A preliminary design for flight testing the FINDS algorithm

This report presents a preliminary design for flight testing the FINDS (Fault Inferring Nonlinear Detection System) algorithm on a target flight computer. The FINDS software was ported onto the target flight computer by reducing the code size by 65%. Several modifications were made to the computational algorithms resulting in a near real-time execution speed. Finally, a new failure detection strategy was developed resulting in a significant improvement in the detection time performance. In particular, low level MLS, IMU and IAS sensor failures are detected instantaneously with the new detection strategy, while accelerometer and the rate gyro failures are detected within the minimum time allowed by the information generated in the sensor residuals based on the point mass equations of motion. All of the results have been demonstrated by using five minutes of sensor flight data for the NASA ATOPS B-737 aircraft in a Microwave Landing System (MLS) environment

Evaluation of a fault tolerant system for an integrated avionics sensor configuration with TSRV flight data

The performance analysis results of a fault inferring nonlinear detection system (FINDS) using sensor flight data for the NASA ATOPS B-737 aircraft in a Microwave Landing System (MLS) environment is presented. First, a statistical analysis of the flight recorded sensor data was made in order to determine the characteristics of sensor inaccuracies. Next, modifications were made to the detection and decision functions in the FINDS algorithm in order to improve false alarm and failure detection performance under real modelling errors present in the flight data. Finally, the failure detection and false alarm performance of the FINDS algorithm were analyzed by injecting bias failures into fourteen sensor outputs over six repetitive runs of the five minute flight data. In general, the detection speed, failure level estimation, and false alarm performance showed a marked improvement over the previously reported simulation runs. In agreement with earlier results, detection speed was faster for filter measurement sensors soon as MLS than for filter input sensors such as flight control accelerometers

Design considerations for flight test of a fault inferring nonlinear detection system algorithm for avionics sensors

The modifications to the design of a fault inferring nonlinear detection system (FINDS) algorithm to accommodate flight computer constraints and the resulting impact on the algorithm performance are summarized. An overview of the flight data-driven FINDS algorithm is presented. This is followed by a brief analysis of the effects of modifications to the algorithm on program size and execution speed. Significant improvements in estimation performance for the aircraft states and normal operating sensor biases, which have resulted from improved noise design parameters and a new steady-state wind model, are documented. The aircraft state and sensor bias estimation performances of the algorithm's extended Kalman filter are presented as a function of update frequency of the piecewise constant filter gains. The results of a new detection system strategy and failure detection performance, as a function of gain update frequency, are also presented

A Screening Pipeline for Antiparasitic Agents Targeting Cryptosporidium Inosine Monophosphate Dehydrogenase

Persistent diarrhea is a leading cause of illness and death among impoverished children, and a growing share of this disease burden can be attributed to the parasite Cryptosporidium. There are no vaccines to prevent Cryptosporidium infection, and the treatment options are limited and unreliable. Critically, no effective treatment exists for children or adults suffering from AIDS. Cryptosporidium presents many technical obstacles for drug discovery; perhaps the most important roadblock is the difficulty of monitoring drug action. Here we have developed a set of methods to accelerate the drug discovery process for cryptosporidiosis. We exploit the opportunities for experimental manipulation in the related parasite Toxoplasma to genetically engineer a Cryptosporidium model. This new model parasite mirrors the metabolism of Cryptosporidium for a particularly promising drug target that supplies the building blocks for DNA and RNA. Drug effectiveness can be assayed through simple fluorescence measurements for many candidates. Using this assay as an initial filter, and adapting other assays to a high throughput format, we identify several novel chemical compounds that exhibit markedly improved anti-cryptosporidial activity and excellent selectivity

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV