PCD in 5 h (i.e. lethal), but at 0.1 mM it did not (sublethal). Specifically, these two doses caused critically different effects on the cells. Both lethal and sublethal doses of acrolein exhausted the cellular glutathione pool in 30 min, while the lethal dose only caused a significant ascorbate decrease and ROS increase in 1-2 h. Prior to such redox changes, we found that acrolein caused significant increases in the activities of caspase-1-like protease (C1LP) and caspase-3-like protease (C3LP), the proteases which trigger PCD. The lethal dose of acrolein increased the C3LP activity 2-fold more than did the sublethal dose. In contrast, C1LP activity increments caused by the two doses were not different. Acrolein and 4-hydroxy-(E)-2-nonenal, another RCS, activated both proteases in a cell-free extract from untreated cells. H2O2 at 1 mM added to the cells increased C1LP and C3LP activities and caused PCD, and the RCS scavenger carnosine suppressed their activation and PCD. However, H2O2 did not activate the proteases in a cell-free extract. Thus the activation of caspase-like proteases, particularly C3LP, by RCS is an initial biochemical event in oxidative signal-stimulated PCD in plants.

  20. Effects of amyloid-β plaque proximity on the axon initial segment of pyramidal cells.

    PubMed

    León-Espinosa, Gonzalo; DeFelipe, Javier; Muñoz, Alberto

    2012-01-01

    The output of cortical pyramidal cells reflects the balance between excitatory inputs of cortical and subcortical origin, and inhibitory inputs from distinct populations of cortical GABAergic interneurons, each of which selectively innervate different domains of neuronal pyramidal cells (i.e., dendrites, soma and axon initial segment [AIS]). In Alzheimer's disease (AD), the presence of amyloid-β (Aβ) plaques alters the synaptic input to pyramidal cells in a number of ways. However, the effects of Aβ plaques on the AIS have still not been investigated to date. This neuronal domain is involved in input integration, as well as action potential initiation and propagation, and it exhibits Ca2+- and activity-dependent structural plasticity. The AIS is innervated by GABAergic axon terminals from chandelier cells, which are thought to exert a strong influence on pyramidal cell output. In the AβPP/PS1 transgenic mouse model of AD, we have investigated the effects of Aβ plaques on the morphological and neurochemical features of the AIS, including the cisternal organelle, using immunocytochemistry and confocal microscopy, as well as studying the innervation of the AIS by chandelier cell axon terminals. There is a strong reduction in GABAergic terminals that appose AIS membrane surfaces that are in contact with Aβ plaques, indicating altered inhibitory synapsis at the AIS. Thus, despite a lack of gross structural alterations in the AIS, this decrease in GABAergic innervation may deregulate AIS activity and contribute to the hyperactivity of neurons in contact with Aβ plaques.

  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. Activated alveolar epithelial cells initiate fibrosis through autocrine and paracrine secretion of connective tissue growth factor.

    PubMed

    Yang, Jibing; Velikoff, Miranda; Canalis, Ernesto; Horowitz, Jeffrey C; Kim, Kevin K

    2014-04-15

    Fibrogenesis involves a pathological accumulation of activated fibroblasts and extensive matrix remodeling. Profibrotic cytokines, such as TGF-β, stimulate fibroblasts to overexpress fibrotic matrix proteins and induce further expression of profibrotic cytokines, resulting in progressive fibrosis. Connective tissue growth factor (CTGF) is a profibrotic cytokine that is indicative of fibroblast activation. Epithelial cells are abundant in the normal lung, but their contribution to fibrogenesis remains poorly defined. Profibrotic cytokines may activate epithelial cells with protein expression and functions that overlap with the functions of active fibroblasts. We found that alveolar epithelial cells undergoing TGF-β-mediated mesenchymal transition in vitro were also capable of activating lung fibroblasts through production of CTGF. Alveolar epithelial cell expression of CTGF was dramatically reduced by inhibition of Rho signaling. CTGF reporter mice demonstrated increased CTGF promoter activity by lung epithelial cells acutely after bleomycin in vivo. Furthermore, mice with lung epithelial cell-specific deletion of CTGF had an attenuated fibrotic response to bleomycin. These studies provide direct evidence that epithelial cell activation initiates a cycle of fibrogenic effector cell activation during progressive fibrosis. Therapy targeted at epithelial cell production of CTGF offers a novel pathway for abrogating this progressive cycle and limiting tissue fibrosis.

  3. Tolerance to staphylococcal enterotoxin B initiated Th1 cell differentiation in mice infected with Candida albicans.

    PubMed Central

    Romani, L; Puccetti, P; Mencacci, A; Spaccapelo, R; Cenci, E; Tonnetti, L; Bistoni, F

    1994-01-01

    Staphylococcal enterotoxin B (SEB) is a bacterial superantigen that specifically activates T cells bearing V beta 8 T-cell receptor domains, which eventually leads to a long-lasting state of clonal anergy accompanied by selective cell death in the targeted CD4+ subset. Because the superantigen is known to promote Th1 cell differentiation in vitro, we have investigated the effect of SEB treatment on the course of Th2-associated progressive disease in mice infected systemically with Candida albicans. On the basis of the kinetics of SEB-induced changes in CD4+ cells and production in sera of interleukin 4 (IL-4), IL-10, and gamma interferon, we obtained evidence that V beta 8+ cell anergy concomitant with infection abolished the early IL-4/IL-10 response of the host to the yeast, ultimately leading to a state of resistance characterized by gamma interferon secretion in vitro by antigen-specific CD4+ cells. In contrast, SEB administered near the time of challenge resulted in accelerated mortality. Significant resistance to infection was also afforded by exposure of mice to a retrovirally encoded endogenous superantigen. These data suggest that CD4+ V beta 8+ T cells play an important role in vivo in the initiation of a Th2 response to C. albicans and that suppression of their activity may alter the qualitative development of the T-cell response and the outcome of infection. PMID:7914883

  4. 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

  5. Serotonin transporter antagonists target tumor-initiating cells in a transgenic mouse model of breast cancer

    PubMed Central

    Hallett, Robin M.; Girgis-Gabardo, Adele; Gwynne, William D.; Giacomelli, Andrew O.; Bisson, Jennifer N.P.; Jensen, Jeremy E.; Dvorkin-Gheva, Anna; Hassell, John A.

    2016-01-01

    Accumulating data suggests that the initiation and progression of human breast tumors is fueled by a rare subpopulation of tumor cells, termed breast tumor-initiating cells (BTIC), which resist radiotherapy and chemotherapy. Consequently, therapies that abrogate BTIC activity are needed to achieve durable cures for breast cancer patients. To identify such therapies we used a sensitive assay to complete a high-throughput screen of small molecules, including approved drugs, with BTIC-rich mouse mammary tumor cell populations. We found that inhibitors of the serotonin reuptake transporter (SERT) and serotonin receptors, which include approved drugs used to treat mood disorders, were potent inhibitors of mouse BTIC activity as determined by functional sphere-forming assays and the initiation of tumor formation by transplant of drug-exposed tumor cells into syngeneic mice. Moreover, sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI), synergized with docetaxel (Taxotere) to shrink mouse breast tumors in vivo. Hence drugs targeting the serotonergic system might be repurposed to treat breast cancer patients to afford more durable breast cancer remissions. PMID:27447971

  6. Ubiquinone-binding site mutagenesis reveals the role of mitochondrial complex II in cell death initiation.

    PubMed

    Kluckova, K; Sticha, M; Cerny, J; Mracek, T; Dong, L; Drahota, Z; Gottlieb, E; Neuzil, J; Rohlena, J

    2015-05-07

    Respiratory complex II (CII, succinate dehydrogenase, SDH) inhibition can induce cell death, but the mechanistic details need clarification. To elucidate the role of reactive oxygen species (ROS) formation upon the ubiquinone-binding (Qp) site blockade, we substituted CII subunit C (SDHC) residues lining the Qp site by site-directed mutagenesis. Cell lines carrying these mutations were characterized on the bases of CII activity and exposed to Qp site inhibitors MitoVES, thenoyltrifluoroacetone (TTFA) and Atpenin A5. We found that I56F and S68A SDHC variants, which support succinate-mediated respiration and maintain low intracellular succinate, were less efficiently inhibited by MitoVES than the wild-type (WT) variant. Importantly, associated ROS generation and cell death induction was also impaired, and cell death in the WT cells was malonate and catalase sensitive. In contrast, the S68A variant was much more susceptible to TTFA inhibition than the I56F variant or the WT CII, which was again reflected by enhanced ROS formation and increased malonate- and catalase-sensitive cell death induction. The R72C variant that accumulates intracellular succinate due to compromised CII activity was resistant to MitoVES and TTFA treatment and did not increase ROS, even though TTFA efficiently generated ROS at low succinate in mitochondria isolated from R72C cells. Similarly, the high-affinity Qp site inhibitor Atpenin A5 rapidly increased intracellular succinate in WT cells but did not induce ROS or cell death, unlike MitoVES and TTFA that upregulated succinate only moderately. These results demonstrate that cell death initiation upon CII inhibition depends on ROS and that the extent of cell death correlates with the potency of inhibition at the Qp site unless intracellular succinate is high. In addition, this validates the Qp site of CII as a target for cell death induction with relevance to cancer therapy.

  7. Ubiquinone-binding site mutagenesis reveals the role of mitochondrial complex II in cell death initiation

    PubMed Central

    Kluckova, K; Sticha, M; Cerny, J; Mracek, T; Dong, L; Drahota, Z; Gottlieb, E; Neuzil, J; Rohlena, J

    2015-01-01

    Respiratory complex II (CII, succinate dehydrogenase, SDH) inhibition can induce cell death, but the mechanistic details need clarification. To elucidate the role of reactive oxygen species (ROS) formation upon the ubiquinone-binding (Qp) site blockade, we substituted CII subunit C (SDHC) residues lining the Qp site by site-directed mutagenesis. Cell lines carrying these mutations were characterized on the bases of CII activity and exposed to Qp site inhibitors MitoVES, thenoyltrifluoroacetone (TTFA) and Atpenin A5. We found that I56F and S68A SDHC variants, which support succinate-mediated respiration and maintain low intracellular succinate, were less efficiently inhibited by MitoVES than the wild-type (WT) variant. Importantly, associated ROS generation and cell death induction was also impaired, and cell death in the WT cells was malonate and catalase sensitive. In contrast, the S68A variant was much more susceptible to TTFA inhibition than the I56F variant or the WT CII, which was again reflected by enhanced ROS formation and increased malonate- and catalase-sensitive cell death induction. The R72C variant that accumulates intracellular succinate due to compromised CII activity was resistant to MitoVES and TTFA treatment and did not increase ROS, even though TTFA efficiently generated ROS at low succinate in mitochondria isolated from R72C cells. Similarly, the high-affinity Qp site inhibitor Atpenin A5 rapidly increased intracellular succinate in WT cells but did not induce ROS or cell death, unlike MitoVES and TTFA that upregulated succinate only moderately. These results demonstrate that cell death initiation upon CII inhibition depends on ROS and that the extent of cell death correlates with the potency of inhibition at the Qp site unless intracellular succinate is high. In addition, this validates the Qp site of CII as a target for cell death induction with relevance to cancer therapy. PMID:25950479

  8. 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.

  9. Unmanned Spacecraft of the United States

    NASA Technical Reports Server (NTRS)

    Cortright, Edgar M.

    1964-01-01

    In 1957 the first earth satellite ushered in the age of space flight. Since that historic event, space exploration has become a major national objective of both the United States and the Soviet Union. These two nations have attempted a total of well over 200 space flight missions. Other nations are also participating in various degrees in what will continue to grow as a cooperative world effort. In the years since 1957, man has successfully flown in earth orbit. He has initiated programs to land on the moon and return. He has made dramatic applications of earth satellites in meteorology, communications, navigation, and geodesy. A host of scientific satellites.continue to advance understanding of the earth's environment, the sun, and the stars. Automated spacecraft are being flown to the moon, deep into interplanetary space, and to the near planets, Mars and Venus. One of the most exciting technological aspects of space exploration has been the development of automated spacecraft. Most of the scientific exploration of space and the useful applications of space flight thus far have been made possible by automated spacecraft. Development of these spacecraft and their many complex subsystems is setting the pace today for many branches of science and technology. Guidance, computer, attitude control, power, telecommunication, instrumentation, and structural subsystems are being subjected to new standards of light weight, high efficiency, extreme accuracy, and unsurpassed reliability and quality. This publication reviews the automated spacecraft which have been developed and flown, or which are under active development in the United States by the National Aeronautics and Space Administration. From the facts and statistics contained herein, certain observations can be made and certain conclusions drawn.

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

    PubMed

    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.

  11. A microRNA-initiated DNAzyme motor operating in living cells

    NASA Astrophysics Data System (ADS)

    Peng, Hanyong; Li, Xing-Fang; Zhang, Hongquan; Le, X. Chris

    2017-03-01

    Synthetic DNA motors have great potential to mimic natural protein motors in cells but the operation of synthetic DNA motors in living cells remains challenging and has not been demonstrated. Here we report a DNAzyme motor that operates in living cells in response to a specific intracellular target. The whole motor system is constructed on a 20 nm gold nanoparticle (AuNP) decorated with hundreds of substrate strands serving as DNA tracks and dozens of DNAzyme molecules each silenced by a locking strand. Intracellular interaction of a target molecule with the motor system initiates the autonomous walking of the motor on the AuNP. An example DNAzyme motor responsive to a specific microRNA enables amplified detection of the specific microRNA in individual cancer cells. Activated by specific intracellular targets, these self-powered DNAzyme motors will have diverse applications in the control and modulation of biological functions.

  12. Platelet-activating Factor Receptor Initiates Contact of Acinetobacter baumannii Expressing Phosphorylcholine with Host Cells

    PubMed Central

    Smani, Younes; Docobo-Pérez, Fernando; López-Rojas, Rafael; Domínguez-Herrera, Juan; Ibáñez-Martínez, José; Pachón, Jerónimo

    2012-01-01

    Adhesion is an initial and important step in Acinetobacter baumannii causing infections. However, the exact molecular mechanism of such a step between A. baumannii and the host cells remains unclear. Here, we demonstrated that the phosphorylcholine (ChoP)-containing outer membrane protein of A. baumannii binds to A549 cells through platelet-activating factor receptor (PAFR), resulting in activation of G protein and intracellular calcium. Upon A. baumannii expressing ChoP binding to PAFR, clathrin and β-arrestins, proteins involved in the direction of the vacuolar movement, are activated during invasion of A. baumannii. PAFR antagonism restricts the dissemination of A. baumannii in the pneumonia model. These results define a role for PAFR in A. baumannii interaction with host cells and suggest a mechanism for the entry of A. baumannii into the cytoplasm of host cells. PMID:22689572

  13. Interplay between ROS and autophagy in cancer cells, from tumor initiation to cancer therapy

    PubMed Central

    Poillet-Perez, Laura; Despouy, Gilles; Delage-Mourroux, Régis; Boyer-Guittaut, Michaël

    2014-01-01

    Cancer formation is a complex and highly regulated multi-step process which is highly dependent of its environment, from the tissue to the patient. This complexity implies the development of specific treatments adapted to each type of tumor. The initial step of cancer formation requires the transformation of a healthy cell to a cancer cell, a process regulated by multiple intracellular and extracellular stimuli. The further steps, from the anarchic proliferation of cancer cells to form a primary tumor to the migration of cancer cells to distant organs to form metastasis, are also highly dependent of the tumor environment but of intracellular molecules and pathways as well. In this review, we will focus on the regulatory role of reactive oxygen species (ROS) and autophagy levels during the course of cancer development, from cellular transformation to the formation of metastasis. These data will allow us to discuss the potential of this molecule or pathway as putative future therapeutic targets. PMID:25590798

  14. Immunomagnetic separation of tumor initiating cells by screening two surface markers

    PubMed Central

    Sun, Chen; Hsieh, Yuan-Pang; Ma, Sai; Geng, Shuo; Cao, Zhenning; Li, Liwu; Lu, Chang

    2017-01-01

    Isolating tumor initiating cells (TICs) often requires screening of multiple surface markers, sometimes with opposite preferences. This creates a challenge for using bead-based immunomagnetic separation (IMS) that typically enriches cells based on one abundant marker. Here, we propose a new strategy that allows isolation of CD44+/CD24− TICs by IMS involving both magnetic beads coated by anti-CD44 antibody and nonmagnetic beads coated by anti-CD24 antibody (referred to as two-bead IMS). Cells enriched with our approach showed significant enhancement in TIC marker expression (examined by flow cytometry) and improved tumorsphere formation efficiency. Our method will extend the application of IMS to cell subsets characterized by multiple markers. PMID:28074882

  15. A microRNA-initiated DNAzyme motor operating in living cells

    PubMed Central

    Peng, Hanyong; Li, Xing-Fang; Zhang, Hongquan; Le, X. Chris

    2017-01-01

    Synthetic DNA motors have great potential to mimic natural protein motors in cells but the operation of synthetic DNA motors in living cells remains challenging and has not been demonstrated. Here we report a DNAzyme motor that operates in living cells in response to a specific intracellular target. The whole motor system is constructed on a 20 nm gold nanoparticle (AuNP) decorated with hundreds of substrate strands serving as DNA tracks and dozens of DNAzyme molecules each silenced by a locking strand. Intracellular interaction of a target molecule with the motor system initiates the autonomous walking of the motor on the AuNP. An example DNAzyme motor responsive to a specific microRNA enables amplified detection of the specific microRNA in individual cancer cells. Activated by specific intracellular targets, these self-powered DNAzyme motors will have diverse applications in the control and modulation of biological functions. PMID:28262725

  16. 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.

  17. 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.

  18. 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.

  19. CD4+ CD25+ regulatory T cells inhibit the maturation but not the initiation of an autoantibody response.

    PubMed

    Fields, Michele L; Hondowicz, Brian D; Metzgar, Michele H; Nish, Simone A; Wharton, Gina N; Picca, Cristina C; Caton, Andrew J; Erikson, Jan

    2005-10-01

    To investigate the mechanism by which T regulatory (Treg) cells may control the early onset of autoimmunity, we have used an adoptive transfer model to track Treg, Th, and anti-chromatin B cell interactions in vivo. We show that anti-chromatin B cells secrete Abs by day 8 in vivo upon provision of undeviated, Th1- or Th2-type CD4+ T cell help, but this secretion is blocked by the coinjection of CD4+ CD25+ Treg cells. Although Treg cells do not interfere with the initial follicular entry or activation of Th or B cells at day 3, ICOS levels on Th cells are decreased. Furthermore, Treg cells must be administered during the initial phases of the Ab response to exert full suppression of autoantibody production. These studies indicate that CD25+ Treg cells act to inhibit the maturation, rather than the initiation, of autoantibody responses.

  20. Retinoic acid derived from the fetal ovary initiates meiosis in mouse germ cells.

    PubMed

    Mu, Xinyi; Wen, Jing; Guo, Meng; Wang, Jianwei; Li, Ge; Wang, Zhengpin; Wang, Yijing; Teng, Zhen; Cui, Yan; Xia, Guoliang

    2013-03-01

    Meiotic initiation of germ cells at 13.5 dpc (days post-coitus) indicates female sex determination in mice. Recent studies reveal that mesonephroi-derived retinoic acid (RA) is the key signal for induction of meiosis. However, whether the mesonephroi is dispensable for meiosis is unclear and the role of the ovary in this meiotic process remains to be clarified. This study provides data that RA derived from fetal ovaries is sufficient to induce germ cell meiosis in a fetal ovary culture system. When fetal ovaries were collected from 11.5 to 13.5 dpc fetuses, isolated and cultured in vitro, germ cells enter meiosis in the absence of mesonephroi. To exclude RA sourcing from mesonephroi, 11.5 dpc urogenital ridges (UGRs; mesonephroi and ovary complexes) were treated with diethylaminobenzaldehyde (DEAB) to block retinaldehyde dehydrogenase (RALDH) activity in the mesonephros and the ovary. Meiosis occurred when DEAB was withdrawn and the mesonephros was removed 2 days later. Furthermore, RALDH1, rather than RALDH2, serves as the major RA synthetase in UGRs from 12.5 to 15.5 dpc. DEAB treatment to the ovary alone was able to block germ cell meiotic entry. We also found that exogenously supplied RA dose-dependently reduced germ cell numbers in ovaries by accelerating the entry into meiosis. These results suggest that ovary-derived RA is responsible for meiosis initiation.

