Science.gov

Sample records for spacecraft cells initial

  1. 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.

  2. Small Spacecraft Technology Initiative Education Program

    NASA Technical Reports Server (NTRS)

    1995-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Harkness, J. D.

    1980-04-01

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

  4. Evaluation program for secondary spacecraft cells: Initial evaluation tests of 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. Advanced spacecraft fuel cell systems

    NASA Technical Reports Server (NTRS)

    Thaller, L. H.

    1972-01-01

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

  9. Active lithium chloride cell for spacecraft power

    NASA Technical Reports Server (NTRS)

    Fleischmann, C. W.; Horning, R. J.

    1988-01-01

    An active thionyl chloride high rate battery is under development for spacecraft operations. It is a 540kC (150 Ah) battery capable of pulses up to 75A. This paper describes the design and initial test data on a 'state-of-the-art' cell that has been selected to be the baseline for the prototype cell for that battery. Initial data indicate that the specification can be met with fresh cells. Data for stored cells and additional environmental test data are in the process of being developed.

  10. 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.

  11. 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.

  12. 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.

  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. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

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

    NASA Technical Reports Server (NTRS)

    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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  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. 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.

  10. 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.

  11. 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.

  12. 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.

  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. 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.

  15. 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.

  16. 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

  17. SSTI- Lewis Spacecraft Nickel-Hydrogen Battery

    NASA Technical Reports Server (NTRS)

    Tobias, R. F.

    1997-01-01

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

  18. 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.

  19. 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.

  20. 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

  1. NWSC nickel cadmium spacecraft cell accelerated life test program data analysis

    NASA Technical Reports Server (NTRS)

    Lander, J.

    1980-01-01

    An analysis of the data leading to a proposed accelerated life test scheme to test a nickel cadmium cell under spacecraft usage conditions is described. The amount and concentration of electrolyte and the amount of precharge in the cell are discussed in relation to the design of the cell and the accelerated test design. A failure analysis of the cell is summarized. The analysis included such environmental test variables as the depth of discharge, the temperature, the amount of recharge and the charge and discharge rate.

  2. 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.

  3. 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

  4. 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.

  5. Tumor initiating cells in malignant gliomas

    PubMed Central

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

    2009-01-01

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

  6. 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

  7. Cell-cycle-specific initiation of replication.

    PubMed

    Nordström, K; Austin, S J

    1993-11-01

    The following characteristics are relevant when replication of chromosomes and plasmids is discussed in relation to the cell cycle: the timing or replication, the selection of molecules for replication, and the coordination of multiple initiation events within a single cell cycle. Several fundamentally different methods have been used to study these processes: Meselson-Stahl density-shift experiments, experiments with the so-called 'baby machine', sorting of cells according to size, and flow cytometry. The evidence for precise timing and co-ordination of chromosome replication in Escherichia coli is overwhelming. Similarly, the high-copy-number plasmid ColE1 and the low-copy-number plasmids R1/R100 without any doubt replicate randomly throughout the cell cycle. Data about the low-copy-number plasmids F and P1 are conflicting. This calls for new types of experiments and for a better understanding of how these plasmids control their replication and partitioning.

  8. 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

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

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

  11. Spacecraft charging

    NASA Technical Reports Server (NTRS)

    Stevens, N. John

    1989-01-01

    The effects of spacecraft charging on spacecraft materials are studied. Spacecraft charging interactions seem to couple environment to system performance through materials. Technology is still developing concerning both environment-driven and operating system-driven interactions. The meeting addressed environment but lacked specific mission requirements, as a result system definition are needed to prioritize interactions.

  12. CDC20 maintains tumor initiating cells

    PubMed Central

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

    2015-01-01

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

  13. WIND Spacecraft Launch

    NASA Technical Reports Server (NTRS)

    1994-01-01

    An international effort to learn more about the complex interaction between the Earth and Sun took another step forward with the launch of WIND spacecraft from Kennedy Space Center (KSC). WIND spacecraft is studded with eight scientific instruments - six US, one French, and one - the first Russian instrument to fly on a US spacecraft - that collected data about the influence of the solar wind on the Earth and its atmosphere. WIND is part of the Global Geospace Science (GGS) initiative, the US contribution to NASA's International Solar Terrestrial Physics (ISTP) program.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Metformin selectively affects human glioblastoma tumor-initiating cell viability

    PubMed Central

    Würth, Roberto; Pattarozzi, Alessandra; Gatti, Monica; Bajetto, Adirana; Corsaro, Alessandro; Parodi, Alessia; Sirito, Rodolfo; Massollo, Michela; Marini, Cecilia; Zona, Gianluigi; Fenoglio, Daniela; Sambuceti, Gianmario; Filaci, Gilberto; Daga, Antonio; Barbieri, Federica; Florio, Tullio

    2013-01-01

    Cancer stem cell theory postulates that a small population of tumor-initiating cells is responsible for the development, progression and recurrence of several malignancies, including glioblastoma. In this perspective, tumor-initiating cells represent the most relevant target to obtain effective cancer treatment. Metformin, a first-line drug for type II diabetes, was reported to possess anticancer properties affecting the survival of cancer stem cells in breast cancer models. We report that metformin treatment reduced the proliferation rate of tumor-initiating cell-enriched cultures isolated from four human glioblastomas. Metformin also impairs tumor-initiating cell spherogenesis, indicating a direct effect on self-renewal mechanisms. Interestingly, analyzing by FACS the antiproliferative effects of metformin on CD133-expressing subpopulation, a component of glioblastoma cancer stem cells, a higher reduction of proliferation was observed as compared with CD133-negative cells, suggesting a certain degree of cancer stem cell selectivity in its effects. In fact, glioblastoma cell differentiation strongly reduced sensitivity to metformin treatment. Metformin effects in tumor-initiating cell-enriched cultures were associated with a powerful inhibition of Akt-dependent cell survival pathway, while this pathway was not affected in differentiated cells. The specificity of metformin antiproliferative effects toward glioblastoma tumor-initiating cells was confirmed by the lack of significant inhibition of normal human stem cells (umbilical cord-derived mesenchymal stem cells) in vitro proliferation after metformin exposure. Altogether, these data clearly suggest that metformin exerts antiproliferative activity on glioblastoma cells, showing a higher specificity toward tumor-initiating cells, and that the inhibition of Akt pathway may represent a possible intracellular target of this effect. PMID:23255107

  2. Spacecraft sterilization.

    NASA Technical Reports Server (NTRS)

    Kalfayan, S. H.

    1972-01-01

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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. ESA Spacecraft Propulsion Activities

    NASA Astrophysics Data System (ADS)

    Saccoccia, G.

    2004-10-01

    ESA is currently involved in several activities related to spacecraft chemical and electric propulsion, from the basic research and development of conventional and new concepts to the manufacturing, AIV and flight control of the propulsion subsystems of several European satellites. In the commercial application field, the strong competition among satellite manufacturers is a major driver for advancements in the area of propulsion, where increasing better performance together with low prices are required. Furthermore, new scientific and Earth observation missions dictate new challenging requirements for propulsion systems and components based on advanced technologies. For all these reasons, the technology area of spacecraft propulsion is in strong evolution and this paper presents an overview of the current European programmes and initiatives in this technology field. Specific attention is devoted in the paper to the performance and flight experience of spacecraft currently in orbit or ready to be launched.

  8. Initiation of human cytomegalovirus infection requires initial interaction with cell surface heparan sulfate.

    PubMed

    Compton, T; Nowlin, D M; Cooper, N R

    1993-04-01

    In this report, we demonstrate that the initial event in human cytomegalovirus (HCMV) infection is attachment to extracellular heparan sulfate. Further, this interaction is important for initiation of infection in fibroblast cells. Using microbinding assays to specifically monitor virus attachment as well as plaque titration assays to measure infectivity, we found that heparin competition as well as enzymatic digestion of cells with heparinase blocked virus attachment, initiation of immediate-early gene expression and infectivity. Other major glycosaminoglycans were found not to be involved in HCMV attachment and infectivity. In addition, HCMV was unable to attach to mutant derivatives of Chinese hamster ovary cells deficient in synthesis of heparan sulfate proteoglycans. Basic fibroblast growth factor, which requires initial interaction with extracellular heparin prior to binding to its high affinity receptor, also inhibited HCMV attachment to cells. Time-course experiments revealed that the initial HCMV binding was sensitive to heparin competition (10 micrograms/ml) or 0.75 M salt washes. The initial heparin-dissociable binding converted rapidly to high affinity (heparin resistant) HCMV attachment. These data suggest that sequential receptor interactions may mediate HCMV adsorption to cells. Heparin affinity chromatography revealed that multiple HCMV envelope glycoproteins, including gB, are capable of binding to heparin.

  9. 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.

  10. Spacecraft Antennas

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

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

  11. Changes of initiation mass and cell dimensions by the 'eclipse'.

    PubMed

    Zaritsky, Arieh; Vischer, Norbert; Rabinovitch, Avinoam

    2007-01-01

    The minimum time (E) required for a new pair of replication origins (oriCs) produced upon initiating a round of replication to be ready to initiate the next round after one cell mass doubling, the 'eclipse', is explained in terms of a minimal distance (l(min)) that the replication forks must move away from oriC before oriCs can 'fire' again. In conditions demanding a scheduled initiation event before the relative distance l(min)/L(0.5) (L being the total chromosome length) is reached, initiation is presumably delayed. Under such circumstances, cell mass at the next initiation would be greater than the usual, constant Mi (cell mass per copy number of oriC) prevailing in steady state of exponential growth. This model can be tested experimentally by extending the replication time C using thymine limitation at short doubling times tau in rich media to reach a relative eclipse E/C < l(min)/L(0.5). It is consistent with results obtained in experiments in which the number of replication 'positions'n (= C/tau) is increased beyond the natural maximum, causing the mean cell size to rise continuously, first by widening, then by lengthening, and finally by splitting its poles. The consequent branching is associated with casting off a small proportion of normal-sized cells and lysing DNA-less cells. Whether or how these phenomena are related to peptidoglycan composition and synthesis are moot questions. PMID:17140410

  12. Prospective Isolation of Clonogenic Mantle Cell Lymphoma Initiating Cells

    PubMed Central

    Chen, Zheng; Ayala, Paul; Wang, Michael; Fayad, Luis; Katz, Ruth L.; Romaguera, Jorge; Caraway, Nancy; Neelapu, Sattva S.; Kwak, Larry W.; Simmons, Paul J.; McCarty, Nami

    2010-01-01

    Here, we have prospectively isolated and characterized, for the first time, clonogenic cells with self-renewal capacities from mantle cell lymphoma (MCL), a particularly deadly form of Non-Hodgkin’s Lymphoma (NHL). Self-renewal and tumorigenic activities were enriched in MCL cell fractions that lacked expression of the prototypic B cell surface marker, CD19. CD45+CD19− cells represented a relatively small fraction of the total MCL tumor cells, however, they recapitulated the heterogeneity of original patient tumors upon transplantation into immunodeficient mice. As few as 100 of these cells displayed self-renewal capacities in secondary and tertiary recipient mice by in vivo limiting dilution assays. Similar to leukemic stem cells, CD45+CD19− MCL cells also displayed a quiescent status as determined by dye efflux assays. In summary, this study is the first to isolate subpopulations of MCL cells that have self-renewal and tumorigenic capacities. Identification and characterization of MCL-ICs is an important first step toward understanding how self-renewal and tumorigenicity are regulated in MCL and designing targeted therapies against MCL-ICs will ultimately lead to improved outcomes for MCL patients. PMID:20851072

  13. 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.

  14. 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.

  15. 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).

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

    NASA Technical Reports Server (NTRS)

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

    1986-01-01

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

  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. Glioma-initiating cells and molecular pathology: implications for therapy.

    PubMed

    Natsume, Atsushi; Kinjo, Sayano; Yuki, Kanako; Kato, Takenori; Ohno, Masasuke; Motomura, Kazuya; Iwami, Kenichiro; Wakabayashi, Toshihiko

    2011-02-01

    There is now compelling evidence that gliomas harbor a small population of cells, termed glioma-initiating cells (GICs), characterized by their ability to undergo self-renewal and initiate tumorigenesis. The development of therapeutic strategies targeted toward GIC signaling may improve the treatment of malignant gliomas. The characterization of GICs provides a clue to elucidating histological heterogeneity and treatment failure. The role of the stem cell marker CD133 in the initiation and progression of brain tumors is still uncertain. Here, we review some of the signaling mechanisms involved in GIC biology, such as phosphatase and tensin homolog (PTEN), sonic hedgehog, Notch, and WNT signaling pathways, maternal embryonic leucine-zipper kinase (MELK), BMI1, and Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling. In addition, we discuss the role of microRNAs in GICs by focusing on microRNA-21 regulation by type I interferon.

  19. 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.

  20. 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.

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

    PubMed Central

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

    2014-01-01

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

  2. Brain metastasis-initiating cells: survival of the fittest.

    PubMed

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

    2014-05-22

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

  3. 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.

  4. 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.

  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. 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

  7. 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.

  8. 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.

  9. 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.

  10. Modeling Cell–Cell Interactions in Regulating Multiple Myeloma Initiating Cell Fate

    PubMed Central

    Peng, Tao; Peng, Huiming; Choi, Dong Soon; Su, Jing; (Jeff) Chang, Chung-Che

    2014-01-01

    Cancer initiating cells have been documented in multiple myeloma and believed to be a key factor that initiates and drives tumor growth, differentiation, metastasis, and recurrence of the diseases. Although myeloma initiating cells (MICs) are likely to share many properties of normal stem cells, the underlying mechanisms regulating the fate of MICs are largely unknown. Studies designed to explore such communication are urgently needed to enhance our ability to predict the fate decisions of MICs (self-renewal, differentiation, and proliferation). In this study, we developed a novel system to understand the intercellular communication between MICs and their niche by seamlessly integrating experimental data and mathematical model. We first designed dynamic cell culture experiments and collected three types of cells (side population cells, progenitor cells, and mature myeloma cells) under various cultural conditions with flow cytometry. Then we developed a lineage model with ordinary differential equations by considering secreted factors, self-renewal, differentiation, and other biological functions of those cells, to model the cell–cell interactions among the three cell types. Particle swarm optimization was employed to estimate the model parameters by fitting the experimental data to the lineage model. The theoretical results show that the correlation coefficient analysis can reflect the feedback loops among the three cell types, the intercellular feedback signaling can regulate cell population dynamics, and the culture strategies can decide cell growth. This study provides a basic framework of studying cell–cell interactions in regulating MICs fate. PMID:24058033

  11. 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.

  12. 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

  13. 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.

  14. A global spacecraft control network for spacecraft autonomy research

    NASA Technical Reports Server (NTRS)

    Kitts, Christopher A.

    1996-01-01

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

  15. TISdb: a database for alternative translation initiation in mammalian cells.

    PubMed

    Wan, Ji; Qian, Shu-Bing

    2014-01-01

    Proper selection of the translation initiation site (TIS) on mRNAs is crucial for the production of desired protein products. Recent studies using ribosome profiling technology uncovered a surprising variety of potential TIS sites in addition to the annotated start codon. The prevailing alternative translation reshapes the landscape of the proteome in terms of diversity and complexity. To identify the hidden coding potential of the transcriptome in mammalian cells, we developed global translation initiation sequencing (GTI-Seq) that maps genome-wide TIS positions at nearly a single nucleotide resolution. To facilitate studies of alternative translation, we created a database of alternative TIS sites identified from human and mouse cell lines based on multiple GTI-Seq replicates. The TISdb, available at http://tisdb.human.cornell.edu, includes 6991 TIS sites from 4961 human genes and 9973 TIS sites from 5668 mouse genes. The TISdb website provides a simple browser interface for query of high-confidence TIS sites and their associated open reading frames. The output of search results provides a user-friendly visualization of TIS information in the context of transcript isoforms. Together, the information in the database provides an easy reference for alternative translation in mammalian cells and will support future investigation of novel translational products.

  16. Mitochondrial control by DRP1 in brain tumor initiating cells.

    PubMed

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

    2015-04-01

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

  17. Modeling of spacecraft charging

    NASA Technical Reports Server (NTRS)

    Whipple, E. C., Jr.

    1977-01-01

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

  18. Computer simulation of spacecraft/environment interaction.

    PubMed

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

    1999-10-01

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

  19. Computer simulation of spacecraft/environment interaction.

    PubMed

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

    1999-10-01

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

  20. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  3. 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

  4. Lean spacecraft avionics trade study

    NASA Technical Reports Server (NTRS)

    Main, John A.

    1994-01-01

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

  5. 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.

  6. Initiation of picornavirus protein synthesis in ascites cell extracts.

    PubMed

    Oberg, B F; Shatkin, A J

    1972-12-01

    The current model of picornavirus protein formation implies that initiation of protein synthesis occurs at a single site on the viral RNA, and that the large polypeptide formed is later cleaved. A direct test of this model was made in vitro by studying the incorporation of [(35)S]methionine from rabbit liver Met-tRNA(M) (Met) and fMet-tRNA(F) (Met) into encephalomyocarditis virus RNA-coded proteins in extracts of Ehrlich ascites cells. The incorporation of N-formylmethionine was complete within 5 min, while utilization of Met-tRNA(M) (Met) continued for 20 min. Tryptic digests of [(35)S]methionine-labeled products from Met-tRNA(M) (Met) analyzed by anion-exchange chromatography yielded more than 30 peptides, as compared to about 15 [(35)S]methionine-labeled peptides from purified encephalomyocarditis virus. In contrast, products labeled with fMet-tRNA(F) (Met) yielded one major (26)S-labeled tryptic peptide. The N-terminal location of methionine in this peptide was verified by Edman degradation. One predominant N-terminal tryptic peptide was also obtained with fMet-tRNA(F) (Met) when mouse Elberfeld and mengo-virus RNAs were used as messengers. On the basis of N-terminal compared with internal labeling of the products, no evidence for in vitro post-translational cleavage was found. The results are consistent with a single initiation site for synthesis of picornavirus proteins.

  7. 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

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

    PubMed

    Askenase, P W; Tsuji, R F

    2000-01-01

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

  9. Initial Fe/O Enhancements in Large, Gradual, Solar Energetic Particle Events: Observations from Widely-Separated Spacecraft, Wind and Ulysses

    NASA Astrophysics Data System (ADS)

    Tylka, A. J.; Ko, Y. K.; Malandraki, O. E.; Dorrian, G.; Marsden, R. G.; Ng, C. K.; Tranquille, C.

    2012-04-01

    Composition measurements are a powerful tool in investigating the acceleration and transport processes that govern the production solar energetic particles (SEPs). A wide array of observational evidence indicates that shocks driven by fast coronal mass ejections are the dominant acceleration mechanism in large, so-called gradual SEP events. However, in some gradual events, the Fe/O ratio above a few MeV/nucleon sometimes shows a very strong enhancement at the beginning of the event, with Fe/O ~ 1, as typical of impulsive SEP events, in which particle acceleration at reconnections sites (such as flares) are believed to dominate. Some researchers have attributed these initial Fe/.O enhancements to a direct flare component; others have explained it in terms of rigidity-dependent SEP transport. We examine this controversy using observations of initial Fe/O enhancements in two large SEP events in 2001 by Wind at L1 and by Ulysses at high heliolatitudes and beyond 1.6 AU. We also examine the implications of these observations to the controversy about how SEPs reach high heliolatitudes, either by cross-field diffusion or by latitudinal expansion of the CME-driven shock. This work has been supported by the NASA Heliophysics Guest Investigator Program under DPR NNH09AK79I and has received funding from the European Commission FP7 Project COMESEP (263252).

  10. 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

    2013-04-01

    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.

  11. 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

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

    PubMed

    Kaur, Sarabpreet; Sahambi, J S

    2016-04-01

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

  13. 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

  14. Implicit Spacecraft Gyro Calibration

    NASA Technical Reports Server (NTRS)

    Harman, Richard; Bar-Itzhack, Itzhack Y.

    2003-01-01

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

  15. 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.

  16. 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.

  17. 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,

  18. 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.

  19. 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.

  20. Tip cell-derived RTK signaling initiates cell movements in the Drosophila stomatogastric nervous system anlage.

    PubMed

    González-Gaitán, M; Jäckle, H

    2000-10-01

    The stomatogastric nervous system (SNS) of Drosophila is a simply organized neural circuitry that innervates the anterior enteric system. Unlike the central and the peripheral nervous systems, the SNS derives from a compact epithelial anlage in which three invagination centers, each giving rise to an invagination fold headed by a tip cell, are generated. Tip cell selection involves lateral inhibition, a process in which Wingless (Wg) activity adjusts the range of Notch signaling. Here we show that RTK signaling mediated by the Drosophila homolog of the epidermal growth factor receptor, DER, plays a key role in two consecutive steps during early SNS development. Like Wg, DER signaling participates in adjusting the range of Notch-dependent lateral inhibition during tip cell selection. Subsequently, tip cells secrete the DER ligand Spitz and trigger local RTK signaling, which initiates morphogenetic movements resulting in the tip cell-directed invaginations within the SNS anlage.

  1. 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.

  2. 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.

  3. 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.

  4. Spacecraft exploration of Mars

    NASA Technical Reports Server (NTRS)

    Snyder, Conway W.; Moroz, Vasilii I.

    1992-01-01

    Soviet and American spacecraft exploration of Mars over the past quarter century is reviewed. Data on the earliest Soviet attempts to send spacecraft to observe the planet are presented. Of the series of spacecraft that were announced (designated Mars 1 to Mars 7), none fulfilled all its scientific goals, but some good photographs and other important data were obtained. Of the six spacecraft in the Mariner series, two failed, but Mariner 4 first revealed the cratered surface of Mars, and Mariner 9 discovered all the major geologic features. The Viking mission, with its two Orbiters, two Landers, and its 6-yr duration, surpassed in quantity and variety of data all other missions combined. The Phobos mission ended in two failures, but the second of the two spacecraft acquired significant new data about Mars and Phobos. An appendix listing special issues of journals containing collections of papers about Mars is provided.

  5. 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.

  6. 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.

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

    PubMed Central

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

    2010-01-01

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

  8. Transposon mutagenesis identifies genes that transform neural stem cells into glioma-initiating cells.

    PubMed

    Koso, Hideto; Takeda, Haruna; Yew, Christopher Chin Kuan; Ward, Jerrold M; Nariai, Naoki; Ueno, Kazuko; Nagasaki, Masao; Watanabe, Sumiko; Rust, Alistair G; Adams, David J; Copeland, Neal G; Jenkins, Nancy A

    2012-10-30

    Neural stem cells (NSCs) are considered to be the cell of origin of glioblastoma multiforme (GBM). However, the genetic alterations that transform NSCs into glioma-initiating cells remain elusive. Using a unique transposon mutagenesis strategy that mutagenizes NSCs in culture, followed by additional rounds of mutagenesis to generate tumors in vivo, we have identified genes and signaling pathways that can transform NSCs into glioma-initiating cells. Mobilization of Sleeping Beauty transposons in NSCs induced the immortalization of astroglial-like cells, which were then able to generate tumors with characteristics of the mesenchymal subtype of GBM on transplantation, consistent with a potential astroglial origin for mesenchymal GBM. Sequence analysis of transposon insertion sites from tumors and immortalized cells identified more than 200 frequently mutated genes, including human GBM-associated genes, such as Met and Nf1, and made it possible to discriminate between genes that function during astroglial immortalization vs. later stages of tumor development. We also functionally validated five GBM candidate genes using a previously undescribed high-throughput method. Finally, we show that even clonally related tumors derived from the same immortalized line have acquired distinct combinations of genetic alterations during tumor development, suggesting that tumor formation in this model system involves competition among genetically variant cells, which is similar to the Darwinian evolutionary processes now thought to generate many human cancers. This mutagenesis strategy is faster and simpler than conventional transposon screens and can potentially be applied to any tissue stem/progenitor cells that can be grown and differentiated in vitro.

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

    SciTech Connect

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

    2002-06-01

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

  10. 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.

  11. 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.

