Improved HIRAP flight calibration technique

A method of removing non-aerodynamic acceleration signals and calibrating the High Resolution Accelerometer Package (HiRAP) has been developed and improved. Twelve HiRAP mission data sets have been analyzed applying the improved in-flight calibration technique. The application of flight calibration factors to the data sets from these missions produced calibrated acceleration levels within +/- 5.7 micro-g of zero during a time in-flight when the acceleration level was known to be less than 1 g. To validate the current in-flight calibration technique, the atmospheric density results, specifically the normal-to-axial density ratios, have been compared with the analysis results obtained with the previous in-flight calibration technique. This comparison shows an improvement (up to 12.4 percent per flight) in the density ratio when the updated in-flight calibration technique is used

Ground and flight calibration assessment of HiRAP accelerometer data from missions STS-35 and STS-40

A method of removing non-aerodynamic signals and calibrating the High Resolution Accelerometer Package (HiRAP) flight data was developed and is discussed for Shuttle Orbiter missions STS-35 and STS-40. These two mission data sets were analyzed using ground (dynamic) calibration data and flight calibrations using a flight calibration technique that was developed and refined over the HiRAP operational lifetime. This technique evolved early in the flight program, since it was recognized that ground calibration factors are insufficient to determine absolute low acceleration levels. The application of flight calibration factors to the data sets from these missions produced calibrated acceleration levels within an accuracy of less than plus or minus 1.5 micro-g of zero during a time in the flight when the acceleration level was known to be less than 1 micro-g. This analysis further confirms the theory that flight calibrations are required in order to obtain the absolute measurement of low-frequency, low-acceleration flight signals

Rarefield-Flow Shuttle Aerodynamics Flight Model

A model of the Shuttle Orbiter rarefied-flow aerodynamic force coefficients has been derived from the ratio of flight acceleration measurements. The in-situ, low-frequency (less than 1Hz), low-level (approximately 1 x 10(exp -6) g) acceleration measurements are made during atmospheric re-entry. The experiment equipment designed and used for this task is the High Resolution Accelerometer Package (HiRAP), one of the sensor packages in the Orbiter Experiments Program. To date, 12 HiRAP re-entry mission data sets spanning a period of about 10 years have been processed. The HiRAP-derived aerodynamics model is described in detail. The model includes normal and axial hypersonic continuum coefficient equations as function of angle of attack, body-flap deflection, and elevon deflection. Normal and axial free molecule flow coefficient equations as a function of angle of attack are also presented, along with flight-derived rarefied-flow transition bridging formulae. Comparisons are made between the aerodynamics model, data from the latest Orbiter Operational Aerodynamic Design Data Book, applicable computer simulations, and wind-tunnel data

Rarefied-flow Shuttle aerodynamics model

A rarefied-flow shuttle aerodynamic model spanning the hypersonic continuum to the free molecule-flow regime was formulated. The model development has evolved from the High Resolution Accelerometer Package (HiRAP) experiment conducted on the Orbiter since 1983. The complete model is described in detail. The model includes normal and axial hypersonic continuum coefficient equations as functions of angle-of-attack, body flap deflection, and elevon deflection. Normal and axial free molecule flow coefficient equations as a function of angle-of-attack are presented, along with flight derived rarefied-flow transition bridging formulae. Comparisons are made with data from the Operational Aerodynamic Design Data Book (OADDB), applicable wind-tunnel data, and recent flight data from STS-35 and STS-40. The flight-derived model aerodynamic force coefficient ratio is in good agreement with the wind-tunnel data and predicts the flight measured force coefficient ratios on STS-35 and STS-40. The model is not, however, in good agreement with the OADDB. But, the current OADDB does not predict the flight data force coefficient ratios of either STS-35 or STS-40 as accurately as the flight-derived model. Also, the OADDB differs with the wind-tunnel force coefficient ratio data

OARE flight maneuvers and calibration measurements on STS-58

The Orbital Acceleration Research Experiment (OARE), which has flown on STS-40, STS-50, and STS-58, contains a three axis accelerometer with a single, nonpendulous, electrostatically suspended proofmass which can resolve accelerations to the nano-g level. The experiment also contains a full calibration station to permit in situ bias and scale factor calibration. This on-orbit calibration capability eliminates the large uncertainty of ground-based calibrations encountered with accelerometers flown in the past on the orbiter, thus providing absolute acceleration measurement accuracy heretofore unachievable. This is the first time accelerometer scale factor measurements have been performed on orbit. A detailed analysis of the calibration process is given along with results of the calibration factors from the on-orbit OARE flight measurements on STS-58. In addition, the analysis of OARE flight maneuver data used to validate the scale factor measurements in the sensor's most sensitive range is also presented. Estimates on calibration uncertainties are discussed. This provides bounds on the STS-58 absolute acceleration measurements for future applications

Implementing NASA's Capability-Driven Approach: Insight into NASA's Processes for Maturing Exploration Systems

NASA is engaged in transforming human spaceflight. The Agency is shifting from an exploration-based program with human activities focused on low Earth orbit (LEO) and targeted robotic missions in deep space to a more sustainable and integrated pioneering approach. Through pioneering, NASA seeks to address national goals to develop the capacity for people to work, learn, operate, live, and thrive safely beyond the Earth for extended periods of time. However, pioneering space involves more than the daunting technical challenges of transportation, maintaining health, and enabling crew productivity for long durations in remote, hostile, and alien environments. This shift also requires a change in operating processes for NASA. The Agency can no longer afford to engineer systems for specific missions and destinations and instead must focus on common capabilities that enable a range of destinations and missions. NASA has codified a capability driven approach, which provides flexible guidance for the development and maturation of common capabilities necessary for human pioneers beyond LEO. This approach has been included in NASA policy and is captured in the Agency's strategic goals. It is currently being implemented across NASA's centers and programs. Throughout 2014, NASA engaged in an Agency-wide process to define and refine exploration-related capabilities and associated gaps, focusing only on those that are critical for human exploration beyond LEO. NASA identified 12 common capabilities ranging from Environmental Control and Life Support Systems to Robotics, and established Agency-wide teams or working groups comprised of subject matter experts that are responsible for the maturation of these exploration capabilities. These teams, called the System Maturation Teams (SMTs) help formulate, guide and resolve performance gaps associated with the identified exploration capabilities. The SMTs are defining performance parameters and goals for each of the 12 capabilities, developing maturation plans and roadmaps for the identified performance gaps, specifying the interfaces between the various capabilities, and ensuring that the capabilities mature and integrate to enable future pioneering missions. By managing system development through the SMTs instead of traditional NASA programs and projects, the Agency is shifting from mission-driven development to a more flexible, capability-driven development. The process NASA uses to establish, integrate, prioritize, and manage the SMTs and associated capabilities is iterative. NASA relies on the Human Exploration and Operation Mission Directorate's SMT Integration Team within Advanced Exploration Systems to coordinate and facilitate the SMT process. The SMT Integration team conducts regular reviews and coordination meetings among the SMTs and has developed a number of tools to help the Agency implement capability driven processes. The SMT Integration team is uniquely positioned to help the Agency coordinate the SMTs and other processes that are making the capability-driven approach a reality. This paper will introduce the SMTs and the 12 key capabilities they represent. The role of the SMTs will be discussed with respect to Agency-wide processes to shift from mission-focused exploration to a capability-driven pioneering approach. Specific examples will be given to highlight systems development and testing within the SMTs. These examples will also show how NASA is using current investments in the International Space Station and future investments to develop and demonstrate capabilities. The paper will conclude by describing next steps and a process for soliciting feedback from the space exploration community to refine NASA's process for developing common exploration capabilities

Autoreactivity and Exceptional CDR Plasticity (but Not Unusual Polyspecificity) Hinder Elicitation of the Anti-HIV Antibody 4E10