  1. Cell adhesion to fibronectin and tenascin: quantitative measurements of initial binding and subsequent strengthening response

    PubMed Central

    1989-01-01

    Cell-substratum adhesion strengths have been quantified using fibroblasts and glioma cells binding to two extracellular matrix proteins, fibronectin and tenascin. A centrifugal force-based adhesion assay was used for the adhesive strength measurements, and the corresponding morphology of the adhesions was visualized by interference reflection microscopy. The initial adhesions as measured at 4 degrees C were on the order of 10(-5)dynes/cell and did not involve the cytoskeleton. Adhesion to fibronectin after 15 min at 37 degrees C were more than an order of magnitude stronger; the strengthening response required cytoskeletal involvement. By contrast to the marked strengthening of adhesion to FN, adhesion to TN was unchanged or weakened after 15 min at 37 degrees C. The absolute strength of adhesion achieved varied according to protein and cell type. When a mixed substratum of fibronectin and tenascin was tested, the presence of tenascin was found to reduce the level of the strengthening of cell adhesion normally observed at 37 degrees C on a substratum of fibronectin alone. Parallel analysis of corresponding interference reflection micrographs showed that differences in the area of cell surface within 10-15 nm of the substratum correlated closely with each of the changes in adhesion observed: after incubation for 15 min on fibronectin at 37 degrees C, glioma cells increased their surface area within close contact to the substrate by integral to 125- fold. Cells on tenascin did not increase their surface area of contact. The increased surface area of contact and the inhibitory activity of cytochalasin b suggest that the adhesive "strengthening" in the 15 min after initial binding brings additional adhesion molecules into the adhesive site and couples the actin cytoskeleton to the adhesion complex. PMID:2477381

  2. Aluminum-Air Power Cell: the M4-cell assembly and initial tests

    SciTech Connect

    Maimoni, A.; Muelder, S.A.; Hui, W.C.

    1985-10-03

    We fabricated, assembled, and tested the modular, wedge-shaped M4 Aluminum-Air Power Cell in a system with a fluidized-bed crystallizer and hydrocyclone separator. Two M4-cell experiments validated the design premises and indicated predictable performance. The combined duration of the M4-1 and M4-2 experiments was almost 9 h. Conductive epoxy bonds are inadequate for bonding the air-cathode metal screen to current collectors; soldered joints using low melting (93/sup 0/C) Indium solder performed satisfactorily. Both experiments were terminated because of problems directly traceable to metallic tin deposited by the stannate corrosion inhibitor. Apart from problems caused by metallic tin, the M4-2 test system performed very satisfactorily. Individual cell pods are readily assembled into single or multicell stacks; it is easy to disassemble the cells after a run to determine cell condition. Air-cathode assembly is the most cumbersome aspect of the M4 cell. We obtained valuable information regarding the evolution of particle-size distribution. We did not observe substantial agglomeration of the smaller crystals. A simple model of secondary nucleation gave a reasonably good fit to the secondary nucleation observed in the M3-3 experiment.

  3. Mantle Cell Hyperplasia of Peripheral Lymph Nodes as Initial Manifestation of Sickle Cell Disease.

    PubMed

    Monabbati, Ahmad; Noori, Sadat; Safaei, Akbar; Ramzi, Mani; Eghbali, Seyedsajjad; Adib, Ali

    2016-01-01

    Sickle cell disease (SCD) is a well known hemoglobinopathy with usual manifestations including anemia, hyperbilirubinemia, and vasoocclusive complications. Despite presence of mild splenomegaly in early phase of the disease, lymphadenopathy is not an often finding of SCD. We introduce an undiagnosed case of SCD who presented in third decade of his life with multiple cervical lymphadenopathies and mild splenomegaly persistent for about five years. Histopathologic examination of the resected lymph nodes showed expansion of the mantle cell layers of secondary follicles as well as several monomorphic mantle cell nodules. To rule out possibility of a malignant process involving lymph nodes, an immunohistochemical panel was ordered which was in favor of benign mantle cell hyperplasia. Immunoglobulin gene rearrangement study showed no clonal bands and confirmed benign nature of the process. Respecting mild abnormalities on Complete Blood Count, peripheral blood smear was reviewed revealing some typical sickle red blood cells as well as rare nucleated red blood cells. Solubility test for hemoglobin (HB) S was positive. Hemoglobin electrophoresis confirmed diagnosis of homozygous HbS disease.

  4. Mantle Cell Hyperplasia of Peripheral Lymph Nodes as Initial Manifestation of Sickle Cell Disease

    PubMed Central

    Monabbati, Ahmad; Noori, Sadat; Safaei, Akbar; Ramzi, Mani; Eghbali, Seyedsajjad

    2016-01-01

    Sickle cell disease (SCD) is a well known hemoglobinopathy with usual manifestations including anemia, hyperbilirubinemia, and vasoocclusive complications. Despite presence of mild splenomegaly in early phase of the disease, lymphadenopathy is not an often finding of SCD. We introduce an undiagnosed case of SCD who presented in third decade of his life with multiple cervical lymphadenopathies and mild splenomegaly persistent for about five years. Histopathologic examination of the resected lymph nodes showed expansion of the mantle cell layers of secondary follicles as well as several monomorphic mantle cell nodules. To rule out possibility of a malignant process involving lymph nodes, an immunohistochemical panel was ordered which was in favor of benign mantle cell hyperplasia. Immunoglobulin gene rearrangement study showed no clonal bands and confirmed benign nature of the process. Respecting mild abnormalities on Complete Blood Count, peripheral blood smear was reviewed revealing some typical sickle red blood cells as well as rare nucleated red blood cells. Solubility test for hemoglobin (HB) S was positive. Hemoglobin electrophoresis confirmed diagnosis of homozygous HbS disease. PMID:27872769

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Heliocentric phasing performance of electric sail spacecraft

    NASA Astrophysics Data System (ADS)

    Mengali, Giovanni; Quarta, Alessandro A.; Aliasi, Generoso

    2016-10-01

    We investigate the heliocentric in-orbit repositioning problem of a spacecraft propelled by an Electric Solar Wind Sail. Given an initial circular parking orbit, we look for the heliocentric trajectory that minimizes the time required for the spacecraft to change its azimuthal position, along the initial orbit, of a (prescribed) phasing angle. The in-orbit repositioning problem can be solved using either a drift ahead or a drift behind maneuver and, in general, the flight times for the two cases are different for a given value of the phasing angle. However, there exists a critical azimuthal position, whose value is numerically found, which univocally establishes whether a drift ahead or behind trajectory is superior in terms of flight time it requires for the maneuver to be completed. We solve the optimization problem using an indirect approach for different values of both the spacecraft maximum propulsive acceleration and the phasing angle, and the solution is then specialized to a repositioning problem along the Earth's heliocentric orbit. Finally, we use the simulation results to obtain a first order estimate of the minimum flight times for a scientific mission towards triangular Lagrangian points of the Sun-[Earth+Moon] system.

  10. 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

  11. 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.

  12. Studying Spacecraft Charging via Numerical Simulations

    NASA Astrophysics Data System (ADS)

    Delzanno, G. L.; Moulton, D.; Meierbachtol, C.; Svyatskiy, D.; Vernon, L.

    2015-12-01

    The electrical charging of spacecraft due to bombarding charged particles can affect their performance and operation. We study this charging using CPIC; a particle-in-cell code specifically designed for studying plasma-material interactions [1]. CPIC is based on multi-block curvilinear meshes, resulting in near-optimal computational performance while maintaining geometric accuracy. Relevant plasma parameters are imported from the SHIELDS framework (currently under development at LANL), which simulates geomagnetic storms and substorms in the Earth's magnetosphere. Simulated spacecraft charging results of representative Van Allen Probe geometries using these plasma parameters will be presented, along with an overview of the code. [1] G.L. Delzanno, E. Camporeale, J.D. Moulton, J.E. Borovsky, E.A. MacDonald, and M.F. Thomsen, "CPIC: A Curvilinear Particle-In-Cell Code for Plasma-Material Interaction Studies," IEEE Trans. Plas. Sci., 41 (12), 3577 (2013).

  13. Disulfiram modulates stemness and metabolism of brain tumor initiating cells in atypical teratoid/rhabdoid tumors

    PubMed Central

    Choi, Seung Ah; Choi, Jung Won; Wang, Kyu-Chang; Phi, Ji Hoon; Lee, Ji Yeoun; Park, Kyung Duk; Eum, Dayoung; Park, Sung-Hye; Kim, Il Han; Kim, Seung-Ki

    2015-01-01

    Background Atypical teratoid/rhabdoid tumors (AT/RT) are among the most malignant pediatric brain tumors. Cells from brain tumors with high aldehyde dehydrogenase (ALDH) activity have a number of characteristics that are similar to brain tumor initiating cells (BTICs). This study aimed to evaluate the therapeutic potential of ALDH inhibition using disulfiram (DSF) against BTICs from AT/RT. Methods Primary cultured BTICs from AT/RT were stained with Aldefluor and isolated by fluorescence activated cell sorting. The therapeutic effect of DSF against BTICs from AT/RT was confirmed in vitro and in vivo. Results AT/RT cells displayed a high expression of ALDH. DSF demonstrated a more potent cytotoxic effect on ALDH+ AT/RT cells compared with standard anticancer agents. Notably, treatment with DSF did not have a considerable effect on normal neural stem cells or fibroblasts. DSF significantly inhibited the ALDH enzyme activity of AT/RT cells. DSF decreased self-renewal ability, cell viability, and proliferation potential and induced apoptosis and cell cycle arrest in ALDH+ AT/RT cells. Importantly, DSF reduced the metabolism of ALDH+ AT/RT cells by increasing the nicotinamide adenine dinucleotide ratio of NAD+/NADH and regulating Silent mating type Information Regulator 2 homolog 1 (SIRT1), nuclear factor-kappaB, Lin28A/B, and miRNA let-7g. Animals in the DSF-treated group demonstrated a reduction of tumor volume (P < .05) and a significant survival benefit (P = .02). Conclusion Our study demonstrated the therapeutic potential of DSF against BTICs from AT/RT and suggested the possibility of ALDH inhibition for clinical application. PMID:25378634

  14. DNA demethylation is initiated in the central cells of Arabidopsis and rice

    PubMed Central

    Park, Kyunghyuk; Kim, M. Yvonne; Vickers, Martin; Park, Jin-Sup; Hyun, Youbong; Okamoto, Takashi; Zilberman, Daniel; Fischer, Robert L.; Feng, Xiaoqi; Choi, Yeonhee; Scholten, Stefan

    2016-01-01

    Cytosine methylation is a DNA modification with important regulatory functions in eukaryotes. In flowering plants, sexual reproduction is accompanied by extensive DNA demethylation, which is required for proper gene expression in the endosperm, a nutritive extraembryonic seed tissue. Endosperm arises from a fusion of a sperm cell carried in the pollen and a female central cell. Endosperm DNA demethylation is observed specifically on the chromosomes inherited from the central cell in Arabidopsis thaliana, rice, and maize, and requires the DEMETER DNA demethylase in Arabidopsis. DEMETER is expressed in the central cell before fertilization, suggesting that endosperm demethylation patterns are inherited from the central cell. Down-regulation of the MET1 DNA methyltransferase has also been proposed to contribute to central cell demethylation. However, with the exception of three maize genes, central cell DNA methylation has not been directly measured, leaving the origin and mechanism of endosperm demethylation uncertain. Here, we report genome-wide analysis of DNA methylation in the central cells of Arabidopsis and rice—species that diverged 150 million years ago—as well as in rice egg cells. We find that DNA demethylation in both species is initiated in central cells, which requires DEMETER in Arabidopsis. However, we do not observe a global reduction of CG methylation that would be indicative of lowered MET1 activity; on the contrary, CG methylation efficiency is elevated in female gametes compared with nonsexual tissues. Our results demonstrate that locus-specific, active DNA demethylation in the central cell is the origin of maternal chromosome hypomethylation in the endosperm. PMID:27956642

  15. Exposure to Brefeldin A promotes initiation of meiosis in murine female germ cells.

    PubMed

    Zhang, Lian-Jun; Chen, Bo; Feng, Xin-Lei; Ma, Hua-Gang; Sun, Li-Lan; Feng, Yan-Min; Liang, Gui-Jin; Cheng, Shun-Feng; Li, Lan; Shen, Wei

    2015-01-01

    In mammals, ontogenesis starts from a fusion of spermatozoon and oocyte, which are produced by reductive nuclear division of a diploid germ cell in a specialised but complex biological process known as meiosis. However, little is known about the mechanism of meiotic initiation in germ cells, although many factors may be responsible for meiosis both in male and female gonads. In this study, 11.5 days post coitum (dpc) female fetal mouse genital ridges were cultured in vitro with exposure to Brefeldin A (BFA) for 6h, and the changes in meiosis were detected. Synaptonemal-complex analysis implied that BFA played a positive role in meiosis initiation and this hypothesis was confirmed by quantitative PCR of meiosis-specific genes: stimulated by retinoic acid gene 8 (Stra8) and deleted in a zoospermia-like (DAZL). At the same time, mRNA expression of retinoic acid synthetase (Raldh2) and retinoic acid (RA) receptors increased in female gonads with in vitro exposure to BFA. Transplanting genital ridges treated with BFA into the kidney capsule of immunodeficient mice demonstrated that the development capacity of female germ cells was normal, while formation of primordial follicles was seen to be a result of accelerated meiosis after exposure to BFA. In conclusion, the study indicated that BFA stimulated meiosis initiation partly by RA signalling and then promoted the development of follicles.

  16. The initiation of lateral roots in the primary roots of maize (Zea mays L.) implies a reactivation of cell proliferation in a group of founder pericycle cells.

    PubMed

    Alarcón, M Victoria; Lloret, Pedro G; Martín-Partido, Gervasio; Salguero, Julio

    2016-03-15

    The initiation of lateral roots (LRs) has generally been viewed as a reactivation of proliferative activity in pericycle cells that are committed to initiate primordia. However, it is also possible that pericycle founder cells that initiate LRs never cease proliferative activity but rather are displaced to the most distal root zones while undertaking successive stages of LR initiation. In this study, we tested these two alternative hypotheses by examining the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into the DNA of meristematic root cells of Zea mays. According to the values for the length of the cell cycle and values for cell displacement along the maize root, our results strongly suggest that pericycle cells that initiate LR primordia ceased proliferative activity upon exiting the meristematic zone. This finding is supported by the existence of a root zone between 4 and 20mm from the root cap junction, in which neither mitotic cells nor labelled nuclei were observed in phloem pericycle cells.

  17. 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.

  18. Combining a BCL2 inhibitor with the retinoid derivative fenretinide targets melanoma cells including melanoma initiating cells.

    PubMed

    Mukherjee, Nabanita; Reuland, Steven N; Lu, Yan; Luo, Yuchun; Lambert, Karoline; Fujita, Mayumi; Robinson, William A; Robinson, Steven E; Norris, David A; Shellman, Yiqun G

    2015-03-01

    Investigations from multiple laboratories support the existence of melanoma initiating cells (MICs) that potentially contribute to melanoma's drug resistance. ABT-737, a small molecule BCL-2/BCL-XL/BCL-W inhibitor, is promising in cancer treatments, but not very effective against melanoma, with the antiapoptotic protein MCL-1 as the main contributor to resistance. The synthetic retinoid fenretinide N-(4-hydroxyphenyl)retinamide (4-HPR) has shown promise for treating breast cancers. Here, we tested whether the combination of ABT-737 with 4-HPR is effective in killing both the bulk of melanoma cells and MICs. The combination synergistically decreased cell viability and caused cell death in multiple melanoma cells lines (carrying either BRAF or NRAS mutations) but not in normal melanocytes. The combination increased the NOXA expression and caspase-dependent MCL-1 degradation. Knocking down NOXA protected cells from combination-induced apoptosis, implicating the role of NOXA in the drug synergy. The combination treatment also disrupted primary spheres (a functional assay for MICs) and decreased the percentage of aldehyde dehydrogenase (high) cells (a marker of MICs) in melanoma cell lines. Moreover, the combination inhibited the self-renewal capacity of MICs, measured by secondary sphere-forming assays. In vivo, the combination inhibited tumor growth. Thus, this combination is a promising treatment strategy for melanoma, regardless of mutation status of BRAF or NRAS.

  19. Interplanetary charged particle models (1974). [and the effects of cosmic exposure upon spacecraft and spacecraft components

    NASA Technical Reports Server (NTRS)

    Divine, N.

    1975-01-01

    The design of space vehicles for operation in interplanetary space is given, based on descriptions of solar wind, solar particle events, and galactic cosmic rays. A state-of-the-art review is presented and design criteria are developed from experiment findings aboard interplanetary and high-altitude earth-orbiting spacecraft. Solar cells were found to be particularly sensitive. Solar protons may also impact the reliability of electric propulsion systems and spacecraft surfaces, as well as causing interference, detector saturation, and spurious signals. Galactic cosmic-ray impact can lead to similar electronic failure and interference and may register in photographic films and other emulsions. It was concluded that solar wind electron measurements might result from differential charging when shadowed portions of the spacecraft acquired a negative charge from electron impact.

  20. Donor exosomes rather than passenger leukocytes initiate alloreactive T cell responses after transplantation

    PubMed Central

    Marino, Jose; Babiker-Mohamed, Mohamed H.; Crosby-Bertorini, Patrick; Paster, Joshua T.; LeGuern, Christian; Germana, Sharon; Abdi, Reza; Uehara, Mayuko; Kim, James I.; Markmann, James F.; Tocco, Georges; Benichou, Gilles

    2016-01-01

    Transplantation of allogeneic organs and tissues represents a lifesaving procedure for a variety of patients affected with end-stage diseases. Although current immunosuppressive therapy prevents early acute rejection, it is associated with nephrotoxicity and increased risks for infection and neoplasia. This stresses the need for selective immune-based therapies relying on manipulation of lymphocyte recognition of donor antigens. The passenger leukocyte theory states that allograft rejection is initiated by recipient T cells recognizing donor major histocompatibility complex (MHC) molecules displayed on graft leukocytes migrating to the host’s lymphoid organs. We revisited this concept in mice transplanted with allogeneic skin, heart, or islet grafts using imaging flow cytometry. We observed no donor cells in the lymph nodes and spleen of skin-grafted mice, but we found high numbers of recipient cells displaying allogeneic MHC molecules (cross-dressed) acquired from donor microvesicles (exosomes). After heart or islet transplantation, we observed few donor leukocytes (100 per million) but large numbers of recipient cells cross-dressed with donor MHC (>90,000 per million). Last, we showed that purified allogeneic exosomes induced proinflammatory alloimmune responses by T cells in vitro and in vivo. Collectively, these results suggest that recipient antigen-presenting cells cross-dressed with donor MHC rather than passenger leukocytes trigger T cell responses after allotransplantation. PMID:27942611

  1. A disintegrin and metalloproteinases 10 and 17 modulate the immunogenicity of glioblastoma-initiating cells

    PubMed Central

    Wolpert, Fabian; Tritschler, Isabel; Steinle, Alexander; Weller,, Michael; Eisele, Günter

    2014-01-01

    Background There are emerging reports that the family of a disintegrin and metalloproteinases (ADAM) are involved in the maintenance of the malignant phenotype of glioblastomas. Notably, ADAM proteases 10 and 17 might impair the immune recognition of glioma cells via the activating immunoreceptor NKG2D by cleavage of its ligands from the cell surface. Glioblastoma-initiating cells (GIC) with stem cell properties have been identified as an attractive target for immunotherapy. However, GIC immunogenicity seems to be low. Methods and Results Here,we show that ADAM10 and ADAM17 are expressed on the cell surface of GIC and contribute to an immunosuppressive phenotype by cleavage of ULBP2. The cell surface expression of ULBP2 is enhanced upon blocking ADAM10 and ADAM17, and treatment with ADAM10 and ADAM17specific inhibitors leads to enhanced immunerecognition of GIC by natural killer cells. Conclusions Therefore, ADAM10 and ADAM17 constitute suitable targets to boost an immune response against GIC. PMID:24327582

  2. The human-induced pluripotent stem cell initiative-data resources for cellular genetics.

    PubMed

    Streeter, Ian; Harrison, Peter W; Faulconbridge, Adam; Flicek, Paul; Parkinson, Helen; Clarke, Laura

    2017-01-04

    The Human Induced Pluripotent Stem Cell Initiative (HipSci) isf establishing a large catalogue of human iPSC lines, arguably the most well characterized collection to date. The HipSci portal enables researchers to choose the right cell line for their experiment, and makes HipSci's rich catalogue of assay data easy to discover and reuse. Each cell line has genomic, transcriptomic, proteomic and cellular phenotyping data. Data are deposited in the appropriate EMBL-EBI archives, including the European Nucleotide Archive (ENA), European Genome-phenome Archive (EGA), ArrayExpress and PRoteomics IDEntifications (PRIDE) databases. The project will make 500 cell lines from healthy individuals, and from 150 patients with rare genetic diseases; these will be available through the European Collection of Authenticated Cell Cultures (ECACC). As of August 2016, 238 cell lines are available for purchase. Project data is presented through the HipSci data portal (http://www.hipsci.org/lines) and is downloadable from the associated FTP site (ftp://ftp.hipsci.ebi.ac.uk/vol1/ftp). The data portal presents a summary matrix of the HipSci cell lines, showing available data types. Each line has its own page containing descriptive metadata, quality information, and links to archived assay data. Analysis results are also available in a Track Hub, allowing visualization in the context of public genomic annotations (http://www.hipsci.org/data/trackhubs).

  3. Effect of surface roughness of ground titanium on initial cell adhesion.

    PubMed

    Huang, Her-Hsiung; Ho, Chun-Te; Lee, Tzu-Hsin; Lee, Tien-Ling; Liao, Ko-Kaung; Chen, Fang-Lung

    2004-11-01

    The effect of surface roughness of ground Ti on the initial adhesion of osteoblast-like U-2 OS cells was investigated in this study. Different numbers (#120, #600, and #1500) of SiC sandpaper and two Al2O3 polishing powder (0.3 and 1 microm) were used to prepare the metal specimens with varying degrees of surface roughness. Surface roughness (Ra) was measured by profilometry. Surface topography was observed using an atomic force microscope. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay was used to measure the optical density (OD) of specimens after 2 h of cell incubation. The OD value was analyzed by one-way ANOVA for analyzing the factor of surface roughness. Crystal violet staining technique was used to characterize the cell spreading. Results showed that the specimen of #1500 Ti (Ra: 0.15 microm) had the highest OD value. The specimens polished with 0.3 and 1 microm Al2O3 powder (Ra: 0.05 and 0.07 microm) exhibited the worst cell adhesion behavior. Contact guidance of cells could be observed on the rougher #600 and #120 specimens (Ra: 0.33 and 1.20 microm). This study concludes that the surface roughness (Ra: 0.05-1.20 microm) of ground Ti has a highly significant influence on the initial adhesion of osteoblast-like U-2 OS cells. The ground Ti with an Ra of 0.15 microm shows the optimal cell adhesion behavior with respect to either the rougher or smoother specimens.

  4. 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

  5. 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.

  6. 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

  7. Bilateral ocular panadnexal mass as initial presentation of systemic blastoid variant of mantle-cell lymphoma.

    PubMed

    Rašić, Dejan M; Knežević, Miroslav; Terzić, Tatjana; Vlajković, Gordana

    A 66-year-old man developed a slowly enlarging, bilateral, painless, periorbital, and orbital swelling with ptosis, nonaxial proptosis, chemosis, exposure keratopathy, and decreased vision in both eyes. He had fever, night sweats, and weight loss (B-symptoms), along with lymphadenopathy and elevated serum lactate dehydrogenase, with no prior history of lymphoma. A transpalpebral incisional biopsy revealed a rare case of mantle-cell lymphoma of blastoid variant, stage IVB. The main immunophenotype characteristics were cyclin D1+, CD5+, CD10-, CD23-, Bcl-6-/+, and a high (up to 80%) Ki-67 proliferation index. Following an excellent response to the immune-chemotherapy treatment plan, all ocular adnexal lymphoma manifestations disappeared completely; however, 13 months after the initial presentation, there was a recurrence of the disease with rapid worsening and death. The blastoid variant of mantle cell lymphoma, a rare subtype of mantle-cell lymphoma, is a highly aggressive neoplasm, ultimately having a fatal outcome. As the initial manifestation of the disease, ocular adnexal region blastoid variant of mantle-cell lymphoma is an exceptional event, with only one previous case reported.

  8. Manipulating CD4+ T cells by optical tweezers for the initiation of cell-cell transfer of HIV-1

    PubMed Central

    McNerney, Gregory P.; Hübner, Wolfgang; Chen, Benjamin K.; Huser, Thomas

    2011-01-01

    Cell-cell interactions through direct contact are very important for cellular communication and coordination – especially for immune cells. The human immunodeficiency virus type I (HIV-1) induces immune cell interactions between CD4+ cells to shuttle between T cells via a virological synapse. A goal to understand the process of cell-cell transmission through virological synapses is to determine the cellular states that allow a chance encounter between cells to become a stable cell-cell adhesion. Here we demonstrate the use of optical tweezers to manipulate uninfected primary CD4+ T cells near HIV Gag-iGFP transfected Jurkat T cells to probe the determinants that induce stable adhesion. When combined with fast 4D confocal fluorescence microscopy, optical tweezers can be utilized to not only facilitate cell-cell contact, but to also allow one to simultaneously track the formation of a virological synapse, and ultimately to enable us to precisely determine all events preceding virus transfer. HIV-1 infected T cell (green) decorated with uninfected primary T cells (red) by manipulating the primary cells with an optical tweezers system PMID:20301121

  9. 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.

  10. Low-Temperature Spacecraft: Challenges/Opportunities

    NASA Technical Reports Server (NTRS)

    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.

  11. 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.

  12. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

    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.

  14. Epigenetic states of cells of origin and tumor evolution drive tumor-initiating cell phenotype and tumor heterogeneity.

    PubMed

    Chow, Kin-Hoe; Shin, Dong-Mi; Jenkins, Molly H; Miller, Emily E; Shih, David J; Choi, Seungbum; Low, Benjamin E; Philip, Vivek; Rybinski, Brad; Bronson, Roderick T; Taylor, Michael D; Yun, Kyuson

    2014-09-01

    A central confounding factor in the development of targeted therapies is tumor cell heterogeneity, particularly in tumor-initiating cells (TIC), within clinically identical tumors. Here, we show how activation of the Sonic Hedgehog (SHH) pathway in neural stem and progenitor cells creates a foundation for tumor cell evolution to heterogeneous states that are histologically indistinguishable but molecularly distinct. In spontaneous medulloblastomas that arise in Patched (Ptch)(+/-) mice, we identified three distinct tumor subtypes. Through cell type-specific activation of the SHH pathway in vivo, we determined that different cells of origin evolved in unique ways to generate these subtypes. Moreover, TICs in each subtype had distinct molecular and cellular phenotypes. At the bulk tumor level, the three tumor subtypes could be distinguished by a 465-gene signature and by differential activation levels of the ERK and AKT pathways. Notably, TICs from different subtypes were differentially sensitive to SHH or AKT pathway inhibitors, highlighting new mechanisms of resistance to targeted therapies. In summary, our results show how evolutionary processes act on distinct cells of origin to contribute to tumoral heterogeneity, at both bulk tumor and TIC levels.

  15. Glial Cell Contribution to Basal Vessel Diameter and Pressure-Initiated Vascular Responses in Rat Retina

    PubMed Central

    Li, Hui; Bui, Bang V.; Cull, Grant; Wang, Fang; Wang, Lin

    2017-01-01

    Purpose The purpose of this study was to test the hypothesis that retinal glial cells modify basal vessel diameter and pressure-initiated vascular regulation in rat retina. Methods In rats, L-2-aminoadipic acid (LAA, 10 nM) was intravitreally injected to inhibit glial cell activity. Twenty-four hours following injection, retinal glial intracellular calcium (Ca2+) was labeled with the fluorescent calcium indicator Fluo-4/AM (F4, 1 mM). At 110 minutes after injection, intraocular pressure (IOP) was elevated from 20 to 50 mm Hg. Prior to and during IOP elevation, Ca2+ and retinal vessel diameter were assessed using a spectral-domain optical coherence tomography/confocal scanning laser ophthalmoscope. Dynamic changes in Ca2+ and diameter from IOP elevation were quantified. The response in LAA-treated eyes was compared with vehicle treated control eyes. Results L-2-Aminoadipic acid treatment significantly reduced F4-positive cells in the retina (LAA, 16 ± 20 vs. control, 55 ± 37 cells/mm2; P = 0.02). Twenty-four hours following LAA treatment, basal venous diameter was increased from 38.9 ± 3.9 to 51.8 ± 6.4 μm (P < 0.0001, n = 20), whereas arterial diameter was unchanged (from 30.3 ± 3.5 to 30.7 ± 2.8 μm; P = 0.64). In response to IOP elevation, LAA-treated eyes showed a smaller increase in glial cell Ca2+ around both arteries and veins in comparison with control (P < 0.001 for both). There was also significantly greater IOP-induced vasoconstriction in both vessel types (P = 0.05 and P = 0.02, respectively; n = 6 each). Conclusions The results suggest that glial cells can modulate basal retinal venous diameter and contribute to pressure-initiated vascular responses. PMID:28055098

  16. Phenotypic differentiation does not affect tumorigenicity of primary human colon cancer initiating cells.

    PubMed

    Dubash, Taronish D; Hoffmann, Christopher M; Oppel, Felix; Giessler, Klara M; Weber, Sarah; Dieter, Sebastian M; Hüllein, Jennifer; Zenz, Thorsten; Herbst, Friederike; Scholl, Claudia; Weichert, Wilko; Werft, Wiebke; Benner, Axel; Schmidt, Manfred; Schneider, Martin; Glimm, Hanno; Ball, Claudia R

    2016-02-28

    Within primary colorectal cancer (CRC) a subfraction of all tumor-initiating cells (TIC) drives long-term progression in serial xenotransplantation. It has been postulated that efficient maintenance of TIC activity in vitro requires serum-free spheroid culture conditions that support a stem-like state of CRC cells. To address whether tumorigenicity is indeed tightly linked to such a stem-like state in spheroids, we transferred TIC-enriched spheroid cultures to serum-containing adherent conditions that should favor their differentiation. Under these conditions, primary CRC cells did no longer grow as spheroids but formed an adherent cell layer, up-regulated colon epithelial differentiation markers, and down-regulated TIC-associated markers. Strikingly, upon xenotransplantation cells cultured under either condition equally efficient formed serially transplantable tumors. Clonal analyses of individual lentivirally marked TIC clones cultured under either culture condition revealed no systematic differences in contributing clone numbers, indicating that phenotypic differentiation does not select for few individual clones adapted to unfavorable culture conditions. Our results reveal that CRC TIC can be propagated under conditions previously thought to induce their elimination. This phenotypic plasticity allows addressing primary human CRC TIC properties in experimental settings based on adherent cell growth.

  17. Conceptual Design of an Electric Sail Technology Demonstration Mission Spacecraft

    NASA Technical Reports Server (NTRS)

    Wiegmann, Bruce M.

    2017-01-01

    There is great interest in examining the outer planets of our solar system and Heliopause region (edge of Solar System) and beyond regions of interstellar space by both the Planetary and Heliophysics communities. These needs are well docu-mented in the recent National Academy of Sciences Decadal Surveys. There is significant interest in developing revolutionary propulsion techniques that will enable such Heliopause scientific missions to be completed within 10 to15 years of the launch date. One such enabling propulsion technique commonly known as Electric Sail (E-Sail) propulsion employs positively charged bare wire tethers that extend radially outward from a rotating spacecraft spinning at a rate of one revolution per hour. Around the positively charged bare-wire tethers, a Debye Sheath is created once positive voltage is applied. This sheath stands off of the bare wire tether at a sheath diameter that is proportional to the voltage in the wire coupled with the flux density of solar wind ions within the solar system (or the location of spacecraft in the solar system. The protons that are expended from the sun (solar wind) at 400 to 800 km/sec are electrostatically repelled away from these positively charged Debye sheaths and propulsive thrust is produced via the resulting momentum transfer. The amount of thrust produced is directly proportional to the total wire length. The Marshall Space Flight Center (MSFC) Electric Sail team is currently funded via a two year Phase II NASA Innovative Advanced Concepts (NIAC) awarded in July 2015. The team's current activities are: 1) Developing a Particle in Cell (PIC) numeric engineering model from the experimental data collected at MSFC's Solar Wind Facility on the interaction between simulated solar wind interaction with a charged bare wire that can be applied to a variety of missions, 2) The development of the necessary tether deployers and tethers to enable successful de-ployment of multiple, multi km length bare tethers

  18. Auxin-mediated cell cycle activation during early lateral root initiation.

    PubMed

    Himanen, Kristiina; Boucheron, Elodie; Vanneste, Steffen; de Almeida Engler, Janice; Inzé, Dirk; Beeckman, Tom

    2002-10-01

    Lateral root formation can be divided into two major phases: pericycle activation and meristem establishment. In Arabidopsis, the first lateral root initiation event is spatially and temporally asynchronous and involves a limited number of cells in the xylem pericycle. To study the molecular regulation during pericycle activation, we developed a lateral root-inducible system. Successive treatments with an auxin transport inhibitor and exogenous auxin were used to prevent the first formative divisions and then to activate the entire pericycle. Our morphological and molecular data show that, in this inducible system, xylem pericycle activation was synchronized and enhanced to cover the entire length of the root. The results also indicate that the inducible system can be considered a novel in planta system for the study of synchronized cell cycle reactivation. In addition, the expression patterns of Kip-Related Protein2 (KRP2) in the pericycle and its ectopic expression data revealed that the cyclin-dependent kinase inhibitor plays a significant role in the regulation of lateral root initiation. KRP2 appears to regulate early lateral root initiation by blocking the G1-to-S transition and to be regulated transcriptionally by auxin.

  19. Spacecraft Re-Entry Impact Point Targeting Using Aerodynamic Drag

    NASA Technical Reports Server (NTRS)

    Omar, Sanny R.; Bevilacqua, Riccardo

    2017-01-01

    The ability to re-enter the atmosphere at a desired location is important for spacecraft containing components that may survive re-entry. While impact point targeting has traditionally been initiated through impulsive burns with chemical thrusters on large vehicles such as the Space Shuttle, and the Soyuz and Apollo capsules, many small spacecraft do not host thrusters and require an alternative means of impact point targeting to ensure that falling debris do not cause harm to persons or property. This paper discusses the use of solely aerodynamic drag force to perform this targeting. It is shown that by deploying and retracting a drag device to vary the ballistic coefficient of the spacecraft, any desired longitude and latitude on the ground can be targeted provided that the maneuvering begins early enough and the latitude is less than the inclination of the orbit. An analytical solution based on perturbations from a numerically propagated trajectory is developed to map the initial state and ballistic coefficient profile of a spacecraft to its impact point. This allows the ballistic coefficient profile necessary to reach a given target point to be rapidly calculated, making it feasible to generate the guidance for the decay trajectory onboard the spacecraft. The ability to target an impact point using aerodynamic drag will enhance the capabilities of small spacecraft and will enable larger space vehicles containing thrusters to save fuel by more effectively leveraging the available aerodynamic drag.

  20. 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.

  1. Spacecraft nonlinear control

    NASA Technical Reports Server (NTRS)

    Sheen, Jyh-Jong; Bishop, Robert H.

    1992-01-01

    The feedback linearization technique is applied to the problem of spacecraft attitude control and momentum management with control moment gyros (CMGs). The feedback linearization consists of a coordinate transformation, which transforms the system to a companion form, and a nonlinear feedback control law to cancel the nonlinear dynamics resulting in a linear equivalent model. Pole placement techniques are then used to place the closed-loop poles. The coordinate transformation proposed here evolves from three output functions of relative degree four, three, and two, respectively. The nonlinear feedback control law is presented. Stability in a neighborhood of a controllable torque equilibrium attitude (TEA) is guaranteed and this fact is demonstrated by the simulation results. An investigation of the nonlinear control law shows that singularities exist in the state space outside the neighborhood of the controllable TEA. The nonlinear control law is simplified by a standard linearization technique and it is shown that the linearized nonlinear controller provides a natural way to select control gains for the multiple-input, multiple-output system. Simulation results using the linearized nonlinear controller show good performance relative to the nonlinear controller in the neighborhood of the TEA.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. Chronic Myelogenous Leukemia- Initiating Cells Require Polycomb Group Protein EZH2.

    PubMed

    Xie, Huafeng; Peng, Cong; Huang, Jialiang; Li, Bin E; Kim, Woojin; Smith, Elenoe C; Fujiwara, Yuko; Qi, Jun; Cheloni, Giulia; Das, Partha P; Nguyen, Minh; Li, Shaoguang; Bradner, James E; Orkin, Stuart H

    2016-11-01

    Tyrosine kinase inhibitors (TKI) have revolutionized chronic myelogenous leukemia (CML) management. Disease eradication, however, is hampered by innate resistance of leukemia-initiating cells (LIC) to TKI-induced killing, which also provides the basis for subsequent emergence of TKI-resistant mutants. We report that EZH2, the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), is overexpressed in CML LICs and required for colony formation and survival and cell-cycle progression of CML cell lines. A critical role for EZH2 is supported by genetic studies in a mouse CML model. Inactivation of Ezh2 in conventional conditional mice and through CRISPR/Cas9-mediated gene editing prevents initiation and maintenance of disease and survival of LICs, irrespective of BCR-ABL1 mutational status, and extends survival. Expression of the EZH2 homolog EZH1 is reduced in EZH2-deficient CML LICs, creating a scenario resembling complete loss of PRC2. EZH2 dependence of CML LICs raises prospects for improved therapy of TKI-resistant CML and/or eradication of disease by addition of EZH2 inhibitors.

  8. Effect of heat-treated titanium surfaces on protein adsorption and osteoblast precursor cell initial attachment.

    PubMed

    Kern, Travis; Yang, Yunzhi; Glover, Renee; Ong, Joo L

    2005-03-01

    The clinical success of dental implants is governed in part by surface properties of implants and their interactions with the surrounding tissues. The objective of this study was to investigate the effect of heat-treated titanium surfaces on protein adsorption and osteoblast precursor cell attachment in vitro. Passivated titanium samples used in this study were either non heat treated or heat treated at 750 degrees C for 90 minutes. It was observed that the contact angle on heat-treated titanium surfaces was statistically lower compared with the non-heat-treated titanium surfaces. The non-heat-treated titanium surface was also observed to be amorphous oxide, whereas heat treatment of titanium resulted in the conversion of amorphous oxide to crystalline anatase oxide. No significant difference in albumin and fibronectin adsorption was observed between the heat-treated and non-heat-treated titanium surfaces. In addition, no significant difference in initial cell attachment was observed between the two groups. It was concluded that heat treatment of titanium resulted in significantly more hydrophilic surfaces compared to non-heat-treated titanium surfaces. However, differences in oxide crystallinity and wettability were not observed to affect protein adsorption and initial osteoblast precursor cell attachment.

  9. 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

  10. Hematuria and decreased kidney function as initial signs of acute B-cell lymphoblastic leukemia.

    PubMed

    Seo-Mayer, Patricia; Kenney, Barton; McNamara, Joseph; Stein, Jeffrey; Moeckel, Gilbert W

    2010-11-01

    We report the case of a 14-year-old boy who presented with hematuria and decreased kidney function as initial manifestations of acute lymphoblastic leukemia (ALL). Computed tomography of the abdomen showed extensive retroperitoneal lymphadenopathy and bilateral nephromegaly. The patient's kidney biopsy specimen showed a dense monomorphous interstitial infiltrate of small round blue cells with significant nuclear atypia. Immunohistochemical workup showed positive staining for CD20, CD10, and terminal deoxynucleotidyl transferase (TdT), consistent with ALL. The patient underwent induction chemotherapy, attained remission 4 weeks after induction, and presently is stable in the consolidation phase of chemotherapy. This is an unusual case of ALL involving both kidneys with initial presenting signs of hematuria and decreased kidney function.

  11. Initiation of T cell signaling by CD45 segregation at ‘close-contacts’

    PubMed Central

    Siebold, Christian; McColl, James; Jönsson, Peter; Palayret, Matthieu; Harlos, Karl; Coles, Charlotte H; Jones, E Yvonne; Lui, Yuan; Huang, Elizabeth; Gilbert, Robert J C; Klenerman, David; Aricescu, A Radu; Davis, Simon J

    2016-01-01

    It has been proposed that the local segregation of kinases and the tyrosine phosphatase CD45 underpins T cell receptor (TCR) triggering, but how segregation would occur and whether it can initiate signaling is unclear. Using structural and biophysical analysis we show that the extracellular region of CD45 is rigid and extends beyond the distance spanned by TCR-ligand complexes, implying that sites of TCR-ligand engagement would sterically exclude CD45. We also show that the formation of new structures characterized by spontaneous sub-micron scale CD45 and kinase segregation, called ‘close-contacts’, initiates signaling even when TCR ligands are absent. Our work reveals the structural basis for, and the unexpectedly potent signaling effects of local CD45 and kinase segregation. TCR ligands could heighten signaling simply by holding receptors in close-contacts. PMID:26998761

  12. 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.

  13. Transient vibration test criteria for spacecraft hardware. [galileo spacecraft

    NASA Technical Reports Server (NTRS)

    Kern, D. L.; Hayes, C. D.

    1984-01-01

    Transient vibration test criteria, developed for spacecraft hardware, provide a test rationale to verify the capability of the hardware to withstand the low and mid frequency transient vibration environments induced by launch vehicle events. A test method, consisting of a series of discrete frequency, limited cycle, modulated sine wave pulses, was developed to avoid the slow swept sine drawbacks, yet provide a repeatable test that would excite all frequencies. The shape of the waveform is that of the classic response of the mass of a one degree of freedom system when it is base-excited by an exponentially decayed sine wave transient. Criteria were developed to define pulse amplitudes, shapes, and center frequencies from spacecraft loads analyses. Test tolerance criteria were also developed and specified. The transient vibration test criteria were implemented on spacecraft flight hardware and provided a more realistic test simulation (i.e., less conservative) for qualification of spacecraft hardware without risk of undertest.

  14. Constitutive expression and activation of stress response genes in cancer stem-like cells/tumour initiating cells: potent targets for cancer stem cell therapy.

    PubMed

    Torigoe, Toshihiko; Hirohashi, Yoshihiko; Yasuda, Kazuyo; Sato, Noriyuki

    2013-08-01

    Cancer stem-like cells (CSCs)/tumour-initiating cells (TICs) are defined as the small population of cancer cells that have stem cell-like phenotypes and high capacity for tumour initiation. These cells may have a huge impact in the field of cancer therapy since they are extremely resistant to standard chemoradiotherapy and thus are likely to be responsible for disease recurrence after therapy. Therefore, extensive efforts are being made to elucidate the pathological and molecular properties of CSCs/TICs and, with this information, to establish efficient anti-CSC/TIC targeting therapies. This review considers recent findings on stress response genes that are preferentially expressed in CSCs/TICs and their roles in tumour-promoting properties. Implications for a novel therapeutic strategy targeting CSCs/TICs are also discussed.

  15. 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.

  16. Cytokinins act directly on lateral root founder cells to inhibit root initiation.

    PubMed

    Laplaze, Laurent; Benkova, Eva; Casimiro, Ilda; Maes, Lies; Vanneste, Steffen; Swarup, Ranjan; Weijers, Dolf; Calvo, Vanessa; Parizot, Boris; Herrera-Rodriguez, Maria Begoña; Offringa, Remko; Graham, Neil; Doumas, Patrick; Friml, Jiri; Bogusz, Didier; Beeckman, Tom; Bennett, Malcolm

    2007-12-01

    In Arabidopsis thaliana, lateral roots are formed from root pericycle cells adjacent to the xylem poles. Lateral root development is regulated antagonistically by the plant hormones auxin and cytokinin. While a great deal is known about how auxin promotes lateral root development, the mechanism of cytokinin repression is still unclear. Elevating cytokinin levels was observed to disrupt lateral root initiation and the regular pattern of divisions that characterizes lateral root development in Arabidopsis. To identify the stage of lateral root development that is sensitive to cytokinins, we targeted the expression of the Agrobacterium tumefaciens cytokinin biosynthesis enzyme isopentenyltransferase to either xylem-pole pericycle cells or young lateral root primordia using GAL4-GFP enhancer trap lines. Transactivation experiments revealed that xylem-pole pericycle cells are sensitive to cytokinins, whereas young lateral root primordia are not. This effect is physiologically significant because transactivation of the Arabidopsis cytokinin degrading enzyme cytokinin oxidase 1 in lateral root founder cells results in increased lateral root formation. We observed that cytokinins perturb the expression of PIN genes in lateral root founder cells and prevent the formation of an auxin gradient that is required to pattern lateral root primordia.

  17. Initiated chemical vapor deposition of thermoresponsive poly(N-vinylcaprolactam) thin films for cell sheet engineering.

    PubMed

    Lee, Bora; Jiao, Alex; Yu, Seungjung; You, Jae Bem; Kim, Deok-Ho; Im, Sung Gap

    2013-08-01

    Poly(N-vinylcaprolactam) (PNVCL) is a thermoresponsive polymer known to be nontoxic, water soluble and biocompatible. Here, PNVCL homopolymer was successfully synthesized for the first time by use of a one-step vapor-phase process, termed initiated chemical vapor deposition (iCVD). Fourier transform infrared spectroscopy results showed that radical polymerization took place from N-vinylcaprolactam monomers without damaging the functional caprolactam ring. A sharp lower critical solution temperature transition was observed at 31°C from the iCVD poly(N-vinylcaprolactam) (PNVCL) film. The thermoresponsive PNVCL surface exhibited a hydrophilic/hydrophobic alteration with external temperature change, which enabled the thermally modulated attachment and detachment of cells. The conformal coverage of PNVCL film on various substrates with complex topography, including fabrics and nanopatterns, was successfully demonstrated, which can further be utilized to fabricate cell sheets with aligned cell morphology. The advantage of this system is that cells cultured on such thermoresponsive surfaces could be recovered as an intact cell sheet by simply lowering the temperature, eliminating the need for conventional enzymatic treatments.

  18. 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

  19. VEGFA activates an epigenetic pathway upregulating ovarian cancer-initiating cells.

    PubMed

    Jang, Kibeom; Kim, Minsoon; Gilbert, Candace A; Simpkins, Fiona; Ince, Tan A; Slingerland, Joyce M

    2017-03-01

    The angiogenic factor, VEGFA, is a therapeutic target in ovarian cancer (OVCA). VEGFA can also stimulate stem-like cells in certain cancers, but mechanisms thereof are poorly understood. Here, we show that VEGFA mediates stem cell actions in primary human OVCA culture and OVCA lines via VEGFR2-dependent Src activation to upregulate Bmi1, tumor spheres, and ALDH1 activity. The VEGFA-mediated increase in spheres was abrogated by Src inhibition or SRC knockdown. VEGFA stimulated sphere formation only in the ALDH1(+) subpopulation and increased OVCA-initiating cells and tumor formation in vivo through Bmi1. In contrast to its action in hemopoietic malignancies, DNA methyl transferase 3A (DNMT3A) appears to play a pro-oncogenic role in ovarian cancer. VEGFA-driven Src increased DNMT3A leading to miR-128-2 methylation and upregulation of Bmi1 to increase stem-like cells. SRC knockdown was rescued by antagomir to miR-128. DNMT3A knockdown prevented VEGFA-driven miR-128-2 loss, and the increase in Bmi1 and tumor spheres. Analysis of over 1,300 primary human OVCAs revealed an aggressive subset in which high VEGFA is associated with miR-128-2 loss. Thus, VEGFA stimulates OVCA stem-like cells through Src-DNMT3A-driven miR-128-2 methylation and Bmi1 upregulation.

  20. 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

  1. Tumor senescence and radioresistant tumor-initiating cells (TICs): let sleeping dogs lie!

    PubMed

    Zafarana, Gaetano; Bristow, Robert G

    2010-01-01

    Preclinical data from cell lines and experimental tumors support the concept that breast cancer-derived tumor-initiating cells (TICs) are relatively resistant to ionizing radiation and chemotherapy. This could be a major determinant of tumor recurrence following treatment. Increased clonogenic survival is observed in CD24-/low/CD44+ TICs derived from mammosphere cultures and is associated with (a) reduced production of reactive oxygen species, (b) attenuated activation of γH2AX and CHK2-p53 DNA damage signaling pathways, (c) reduced propensity for ionizing radiation-induced apoptosis, and (d) altered DNA double-strand or DNA single-strand break repair. However, recent data have shed further light on TIC radioresistance as irradiated TICs are resistant to tumor cell senescence following DNA damage. Taken together, the cumulative data support a model in which DNA damage signaling and repair pathways are altered in TICs and lead to an altered mode of cell death with unique consequences for long-term clonogen survival. The study of TIC senescence lays the foundation for future experiments in isogenic models designed to directly test the capacity for senescence and local control (that is, not solely local regression) and spontaneous metastases following treatment in vivo. The study also supports the targeting of tumor cell senescence pathways to increase TIC clonogen kill if the targeting also maintains the therapeutic ratio.

  2. Paracrine WNT5A Signaling Inhibits Expansion of Tumor-Initiating Cells.

    PubMed

    Borcherding, Nicholas; Kusner, David; Kolb, Ryan; Xie, Qing; Li, Wei; Yuan, Fang; Velez, Gabriel; Askeland, Ryan; Weigel, Ronald J; Zhang, Weizhou

    2015-05-15

    It is not well understood how paracrine communication between basal and luminal cell populations in the mammary gland affects tumorigenesis. During ErbB2-induced mammary tumorigenesis, enriched mammary stem cells that represent a subpopulation of basal cells exhibit enhanced tumorigenic capacity compared with the corresponding luminal progenitors. Transcript profiling of tumors derived from basal and luminal tumor-initiating cells (TIC) revealed preferential loss of the noncanonical Wnt ligand WNT5A in basal TIC-derived tumors. Heterozygous loss of WNT5A was correlated with shorter survival of breast cancer patients. In a mouse model of ErbB2-induced breast cancer, Wnt5a heterozygosity promoted tumor multiplicity and pulmonary metastasis. As a TGFβ substrate, luminal cell-produced WNT5A induced a feed-forward loop to activate SMAD2 in a RYK and TGFβR1-dependent manner to limit the expansion of basal TIC in a paracrine fashion, a potential explanation for the suppressive effect of WNT5A in mammary tumorigenesis. Our results identify the WNT5A/RYK module as a spatial regulator of the TGFβ-SMAD signaling pathway in the context of mammary gland development and carcinogenesis, offering a new perspective on tumor suppression provided by basal-luminal cross-talk in normal mammary tissue.

  3. Paracrine WNT5A signaling inhibits expansion of tumor-initiating cells

    PubMed Central

    Borcherding, Nicholas; Kusner, David; Kolb, Ryan; Xie, Qing; Li, Wei; Yuan, Fang; Velez, Gabriel; Askeland, Ryan; Weigel, Ronald J.; Zhang, Weizhou

    2015-01-01

    It is not well understood how paracrine communication between basal and luminal cell populations in the mammary gland affects tumorigenesis. During ErbB2-induced mammary tumorigenesis, enriched mammary stem cells that represent a subpopulation of basal cells exhibit enhanced tumorigenic capacity compared to the corresponding luminal progenitors. Transcript profiling of tumors derived from basal and luminal tumor-initiating cells (TIC) revealed preferential loss of the noncanonical Wnt ligand WNT5A in basal TIC-derived tumors. Heterozygous loss of WNT5A was correlated with shorter survival of breast cancer patients. In a mouse model of ErbB2-induced breast cancer, Wnt5a heterozygosity promoted tumor multiplicity and pulmonary metastasis. As a TGFβ substrate, luminal cell-produced WNT5A induced a feed-forward loop to activate SMAD2 in a RYK and TGFβR1-dependent manner to limit the expansion of basal TIC in a paracrine fashion, a potential explanation for the suppressive effect of WNT5A in mammary tumorigenesis. Our results identify the WNT5A/RYK module as a spatial regulator of TGFβ/SMAD signaling pathway in the context of mammary gland development and carcinogenesis, offering a new perspective on tumor suppression provided by basal-luminal crosstalk in normal mammary tissue. PMID:25769722

  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. 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

  6. Modeling Meteor Flares for Spacecraft Safety

    NASA Technical Reports Server (NTRS)

    Ehlert, Steven

    2017-01-01

    NASA's Meteoroid Environment Office (MEO) is tasked with assisting spacecraft operators and engineers in quantifying the threat the meteoroid environment poses to their individual missions. A more complete understanding of the meteoroid environment for this application requires extensive observations. One manner by which the MEO observes meteors is with dedicated video camera systems that operate nightly. Connecting the observational data from these video cameras to the relevant physical properties of the ablating meteoroids, however, is subject to sizable observational and theoretical uncertainties. Arguably the most troublesome theoretical uncertainty in ablation is a model for the structure of meteoroids, as observations clearly show behaviors wholly inconsistent with meteoroids being homogeneous spheres. Further complicating the interpretation of the observations in the context of spacecraft risk is the ubiquitous process of fragmentation and the flares it can produce, which greatly muddles any attempts to estimating initial meteoroid masses. In this talk a method of estimating the mass distribution of fragments in flaring meteors using high resolution video observations will be dis- cussed. Such measurements provide an important step in better understanding of the structure and fragmentation process of the parent meteoroids producing these flares, which in turn may lead to better constraints on meteoroid masses and reduced uncertainties in spacecraft risk.

  7. 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

  8. 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.

  9. Immunodominant fragments of myelin basic protein initiate T cell-dependent pain

    PubMed Central

    2012-01-01

    Background The myelin sheath provides electrical insulation of mechanosensory Aβ-afferent fibers. Myelin-degrading matrix metalloproteinases (MMPs) damage the myelin sheath. The resulting electrical instability of Aβ-fibers is believed to activate the nociceptive circuitry in Aβ-fibers and initiate pain from innocuous tactile stimulation (mechanical allodynia). The precise molecular mechanisms, responsible for the development of this neuropathic pain state after nerve injury (for example, chronic constriction injury, CCI), are not well understood. Methods and results Using mass spectrometry of the whole sciatic nerve proteome followed by bioinformatics analyses, we determined that the pathways, which are classified as the Infectious Disease and T-helper cell signaling, are readily activated in the nerves post-CCI. Inhibition of MMP-9/MMP-2 suppressed CCI-induced mechanical allodynia and concomitant TNF-α and IL-17A expression in nerves. MMP-9 proteolysis of myelin basic protein (MBP) generated the MBP84-104 and MBP68-86 digest peptides, which are prominent immunogenic epitopes. In agreement, the endogenous MBP69-86 epitope co-localized with MHCII and MMP-9 in Schwann cells and along the nodes of Ranvier. Administration of either the MBP84-104 or MBP68-86 peptides into the naïve nerve rapidly produced robust mechanical allodynia with a concomitant increase in T cells and MHCII-reactive cell populations at the injection site. As shown by the genome-wide expression profiling, a single intraneural MBP84-104 injection stimulated the inflammatory, immune cell trafficking, and antigen presentation pathways in the injected naïve nerves and the associated spinal cords. Both MBP84-104-induced mechanical allodynia and characteristic pathway activation were remarkably less prominent in the T cell-deficient athymic nude rats. Conclusions These data implicate MBP as a novel mediator of pain. Furthermore, the action of MMPs expressed within 1 day post-injury is critical

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

    PubMed Central

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

    2016-01-01

    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. Significance In most clinical trials using adipose-derived stem cells (ASCs), the cells have been expanded in culture media supplemented with fetal calf serum. However, there is much interest in replacing fetal calf serum with human platelet lysate or using completely serum- and xenogeneic

  11. 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).

  12. 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.

  13. 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.

  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. STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity.

    PubMed

    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

    2015-12-15

    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.

  16. 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

  17. 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

  18. 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.

  19. Neuronal Transcriptional Repressor REST Suppresses an Atoh7-Independent Program for Initiating Retinal Ganglion Cell Development

    PubMed Central

    Mao, Chai-An; Tsai, Wen-Wei; Cho, Jang-Hyeon; Pan, Ping; Barton, Michelle Craig; Klein, William H.

    2010-01-01

    As neuronal progenitors differentiate into neurons, they acquire a unique set of transcription factors. The transcriptional repressor REST prevents progenitors from undergoing differentiation. Notably, REST binding sites are often associated with retinal ganglion cell (RGC) genes whose expression in the retina is positively controlled by Atoh7, a factor essential for RGC formation. The key regulators that enable a retinal progenitor cell (RPC) to commit to an RGC fate have not been identified. We show here that REST suppresses RGC gene expression in RPCs. REST inactivation causes aberrant expression of RGC transcription factors in proliferating RPCs, independent of Atoh7, resulting in increased RGC formation. Strikingly, inactivating REST in Atoh7-null retinas restores transcription factor expression, which partially activates downstream RGC genes but is insufficient to prevent RGC loss. Our results demonstrate an Atoh7-independent program for initial activation of RGC genes and suggest a novel role for REST in preventing premature expression in RPCs. PMID:20969844

  20. AMPK protects leukemia-initiating cells in myeloid leukemias from metabolic stress in the bone marrow

    PubMed Central

    Saito, Yusuke; Chapple, Richard H.; Lin, Angelique; Kitano, Ayumi; Nakada, Daisuke

    2015-01-01

    SUMMARY How cancer cells adapt to metabolically adverse conditions in patients and strive to proliferate is a fundamental question in cancer biology. Here we show that AMP-activated protein kinase (AMPK), a metabolic checkpoint kinase, confers metabolic stress resistance to leukemia-initiating cells (LICs) and promotes leukemogenesis. Upon dietary restriction, MLL-AF9-induced murine AML activated AMPK and maintained leukemogenic potential. AMPK deletion significantly delayed leukemogenesis and depleted LICs by reducing the expression of glucose transporter 1 (Glut1), compromising glucose flux, and increasing oxidative stress and DNA damage. LICs were particularly dependent on AMPK to suppress oxidative stress in the hypoglycemic bone marrow environment. Strikingly, AMPK inhibition synergized with physiological metabolic stress caused by dietary restriction and profoundly suppressed leukemogenesis. Our results indicate that AMPK protects LICs from metabolic stress, and that combining AMPK inhibition with physiological metabolic stress potently suppresses AML by inducing oxidative stress and DNA damage. PMID:26440282

  1. 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.

  2. 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.

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. Spacecraft attitude dynamics and control

    NASA Astrophysics Data System (ADS)

    Chobotov, Vladimir A.

    This overview of spacecraft dynamics encompasses the fundamentals of kinematics, rigid-body dynamics, linear control theory, orbital environmental effects, and the stability of motion. The theoretical treatment of each issue is complemented by specific references to spacecraft control systems based on spin, dual-spin, three-axis-active, and reaction-wheel methodologies. Also examined are control-moment-gyro, gravity-gradient, and magnetic control systems with attention given to key issues such as nutation damping, separation dynamics of spinning bodies, and tethers. Environmental effects that impinge on the application of spacecraft-attitude dynamics are shown to be important, and consideration is given to gravitation, solar radiation, aerodynamics, and geomagnetics. The publication gives analytical methods for examining the practical implementation of the control techniques as they apply to spacecraft.

  8. Treating brain tumor–initiating cells using a combination of myxoma virus and rapamycin

    PubMed Central

    Zemp, Franz J.; Lun, Xueqing; McKenzie, Brienne A.; Zhou, Hongyuan; Maxwell, Lori; Sun, Beichen; Kelly, John J.P.; Stechishin, Owen; Luchman, Artee; Weiss, Samuel; Cairncross, J. Gregory; Hamilton, Mark G.; Rabinovich, Brian A.; Rahman, Masmudur M.; Mohamed, Mohamed R.; Smallwood, Sherin; Senger, Donna L.; Bell, John; McFadden, Grant; Forsyth, Peter A.

    2013-01-01

    Background Intratumoral heterogeneity in glioblastoma multiforme (GBM) poses a significant barrier to therapy in certain subpopulation such as the tumor-initiating cell population, being shown to be refractory to conventional therapies. Oncolytic virotherapy has the potential to target multiple compartments within the tumor and thus circumvent some of the barriers facing conventional therapies. In this study, we investigate the oncolytic potential of myxoma virus (MYXV) alone and in combination with rapamycin in vitro and in vivo using human brain tumor–initiating cells (BTICs). Methods We cultured fresh GBM specimens as neurospheres and assayed their growth characteristics in vivo. We then tested the susceptibility of BTICs to MYXV infection with or without rapamycin in vitro and assessed viral biodistribution/survival in vivo in orthotopic xenografts. Results The cultured neurospheres were found to retain stem cell markers in vivo, and they closely resembled human infiltrative GBM. In this study we determined that (i) all patient-derived BTICs tested, including those resistant to temozolomide, were susceptible to MYXV replication and killing in vitro; (ii) MYXV replicated within BTICs in vivo, and intratumoral administration of MYXV significantly prolonged survival of BTIC-bearing mice; (iii) combination therapy with MYXV and rapamycin improved antitumor activity, even in mice bearing “advanced” BTIC tumors; (iv) MYXV treatment decreased expression of stem cell markers in vitro and in vivo. Conclusions Our study suggests that MYXV in combination with rapamycin infects and kills both the BTICs and the differentiated compartments of GBM and may be an effective treatment even in TMZ-resistant patients. PMID:23585629

  9. Space Weathering Experiments on Spacecraft Materials

    NASA Technical Reports Server (NTRS)

    Cooper, R.; Cowardin, H.; Engelhar, D.; Plis, Elena; Hoffman, R.

    2017-01-01

    A project to investigate space environment effects on specific materials with interest to remote sensing was initiated in 2016. The goal of the project is to better characterize changes in the optical properties of polymers and Mylar, specifically those found in multi-layered spacecraft insulation, due to electron bombardment. Previous analysis shows that chemical bonds break and potentially reform when exposed to high energy electrons. Among other properties these chemical changes altered the optical reflectance as documented in laboratory analysis. This paper presents results of the initial experiment results focused on the exposure of materials to various fluences of high energy electrons, used to simulate a portion of the geosynchronous space environment. The paper illustrates how the spectral reflectance changes as a function of time on orbit with respect to GEO environmental factors and investigates the survivability of the material after multiple electron doses. These results provide a baseline for analysis of aging effects on satellite systems used for remote sensing. They also provide preliminary analysis on what materials are most likely to encompass the high area-to-mass population of space debris in the geosynchronous environment. Lastly, the paper provides the results of the initial experimentation as a proof of concept for space aging on polymers and Mylar for conducting more experiments with a larger subset of spacecraft materials.

  10. Plasma Interactions With Spacecraft (I)

    DTIC Science & Technology

    2009-04-01

    various plasma engineering concerns including surface discharges due to meteoroid impact and spacecraft contamination due to electric propulsion plasma...discharges due to meteoroid impact and spacecraft contamination due to electric propulsion plasma plume effects. The goal of this effort is to...Enhanced Radiation Belts in Lake Arrowhead, California on March 3-6, 2008. Dr. Mandell also attended the DSX System CDR, Breckenridge, Colorado, May 6-8

  11. 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.

  12. Recent Advances in Spacecraft Charging

    DTIC Science & Technology

    1994-03-08

    divergence. The with partial successes [Cohen, etal., 1981; Cohen and transverse energy gained by a diverging beam Lai, 1982; Olsen , 1985; Werner, 1988]. When...probes, J AppL Phys., Technology Conference, R.C. Olsen (ed), Naval 63, 5674-5677, 1988. Postgraduate School, Mornterey, 1989. Neubert, T., MJ...Dec., 1993. Olsen , R.C., Modification of spacecraft potentials by Wang, J. and D.E_ Hastings, Ionospheric plasma flow plasma emission, J. Spacecraft

  13. 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.

  14. 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.

  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.

  16. Endothelin A receptor activation on mesangial cells initiates Alport glomerular disease.

    PubMed

    Dufek, Brianna; Meehan, Daniel T; Delimont, Duane; Cheung, Linda; Gratton, Michael Anne; Phillips, Grady; Song, Wenping; Liu, Shiguang; Cosgrove, Dominic

    2016-08-01

    Recent work demonstrates that Alport glomerular disease is mediated through a biomechanical strain-sensitive activation of mesangial actin dynamics. This occurs through a Rac1/CDC42 cross-talk mechanism that results in the invasion of the subcapillary spaces by mesangial filopodia. The filopodia deposit mesangial matrix proteins in the glomerular basement membrane, including laminin 211, which activates focal adhesion kinase in podocytes culminating in the up-regulation of proinflammatory cytokines and metalloproteinases. These events drive the progression of glomerulonephritis. Here we test whether endothelial cell-derived endothelin-1 is up-regulated in Alport glomeruli and further elevated by hypertension. Treatment of cultured mesangial cells with endothelin-1 activates the formation of drebrin-positive actin microspikes. These microspikes do not form when cells are treated with the endothelin A receptor antagonist sitaxentan or under conditions of small, interfering RNA knockdown of endothelin A receptor mRNA. Treatment of Alport mice with sitaxentan results in delayed onset of proteinuria, normalized glomerular basement membrane morphology, inhibition of mesangial filopodial invasion of the glomerular capillaries, normalization of glomerular expression of metalloproteinases and proinflammatory cytokines, increased life span, and prevention of glomerulosclerosis and interstitial fibrosis. Thus endothelin A receptor activation on mesangial cells is a key event in initiation of Alport glomerular disease in this model.

  17. RBPJ maintains brain tumor–initiating cells through CDK9-mediated transcriptional elongation

    PubMed Central

    Xie, Qi; Wu, Qiulian; Kim, Leo; Miller, Tyler E.; Liau, Brian B.; Mack, Stephen C.; Yang, Kailin; Factor, Daniel C.; Fang, Xiaoguang; Huang, Zhi; Zhou, Wenchao; Alazem, Kareem; Wang, Xiuxing; Bernstein, Bradley E.; Bao, Shideng; Rich, Jeremy N.

    2016-01-01

    Glioblastomas co-opt stem cell regulatory pathways to maintain brain tumor–initiating cells (BTICs), also known as cancer stem cells. NOTCH signaling has been a molecular target in BTICs, but NOTCH antagonists have demonstrated limited efficacy in clinical trials. Recombining binding protein suppressor of hairless (RBPJ) is considered a central transcriptional mediator of NOTCH activity. Here, we report that pharmacologic NOTCH inhibitors were less effective than targeting RBPJ in suppressing tumor growth. While NOTCH inhibitors decreased canonical NOTCH gene expression, RBPJ regulated a distinct profile of genes critical to BTIC stemness and cell cycle progression. RBPJ was preferentially expressed by BTICs and required for BTIC self-renewal and tumor growth. MYC, a key BTIC regulator, bound the RBPJ promoter and treatment with a bromodomain and extraterminal domain (BET) family bromodomain inhibitor decreased MYC and RBPJ expression. Proteomic studies demonstrated that RBPJ binds CDK9, a component of positive transcription elongation factor b (P-TEFb), to target gene promoters, enhancing transcriptional elongation. Collectively, RBPJ links MYC and transcriptional control through CDK9, providing potential nodes of fragility for therapeutic intervention, potentially distinct from NOTCH. PMID:27322055

  18. RBPJ maintains brain tumor-initiating cells through CDK9-mediated transcriptional elongation.

    PubMed

    Xie, Qi; Wu, Qiulian; Kim, Leo; Miller, Tyler E; Liau, Brian B; Mack, Stephen C; Yang, Kailin; Factor, Daniel C; Fang, Xiaoguang; Huang, Zhi; Zhou, Wenchao; Alazem, Kareem; Wang, Xiuxing; Bernstein, Bradley E; Bao, Shideng; Rich, Jeremy N

    2016-07-01

    Glioblastomas co-opt stem cell regulatory pathways to maintain brain tumor-initiating cells (BTICs), also known as cancer stem cells. NOTCH signaling has been a molecular target in BTICs, but NOTCH antagonists have demonstrated limited efficacy in clinical trials. Recombining binding protein suppressor of hairless (RBPJ) is considered a central transcriptional mediator of NOTCH activity. Here, we report that pharmacologic NOTCH inhibitors were less effective than targeting RBPJ in suppressing tumor growth. While NOTCH inhibitors decreased canonical NOTCH gene expression, RBPJ regulated a distinct profile of genes critical to BTIC stemness and cell cycle progression. RBPJ was preferentially expressed by BTICs and required for BTIC self-renewal and tumor growth. MYC, a key BTIC regulator, bound the RBPJ promoter and treatment with a bromodomain and extraterminal domain (BET) family bromodomain inhibitor decreased MYC and RBPJ expression. Proteomic studies demonstrated that RBPJ binds CDK9, a component of positive transcription elongation factor b (P-TEFb), to target gene promoters, enhancing transcriptional elongation. Collectively, RBPJ links MYC and transcriptional control through CDK9, providing potential nodes of fragility for therapeutic intervention, potentially distinct from NOTCH.

  19. Neutrophils support lung colonization of metastasis-initiating breast cancer cells

    PubMed Central

    Wculek, Stefanie K.; Malanchi, Ilaria

    2015-01-01

    Despite progress in the development of drugs efficiently targeting cancer cells, treatments of metastatic tumours are often ineffective. The now well established dependency of cancer cells on their microenvironment1 suggests that targeting the non-cancer cell component of the tumour might form the basis for the development of novel therapeutic approaches. However, the as yet poorly characterised 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 tumourigenesis is still controversial2-4. 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 tissue by selectively expanding the sub-pool of cancer cells that retain high tumorigenic potential. Genetic or pharmacologic 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

  20. 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.

  1. The role of neutrophils and monocytic cells in controlling the initiation of Clostridium perfringens gas gangrene.

    PubMed

    O'Brien, David K; Therit, Blair H; Woodman, Michael E; Melville, Stephen B

    2007-06-01

    Clostridium perfringens is a common cause of the fatal disease gas gangrene (myonecrosis). Established gas gangrene is notable for a profound absence of neutrophils and monocytic cells (phagocytes), and it has been suggested that the bactericidal activities of these cells play an insignificant role in controlling the progression of the infection. However, large inocula of bacteria are needed to establish an infection in experimental animals, suggesting phagocytes may play a role in inhibiting the initiation of gangrene. Examination of tissue sections of mice infected with a lethal (1 x 10(9)) or sublethal (1 x 10(6)) inoculum of C. perfringens revealed that phagocyte infiltration in the first 3 h postinfection was inhibited with a lethal dose but not with a sublethal dose, indicating that exclusion of phagocytes begins very early in the infection cycle. Experiments in which mice were depleted of either circulating monocytes or neutrophils before infection with C. perfringens showed that monocytes play a role in inhibiting the onset of gas gangrene at intermediate inocula but, although neutrophils can slow the onset of the infection, they are not protective. These results suggest that treatments designed to increase monocyte infiltration and activate macrophages may lead to increased resistance to the initiation of gas gangrene.

  2. Targeting pancreatitis blocks tumor-initiating stem cells and pancreatic cancer progression

    PubMed Central

    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.

    2015-01-01

    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

  3. 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

  4. 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

  5. Clinical grade isolation of regulatory T cells from G-CSF mobilized peripheral blood improves with initial depletion of monocytes.

    PubMed

    Patel, Pritesh; Mahmud, Dolores; Park, Youngmin; Yoshinaga, Kazumi; Mahmud, Nadim; Rondelli, Damiano

    2015-01-01

    Clinical isolation of circulating CD4(+)CD25(+) regulatory T cells (Tregs) from peripheral blood mononuclear cells is usually performed by CD4(+) cell negative selection followed by CD25(+) cell positive selection. Although G-CSF mobilized peripheral blood (G-PBSC) contains a high number of Tregs, a high number of monocytes in G-PBSC limits Treg isolation. Using a small scale device (MidiMACS, Miltenyi) we initially demonstrated that an initial depletion of monocytes would be necessary to obtaina separation of CD4(+)CD25(+)FoxP3(+)CD127(-) cells from G-PBSC (G-Tregs) with a consistent purity >70% and inhibitory activity of T cell alloreactivity in-vitro. We then validated the same approach in a clinical scale setting by separating G-Tregs with clinically available antibodies to perform a CD8(+)CD19(+)CD14(+) cell depletion followed by CD25(+) cell selection (2-step process) or by adding an initial CD14(+) cell depletion (3-step process) using a CliniMACS column. The 3-step approach resulted in a better purity (81±12% vs. 35±33%) and yield (66% vs. 39%). Clinically isolated G-Tregs were also FoxP3(+)CD127(dim) and functionally suppressive in-vitro. Our findings suggest that a better and more consistent purity of Tregs can be achieved from G-PBSC by an initial single depletion of monocytes prior to selection of CD4(+)CD25(+) cells.

  6. Clinical grade isolation of regulatory T cells from G-CSF mobilized peripheral blood improves with initial depletion of monocytes

    PubMed Central

    Patel, Pritesh; Mahmud, Dolores; Park, Youngmin; Yoshinaga, Kazumi; Mahmud, Nadim; Rondelli, Damiano

    2015-01-01

    Clinical isolation of circulating CD4+CD25+ regulatory T cells (Tregs) from peripheral blood mononuclear cells is usually performed by CD4+ cell negative selection followed by CD25+ cell positive selection. Although G-CSF mobilized peripheral blood (G-PBSC) contains a high number of Tregs, a high number of monocytes in G-PBSC limits Treg isolation. Using a small scale device (MidiMACS, Miltenyi) we initially demonstrated that an initial depletion of monocytes would be necessary to obtaina separation of CD4+CD25+FoxP3+CD127- cells from G-PBSC (G-Tregs) with a consistent purity >70% and inhibitory activity of T cell alloreactivity in-vitro. We then validated the same approach in a clinical scale setting by separating G-Tregs with clinically available antibodies to perform a CD8+CD19+CD14+ cell depletion followed by CD25+ cell selection (2-step process) or by adding an initial CD14+ cell depletion (3-step process) using a CliniMACS column. The 3-step approach resulted in a better purity (81±12% vs. 35±33%) and yield (66% vs. 39%). Clinically isolated G-Tregs were also FoxP3+CD127dim and functionally suppressive in-vitro. Our findings suggest that a better and more consistent purity of Tregs can be achieved from G-PBSC by an initial single depletion of monocytes prior to selection of CD4+CD25+ cells. PMID:27069755

  7. P02.07INTERFERON-β MODULATES THE INNATE IMMUNE RESPONSE AGAINST GLIOBLASTOMA INITIATING CELLS

    PubMed Central

    Wolpert, F.; Happold, C.; Roth, P.; Reifenberger, G.; Weller, M.; Eisele, G.

    2014-01-01

    The prognosis of glioblastoma remains dismal. Immunotherapy is a promising approach with the need of well-defined targets and potent adjuvants. Glioma-initiating cells (GIC) with stem cell properties are such an attractive target for immunotherapy. However, the immunogenicity of GIC seems limited. Interferon (IFN)-β exerts immune-activating effects like enhanced antigen processing, up-regulation of co-stimulatory molecules and enhanced natural killer (NK) cell activity and thus might enhance an immune response against GIC. Moreover, IFN-β exerts direct anti-GIC cell activities. Thus, IFN-β warrants being further evaluated as an adjuvant for anti-glioblastoma immunotherapies. Here we define the net effect of IFN-β treatment on the innate immunogenicity of GIC. Employing Affymetrix-based transcriptomic profiling, we identified alterations in the expression of several immune regulatory genes in a panel of well-defined GIC lines upon treatment with IFN-β. The up-regulation of immunosuppressive human leukocyte antigen (HLA)-E was contrasted by enhanced surface levels of immune activating nectin-2 while the level of NKG2D ligands remained largely unaltered. In NK cell lysis assays, the immunogenicity of 2 of 3 GIC lines was increased upon IFN-β treatment and further enhanced upon gene silencing of HLA-E using RNA interference. Our data indicate that treatment with IFN-β alters the innate immunogenicity of GIC by increased expression of nectin-2, reverted in part by the concurrent upregulation of HLA-E.

  8. Breast tumour initiating cell fate is regulated by microenvironmental cues from an extracellular matrix.

    PubMed

    Saha, Sharmistha; Lo, Pang-Kuo; Duan, Xinrui; Chen, Hexin; Wang, Qian

    2012-08-01

    Cancer stem cells, also known as tumour-initiating cells (TICs), are identified as highly tumorigenic population within tumours and hypothesized to be main regulators in tumour growth, metastasis and relapse. Evidence also suggests that a tumour microenvironment plays a critical role in the development and progression of cancer, by constantly modulating cell-matrix interactions. Scientists have tried to characterize and identify the TIC population but the actual combination of extracellular components in deciphering the fate of TICs has not been explored. The basic unanswered question is the phenotypic stability of this TIC population in a tissue extracellular matrix setting. The in vivo complexity makes it difficult to identify parameters in a diverse milieu that affect TICs behaviour. Herein we studied how the TIC population would respond when subjected to a unique microenvironment composed of different extracellular proteins. The TIC-enriched population isolated from a Her2/neu-induced mouse mammary tumour was cultured on collagen, fibronectin and laminin coated substrates for one to two weeks. Our observations indicate that a laminin substrate can maintain the majority of the self-renewing and tumorigenic TIC population, whereas collagen induced a more differentiated phenotype of the cells. Also interestingly, fibronectin substrates dictated an invasive phenotype of TICs as evidenced from the EMT-related gene expression pattern. The results of this study signify that the microenvironmental cues play a considerable role in tumour relapse and progression by altering the cancer stem cell behaviour and thus this knowledge could be used to design novel cancer therapeutics.

  9. 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

  10. 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.

  11. Spacecraft Robustness to Orbital Debris: Guidelines & Recommendations

    NASA Astrophysics Data System (ADS)

    Heinrich, S.; Legloire, D.; Tromba, A.; Tholot, M.; Nold, O.

    2013-09-01

    The ever increasing number of orbital debris has already led the space community to implement guidelines and requirements for "cleaner" and "safer" space operations as non-debris generating missions and end of mission disposal in order to get preserved orbits rid of space junks. It is nowadays well-known that man-made orbital debris impacts are now a higher threat than natural micro-meteoroids and that recent events intentionally or accidentally generated so many new debris that may initiate a cascade chain effect known as "the Kessler Syndrome" potentially jeopardizing the useful orbits.The main recommendations on satellite design is to demonstrate an acceptable Probability of Non-Penetration (PNP) with regard to small population (<5cm) of MMOD (Micro-Meteoroids and Orbital Debris). Compliance implies to think about spacecraft robustness as redundancies, segregations and shielding devices (as implemented in crewed missions but in a more complex mass - cost - criticality trade- off). Consequently the need is non-only to demonstrate the PNP compliance requirement but also the PNF (probability of Non-Failure) per impact location on all parts of the vehicle and investigate the probabilities for the different fatal scenarios: loss of mission, loss of spacecraft (space environment critical) and spacecraft fragmentation (space environment catastrophic).The recent THALES experience known on ESA Sentinel-3, of increasing need of robustness has led the ALTRAN company to initiate an internal innovative working group on those topics which conclusions may be attractive for their prime manufacturer customers.The intention of this paper is to present a status of this study : * Regulations, requirements and tools available * Detailed FMECA studies dedicated specifically to the MMOD risks with the introduction of new of probability and criticality classification scales. * Examples of design risks assessment with regard to the specific MMOD impact risks. * Lessons learnt on

  12. Monocytes initiate a cycle of leukocyte recruitment when cocultured with endothelial cells.

    PubMed

    Tsouknos, Andreas; Nash, Gerard B; Rainger, G Ed

    2003-09-01

    During the development of atherosclerotic plaque, monocytes and T-lymphocytes are recruited to the arterial intima by endothelial cells (EC) lining the vessel. This process is associated with chronic arterial inflammation and requires the activation-dependent expression of adhesion receptors and chemokines on EC. Here we show that monocytes can activate cocultured EC so that they support the adhesion, activation and transmigration of a secondary bolus of flowing peripheral blood monocytes or lymphocytes. The number of adherent leukocytes and their behaviour was comparable to that seen on EC activated with tumour necrosis factor-alpha (TNF-alpha). Depending upon the duration of endothelial cell/monocyte coculture different patterns of adhesion receptors were utilised by leukocytes. After 4 h coculture, antibodies against E-selectin, P-selectin and vascular cell adhesion molecule-1 (VCAM-1) reduced mononuclear leukocyte adhesion. After 24 h coculture, antibodies against E-selectin and VCAM-1 but not P-selectin were effective. Immunofluorescence analysis confirmed that monocyte coculture induced endothelial expression of E-selectin and VCAM-1, while P-selectin was at the limit of detection. We conclude that EC stimulated by monocytes can support the adhesion of flowing mononuclear leukocytes. We hypothesise that this mode of EC activation and leukocyte recruitment could initiate a self-perpetuating cycle of inflammation that could be relevant to atherogenesis and other chronic inflammatory disease states.

  13. Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation.

    PubMed

    Nasr, Rihab; Guillemin, Marie-Claude; Ferhi, Omar; Soilihi, Hassan; Peres, Laurent; Berthier, Caroline; Rousselot, Philippe; Robledo-Sarmiento, Macarena; Lallemand-Breitenbach, Valérie; Gourmel, Bernard; Vitoux, Dominique; Pandolfi, Pier Paolo; Rochette-Egly, Cécile; Zhu, Jun; de Thé, Hugues

    2008-12-01

    Retinoic acid and arsenic trioxide target the protein stability and transcriptional repression activity of the fusion oncoprotein PML-RARA, resulting in regression of acute promyelocytic leukemia (APL). Phenotypically, retinoic acid induces differentiation of APL cells. Here we show that retinoic acid also triggers growth arrest of leukemia-initiating cells (LICs) ex vivo and their clearance in PML-RARA mouse APL in vivo. Retinoic acid treatment of mouse APLs expressing the fusion protein PLZF-RARA triggers full differentiation, but not LIC loss or disease remission, establishing that differentiation and LIC loss can be uncoupled. Although retinoic acid and arsenic synergize to clear LICs through cooperative PML-RARA degradation, this combination does not enhance differentiation. A cyclic AMP (cAMP)-dependent phosphorylation site in PML-RARA is crucial for retinoic acid-induced PML-RARA degradation and LIC clearance. Moreover, activation of cAMP signaling enhances LIC loss by retinoic acid, identifying cAMP as another potential APL therapy. Thus, whereas transcriptional activation of PML-RARA is likely to control differentiation, its catabolism triggers LIC eradication and long-term remission of mouse APL. Therapy-triggered degradation of oncoproteins could be a general strategy to eradicate cancer stem cells.

  14. Interferon-β Modulates the Innate Immune Response against Glioblastoma Initiating Cells

    PubMed Central

    Wolpert, Fabian; Happold, Caroline; Reifenberger, Guido; Florea, Ana-Maria; Deenen, René; Roth, Patrick; Neidert, Marian Christoph; Lamszus, Katrin; Westphal, Manfred; Weller, Michael; Eisele, Günter

    2015-01-01

    Immunotherapy targeting glioblastoma initiating cells (GIC) is considered a promising strategy. However, GIC are prone to evade immune response and there is a need for potent adjuvants. IFN-β might enhance the immune response and here we define its net effect on the innate immunogenicity of GIC. The transcriptomes of GIC treated with IFN-β and controls were assessed by microarray-based expression profiling for altered expression of immune regulatory genes. Several genes involved in adaptive and innate immune responses were regulated by IFN-β. We validated these results using reverse transcription (RT)-PCR and flow cytometry for corresponding protein levels. The up-regulation of the NK cell inhibitory molecules HLA-E and MHC class I was balanced by immune stimulating effects including the up-regulation of nectin-2. In 3 out of 5 GIC lines tested we found a net immune stimulating effect of IFN-β in cytotoxicity assays using NKL cells as effectors. IFN-β therefore warrants further investigation as an adjuvant for immunotherapy targeting GIC. PMID:26441059

  15. Spatial and temporal action of chicken primordial germ cells during initial migration.

    PubMed

    Kang, Kyung Soo; Lee, Hyung Chul; Kim, Hyun Jeong; Lee, Hyo Gun; Kim, Young Min; Lee, Hong Jo; Park, Young Hyun; Yang, Seo Yeong; Rengaraj, Deivendran; Park, Tae Sub; Han, Jae Yong

    2015-02-01

    In most animals, primordial germ cells (PGCs) originate from an extragonadal region and migrate across the embryo to the gonads, where they differentiate and function. During their migration, PGCs move passively by morphogenetic movement of the embryo or move actively through signaling molecules. To uncover the underlying mechanism of first-phase PGC migration toward the germinal crescent in chickens, we investigated the spatial and temporal action of PGCs during primitive streak formation. Exogenously transplanted PGCs migrated toward the anterior region of the embryo and the embryonic gonads when they were transplanted into the subgerminal cavity, but not into the posterior marginal zone, in Eyal-Giladi and Kochav stage X embryos. These results indicate that for passive migration toward the anterior region the initial location of PGCs should be the central region. Notably, although PGCs and DF-1 cells migrated passively toward the anterior region, only PGCs migrated to the germinal crescent, where endogenous PGCs mainly reside, by active movement. In a live-imaging experiment with green fluorescence protein-expressing transgenic embryos, exogenous PGCs demonstrated markedly faster migration when they reached the anterior one-third of the embryo, while somatic cells showed epiblast movement with constant speed. Also, migrating PGCs exhibited successive contraction and expansion indicating their active migration. Our results suggest that chicken PGCs use sequential passive and active forces to migrate toward the germinal crescent.

  16. Interferon-β Modulates the Innate Immune Response against Glioblastoma Initiating Cells.

    PubMed

    Wolpert, Fabian; Happold, Caroline; Reifenberger, Guido; Florea, Ana-Maria; Deenen, René; Roth, Patrick; Neidert, Marian Christoph; Lamszus, Katrin; Westphal, Manfred; Weller, Michael; Eisele, Günter

    2015-01-01

    Immunotherapy targeting glioblastoma initiating cells (GIC) is considered a promising strategy. However, GIC are prone to evade immune response and there is a need for potent adjuvants. IFN-β might enhance the immune response and here we define its net effect on the innate immunogenicity of GIC. The transcriptomes of GIC treated with IFN-β and controls were assessed by microarray-based expression profiling for altered expression of immune regulatory genes. Several genes involved in adaptive and innate immune responses were regulated by IFN-β. We validated these results using reverse transcription (RT)-PCR and flow cytometry for corresponding protein levels. The up-regulation of the NK cell inhibitory molecules HLA-E and MHC class I was balanced by immune stimulating effects including the up-regulation of nectin-2. In 3 out of 5 GIC lines tested we found a net immune stimulating effect of IFN-β in cytotoxicity assays using NKL cells as effectors. IFN-β therefore warrants further investigation as an adjuvant for immunotherapy targeting GIC.

  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. 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.

  20. Myd88 Initiates Early Innate Immune Responses and Promotes CD4 T Cells during Coronavirus Encephalomyelitis

    PubMed Central

    Butchi, Niranjan; Kapil, Parul; Puntambekar, Shweta; Stohlman, Stephen A.; Hinton, David R.

    2015-01-01

    factors, adaptive immunity, and pathology is pathogen dependent. These results reveal that Myd88 protects from lethal neurotropic coronavirus-induced encephalomyelitis by accelerating but not enhancing the induction of IFN-α/β, as well as by promoting peripheral activation and CNS accumulation of virus-specific CD4 T cells secreting IFN-γ. By controlling both early innate immune responses and CD4 T cell-mediated antiviral IFN-γ, Myd88 signaling limits the initial viral dissemination and is vital for T cell-mediated control of viral loads. Uncontrolled viral replication in the absence of Myd88 leads to severe demyelination and pathology despite overall reduced inflammatory responses. These data support a vital role of Myd88 signaling in protective antimicrobial functions in the CNS by promoting proinflammatory mediators and T cell-mediated IFN-γ production. PMID:26136579

  1. Minimum dV for Targeted Spacecraft Disposal

    NASA Technical Reports Server (NTRS)

    Bacon, John

    2017-01-01

    The density scale height of the Earth's atmosphere undergoes significant reduction in the final phases of a natural decay. It can be shown that for most realistic ballistic numbers, it is possible to exploit this effect to amplify available spacecraft dV by using it at the penultimate perigee to penetrate into higher drag regions at final apogee. The drag at this lower pass can more effectively propel a spacecraft towards the final target region than applying the same dV direct Hohmann transfer at that final apogee. This study analyzes the potential use of this effect-- in combination with small phasing burns--to calculate the absolute minimum delta-V that would be required to reliably guide a spacecraft to any specified safe unoccupied ocean region as a function of ballistic number, orbit inclination, and initial eccentricity. This calculation is made for controllable spacecraft in several orbit inclinations and eccentricities with arbitrary initial LAN and ArgP one week before final entry, under three-sigma atmospheric perturbations. The study analyzes the dV required under varying levels of final controllable altitude at which dV may be imparted, and various definitions of the length and location of a "safe" disposal area. The goal of such research is to improve public safety by creating assured safe disposal strategies for low-dV and/or low-thrust spacecraft that under more traditional strategies would need to be abandoned to a fully random decay.

  2. Cancer initiating-cells are enriched in the CA9 positive fraction of primary cervix cancer xenografts

    PubMed Central

    Marie-Egyptienne, Delphine Tamara; Chaudary, Naz; Kalliomäki, Tuula; Hedley, David William; Hill, Richard Peter

    2017-01-01

    Numerous studies have suggested that Cancer Initiating Cells (CIC) can be identified/enriched in cell populations obtained from solid tumors based on the expression of cell surface marker proteins. We used early passage primary cervix cancer xenografts to sort cells based on the expression of the intrinsic hypoxia marker Carbonic Anhydrase 9 (CA9) and tested their cancer initiation potential by limiting dilution assay. We demonstrated that CICs are significantly enriched in the CA9+ fraction in 5/6 models studied. Analyses of the expression of the stem cell markers Oct4, Notch1, Sca-1 & Bmi1 showed a trend toward an increase in the CA9+ populations, albeit not significant. We present evidence that enhanced autophagy does not play a role in the enhanced growth of the CA9+ cells. Our study suggests a direct in vivo functional link between hypoxic cells and CICs in primary cervix cancer xenografts. PMID:27901496

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. PTEN loss represses glioblastoma tumor initiating cell differentiation via inactivation of Lgl1

    PubMed Central

    Gont, Alexander; Hanson, Jennifer E L; Lavictoire, Sylvie J; Parolin, Doris A E; Daneshmand, Manijeh; Restall, Ian J; Soucie, Mathieu; Nicholas, Garth; Woulfe, John; Kassam, Amin; Da Silva, Vasco F; Lorimer, Ian AJ

    2013-01-01

    Glioblastoma multiforme is an aggressive and incurable type of brain tumor. A subset of undifferentiated glioblastoma cells, known as glioblastoma tumor initiating cells (GTICs), has an essential role in the malignancy of this disease and also appears to mediate resistance to radiation therapy and chemotherapy. GTICs retain the ability to differentiate into cells with reduced malignant potential, but the signaling pathways controlling differentiation are not fully understood at this time. PTEN loss is a very common in glioblastoma multiforme and leads to aberrant activation of the phosphoinositide 3-kinase pathway. Increased signalling through this pathway leads to activation of multiple protein kinases, including atypical protein kinase C. In Drosophila, active atypical protein kinase C has been shown to promote the self-renewal of neuroblasts, inhibiting their differentiation along a neuronal lineage. This effect is mediated by atypical protein kinase c-mediated phosphorylation and inactivation of Lgl, a protein that was first characterized as a tumour suppressor in Drosophila. The effects of the atypical protein kinase C/Lgl pathway on the differentiation status of GTICs, and its potential link to PTEN loss, have not been assessed previously. Here we show that PTEN loss leads to the phosphorylation and inactivation of Lgl by atypical protein kinase C in glioblastoma cells. Re-expression of PTEN in GTICs promoted their differentiation along a neuronal lineage. This effect was also seen when atypical protein kinase C was knocked down using RNA interference, and when a non-phosphorylatable, constitutively active form of Lgl was expressed in GTICs. Thus PTEN loss, acting via atypical protein kinase C activation and Lgl inactivation, helps to maintain GTICs in an undifferentiated state. PMID:23907540

  9. PTEN loss represses glioblastoma tumor initiating cell differentiation via inactivation of Lgl1.

    PubMed

    Gont, Alexander; Hanson, Jennifer E L; Lavictoire, Sylvie J; Parolin, Doris A; Daneshmand, Manijeh; Restall, Ian J; Soucie, Mathieu; Nicholas, Garth; Woulfe, John; Kassam, Amin; Da Silva, Vasco F; Lorimer, Ian A J

    2013-08-01

    Glioblastoma multiforme is an aggressive and incurable type of brain tumor. A subset of undifferentiated glioblastoma cells, known as glioblastoma tumor initiating cells (GTICs), has an essential role in the malignancy of this disease and also appears to mediate resistance to radiation therapy and chemotherapy. GTICs retain the ability to differentiate into cells with reduced malignant potential, but the signaling pathways controlling differentiation are not fully understood at this time. PTEN loss is a very common in glioblastoma multiforme and leads to aberrant activation of the phosphoinositide 3-kinase pathway. Increased signalling through this pathway leads to activation of multiple protein kinases, including atypical protein kinase C. In Drosophila, active atypical protein kinase C has been shown to promote the self-renewal of neuroblasts, inhibiting their differentiation along a neuronal lineage. This effect is mediated by atypical protein kinase c-mediated phosphorylation and inactivation of Lgl, a protein that was first characterized as a tumour suppressor in Drosophila. The effects of the atypical protein kinase C/Lgl pathway on the differentiation status of GTICs, and its potential link to PTEN loss, have not been assessed previously. Here we show that PTEN loss leads to the phosphorylation and inactivation of Lgl by atypical protein kinase C in glioblastoma cells. Re-expression of PTEN in GTICs promoted their differentiation along a neuronal lineage. This effect was also seen when atypical protein kinase C was knocked down using RNA interference, and when a non-phosphorylatable, constitutively active form of Lgl was expressed in GTICs. Thus PTEN loss, acting via atypical protein kinase C activation and Lgl inactivation, helps to maintain GTICs in an undifferentiated state.

  10. Tumor-derived mesenchymal stem cells and orthotopic site increase the tumor initiation potential of putative mouse mammary cancer stem cells derived from MMTV-PyMT mice.

    PubMed

    Lanza, Denise Grant; Ma, Jun; Guest, Ian; Uk-Lim, Chang; Glinskii, Anna; Glinsky, Gennadi; Sell, Stewart

    2012-12-01

    The ability to transplant mammary cancer stem cells, identified by the phenotype CD24(+)CD29(+)CD49f(+)Sca-1(low), is dependent on the microenvironment in which the cells are placed. Using the MMTV-PyMT mouse model of mammary cancer, we now report two methods of tumor growth enhancement: contributions of tumor stroma in the form of tumor-derived mesenchymal stem cells and orthotopic vs. heterotopic transplantation sites. To support evidence of stem cell function, tumor-derived mesenchymal stem cells differentiated into adipocyte- and osteocyte-like cells after culture in specific medium. Co-injection of tumor-initiating cells with tumor-derived mesenchymal stem cells significantly increased tumor initiation compared to subcutaneous injection of TICs alone; co-injection also allowed tumor initiation with a single TIC. Interestingly, we observed the formation of sarcomas after co-injections of tumor-derived mesenchymal stem cells or mouse embryonic fibroblasts with TICs; sarcomas are not observed in spontaneous MMTV-PyMT tumors and rarely observed in injections of TICs alone. Tumor initiation was also significantly increased in the orthotopic injection site compared to heterotopic injections. We conclude that tumor stroma and orthotopic sites both enhance tumor initiation by mammary cancer stem cells.

  11. Functional role of T-cell receptor nanoclusters in signal initiation and antigen discrimination

    PubMed Central

    Tabarin, Thibault; Yamamoto, Yui; Ma, Yuanqing; Nicovich, Philip R.; Bridgeman, John S.; Cohnen, André; Benzing, Carola; Gao, Yijun; Crowther, Michael D.; Tungatt, Katie; Dolton, Garry; Sewell, Andrew K.; Price, David A.; Acuto, Oreste; Parton, Robert G.; Gooding, J. Justin; Rossy, Jérémie; Rossjohn, Jamie; Gaus, Katharina

    2016-01-01

    Antigen recognition by the T-cell receptor (TCR) is a hallmark of the adaptive immune system. When the TCR engages a peptide bound to the restricting major histocompatibility complex molecule (pMHC), it transmits a signal via the associated CD3 complex. How the extracellular antigen recognition event leads to intracellular phosphorylation remains unclear. Here, we used single-molecule localization microscopy to quantify the organization of TCR–CD3 complexes into nanoscale clusters and to distinguish between triggered and nontriggered TCR–CD3 complexes. We found that only TCR–CD3 complexes in dense clusters were phosphorylated and associated with downstream signaling proteins, demonstrating that the molecular density within clusters dictates signal initiation. Moreover, both pMHC dose and TCR–pMHC affinity determined the density of TCR–CD3 clusters, which scaled with overall phosphorylation levels. Thus, TCR–CD3 clustering translates antigen recognition by the TCR into signal initiation by the CD3 complex, and the formation of dense signaling-competent clusters is a process of antigen discrimination. PMID:27573839

  12. Phosphorylation of LKB1/Par-4 Establishes Schwann Cell Polarity to Initiate and Control Myelin Extent

    PubMed Central

    Shen, Yun-An A.; Chen, Yan; Dao, Dang Q.; Mayoral, Sonia R.; Wu, Laiman; Meijer, Dies; Ullian, Erik M.; Chan, Jonah R.; Lu, Q. Richard

    2014-01-01

    The Schwann cell (SC)-axon interface represents a membrane specialization that integrates axonal signals to coordinate cytoskeletal dynamics resulting in myelination. Here we show that LKB1/Par-4 is asymmetrically localized to the SC-axon interface and colocalizes with the polarity protein Par-3. Using purified SCs and myelinating cocultures, we demonstrate that localization is dependent on the phosphorylation of LKB1 at serine-431. SC-specific deletion of LKB1 significantly attenuates developmental myelination, delaying the initiation and altering the myelin extent into adulthood, resulting in a 30% reduction in the conduction velocity along adult sciatic nerves. Phosphorylation of LKB1 by protein kinase A is essential to establish the asymmetric localization of LKB1 and Par-3 and rescues the delay in myelination observed in the SC-specific knockout of LKB1. Our findings suggest that SC polarity may coordinate multiple signaling complexes that couple SC-axon contact to the redistribution of specific membrane components necessary to initiate and control myelin extent. PMID:25255972

  13. Functional role of T-cell receptor nanoclusters in signal initiation and antigen discrimination.

    PubMed

    Pageon, Sophie V; Tabarin, Thibault; Yamamoto, Yui; Ma, Yuanqing; Bridgeman, John S; Cohnen, André; Benzing, Carola; Gao, Yijun; Crowther, Michael D; Tungatt, Katie; Dolton, Garry; Sewell, Andrew K; Price, David A; Acuto, Oreste; Parton, Robert G; Gooding, J Justin; Rossy, Jérémie; Rossjohn, Jamie; Gaus, Katharina

    2016-09-13

    Antigen recognition by the T-cell receptor (TCR) is a hallmark of the adaptive immune system. When the TCR engages a peptide bound to the restricting major histocompatibility complex molecule (pMHC), it transmits a signal via the associated CD3 complex. How the extracellular antigen recognition event leads to intracellular phosphorylation remains unclear. Here, we used single-molecule localization microscopy to quantify the organization of TCR-CD3 complexes into nanoscale clusters and to distinguish between triggered and nontriggered TCR-CD3 complexes. We found that only TCR-CD3 complexes in dense clusters were phosphorylated and associated with downstream signaling proteins, demonstrating that the molecular density within clusters dictates signal initiation. Moreover, both pMHC dose and TCR-pMHC affinity determined the density of TCR-CD3 clusters, which scaled with overall phosphorylation levels. Thus, TCR-CD3 clustering translates antigen recognition by the TCR into signal initiation by the CD3 complex, and the formation of dense signaling-competent clusters is a process of antigen discrimination.

  14. Giant cell tumor of the bone: aggressive case initially treated with denosumab and intralesional surgery.

    PubMed

    von Borstel, Donald; A Taguibao, Roberto; A Strle, Nicholas; E Burns, Joseph

    2017-04-01

    Giant cell tumor of the bone (GCTB) is a locally aggressive benign tumor, which has historically been treated with wide surgical excision. We report a case of a 29-year-old male with histology-proven GCTB of the distal ulna. The initial imaging study was a contrast-enhanced magnetic resonance imaging (MRI) examination of the left wrist, which was from an outside facility performed before presenting to our institution. On the initial MRI, the lesion had homogenous T2-hyperintense and T1-hypointense signal with expansive remodeling of the osseous contour. A radiographic study performed upon presentation to our institution 1 month later showed progression of the lesion with atypical imaging characteristics. After confirming the diagnosis, denosumab therapy was implemented allowing for reconstitution of bone and intralesional treatment. The patient was treated with five doses of denosumab over the duration of 7 weeks. Therapeutic changes of the GCTB were evaluated by radiography and a post-treatment MRI. This MRI was interpreted as suspicious for worsening disease due to the imaging appearance of intralesional signal heterogeneity, increased perilesional fluid-like signal, and circumferential cortical irregularity. However, on subsequent intralesional curettage and bone autografting 6 weeks later, no giant cells were seen on the specimen. Thus, the appearance on the MRI, rather than representing a manifestation of lesion aggressiveness or a non-responding tumor, conversely represented the imaging appearance of a positive response to denosumab therapy. On follow-up evaluation, 5 months after intralesional treatment, the patient had recurrent disease and is now scheduled for wide-excision with joint prosthesis.

  15. Impact of initial biofilm growth on the anode impedance of microbial fuel cells.

    PubMed

    Ramasamy, Ramaraja P; Ren, Zhiyong; Mench, Matthew M; Regan, John M

    2008-09-01

    Electrochemical impedance spectroscopy (EIS) was used to study the behavior of a microbial fuel cell (MFC) during initial biofilm growth in an acetate-fed, two-chamber MFC system with ferricyanide in the cathode. EIS experiments were performed both on the full cell (between cathode and anode) as well as on individual electrodes. The Nyquist plots of the EIS data were fitted with an equivalent electrical circuit to estimate the contributions of various intrinsic resistances to the overall internal MFC impedance. During initial development of the anode biofilm, the anode polarization resistance was found to decrease by over 70% at open circuit and by over 45% at 27 microA/cm(2), and a simultaneous increase in power density by about 120% was observed. The exchange current density for the bio-electrochemical reaction on the anode was estimated to be in the range of 40-60 nA/cm(2) for an immature biofilm after 5 days of closed circuit operation, which increased to around 182 nA/cm(2) after more than 3 weeks of operation and stable performance in an identical parallel system. The polarization resistance of the anode was 30-40 times higher than that of the ferricyanide cathode for the conditions tested, even with an established biofilm. For a two-chamber MFC system with a Nafion 117 membrane and an inter-electrode spacing of 15 cm, the membrane and electrolyte solution dominate the ohmic resistance and contribute to over 95% of the MFC internal impedance. Detailed EIS analyses provide new insights into the dominant kinetic resistance of the anode bio-electrochemical reaction and its influence on the overall power output of the MFC system, even in the high internal resistance system used in this study. These results suggest that new strategies to address this kinetic constraint of the anode bio-electrochemical reactions are needed to complement the reduction of ohmic resistance in modern designs.

  16. 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.

  17. 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.

  18. How to feed a spacecraft

    NASA Astrophysics Data System (ADS)

    McLaughlin, William

    1987-01-01

    The uplink process between ground computers and the spacecraft computer is examined. Data is uplinked to a spacecraft by a load (a sequence of preplanned commands) or by real-time commands; the differences between these two types of uplinks are discussed. The sequencing of a load involves: (1) request generation, (2) request integration, (3) reference generation, and (4) transmitting the load. The functions of each of the sequencing steps are described. The development of new sequencing methods using expert systems and AI is being studied. A symbolic processing software which has the ability to transmit data typed into a computer in English was developed. Consideration is given to the composition, capabilities of the parser, and application of the symbolic processing software to the Comet Renedezvous Asteroid Flyby spacecraft.

  19. Spacecraft Design Thermal Control Subsystem

    NASA Technical Reports Server (NTRS)

    Miyake, Robert N.

    2003-01-01

    This slide presentation reviews the functions of the thermal control subsystem engineers in the design of spacecraft. The goal of the thermal control subsystem that will be used in a spacecraft is to maintain the temperature of all spacecraft components, subsystems, and all the flight systems within specified limits for all flight modes from launch to the end of the mission. For most thermal control subsystems the mass, power and control and sensing systems must be kept below 10% of the total flight system resources. This means that the thermal control engineer is involved in all other flight systems designs. The two concepts of thermal control, passive and active are reviewed and the use of thermal modeling tools are explained. The testing of the thermal control is also reviewed.

  20. Swarms: Optimum aggregations of spacecraft

    NASA Technical Reports Server (NTRS)

    Mayer, H. L.

    1980-01-01

    Swarms are aggregations of spacecraft or elements of a space system which are cooperative in function, but physically isolated or only loosely connected. For some missions the swarm configuration may be optimum compared to a group of completely independent spacecraft or a complex rigidly integrated spacecraft or space platform. General features of swarms are induced by considering an ensemble of 26 swarms, examples ranging from Earth centered swarms for commercial application to swarms for exploring minor planets. A concept for a low altitude swarm as a substitute for a space platform is proposed and a preliminary design studied. The salient design feature is the web of tethers holding the 30 km swarm in a rigid two dimensional array in the orbital plane. A mathematical discussion and tutorial in tether technology and in some aspects of the distribution of services (mass, energy, and information to swarm elements) are included.

  1. Conductive spacecraft materials development program

    NASA Technical Reports Server (NTRS)

    Lehn, W. L.

    1977-01-01

    The objectives of this program are to provide design criteria, techniques, materials, and test methods to ensure control of absolute and differential charging of spacecraft surfaces. The control of absolute and differential charging of spacecraft cannot be effected without the development of new and improved or modified materials or techniques that will provide electrical continuity over the surface of the spacecraft. The materials' photoemission, secondary emission, thermooptical, physical, and electrical properties in the space vacuum environment both in the presence and absence of electrical stress and ultraviolet, electron, and particulate radiation, are important to the achievement of charge control. The materials must be stable or have predictable response to exposure to the space environment for long periods of time. The materials of interest include conductive polymers, paints, transparent films and coatings as well as fabric coating interweaves.

  2. 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.

  3. Fire safety applications for spacecraft

    NASA Technical Reports Server (NTRS)

    Friedman, Robert; Olson, Sandra L.

    1989-01-01

    Fire safety for spacecraft is reviewed by first describing current practices, many of which are adapted directly from aircraft. Then, current analyses and experimental knowledge in low-gravity combustion, with implications for fire safety are discussed. In orbiting spacecraft, the detection and suppression of flames are strongly affected by the large reduction in buoyant flows under low gravity. Generally, combustion intensity is reduced in low gravity. There are some notable exceptions, however, one example being the strong enhancement of flames by low-velocity ventilation flows in space. Finally, the future requirements in fire safety, particularly the needs of long-duration space stations in fire prevention, detection, extinguishment, and atmospheric control are examined. The goal of spacecraft fire-safety investigations is the establishment of trade-offs that promote maximum safety without hampering the useful human and scientific activities in space.

  4. Universal Controller for Spacecraft Mechanisms

    NASA Technical Reports Server (NTRS)

    Levanas, Greg; McCarthy, Thomas; Hunter, Don; Buchanan, Christine; Johnson, Michael; Cozy, Raymond; Morgan, Albert; Tran, Hung

    2006-01-01

    An electronic control unit has been fabricated and tested that can be replicated as a universal interface between the electronic infrastructure of a spacecraft and a brushless-motor (or other electromechanical actuator) driven mechanism that performs a specific mechanical function within the overall spacecraft system. The unit includes interfaces to a variety of spacecraft sensors, power outputs, and has selectable actuator control parameters making the assembly a mechanism controller. Several control topologies are selectable and reconfigurable at any time. This allows the same actuator to perform different functions during the mission life of the spacecraft. The unit includes complementary metal oxide/semiconductor electronic components on a circuit board of a type called rigid flex (signifying flexible printed wiring along with a rigid substrate). The rigid flex board is folded to make the unit fit into a housing on the back of a motor. The assembly has redundant critical interfaces, allowing the controller to perform time-critical operations when no human interface with the hardware is possible. The controller is designed to function over a wide temperature range without the need for thermal control, including withstanding significant thermal cycling, making it usable in nearly all environments that spacecraft or landers will endure. A prototype has withstood 1,500 thermal cycles between 120 and +85 C without significant deterioration of its packaging or electronic function. Because there is no need for thermal control and the unit is addressed through a serial bus interface, the cabling and other system hardware are substantially reduced in quantity and complexity, with corresponding reductions in overall spacecraft mass and cost.

  5. Meiotic recombination initiated by a double-strand break in rad50{Delta} yeast cells otherwise unable to initiate meiotic recombination

    SciTech Connect

    Malkova, A.; Haber, J.E.; Dawson, D.

    1996-06-01

    Meiotic recombination in Saccharomyces cerevisiae is initiated by double-strand breaks (DSBs). We have developed a system to compare the properties of meiotic DSBs with those created by the site-specific HO endonuclease. HO endonuclease was expressed under the control of the meiotic-specific SPO13 promoter, creating a DSB at a single site on one of yeast`s 16 chromosomes. In Rad{sup +} strains the times of appearance of the HO-induced DSBs and of subsequent recombinants are coincident with those induced by normal meiotic DSBs. Physical monitoring of DNA showed that SPO13::HO induced gene conversions both in Rad{sup +} and in rad50{Delta} cells that cannot initiate normal meiotic DSBs. We find that the RAD50 gene is important, but not essential, for recombination even after a DSB has been created in a meiotic cell. In rad50{Delta} cells, some DSBs are not repaired until a broken chromosome has been packaged into a spore and is subsequently germinated. This suggests that a broken chromosome does not signal an arrest of progression through meiosis. The recombination defect in rad50{Delta} diploids is not, however, meiotic specific, as mitotic rad50 diploids, experiencing an HO-induced DSB, exhibit similar departures from wild-type recombination. 57 refs., 5 figs., 3 tabs.

  6. Immunomodulating and Immunoresistance Properties of Cancer-Initiating Cells: Implications for the Clinical Success of Immunotherapy.

    PubMed

    Maccalli, Cristina; Parmiani, Giorgio; Ferrone, Soldano

    2017-04-01

    Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient's immune system can mount an immune response, which is effective in controlling tumor growth. However, a high proportion of patients is resistant or acquires resistance to these therapeutic strategies. The latter findings may reflect, at least in some cases, the inability of the immunotherapeutic strategies used to eradicate CICs. The CICs that escape immune recognition and destruction may give rise to new tumors in the same organ site or through the metastatic colonization in other anatomic sites. Identification of novel therapeutic approaches that can eradicate CICs is a major challenge in the cancer therapy area. An improved understanding of the interactions of CICs with immune system and with tumor microenvironment may contribute to optimize the available therapies and to design novel combination treatments for cancer therapy.

  7. Mechanical Failure of Fine Root Cortical Cells Initiates Plant Hydraulic Decline during Drought1[OPEN

    PubMed Central

    McElrone, Andrew J.

    2016-01-01

    Root systems perform the crucial task of absorbing water from the soil to meet the demands of a transpiring canopy. Roots are thought to operate like electrical fuses, which break when carrying an excessive load under conditions of drought stress. Yet the exact site and sequence of this dysfunction in roots remain elusive. Using in vivo x-ray computed microtomography, we found that drought-induced mechanical failure (i.e. lacunae formation) in fine root cortical cells is the initial and primary driver of reduced fine root hydraulic conductivity (Lpr) under mild to moderate drought stress. Cortical lacunae started forming under mild drought stress (−0.6 MPa Ψstem), coincided with a dramatic reduction in Lpr, and preceded root shrinkage or significant xylem embolism. Only under increased drought stress was embolism formation observed in the root xylem, and it appeared first in the fine roots (50% loss of hydraulic conductivity [P50] reached at −1.8 MPa) and then in older, coarse roots (P50 = −3.5 MPa). These results suggest that cortical cells in fine roots function like hydraulic fuses that decouple plants from drying soil, thus preserving the hydraulic integrity of the plant’s vascular system under early stages of drought stress. Cortical lacunae formation led to permanent structural damage of the root cortex and nonrecoverable Lpr, pointing to a role in fine root mortality and turnover under drought stress. PMID:27621427

  8. The Cancer Cell Map Initiative: Defining the Hallmark Networks of Cancer

    PubMed Central

    Krogan, Nevan J.; Lippman, Scott; Agard, David A.; Ashworth, Alan; Ideker, Trey

    2017-01-01

    Progress in DNA sequencing has revealed the startling complexity of cancer genomes, which typically carry thousands of somatic mutations. However, it remains unclear which are the key driver mutations or dependencies in a given cancer and how these influence pathogenesis and response to therapy. Although tumors of similar types and clinical outcomes can have patterns of mutations that are strikingly different, it is becoming apparent that these mutations recurrently hijack the same hallmark molecular pathways and networks. For this reason, it is likely that successful interpretation of cancer genomes will require comprehensive knowledge of the molecular networks under selective pressure in oncogenesis. Here we announce the creation of a new effort, called The Cancer Cell Map Initiative (CCMI), aimed at systematically detailing these complex interactions among cancer genes and how they differ between diseased and healthy states. We discuss recent progress that enables creation of these Cancer Cell Maps across a range of tumor types and how they can be used to target networks disrupted in individual patients, significantly accelerating the development of precision medicine. PMID:26000852

  9. The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled

    PubMed Central

    Gupta, Tripti; Kumar, Arun; Cattenoz, Pierre B.; VijayRaghavan, K; Giangrande, Angela

    2016-01-01

    Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules implicated in cell interactions also control collective migration, but their precise role and the finely tuned expression that orchestrates this complex developmental process are poorly understood. Here, we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the developing Drosophila wing. Frazzled expression is induced by the transcription factor Glide/Gcm in a dose-dependent manner. Thus, the glial determinant also regulates the efficiency of collective migration. NetrinB but not NetrinA serves as a chemoattractant and Unc5 contributes as a repellant Netrin receptor for glia migration. Our model includes strict spatial localization of a ligand, a cell autonomously acting receptor and a fate determinant that act coordinately to direct glia toward their final destination. DOI: http://dx.doi.org/10.7554/eLife.15983.001 PMID:27740455

  10. Mechanical Failure of Fine Root Cortical Cells Initiates Plant Hydraulic Decline during Drought.

    PubMed

    Cuneo, Italo F; Knipfer, Thorsten; Brodersen, Craig R; McElrone, Andrew J

    2016-11-01

    Root systems perform the crucial task of absorbing water from the soil to meet the demands of a transpiring canopy. Roots are thought to operate like electrical fuses, which break when carrying an excessive load under conditions of drought stress. Yet the exact site and sequence of this dysfunction in roots remain elusive. Using in vivo x-ray computed microtomography, we found that drought-induced mechanical failure (i.e. lacunae formation) in fine root cortical cells is the initial and primary driver of reduced fine root hydraulic conductivity (Lpr) under mild to moderate drought stress. Cortical lacunae started forming under mild drought stress (-0.6 MPa Ψstem), coincided with a dramatic reduction in Lpr, and preceded root shrinkage or significant xylem embolism. Only under increased drought stress was embolism formation observed in the root xylem, and it appeared first in the fine roots (50% loss of hydraulic conductivity [P50] reached at -1.8 MPa) and then in older, coarse roots (P50 = -3.5 MPa). These results suggest that cortical cells in fine roots function like hydraulic fuses that decouple plants from drying soil, thus preserving the hydraulic integrity of the plant's vascular system under early stages of drought stress. Cortical lacunae formation led to permanent structural damage of the root cortex and nonrecoverable Lpr, pointing to a role in fine root mortality and turnover under drought stress.

  11. Mast cells are key mediators of cathelicidin-initiated skin inflammation in rosacea.

    PubMed

    Muto, Yumiko; Wang, Zhenping; Vanderberghe, Matthieu; Two, Aimee; Gallo, Richard L; Di Nardo, Anna

    2014-11-01

    Rosacea is a chronic inflammatory skin disease whose pathophysiological mechanism is still unclear. However, it is known that mast cell (MC) numbers are increased in the dermis of rosacea patients. MC proteases not only recruit other immune cells, which amplify the inflammatory response, but also cause vasodilation and angiogenesis. MCs are also one of the primary sources of cathelicidin LL-37 (Cath LL-37), an antimicrobial peptide that has been shown to be an enabler of rosacea pathogenesis. Here, we demonstrate that MCs are key mediators of cathelicidin-initiated skin inflammation. After Cath LL-37 injection into the dermis, MC-deficient B6.Cg-Kit(W-sh)/HNihrJaeBsmJ (KitW-sh) mice did not develop rosacea-like features. Conversely, chymase (P<0.001), tryptase, and Mmp9 (P<0.01) mRNA levels were significantly higher in C57BL/6 wild-type (WT) mice. Treating WT mice with an MC stabilizer significantly decreased the expressions of Mmp9 and Cxcl2 (P<0.01). Our data were confirmed on erythematotelangiectatic rosacea subjects who showed a decrease in matrix metalloproteinase activity (P<0.05), after 8 weeks of topical cromolyn treatment. We conclude that MCs have a central role in the development of inflammation subsequent to Cath LL-37 activation and that downregulation of activated MCs may be a therapy for rosacea treatment.

  12. Optimization of the tissue source, malignancy, and initial substrate of tumor cell-derived matrices to increase cancer cell chemoresistance against 5-fluorouracil.

    PubMed

    Hoshiba, Takashi; Tanaka, Masaru

    2015-02-13

    The low chemoresistance of in vitro cancer cells inhibits the development of new anti-cancer drugs. Thus, development of a new in vitro culture system is required to increase the chemoresistance of in vitro cancer cells. Tumor cell-derived matrices have been reported to increase the chemoresistance of in vitro cancer cells. However, it remains unclear how tissue sources and the malignancy of cells used for the preparation of matrices affect the chemoresistance of tumor cell-derived matrices. Moreover, it remains unclear how the initial substrates used for the preparation of matrices affect the chemoresistance. In this study, we compared the effects of tissue sources and the malignancy of tumor cells, as well as the effect of the initial substrates on chemoresistance against 5-fluorouracil (5-FU). The chemoresistance of breast and colon cancer cells against 5-FU increased on matrices prepared with cells derived from the corresponding original tissues with higher malignancy. Moreover, the chemoresistance against 5-FU was altered on matrices prepared using different initial substrates that exhibited different characteristics of protein adsorption. Taken together, these results indicated that the appropriate selection of tissue sources, malignancy of tumor cells, and initial substrates used for matrix preparation is important for the preparation of tumor cell-derived matrices for chemoresistance assays.

  13. Training for spacecraft technical analysts

    NASA Technical Reports Server (NTRS)

    Ayres, Thomas J.; Bryant, Larry

    1989-01-01

    Deep space missions such as Voyager rely upon a large team of expert analysts who monitor activity in the various engineering subsystems of the spacecraft and plan operations. Senior teammembers generally come from the spacecraft designers, and new analysts receive on-the-job training. Neither of these methods will suffice for the creation of a new team in the middle of a mission, which may be the situation during the Magellan mission. New approaches are recommended, including electronic documentation, explicit cognitive modeling, and coached practice with archived data.

  14. Human factors in spacecraft design.

    PubMed

    Harrison, A A; Connors, M M

    1990-01-01

    This paper describes some of the salient implications of evolving mission parameters for spacecraft design. Among the requirements for future spacecraft are new, higher standards of living, increased support of human productivity, and greater accommodation of physical and cultural variability. Design issues include volumetric allowances, architecture and layouts, closed life support systems, health maintenance systems, recreational facilities, automation, privacy, and decor. An understanding of behavioral responses to design elements is a precondition for critical design decisions. Human factors research results must be taken into account early in the course of the design process.

  15. Human factors in spacecraft design

    NASA Technical Reports Server (NTRS)

    Harrison, Albert A.; Connors, Mary M.

    1990-01-01

    This paper describes some of the salient implications of evolving mission parameters for spacecraft design. Among the requirements for future spacecraft are new, higher standards of living, increased support of human productivity, and greater accommodation of physical and cultural variability. Design issues include volumetric allowances, architecture and layouts, closed life support systems, health maintenance systems, recreational facilities, automation, privacy, and decor. An understanding of behavioral responses to design elements is a precondition for critical design decisions. Human factors research results must be taken into account early in the course of the design process.