  12. Glioma-Initiating Cell Elimination by Metformin Activation of FOXO3 via AMPK

    PubMed Central

    Sunayama, Jun; Okada, Masashi; Watanabe, Eriko; Seino, Shizuka; Shibuya, Keita; Suzuki, Kaori; Narita, Yoshitaka; Shibui, Soichiro; Kayama, Takamasa

    2012-01-01

    Control of the cancer stem/initiating cell population is considered key to realizing the long-term survival of glioblastoma patients. Recently, we demonstrated that FOXO3 activation is sufficient to induce differentiation of glioma-initiating cells having stem-like properties and inhibit their tumor-initiating potential. Here we identified metformin, an antidiabetic agent, as a therapeutic activator of FOXO3. Metformin activated FOXO3 and promoted differentiation of such stem-like glioma-initiating cells into nontumorigenic cells. Furthermore, metformin promoted FOXO3 activation and differentiation via AMP-activated protein kinase (AMPK) activation, which was sensitive to extracellular glucose availability. Importantly, transient, systemic administration of metformin depleted the self-renewing and tumor-initiating cell population within established tumors, inhibited tumor formation by stem-like glioma-initiating cells in the brain, and provided a substantial survival benefit. Our findings demonstrate that targeting glioma-initiating cells via the AMPK-FOXO3 axis is a viable therapeutic strategy against glioblastoma, with metformin being the most clinically relevant drug ever reported for targeting of glioma-initiating cells. Our results also establish a novel, direct link between glucose metabolism and cancer stem/initiating cells. PMID:23197693

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

    PubMed

    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; Woodhoo, Ashwin; Jessen, Kristján R

    2015-07-01

    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.

  14. Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche.

    PubMed

    Davis, Hayley; Irshad, Shazia; Bansal, Mukesh; Rafferty, Hannah; Boitsova, Tatjana; Bardella, Chiara; Jaeger, Emma; Lewis, Annabelle; Freeman-Mills, Luke; Giner, Francesc C; Rodenas-Cuadrado, Pedro; Mallappa, Sreelakshmi; Clark, Susan; Thomas, Huw; Jeffery, Rosemary; Poulsom, Richard; Rodriguez-Justo, Manuel; Novelli, Marco; Chetty, Runjan; Silver, Andrew; Sansom, Owen J; Greten, Florian R; Wang, Lai Mun; East, James E; Tomlinson, Ian; Leedham, Simon J

    2015-01-01

    Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell fate that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem cell is not the sole cell of origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps.

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

    PubMed

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

    2012-04-01

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

  16. Surviving atmospheric spacecraft breakup.

    PubMed

    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.

  17. 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.

  18. 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.

  19. 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.

  20. Mars Global Surveyor Spacecraft

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Jet Propulsion Laboratory (JPL) workers in the Payload Hazardous Servicing Facility (PHSF) prepare the Mars Global Surveyor spacecraft for transfer to the launch pad by placing it in a protective canister. The Surveyor spacecraft (upper) is already mated to its solid propellant upper stage booster (lower), which is actually the third stage of the Delta II expendable launch vehicle that will propel the spacecraft on its interplanetary journey to the Red Planet. Once at Launch Pad 17A on Cape Canaveral Air Station, the spacecraft and booster assembly will be stacked atop the Delta vehicle. The Surveyor is slated for liftoff on Nov. 6, 1996 at the beginning of a 20 day launch period.

  1. 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.

  2. 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.

  3. Mecury Spacecraft Boilerplate

    NASA Technical Reports Server (NTRS)

    1944-01-01

    Boilerplate Mercury spacecraft being manufactured 'in-house' by Langley technicians. The capsules were designed to test spacecraft recovery systems. The escape tower and rocket motors shown on the completed capsule would be removed before shipping and finally assembly for launching at Wallops Island. Design of the Little Joe capsules began at Langley before McDonnell started on the design of the Mercury capsule.

  4. 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

  5. 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.

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

    PubMed

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

    2016-05-01

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

  7. 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.

  8. Advanced nickel-hydrogen spacecraft battery development

    NASA Astrophysics Data System (ADS)

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

    1994-02-01

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

  9. Spacecraft environments interactions: Protecting against the effects of spacecraft charging

    NASA Technical Reports Server (NTRS)

    Herr, J. L.; Mccollum, M. B.

    1994-01-01

    The effects of the natural space environments on spacecraft design, development, and operation are the topic of a series of NASA Reference Publications currently being developed by the Electromagnetics and Environments Branch, Systems Analysis and Integration Laboratory, Marshall Space Flight Center. This primer, second in the series, describes the interactions between a spacecraft and the natural space plasma. Under certain environmental/spacecraft conditions, these interactions result in the phenomenon known as spacecraft charging. It is the focus of this publication to describe the phenomenon of spacecraft charging and its possible adverse effects on spacecraft and to present the key elements of a Spacecraft Charging Effects Protection Plan.

  10. 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.

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

    PubMed Central

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

    2014-01-01

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

  12. Chloroplast Dedifferentiation in Mechanically Isolated Asparagus Cells during Culture Initiation.

    PubMed

    Harikrishna, K; Darby, R; Draper, J

    1992-11-01

    Mechanically isolated asparagus (Asparagus officinalis) mesophyll cells dedifferentiate and divide when cultured in the dark in a medium containing sucrose. A strong correlation was observed between the onset of cell division and a loss of photosynthetic capacity. For the first 8 to 9 d of culture, there was no change in chloroplast size or morphology. However, following this period, the chloroplasts divided to form smaller proplastid-like structures. The gross chlorophyll content of the cell population did not change, suggesting that the loss of photosynthetic potential was not by senescence. Northern analysis showed that mRNA of the small subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase was undetectable within 1 d postisolation, which was quicker than in dark-treated plants. The mRNA of the large subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase decreased to low levels within 2 d of cell isolation. Both the large and small subunits of ribulose 1,5-bisphosphate carboxylase/oxygenase protein showed a gradual reduction in abundance, falling to basal levels by days 6 to 7, which coincided with the onset of rapid cell division. A similar trend was observed with chloroplast rRNA molecules, which decreased to basal levels by day 6 in culture.

  13. The Phytoalexin Resveratrol Regulates the Initiation of Hypersensitive Cell Death in Vitis Cell

    PubMed Central

    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. PMID:22053190

  14. Spacecraft Charging at Geosynchronous Altitude: Application Development

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Cooke, D. L.

    2002-12-01

    We report on progress made toward the development of a geosynchronous spacecraft surface charging application that combines environmental results from the Magnetospheric Specification Model (MSM) with a minimal spacecraft approximation. Surface charging is identified as a net electron current to the kapton spacecraft determined by integrating electron, proton, and oxygen fluxes along with secondary and backscatter yields specified as a function of energy. A validation study of the MSM, covering 20-50 keV electrons from the Charge Control System (CCS) on a DSCS III B-7 spacecraft, indicated that the MSM consistently tracked the diurnal and seasonal variations of this energetic portion of the surface charging particle population [Hilmer and Ginet, J. Atmos. and Solar-Terr. Phys., 62, 1275, 2000]. Initial comparisons of on-orbit spacecraft frame charging measurements from CCS with results obtained using MSM output indicated that the MSM produced ion and electron fluxes, as well as evolving electron spectral features, well enough to reproduce geosynchronous spacecraft charging current densities in the two largest of three events studied in the geosynchronous environment. [Hilmer et al., Proc. of 7th SCTC, 23-27 April 2001, ESA SP-476, 235, 2001]. We will provide an overview of the updated MSM/charging algorithm simulations performed using a variety of input parameter combinations in order to quantify the potential benefits of integrating MSM environment specification with advanced charging codes such as NASCAP-2K to produce system-specific charging applications.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Taurus Lightweight Manned Spacecraft Earth orbiting vehicle

    NASA Astrophysics Data System (ADS)

    Bosset, M.

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

  20. Spacecraft Environment Interactions

    NASA Technical Reports Server (NTRS)

    Garrett, Henry B.; Jun, Insoo

    2011-01-01

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

  1. Predicting clinical outcome in feline oral squamous cell carcinoma: tumour initiating cells, telomeres and telomerase.

    PubMed

    Yoshikawa, H; Maranon, D G; Battaglia, C L R; Ehrhart, E J; Charles, J B; Bailey, S M; LaRue, S M

    2014-09-11

    Feline oral squamous cell carcinoma (SCC) has very poor prognosis. Here, a retrospective pilot study was conducted on 20 feline oral SCC patients who underwent stereotactic radiation therapy (SRT), to evaluate: (1) the value of putative tumour initiating cell (TIC) markers of human head and neck SCC (CD44, Bmi-1); (2) telomere length (TL) specifically in putative TICs; and (3) tumour relative telomerase activity (TA). Significant inverse correlations were found between treatment outcomes and Bmi-1 expression, supporting the predictive value of Bmi-1 as a negative prognostic indicator. While TL exhibited a wide range of variability, particularly in very short fractions, many tumours possessed high levels of TA, which correlated with high levels of Bmi-1, Ki67 and EGFR. Taken together, our results imply that Bmi-1 and telomerase may represent novel therapeutic targets in feline oral SCC, as their inhibition - in combination with SRT - would be expected to have beneficial treatment outcome. PMID:25212092

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

    PubMed Central

    Insel, Thomas R.; Koroshetz, Walter

    2015-01-01

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

  3. Disseminated intravascular large-cell lymphoma with initial presentation mimicking Guillain-Barré syndrome.

    PubMed

    Jiang, Qin Li; Pytel, Peter; Rowin, Julie

    2010-07-01

    We report a patient with intravascular large B-cell lymphoma who initially presented with acute ascending weakness and sensory changes. Electrodiagnostic testing and cerebral spinal fluid (CSF) studies were initially suggestive of a demyelinating polyneuropathy. Further clinical evaluation and testing were consistent with mononeuropathy multiplex. Autopsy revealed disseminated intravascular large-cell lymphoma. Intravascular large-cell lymphoma should be considered in the differential diagnosis of a rapidly evolving neuropathy associated with other organ involvement.

  4. 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.

  5. 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

  6. 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.

  7. Targeting of leukemia-initiating cells in acute promyelocytic leukemia

    PubMed Central

    Lo-Coco, Francesco

    2015-01-01

    Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with peculiar molecular, phenotypic and clinical features and unique therapeutic response to specific treatments. The disease is characterized by a single, pathognomonic molecular event, consisting of the translocation t(15;17) which gives rise to the PML/retinoic acid receptor α (RARα) hybrid protein. The development of this leukemia is mainly related to the fusion oncoprotein PML/RARα, acting as an altered RAR mediating abnormal signalling and repression of myeloid differentiation, with consequent accumulation of undifferentiated promyelocytes. The prognosis of APL has dramatically been improved with the introduction in therapy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). The main effect of these two drugs is linked to the targeting of either RAR moiety of the PML/RARα molecule and induction of cell differentiation (ATRA) or of the PML moiety of the fusion protein and induction of leukemic cell apoptosis, including leukemic progenitors (mostly induced by ATO). These two drugs exhibited excellent synergism and determine a very high rate of durable remissions in low/intermediate-risk APLs, when administered in the absence of any chemotherapeutic drug. The strong synergism and the marked clinical efficacy of these two agents when administered together seem to be related to their capacity to induce PML/RARα degradation and complete eradication of leukemia stem cells. PMID:27358876

  8. 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.

  9. 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.

  10. Multimission modular spacecraft (MMS)

    NASA Technical Reports Server (NTRS)

    Falkenhayn, Edward, Jr.

    1988-01-01

    This paper discusses the design requirements for the low-cost standard spacecraft development which has come to be known as the Multimission Modular Spacecraft (MMS). The paper presents the wide range of launch configurations of the MMS users, the population of programs using the MMS, and the cost effectiveness of the MMS concept. The paper addresses the in-orbit serviceability of the design as demonstrated by the successful SMM repair, and the recent selection of MMS for the Explorer Platform, which features in-orbit payload exchanges.

  11. Spacecraft Attitude Determination Methods

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  12. 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.

  13. 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

  14. Ultraviolet and charged particle irradiation of proposed solar cell coverslide materials and conductive coatings for the Helios spacecraft

    NASA Technical Reports Server (NTRS)

    Fry, J.; Nicoletta, C. A.

    1972-01-01

    Coverslide materials consisting of Corning 7940 fused silica, multilayers of titanium and manganese oxides (blue reflector), and indium oxide (conductive-coating) were exposed to 16 UVSC up to 800 EUVSH in vacuum. Slight changes in optical transmittance and optical absorptance were found in the (200-360) millimicron regions of the fused silica and conductive coating respectively. Exposure to 4 KeV protons and 4.5 KeV electrons in vacuum, produced decreases of several percent in transmittance, (200-360) millimicron region in the fused silicas after total fluxes less or = 10 to the 14th power particles/sq cm. Sheet resistance of the conductive coating increased above 1.0 kilo-ohm/square after a total flux less or = 10 to the 14th power particles/sq cm. Solar cells with coverglasses utilizing the indium oxide conductive coating were exposed to 1 Mev electrons and 1 Mev protons in air and in vacuum. Total fluxes ranged from 10 to the 11th power particles/sq cm to 10 to the 15th power particle/sq cm. There was no appreciable degradation in the resistance of the conductive coating during or after these tests.

  15. 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

  16. 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

  17. CCD architecture for spacecraft SAR image processing

    NASA Technical Reports Server (NTRS)

    Arens, W. E.

    1977-01-01

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

  18. Galileo spacecraft high gain antenna offset calibration

    NASA Technical Reports Server (NTRS)

    Hayati, S. A.

    1982-01-01

    A mathematical model for the estimation of the dual-spin Galileo spacecraft high gain antenna misalignment is developed. The feasibility of the proposed technique is investigated by means of a simulation study. In-flight parameter estimation requires the development of a stochastic model of the spacecraft rotational biases and the earth-received signal strength measurements. The signal strength measurements for X-band frequency are used as observations to estimate the rotational biases and their corresponding uncertainties. The simulation study shows that the initial ground measured uncertainties of .6 mrad can be reduced by a factor of ten.

  19. 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.

  20. Unmanned spacecraft for research

    NASA Technical Reports Server (NTRS)

    Graves, C. D.

    1972-01-01

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

  1. 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.

  2. Microbial contamination of spacecraft

    NASA Technical Reports Server (NTRS)

    Pierson, D. L.

    2001-01-01

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

  3. Microbial contamination of spacecraft.

    PubMed

    Pierson, D L

    2001-06-01

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

  4. Cell cycle regulation and cell type-specific localization of the FtsZ division initiation protein in Caulobacter.

    PubMed Central

    Quardokus, E; Din, N; Brun, Y V

    1996-01-01

    Many genes involved in cell division and DNA replication and their protein products have been identified in bacteria; however, little is known about the cell cycle regulation of the intracellular concentration of these proteins. It has been shown that the level of the tubulin-like GTPase FtsZ is critical for the initiation of cell division in bacteria. We show that the concentration of FtsZ varies dramatically during the cell cycle of Caulobacter crescentus. Caulobacter produce two different cell types at each cell division: (i) a sessile stalked cell that can initiate DNA replication immediately after cell division and (ii) a motile swarmer cell in which DNA replication is blocked. After cell division, only the stalked cell contains FtsZ. FtsZ is synthesized slightly before the swarmer cells differentiate into stalked cells and the intracellular concentration of FtsZ is maximal at the beginning of cell division. Late in the cell cycle, after the completion of chromosome replication, the level of FtsZ decreases dramatically. This decrease is probably mostly due to the degradation of FtsZ in the swarmer compartment of the predivisional cell. Thus, the variation of FtsZ concentration parallels the pattern of DNA synthesis. Constitutive expression of FtsZ leads to defects in stalk biosynthesis suggesting a role for FtsZ in this developmental process in addition to its role in cell division. Images Fig. 2 Fig. 3 Fig. 4 PMID:8692812

  5. 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

  6. 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

  7. 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

  8. 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.

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

    PubMed

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

    2016-02-15

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

  10. 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...

  11. 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 ...

  12. 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.

  13. 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.

  14. 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.

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

    PubMed

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

    2011-10-15

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

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

    NASA Technical Reports Server (NTRS)

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

    1978-01-01

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

  17. Coordination challenges for autonomous spacecraft

    NASA Technical Reports Server (NTRS)

    Clement, B. J.; Barrett, A.

    2002-01-01

    While past flight projects involved a single spacecraft in isolation, over forty proposed future missions involve multiple coordinated spacecraft. This paper presents characteristics of such missions in terms of properties of the phenomena being measured as well as the rationale for using multiple spacecraft. We describe the coordination problems associated with operating these missions and identify needed technologies.

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

    PubMed Central

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

    2007-01-01

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

  19. 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

  20. 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.

  1. Spacecraft crew escape

    NASA Astrophysics Data System (ADS)

    Miller, B. A.

    Safe crew escape from spacecraft is extremely difficult to engineer and has large cost and vehicle payload penalties. Because of these factors calculated risks have apparently been taken and only the most rudimentary means of crew protecion have been provided for space programs. Although designed for maximum reliability and safety a calculated risk is taken that on-balance it is more acceptable to risk the loss of possibly some or all occupants than introduce the mass, cost and complexity of an escape system. This philosophy was accepted until the Challenger tragedy. It is now clear that the use of this previously acceptable logic is invalid and that provisions must be made for spacecraft crew escape in the event of a catastrophic accident. This paper reviews the funded studies and subsequent proposals undertaken by Martin-Baker for the use of both encapsullated and open ejection seats for the Hermes Spaceplane. The technical difficulties, special innovations and future applications are also discussed.

  2. LEO Spacecraft Charging Guidelines

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

  3. Homozygously deleted gene DACH1 regulates tumor-initiating activity of glioma cells

    PubMed Central

    Watanabe, Akira; Ogiwara, Hideki; Ehata, Shogo; Mukasa, Akitake; Ishikawa, Shumpei; Maeda, Daichi; Ueki, Keisuke; Ino, Yasushi; Todo, Tomoki; Yamada, Yasuhiro; Fukayama, Masashi; Saito, Nobuhito; Miyazono, Kohei; Aburatani, Hiroyuki

    2011-01-01

    Loss or reduction in function of tumor suppressor genes contributes to tumorigenesis. Here, by allelic DNA copy number analysis using single-nucleotide polymorphism genotyping array and mass spectrometry, we report homozygous deletion in glioblastoma multiformes at chromosome 13q21, where DACH1 gene is located. We found decreased cell proliferation of a series of glioma cell lines by forced expression of DACH1. We then generated U87TR-Da glioma cells, where DACH1 expression could be activated by exposure of the cells to doxycycline. Both ex vivo cellular proliferation and in vivo growth of s.c. transplanted tumors in mice are reduced in U87TR-Da cells with DACH1 expression (U87-DACH1-high), compared with DACH1-nonexpressing U87TR-Da cells (U87-DACH1-low). U87-DACH1-low cells form spheroids with CD133 and Nestin expression in serum-free medium but U87-DACH1-high cells do not. Compared with spheroid-forming U87-DACH1-low cells, adherent U87-DACH1-high cells display lower tumorigenicity, indicating DACH1 decreases the number of tumor-initiating cells. Gene expression analysis and chromatin immunoprecipitation assay reveal that fibroblast growth factor 2 (FGF2/bFGF) is transcriptionally repressed by DACH1, especially in cells cultured in serum-free medium. Exogenous bFGF rescues spheroid-forming activity and tumorigenicity of the U87-DACH1-high cells, suggesting that loss of DACH1 increases the number of tumor-initiating cells through transcriptional activation of bFGF. These results illustrate that DACH1 is a distinctive tumor suppressor, which does not only suppress growth of tumor cells but also regulates bFGF-mediated tumor-initiating activity of glioma cells. PMID:21750150

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. Optical control demonstrates switch-like PIP3 dynamics underlying the initiation of immune cell migration.

    PubMed

    Karunarathne, W K Ajith; Giri, Lopamudra; Patel, Anilkumar K; Venkatesh, Kareenhalli V; Gautam, N

    2013-04-23

    There is a dearth of approaches to experimentally direct cell migration by continuously varying signal input to a single cell, evoking all possible migratory responses and quantitatively monitoring the cellular and molecular response dynamics. Here we used a visual blue opsin to recruit the endogenous G-protein network that mediates immune cell migration. Specific optical inputs to this optical trigger of signaling helped steer migration in all possible directions with precision. Spectrally selective imaging was used to monitor cell-wide phosphatidylinositol (3,4,5)-triphosphate (PIP3), cytoskeletal, and cellular dynamics. A switch-like PIP3 increase at the cell front and a decrease at the back were identified, underlying the decisive migratory response. Migration was initiated at the rapidly increasing switch stage of PIP3 dynamics. This result explains how a migratory cell filters background fluctuations in the intensity of an extracellular signal but responds by initiating directionally sensitive migration to a persistent signal gradient across the cell. A two-compartment computational model incorporating a localized activator that is antagonistic to a diffusible inhibitor was able to simulate the switch-like PIP3 response. It was also able simulate the slow dissipation of PIP3 on signal termination. The ability to independently apply similar signaling inputs to single cells detected two cell populations with distinct thresholds for migration initiation. Overall the optical approach here can be applied to understand G-protein-coupled receptor network control of other cell behaviors.

  10. 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.

  11. Progesterone regulates chicken embryonic germ cell meiotic initiation independent of retinoic acid signaling.

    PubMed

    Mi, Yuling; He, Bin; Li, Jian; Zhang, Caiqiao

    2014-07-15

    The signaling molecule retinoic acid (RA) is known to trigger germ cells to enter meiosis. However, RA may not be the only secreted inducer of meiosis. Our previous data indicate that luteinizing hormone also promotes germ cell meiotic initiation by upregulating 3βHSDII transcription. Here, using chicken embryos, we investigate the role of progesterone (P4) in regulating germ cell meiotic initiation. Progesterone treatment at embryonic Day 9.5 accelerated germ cell meiosis entry in the female chicken embryos. However, P4 treatment in vivo did no influence on testicular germ cells but triggered their meiotic initiation in the cultured testes. As treatment with an RA receptor (RAR) inhibitor did not block the stimulatory effect of P4 on germ cell meiotic initiation, this P4 stimulatory effect seems to be independent of RAR-mediated signaling. The abundance of RA metabolism-related enzymes and RAR (RARβ) mRNAs did not differ significantly between P4-treated and control individuals. The RA concentration in the ovaries remained unchanged by P4 treatment in vivo. Because no inhibition by the P4 receptor (PR) nuclear receptor antagonist mifepristone on P4 effect was observed in either in vitro or in vivo experiments, the effect of P4 on germ cell meiotic initiation is probably mediated by membrane PRs (mPR). The mPRα, mPRβ, and mPRγ mRNAs were all expressed in the embryonic ovaries. The expression of mPRα and mPRβ was higher than that of mPRγ. Immunohistochemical results showed that mPRα-positive cells were mainly scattered in the ovarian cortex area where most germ cells were distributed. The mPRβ-positive cells were widely distributed in the ovaries, and positive cells were clustered with a similar morphology to that of germ cell clusters. In conclusion, P4 may regulate embryonic germ cell meiotic initiation independent of RA signaling through the membrane PRs. This study provides a new insight into the mechanisms of germ cell meiotic initiation in the chicken

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

    SciTech Connect

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

    2012-01-01

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

  13. 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.

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

    SciTech Connect

    Kulkarni, M.

    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. 5 refs.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Maintenance of Leukemia-Initiating Cells Is Regulated by the CDK Inhibitor Inca1

    PubMed Central

    Bäumer, Nicole; Bäumer, Sebastian; Berkenfeld, Frank; Stehling, Martin; Köhler, Gabriele; Berdel, Wolfgang E.; Müller-Tidow, Carsten; Tschanter, Petra

    2014-01-01

    Functional differences between healthy progenitor and cancer initiating cells may provide unique opportunities for targeted therapy approaches. Hematopoietic stem cells are tightly controlled by a network of CDK inhibitors that govern proliferation and prevent stem cell exhaustion. Loss of Inca1 led to an increased number of short-term hematopoietic stem cells in older mice, but Inca1 seems largely dispensable for normal hematopoiesis. On the other hand, Inca1-deficiency enhanced cell cycling upon cytotoxic stress and accelerated bone marrow exhaustion. Moreover, AML1-ETO9a-induced proliferation was not sustained in Inca1-deficient cells in vivo. As a consequence, leukemia induction and leukemia maintenance were severely impaired in Inca1−/− bone marrow cells. The re-initiation of leukemia was also significantly inhibited in absence of Inca1−/− in MLL—AF9- and c-myc/BCL2-positive leukemia mouse models. These findings indicate distinct functional properties of Inca1 in normal hematopoietic cells compared to leukemia initiating cells. Such functional differences might be used to design specific therapy approaches in leukemia. PMID:25525809

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

    PubMed

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

    1995-05-15

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

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

    PubMed

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

    2016-01-14

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

  3. 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.

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

    PubMed

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

    2016-08-01

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

  5. Outsmart tumor exosomes to steal the cancer initiating cell its niche.

    PubMed

    Thuma, Florian; Zöller, Margot

    2014-10-01

    Exosomes are small vesicles that derive from endosomes and are delivered by many cells, including tumor cells that are a particular rich source of exosomes. Exosomes are suggested to be the most potent intercellular communicators. Being recovered in all body fluids, they can communicate with neighboring as well as distant cells. The latter was first described for dendritic cell exosomes that can initiate T cell activation. However, tumor exosomes (TEX) may impede this crosstalk. Besides with hematopoietic cells, TEX communicate with the tumor cell itself, but also with host stroma cells and endothelial cells. This crosstalk received much attention as there is strong evidence that TEX account for angiogenesis and premetastatic niche formation, which may proceed directly via binding and uptake of TEX by cells in the premetastatic organ or indirectly via TEX being taken up by hematopoietic progenitors in the bone marrow (BM), which mature toward lineages with immunosuppressive features or are forced toward premature release from the BM and homing into premetastatic organs. Knowing these deleterious activities of TEX, it becomes demanding to search for modes of therapeutic interference. I here introduce our hypothesis that metastasis formation may be hampered by tailored exosomes that outsmart TEX. The essential prerequisites are an in depth knowledge on TEX binding, uptake, binding-initiated signal transduction and uptake-promoted target cell reprogramming. PMID:24631836

  6. 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.

  7. Tumor initiating potential of side population cells in human gastric cancer.

    PubMed

    Fukuda, Kazumasa; Saikawa, Yoshiro; Ohashi, Masaki; Kumagai, Koshi; Kitajima, Masaki; Okano, Hideyuki; Matsuzaki, Yumi; Kitagawa, Yuko

    2009-05-01

    Side population (SP) cells are a small subpopulation of cells with enriched source of gastric tumor-initiating cells (TICs) with stem-like cell property that are characterized by high efflux ability of Hoechst 33342 dye, reflecting high expression of several subtypes of the ATP-binding cassette transporter family that is characteristic of stem cells. The present study is the first to discover and characterize SP cells within gastric cancer (GC) tumors. In this study, human GC cell lines (MKN45, KATOIII, MKN74, MKN28 and MKN1) were analyzed using flow cytometry for SP cell isolation, and all GC cell lines showed a distinct fraction of SP cells, ranging from 0.02+/-0.001 to 1.93+/-0.16%. Among these cell lines, MKN45 cultures possessed the highest percentage of SP cells. Using MKN45 cells, we demonstrated stem cell-like characteristics of SP cells of the cell lines as a possible subpopulation with enriched TICs, as indicated by ABC transporter gene expression (MDR1 and BCPR1), chemo-resistance and tumorigenicity in vivo. In addition, we report the first identification and isolation of SP cells from clinical GC tissues as well as human GC cell lines. These SP cells demonstrate higher tumorigenicity in vivo than does the overall cell population in the parent tissue. In conclusion, we demonstrate that solid tumor tissue such as human GC contains TICs, with the existence of heterogeneity and distinct hierarchy in malignancy, suggesting the future possibility of a novel therapeutic tool targeting TICs for overcoming this malignant disease. PMID:19360333

  8. Acetate is a superior substrate for microbial fuel cell initiation preceding bioethanol effluent utilization.

    PubMed

    Sun, Guotao; Thygesen, Anders; Meyer, Anne S

    2015-06-01

    This study assessed cell voltage development, electricity recovery, and microbial community composition in response to initial substrate including acetate, xylose, acetate/xylose 1:1 mixture (ace/xyl), and bioethanol effluent (BE) during microbial fuel cell (MFC) operation at 1000 Ω external resistance. The BE mainly contained 20.5 g/L xylose, 1.8 g/L arabinose, and 2.5 g/L propionic acid. The MFCs initially fed with acetate showed shorter initiation time (1 day), higher average cell voltage (634 ± 9 mV), and higher coulombic efficiency (31.5 ± 0.5 %) than those initially fed with ace/xyl or xylose. However, BE-initiated MFCs only generated 162 ± 1 mV. The acetate-initiated MFCs exhibited longer adaptation time (21 h) and lower cell voltage (645 ± 10 mV) when the substrate was switched to xylose, whereas substrate switching to BE produced the highest voltage (656 mV), maximum power density (362 ± 27 mW/m(2)), maximum current density (709 ± 27 mA/m(2)), and coulombic efficiency (25 ± 0.5 %) in the acetate-initiated MFCs. The microbial community in acetate-initiated MFCs was less diverse and contained more electrogenic bacteria (13.9 ± 0.4 %) including Geobacter sulfurreducens and Desulfuromonas acetexigen than the MFCs initially fed with ace/xyl, xylose, and BE. After switching the substrate to xylose and subsequently to BE, the microbial community in the acetate-initiated MFCs became more diverse, while no significant changes were observed in ace/xyl-, xylose-, and BE-initiated MFCs. The results showed that initial substrate affected the power generation and the capability to adapt to the substrate alteration in MFCs. Acetate-initiated MFCs showed best performance in utilizing BE. PMID:25794875

  9. 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

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

    PubMed

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

    2016-01-01

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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Gimballing Spacecraft Thruster

    NASA Technical Reports Server (NTRS)

    Pickens, Tim; Bossard, John

    2010-01-01

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

  16. 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.

  17. 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.

  18. 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.

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

    PubMed

    Bezmalinović, Dario; Radošević, Jagoda; Barbir, Frano

    2015-01-01

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

  20. Established breast cancer stem cell markers do not correlate with in vivo tumorigenicity of tumor-initiating cells.

    PubMed

    Lehmann, Christian; Jobs, Gabriele; Thomas, Markus; Burtscher, Helmut; Kubbies, Manfred

    2012-12-01

    The tumor-initiating capacity of primary human breast cancer cells is maintained in vitro by culturing these cells as spheres/aggregates. Inoculation of small cell numbers derived from these non-adherent cultures leads to rapid xenograft tumor formation in mice. Accordingly, injection of more differentiated monolayer cells derived from spheres results in significantly decelerated tumor growth. For our study, two breast cancer cell lines were generated from primary tumors and cultured as mammospheres or as their adherent counterparts. We examined the in vivo tumorigenicity of these cells by injecting serial dilutions into immunodeficient mice. Inoculation of 106 cells per mouse led to rapid tumor formation, irrespective of cell line or culture conditions. However, after injection of only 103 cells, solely sphere cells were highly tumorigenic. In vitro, we investigated differentiation markers, established breast CSC markers and conducted mRNA profiling. Cytokeratin 5 and 18 were increased in both monolayer cell types, indicating a more differentiated phenotype. All cell lines were CD24(-)/CD44(+) and did not express CD133, CD326 or E-cadherin. ALDH1 activity was not detectable in any cell line. A verapamil‑sensitive Hoechst side population was present in sphere cells, but there was no correlation with tumorigenicity in vivo. mRNA profiling did not reveal upregulation of relevant transcription factors. In vitro cell cycle kinetics and in vivo tumor doubling times displayed no difference between sphere and monolayer cultures. Our data indicate that intrinsic genetic and functional markers investigated are not indicative of the in vivo tumori-genicity of putative breast tumor-initiating cells.

  1. 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.

  2. [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.

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

    PubMed

    Avgustinova, Alexandra; Benitah, Salvador Aznar

    2016-02-01

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

  4. 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.

  5. Electromagnetic propulsion for spacecraft

    NASA Technical Reports Server (NTRS)

    Myers, Roger M.

    1993-01-01

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

  6. 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.

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

    PubMed

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

    2016-05-01

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

  8. 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.

  9. Space power systems - 'Spacecraft 2000'

    NASA Technical Reports Server (NTRS)

    Faymon, K. A.

    1985-01-01

    The program 'Spacecraft 2000' has the objective to identify critical, high-payoff, potential spacecraft technologies, taking into account the formulation, advocation, and the management of the requisite technology development programs. This program represents a joint NASA-industry program. The technology areas addressed by 'Spacecraft 2000' are related to spacecraft power/energy storage, thermal control/thermal management, power management and distribution, autonomous operation-control, on-board system integration, spacecraft environmental interactions, secondary propulsion, communications technologies, a total system response approach, and system-subsystem technology verification. The expected benefits of a development of advanced technologies include decreased spacecraft bus system weights, decreased mission costs, increased reliability/lifetimes, and increased operational flexibility.

  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. Spacecraft telecommunications system mass estimates

    NASA Astrophysics Data System (ADS)

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

    1988-02-01

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

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

    PubMed

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

    2015-07-23

    In many mouse models of skin cancer, only a few tumors typically form even though many cells competent for tumorigenesis receive the same oncogenic stimuli. These observations suggest an active selection process for tumor-initiating cells. Here, we use quantitative mRNA- and miR-Seq to determine the impact of Hras(G12V) on the transcriptome of keratinocytes. We discover that microRNA-203 is downregulated by Hras(G12V). Using a knockout mouse model, we demonstrate that loss of microRNA-203 promotes selection and expansion of tumor-initiating cells. Conversely, restoration of microRNA-203 using an inducible model potently inhibits proliferation of these cells. We comprehensively identify microRNA-203 targets required for Hras-initiated tumorigenesis. These targets include critical regulators of the Ras pathway and essential genes required for cell division. This study establishes a role for the loss of microRNA-203 in promoting selection and expansion of Hras mutated cells and identifies a mechanism through which microRNA-203 antagonizes Hras-mediated tumorigenesis.

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

    PubMed Central

    Friday, Andrew J.; Keiper, Brett D.

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. Large heterogeneity of mitochondrial DNA transcription and initiation of replication exposed by single-cell imaging.

    PubMed

    Chatre, Laurent; Ricchetti, Miria

    2013-02-15

    Mitochondrial DNA (mtDNA) replication and transcription are crucial for cell function, but these processes are poorly understood at the single-cell level. We describe a novel fluorescence in situ hybridization protocol, called mTRIP (mitochondrial transcription and replication imaging protocol), that reveals simultaneously mtDNA and RNA, and that can also be coupled to immunofluorescence for in situ protein examination. mTRIP reveals mitochondrial structures engaged in initiation of DNA replication by identification of a specific sequence in the regulatory D-loop, as well as unique transcription profiles in single human cells. We observe and quantify at least three classes of mitochondrial structures: (i) replication initiation active and transcript-positive (Ia-Tp); (ii) replication initiation silent and transcript-positive (Is-Tp); and (iii) replication initiation silent and transcript-negative (Is-Tn). Thus, individual mitochondria are dramatically heterogeneous within the same cell. Moreover, mTRIP exposes a mosaic of distinct nucleic acid patterns in the D-loop, including H-strand versus L-strand transcripts, and uncoupled rRNA transcription and mtDNA initiation of replication, which might have functional consequences in the regulation of the mtDNA. Finally, mTRIP identifies altered mtDNA processing in cells with unbalanced mtDNA content and function, including in human mitochondrial disorders. Thus, mTRIP reveals qualitative and quantitative alterations that provide additional tools for elucidating the dynamics of mtDNA processing in single cells and mitochondrial dysfunction in diseases.

  16. 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.

  17. 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.

  18. [Mast cell-derived exosome participates in acupoint-stimulation initiated local network activities].

    PubMed

    Chen, Bo; Li, Ming-yue; Guo, Yi; Zhao, Xue; Liu, Yang-yang

    2015-02-01

    The exosome, released from mast cells, T cells, B cells and many other types of cells, is the common form of vesicle transportation between cells and participates in the exchange of information between cells, and may be also involved in acupuncture induced clinical effects. In the present paper, the authors reviewed recent development of researches on this field from 1) acupuncture stimulation induces changes of number and function of mast cells in the local acupoint area, probably being the key factor for initiating acupuncture effect; 2) acupuncture stimulation induces release of neurotransmitters, hormones, cytokines, Ca2+, etc., in the local acupoint region, possibly being closely associated with the production of clinical effects; 3) acupuncture stimulation results in excitation of sensory afferent nerve fibers, triggering neuro-regulation; 4) exosomes derived from mast cells contain multiple neurotransmitters, hormones, cytokines, etc. to activate immune cells and sensory afferent fibers, inducing immuno-regulation and neuro-regulation; and 5) acupuncture stimulation induced release of Ca2+, ATP, etc. may potentiate release and transportation of exosomes. However, current researches are lack of excavation of network connection and transformation from basic research to clinical application. The authors hold that the exosome, released from mast cells by needling acupoints, acts as a messenger in network connection of nerve-mast cell-signal molecule in the body and may be one of the key factors of therapeutic effects.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

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

    PubMed

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

    2016-07-01

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

  6. 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.

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

    PubMed Central

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

    2014-01-01

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

  8. Krt19(+)/Lgr5(-) Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine.

    PubMed

    Asfaha, Samuel; Hayakawa, Yoku; Muley, Ashlesha; Stokes, Sarah; Graham, Trevor A; Ericksen, Russell E; Westphalen, Christoph B; von Burstin, Johannes; Mastracci, Teresa L; Worthley, Daniel L; Guha, Chandhan; Quante, Michael; Rustgi, Anil K; Wang, Timothy C

    2015-06-01

    Epithelium of the colon and intestine are renewed every 3 days. In the intestine there are at least two principal stem cell pools. The first contains rapid cycling crypt-based columnar (CBC) Lgr5(+) cells, and the second is composed of slower cycling Bmi1-expressing cells at the +4 position above the crypt base. In the colon, however, the identification of Lgr5(-) stem cell pools has proven more challenging. Here, we demonstrate that the intermediate filament keratin-19 (Krt19) marks long-lived, radiation-resistant cells above the crypt base that generate Lgr5(+) CBCs in the colon and intestine. In colorectal cancer models, Krt19(+) cancer-initiating cells are also radioresistant, while Lgr5(+) stem cells are radiosensitive. Moreover, Lgr5(+) stem cells are dispensable in both the normal and neoplastic colonic epithelium, as ablation of Lgr5(+) stem cells results in their regeneration from Krt19-expressing cells. Thus, Krt19(+) stem cells are a discrete target relevant for cancer therapy.

  9. 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. PMID:25404150

  10. Fine tuning of IRF-4 expression by SWAP-70 controls the initiation of plasma cell development.

    PubMed

    Chopin, Michaël; Chacón-Martínez, Carlos Andrés; Jessberger, Rolf

    2011-10-01

    The generation of plasma cells (PCs) is key for proper humoral immune responses. The transcription factors IRF-4 and BLIMP-1 (B-lymphocyte induce maturation protein-1) control PC commitment, but the underlying regulatory mechanisms are incompletely understood. Here we have identified SWAP-70 as being critically involved in Toll-like receptor (TLR)-triggered PC differentiation. Upon activation through various TLRs, Swap-70(-/-) B cells were activated and proliferated normally. However, expression of BLIMP-1 was markedly reduced and PC differentiation was impaired. Four hours of LPS stimulation were sufficient to drive PC differentiation, and SWAP-70 was required during this initial period. Swap-70(-/-) B cells pre-activated in vitro failed to efficiently differentiate into PCs upon adoptive transfer into recipient mice. Re-introduction of SWAP-70 into Swap-70(-/-) B cells rescued their development into PCs, and SWAP-70 over-expression in wild-type (WT) B cells increased PC generation. In the absence of SWAP-70, IRF-4 protein levels were reduced and the IRF-4(high) B220(+) CD138(-) compartment, including PC precursors, was strongly diminished. Ectopic expression of SWAP-70 increases IRF-4 protein levels and PC differentiation in WT and Swap-70(-/-) B cells, and IRF-4 over-expression in Swap-70(-/-) B cells elevates PC differentiation to WT levels. Thus, in a dose-dependent manner, SWAP-70 controls IRF-4 protein expression and thereby regulates the initiation of PC differentiation.

  11. 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).

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  14. 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

  15. Detection of Initiator Caspase Induced Proximity in Single Cells by Caspase Bimolecular Fluorescence Complementation.

    PubMed

    Parsons, Melissa J; Fassio, Sara R; Bouchier-Hayes, Lisa

    2016-01-01

    The caspase family of proteases includes key regulators of apoptosis and inflammation. The caspases can be divided into two groups, the initiator caspases and the executioner caspases. Initiator caspases include caspase-2, caspase-8, and caspase-9 and are activated by proximity-induced dimerization upon recruitment to large molecular weight protein complexes called activation platforms. This protocol describes an imaging-based technique called caspase Bimolecular Fluorescence Complementation (BiFC) that measures induced proximity of initiator caspases. This method uses nonfluorescent fragments of the fluorescent protein Venus fused to initiator caspase monomers. When the caspase is recruited to its activation platform, the resulting induced proximity of the caspase monomers facilitates refolding of the Venus fragments into the full molecule, reconstituting its fluorescence. Thus, the assembly of initiator caspase activation platforms can be followed in single cells in real time. Induced proximity is the most apical step in the activation of initiator caspases, and therefore, caspase BiFC is a robust and specific method to measure initiator caspase activation. PMID:27108430

  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. 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.

  18. N° 28-1998: SOHO spacecraft contacted

    NASA Astrophysics Data System (ADS)

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

  19. The Galeleo spacecraft magnetometer boom

    NASA Technical Reports Server (NTRS)

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

    1985-01-01

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

  20. Active Spacecraft Potential Control Investigation

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  1. On-orbit spacecraft reliability

    NASA Technical Reports Server (NTRS)

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

    1978-01-01

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

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

    PubMed

    Arai, Toshiaki; Ochiai, Kuniyasu; Senpuku, Hidenobu

    2015-02-01

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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. Initiation and execution of lipotoxic ER stress in pancreatic β-cells

    PubMed Central

    Cunha, Daniel A.; Hekerman, Paul; Ladrière, Laurence; Bazarra-Castro, Angie; Ortis, Fernanda; Wakeham, Marion C.; Moore, Fabrice; Rasschaert, Joanne; Cardozo, Alessandra K.; Bellomo, Elisa; Overbergh, Lutgart; Mathieu, Chantal; Lupi, Roberto; Hai, Tsonwin; Herchuelz, Andre; Marchetti, Piero; Rutter, Guy A.; Eizirik, Décio L.; Cnop, Miriam

    2013-01-01

    Summary Free fatty acids (FFA) cause apoptosis of pancreatic β-cells and might contribute to β-cell loss in type 2 diabetes via the induction of endoplasmic reticulum (ER) stress. We studied here the molecular mechanisms implicated in FFA-induced ER stress initiation and apoptosis in INS-1E cells, FACS-purified primary β-cells and human islets exposed to oleate and/or palmitate. Treatment with saturated and/or unsaturated FFA led to differential ER stress signaling. Palmitate induced more apoptosis and markedly activated the IRE1, PERK and ATF6 pathways, owing to a sustained depletion of ER Ca2+ stores, whereas the unsaturated FFA oleate led to milder PERK and IRE1 activation and comparable ATF6 signaling. Non-metabolizable methyl-FFA analogs induced neither ER stress nor β-cell apoptosis. The FFA-induced ER stress response was not modified by high glucose concentrations, suggesting that ER stress in primary β-cells is primarily lipotoxic, and not glucolipotoxic. Palmitate, but not oleate, activated JNK. JNK inhibitors reduced palmitate-mediated AP-1 activation and apoptosis. Blocking the transcription factor CHOP delayed palmitate-induced β-cell apoptosis. In conclusion, saturated FFA induce ER stress via ER Ca2+ depletion. The IRE1 and resulting JNK activation contribute to β-cell apoptosis. PERK activation by palmitate also contributes to β-cell apoptosis via CHOP. PMID:18559892

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

    PubMed

    Lilly, Jacob L; Berron, Brad J

    2016-06-01

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

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

    PubMed

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

    2016-01-01

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

  10. 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

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

    PubMed

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

    1999-09-01

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

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

    PubMed

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

    2016-05-01

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

  13. Zoledronate sensitizes neuroblastoma-derived tumor-initiating cells to cytolysis mediated by human γδ T cells.

    PubMed

    Nishio, Nobuhiro; Fujita, Mitsugu; Tanaka, Yoshimasa; Maki, Hiroyuki; Zhang, Rong; Hirosawa, Tomoya; Demachi-Okamura, Ayako; Uemura, Yasushi; Taguchi, Osamu; Takahashi, Yoshiyuki; Kojima, Seiji; Kuzushima, Kiyotaka

    2012-10-01

    Neuroblastoma is the most common extracranial solid tumor in children that is refractory to intensive multimodal therapy. In particular, tumor-initiating cells (TICs) derived from neuroblastoma are believed responsible for tumor formation and resistance to the conventional therapy; an optimal strategy therefore should target this population. Technically, TICs can be enriched from neuroblastoma-derived spheres when the tumor cells are cultured in a serum-free medium supplemented with certain growth factors. Recently, a line of evidence has suggested antitumor potential of Vγ9Vδ2 T cells (γδ T cells), a T-cell population that recognizes and kills target cells independent of surface HLA expressions. Furthermore, a mevalonate pathway inhibitor, zoledronate, has been reported to enhance cytolytic activity of γδ T cells. On the basis of these findings, we hypothesized that zoledronate would sensitize neuroblastoma TICs to γδ T-cell-mediated cytolysis and promote therapeutic efficacy against neuroblastoma. In the current study, we show that zoledronate efficiently sensitizes both neuroblastoma-derived adherent cells and sphere-forming cells to γδ T-cell-mediated cytolysis. Subsequently, in vitro colony formation inhibition assay and in vivo animal studies reveal that the presence of γδ T cells decelerates outgrowth of neuroblastoma TICs. We finally show that addition of interleukin-15 and/or interleukin-18 in culture enhances the cytolytic activity of γδ T cells. On the basis of these data, we conclude that ex vivo expanded γδ T cells are a promising tool for antineuroblastoma immunotherapy with options for further improvement.

  14. Low-Temperature Spacecraft: Challenges/Opportunities

    NASA Astrophysics Data System (ADS)

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

    2001-01-01

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

  15. 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

    2015-01-01

    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

  16. 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

  17. Research on advanced spacecraft

    NASA Astrophysics Data System (ADS)

    Iwata, Tsutomu; Etou, Takao; Imai, Ryouichi; Oota, Kazuo; Kaneko, Yutaka; Maeda, Toshihide; Takano, Yutaka

    1992-08-01

    Engineering test satellite systems to validate element technologies required for spacecraft composing advanced space infrastructures are studied. Case studies are conducted on element technologies for diversified manned space technology and the outline of the engineering test satellite systems is demonstrated. Debris observing systems, their debris collection and retrieval methods which are being reviewed in many countries are examined. Technical problems are picked up, and the fundamental concept of experiment satellites is determined. Missions deemed to be suitable for micro-satellites and various civil on-ground technologies focusing on electronic technology applicable to them are picked up. Functions of extravehicular operation systems required by the missions, and fundamental concept of the systems and subsystems are made clear. Missions to which artificial gravity experiment satellites that are effective are examined and preparatory review is conducted on artificial gravity generation methods, methods to retrieve experiment equipment and samples, and outline of the satellite systems. Technical problems of engineering test satellites to validate on-orbit cryogenic propellant storage and transportation technologies are picked up and the fundamental concept of the satellites are determined. A review is conducted on electrical propulsion Orbit Transfer Vehicle (OTV) technology satellite to validate fundamental technology for large electrical propulsion engine and electrical propulsion engine OTV operation technology, and to pick up problems on the orbit of electrical propulsion OTV.

  18. 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.

  19. 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.

  20. 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.

  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. GLAS Spacecraft Pointing Study

    NASA Technical Reports Server (NTRS)

    Born, George H.; Gold, Kenn; Ondrey, Michael; Kubitschek, Dan; Axelrad, Penina; Komjathy, Attila

    1998-01-01

    Science requirements for the GLAS mission demand that the laser altimeter be pointed to within 50 m of the location of the previous repeat ground track. The satellite will be flown in a repeat orbit of 182 days. Operationally, the required pointing information will be determined on the ground using the nominal ground track, to which pointing is desired, and the current propagated orbit of the satellite as inputs to the roll computation algorithm developed by CCAR. The roll profile will be used to generate a set of fit coefficients which can be uploaded on a daily basis and used by the on-board attitude control system. In addition, an algorithm has been developed for computation of the associated command quaternions which will be necessary when pointing at targets of opportunity. It may be desirable in the future to perform the roll calculation in an autonomous real-time mode on-board the spacecraft. GPS can provide near real-time tracking of the satellite, and the nominal ground track can be stored in the on-board computer. It will be necessary to choose the spacing of this nominal ground track to meet storage requirements in the on-board environment. Several methods for generating the roll profile from a sparse reference ground track are presented.

  3. Aluminum-air power cell: The M4-cell assembly and initial tests

    NASA Astrophysics Data System (ADS)

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

    1985-10-01

    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 (93C) 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.

  4. Helicobacter pylori Disrupts Host Cell Membranes, Initiating a Repair Response and Cell Proliferation

    PubMed Central

    Lin, Li-Ling; Huang, Hsuan-Cheng; Ogihara, Satoshi; Wang, Jin-Town; Wu, Meng-Chuan; McNeil, Paul L.; Chen, Chiung-Nien; Juan, Hsueh-Fen

    2012-01-01

    Helicobacter pylori (H. pylori), the human stomach pathogen, lives on the inner surface of the stomach and causes chronic gastritis, peptic ulcer, and gastric cancer. Plasma membrane repair response is a matter of life and death for human cells against physical and biological damage. We here test the hypothesis that H. pylori also causes plasma membrane disruption injury, and that not only a membrane repair response but also a cell proliferation response are thereby activated. Vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA) have been considered to be major H. pylori virulence factors. Gastric cancer cells were infected with H. pylori wild type (vacA+/cagA+), single mutant (ΔvacA or ΔcagA) or double mutant (ΔvacA/ΔcagA) strains and plasma membrane disruption events and consequent activation of membrane repair components monitored. H. pylori disrupts the host cell plasma membrane, allowing localized dye and extracellular Ca2+ influx. Ca2+-triggered members of the annexin family, A1 and A4, translocate, in response to injury, to the plasma membrane, and cell surface expression of an exocytotic maker of repair, LAMP-2, increases. Additional forms of plasma membrane disruption, unrelated to H. pylori exposure, also promote host cell proliferation. We propose that H. pylori activation of a plasma membrane repair is pro-proliferative. This study might therefore provide new insight into potential mechanisms of H. pylori-induced gastric carcinogenesis. PMID:22949854

  5. 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.

  6. Haematuria as an uncommon initial presenting symptom of metastatic squamous cell carcinoma (SCC) to kidney.

    PubMed

    Kawsar, Hameem I; Spiro, Timothy P; Daw, Hamed A

    2011-01-01

    A 47-year-old female presented with a 2-week history of painless haematuria. Urine dipstick showed moderate leucocytes. Blood and urine cultures were negative and cytology was negative for malignant cells. Flexible cystoscopy was negative for any bladder pathology. An ultrasonogram of the abdomen showed a mass in the left kidney. CT showed a mass-like lesion within the left kidney suspicious for renal carcinoma, and cavitary lesions in both lungs. Biopsy of the lung showed clusters of atypical cells suspicious for squamous cell carcinoma (SCC), and left kidney lesion showed malignant cells derived from SCC. A whole body positron emission tomography/CT showed lesions in the lungs, left kidney and skeleton. Complete clinical examination, laboratory and imaging studies did not reveal any site of primary tumour in any part of the body. Haematuria is a very unusual initial presentation of metastatic tumour to kidney. PMID:22688475

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2005-01-01

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

  9. T-Cell Subsets Predict Mortality in Malnourished Zambian Adults Initiating Antiretroviral Therapy

    PubMed Central

    Chisenga, Caroline C.; Filteau, Suzanne; Siame, Joshua; Chisenga, Molly; Prendergast, Andrew J.; Kelly, Paul

    2015-01-01

    Objective To estimate the prognostic value of T-cell subsets in Zambian patients initiating antiretroviral therapy (ART), and to assess the impact of a nutritional intervention on T-cell subsets. Methods This was a sub-study of a randomised clinical trial of a nutritional intervention for malnourished adults initiating ART. Participants in a randomised controlled trial (NUSTART trial) were enrolled between April and December 2012. Participants received lipid-based nutritional supplement either with or without additional vitamins and minerals. Immunophenotyping was undertaken at baseline and, in survivors, after 12 weeks of ART to characterize T-cell subsets using the markers CD3, CD4, CD8, CD45RA, CCR7, CD28, CD57, CD31, α4β7, Ki67, CD25 and HLA-DR. Univariate and multivariate survival analysis was performed, and responses to treatment were analysed using the Wicoxon rank-sum test. Results Among 181 adults, 36 (20%) died by 12 weeks after starting ART. In univariate analysis, patients who died had fewer proliferating, more naïve and fewer gut homing CD4+ T-cells compared to survivors; and more senescent and fewer proliferating CD8+ T-cells. In a multivariate Cox regression model high naïve CD4+, low proliferating CD4+, high senescent CD8+ and low proliferating CD8+ subsets were independently associated with increased risk of death. Recent CD4+ thymic emigrants increased less between recruitment and 12 weeks of ART in the intervention group compared to the control group. Conclusions Specific CD4+ T-cell subsets are of considerable prognostic significance for patients initiating ART in Zambia, but only thymic output responded to this nutritional intervention. PMID:26083409

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

    PubMed

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

    2014-11-01

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

  11. Decisive role of apurinic/apyrimidinic endonuclease/Ref-1 in initiation of cell death.

    PubMed

    Cho, Kyoung Joo; Kim, Hyun Jeong; Park, Soo Chul; Kim, Hyun Woo; Kim, Gyung Whan

    2010-11-01

    The apurinic/apyrimidinic endonuclease/redox effector factor-1 (APE/Ref-1) is involved in the base excision repair of apurinic/apyrimidinic sites induced by oxidative DNA damage. APE/Ref-1 was decreased by kainic acid (KA) injury in a time-dependent manner at the level of proteins, not transcripts. We investigated whether alteration of APE/Ref-1 amounts would influence hippocampal cell fate, survival or death, after KA injury. Overexpression of APE/Ref-1 using adenovirus and restoration of APE small peptides significantly reduced KA-induced hippocampal cell death. Both silencing of APE/Ref-1 by siRNA and inhibition of endonuclease by an antibody significantly increased caspase-3 activity and apoptotic cell death triggered from the early time after exposure to KA. These findings suggest that cell death is initiated by reducing APE/Ref-1 protein and inhibiting its repair function in spite of enough protein amounts. In conclusion, APE/Ref-1 may be a regulator of cell death initiation, and APE small peptides could provide molecular mechanism-based therapies for neuroprotection in progressive excitotoxic neuronal damage.

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

    PubMed Central

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

    2003-01-01

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

  13. [The Langerhans cell histiocytosis with thymic localization as initial and exclusive place].

    PubMed

    Hernández Pérez, J M; Franquet Casas, T; Rodríguez, S; Giménez, A

    2007-10-01

    The Langerhans' cell histiocytosis (LCH), also known as Histiocitosis X it is an illness not very frequent granulomatosus etiology not clarified yet, that it can have different manifestations and localizations, however the thymic localization as initial and exclusive place gives presentation HCL it is quite unusual. The present case is presented a patient that debuted with a clinical unspecific, where the tests give image they put she gives apparent a mass in previous mediastinum and that after the pathologic and immunohistochemical analysis they evidenced a proliferation Langerhans s cells and eosinophils it being positive for CD1a and S-100 confirming the diagnosis of the LCH.

  14. Metformin selectively affects human glioblastoma tumor-initiating cell viability: A role for metformin-induced inhibition of Akt.

    PubMed

    Würth, Roberto; Pattarozzi, Alessandra; Gatti, Monica; Bajetto, Adirano; Corsaro, Alessandro; Parodi, Alessia; Sirito, Rodolfo; Massollo, Michela; Marini, Cecilia; Zona, Gianluigi; Fenoglio, Daniela; Sambuceti, Gianmario; Filaci, Gilberto; Daga, Antonio; Barbieri, Federica; Florio, Tullio

    2013-01-01

    Cancer stem cell theory postulates that a small population of tumor-initiating cells is responsible for the development, progression and recurrence of several malignancies, including glioblastoma. In this perspective, tumor-initiating cells represent the most relevant target to obtain effective cancer treatment. Metformin, a first-line drug for type II diabetes, was reported to possess anticancer properties affecting the survival of cancer stem cells in breast cancer models. We report that metformin treatment reduced the proliferation rate of tumor-initiating cell-enriched cultures isolated from four human glioblastomas. Metformin also impairs tumor-initiating cell spherogenesis, indicating a direct effect on self-renewal mechanisms. Interestingly, analyzing by FACS the antiproliferative effects of metformin on CD133-expressing subpopulation, a component of glioblastoma cancer stem cells, a higher reduction of proliferation was observed as compared with CD133-negative cells, suggesting a certain degree of cancer stem cell selectivity in its effects. In fact, glioblastoma cell differentiation strongly reduced sensitivity to metformin treatment. Metformin effects in tumor-initiating cell-enriched cultures were associated with a powerful inhibition of Akt-dependent cell survival pathway, while this pathway was not affected in differentiated cells. The specificity of metformin antiproliferative effects toward glioblastoma tumor-initiating cells was confirmed by the lack of significant inhibition of normal human stem cells (umbilical cord-derived mesenchymal stem cells) in vitro proliferation after metformin exposure. Altogether, these data clearly suggest that metformin exerts antiproliferative activity on glioblastoma cells, showing a higher specificity toward tumor-initiating cells, and that the inhibition of Akt pathway may represent a possible intracellular target of this effect.

  15. 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.

  16. 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.

  17. POWOW: A Modular, High Power Spacecraft Concept

    NASA Technical Reports Server (NTRS)

    Brandhorst, Henry W., Jr.

    2000-01-01

    A robust space infrastructure encompasses a broad range of mission needs along with an imperative to reduce costs of satellites meeting those needs. A critical commodity for science, commercial and civil satellites is power at an affordable cost. The POWOW (POwer WithOut Wires) spacecraft concept was created to provide, at one end of the scale, multi-megawatts of power yet also be composed of modules that can meet spacecraft needs in the kilowatt range. With support from the NASA-sponsored Space Solar Power Exploratory Research and Technology Program, the POWOW spacecraft concept was designed to meet Mars mission needs - while at the same time having elements applicable to a range of other missions. At Mars, the vehicle would reside in an aerosynchronous orbit and beam power to a variety of locations on the surface. It is the purpose of this paper to present the latest concept design results. The Space Power Institute along with four companies: Able Engineering, Inc., Entech, Inc., Primex Aerospace Co., and TECSTAR have produced a modular, power-rich electrically propelled spacecraft design that meets these requirements. In addition, it also meets a range of civil and commercial needs. The spacecraft design is based on multijunction Ill-V solar cells, the new Stretched Lens Aurora (SLA) module, a lightweight array design based on a multiplicity of 8 kW end-of-life subarrays and electric thrusters. The solar cells have excellent radiation resistance and efficiencies above 30%. The SLA has a concentration ratio up to 15x while maintaining an operating temperature of 80 C. The design of the 8 kW array building block will be presented and its applicability to commercial and government missions will be discussed. Electric propulsion options include Hall, MPD and ion thrusters of various power levels and trade studies have been conducted to define the most advantageous options. The present baseline spacecraft design providing 900 kW using technologies expected to be

  18. 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.

  19. 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.

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

    PubMed

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

    2016-09-01

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

  1. 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.

  2. Spacecraft Charging Applications for Geosynchronous Altitude with the MSM

    NASA Astrophysics Data System (ADS)

    Hilmer, R.

    The Rice University Magnetospheric Specification Model (MSM) addresses electron and ion populations relevant to surface charging at geosynchronous altitude. An extensive validation study of the MSM, using 20-50 keV electron flux measurements made by the Charge Control System (CCS) on a DSCS III B-7 spacecraft, indicated that the model consistently tracks both diurnal and seasonal activity related electron variations [Hilmer and Ginet, J. Atmos. and Solar-Terr. Phys., 62, 1275, 2000]. Because the model is driven by geomagnetic indices and geophysical parameters such as the solar wind, the successful merging of MSM particle specifications with surface charging algorithms could present the possibility of predicting charging conditions on a spacecraft. A consistent MSM feature, beneficial to any future spacecraft charging applications, is its ability to balance an ion population with electrons and their evolving spectral features to produce spacecraft charging current densities in the geosynchronous environment. Initial comparisons of on-orbit spacecraft frame charging measurements from CCS with results obtained by applying a charging algorithm driven by MSM output to a minimum spacecraft description showed promise [Hilmer et al., Proc. 7th Spacecraft Charging Technology Conference, 23-27 April 2001, ESA SP-476, 235, 2001]. The method successfully specified the occurrence of the two largest of three spacecraft charging events studied. Our simple approximation identifies charging as a net electron current to the spacecraft determined by integrating electron, proton, and oxygen fluxes along with secondary and backscatter yields specified as a function of energy. An overview of updated MSM/charging algorithm simulations performed using a variety of input parameter combinations is given. With the understanding gained from this study, we hope to be able to quantify the potential benefits of integrating MSM environment specification with advanced charging codes such as

  3. 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.

  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. Spacecraft contamination prediction and testing techniques

    NASA Technical Reports Server (NTRS)

    Jeffery, J. A.; Maag, C. R.; Morelli, F. A.

    1981-01-01

    Techniques used in the prediction of spacecraft contamination for the Galileo Jupiter Orbiter and in the determination of the effects of such contamination are presented. Following a quick-look assessment of the contributions of ground-based initial contaminant loading, launch vehicle interface effects, vacuum-exposed outgassing deposition and attitude control thruster impingement and venting to the spacecraft contamination burden, the evaluations centered on the effects of the attitude control thruster on the scan platform optics, including calculations of thruster flowfields and a high-fidelity computer simulation of contaminant distribution. The evaluations revealed a considerable problem with thruster contamination, which could be solved by the use of a thrust shield and the avoidance of thruster operation at certain scan platform orientations. The effects of the various possible contaminants on spacecraft thermal and optical system performances were also investigated in studies of the optical transmittance of deposited monomethyl hydrazine nitrate, vacuum optical degradation due to contaminant outgassing and re-emission outgassing, and an operational satellite contaminant monitor on the NOAA-C satellite. It is concluded that with a good evaluation and testing program, contamination control may become a necessary portion of system design procedures, and recommendations for the implementation of various practices and tests to minimize contamination effects are presented.

  6. 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.

  7. Notch pathway activation targets AML-initiating cell homeostasis and differentiation

    PubMed Central

    Ntziachristos, Panagiotis; Ndiaye-Lobry, Delphine; Oh, Philmo; Cimmino, Luisa; Zhu, Nan; Araldi, Elisa; Hu, Wenhuo; Freund, Jacquelyn; Abdel-Wahab, Omar; Ibrahim, Sherif; Skokos, Dimitris; Armstrong, Scott A.; Levine, Ross L.; Park, Christopher Y.

    2013-01-01

    Notch signaling pathway activation is known to contribute to the pathogenesis of a spectrum of human malignancies, including T cell leukemia. However, recent studies have implicated the Notch pathway as a tumor suppressor in myeloproliferative neoplasms and several solid tumors. Here we report a novel tumor suppressor role for Notch signaling in acute myeloid leukemia (AML) and demonstrate that Notch pathway activation could represent a therapeutic strategy in this disease. We show that Notch signaling is silenced in human AML samples, as well as in AML-initiating cells in an animal model of the disease. In vivo activation of Notch signaling using genetic Notch gain of function models or in vitro using synthetic Notch ligand induces rapid cell cycle arrest, differentiation, and apoptosis of AML-initiating cells. Moreover, we demonstrate that Notch inactivation cooperates in vivo with loss of the myeloid tumor suppressor Tet2 to induce AML-like disease. These data demonstrate a novel tumor suppressor role for Notch signaling in AML and elucidate the potential therapeutic use of Notch receptor agonists in the treatment of this devastating leukemia. PMID:23359070

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

    PubMed

    Koliaraki, Vasiliki; Pasparakis, Manolis; Kollias, George

    2015-12-14

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

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

    PubMed

    Singh, Prashant Kumar; Shrivastava, Alok Kumar

    2016-07-01

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

  10. The two chromosomes of Vibrio cholerae are initiated at different time points in the cell cycle

    PubMed Central

    Rasmussen, Tue; Jensen, Rasmus Bugge; Skovgaard, Ole

    2007-01-01

    The bacterium Vibrio cholerae, the cause of the diarrhoeal disease cholera, has its genome divided between two chromosomes, a feature uncommon for bacteria. The two chromosomes are of different sizes and different initiator molecules control their replication independently. Using novel methods for analysing flow cytometry data and marker frequency analysis, we show that the small chromosome II is replicated late in the C period of the cell cycle, where most of chromosome I has been replicated. Owing to the delay in initiation of chromosome II, the two chromosomes terminate replication at approximately the same time and the average number of replication origins per cell is higher for chromosome I than for chromosome II. Analysis of cell-cycle parameters shows that chromosome replication and segregation is exceptionally fast in V. cholerae. The divided genome and delayed replication of chromosome II may reduce the metabolic burden and complexity of chromosome replication by postponing DNA synthesis to the last part of the cell cycle and reducing the need for overlapping replication cycles during rapid proliferation. PMID:17557077

  11. 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

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

    PubMed

    Koliaraki, Vasiliki; Pasparakis, Manolis; Kollias, George

    2015-12-14

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

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

    PubMed Central

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

    2015-01-01

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

  14. 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).

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

    PubMed Central

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

    2009-01-01

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

  16. Tumour-initiating capacity is independent of epithelial–mesenchymal transition status in breast cancer cell lines

    PubMed Central

    Xie, G; Ji, A; Yuan, Q; Jin, Z; Yuan, Y; Ren, C; Guo, Z; Yao, Q; Yang, K; Lin, X; Chen, L

    2014-01-01

    Background: Epithelial–mesenchymal transition (EMT) and cancer stem cells (CSCs) are considered to be crucial for cancer biology. The purpose of this study was to determine whether EMT directly led to the acquisition of tumour-initiating capacity in breast cancer cell lines. Methods: Epithelial–mesenchymal transition was induced in five breast cancer cell lines and one normal breast cell line by EMT-related cytokine stimulation. Mesenchymal–epithelial transition (MET) was induced by stably overexpressing miR-200c in three mesenchymal-like breast cancer cell lines. Molecular expression and cell function analysis were performed to evaluate the effect of EMT or MET on tumour-initiating capacity and other biological characteristics. Results: The induction of EMT did not enhance tumour-initiating capacity but, instead, conferred a CD44+/CD24−/low phenotype as well as cell proliferation, migration, and resistance to doxorubicin and radiation on breast cancer cell lines. Furthermore, MET did not lead to inhibition or loss of the tumour-initiating capacity in mesenchymal-like breast cancer cell lines, but it markedly attenuated other malignant properties, including proliferation, invasion, and resistance to therapy. Conclusions: Epithelial–mesenchymal transition does not alter tumour-initiating capacity of breast cancer cells but some other biological characteristics. Therefore, EMT and tumour-initiating capacity may not be directly linked in breast cancer cell lines. PMID:24755887

  17. 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.

  18. 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.

  19. 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...

  20. 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.

  1. 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.

  2. 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.

  3. 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.

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

    PubMed

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

    2014-04-01

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

  5. 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.

  6. 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

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

    PubMed

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

    2016-01-01

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

  8. 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.

  9. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2014-10-01

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

  14. 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.

  15. 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.

  16. Attitude control of spacecraft using neural networks

    NASA Technical Reports Server (NTRS)

    Vadali, Srinivas R.; Krishnan, S.; Singh, T.

    1993-01-01

    This paper investigates the use of radial basis function neural networks for adaptive attitude control and momentum management of spacecraft. In the first part of the paper, neural networks are trained to learn from a family of open-loop optimal controls parameterized by the initial states and times-to-go. The trained is then used for closed-loop control. In the second part of the paper, neural networks are used for direct adaptive control in the presence of unmodeled effects and parameter uncertainty. The control and learning laws are derived using the method of Lyapunov.

  17. 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

  18. A Critical Role for Proinflammatory Behavior of Smooth Muscle Cells in Hemodynamic Initiation of Intracranial Aneurysm

    PubMed Central

    Mandelbaum, Max; Kolega, John; Dolan, Jennifer M.; Siddiqui, Adnan H.; Meng, Hui

    2013-01-01

    Background Intracranial aneurysm initiation is poorly understood, although hemodynamic insult is believed to play an important role in triggering the pathology. It has recently been found in a rabbit model that while macrophages are absent during hemodynamic aneurysm initiation, matrix metalloproteinases (MMPs) are elevated and co-localize with smooth muscle cells (SMCs). This study investigates whether SMCs play a mechanistic role in aneurysm initiation triggered by hemodynamics. Methods Aneurysmal damage was induced at the basilar terminus via bilateral common carotid artery ligation in rabbits (n = 45, plus 7 sham controls). 16 ligated rabbits were treated with doxycycline to inhibit MMPs, 7 received clodronate liposomes to deplete circulating monocytes, and the rest received no drug. Effects of the treatments on aneurysm development were assessed histologically 5 days and 6 months after ligation. MMP production and expression of inflammatory markers by SMCs was monitored by immunohistochemistry and in situ hybridization. Results Treatment with doxycycline attenuated aneurysmal development examined at 5 days and 6 months, suggesting that MMPs contribute to aneurysm initiation. However, systemic depletion of macrophages did not decrease MMPs or suppress aneurysmal development. Immunofluorescence showed that during aneurysm initiation MMP-2 and MMP-9 were distributed in SMCs, and in situ hybridization indicated that they were transcribed by SMCs. In regions of early aneurysmal lesion, SMCs exhibited decreased expression of smooth muscle actin and increased NF-κB and MCP-1 expressions. Conclusions During aneurysm initiation triggered by hemodynamics, SMCs rather than macrophages are responsible for MMP production that is critical for aneurysmal lesion development. These SMCs exhibit proinflammatory behavior. PMID:24023941

  19. CD40 signaling in human dendritic cells is initiated within membrane rafts

    PubMed Central

    Vidalain, Pierre-Olivier; Azocar, Olga; Servet-Delprat, Christine; Rabourdin-Combe, Chantal; Gerlier, Denis; Manié, Serge

    2000-01-01

    Despite CD40’s role in stimulating dendritic cells (DCs) for efficient specific T-cell stimulation, its signal transduction components in DCs are still poorly documented. We show that CD40 receptors on human monocyte-derived DCs associate with sphingolipid- and cholesterol-rich plasma membrane microdomains, termed membrane rafts. Following engagement, CD40 utilizes membrane raft-associated Lyn Src family kinase, and possibly other raft-associated Src family kinases, to initiate tyrosine phosphorylation of intracellular substrates. CD40 engagement also leads to a membrane raft-restricted recruitment of tumor necrosis factor (TNF) receptor-associated factor (TRAF) 3 and, to a lesser extent, TRAF2, to CD40’s cytoplasmic tail. Thus, the membrane raft structure plays an integral role in proximal events of CD40 signaling in DCs. We demonstrate that stimulation of Src family kinase within membrane rafts initiates a pathway implicating ERK activation, which leads to interleukin (IL)-1α/β and IL-1Ra mRNA production and contributes to p38-dependent IL-12 mRNA production. These results provide the first evidence that membrane rafts play a critical role in initiation of CD40 signaling in DCs, and delineate the outcome of CD40-mediated pathways on cytokine production. PMID:10880443

  20. Fuel Cell Research at NASA GRC

    NASA Technical Reports Server (NTRS)

    Perez-Davis, Marla E.; Lyons, Valerie (Technical Monitor)

    2002-01-01

    An overview of NASA GRC (Glenn Research Center) initiatives and challenges in fuel cell technology. The research and development of fuel cells and regenerative fuel cell systems for a wide variety of applications, including earth-based and planetary aircraft, spacecraft, planetary surface power, and terrestrial use are discussed.

  1. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  4. Initial ICRF heating experiments in the TMX-U central cell

    SciTech Connect

    Molvik, A.W.; Falabella, S.; Moore, T.

    1983-02-18

    An ion-cyclotron range of frequencies (ICRF) heating system has been installed in the Tandem Mirror Experiment-Upgrade (TMX-U) central cell. Our initial objective is to heat low density ions in the near field of the antenna. This heating reduces the collisionality of central cell ions, which decreases the filling rate of the thermal barrier by passing ions from the central cell. From power- and particle-balance calculations, we determined that 60 kW of absorbed power is sufficient to heat plasma densities of up to 2 x 10/sup 12/ cm/sup -3/. These power requirements are consistent with ion heating results from the Phaedrus tandem mirror. Based on this, we have installed a 200-kW oscillator/power amplifier, tunable to as low as 1.5 MHz. It drives a 110/sup 0/, 9 1/2-turn loop antenna that has a commercially built Faraday shield and matching network. The system has been tuned with plasma and is being used for the initial heating studies at the ion-cyclotron frequency ..omega../sub ci/.