The broadly-neutralizing anti-HIV antibody 4E10 recognizes an epitope in the membrane-proximal external region of the HIV envelope protein gp41. Previous attempts to elicit 4E10 by vaccination with envelope-derived or reverse-engineered immunogens have failed. It was presumed that the ontogeny of 4E10-equivalent responses was blocked by inherent autoreactivity and exceptional polyreactivity. We generated 4E10 heavy-chain knock-in mice, which displayed significant B cell dysregulation, consistent with recognition of autoantigen/s by 4E10 and the presumption that tolerance mechanisms may hinder the elicitation of 4E10 or 4E10-equivalent responses. Previously proposed candidate 4E10 autoantigens include the mitochondrial lipid cardiolipin and a nuclear splicing factor, 3B3. However, using carefully-controlled assays, 4E10 bound only weakly to cardiolipin-containing liposomes, but also bound negatively-charged, non-cardiolipin-containing liposomes comparably poorly. 4E10/liposome binding was predominantly mediated by electrostatic interactions rather than presumed hydrophobic interactions. The crystal structure of 4E10 free of bound ligands showed a dramatic restructuring of the combining site, occluding the HIV epitope binding site and revealing profound flexibility, but creating an electropositive pocket consistent with non-specific binding of phospholipid headgroups. These results strongly suggested that antigens other than cardiolipin mediate 4E10 autoreactivity. Using a synthetic peptide library spanning the human proteome, we determined that 4E10 displays limited and focused, but unexceptional, polyspecificity. We also identified a novel autoepitope shared by three ER-resident inositol trisphosphate receptors, validated through binding studies and immunohistochemistry. Tissue staining with 4E10 demonstrated reactivity consistent with the type 1 inositol trisphosphate receptor as the most likely candidate autoantigen, but is inconsistent with splicing factor 3B3. These results demonstrate that 4E10 recognition of liposomes competes with MPER recognition and that HIV antigen and autoepitope recognition may be distinct enough to permit eliciting 4E10-like antibodies, evading autoimmunity through directed engineering. However, 4E10 combining site flexibility, exceptional for a highly-matured antibody, may preclude eliciting 4E10 by conventional immunization strategies

Ontogeny of Recognition Specificity and Functionality for the Broadly Neutralizing Anti-HIV Antibody 4E10

The process of antibody ontogeny typically improves affinity, on-rate, and thermostability, narrows polyspecificity, and rigidifies the combining site to the conformer optimal for binding from the broader ensemble accessible to the precursor. However, many broadly-neutralizing anti-HIV antibodies incorporate unusual structural elements and recognition specificities or properties that often lead to autoreactivity. The ontogeny of 4E10, an autoreactive antibody with unexpected combining site flexibility, was delineated through structural and biophysical comparisons of the mature antibody with multiple potential precursors. 4E10 gained affinity primarily by off-rate enhancement through a small number of mutations to a highly conserved recognition surface. Controverting the conventional paradigm, the combining site gained flexibility and autoreactivity during ontogeny, while losing thermostability, though polyspecificity was unaffected. Details of the recognition mechanism, including inferred global effects due to 4E10 binding, suggest that neutralization by 4E10 may involve mechanisms beyond simply binding, also requiring the ability of the antibody to induce conformational changes distant from its binding site. 4E10 is, therefore, unlikely to be re-elicited by conventional vaccination strategies

Packaged and Free Satellite Tobacco Mosaic Virus (STMV) RNA Genomes Adopt Distinct Conformational States

The RNA genomes of viruses likely undergo multiple functionally important conformational changes during their replication cycles, changes that are poorly understood at present. We used two complementary in-solution RNA structure probing strategies (SHAPE-MaP and RING-MaP) to examine the structure of the RNA genome of satellite tobacco mosaic virus inside authentic virions and in a capsid-free state. Both RNA states feature similar three-domain architectures in which each major replicative functiontranslation, capsid coding, and genome synthesisfall into distinct domains. There are, however, large conformational differences between the in-virion and capsid-free states, primarily in one arm of the central T domain. These data support a model in which the packaged capsid-bound RNA is constrained in a local high-energy conformation by the native capsid shell. The removal of the viral capsid then allows the RNA genome to relax into a more thermodynamically stable conformation. The RNA architecture of the central T domain thus likely changes during capsid assembly and disassembly and may play a role in genome packaging