  16. Viking I Spacecraft in Cleanroom

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The planetary landing spacecraft Viking, which includes stereo cameras, a weather station, an automated stereo analysis laboratory and a biology instrument that can detect life, is under assembly at Martin Marietta Aerospace near Denver, Colorado. This Viking spacecraft will travel more than 460 million miles from Earth to a soft landing on Mars in 1976 to explore the surface and atmosphere of the red planet. Martin Marietta is prime and integration contractor for the Viking mission to NASA's Langley Research Center, Hampton, Virginia. The lander will be powered by two nuclear generators.

  17. Tools Automate Spacecraft Testing, Operation

    NASA Technical Reports Server (NTRS)

    2010-01-01

    "NASA began the Small Explorer (SMEX) program to develop spacecraft to advance astrophysics and space physics. As one of the entities supporting software development at Goddard Space Flight Center, the Hammers Company Inc. (tHC Inc.), of Greenbelt, Maryland, developed the Integrated Test and Operations System to support SMEX. Later, the company received additional Small Business Innovation Research (SBIR) funding from Goddard for a tool to facilitate the development of flight software called VirtualSat. NASA uses the tools to support 15 satellites, and the aerospace industry is using them to develop science instruments, spacecraft computer systems, and navigation and control software."

  18. Spacecraft instrument technology and cosmochemistry.

    PubMed

    McSween, Harry Y; McNutt, Ralph L; Prettyman, Thomas H

    2011-11-29

    Measurements by instruments on spacecraft have significantly advanced cosmochemistry. Spacecraft missions impose serious limitations on instrument volume, mass, and power, so adaptation of laboratory instruments drives technology. We describe three examples of flight instruments that collected cosmochemical data. Element analyses by Alpha Particle X-ray Spectrometers on the Mars Exploration Rovers have revealed the nature of volcanic rocks and sedimentary deposits on Mars. The Gamma Ray Spectrometer on the Lunar Prospector orbiter provided a global database of element abundances that resulted in a new understanding of the Moon's crust. The Ion and Neutral Mass Spectrometer on Cassini has analyzed the chemical compositions of the atmosphere of Titan and active plumes on Enceladus.

  19. Mapping of ESE-1 subdomains required to initiate mammary epithelial cell transformation via a cytoplasmic mechanism

    PubMed Central

    2011-01-01

    Background The ETS family transcription factor ESE-1 is often overexpressed in human breast cancer. ESE-1 initiates transformation of MCF-12A cells via a non-transcriptional, cytoplasmic process that is mediated by a unique 40-amino acid serine and aspartic acid rich (SAR) subdomain, whereas, ESE-1's nuclear transcriptional property is required to maintain the transformed phenotype of MCF7, ZR-75-1 and T47D breast cancer cells. Results To map the minimal functional nuclear localization (NLS) and nuclear export (NES) signals, we fused in-frame putative NLS and NES motifs between GFP and the SAR domain. Using these GFP constructs as reporters of subcellular localization, we mapped a single NLS to six basic amino acids (242HGKRRR247) in the AT-hook and two CRM1-dependent NES motifs, one to the pointed domain (NES1: 102LCNCALEELRL112) and another to the DNA binding domain (DBD), (NES2: 275LWEFIRDILI284). Moreover, analysis of a putative NLS located in the DBD (316GQKKKNSN323) by a similar GFP-SAR reporter or by internal deletion of the DBD, revealed this sequence to lack NLS activity. To assess the role of NES2 in regulating ESE-1 subcellular localization and subsequent transformation potency, we site-specifically mutagenized NES2, within full-length GFP-ESE-1 and GFP-NES2-SAR reporter constructs. These studies show that site-specific mutation of NES2 completely abrogates ESE-1 transforming activity. Furthermore, we show that exclusive cytoplasmic targeting of the SAR domain is sufficient to initiate transformation, and we report that an intact SAR domain is required, since block mutagenesis reveals that an intact SAR domain is necessary to maintain its full transforming potency. Finally, using a monoclonal antibody targeting the SAR domain, we demonstrate that the SAR domain contains a region accessible for protein - protein interactions. Conclusions These data highlight that ESE-1 contains NLS and NES signals that play a critical role in regulating its subcellular

  20. Newly developed initial-flow cell filtrometer and the comparison with viscometry and ektacytometry on erythrocyte deformability.

    PubMed

    Peng, J; Liao, F L; Yin, X J

    1998-07-01

    According to Hanss's initial-flow rate method, F. Liao designed a new cell filtrometer in the early 1990s. The parameters, cell initial transit time (Tc) and membrane clogging rate (CR), can be determined by a single measurement with timing accuracy of 1 ms. The new cell filtrometer has two valuable features: a button-pushing operation to control electromagnetic valves; and an autocirculation of fluid in the cell filtrometer resulting in the same volume of leading fluid. A series of comparisons of the new filtrometry with viscometry or ektacytometry shows that the instrument seems to be more sensitive in detecting subpopulations of glutaraldehyde-hardened cells and the shift of deformability for all the cells. The reproducibility of the filtrometer for different membranes made in China and the USA is reasonable (CV < 5% for Tc). Preliminary application of the filtrometer indicates that it might be useful for trial study and routine clinical application.

  1. Advanced solar-propelled cargo spacecraft for Mars missions

    NASA Technical Reports Server (NTRS)

    Auziasdeturenne, J.; Beall, M.; Burianek, J.; Cinniger, A.; Dunmire, B.; Haberman, E.; Iwamoto, J.; Johnson, S.; Mccracken, S.; Miller, M.

    1989-01-01

    At the University of Washington, three concepts for an unmanned, solar powered, cargo spacecraft for Mars-support missions have been 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 mangetoplasmadynamic (MPD) arc system. The SRA directly converts solar energy to thermal energy in the propellant through a novel process developed at the University of Washington. A solar concentrator focuses sunlight into an absorption chamber. A mixture of hydrogen and potassium vapor absorbs the incident radiation and is heated to approximately 3700 K. The hot propellant gas exhausts through a nozzle to produce thrust. The SRA has an I(sub sp) of approximately 1000 sec and produces a thrust of 2940 N using two thrust chambers. In the SPL system, a pair of solar-pumped, multi-megawatt, CO2 lasers in sun-synchronous Earth orbit converts solar energy to laser energy. The laser beams are transmitted to the spacecraft via laser relay satellites. The laser energy heats the hydrogen propellant through a plasma breakdown process in the center of an absorption chamber. Propellant flowing through the chamber, heated by the plasma core, expands through a nozzle to produce thrust. The SPL has an I(sub sp) of 1285 sec and produces a thrust of 1200 N using two thrust chambers. The MPD system uses indium phosphide solar cells to convert sunlight to electricity, which powers the propulsion system. In this system, the argon propellant is ionized and electromagnetically accelerated by a magnetoplasmadynamic arc to produce thrust. The MPD spacecraft has an I(sub sp) of 2490 sec and produces a thrust of 100 N. 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

  2. Reconstitution of CD4 T Cells in Bronchoalveolar Lavage Fluid after Initiation of Highly Active Antiretroviral Therapy▿

    PubMed Central

    Knox, Kenneth S.; Vinton, Carol; Hage, Chadi A.; Kohli, Lisa M.; Twigg, Homer L.; Klatt, Nichole R.; Zwickl, Beth; Waltz, Jeffrey; Goldman, Mitchell; Douek, Daniel C.; Brenchley, Jason M.

    2010-01-01

    The massive depletion of gastrointestinal-tract CD4 T cells is a hallmark of the acute phase of HIV infection. In contrast, the depletion of the lower-respiratory-tract mucosal CD4 T cells as measured in bronchoalveolar lavage (BAL) fluid is more moderate and similar to the depletion of CD4 T cells observed in peripheral blood (PB). To understand better the dynamics of disease pathogenesis and the potential for the reconstitution of CD4 T cells in the lung and PB following the administration of effective antiretroviral therapy, we studied cell-associated viral loads, CD4 T-cell frequencies, and phenotypic and functional profiles of antigen-specific CD4 T cells from BAL fluid and blood before and after the initiation of highly active antiretroviral therapy (HAART). The major findings to emerge were the following: (i) BAL CD4 T cells are not massively depleted or preferentially infected by HIV compared to levels for PB; (ii) BAL CD4 T cells reconstitute after the initiation of HAART, and their infection frequencies decrease; (iii) BAL CD4 T-cell reconstitution appears to occur via the local proliferation of resident BAL CD4 T cells rather than redistribution; and (iv) BAL CD4 T cells are more polyfunctional than CD4 T cells in blood, and their functional profile is relatively unchanged after the initiation of HAART. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might aid in the reconstitution of mucosal CD4 T cells. PMID:20610726

  3. Novel population of small tumour-initiating stem cells in the ovaries of women with borderline ovarian cancer

    PubMed Central

    Virant-Klun, Irma; Stimpfel, Martin

    2016-01-01

    Small stem cells with diameters of up to 5 μm previously isolated from adult human ovaries indicated pluripotency and germinal lineage, especially primordial germ cells, and developed into primitive oocyte-like cells in vitro. Here, we show that a comparable population of small stem cells can be found in the ovarian tissue of women with borderline ovarian cancer, which, in contrast to small stem cells in “healthy” ovaries, formed spontaneous tumour-like structures and expressed some markers related to pluripotency and germinal lineage. The gene expression profile of these small putative cancer stem cells differed from similar cells sorted from “healthy” ovaries by 132 upregulated and 97 downregulated genes, including some important forkhead box and homeobox genes related to transcription regulation, developmental processes, embryogenesis, and ovarian cancer. These putative cancer stem cells are suggested to be a novel population of ovarian tumour-initiating cells in humans. PMID:27703207

  4. Targeting cancer-initiating cell drug-resistance: a roadmap to a new-generation of cancer therapies?

    PubMed

    Alama, Angela; Orengo, Anna Maria; Ferrini, Silvano; Gangemi, Rosaria

    2012-05-01

    The occurrence of drug resistance in oncology accounts for treatment failure and relapse of diverse tumor types. Cancers contain cells at various stages of differentiation together with a limited number of 'cancer-initiating cells' able to self-renew and divide asymmetrically, driving tumorigenesis. Cancer-initiating cells display a range of self-defense systems that include almost all mechanisms of drug-resistance. Different molecular pathways and markers, identified in this malignant sub-population, are becoming targets for novel compounds and for monoclonal antibodies, which may be combined with conventional drugs. These interventions might eliminate drug-resistant cancer-initiating cells and lead to remission or cure of cancer patients.

  5. Attitude reorientation of spacecraft by means of impulse coning

    NASA Technical Reports Server (NTRS)

    Martz, C. W.

    1977-01-01

    Minimum maneuver costs for attitude reorientation of spacecraft of all possible inertial distribution over a wide range of maneuver angles by use of the impulse coning method of reorientation was studied. Maneuver cost is proportional to the product of fuel consumed and time expended during a maneuver. Assumptions included impulsive external control torques, rigid-body spacecraft, rest-to-rest maneuvers, and no disturbance torques. Also, coning maneuvers were constrained to have equal initial and final cone angles. Maneuver costs are presented for general reorientations as well as for spin-axis reorientations where final attitude about the spin axis is arbitrary.

  6. Sealed-cell nickel-cadmium battery applications manual

    NASA Technical Reports Server (NTRS)

    Scott, W. R.; Rusta, D. W.

    1979-01-01

    The design, procurement, testing, and application of aerospace quality, hermetically sealed nickel-cadmium cells and batteries are presented. Cell technology, cell and battery development, and spacecraft applications are emphasized. Long term performance is discussed in terms of the effect of initial design, process, and application variables. Design guidelines and practices are given.

  7. 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.

  8. Space Exploration Initiative

    NASA Technical Reports Server (NTRS)

    1990-01-01

    An overview of President Bush's Space Exploration Initiative (SEI) and it's three main components, Space Station Freedom, a Permanent Lunar Base, and a Manned Mission to Mars is provided. Computer simulations of the Space Station Freedom and Permanent Lunar Base are shown, and an animated sequence describes a Mars mission where heavy lift vehicle will bring components of a Mars Spacecraft into orbit, where it will be put together by astronauts using a robotic arm. The Mars spacecraft is shown orbiting Mars and discharging a lander to the surface, carrying human explorers. The video also details the SEI's Outreach Program, designed to garner interest in and ideas for Space Exploration.

  9. RGD-modifided oncolytic adenovirus exhibited potent cytotoxic effect on CAR-negative bladder cancer-initiating cells.

    PubMed

    Yang, Y; Xu, H; Shen, J; Yang, Y; Wu, S; Xiao, J; Xu, Y; Liu, X-Y; Chu, L

    2015-05-14

    Cancer-initiating cell (CIC) is critical in cancer development, maintenance and recurrence. The reverse expression pattern of coxsackie and adenovirus receptor (CAR) and αν integrin in bladder cancer decreases the infection efficiency of adenovirus. We constructed Arg-Gly-Asp (RGD)-modified oncolytic adenovirus, carrying EGFP or TNF-related apoptosis-inducing ligand (TRAIL) gene (Onco(Ad).RGD-hTERT-EGFP/TRAIL), and applied them to CAR-negative bladder cancer T24 cells and cancer-initiating T24 sphere cells. Onco(Ad).RGD-hTERT-EGFP had enhanced infection ability and cytotoxic effect on T24 cells and T24 sphere cells, but little cytoxicity on normal urothelial SV-HUC-1 cells compared with the unmodified virus Onco(Ad).hTERT-EGFP. Notably, Onco(Ad).RGD-hTERT-TRAIL induced apoptosis in T24 cells and T24 sphere cells. Furthermore, it completely inhibited xenograft initiation established by the oncolytic adenovirus-pretreated T24 sphere cells, and significantly suppressed tumor growth by intratumoral injection. These results provided a promising therapeutic strategy for CAR-negative bladder cancer through targeting CICs.

  10. Spacecraft fabrication and test MODIL. Final report

    SciTech Connect

    Saito, T.T.

    1994-05-01

    This report covers the period from October 1992 through the close of the project. FY 92 closed out with the successful briefing to industry and with many potential and important initiatives in the spacecraft arena. Due to the funding uncertainties, we were directed to proceed as if our funding would be approximately the same as FY 92 ($2M), but not to make any major new commitments. However, the MODIL`s FY 93 funding was reduced to $810K and we were directed to concentrate on the cryocooler area. The cryocooler effort completed its demonstration project. The final meetings with the cryocooler fabricators were very encouraging as we witnessed the enthusiastic reception of technology to help them reduce fabrication uncertainties. Support of the USAF Phillips Laboratory cryocooler program was continued including kick-off meetings for the Prototype Spacecraft Cryocooler (PSC). Under Phillips Laboratory support, Gill Cruz visited British Aerospace and Lucas Aerospace in the United Kingdom to assess their manufacturing capabilities. In the Automated Spacecraft & Assembly Project (ASAP), contracts were pursued for the analysis by four Brilliant Eyes prime contractors to provide a proprietary snap shot of their current status of Integrated Product Development. In the materials and structure thrust the final analysis was completed of the samples made under the contract (``Partial Automation of Matched Metal Net Shape Molding of Continuous Fiber Composites``) to SPARTA. The Precision Technologies thrust funded the Jet Propulsion Laboratory to prepare a plan to develop a Computer Aided Alignment capability to significantly reduce the time for alignment and even possibly provide real time and remote alignment capability of systems in flight.

  11. Piwil2 is reactivated by HPV oncoproteins and initiates cell reprogramming via epigenetic regulation during cervical cancer tumorigenesis

    PubMed Central

    Feng, Dingqing; Yan, Keqin; Zhou, Ying; Liang, Haiyan; Liang, Jing; Zhao, Weidong; Dong, Zhongjun; Ling, Bin

    2016-01-01

    The human papillomavirus (HPV) oncoproteins E6 and E7 are risk factors that are primarily responsible for the initiation and progression of cervical cancer, and they play a key role in immortalization and transformation by reprogramming differentiating host epithelial cells. It is unclear how cervical epithelial cells transform into tumor-initiating cells (TICs). Here, we observed that the germ stem cell protein Piwil2 is expressed in pre-cancerous and malignant lesions of the cervix and cervical cancer cell lines with the exception of the non-HPV-infected C33a cell line. Knockdown of Piwil2 by shRNA led to a marked reduction in proliferation and colony formation, in vivo tumorigenicity, chemo-resistance, and the proportion of cancer stem-like cells. In contrast, Piwil2 overexpression induced malignant transformation of HaCaT cells and the acquisition of tumor-initiating capabilities. Gene-set enrichment analysis revealed embryonic stem cell (ESC) identity, malignant biological behavior, and specifically, activation targets of the cell reprogramming factors c-Myc, Klf4, Nanog, Oct4, and Sox2 in Piwil2-overexpressing HaCaT cells. We further confirmed that E6 and E7 reactivated Piwil2 and that E6 and E7 overexpression resulted in a similar gene-set enrichment pattern as Piwil2 overexpression in HaCaT cells. Moreover, Piwil2 overexpression or E6 and E7 activation induced H3K9 acetylation but reduced H3K9 trimethylation, which contributed to the epigenetic reprogramming and ESC signature maintenance, as predicted previously. Our study demonstrates that Piwil2, reactivated by the HPV oncoproteins E6 and E7, plays an essential role in the transformation of cervical epithelial cells to TICs via epigenetics-based cell reprogramming. PMID:27602489

  12. CD4+ T cell counts in initiation of antiretroviral therapy in HIV infected asymptomatic individuals; controversies and inconsistencies.

    PubMed

    Maina, E K; Bonney, E Y; Bukusi, E A; Sedegah, M; Lartey, M; Ampofo, W K

    2015-12-01

    The primary goal when devising strategies to define the start of therapy in HIV infected individuals is to avoid HIV disease progression and toxicity from antiretroviral therapy (ART). Intermediate goals includes, avoiding resistance by suppressing HIV replication, reducing transmission, limiting spread and diversity of HIV within the body and protecting the immune system from harm. The question of how early or late to start ART and achieve both primary and intermediate goals has dominated HIV research. The distinction between early and late treatment of HIV infection is currently a matter of CD4+ T cells count, a marker of immune status, rather than on viral load, a marker of virus replication. Discussions about respective benefits of early or delayed therapy, as well as the best CD4+ T cell threshold during the course of HIV infection at which ART is initiated remains inconclusive. Guidelines issued by various agencies, provide different initiation recommendations. This can be confusing for clinicians and policy-makers when determining the best time to initiate therapy. Optimizing ART initiation strategies are clearly complex and must be balanced between individual and broader public health needs. This review assesses available data that contributes to the debate on optimal time to initiate therapy in HIV-infected asymptomatic individuals. We also review reports on CD4+ T cell threshold to guide initiation of ART and finally discuss arguments for and against early or late initiation of ART.

  13. Implementation of a Process for Initial Transcranial Doppler Ultrasonography in Children With Sickle Cell Anemia

    PubMed Central

    Crosby, Lori E.; Joffe, Naomi E.; Davis, Blair; Quinn, Charles T.; Shook, Lisa; Morgan, Darice; Simmons, Kenya; Kalinyak, Karen A.

    2016-01-01

    Stroke, a devastating complication of sickle cell anemia (SCA), can cause irreversible brain injury with physical and cognitive deficits. Transcranial Doppler ultrasonography (TCD) is a non-invasive tool for identifying children with SCA at highest risk of stroke. National guidelines recommend that TCD screening begin at age 2 years, yet there is research to suggest less than half of young children undergo screening. The purpose of this project was to use quality improvement methods to improve the proportion of patients aged 24–27 months who successfully completed their initial TCD from 25% to 75% by December 31, 2013. Quality improvement methods (e.g., process mapping, simplified failure mode effect analysis, and plan–do–study–act cycles) were used to develop and test processes for identifying eligible patients, scheduling TCDs, preparing children and families for the first TCD, and monitoring outcomes (i.e., TCD protocol). Progress was tracked using a report of eligible patients and a chart showing the age in months for the first successful TCD (population metric). As of December 2013, 100% of eligible patients successfully completed their initial TCD screen; this improvement was maintained for the next 20 months. In November 2014, a Welch’s one-way ANOVA was conducted. Results showed a statistically significant difference between the average age of first TCD for eligible patients born in 2009 and eligible patients born during the intervention period (2010–2013; F[1,11.712]=16.03, p=0.002). Use of quality improvement methods to implement a TCD protocol was associated with improved TCD screening rates in young children with SCA. PMID:27320459

  14. Nonlinearities in spacecraft structural dynamics

    NASA Technical Repor