  5. Microtubule plus end–associated CLIP-170 initiates HSV-1 retrograde transport in primary human cells

    PubMed Central

    Jovasevic, Vladimir

    2015-01-01

    Dynamic microtubules (MTs) continuously explore the intracellular environment and, through specialized plus end–tracking proteins (+TIPs), engage a variety of targets. However, the nature of cargoes that require +TIP-mediated capture for their movement on MTs remains poorly understood. Using RNA interference and dominant-negative approaches, combined with live cell imaging, we show that herpes simplex virus particles that have entered primary human cells exploit a +TIP complex comprising end-binding protein 1 (EB1), cytoplasmic linker protein 170 (CLIP-170), and dynactin-1 (DCTN1) to initiate retrograde transport. Depletion of these +TIPs completely blocked post-entry long-range transport of virus particles and suppressed infection ∼5,000-fold, whereas transferrin uptake, early endosome organization, and dynein-dependent movement of lysosomes and mitochondria remained unaffected. These findings provide the first insights into the earliest stages of viral engagement of MTs through specific +TIPs, akin to receptors, with therapeutic implications, and identify herpesvirus particles as one of a very limited number of cargoes absolutely dependent on CLIP-170–mediated capture to initiate transport in primary human cells. PMID:26504169

  6. 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. 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

  8. N-Acetylcysteine blocks formation of cancer-initiating estrogen-DNA adducts in cells

    PubMed Central

    Zahid, Muhammad; Saeed, Muhammad; Ali, Mohammed F.; Rogan, Eleanor G.; Cavalieri, Ercole L.

    2010-01-01

    Catechol estrogens, especially 4-hydroxylated metabolites of 17β-estradiol (E2), are responsible for estrogen-induced carcinogenesis. 4-Hydroxyestradiol (4-OHE2), a major metabolite of E2 formed preferentially by cytochrome P-450 1B1, is oxidized to E2-3,4-quinone, which can react with DNA to yield the depurinating adducts 4-OHE2-1-N3Ade and 4-OHE2-1-N7Gua. The apurinic sites generated by the loss of these depurinating adducts induce mutations that could lead to cancer initiation. In the present study, we have evaluated the effects of N-acetycysteine (NAcCys) on the metabolism of two cell lines, MCF-10F (a normal human breast epithelial cell line) and E6 (a normal mouse mammary epithelial cell line), treated with 4-OHE2 or its reactive metabolite, E2-3,4-quinone. Extensive HPLC with electrochemical detection and UPLC-MS/MS analyses of the cell media demonstrated that the presence of NAcCys very efficiently shifted the estrogen metabolism towards protective methoxylation and conjugation pathways in multiple ways, while formation of depurinating DNA adducts was inhibited. Protection by NAcCys appears to be similar in both cell lines irrespective of their origin (human or mouse) or the presence of estrogen receptor-alpha. This finding suggests that NAcCys, a common dietary supplement, could be used as a potential chemopreventive agent to block the initial step in the genotoxicity caused by catechol estrogen quinones. PMID:20472053

  9. 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

  10. Plasma Cell Neoplasm Manifesting Initially as a Sub-Cutaneous Supra-Orbital Swelling.

    PubMed

    Jaiswal, Riddhi; Agarwal, Garima; Singh, Sudhir

    2016-01-01

    Multiple myeloma is a plasma cell neoplasm seen usually in patients over 50 years of age. Some cases may be asymptomatic initially and are detected during a routine test like complete blood count. They only require a close follow-up and monitoring. However, around 1% of these monoclonal gammopathy of undetermined significance progress to multiple myeloma every year and then they need to be taken care of by chemotherapy, targeted therapy, bisphosphonates and 6 monthly urine and bone examinations. Here, we present a case of 35-year-old female with an initial symptom of a vague backache along with a left subcutaneous supra-orbital swelling which was diagnosed as multiple myeloma by aspiration cytology and confirmed by ancillary tests. She has since been on treatment with bortezomib and prednisone and is responding well. PMID:26955130

  11. Substrate-Initiated Synthesis of Cell-Penetrating Poly(disulfide)s

    PubMed Central

    Molinard, Guillaume; Roux, Aurélien; Sakai, Naomi; Matile, Stefan

    2015-01-01

    Lessons from surface-initiated polymerization are applied to grow cell-penetrating poly(disulfide)s directly on substrates of free choice. Reductive depolymerization after cellular uptake should then release the native substrates and minimize toxicity. In the presence of thiolated substrates, propagators containing a strained disulfide from asparagusic or, preferably, lipoic acid and a guanidinium cation polymerize into poly(disulfide)s in less than 5 min at room temperature at pH 7. Substrate-initiated polymerization of cationic poly(disulfide)s and their depolymerization with dithiothreitol causes the appearance and disappearance of transport activity in fluorogenic vesicles. The same process is further characterized by gel-permeation chromatography and fluorescence resonance energy transfer. PMID:23363440

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. Stress-associated erythropoiesis initiation is regulated by type 1 conventional dendritic cells

    PubMed Central

    Kim, Taeg S.; Hanak, Mark; Trampont, Paul C.; Braciale, Thomas J.

    2015-01-01

    Erythropoiesis is an important response to certain types of stress, including hypoxia, hemorrhage, bone marrow suppression, and anemia, that result in inadequate tissue oxygenation. This stress-induced erythropoiesis is distinct from basal red blood cell generation; however, neither the cellular nor the molecular factors that regulate this process are fully understood. Here, we report that type 1 conventional dendritic cells (cDC1s), which are defined by expression of CD8α in the mouse and XCR1 and CLEC9 in humans, are critical for induction of erythropoiesis in response to stress. Specifically, using murine models, we determined that engagement of a stress sensor, CD24, on cDC1s upregulates expression of the Kit ligand stem cell factor on these cells. The increased expression of stem cell factor resulted in Kit-mediated proliferative expansion of early erythroid progenitors and, ultimately, transient reticulocytosis in the circulation. Moreover, this stress response was triggered in part by alarmin recognition and was blunted in CD24 sensor– and CD8α+ DC-deficient animals. The contribution of the cDC1 subset to the initiation of stress erythropoiesis was distinct from the well-recognized role of macrophages in supporting late erythroid maturation. Together, these findings offer insight into the mechanism of stress erythropoiesis and into disorders of erythrocyte generation associated with stress. PMID:26389678

  18. Toll-like receptor 11-initiated innate immune response in male mouse germ cells.

    PubMed

    Chen, Qiaoyuan; Zhu, Weiwei; Liu, Zhenghui; Yan, Keqin; Zhao, Shutao; Han, Daishu

    2014-02-01

    Toxoplasma gondii and uropathogenic Escherichia coli (UPEC) may infect the testis and impair testicular function. Mechanisms underlying testicular innate immune response to these two pathogens remain to be clarified. The present study examined the function of TLR11, which can be recognized by T. gondii-derived profilin and UPEC, in initiating innate immune response in male mouse germ cells. TLR11 is predominantly expressed in spermatids. Profilin and UPEC induced the expressions of different inflammatory cytokine profiles in the germ cells. In particular, profilin induced the expressions of macrophage chemotactic protein 1 (MCP1), interleukin 12 (IL12), and interferon gamma (IFNG) through nuclear factor KB (NFKB) activation. UPEC induced the expressions of MCP1, IL12, and IFNG, as well as tumor necrosis factor alpha (TNFA), IL6, and IFNB, through the activation of NFKB, IFN regulatory factor 3, and mitogen-activated protein kinases. Evidence showed that profilin induced the innate response in male germ cells through TLR11 signaling, and UPEC triggered the response through TLR11 and other TLR-signaling pathways. We also provided evidence that local injection of profilin or UPEC induces the innate immune response in the germ cells. Data describe TLR11-mediated innate immune function of male germ cells in response to T. gondii profilin and UPEC stimulations. This system may play a role in testicular defense against T. gondii and UPEC infections in mice.

  19. 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

  20. Chemical Screening Identifies EUrd as a Novel Inhibitor Against Temozolomide-Resistant Glioblastoma-Initiating Cells.

    PubMed

    Tsukamoto, Yoshihiro; Ohtsu, Naoki; Echizenya, Smile; Otsuguro, Satoko; Ogura, Ryosuke; Natsumeda, Manabu; Isogawa, Mizuho; Aoki, Hiroshi; Ichikawa, Satoshi; Sakaitani, Masahiro; Matsuda, Akira; Maenaka, Katsumi; Fujii, Yukihiko; Kondo, Toru

    2016-08-01

    Glioblastoma (GBM), one of the most malignant human cancers, frequently recurs despite multimodal treatment with surgery and chemo/radiotherapies. GBM-initiating cells (GICs) are the likely cell-of-origin in recurrences, as they proliferate indefinitely, form tumors in vivo, and are resistant to chemo/radiotherapies. It is therefore crucial to find chemicals that specifically kill GICs. We established temozolomide (the standard medicine for GBM)-resistant GICs (GICRs) and used the cells for chemical screening. Here, we identified 1-(3-C-ethynyl-β-d-ribopentofuranosyl) uracil (EUrd) as a selective drug for targeting GICRs. EUrd induced the death in GICRs more effectively than their parental GICs, while it was less toxic to normal neural stem cells. We demonstrate that the cytotoxic effect of EUrd on GICRs partly depended on the increased expression of uridine-cytidine kinase-like 1 (UCKL1) and the decreased one of 5'-nucleotidase cytosolic III (NT5C3), which regulate uridine-monophosphate synthesis positively and negatively respectively. Together, these findings suggest that EUrd can be used as a new therapeutic drug for GBM with the expression of surrogate markers UCKL1 and NT5C3. Stem Cells 2016;34:2016-2025.

  1. Co-Transcriptomes of Initial Interactions In Vitro between Streptococcus Pneumoniae and Human Pleural Mesothelial Cells.

    PubMed

    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

  2. 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

  3. Eukaryotic initiation factor 3C silencing inhibits cell proliferation and promotes apoptosis in human glioma.

    PubMed

    Hao, Jinmin; Wang, Zhiming; Wang, Yaowu; Liang, Zhaohui; Zhang, Xin; Zhao, Zongmao; Jiao, Baohua

    2015-06-01

    Eukaryotic initiation factor 3, subunit c (eIF3c), an oncogene overexpressed in human cancers, plays an important role in cell tumorigenesis and proliferation. However, studies assessing its function in gliomas are scarce. The present study evaluated for the first time, the role of eIF3c in gliomas. Immunohistochemistry was carried out to assess eIF3c expression in 95 human glioma samples and normal brain tissues. Then, the eIF3c mRNA levels were detected in tumor and normal brain specimens by quantitative RT-PCR. In addition, eIF3c mRNA levels were assessed in four glioma cell lines (U87, U251, A172 and U373) by semi-quantitative RT-PCR. The RNA interference (RNAi) technology was employed to knock down the eIF3c gene in the U251 cells. Western blot analysis, BrdU assay and flow cytometry were used to measure eIF3c protein levels, cell proliferation, cell apoptosis and cell cycle, respectively. The eIF3c protein was overexpressed in the human glioma specimens. In agreement, the eIF3c mRNA expression levels were significantly higher in the human glioma tissues compared with the normal brain samples (P<0.0001). In addition, eIF3c mRNA was detected in all the glioma cell lines. Silencing the eIF3c gene in the U251 cells by RNAi significantly suppressed cell proliferation (P<0.01) and increased apoptosis (P<0.01). Finally, a stark decrease was observed in the G1 phase cell number (P<0.01), while the S and G2 phase cells were significantly increased (P<0.01) after eIF3c knockdown. These findings suggest that eIF3c is overexpressed in human gliomas and essential for their proliferation and survival. Therefore, inhibiting eIF3c expression may constitute an effective therapy for human glioma.

  4. 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.

  5. 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

  6. SF3B1 mutant MDS-initiating cells may arise from the haematopoietic stem cell compartment.

    PubMed

    Mian, Syed A; Rouault-Pierre, Kevin; Smith, Alexander E; Seidl, Thomas; Pizzitola, Irene; Kizilors, Aytug; Kulasekararaj, Austin G; Bonnet, Dominique; Mufti, Ghulam J

    2015-12-08

    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.

  7. 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.

  8. Mobilized dental pulp stem cells for pulp regeneration: initiation of clinical trial.

    PubMed

    Nakashima, Misako; Iohara, Koichiro

    2014-04-01

    Stem cell therapy is a potential strategy to regenerate the dentin-pulp complex, enabling the conservation and restoration of functional teeth. We assessed the efficacy and safety of pulp stem cell transplantation as a prelude before the initiation of clinical trials. Granulocyte-colony stimulating factor (G-CSF) induces subsets of dental pulp stem cells to form mobilized dental pulp stem cells (MDPSCs). Good manufacturing practice is a prerequisite for the isolation and expansion of MDPSCs that are enriched in stem cells, expressing a high level of trophic factors with properties of high proliferation, migration, and antiapoptotic effects and endowed with regenerative potential. The quality of clinical-grade MDPSCs was assured by the absence of abnormalities/aberrations in karyotype and the lack of tumor formation after transplantation in immunodeficient mice. Autologous transplantation of MDPSCs with G-CSF in pulpectomized teeth in dogs augmented the regeneration of pulp tissue. The combinatorial trophic effects of MDPSCs and G-CSF on cell migration, antiapoptosis, immunosuppression, and neurite outgrowth were also confirmed in vitro. Furthermore, MDPSCs from the aged donors were as potent as the young donors. It is noteworthy that there were no significant age-related changes in biological properties such as stability, regenerative potential, and expression of the senescence markers in MDPSCs. On the other hand, autologous transplantation of MDPSCs with G-CSF induced less regenerated pulp tissue in the aged dogs compared with the young dogs. In conclusion, the preclinical safety, feasibility, and efficacy of pulp regeneration by MDPSCs and G-CSF were established. Therefore, the standardization and establishment of regulatory guidelines for stem cell therapy in clinical endodontics is now a reality.

  9. 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

  10. Inhibition of Phosphatidylcholine-Specific Phospholipase C Interferes with Proliferation and Survival of Tumor Initiating Cells in Squamous Cell Carcinoma

    PubMed Central

    Ferri, Renata; Mercurio, Laura; Canevari, Silvana; Podo, Franca; Miotti, Silvia; Iorio, Egidio

    2015-01-01

    Purpose The role of phosphatidylcholine-specific phospholipase C (PC-PLC), the enzyme involved in cell differentiation and proliferation, has not yet been explored in tumor initiating cells (TICs). We investigated PC-PLC expression and effects of PC-PLC inhibition in two adherent (AD) squamous carcinoma cell lines (A431 and CaSki), with different proliferative and stemness potential, and in TIC-enriched floating spheres (SPH) originated from them. Results Compared with immortalized non-tumoral keratinocytes (HaCaT) A431-AD cells showed 2.5-fold higher PC-PLC activity, nuclear localization of a 66-kDa PC-PLC isoform, but a similar distribution of the enzyme on plasma membrane and in cytoplasmic compartments. Compared with A431-AD, A431-SPH cells showed about 2.8-fold lower PC-PLC protein and activity levels, but similar nuclear content. Exposure of adherent cells to the PC-PLC inhibitor D609 (48h) induced a 50% reduction of cell proliferation at doses comprised between 33 and 50 μg/ml, without inducing any relevant cytotoxic effect (cell viability 95±5%). In A431-SPH and CaSki-SPH D609 induced both cytostatic and cytotoxic effects at about 20 to 30-fold lower doses (IC50 ranging between 1.2 and 1.6 μg/ml). Furthermore, D609 treatment of A431-AD and CaSki-AD cells affected the sphere-forming efficiency, which dropped in both cells, and induced down-modulation of stem-related markers mRNA levels (Oct4, Nestin, Nanog and ALDH1 in A431; Nestin and ALDH1 in CaSki cells). Conclusions These data suggest that the inhibition of PC-PLC activity may represent a new therapeutic approach to selectively target the most aggressive and tumor promoting sub-population of floating spheres originated from squamous cancer cells possessing different proliferative and stemness potential. PMID:26402860

  11. 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.

  12. Photoreceptor Ablation Initiates the Immediate Loss of Glutamate Receptors in Postsynaptic Bipolar Cells in Retina

    PubMed Central

    2015-01-01

    Structural changes underlying neurodegenerative diseases include dismantling of synapses, degradation of circuitry, and even massive rewiring. Our limited understanding of synapse dismantling stems from the inability to control the timing and extent of cell death. In this study, selective ablation of cone photoreceptors in live mouse retina and tracking of postsynaptic partners at the cone-to-ON cone bipolar cell synapse reveals that early reaction to cone loss involves rapid and local changes in postsynaptic glutamate receptor distribution. Glutamate receptors disappear with a time constant of 2 h. Furthermore, binding of glutamate receptors by agonists and antagonists is insufficient to rescue glutamate receptor loss, suggesting that receptor allocation depends on the physical presence of cones. These findings demonstrate that the initial step in synapse disassembly involves postsynaptic receptor loss rather than dendritic retraction, providing insight into the early stages of neurodegenerative disease. PMID:25673837

  13. 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…

  14. Chromium(VI) stimulates Fyn to initiate innate immune gene induction in human airway epithelial cells

    PubMed Central

    Nemec, Antonia A.; Zubritsky, Lindsey M.; Barchowsky, Aaron

    2009-01-01

    Mechanisms for pathogenic metal signaling in airway injury or disease promotion are poorly understood. It is widely believed that one mechanism for pathogenic and possible carcinogenic effects of inhaled chromium (Cr(VI)) is inhibition of inducible gene transactivation. However, we recently reported that Cr(VI) inhibition of Sp1-dependent transactivation required signal transducer and activator of transcription 1 (STAT1)-dependent expression of an inhibitory protein in airway epithelium. Thus, Cr(VI) exposures can induce genes and we hypothesized this induction resulted from Cr(VI) signaling through an innate immune-like STAT1-dependent pathway initiated by Fyn. Exposure of human airway epithelial (BEAS-2B) cells to Cr(VI) selectively transactivated STAT-responsive interferon-stimulated response element (ISRE) and induced ISRE-driven transactivation of interferon regulatory factor 7 (IRF7), without affecting the gamma interferon-activated site (GAS)-driven IRF1 expression. Cr(VI)-induced IRF7 was absent or greatly reduced in cells that lacked STAT1, were treated with the Src family kinase inhibitor, PP2, or lacked Fyn. Expressing Fyn, but not Src, in mouse embryonic fibroblasts cells null for Src, Yes, and Fyn restored Cr(VI)-stimulated STAT1 tyrosine phosphorylation and IRF7 expression. Finally, shRNA knockdown of Fyn in BEAS-2B cells prevented Cr(VI)-activated STAT1 transactivation of IRF7. These data support a novel mechanism through which Cr(VI) stimulates Fyn to initiate interferon-like signaling for STAT1-dependent gene transactivation. PMID:19994902

  15. 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.

  16. Oncogenic mTOR signalling recruits myeloid-derived suppressor cells to promote tumour initiation.

    PubMed

    Welte, Thomas; Kim, Ik Sun; Tian, Lin; Gao, Xia; Wang, Hai; Li, June; Holdman, Xue B; Herschkowitz, Jason I; Pond, Adam; Xie, Guorui; Kurley, Sarah; Nguyen, Tuan; Liao, Lan; Dobrolecki, Lacey E; Pang, Lan; Mo, Qianxing; Edwards, Dean P; Huang, Shixia; Xin, Li; Xu, Jianming; Li, Yi; Lewis, Michael T; Wang, Tian; Westbrook, Thomas F; Rosen, Jeffrey M; Zhang, Xiang H-F

    2016-06-01

    Myeloid-derived suppressor cells (MDSCs) play critical roles in primary and metastatic cancer progression. MDSC regulation is widely variable even among patients harbouring the same type of malignancy, and the mechanisms governing such heterogeneity are largely unknown. Here, integrating human tumour genomics and syngeneic mammary tumour models, we demonstrate that mTOR signalling in cancer cells dictates a mammary tumour's ability to stimulate MDSC accumulation through regulating G-CSF. Inhibiting this pathway or its activators (for example, FGFR) impairs tumour progression, which is partially rescued by restoring MDSCs or G-CSF. Tumour-initiating cells (TICs) exhibit elevated G-CSF. MDSCs reciprocally increase TIC frequency through activating Notch in tumour cells, forming a feedforward loop. Analyses of primary breast cancers and patient-derived xenografts corroborate these mechanisms in patients. These findings establish a non-canonical oncogenic role of mTOR signalling in recruiting pro-tumorigenic MDSCs and show how defined cancer subsets may evolve to promote and depend on a distinct immune microenvironment. PMID:27183469

  17. Erythropoietin promotes breast tumorigenesis through tumor-initiating cell self-renewal.

    PubMed

    Zhou, Bing; Damrauer, Jeffrey S; Bailey, Sean T; Hadzic, Tanja; Jeong, Youngtae; Clark, Kelly; Fan, Cheng; Murphy, Laura; Lee, Cleo Y; Troester, Melissa A; Miller, C Ryan; Jin, Jian; Darr, David; Perou, Charles M; Levine, Ross L; Diehn, Maximilian; Kim, William Y

    2014-02-01

    Erythropoietin (EPO) is a hormone that induces red blood cell production. In its recombinant form, EPO is the one of most prescribed drugs to treat anemia, including that arising in cancer patients. In randomized trials, EPO administration to cancer patients has been associated with decreased survival. Here, we investigated the impact of EPO modulation on tumorigenesis. Using genetically engineered mouse models of breast cancer, we found that EPO promoted tumorigenesis by activating JAK/STAT signaling in breast tumor-initiating cells (TICs) and promoted TIC self renewal. We determined that EPO was induced by hypoxia in breast cancer cell lines, but not in human mammary epithelial cells. Additionally, we demonstrated that high levels of endogenous EPO gene expression correlated with shortened relapse-free survival and that pharmacologic JAK2 inhibition was synergistic with chemotherapy for tumor growth inhibition in vivo. These data define an active role for endogenous EPO in breast cancer progression and breast TIC self-renewal and reveal a potential application of EPO pathway inhibition in breast cancer therapy. PMID:24435044

  18. Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation factor 4E.

    PubMed Central

    Rousseau, D; Kaspar, R; Rosenwald, I; Gehrke, L; Sonenberg, N

    1996-01-01

    The structure of m7GpppN (where N is any nucleotide), termed cap, is present at the 5' end of all eukaryotic cellular mRNAs (except organellar). The eukaryotic initiation factor 4E (eIF-4E) binds to the cap and facilitates the formation of translation initiation complexes. eIF-4E is implicated in control of cell growth, as its overexpression causes malignant transformation of rodent cells and deregulates HeLa cell growth. It was suggested that overexpression of eIF-4E results in the enhanced translation of poorly translated mRNAs that encode growth-promoting proteins. Indeed, enhanced expression of several proteins, including cyclin D1 and ornithine decarboxylase (ODC), was documented in eIF-4E-overexpressing NTH 3T3 cells. However, the mechanism underlying this increase has not been elucidated. Here, we studied the mode by which eIF-4E increases the expression of cyclin D1 and ODC. We show that the increase in the amount of cyclin D1 and ODC is directly proportional to the degree of eIF-4E overexpression. Two mechanisms, which are not mutually exclusive, are responsible for the increase. In eIF-4E-overexpressing cells the rate of translation initiation of ODC mRNA was increased inasmuch as the mRNA sedimented with heavier polysomes. For cyclin D1 mRNA, translation initiation was not increased, but rather its amount in the cytoplasm increased, without a significant increase in total mRNA. Whereas, in the parental NIH 3T3 cell line, a large proportion of the cyclin D1 mRNA was confined to the nucleus, in eIF-4E-overexpressing cells the vast majority of the mRNA was present in the cytoplasm. These results indicate that eIF-4E affects directly or indirectly mRNA nucleocytoplasmic transport, in addition to its role in translation initiation. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8577715

  19. 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

  20. Degradation mechanism of alkyl carbonate solvents used in lithium-ion cells during initial charging

    NASA Astrophysics Data System (ADS)

    Yoshida, H.; Fukunaga, T.; Hazama, T.; Terasaki, M.; Mizutani, M.; Yamachi, M.

    The degradation mechanism of electrolytes in the lithium-ion cell with LiCoO 2 and graphite electrodes was investigated by analyzing: (i) the composition of generated gases; (ii) thin films formed on the electrode, and (iii) the compositional change of the electrolyte during the initial charging. The solvents in this work were ethylene carbonate (EC), dimethyl carbonate (DMC), ethylmethyl carbonate (EMC) and diethyl carbonate (DEC). LiPF 6 was used as a salt. In the one- to three-component systems containing EC, carbon monoxide and ethane were detected, whereas Li 2CO 3, RCOOLi and (CH 2OLi) 2 were the main components of the surface film on the negative electrode. From these results, it can be assumed that the decomposition of the systems was mainly due to the reductive reaction of EC at the initial charging. Through the additional analysis of the electrolyte composition, it was confirmed that the dialkyl-2,5-dioxahexane carboxylate was produced in the electrolyte after initial charging. This suggests the occurrence of trans-esterification.

  1. Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells

    PubMed Central

    Yang, Chi-Chun; Suzuki, Masahiro; Yamakawa, Shiori; Uno, Syuzi; Ishii, Ai; Yamazaki, Satoshi; Fukatsu, Rino; Fujisawa, Ryo; Sakimura, Kenji; Tsurimoto, Toshiki; Masai, Hisao

    2016-01-01

    Claspin transmits replication stress signal from ATR to Chk1 effector kinase as a mediator. It also plays a role in efficient replication fork progression during normal growth. Here we have generated conditional knockout of Claspin and show that Claspin knockout mice are dead by E12.5 and Claspin knockout mouse embryonic fibroblast (MEF) cells show defect in S phase. Using the mutant cell lines, we report the crucial roles of the acidic patch (AP) near the C terminus of Claspin in initiation of DNA replication. Cdc7 kinase binds to AP and this binding is required for phosphorylation of Mcm. AP is involved also in intramolecular interaction with a N-terminal segment, masking the DNA-binding domain and a newly identified PIP motif, and Cdc7-mediated phosphorylation reduces the intramolecular interaction. Our results suggest a new role of Claspin in initiation of DNA replication during normal S phase through the recruitment of Cdc7 that facilitates phosphorylation of Mcm proteins. PMID:27401717

  2. 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.

  3. 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.

  4. Inner Heliospheric Sentinels Spacecraft Concept

    NASA Astrophysics Data System (ADS)

    Conde, R. F.; Potocki, K. A.; Szabo, A.; Kirby, K. W.; Maldonado, H. M.; Adamsen, P. B.; Bokulic, R. S.; Dakermanji, G.; Dellinger, W. F.; Downing, J. P.; Ercol, C. J.; Folta, D. C.; Fielhauer, K. B.; Kelley, J. S.; Le, B. Q.; Leary, B. A.; Lewis, W. S.; Ling, S. X.; Marr, G.; Malouf, P. M.; Napollilo, D. H.; Persons, D. F.; Troll, J. R.; Wallis, R. E.; Lin, R. P.

    2007-01-01

    The Sentinels mission is a key component of NASA's Living With a Star (LWS) program. The Sentinels Science and Technology Definition Team (STDT) has completed a study to define the science objectives, measurement requirements and observational strategies, and mission design for the Sentinels mission. The Inner Heliospheric Sentinels (IHS) are one of the three flight elements [the others are the Near Earth Sentinel and Far Side Sentinel] that make up the Sentinels mission. The four spin-stabilized IHS spacecraft are in elliptical heliocentric orbit with perihelia at ~0.25 AU and aphelia at ~0.75 AU. This orbit presents unique spacecraft thermal control and power challenges. This study has demonstrated mission feasibility by developing a spacecraft design concept using conventional technologies that satisfies the science and mission requirements defined by the Sentinels STDT.

  5. 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.

  6. 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.

  7. Differential spacecraft tracking by interferometry

    NASA Technical Reports Server (NTRS)

    Border, James S.; Folkner, William M.

    1990-01-01

    This study estimates measurement system errors for two space vehicles on the surface of Mars, and for two Mars orbiting spacecraft, which are being tracked by differential interferometry. In these examples, signals from all spacecraft lie within the same beamwidth of an earth-based radio antenna. The measurements of all spacecraft signals are made simultaneously; errors that scale with angular source separation or with temporal separation between measurement epochs are practically removed. It is shown that errors due to system thermal noise and to systematic effects within ground receiver electronics dominate, except for geometries when signals pass close to the sun, when solar plasma becomes the dominant error source. The instantaneous relative position of two orbiters may be measured to within ten meters, leading to 50-meter three-dimensional orbital accuracy.

  8. Artist concept of Galileo spacecraft

    NASA Technical Reports Server (NTRS)

    1988-01-01

    Galileo spacecraft is illustrated in artist concept. Gallileo, named for the Italian astronomer, physicist and mathematician who is credited with construction of the first complete, practical telescope in 1620, will make detailed studies of Jupiter. A cooperative program with the Federal Republic of Germany the Galileo mission will amplify information acquired by two Voyager spacecraft in their brief flybys. Galileo is a two-element system that includes a Jupiter-orbiting observatory and an entry probe. Jet Propulsion Laboratory (JPL) is Galileo project manager and builder of the main spacecraft. Ames Research Center (ARC) has responsibility for the entry probe, which was built by Hughes Aircraft Company and General Electric. Galileo will be deployed from the payload bay (PLB) of Atlantis, Orbiter Vehicle (OV) 104, during mission STS-34.

  9. 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.

  10. 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.

  11. 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."

  12. 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.

  13. 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.

  14. Multimission Modular Spacecraft (MMS). A serviceable design spacecraft

    NASA Technical Reports Server (NTRS)

    Falkenhayn, Edward

    1987-01-01

    A standard spacecraft bus compatible with NASA launch vehicles, including STS, for four reference missions (Sun, Earth, stellar pointing from low Earth orbit, Earth pointing from geostationary orbit) was designed. The modular serviceable design stems from its use of passive acme screws for module attachment and scoop proof electrical connectors for electrical interfaces. A flight support system includes command and telemetry links.

  15. 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.

  16. 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

  17. Electrochemical deposition and surface-initiated RAFT polymerization: protein and cell-resistant PPEGMEMA polymer brushes.

    PubMed

    Tria, Maria Celeste R; Grande, Carlos David T; Ponnapati, Ramakrishna R; Advincula, Rigoberto C

    2010-12-13

    This paper introduces a novel and versatile method of grafting protein and cell-resistant poly(poly ethylene glycol methyl ether methacrylate) (PPEGMEMA) brushes on conducting Au surface. The process started with the electrochemical deposition and full characterization of an electro-active chain transfer agent (CTA) on the Au surface. The electrochemical behavior of the CTA was investigated by cyclic voltammetry (CV) while the deposition and stability of the CTA on the surface were confirmed by ellipsometry, contact angle, and X-ray photoelectron spectroscopy (XPS). The capability of the electrodeposited CTA to mediate surface-initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization on both the polymethyl methacrylate (PMMA; model polymer) and PPEGMEMA brushes was demonstrated by the increase in thicknesses of the films after polymerization. Contact angles also decreased with the incorporation of the more hydrophilic brushes. Significant changes in the morphologies of the films before and after polymerization were also observed with atomic force microscopy (AFM) analyses. Furthermore, XPS results showed an increase in the O 1s peak intensity relative to C 1s after polymerizations, which confirmed the grafting of polyethyleneglycol (PEG) bearing brushes. The ability of the PPEGMEMA-modified Au surface to resist nonspecific adhesion of proteins and cells was monitored and confirmed by XPS, ellipsometry, contact angle, AFM, and fluorescence imaging. The new method presented has potential application as robust protein and cell-resistant coatings for electrically conducting electrodes and biomedical devices.

  18. 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. PMID:26441059

  19. 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

  20. Intrinsic differences in the initiation of B cell receptor signaling favor responses of human IgG(+) memory B cells over IgM(+) naive B cells.

    PubMed

    Davey, Angel M; Pierce, Susan K

    2012-04-01

    The acquisition of long-lived memory B cells (MBCs) is critical for the defense against many infectious diseases. Despite their importance, little is known about how Ags trigger human MBCs, even though our understanding of the molecular basis of Ag activation of B cells in model systems has advanced considerably. In this study, we use quantitative, high-resolution, live-cell imaging at the single-cell and single-molecule levels to describe the earliest Ag-driven events in human isotype-switched, IgG-expressing MBCs and compare them with those in IgM-expressing naive B cells. We show that human MBCs are more robust than naive B cells at each step in the initiation of BCR signaling, including interrogation of Ag-containing membranes, formation of submicroscopic BCR oligomers, and recruitment and activation of signaling-associated kinases. Despite their robust response to Ag, MBCs remain highly sensitive to FcγRIIB-mediated inhibition. We also demonstrate that in the absence of Ag, a portion of MBC receptors spontaneously oligomerized, and phosphorylated kinases accumulated at the membrane and speculate that heightened constitutive signaling may play a role in maintaining MBC longevity. Using high-resolution imaging, we have provided a description of the earliest events in the Ag activation of MBCs and evidence for acquired cell-intrinsic differences in the initiation of BCR signaling in human naive and MBCs.

  1. 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

  2. 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.

  3. Airborne particulate matter in spacecraft

    NASA Technical Reports Server (NTRS)

    1988-01-01

    Acceptability limits and sampling and monitoring strategies for airborne particles in spacecraft were considered. Based on instances of eye and respiratory tract irritation reported by Shuttle flight crews, the following acceptability limits for airborne particles were recommended: for flights of 1 week or less duration (1 mg/cu m for particles less than 10 microns in aerodynamic diameter (AD) plus 1 mg/cu m for particles 10 to 100 microns in AD); and for flights greater than 1 week and up to 6 months in duration (0.2 mg/cu m for particles less than 10 microns in AD plus 0.2 mg/cu m for particles 10 to 100 microns in AD. These numerical limits were recommended to aid in spacecraft atmosphere design which should aim at particulate levels that are a low as reasonably achievable. Sampling of spacecraft atmospheres for particles should include size-fractionated samples of 0 to 10, 10 to 100, and greater than 100 micron particles for mass concentration measurement and elementary chemical analysis by nondestructive analysis techniques. Morphological and chemical analyses of single particles should also be made to aid in identifying airborne particulate sources. Air cleaning systems based on inertial collection principles and fine particle collection devices based on electrostatic precipitation and filtration should be considered for incorporation into spacecraft air circulation systems. It was also recommended that research be carried out in space in the areas of health effects and particle characterization.

  4. Spacecraft Modularity for Serviceable Satellites

    NASA Technical Reports Server (NTRS)

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

    2015-01-01

    Satellite servicing has been a proven capability of NASA since the first servicing missions in the 1980s with astronauts on the space shuttle. This capability enabled the on-orbit assembly of the International Space Station (ISS) and saved the Hubble Space Telescope (HST) mission following the discovery of the flawed primary mirror. The effectiveness and scope of servicing opportunities, especially using robotic servicers, is a function of how cooperative a spacecraft is. In this paper, modularity will be presented as a critical design aspect for a spacecraft that is cooperative from a servicing perspective. Different features of modularity are discussed using examples from HST and the Multimission Modular Spacecraft (MMS) program from the 1980s and 1990s. The benefits of modularity will be presented including those directly related to servicing and those outside of servicing including reduced costs and increased flexibility. The new Reconfigurable Operational spacecraft for Science and Exploration (ROSE) concept is introduced as an affordable implementation of modularity that provides cost savings and flexibility. Key aspects of the ROSE architecture are discussed such as the module design and the distributed avionics architecture. The ROSE concept builds on the experience from MMS and due to its modularity, would be highly suitable as a future client for on-orbit servicing.

  5. Spacecraft materials HCl susceptibility assessments

    NASA Astrophysics Data System (ADS)

    Chu, C.-T.; Liu, De-Ling; Kim, Hyun; Alaan, Diana R.

    2014-09-01

    The susceptibility of spacecraft materials to HCl exposure was investigated in light of concerns to potential contamination during evolved expendable launch vehicle (EELV) overflight scenarios. Overflight refers to the circumstance where one spacecraft, resident on a launch pad, may be exposed to HCl generated from an earlier solid rocket launch at an adjacent pad. One aspect of the overflight risk assessments involves spacecraft materials susceptibility to HCl exposure. This study examined a wide range of spacecraft materials after being exposed to HCl vapor in a well-characterized facility. Sample thermal/optical and electrostatic dissipation properties, as well as surface chemical and morphological features, were characterized before and after the HCl exposure. All materials tested, except for indium tin oxide (ITO) coated Kapton film, showed no significant degradation after HCl exposure of up to 4800 ppb-hr. The ITO coated Kapton sample showed slight signs of degradation after being exposed to 500 ppb-hr HCl, as the surface resistance was increased by a factor of 5. However, the potential HCl dose inside the payload fairing (PLF) was estimated to be far below 500 ppb-hr in an EELV overflight event. These results, along with other relevant laboratory test data on the HCl removal efficiency of the filtration media used on the launch sites, provide the technical rationale that properly filtered air as the PLF purge should pose little risk in terms of HCl contamination under EELV overflight scenarios.

  6. Microbial Contamination in the Spacecraft

    NASA Technical Reports Server (NTRS)

    Pierson, Duane L.

    2001-01-01

    Spacecraft and space habitats supporting human exploration contain a diverse population of microorganisms. Microorganisms may threaten human habitation in many ways that directly or indirectly impact the health, safety, or performance of astronauts. The ability to produce and maintain spacecraft and space stations with environments suitable for human habitation has been established over 40 years of human spaceflight. An extensive database of environmental microbiological parameters has been provided for short-term (< 20 days) spaceflight 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 spaceflight on biological functions and population dynamics of microorganisms in spacecraft.

  7. Analyzing Dynamics of Cooperating Spacecraft

    NASA Technical Reports Server (NTRS)

    Hughes, Stephen P.; Folta, David C.; Conway, Darrel J.

    2004-01-01

    A software library has been developed to enable high-fidelity computational simulation of the dynamics of multiple spacecraft distributed over a region of outer space and acting with a common purpose. All of the modeling capabilities afforded by this software are available independently in other, separate software systems, but have not previously been brought together in a single system. A user can choose among several dynamical models, many high-fidelity environment models, and several numerical-integration schemes. The user can select whether to use models that assume weak coupling between spacecraft, or strong coupling in the case of feedback control or tethering of spacecraft to each other. For weak coupling, spacecraft orbits are propagated independently, and are synchronized in time by controlling the step size of the integration. For strong coupling, the orbits are integrated simultaneously. Among the integration schemes that the user can choose are Runge-Kutta Verner, Prince-Dormand, Adams-Bashforth-Moulton, and Bulirsh- Stoer. Comparisons of performance are included for both the weak- and strongcoupling dynamical models for all of the numerical integrators.

  8. 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

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

    PubMed Central

    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

    2016-01-01

    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

  10. 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. PMID:27573839

  11. Design and Flight Performance of NOAA-K Spacecraft Batteries

    NASA Technical Reports Server (NTRS)

    Rao, Gopalakrishna M.; Chetty, P. R. K.; Spitzer, Tom; Chilelli, P.

    1998-01-01

    The US National Oceanic and Atmospheric Administration (NOAA) operates the Polar Operational Environmental Satellite (POES) spacecraft (among others) to support weather forecasting, severe storm tracking, and meteorological research by the National Weather Service (NWS). The latest in the POES series of spacecraft, named as NOAA-KLMNN', one is in orbit and four more are in various phases of development. The NOAA-K spacecraft was launched on May 13, 1998. Each of these spacecraft carry three Nickel-Cadmium batteries designed and manufactured by Lockheed Martin. The battery, which consists of seventeen 40 Ah cells manufactured by SAFT, provides the spacecraft power during the ascent phase, orbital eclipse and when the power demand is in excess of the solar array capability. The NOAA-K satellite is in a 98 degree inclination, 7:30AM ascending node orbit. In this orbit the satellite experiences earth occultation only 25% of the year. This paper provides a brief overview of the power subsystem, followed by the battery design and qualification, the cell life cycle test data, and the performance during launch and in orbit.

  12. Design and Flight Performance of NOAA-K Spacecraft Batteries

    NASA Technical Reports Server (NTRS)

    Rao, Gopalakrishna M.; Chetty, P. R. K.; Spitzer, Tom; Chilelli, P.

    1999-01-01

    The US National Oceanic and Atmospheric Administration (NOAA) operates the Polar Operational Environmental Satellite (POES) spacecraft (among others) to support weather forecasting, severe storm tracking, and meteorological research by the National Weather Service (NWS). The latest in the POES series of spacecraft, named as NOAA-KLMNN, is in orbit and four more are in various phases of development. The NOAA-K spacecraft was launched on May 13, 1998. Each of these spacecraft carry three Nickel-Cadmium batteries designed and manufactured by Lockheed Martin. The battery, which consists of seventeen 40 Ah cells manufactured by SAFT, provides the spacecraft power during the ascent phase, orbital eclipse and when the power demand is in excess of the solar array capability. The NOAA-K satellite is in a 98 degree inclination, 7:30AM ascending node orbit. In this orbit the satellite experiences earth occultation only 25% of the year. This paper provides a brief overview of the power subsystem, followed by the battery design and qualification, the cell life cycle test data, and the performance during launch and in orbit.

  13. Investigation of nickel hydrogen battery technology for the RADARSAT spacecraft

    NASA Technical Reports Server (NTRS)

    Mccoy, D. A.; Lackner, J. L.

    1986-01-01

    The low Earth orbit (LEO) operations of the RADARSAT spacecraft require high performance batteries to provide energy to the payload and platform during eclipse period. Nickel Hydrogen cells are currently competing with the more traditional Nickel Cadmium cells for high performance spacecraft applications at geostationary Earth orbit (GEO) and Leo. Nickel Hydrogen cells appear better suited for high power applications where high currents and high Depths of Discharge are required. Although a number of GEO missions have flown with Nickel Hydrogen batteries, it is not readily apparent that the LEO version of the Nickel Hydrogen cell is able to withstand the extended cycle lifetime (5 years) of the RADARSAT mission. The problems associated with Nickel Hydrogen cells are discussed in the contex of RADARSAT mission and a test program designed to characterize cell performance is presented.

  14. An investigation of nonlinear control of spacecraft attitude

    NASA Astrophysics Data System (ADS)

    Binette, Mark Richard

    The design of controllers subject to the nonlinear H-infinity criterion is explored. The plants to be controlled are the attitude motion of spacecraft, subject to some disturbance torque. Two cases are considered: the regulation about an inertially-fixed direction, and an Earth-pointing spacecraft in a circular orbit, subject to the gravity-gradient torque. The spacecraft attitude is described using the modified Rodrigues parameters. A series of controllers are designed using the nonlinear H-infinity control criterion, and are subsequently generated using a Taylor series expansion to approximate solutions of the relevant Hamilton-Jacobi equations. The controllers are compared, using both input-output and initial condition simulations. A proof is used to demonstrate that the linearized controller solves the H-infinity control problem for the inertial pointing problem when describing the plant using the modified Rodrigues parameters.

  15. Spacecraft dynamics due to elastic ring antenna deployment

    NASA Astrophysics Data System (ADS)

    Makarov, Alexandr L.; Khoroshilov, Viktor S.; Zakrzhevskii, Alexandr E.

    2011-09-01

    In this paper the dynamics of a spacecraft with a system of stabilization out-of-operation is studied. The deployment of the ring flexible antenna is performed after placing the spacecraft into orbit and damping the initially undesired rotations by a special jet-propelled system. Basically the antenna is a pre-stressed tape reeled on a special drum. Deploying from the drum, the tape takes the shape of an elastic ring of 30 m in diameter. The objective of the study is the mechanical and computational modelling of the spacecraft dynamics. The equations of motion are derived in Lagrangian form. Numerical simulations of operational mode of the system are performed. As it is shown in main result, which restrictions must be imposed on parameters of the process of deployment for maintenance of the shape of the deployed design.

  16. Enhanced Attitude Control Experiment for SSTI Lewis Spacecraft

    NASA Technical Reports Server (NTRS)

    Maghami, Peoman G.

    1997-01-01

    The enhanced attitude control system experiment is a technology demonstration experiment on the NASA's small spacecraft technology initiative program's Lewis spacecraft to evaluate advanced attitude control strategies. The purpose of the enhanced attitude control system experiment is to evaluate the feasibility of designing and implementing robust multi-input/multi-output attitude control strategies for enhanced pointing performance of spacecraft to improve the quality of the measurements of the science instruments. Different control design strategies based on modern and robust control theories are being considered for the enhanced attitude control system experiment. This paper describes the experiment as well as the design and synthesis of a mixed H(sub 2)/H(sub infinity) controller for attitude control. The control synthesis uses a nonlinear programming technique to tune the controller parameters and impose robustness and performance constraints. Simulations are carried out to demonstrate the feasibility of the proposed attitude control design strategy. Introduction

  17. 78 FR 27219 - Dominion Bridgeport Fuel Cell, LLC; Supplemental Notice That Initial Market-Based Rate Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-09

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Dominion Bridgeport Fuel Cell, LLC; Supplemental Notice That Initial Market... in the above-referenced proceeding of Dominion Bridgeport Fuel Cell, LLC's application for...

  18. 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.

  19. Developing Generic Software for Spacecraft Avionics

    NASA Technical Reports Server (NTRS)

    Smith, Joseph

    2003-01-01

    A proposed approach to the development of software for spacecraft avionics is based partly on a concept of generic software that could be tailored to satisfy requirements for specific missions. The proposed approach would stand in contrast to the conventional approach of first defining avionics requirements for a specific mission, then developing software specific to those requirements. The proposed approach might also be adaptable to programming computers that control and monitor other complex equipment systems that range in scale from automobiles to factories. The concept of a spacecraft avionics functional model (SAFM) is a major element of the proposed approach. An SAFM would be, essentially, a systematic and hierarchical description of the functionality required of the avionics software (and hardware) for a given mission. Although the initial input information used to start the construction of an SAFM would typically amount to a high-level description, the SAFM would thereafter be decomposed to a low level. The resulting low-level version of the model would be used to develop a set of generic requirements that could be expected to include a large fraction of all requirements for a large fraction of all missions. The generic requirements would be used to develop software modules that could be included in, or excluded from, the final flight software to satisfy the requirements of a specific mission.

  20. Prosomatostatin II processing is initiated in the trans-Golgi network of anglerfish pancreatic cells.

    PubMed

    Bourdais, J; Devilliers, G; Girard, R; Morel, A; Benedetti, L; Cohen, P

    1990-08-16

    Anglerfish prosomatostatin II, the precursor of somatostatin-28 II, is produced in different cells from prosomatostatin I, by a cleavage at Arg73. Antibodies were raised against the carboxy-terminal [64-72] portion of the precursor II upstream from somatostatin-28 II sequence. These antibodies recognized only this epitope when unmasked from the entire precursor, allowing the detection of the [1-72] domain which was isolated from pancreatic islets extracts. The antibodies were used to monitor the peptide bond cleavage occurring at the carboxy terminus of Arg73 to generate somatostatin-28 II. Immunocytochemistry revealed labeling both in the vesicles budding from the trans-Golgi network and in the dense core granules. Together, these data support the conclusions that i) prohormone processing is initiated in the Golgi apparatus of the pancreatic islet cells; ii) the "non-hormonal" [1-72] amino-terminal domain of the precursor may be involved in some intra and/or extra-cellular function(s). PMID:1975170

  1. 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.

  2. Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans.

    PubMed

    Stapelberg, Michael; Zobalova, Renata; Nguyen, Maria Nga; Walker, Tom; Stantic, Marina; Goodwin, Jacob; Pasdar, Elham Alizadeh; Thai, Thuan; Prokopova, Katerina; Yan, Bing; Hall, Susan; de Pennington, Nicholas; Thomas, Shane R; Grant, Gary; Stursa, Jan; Bajzikova, Martina; Meedeniya, Adrian C B; Truksa, Jaroslav; Ralph, Stephen J; Ansorge, Olaf; Dong, Lan-Feng; Neuzil, Jiri

    2014-02-01

    Tumor-initiating cells (TICs) often survive therapy and give rise to second-line tumors. We tested the plausibility of sphere cultures as models of TICs. Microarray data and microRNA data analysis confirmed the validity of spheres as models of TICs for breast and prostate cancer as well as mesothelioma cell lines. Microarray data analysis revealed the Trp pathway as the only pathway upregulated significantly in all types of studied TICs, with increased levels of indoleamine-2,3-dioxygenase-1 (IDO1), the rate-limiting enzyme of Trp metabolism along the kynurenine pathway. All types of TICs also expressed higher levels of the Trp uptake system consisting of CD98 and LAT1 with functional consequences. IDO1 expression was regulated via both transcriptional and posttranscriptional mechanisms, depending on the cancer type. Serial transplantation of TICs in mice resulted in gradually increased IDO1. Mitocans, represented by α-tocopheryl succinate and mitochondrially targeted vitamin E succinate (MitoVES), suppressed IDO1 in TICs. MitoVES suppressed IDO1 in TICs with functional mitochondrial complex II, involving transcriptional and posttranscriptional mechanisms. IDO1 increase and its suppression by VE analogues were replicated in TICs from primary human glioblastomas. Our work indicates that IDO1 is increased in TICs and that mitocans suppress the protein. PMID:24145120

  3. Role of Ca2+ signaling in initiation of stretch-induced apoptosis in neonatal heart cells.

    PubMed

    Liao, Xu Dong; Tang, Ai Hui; Chen, Quan; Jin, Hai Jing; Wu, Cai Hong; Chen, Lan-Ying; Wang, Shi Qiang

    2003-10-17

    Abnormal mechanical load, as seen in hypertension, is found to induce heart cell apoptosis, yet the signaling link between cell stretch and apoptotic pathways is not known. Using an in vitro stretch model mimicking diastolic pressure stress, here we show that Ca(2+) signaling participates essentially in the early stage of stretch-induced apoptosis. In neonatal rat cardiomyocytes, the moderate 20% stretch resulted in tonic elevation of intracellular free Ca(2+) ([Ca(2+)](i)). Buffering [Ca(2+)](i) by EGTA-AM, suppressing ryanodine-sensitive Ca(2+) release, and blocking L-type Ca(2+) channels all prevented the stretch-induced apoptosis as assessed by phosphatidylserine exposure and nuclear fragmentation. Notably, Ca(2+) suppression also prevented known stretch-activated apoptotic events, including caspase-3/-9 activation, mitochondrial membrane potential corruption, and reactive oxygen species production, suggesting that Ca(2+) signaling is the upstream of these events. Since [Ca(2+)](i) did not change without activating mechanosensitive Ca(2+) entry, we conclude that stretch-induced Ca(2+) entry, via the Ca(2+)-induced Ca(2+) release mechanism, plays an important role in initiating apoptotic signaling during mechanical stress.

  4. Effect of component compression on the initial performance of an IPV nickel-hydrogen cell

    NASA Technical Reports Server (NTRS)

    Gahn, Randall F.

    1987-01-01

    An experimental method was developed for evaluating the effect of component compression on the charge and discharge voltage characteristics of a 3 1/2 in. diameter boiler plate cell. A standard boiler plate pressure vessel was modified by the addition of a mechanical feedthrough on the bottom of the vessel which permitted different compressions to be applied to the components without disturbing the integrity of the stack. Compression loadings from 0.94 to 27.4 psi were applied by suspending weights from the feedthrough rod. Cell voltages were measured for 0.96-C, 55-min charge and for 1.37-C, 35-min and 2-C, 24-min discharges. An initial change in voltage performance on both charge and discharge as the loading increased was attributed to seating of the components. Subsequent variation of the compression from 2.97 to 27.4 psi caused only minor changes in either the charge or the discharge voltages. Several one month open-circuit voltage stands and 1100 cycles under LEO conditions at the maximum loading have produced no change in performance.

  5. Electrical Grounding Architecture for Unmanned Spacecraft

    NASA Technical Reports Server (NTRS)

    1998-01-01

    This handbook is approved for use by NASA Headquarters and all NASA Centers and is intended to provide a common framework for consistent practices across NASA programs. This handbook was developed to describe electrical grounding design architecture options for unmanned spacecraft. This handbook is written for spacecraft system engineers, power engineers, and electromagnetic compatibility (EMC) engineers. Spacecraft grounding architecture is a system-level decision which must be established at the earliest point in spacecraft design. All other grounding design must be coordinated with and be consistent with the system-level architecture. This handbook assumes that there is no one single 'correct' design for spacecraft grounding architecture. There have been many successful satellite and spacecraft programs from NASA, using a variety of grounding architectures with different levels of complexity. However, some design principles learned over the years apply to all types of spacecraft development. This handbook summarizes those principles to help guide spacecraft grounding architecture design for NASA and others.

  6. Second Venus spacecraft set for launch

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The launch phase of the Pioneer Venus Multiprobe spacecraft and cruise phases of both the Pioneer Venus Orbiter and the Multiprobe spacecraft are covered. Material pertinent to the Venus encounter is included.

  7. 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

  8. 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. PMID:9699032

  9. 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.

  10. 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

  11. Spiral ganglion cells and macrophages initiate neuro-inflammation and scarring following cochlear implantation

    PubMed Central

    Bas, Esperanza; Goncalves, Stefania; Adams, Michelle; Dinh, Christine T.; Bas, Jose M.; Van De Water, Thomas R.; Eshraghi, Adrien A.

    2015-01-01

    Conservation of a patient's residual hearing and prevention of fibrous tissue/new bone formation around an electrode array are some of the major challenges in cochlear implant (CI) surgery. Although it is well-known that fibrotic tissue formation around the electrode array can interfere with hearing performance in implanted patients, and that associated intracochlear inflammation can initiate loss of residual hearing, little is known about the molecular and cellular mechanisms that promote this response in the cochlea. In vitro studies in neonatal rats and in vivo studies in adult mice were performed to gain insight into the pro-inflammatory, proliferative, and remodeling phases of pathological wound healing that occur in the cochlea following an electrode analog insertion. Resident Schwann cells (SC), macrophages, and fibroblasts had a prominent role in the inflammatory process in the cochlea. Leukocytes were recruited to the cochlea following insertion of a nylon filament in adult mice, where contributed to the inflammatory response. The reparative stages in wound healing are characterized by persistent neuro-inflammation of spiral ganglion neurons (SGN) and expression of regenerative monocytes/macrophages in the cochlea. Accordingly, genes involved in extracellular matrix (ECM) deposition and remodeling were up-regulated in implanted cochleae. Maturation of scar tissue occurs in the remodeling phase of wound healing in the cochlea. Similar to other damaged peripheral nerves, M2 macrophages and de-differentiated SC were observed in damaged cochleae and may play a role in cell survival and axonal regeneration. In conclusion, the insertion of an electrode analog into the cochlea is associated with robust early and chronic inflammatory responses characterized by recruitment of leukocytes and expression of pro-inflammatory cytokines that promote intracochlear fibrosis and loss of the auditory hair cells (HC) and SGN important for hearing after CI surgery. PMID

  12. Mitochondria-derived hydrogen peroxide selectively enhances T cell receptor-initiated signal transduction.

    PubMed

    Gill, Tejpal; Levine, Alan D

    2013-09-01

    T cell receptor (TCR)-initiated signal transduction is reported to increase production of intracellular reactive oxygen species, such as superoxide (O2˙(-)) and hydrogen peroxide (H2O2), as second messengers. Although H2O2 can modulate signal transduction by inactivating protein phosphatases, the mechanism and the subcellular localization of intracellular H2O2 as a second messenger of the TCR are not known. The antioxidant enzyme superoxide dismutase (SOD) catalyzes the dismutation of highly reactive O2˙(-) into H2O2 and thus acts as an intracellular generator of H2O2. As charged O2˙(-) is unable to diffuse through intracellular membranes, cells express distinct SOD isoforms in the cytosol (Cu,Zn-SOD) and mitochondria (Mn-SOD), where they locally scavenge O2˙(-) leading to production of H2O2. A 2-fold organelle-specific overexpression of either SOD in Jurkat T cell lines increases intracellular production of H2O2 but does not alter the levels of intracellular H2O2 scavenging enzymes such as catalase, membrane-bound peroxiredoxin1 (Prx1), and cytosolic Prx2. We report that overexpression of Mn-SOD enhances tyrosine phosphorylation of TCR-associated membrane proximal signal transduction molecules Lck, LAT, ZAP70, PLCγ1, and SLP76 within 1 min of TCR cross-linking. This increase in mitochondrial H2O2 specifically modulates MAPK signaling through the JNK/cJun pathway, whereas overexpressing Cu,Zn-SOD had no effect on any of these TCR-mediated signaling molecules. As mitochondria translocate to the immunological synapse during TCR activation, we hypothesize this translocation provides the effective concentration of H2O2 required to selectively modulate downstream signal transduction pathways.

  13. Translation initiation requires cell division cycle 123 (Cdc123) to facilitate biogenesis of the eukaryotic initiation factor 2 (eIF2).

    PubMed

    Perzlmaier, Angelika F; Richter, Frank; Seufert, Wolfgang

    2013-07-26

    The eukaryotic translation initiation factor 2 (eIF2) is central to the onset of protein synthesis and its modulation in response to physiological demands. eIF2, a heterotrimeric G-protein, is activated by guanine nucleotide exchange to deliver the initiator methionyl-tRNA to the ribosome. Here we report that assembly of the eIF2 complex in vivo depends on Cdc123, a cell proliferation protein conserved among eukaryotes. Mutations of CDC123 in budding yeast reduced the association of eIF2 subunits, diminished polysome levels, and increased GCN4 expression indicating that Cdc123 is critical for eIF2 activity. Cdc123 bound the unassembled eIF2γ subunit, but not the eIF2 complex, and the C-terminal domain III region of eIF2γ was both necessary and sufficient for Cdc123 binding. Alterations of the binding site revealed a strict correlation between Cdc123 binding, the biological function of eIF2γ, and its ability to assemble with eIF2α and eIF2β. Interestingly, high levels of Cdc123 neutralized the assembly defect and restored the biological function of an eIF2γ mutant. Moreover, the combined overexpression of eIF2 subunits rescued an otherwise inviable cdc123 deletion mutant. Thus, Cdc123 is a specific eIF2 assembly factor indispensable for the onset of protein synthesis. Human Cdc123 is encoded by a disease risk locus, and, therefore, eIF2 biogenesis control by Cdc123 may prove relevant for normal cell physiology and human health. This work identifies a novel step in the eukaryotic translation initiation pathway and assigns a biochemical function to a protein that is essential for growth and viability of eukaryotic cells.

  14. 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. PMID:26905196

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

    PubMed Central

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

    2015-01-01

    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 (OncoAd.RGD-hTERT-EGFP/TRAIL), and applied them to CAR-negative bladder cancer T24 cells and cancer-initiating T24 sphere cells. OncoAd.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 OncoAd.hTERT-EGFP. Notably, OncoAd.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. PMID:25973680

  16. SAS-A spacecraft magnetic tests

    NASA Technical Reports Server (NTRS)

    Boyle, J. C.

    1970-01-01

    Magnetic tests were conducted on the spacecraft for: (1) alignment, compensation, calibration, and bias determination for the spacecraft three-axis vector magnetometer; (2) determination of permanent, induced, and stray magnetic moments of the spacecraft and compensation of permanent magnetic moments by permanent magnets; and (3) evaluation of the spin and attitude control system.

  17. Spacecraft and their Boosters. Aerospace Education I.

    ERIC Educational Resources Information Center

    Coard, E. A.

    This book, one in the series on Aerospace Education I, provides a description of some of the discoveries that spacecraft have made possible and of the experience that American astronauts have had in piloting spacecraft. The basic principles behind the operation of spacecraft and their boosters are explained. Descriptions are also included on…

  18. Low-Cost, Class D Testing of Spacecraft Photovoltaic Systems Can Reduce Risk

    NASA Technical Reports Server (NTRS)

    Forgione, Joshua B.; Kojima, Gilbert K.; Hanel, Robert; Mallinson, Mark V.

    2014-01-01

    The end-to-end verification of a spacecraft photovoltaic power generation system requires light! Specifically, the standard practice for doing so is the Large Area Pulsed Solar Simulation (LAPSS). A LAPSS test can characterize a photovoltaic system's efficiency via its response to rapidly applied impulses of simulated sunlight. However, a Class D program on a constrained budget and schedule may not have the resources to ship an entire satellite for a LAPSS test alone. Such was the case with the Lunar Atmospheric and Dust Environment Explorer (LADEE) program, which was also averse to the risk of hardware damage during shipment. When the Electrical Power System (EPS) team was denied a spacecraft-level LAPSS test, the lack of an end-to-end power generation test elevated to a project-level technical risk. The team pulled together very limited resources to not only eliminate the risk, but build a process to monitor the health of the system through mission operations. We discuss a process for performing a low-cost, end-to-end test of the LADEE photovoltaic system. The approach combines system-level functional test, panel-level performance results, and periodic inspection (and repair) up until launch. Following launch, mission operations tools are utilized to assess system performance based on a scant amount of data. The process starts in manufacturing at the subcontractor. The panel manufacturer provides functional test and LAPSS data on each individual panel. We apply an initial assumption that the per-panel performance is sufficient to meet the power generation requirements. The manufacturer's data is also carried as the performance allocation for each panel during EPS system modeling and initial mission operations. During integration and test, a high-power, professional theater lamp system provides simulated sunlight to each panel on the spacecraft, thereby permitting a true end-to-end system test. A passing test results in a step response to nearly full-rated current

  19. Initiation of Hippo signaling is linked to polarity rather than to cell position in the pre-implantation mouse embryo.

    PubMed

    Anani, Shihadeh; Bhat, Shivani; Honma-Yamanaka, Nobuko; Krawchuk, Dayana; Yamanaka, Yojiro

    2014-07-01

    In the mouse embryo, asymmetric divisions during the 8-16 cell division generate two cell types, polar and apolar cells, that are allocated to outer and inner positions, respectively. This outer/inner configuration is the first sign of the formation of the first two cell lineages: trophectoderm (TE) and inner cell mass (ICM). Outer polar cells become TE and give rise to the placenta, whereas inner apolar cells become ICM and give rise to the embryo proper and yolk sac. Here, we analyze the frequency of asymmetric divisions during the 8-16 cell division and assess the relationships between cell polarity, cell and nuclear position, and Hippo signaling activation, the pathway that initiates lineage-specific gene expression in 16-cell embryos. Although the frequency of asymmetric divisions varied in each embryo, we found that more than six blastomeres divided asymmetrically in most embryos. Interestingly, many apolar cells in 16-cell embryos were located at outer positions, whereas only one or two apolar cells were located at inner positions. Live imaging analysis showed that outer apolar cells were eventually internalized by surrounding polar cells. Using isolated 8-cell blastomeres, we carefully analyzed the internalization process of apolar cells and found indications of higher cortical tension in apolar cells than in polar cells. Last, we found that apolar cells activate Hippo signaling prior to taking inner positions. Our results suggest that polar and apolar cells have intrinsic differences that establish outer/inner configuration and differentially regulate Hippo signaling to activate lineage-specific gene expression programs. PMID:24948601

  20. Spacecraft Tests of General Relativity

    NASA Technical Reports Server (NTRS)

    Anderson, John D.

    1997-01-01

    Current spacecraft tests of general relativity depend on coherent radio tracking referred to atomic frequency standards at the ground stations. This paper addresses the possibility of improved tests using essentially the current system, but with the added possibility of a space-borne atomic clock. Outside of the obvious measurement of the gravitational frequency shift of the spacecraft clock, a successor to the suborbital flight of a Scout D rocket in 1976 (GP-A Project), other metric tests would benefit most directly by a possible improved sensitivity for the reduced coherent data. For purposes of illustration, two possible missions are discussed. The first is a highly eccentric Earth orbiter, and the second a solar-conjunction experiment to measure the Shapiro time delay using coherent Doppler data instead of the conventional ranging modulation.

  1. MIDN: a spacecraft microdosimeter mission.

    PubMed

    Pisacane, V L; Ziegler, J F; Nelson, M E; Caylor, M; Flake, D; Heyen, L; Youngborg, E; Rosenfeld, A B; Cucinotta, F; Zaider, M; Dicello, J F

    2006-01-01

    MIDN (MIcroDosimetry iNstrument) is a payload on the MidSTAR-I spacecraft (Midshipman Space Technology Applications Research) under development at the United States Naval Academy. MIDN is a solid-state system being designed and constructed to measure microdosimetric spectra to determine radiation quality factors for space environments. Radiation is a critical threat to the health of astronauts and to the success of missions in low-Earth orbit and space exploration. The system will consist of three separate sensors, one external to the spacecraft, one internal and one embedded in polyethylene. Design goals are mass <3 kg and power <2 W. The MidSTAR-I mission in 2006 will provide an opportunity to evaluate a preliminary version of this system. Its low power and mass makes it useful for the International Space Station and manned and unmanned interplanetary missions as a real-time system to assess and alert astronauts to enhanced radiation environments. PMID:16785245

  2. Contingent plan structures for spacecraft

    NASA Technical Reports Server (NTRS)

    Drummond, M.; Currie, K.; Tate, A.

    1987-01-01

    Most current AI planners build partially ordered plan structures which delay decisions on action ordering. Such structures cannot easily represent contingent actions. A representation which can is presented. The representation has some other useful features: it provides a good account of the causal structure of a plan, can be used to describe disjunctive actions, and it offers a planner the opportunity of even less commitment than the classical partial order on actions. The use of this representation is demonstrated in an on-board spacecraft activity sequencing problem. Contingent plan execution in a spacecraft context highlights the requirements for a fully disjunctive representation, since communication delays often prohibit extensive ground-based accounting for remotely sensed information and replanning on execution failure.

  3. Spacecraft materials and coatings experiments

    NASA Technical Reports Server (NTRS)

    Slemp, Wayne S.

    1992-01-01

    The 5.8-year exposure data from the Long Duration Experiment Facility (LDEF) has demonstrated the benefits of long-term exposure in low Earth orbit (LEO) for understanding the behavior of spacecraft materials and coatings for use in extended space missions. The Space Station Freedom represents the next large area spacecraft available in NASA planned missions for obtaining this long term space exposure data. The advantages of using the Space Station Freedom for these studies are presented. Discrepancies between short-term flight exposure result from Shuttle Orbiter experiments and the long-term LDEF results are shown. The major objectives and benefits of conducting materials and coatings experiments on Space Station Freedom are emphasized.

  4. Spacecraft instrument technology and cosmochemistry

    PubMed Central

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

    2011-01-01

    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. PMID:21402932

  5. Fire extinguishers for manned spacecraft

    NASA Astrophysics Data System (ADS)

    Kopylov, S.; Smirnov, N. V.; Tanklevsky, L. T.

    2015-04-01

    Based on an analysis of fires in the oxygen-enriched atmosphere conditions in spacecraft and other sealed chambers of various purposes, the most dangerous groups of fires are identified. For this purpose, groups were compiled to analyze dependences that describe the increase of fire hazard to a critical value. A criterion for determining timely and effective fire extinguishing was offered. Fire experiments in oxygen-enriched atmosphere conditions were conducted, and an array of experimental data on the mass burning rate of materials and their extinguishing by water mist was obtained. Relationships colligating an array of experimental data were offered. Experimental and analytical studies were taken as a basis for hand fire extinguisher implementation for manned spacecraft.

  6. Foam Core Shielding for Spacecraft

    NASA Technical Reports Server (NTRS)

    Adams, Marc

    2007-01-01

    A foam core shield (FCS) system is now being developed to supplant multilayer insulation (MLI) systems heretofore installed on spacecraft for thermal management and protection against meteoroid impacts. A typical FCS system consists of a core sandwiched between a face sheet and a back sheet. The core can consist of any of a variety of low-to-medium-density polymeric or inorganic foams chosen to satisfy application-specific requirements regarding heat transfer and temperature. The face sheet serves to shock and thereby shatter incident meteoroids, and is coated on its outer surface to optimize its absorptance and emittance for regulation of temperature. The back sheet can be dimpled to minimize undesired thermal contact with the underlying spacecraft component and can be metallized on the surface facing the component to optimize its absorptance and emittance. The FCS systems can perform better than do MLI systems, at lower mass and lower cost and with greater volumetric efficiency.

  7. Spacecraft dynamics and space exploration

    NASA Astrophysics Data System (ADS)

    Tiulin, G. A.

    The papers presented in this volume provide an overview of recent theoretical and experimental research related to spacecraft dynamics and space exploration, with particular attention given to the libration and rotational motion of spacecraft containing a liquid. Topics discussed include resonance phenomena in the rotational motions of artificial and natural celestial bodies, simulation of the dynamics of launch vehicles, the motion of a rigid body whose cavity is partially filled with a liquid, and a rapidly converging variational algorithm in the problem of the natural vibrations of a liquid in a container. Papers are also presented on a study of transient processes in the case of large perturbations of a free liquid surface in a closed compartment, the motion of a rigid body with a liquid whose free surface is covered by a nonlinearly deformed shell, and an experimental study of the stability of the rotational motion of liquid-filled bodies.

  8. Doppler tracking of planetary spacecraft

    NASA Technical Reports Server (NTRS)

    Kinman, Peter W.

    1992-01-01

    This article concerns the measurement of Doppler shift on microwave links that connect planetary spacecraft with the Deep Space Network. Such measurements are made by tracking the Doppler effect with phase-locked loop receivers. A description of equipment and techniques as well as a summary of the appropriate mathematical models are given. The two-way Doppler shift is measured by transmitting a highly-stable microwave (uplink) carrier from a ground station, having the spacecraft coherently transpond this carrier, and using a phase-locked loop receiver at the ground station to track the returned (downlink) carrier. The largest sources of measurement error are usually plasma noise and thermal noise. The plasma noise, which may originate in the ionosphere or the solar corona, is discussed; and a technique to partially calibrate its effect, involving the use of two simultaneous downlink carriers that are coherently related, is described. Range measurements employing Doppler rate-aiding are also described.

  9. 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. PMID:21402932

  10. Spacecraft component heater control system

    NASA Technical Reports Server (NTRS)

    Bachtel, Frederick D. (Inventor); Owen, James W. (Inventor)

    1989-01-01

    A heater control circuit is disclosed as being constructed in a single integrated circuit, with the integrated circuit conveniently mounted proximate to a spacecraft component requiring temperature control. Redundant heater controllers control power applied to strip heaters disposed to provide heat to a component responsive to sensed temperature from temperature sensors. Signals from these sensors are digitized and compared with a dead band temperature and set point temperature stored in memory to generate an error signal if the sensed temperature is outside the parameter stored in the memory. This error signal is utilized by a microprocessor to selectively instruct the heater controllers to apply power to the strip heaters. If necessary, the spacecraft central processor may access or interrogate the microprocessor in order to alter the set point temperature and dead band temperature range to obtain operational data relating to the operation of an integrated circuit for relaying to the ground control, or to switch off faulty components.

  11. 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.

  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. PMID:26475399

  13. Teaching old spacecraft new tricks

    NASA Technical Reports Server (NTRS)

    Farquhar, Robert; Dunham, David

    1988-01-01

    The technique of sending existing space probes on extended mission by altering their orbital paths with gravity-assist maneuvers and relatively brief rocket firings is examined. The use of the technique to convert the International Sun-Earth Explorer 3 mission into the International Cometary Explorer mission is discussed. Other examples are considered, including the extension of the Giotto mission and the retargeting of the Sakigake spacecraft. The original and altered trajectories of these three missions are illustrated.

  14. Outgassing data for spacecraft materials

    NASA Technical Reports Server (NTRS)

    Campbell, W. A., Jr.; Marriott, R. S.; Park, J. J.

    1980-01-01

    A system for determining the mass loss in vacuum and for collecting the outgassed compounds was developed. Outgassing data, derived from tests at 398 K (125 degrees C) for 24 hours in vacuum as per ASTM E 59577, are compiled for numerous materials for spacecraft use. The data presented are the total mass loss (TML) and the collected volatile condensable materials (CVCM). The various materials are compiled by likely usage and alphabetically.

  15. Radiation effects in spacecraft electronics

    NASA Technical Reports Server (NTRS)

    Raymond, James P.

    1989-01-01

    Effects on the internal spacecraft electronics due to exposure to the natural and enhanced space radiation environment will be reviewed. The emphasis will be placed on the description of the nature of both the exposure environment and failure mechanisms in semiconductors. Understanding both the system environment and device effects is critical in the use of laboratory simulation environments to obtain the data necessary to design and qualify components for successful application.

  16. Plasma sources for spacecraft neutralization

    NASA Technical Reports Server (NTRS)

    Davis, V. A.; Katz, I.; Mandell, M. J.

    1990-01-01

    The principles of the operation of plasma sources for the neutralization of the surface of a spacecraft traveling in the presence of hot plasma are discussed with special attention given to the hollow-cathode-based plasma contactors. Techiques are developed that allow the calculation of the potentials and particle densities in the near environment of a hollow cathode plasma contactor in both the test tank and the LEO environment. The techniques and codes were validated by comparison of calculated and measured results.

  17. Spacecraft control/flexible structures interaction study

    NASA Technical Reports Server (NTRS)

    Kaplan, M. H.; Hillard, S. E.

    1974-01-01

    An initial study to begin development of a flight experiment to measure spacecraft control/flexible structure interactions was completed. The approach consisted of developing the equations of motion for a vehicle possessing a flexible solar array, then linearizing about some nominal motion of the craft. A set of solutions is assumed for array deflection using a continuous normal mode method and important parameters are identified. Interrelationships between these parameters, measurement techniques, and input requirements are discussed which assure minimization of special vehicle maneuvers and optimization of data to be obtained during the normal flight sequence. Limited consideration is given to flight data retrieval and processing techniques as correlated with the requirements imposed by the measurement system. Results indicate that inflight measurement of the bending and torsional mode shapes and respective frequencies, and damping ratios, is necessary. Other parameters may be measured from design data.

  18. NASA Thermal Control Technologies for Robotic Spacecraft

    NASA Technical Reports Server (NTRS)

    Swanson, Theodore D.; Birur, Gajanana C.

