Weighted Least Squared Approach to Fault Detection and Isolation for GPS Integrity Monitoring

Reliability of a global navigation satellite system is one of great importance for global navigation purposes. Therefore, an integrity monitoring system is an inseparable part of aviation navigation system. Failures or faults due to malfunctions in the systems should be detected to keep the integrity of the system intact. In order to solve the problem that least squares method detects and isolates a satellite fault for GPS integrity monitoring, in this paper, a weighted least squares algorithm is proposed for satellite fault detection and isolation. The algorithm adopts the diagonal elements of the covariance matrix of GPS measurement equation as the weighted factor. Firstly, the weighted least squares approach for satellite fault detection establishes the test statistic by the sum of the squares of the pseudo-range residuals of each satellite for GPS. Then, the detection threshold is obtained by the false alarm rate of the fault detection, probability density function and visiable satellite number.The effectiveness of the proposed approach is illustrated in a problem of GPS (Global Positioning System) autonomous integrity monitoring system. Through the real raw measured GPS data，based on least squares RAIM method and the weighted least squares RAIM approach, the performance of the two algorithms is compared. The results show that the proposed RAIM approach is superior to the least squares RAIM algorithm in the sensitivity of fault detection and fault isolation performance for GPS integrity monitoring

Particle Filtering Approach for GNSS RAIM and FPGA Implementation

The integrity monitoring system, as an integral part of aviation navigation system for global navigation satellite system (GNSS), should detect and isolated Failures or faults caused by system failures to maintain the integrity of the GNSS. The pseudorange residual noise of navigation satellites does not completely follow the Gaussian distribution, the performance of traditional filtering algorithms (such as the Kalman filtering) may be reduced due to non-Gaussian noise. The particle filter algorithm has great advantage to dealing with the nonlinear and non-Gaussian system. in this paper, the particle filter algorithm is applied to GNSS receiver autonomous integrity monitoring(RAIM) to detect the fault of navigation satellite. Firstly, Log likelihood ratio (LLR) testing is established; and then, the consistency between the state estimation of the main particle filter and the auxiliary particle filter is checked to determine whether the navigation satellite has failed; finally, the novel RAIM algorithm is undertaken by field programmable gate array (FPGA), the modules of the proposed RAIM algorithm is implemented. The effectiveness of the proposed approach is illustrated in a problem of GPS (Global Positioning System) autonomous integrity monitoring system, the algorithm and its implementation can be embeded in GNSS receiver

Co-activation of Taxonomic and Thematic Relations in Spoken Word Comprehension: Evidence From Eye Movements

Evidence from behavior, computational linguistics, and neuroscience studies supported that semantic knowledge is represented in (at least) two semantic systems (i.e., taxonomic and thematic systems). It remains unclear whether, and to what extent taxonomic and thematic relations are co-activated. The present study investigated the co-activation of the two types of semantic representations when both types of semantic relations are simultaneously presented. In a visual-world task, participants listened to a spoken target word and looked at a visual display consisted of a taxonomic competitor, a thematic competitor and two distractors. Growth curve analyses revealed that both taxonomic and thematic competitors attracted visual attention during the processing of the target word but taxonomic competitor received more looks than thematic competitor. Moreover, although fixations on taxonomic competitor rose faster than thematic competitor, these two types of competitors started to attract more fixations than distractor in a similar time window. These findings indicate that taxonomic and thematic relations are co-activated by the spoken word, the activation of taxonomic relation is stronger and rise faster than thematic relation

DNA replication in early S phase pauses near newly activated origins

During the S phase of the cell cycle, the entire genome is replicated. There is a high level of orderliness to this process through the temporally and topologically coordinated activation of many replication origins situated along chromosomes. We investigated the program of replication from origins initiating in early S phase by labeling synchronized normal human fibroblasts (NHF1) with nucleotide analogs for various pulse times and measuring labeled tracks in combed DNA fibers. Our analysis showed that replication forks progress 9–35 kilobases from newly initiated origins, followed by a pause in synthesis before replication resumes. Pausing was not observed near origins that initiated in the middle of S phase. No evidence for pausing near origins was found at the beginning of the S phase in glioblastoma T98G cells. Treatment with the S phase checkpoint inhibitor caffeine abrogated pausing in NHF1 cells in early S phase. This suggests that pausing may comprise a novel aspect of the intra-S phase checkpoint pathway or a related new early S checkpoint. Further, it is possible that the loss of this regulatory process in cancer cells such as T98G could be a contributing factor in the genetic instability that typifies cancers

Time course investigation of PPARα- and Kupffer cell-dependent effects of WY-14,643 in mouse liver using microarray gene expression

