A knowledge-based system design/information tool

The objective of this effort was to develop a Knowledge Capture System (KCS) for the Integrated Test Facility (ITF) at the Dryden Flight Research Facility (DFRF). The DFRF is a NASA Ames Research Center (ARC) facility. This system was used to capture the design and implementation information for NASA's high angle-of-attack research vehicle (HARV), a modified F/A-18A. In particular, the KCS was used to capture specific characteristics of the design of the HARV fly-by-wire (FBW) flight control system (FCS). The KCS utilizes artificial intelligence (AI) knowledge-based system (KBS) technology. The KCS enables the user to capture the following characteristics of automated systems: the system design; the hardware (H/W) design and implementation; the software (S/W) design and implementation; and the utilities (electrical and hydraulic) design and implementation. A generic version of the KCS was developed which can be used to capture the design information for any automated system. The deliverable items for this project consist of the prototype generic KCS and an application, which captures selected design characteristics of the HARV FCS

Model authoring system for fail safe analysis

The Model Authoring System is a prototype software application for generating fault tree analyses and failure mode and effects analyses for circuit designs. Utilizing established artificial intelligence and expert system techniques, the circuits are modeled as a frame-based knowledge base in an expert system shell, which allows the use of object oriented programming and an inference engine. The behavior of the circuit is then captured through IF-THEN rules, which then are searched to generate either a graphical fault tree analysis or failure modes and effects analysis. Sophisticated authoring techniques allow the circuit to be easily modeled, permit its behavior to be quickly defined, and provide abstraction features to deal with complexity

A Model of the Chicxulub Impact Basin Based on Evaluation of Geophysical Data, Well Logs, and Drill Core Samples

Abundant evidence now shows that the buried Chicxulub structure in northern Yucatan, Mexico, is indeed the intensely sought-after source of the ejecta found world-wide at the Cretaceous-Tertiary (K/T) boundary. In addition to large-scale concentric patterns in gravity and magnetic data over the structure, recent analyses of drill-core samples reveal a lithological assemblage similar to that observed at other terrestrial craters. This assemblage comprises suevite breccias, ejecta deposit breccias (Bunte Breccia equivalents), fine-grained impact melt rocks, and melt-matrix breccias. All these impact-produced lithologies contain diagnostic evidence of shock metamorphism, including planar deformation features in quartz, feldspar, and zircons; diaplectic glasses of quartz and feldspar; and fused mineral melts and whole-rock melts. In addition, elevated concentrations of Ir, Re, and Os, in meteoritic relative proportions, have been detected in some melt-rock samples from the center of the structure. Isotopic analyses, magnetization of melt-rock samples, and local stratigraphic constraints identify this crater as the source of K/T boundary deposits

Blazar 3C 454.3 in Outburst and Quiescence During 2005-2007: Two Variable Synchrotron Emission Peaks

We monitored the flaring blazar 3C 454.3 during 2005 June-July with the Spitzer Infrared Spectrograph (IRS: 15 epochs), Infrared Array Camera (IRAC: 12 epochs) and Multiband Imaging Photometer (MIPS: 2 epochs). We also made Spitzer IRS, IRAC, and MIPS observations from 2006 December-2007 January when the source was in a low state, the latter simultaneous with a single Chandra X-ray observation. In addition, we present optical and sub-mm monitoring data. The 2005-2007 period saw 3 major outbursts. We present evidence that the radio-optical SED actually consists of two variable synchrotron peaks, the primary at IR and the secondary at sub-mm wavelengths. The lag between the optical and sub-mm outbursts may indicate that these two peaks arise from two distinct regions along the jet separated by a distance of 0.07-5 pc. The flux at 5-35 microns varied by a factor of 40 and the IR peak varied in frequency from <1E13 Hz to 4E13 Hz between the highest and lowest states in 2005 and 2006, respectively. Variability was well correlated across the mid-IR band, with no measurable lag. Flares that doubled in flux occurred on a time scale of 3 days. The IR SED peak moved to higher frequency as a flare brightened, then returned to lower frequency as it decayed. The fractional variability amplitude increased with frequency, which we attribute to decreasing synchrotron-self absorption optical depth. Mid-IR flares may signal the re-energization of a shock that runs into inhomogeneities along the pre-existing jet or in the external medium. The synchrotron peak frequencies during each major outburst may depend upon both the distance from the jet apex and the physical conditions in the shocks. Variation of the Doppler parameter along a curved or helical jet is another possibility. Frequency variability of the IR synchrotron peak may have important consequences for the interpretation of the blazar sequence, and the presence of a secondary peak may give insight into jet structure.Comment: 38 pages, 15 figures, submitted to ApJS, comments welcom

Unification of Luminous Type 1 Quasars through CIV Emission

Using a sample of 30,000 quasars from SDSS-DR7, we explore the range of properties exhibited by high-ionization, broad emission lines, such as CIV 1549. Specifically we investigate the anti-correlation between L_UV and emission line EQW (the Baldwin Effect) and the "blueshifting" of high-ionization emission lines. The blueshift of the CIV emission line is nearly ubiquitous, with a mean shift of 810 km/s for radio-quiet (RQ) quasars and 360 km/s for radio-loud (RL) quasars, and the Baldwin Effect is present in both RQ and RL samples. Composite spectra are constructed as a function of CIV emission line properties in attempt to reveal empirical relationships between different line species and the SED. Within a two-component disk+wind model of the broad emission line region (BELR), where the wind filters the continuum seen by the disk component, we find that RL quasars are consistent with being dominated by the disk component, while BALQSOs are consistent with being dominated by the wind component. Some RQ objects have emission line features similar to RL quasars; they may simply have insufficient black hole (BH) spin to form radio jets. Our results suggest that there could be significant systematic errors in the determination of L_bol and BH mass that make it difficult to place these findings in a more physical context. However, it is possible to classify quasars in a paradigm where the diversity of BELR parameters are due to differences in an accretion disk wind between quasars (and over time); these differences are underlain primarily by the SED, which ultimately must be tied to BH mass and accretion rate.Comment: 51 pages, 18 figures, accepted by AJ, revised version includes various modifications based on the referee's comment

The role of P2 receptors in controlling infections by intracellular pathogens

A growing number of studies have demonstrated the importance of ATPe-signalling via P2 receptors as an important component of the inflammatory response to infection. More recent studies have shown that ATPe can also have a direct effect on infection by intracellular pathogens, by modulating membrane trafficking in cells that contain vacuoles that harbour intracellular pathogens, such as mycobacteria and chlamydiae. A conserved mechanism appears to be involved in controlling infection by both of these pathogens, as a role for phospholipase D in inducing fusion between lysosomes and the vacuoles has been demonstrated. Other P2-dependent mechanisms are most likely operative in the cases of pathogens, such as Leishmania, which survive in an acidic phagolysosomal-like compartment. ATPe may function as a ‘danger signal–that alerts the immune system to the presence of intracellular pathogens that damage the host cell, while different intracellular pathogens have evolved enzymes or other mechanisms to inhibit ATPe-mediated signalling, which should, thus, be viewed as virulence factors for these pathogens

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

DNA replication defect in the Escherichia coli cgtA (ts) mutant arising from reduced DnaA levels

In Escherichia coli and other bacteria, the ribosome-associated CgtA GTP-binding protein plays a critical role in many basic cellular processes, including the control of DNA replication and/or segregation. However, the mechanism of this control is largely unknown. Here we report that ectopic expression of the dnaA gene partially restored both early growth in liquid medium and DNA synthesis defects of the cgtA (ts) mutant. Amounts of DnaA protein in the cgtA (ts) mutant incubated at elevated (42°C) temperature were significantly lower relative to wild-type bacteria. Both level of dnaA mRNA and transcriptional activity of the dnaA promoter- lacZ fusion were decreased in the CgtA-deficient cells. The effects of ectopic expression of dnaA were specific as analogous expression of another gene coding for a replication regulator, seqA , had no significant changes in growth and DNA synthesis in the cgtA mutant. Thus, it appears that the DNA replication defect in this mutant is a consequence of reduced DnaA levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45857/1/203_2006_Article_99.pd

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Scoping review of patient- and family-oriented outcomes and measures for chronic pediatric disease.

Improvements in health care for children with chronic diseases must be informed by research that emphasizes outcomes of importance to patients and families. To support a program of research in the field of rare inborn errors of metabolism (IEM), we conducted a broad scoping review of primary studies that: (i) focused on chronic pediatric diseases similar to IEM in etiology or manifestations and in complexity of management; (ii) reported patient- and/or family-oriented outcomes; and (iii) measured these outcomes using self-administered tools.We developed a comprehensive review protocol and implemented an electronic search strategy to identify relevant citations in Medline, EMBASE, DARE and Cochrane. Two reviewers applied pre-specified criteria to titles/abstracts using a liberal accelerated approach. Articles eligible for full-text review were screened by two independent reviewers with discrepancies resolved by consensus. One researcher abstracted data on study characteristics, patient- and family-oriented outcomes, and self-administered measures. Data were validated by a second researcher.4,118 citations were screened with 304 articles included. Across all included reports, the most-represented diseases were diabetes (35%), cerebral palsy (23%) and epilepsy (18%). We identified 43 unique patient- and family-oriented outcomes from among five emergent domains, with mental health outcomes appearing most frequently. The studies reported the use of 405 independent self-administered measures of these outcomes.Patient- and family-oriented research investigating chronic pediatric diseases emphasizes mental health and appears to be relatively well-developed in the diabetes literature. Future research can build on this foundation while identifying additional outcomes that are priorities for patients and families