    2003-01-01

    Technology development is inevitably a dynamic process in search of an elusive goal. It is never truly clear whether the need for a particular technology drives its development, or the existence of a new capability initiates new applications. Technology development for the thermal control of spacecraft presents an excellent example of this situation. Nevertheless, it is imperative to have a basic plan to help guide and focus such an effort. Although this plan will be a living document that changes with time to reflect technological developments, perceived needs, perceived opportunities, and the ever-changing funding environment, it is still a very useful tool. This presentation summarizes the current efforts at NASA/Goddard and NASA/JPL to develop new thermal control technology for future robotic NASA missions.

  19. NASA Thermal Control Technologies for Robotic Spacecraft

    NASA Technical Reports Server (NTRS)

    Swanson, Theodore D.; Biur, Gajanana C.

    2002-01-01

    Technology development is inevitably a dynamic process in search of an elusive goal. It is never truly clear whether the need for a particular technology drives its development, or the existence of a new capability initiates new applications. Technology development for the thermal control of spacecraft presents an excellent example of this situation. Nevertheless, it is imperative to have a basic plan to help guide and focus such an effort. Although this plan will be a living document that changes with time to reflect technological developments, perceived needs, perceived opportunities, and the ever-changing funding environment, it is still a very useful tool. This presentation summarizes the current efforts at NASA/Goddard and NASA/JPL to develop new thermal control technology for future NASA missions.

  20. Spacecraft formation flying for Earth-crossing object deflections using a power limited laser ablating

    NASA Astrophysics Data System (ADS)

    Yoo, Sung-Moon; Song, Young-Joo; Park, Sang-Young; Choi, Kyu-Hong

    2009-06-01

    A formation flying strategy with an Earth-crossing object (ECO) is proposed to avoid the Earth collision. Assuming that a future conceptual spacecraft equipped with a powerful laser ablation tool already rendezvoused with a fictitious Earth collision object, the optimal required laser operating duration and direction histories are accurately derived to miss the Earth. Based on these results, the concept of formation flying between the object and the spacecraft is applied and analyzed as to establish the spacecraft's orbital motion design strategy. A fictitious "Apophis"-like object is established to impact with the Earth and two major deflection scenarios are designed and analyzed. These scenarios include the cases for the both short and long laser operating duration to avoid the Earth impact. Also, requirement of onboard laser tool's for both cases are discussed. As a result, the optimal initial conditions for the spacecraft to maintain its relative trajectory to the object are discovered. Additionally, the discovered optimal initial conditions also satisfied the optimal required laser operating conditions with no additional spacecraft's own fuel expenditure to achieve the spacecraft formation flying with the ECO. The initial conditions founded in the current research can be used as a spacecraft's initial rendezvous points with the ECO when designing the future deflection missions with laser ablation tools. The results with proposed strategy are expected to make more advances in the fields of the conceptual studies, especially for the future deflection missions using powerful laser ablation tools.

  1. 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

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

    PubMed

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

    2016-07-01

    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

  3. Resveratrol and N-acetylcysteine block the cancer-initiating step in MCF-10F cells

    PubMed Central

    Zahid, Muhammad; Saeed, Muhammad; Beseler, Cheryl; Rogan, Eleanor G.; Cavalieri, Ercole L.

    2015-01-01

    Substantial evidence suggests that catechol estrogen-3,4-quinones react with DNA to form predominantly the depurinating adducts 4-hydroxyestrone (estradiol)-1-N3Ade [4-OHE1(E2)-1-N3Ade] and 4-OHE1(E2)-1-N7Gua. Apurinic sites resulting from these adducts generate critical mutations that can initiate cancer. The paradigm of cancer initiation is based on an imbalance in estrogen metabolism between activating pathways that lead to estrogen–DNA adducts and deactivating pathways that lead to estrogen metabolites and conjugates. This imbalance can be improved to minimize formation of adducts by using antioxidants, such as resveratrol (Resv) and N-acetylcysteine (NAcCys). To compare the ability of Resv and NAcCys to block formation of estrogen–DNA adducts, we used the human breast epithelial cell line MCF-10F treated with 4-OHE2. Resv and NAcCys directed the metabolism of 4-OHE2 toward protective pathways. NAcCys reacted with the quinones and reduced the semiquinones to catechols. This pathway was also carried out by Resv. In addition, Resv induced the protective enzyme quinone reductase, which reduces E1(E2)-3,4-quinones to 4-OHE1(E2). Resv was more effective at increasing the amount of 4-OCH3E1(E2) than NAcCys. Inhibition of estrogen–DNA adduct formation was similar at lower doses, but at higher doses Resv was about 50% more effective than NAcCys. Their combined effects were additive. Therefore, these two antioxidants provide an excellent combination to protect catechol estrogens from oxidation to catechol quinones. PMID:20934508

  4. Energy Storage Flywheels on Spacecraft

    NASA Technical Reports Server (NTRS)

    Bartlett, Robert O.; Brown, Gary; Levinthal, Joel; Brodeur, Stephen (Technical Monitor)

    2002-01-01

    With advances in carbon composite material, magnetic bearings, microprocessors, and high-speed power switching devices, work has begun on a space qualifiable Energy Momentum Wheel (EMW). An EMW is a device that can be used on a satellite to store energy, like a chemical battery, and manage angular momentum, like a reaction wheel. These combined functions are achieved by the simultaneous and balanced operation of two or more energy storage flywheels. An energy storage flywheel typically consists of a carbon composite rotor driven by a brushless DC motor/generator. Each rotor has a relatively large angular moment of inertia and is suspended on magnetic bearings to minimize energy loss. The use of flywheel batteries on spacecraft will increase system efficiencies (mass and power), while reducing design-production time and life-cycle cost. This paper will present a discussion of flywheel battery design considerations and a simulation of spacecraft system performance utilizing four flywheel batteries to combine energy storage and momentum management for a typical LEO satellite. A proposed set of control laws and an engineering animation will also be presented. Once flight qualified and demonstrated, space flywheel batteries may alter the architecture of most medium and high-powered spacecraft.

  5. Worldwide Spacecraft Crew Hatch History

    NASA Technical Reports Server (NTRS)

    Johnson, Gary

    2009-01-01

    The JSC Flight Safety Office has developed this compilation of historical information on spacecraft crew hatches to assist the Safety Tech Authority in the evaluation and analysis of worldwide spacecraft crew hatch design and performance. The document is prepared by SAIC s Gary Johnson, former NASA JSC S&MA Associate Director for Technical. Mr. Johnson s previous experience brings expert knowledge to assess the relevancy of data presented. He has experience with six (6) of the NASA spacecraft programs that are covered in this document: Apollo; Skylab; Apollo Soyuz Test Project (ASTP), Space Shuttle, ISS and the Shuttle/Mir Program. Mr. Johnson is also intimately familiar with the JSC Design and Procedures Standard, JPR 8080.5, having been one of its original developers. The observations and findings are presented first by country and organized within each country section by program in chronological order of emergence. A host of reference sources used to augment the personal observations and comments of the author are named within the text and/or listed in the reference section of this document. Careful attention to the selection and inclusion of photos, drawings and diagrams is used to give visual association and clarity to the topic areas examined.

  6. EVA dosimetry in manned spacecraft.

    PubMed

    Thomson, I

    1999-12-01

    Extra Vehicular Activity (EVA) will become a large part of the astronaut's work on board the International Space Station (ISS). It is already well known that long duration space missions inside a spacecraft lead to radiation doses which are high enough to be a significant health risk to the crew. The doses received during EVA, however, have not been quantified to the same degree. This paper reviews the space radiation environment and the current dose limits to critical organs. Results of preliminary radiation dosimetry experiments on the external surface of the BION series of satellites indicate that EVA doses will vary considerably due to a number of factors such as EVA suit shielding, temporal fluctuations and spacecraft orbit and shielding. It is concluded that measurement of doses to crew members who engage in EVA should be done on board the spacecraft. An experiment is described which will lead the way to implementing this plan on the ISS. It is expected that results of this experiment will help future crew mitigate the risks of ionising radiation in space.

  7. Paneth Cell-Rich Regions Separated by a Cluster of Lgr5+ Cells Initiate Crypt Fission in the Intestinal Stem Cell Niche.

    PubMed

    Langlands, Alistair J; Almet, Axel A; Appleton, Paul L; Newton, Ian P; Osborne, James M; Näthke, Inke S

    2016-06-01

    The crypts of the intestinal epithelium house the stem cells that ensure the continual renewal of the epithelial cells that line the intestinal tract. Crypt number increases by a process called crypt fission, the division of a single crypt into two daughter crypts. Fission drives normal tissue growth and maintenance. Correspondingly, it becomes less frequent in adulthood. Importantly, fission is reactivated to drive adenoma growth. The mechanisms governing fission are poorly understood. However, only by knowing how normal fission operates can cancer-associated changes be elucidated. We studied normal fission in tissue in three dimensions using high-resolution imaging and used intestinal organoids to identify underlying mechanisms. We discovered that both the number and relative position of Paneth cells and Lgr5+ cells are important for fission. Furthermore, the higher stiffness and increased adhesion of Paneth cells are involved in determining the site of fission. Formation of a cluster of Lgr5+ cells between at least two Paneth-cell-rich domains establishes the site for the upward invagination that initiates fission. PMID:27348469

  8. Paneth Cell-Rich Regions Separated by a Cluster of Lgr5+ Cells Initiate Crypt Fission in the Intestinal Stem Cell Niche

    PubMed Central

    Langlands, Alistair J.; Almet, Axel A.; Appleton, Paul L.; Newton, Ian P.; Osborne, James M.; Näthke, Inke S.

    2016-01-01

    The crypts of the intestinal epithelium house the stem cells that ensure the continual renewal of the epithelial cells that line the intestinal tract. Crypt number increases by a process called crypt fission, the division of a single crypt into two daughter crypts. Fission drives normal tissue growth and maintenance. Correspondingly, it becomes less frequent in adulthood. Importantly, fission is reactivated to drive adenoma growth. The mechanisms governing fission are poorly understood. However, only by knowing how normal fission operates can cancer-associated changes be elucidated. We studied normal fission in tissue in three dimensions using high-resolution imaging and used intestinal organoids to identify underlying mechanisms. We discovered that both the number and relative position of Paneth cells and Lgr5+ cells are important for fission. Furthermore, the higher stiffness and increased adhesion of Paneth cells are involved in determining the site of fission. Formation of a cluster of Lgr5+ cells between at least two Paneth-cell-rich domains establishes the site for the upward invagination that initiates fission. PMID:27348469

  9. Merits of flywheels for spacecraft energy storage

    NASA Technical Reports Server (NTRS)

    Gross, S.

    1984-01-01

    Flywheel energy storage systems which have a very good potential for use in spacecraft are discussed. This system can be superior to alkaline secondary batteries and regenerable 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. 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 characteristics which would be useful for military applications. The major disadvantages of flywheel energy storage systems are that: power is not available during the launch phase without special provisions; and in flight failure of units may force shutdown of good counter rotating units, amplifying the effects of failure and limiting power distribution system options; no inherent emergency power capability unless specifically designed for, and a high level of complexity compared with batteries. The potential advantages of the flywheel energy storage system far outweigh the disadvantages.

  10. CD8+ T Cell Clones Specific for the 5T4 Antigen Target Renal Cell Carcinoma Tumor-Initiating Cells in a Murine Xenograft Model

    PubMed Central

    Tykodi, Scott S.; Satoh, Shoko; Deming, Janise D.; Chou, Jeffrey; Harrop, Richard; Warren, Edus H.

    2012-01-01

    The tumor antigen 5T4 is frequently expressed at high levels on renal cell carcinoma (RCC) and other epithelial carcinomas. Surveys of normal tissues demonstrate abundant 5T4 expression on placental trophoblast cells with limited expression elsewhere. 5T4 is the target for a therapeutic cancer vaccine (MVA-5T4) that elicits 5T4-specific serological, proliferative, and CTL responses. However, the anti-tumor activity of 5T4-specific CTL has not been extensively characterized. CD8+ T cells from HLA-A2+ healthy donors (n=4) or RCC patients (n=2) were stimulated in vitro with the HLA-A2-binding nonamer peptides 5T417–25 or 5T497–105 and screened by flow cytometry with specific tetramers (TET). CD8+/TET+ T cell clones specific for 5T417–25 or 5T497–105 peptide were isolated from 4/6 and 1/4 donors respectively. A subset of clones specific for 5T417–25 was cytolytic for MVA-5T4 infected HLA-A2+ LCL target cells and for constitutively HLA-A2- and 5T4- expressing RCC tumor cell lines (including A498 RCC). In a xenoengraftment assay, the co-inoculation of a representative 5T417–25-specific CTL clone with A498 RCC tumors cells into immune deficient mice completely prevented growth of A498 tumors. Taken together, these data demonstrate high avidity CD8+ CTL able to recognize the naturally-processed 5T417–25 epitope on RCC tumor cells including putative tumor-initiating cells are present in peripheral blood of both healthy donors and RCC patients. CD8+ T cell immunity targeting 5T417–25 is therefore of substantial interest both as a potential target for further development of vaccination or adoptive cellular immunotherapy and for immune monitoring studies in association with nonspecific immunotherapies. PMID:22892449

  11. Transcriptome analysis of basal and luminal tumor-initiating cells in ErbB2-driven breast cancer

    PubMed Central

    Borcherding, Nicholas; Bormann, Nicholas; Kusner, David; Kolb, Ryan; Zhang, Weizhou

    2015-01-01

    Breast cancer is the leading cause of cancer-related mortality for females worldwide [1]. Improving early screening strategies and understanding the events that lead to tumor initiation have led to demonstrable improvements in clinical outcome. Our previous work revealed a variance in the tumorigenic capacity between different mammary epithelial cell populations in an MMTV-ErbB2 mouse model. In order to greater understand how different mammary epithelial cells influence the tumorigenic capacity in ErbB2-induced breast cancer, we transplanted different cell populations from pre-neoplastic MMTV-ErbB2 female mice into recipient mice for tumorigenic study. We found that different mammary epithelial cells bear different tumorigenic potentials even when induced by the same ErbB2 proto-oncogene. To understand the difference in tumors formed from different epithelial cells, we performed gene expression profiling using these tumors (GSE64487). Several genes were further validated using real-time reverse transcription polymerase chain reaction (RT-PCR). Here we provide further details on the experimental methods and microarray analysis. This data provides a resource to further understanding how different mammary cell populations can initiate ErbB2-driven tumors and the role of these cell populations as putative tumor-initiating cells (TICs). PMID:26167451

  12. Best-Fit Conic Approximation of Spacecraft Trajectory

    NASA Technical Reports Server (NTRS)

    Singh, Gurkipal

    2005-01-01

    A computer program calculates a best conic fit of a given spacecraft trajectory. Spacecraft trajectories are often propagated as conics onboard. The conic-section parameters as a result of the best-conic-fit are uplinked to computers aboard the spacecraft for use in updating predictions of the spacecraft trajectory for operational purposes. In the initial application for which this program was written, there is a requirement to fit a single conic section (necessitated by onboard memory constraints) accurate within 200 microradians to a sequence of positions measured over a 4.7-hour interval. The present program supplants a prior one that could not cover the interval with fewer than four successive conic sections. The present program is based on formulating the best-fit conic problem as a parameter-optimization problem and solving the problem numerically, on the ground, by use of a modified steepest-descent algorithm. For the purpose of this algorithm, optimization is defined as minimization of the maximum directional propagation error across the fit interval. In the specific initial application, the program generates a single 4.7-hour conic, the directional propagation of which is accurate to within 34 microradians easily exceeding the mission constraints by a wide margin.

  13. Testing of typical spacecraft materials in a simulated substorm environment

    NASA Technical Reports Server (NTRS)

    Stephens, N. J.; Berkopec, F. D.; Staskus, J. V.; Blech, R. A.; Narciso, S. J.

    1976-01-01

    An investigation to determine spacecraft materials characteristics under charging conditions was conducted at the Lewis Research Center substorm simulation facility. The test specimens were spacecraft paints, silvered Teflon, thermal blankets and solar array segments. The samples, ranging in size from 300 to 1,000 sq cm were exposed to monoenergetic electron energies from 2 to 20 keV at a current density of 1 nA sq cm. The samples generally behaved as capacitors with strong voltage gradients at their edges. The charging characteristics of the silvered Teflon, Kapton, and solar cell covers were controlled by the secondary emission characteristics. Insulators that did not discharge were the spacecraft paints and the quartz fiber cloth thermal blanket sample. All other samples did experience discharges when the surface voltage reached -8 to -16 kV. The discharges were photographed. The breakdown voltage for each sample was determined and the average energy lost in the discharge was computed.

  14. Spacecraft Jitter Attenuation Using Embedded Piezoelectric Actuators

    NASA Technical Reports Server (NTRS)

    Belvin, W. Keith

    1995-01-01

    Remote sensing from spacecraft requires precise pointing of measurement devices in order to achieve adequate spatial resolution. Unfortunately, various spacecraft disturbances induce vibrational jitter in the remote sensing instruments. The NASA Langley Research Center has performed analysis, simulations, and ground tests to identify the more promising technologies for minimizing spacecraft pointing jitter. These studies have shown that the use of smart materials to reduce spacecraft jitter is an excellent match between a maturing technology and an operational need. This paper describes the use of embedding piezoelectric actuators for vibration control and payload isolation. In addition, recent advances in modeling, simulation, and testing of spacecraft pointing jitter are discussed.

  15. Spacecraft

    NASA Technical Reports Server (NTRS)

    Clark, John F.; Haggerty, James J.; Woodburn, John H.

    1961-01-01

    In this twentieth century, we are privileged to witness the first steps toward realization of an age-old dream: the exploration of space. Already, in the first few years of the Space Age, man has been able to penetrate the layer of atmosphere which surrounds his planet and to venture briefly into space. Scores of man-made objects have been thrust into space, some of them to roam the solar system forever. Behind each space mission are years of patient research, thousands of man-hours of labor, and large sums of money. Because the sums involved are so enormous, the question is frequently asked, "Is it worth it?" Many people want to know what return this huge investment will bring to mankind. The return on the investment is knowledge. The accumulation of knowledge over the centuries has made possible our advanced way of life. As we unlock more and more of the secrets of the universe through space exploration, we add new volumes to the encyclopedia of man's knowledge. This will be applied to the benefit of mankind. For the practical-minded, there are concrete benefits to our way of life. Although we are still in the Stone Age of space exploration, a number of immediate applications of space technology are already apparent. For instance, imagine the benefits of an absolutely perfect system of predicting the weather. Or, going a step further, even changing the weather. And wouldn't it be fascinating to watch the next Olympic games, telecast from Tokyo, on your TV set? These are just a few of the practical benefits made possible by space technology.

  16. EGCG inhibits the growth and tumorigenicity of nasopharyngeal tumor-initiating cells through attenuation of STAT3 activation.

    PubMed

    Lin, Chien-Hung; Chao, Li-Keng; Hung, Peir-Haur; Chen, Yann-Jang

    2014-01-01

    A subset of cancer cells, termed cancer stem cells (CSCs) or tumor-initiating cells (TICs) could initiate tumors and are responsible for tumor recurrence and chemotherapeutic resistance. In this study, we enriched TICs in nasopharyngeal carcinoma (NPC) by the spheres formation and characterized the stem-like signatures such as self-renewal, proliferation, chemoresistance and tumorigenicity. By this method, we investigated that epigallocathechin gallate (EGCG), the major polyphenol in green tea could target TICs and potently inhibit sphere formation, eliminate the stem-like properties and enhance chemosensitivity in NPC through attenuation of STAT3 activation, which could be important in regulating the stemness expression in NPC. Our results demonstrated that STAT3 pathway plays an important role in mediating tumor-initiating capacities in NPC and suggest that inactivation of STAT3 with EGCG may represent a potential preventive and therapeutic approach for NPC. PMID:24966947

  17. Circular Couette cell for two-dimensional turbulence experiments in sheared flow: initial results.

    NASA Astrophysics Data System (ADS)

    Ulmen, John V.; Fontana, Paul W.; Kearney-Fischer, Martin

    2006-03-01

    An experiment to study turbulence in quasi-two-dimensional flows with a controlled mean flow shear has been built. Experiments are underway to investigate the suppression of turbulent transport by sheared flow as seen in geostrophic flows and laboratory fusion plasmas. The apparatus, a circular Couette cell, uses a liquid film of dilute soap solution suspended freely in an annular channel with a rotating outer boundary. The channel is 7 cm wide with an average radius of 46.5 cm, and can be rotated at angular speeds exceeding 10 rad/s. Mean flow profiles will be presented showing the effect of air resistance on the flow; damping lengths on the order of 1 mm are observed. Turbulence is driven independently via electromagnetic forcing. The rate of turbulence injection can be varied continuously, and its spatial scale corresponds to the spatial frequency of an array of NdFeB magnets. Diagnostics include particle imaging velocimetry, two-point laser Doppler velocimetry, and thickness measurements via reflection interferometry. Initial results and plans for upcoming measurements will be presented.

  18. Two-dimensional turbulence experiments in sheared flow using circular Couette cell: initial results.

    NASA Astrophysics Data System (ADS)

    Kearney-Fischer, Martin; Fontana, Paul; Windell, Simon; Rogers, Sean

    2007-03-01

    An experiment to study turbulence in quasi-two-dimensional flows with a controlled mean flow shear has been built. Experiments are underway to investigate the suppression of turbulent transport by sheared flow as seen in geostrophic flows and laboratory fusion plasmas. The apparatus, a circular Couette cell, uses a liquid film of dilute soap solution suspended freely in an annular channel with a rotating outer boundary. The channel is 7 cm wide with an average radius of 46.5 cm, and can be rotated at angular speeds exceeding 10 rad/s. Turbulence is driven independently via electromagnetic forcing. The rate of turbulence injection can be varied continuously, and its spatial scale corresponds to the spatial frequency of an array of NdFeB magnets. Diagnostics include particle imaging velocimetry, two-point laser Doppler velocimetry, and thickness measurements via reflection interferometry. Initial analysis will be presented which indicates the existence of both turbulent suppression and expansion in high and low frequency regimes respectively. Plans for further analysis will also be presented.

  19. Cell Length Independent PBRB Model for Simulations of HE Reaction Initiation, Growth, and Detonation

    NASA Astrophysics Data System (ADS)

    Dwivedi, Sunil

    2015-06-01

    It has been our focus to use the Physics Based Reaction Burn (PBRB) model to simulate reaction initiation, growth, and detonation of HE composites at the mesoscale. The idealization of hot spots as planar surfaces reduces the 3D model to a 1D hot spot cell (1DHSC) model. The idealization also renders the model dependent on the 1DHSC length and mesh size. New developments are presented making the PBRB model 1DHSC length independent. First, the accurate prediction of the gas-solid interface temperature and thermal gradient are essential, achieved through a finite difference scheme with 500-2000 thermal grid points. Second, keeping the burn mass constant while varying the 1DHSC length is essential, achieved by varying the hot spot specific surface area. 1D and 2D simulation results are presented for shock response of RDX at 1 km/s and 2 km/s impact velocities. The 5, 10, and 50 micro meters 1DHSC lengths yield near identical run-to-detonation, time-to-detonation, and detonation velocity in agreement with experimental data. It is concluded that the new developments make the PBRB model well suited as a generic EOS model for HE composites. - Dr. John Brennan, ARL is acknowledged for his interactions and support. This work is supported in part by ARL Grant W911NF-12-2-0053 and DTRA Grant HDTRA1-12-1-0004.

  20. PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells

    PubMed Central

    Rogers, Samuel; Fey, Dirk; McCloy, Rachael A.; Parker, Benjamin L.; Mitchell, Nicholas J.; Payne, Richard J.; Daly, Roger J.; James, David E.; Caldon, C. Elizabeth; Watkins, D. Neil; Croucher, David R.; Burgess, Andrew

    2016-01-01

    ABSTRACT Entry into mitosis is driven by the phosphorylation of thousands of substrates, under the master control of Cdk1. During entry into mitosis, Cdk1, in collaboration with MASTL kinase, represses the activity of the major mitotic protein phosphatases, PP1 and PP2A, thereby ensuring mitotic substrates remain phosphorylated. For cells to complete and exit mitosis, these phosphorylation events must be removed, and hence, phosphatase activity must be reactivated. This reactivation of phosphatase activity presumably requires the inhibition of MASTL; however, it is not currently understood what deactivates MASTL and how this is achieved. In this study, we identified that PP1 is associated with, and capable of partially dephosphorylating and deactivating, MASTL during mitotic exit. Using mathematical modelling, we were able to confirm that deactivation of MASTL is essential for mitotic exit. Furthermore, small decreases in Cdk1 activity during metaphase are sufficient to initiate the reactivation of PP1, which in turn partially deactivates MASTL to release inhibition of PP2A and, hence, create a feedback loop. This feedback loop drives complete deactivation of MASTL, ensuring a strong switch-like activation of phosphatase activity during mitotic exit. PMID:26872783