Administration of peroxisome proliferators to rodents causes proliferation of peroxisomes, induction of β-oxidation enzymes, hepatocelluar hypertrophy and hyperplasia, with chronic exposure ultimately leading to hepatocellular carcinomas. Many responses associated with peroxisome proliferators are nuclear receptor-mediated events involving peroxisome proliferators-activated receptor alpha (PPARα). A role for nuclear receptor-independent events has also been shown, with evidence of Kupffer cell-mediated free radical production, presumably through NAPDH oxidase, induction of redox-sensitive transcription factors involved in cytokine production and cytokine-mediated cell replication following acute treatment with peroxisome proliferators in rodents. Recent studies have demonstrated, by using p47phox-null mice which are deficient in NADPH oxidase, that this enzyme is not related to the phenotypic events caused by prolonged administration of peroxisome proliferators. In an effort to determine the timing of the transition from Kupffer cell- to PPARα-dependent modulation of peroxisome proliferator effects, gene expression was assessed in liver from Pparα-null, p47phox-null and corresponding wild-type mice following treatment with 4-chloro-6-(2,3-xylidino)-pyrimidynylthioacetic acid (WY-14,643) for 8 h, 24 h, 72 h, 1 wk, or 4 wks. WY-14,643-induced gene expression in p47phox-null mouse liver differed substantially from wild-type mice at acute doses and striking differences in baseline expression of immune related genes were evident. Pathway mapping of genes that respond to WY-14,643 in a time- and dose-dependent manner demonstrates suppression of immune response, cell death and signal transduction and promotion of lipid metabolism, cell cycle and DNA repair. Furthermore, these pathways were largely dependent on PPARα, not NADPH oxidase demonstrating a temporal shift in response to peroxisome proliferators. Overall, this study shows that NADPH oxidase-dependent events, while detectable following acute treatment, are transient and short-lived. To the contrary, a strong PPARα-specific gene signature was evident in mice that were continually exposed to WY-14,643

Defective Cell Cycle Checkpoint Functions in Melanoma Are Associated with Altered Patterns of Gene Expression

Defects in DNA damage responses may underlie genetic instability and malignant progression in melanoma. Cultures of normal human melanocytes (NHMs) and melanoma lines were analyzed to determine whether global patterns of gene expression could predict the efficacy of DNA damage cell cycle checkpoints that arrest growth and suppress genetic instability. NHMs displayed effective G1 and G2 checkpoint responses to ionizing radiation-induced DNA damage. A majority of melanoma cell lines (11/16) displayed significant quantitative defects in one or both checkpoints. Melanomas with B-RAF mutations as a class displayed a significant defect in DNA damage G2 checkpoint function. In contrast the epithelial-like subtype of melanomas with wild-type N-RAS and B-RAF alleles displayed an effective G2 checkpoint but a significant defect in G1 checkpoint function. RNA expression profiling revealed that melanoma lines with defects in the DNA damage G1 checkpoint displayed reduced expression of p53 transcriptional targets, such as CDKN1A and DDB2, and enhanced expression of proliferation-associated genes, such as CDC7 and GEMININ. A Bayesian analysis tool was more accurate than significance analysis of microarrays for predicting checkpoint function using a leave-one-out method. The results suggest that defects in DNA damage checkpoints may be recognized in melanomas through analysis of gene expression

Microhomology-mediated end joining drives complex rearrangements and overexpression of MYC and PVT1 in multiple myeloma

MYC is a widely acting transcription factor and its deregulation is a crucial event in many human cancers. MYC is important biologically and clinically in multiple myeloma, but the mechanisms underlying its dysregulation are poorly understood. We show that MYC rearrangements are present in 36.0% of newly diagnosed myeloma patients, as detected in the largest set of next generation sequencing data to date (n=1,267). Rearrangements were complex and associated with increased expression of MYC and PVT1, but not other genes at 8q24. The highest effect on gene expression was detected in cases where the MYC locus is juxtaposed next to super-enhancers associated with genes such as IGH, IGK, IGL, TXNDC5/BMP6, FAM46C and FOXO3. We identified three hotspots of recombination at 8q24, one of which is enriched for IGH-MYC translocations. Breakpoint analysis indicates primary myeloma rearrangements involving the IGH locus occur through non-homologous end joining, whereas secondary MYC rearrangements occur through microhomology-mediated end joining. This mechanism is different to lymphomas, where non-homologous end joining generates MYC rearrangements. Rearrangements resulted in overexpression of key genes and chromatin immunoprecipitation-sequencing identified that HK2, a member of the glucose metabolism pathway, is directly over-expressed through binding of MYC at its promoter

A high-risk, Double-Hit, group of newly diagnosed myeloma identified by genomic analysis

Patients with newly diagnosed multiple myeloma (NDMM) with high-risk disease are in need of new treatment strategies to improve the outcomes. Multiple clinical, cytogenetic, or gene expression features have been used to identify high-risk patients, each of which has significant weaknesses. Inclusion of molecular features into risk stratification could resolve the current challenges. In a genome-wide analysis of the largest set of molecular and clinical data established to date from NDMM, as part of the Myeloma Genome Project, we have defined DNA drivers of aggressive clinical behavior. Whole-genome and exome data from 1273 NDMM patients identified genetic factors that contribute significantly to progression free survival (PFS) and overall survival (OS) (cumulative R2 = 18.4% and 25.2%, respectively). Integrating DNA drivers and clinical data into a Cox model using 784 patients with ISS, age, PFS, OS, and genomic data, the model has a cumlative R2 of 34.3% for PFS and 46.5% for OS. A high-risk subgroup was defined by recursive partitioning using either a) bi-allelic TP53 inactivation or b) amplification (≥4 copies) of CKS1B (1q21) on the background of International Staging System III, comprising 6.1% of the population (median PFS = 15.4 months; OS = 20.7 months) that was validated in an independent dataset. Double-Hit patients have a dire prognosis despite modern therapies and should be considered for novel therapeutic approaches