Framework for a space shuttle main engine health monitoring system

A framework developed for a health management system (HMS) which is directed at improving the safety of operation of the Space Shuttle Main Engine (SSME) is summarized. An emphasis was placed on near term technology through requirements to use existing SSME instrumentation and to demonstrate the HMS during SSME ground tests within five years. The HMS framework was developed through an analysis of SSME failure modes, fault detection algorithms, sensor technologies, and hardware architectures. A key feature of the HMS framework design is that a clear path from the ground test system to a flight HMS was maintained. Fault detection techniques based on time series, nonlinear regression, and clustering algorithms were developed and demonstrated on data from SSME ground test failures. The fault detection algorithms exhibited 100 percent detection of faults, had an extremely low false alarm rate, and were robust to sensor loss. These algorithms were incorporated into a hierarchical decision making strategy for overall assessment of SSME health. A preliminary design for a hardware architecture capable of supporting real time operation of the HMS functions was developed. Utilizing modular, commercial off-the-shelf components produced a reliable low cost design with the flexibility to incorporate advances in algorithm and sensor technology as they become available

Mutations in the E2 glycoprotein and the 3\u27 untranslated region enhance chikungunya virus virulence in mice

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes debilitating musculoskeletal pain and inflammation and can persist for months to years after acute infection. Although studies of humans and experimentally infected animals suggest that CHIKV infection persists in musculoskeletal tissues, the mechanisms for this remain poorly understood. To evaluate this further, we isolated CHIKV from the serum of persistently infected Rag1 -/- mice at day 28. When inoculated into naive wild-type (WT) mice, this persistently circulating CHIKV strain displayed a capacity for earlier dissemination and greater pathogenicity than the parental virus. Sequence analysis revealed a nonsynonymous mutation in the E2 glycoprotein (E2 K200R) and a deletion within the 3' untranslated region (3'-UTR). The introduction of these changes into the parental virus conferred enhanced virulence in mice, although primary tropism for musculoskeletal tissues was maintained. The E2 K200R mutation was largely responsible for enhanced viral dissemination and pathogenicity, although these effects were augmented by the 3'- UTR deletion. Finally, studies with Irf3/Irf7 -/- and Ifnar1 -/- mice suggest that the E2 K200R mutation enhances viral dissemination from the site of inoculation independently of interferon regulatory factor 3 (IRF3)-, IRF7-, and IFNAR1-mediated responses. As our findings reveal viral determinants of CHIKV dissemination and pathogenicity, their further study should help to elucidate host-virus interactions that determine acute and chronic CHIKV infection

Strategies for successful technology integration

Thesis (M.S.)--Massachusetts Institute of Technology, Sloan School of Management, 1997.Includes bibliographical references (leaves 78-80).by Michael W. Hawman.M.S

Pathogenic Chikungunya Virus Evades B Cell Responses to Establish Persistence

Chikungunya virus (CHIKV) and related alphaviruses cause epidemics of acute and chronic musculoskeletal disease. To investigate the mechanisms underlying the failure of immune clearance of CHIKV, we studied mice infected with an attenuated CHIKV strain (181/25) and the pathogenic parental strain (AF15561), which differ by five amino acids. Whereas AF15561 infection of wild-type mice results in viral persistence in joint tissues, 181/25 is cleared. In contrast, 181/25 infection of μMT mice lacking mature B cells results in viral persistence in joint tissues, suggesting that virus-specific antibody is required for clearance of infection. Mapping studies demonstrated that a highly conserved glycine at position 82 in the A domain of the E2 glycoprotein impedes clearance and neutralization of multiple CHIKV strains. Remarkably, murine and human antibodies targeting E2 domain B failed to neutralize pathogenic CHIKV strains efficiently. Our data suggest that pathogenic CHIKV strains evade E2 domain-B-neutralizing antibodies to establish persistence