Methods for Detection and Correction of Sudden Pixel Sensitivity Drops

PDC 8.0 includes implementation of a new algorithm to detect and correct step discontinuities appearing in roughly one of every twenty stellar light curves during a given quarter. An example of such a discontinuity in an actual light curve is shown in fig. 1. The majority of such discontinuities are believed to result from high-energy particles (either cosmic or solar in origin) striking the photometer and causing permanent local changes (typically -0.5% in summed apertures) in quantum efficiency, though a partial exponential recovery is often observed. Since these features, dubbed sudden pixel sensitivity dropouts (SPSDs), are uncorrelated across targets they cannot be properly accounted for by the current detrending algorithm. PDC de-trending is based on the assumption that features in flux time series are due either to intrinsic stellar phenomena or to systematic errors and that systematics will exhibit measurable correlations across targets. SPSD events violate these assumptions and their successful removal not only rectifies the flux values of affected targets, but demonstrably improves the overall performance of PDC de-trending

Scanning and Transmission Electron Microscopy of Bacterial Attachment to Mucosal Surfaces with Particular Reference to the Human Fallopian Tube

Neisseria gonorrhoeae and Chlamydia trachomatis are the common bacteria isolated from bacterial cervicitis and are the leading etiological agents for pelvic inflammatory disease. Neisseria gonorrhoeae cause infection of the mucosa of fallopian tubes in organ culture by (a) attaching to microvilli of nonciliated cells, (b) phagocytosis by these cells, (c) transport across and exocytosis from the epithelial cells. In contrast the Chlamydia attach to the epithelial surface without apparent ligand binding and are taken into the cytoplasm of the epithelial cell. Exocytosis of Chlamydia is into the tubal lumen and not into the subepithelial spaces. The ciliated epithelial cells of the fallopian tube are damaged by a gonococcal toxin but chlamydia do not exhibit such activity. These observations suggest that the mechanism of attachment to and invasion of the mucosal epithelium by gonococci and chlamydia are quite different and their potential for disease production occurs by different methods

Advancing liquid atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry toward ultra-high-throughput analysis

Label-free high-throughput screening using mass spectrometry has the potential to provide rapid large-scale sample analysis at a speed of more than one sample per second. Such speed is important for compound library, assay and future clinical screening of millions of samples within a reasonable time frame. Herein, we present a liquid atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) setup for high-throughput large-scale sample analysis (>5 samples per second) for three substance classes (peptides, antibiotics and lipids). Liquid support matrices (LSM) were used for the analysis of standard substances as well as complex biological fluids (milk). Throughput and analytical robustness were mainly dependent on the complexity of the sample composition and the current limitations of the commercial hardware. However, the ultimate limits of liquid AP-MALDI in sample throughput can be conservatively estimated to be beyond 10-20 samples per second. This level of analytical speed is highly competitive compared with other label-free MS methods, including electrospray ionization and solid state MALDI, as well as MS methods using multiplexing by labelling, which in principle can also be used in combination with liquid AP-MALDI MS

Automated Spacecraft Docking Using a Vision-Based Relative Navigation Sensor

Automated spacecraft docking is a concept of operations with several important potential applications. One application that has received a great deal of attention recently is that of an automated docking capable unmanned re-supply spacecraft. In addition to being useful for re-supplying orbiting space stations, automated shuttles would also greatly facilitate the manned exploration of nearby space objects, including the Moon, near-Earth asteroids, or Mars. These vehicles would allow for longer duration human missions than otherwise possible and could even accelerate human colonization of other worlds. This thesis develops an optimal docking controller for an automated docking capable spacecraft. An innovative vision-based relative navigation system called VisNav is used to provide real-time relative position and orientation estimates, while a Kalman post-filter generates relative velocity and angular rate estimates from the VisNav output. The controller's performance robustness is evaluated in a closed-loop automated spacecraft docking simulation of a scenario in circular lunar orbit. The simulation uses realistic dynamical models of the two vehicles, both based on the European Automated Transfer Vehicle. A high-fidelity model of the VisNav sensor adds realism to the simulated relative navigation measurements. The docking controller's performance is evaluated in the presence of measurement noise, with the cases of sensor noise only, vehicle mass errors plus sensor noise, errors in vehicle moments of inertia plus sensor noise, initial starting position errors plus sensor noise, and initial relative attitude errors plus sensor noise each being considered. It was found that for the chosen cases and docking scenario, the final controller was robust to both types of mass property modeling errors, as well as both types of initial condition modeling errors, even in the presence of sensor noise. The VisNav system was found to perform satisfactorily in all test cases, with excellent estimate error convergence characteristics for the scenario considered. These results demonstrate preliminary feasibility of the presented docking system, including VisNav, for space-based automated docking applications

A Process for Comparing Dynamics of Distributed Space Systems Simulations

The paper describes a process that was developed for comparing the primary orbital dynamics behavior between space systems distributed simulations. This process is used to characterize and understand the fundamental fidelities and compatibilities of the modeling of orbital dynamics between spacecraft simulations. This is required for high-latency distributed simulations such as NASA s Integrated Mission Simulation and must be understood when reporting results from simulation executions. This paper presents 10 principal comparison tests along with their rationale and examples of the results. The Integrated Mission Simulation (IMSim) (formerly know as the Distributed Space Exploration Simulation (DSES)) is a NASA research and development project focusing on the technologies and processes that are related to the collaborative simulation of complex space systems involved in the exploration of our solar system. Currently, the NASA centers that are actively participating in the IMSim project are the Ames Research Center, the Jet Propulsion Laboratory (JPL), the Johnson Space Center (JSC), the Kennedy Space Center, the Langley Research Center and the Marshall Space Flight Center. In concept, each center participating in IMSim has its own set of simulation models and environment(s). These simulation tools are used to build the various simulation products that are used for scientific investigation, engineering analysis, system design, training, planning, operations and more. Working individually, these production simulations provide important data to various NASA projects

Scanning Electron Microscopy Studies of Staphylococcal Adherence to Heart Valve Endothelial Cells in Organ Culture: An In Vitro Model of Acute Endocarditis

Organ cultures of human heart valves were used as a model to study the initial pathobiology of acute infective bacterial endocarditis. We used Staphylococcus aureus isolated from a case of infective endocarditis to infect the in vitro culture of the heart valves. Using scanning electron microscopy, we assessed the initial damage, attachment to and invasion of the endothelial cell layer by staphylococci. Our results indicate there is initial damage to the endothelium prior to observation of staphylococci attaching to the endothelial cell. By 12 h post infection, there is significant attachment and damage. At 24 h after infection, destruction of the heart valve endothelium is complete. The attachment and destruction arc progressive events and can be correlated quantitatively with bacterial numbers from the culture medium and those attached to the valves. This is correlated with increasing adherence ratios of the attaching staphylococci

Production and analysis of multiply charged negative ions by liquid atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry

RATIONALE: Liquid AP-MALDI has been shown to enable the production of ESI-like multiply charged analyte ions with little sample consumption and long-lasting, robust ion yield for sensitive analysis by mass spectrometry. Previous reports have focused on positive ion production. Here, we report an initial optimisation of liquid AP-MALDI for ESI-like negative ion production and its application to the analysis of peptides/proteins, DNA and lipids. METHODS: The instrumentation employed for this study is identical to that of earlier liquid AP-MALDI MS studies for positive analyte ion production with a simple non-commercial AP ion source that is attached to a Waters Synapt G2-Si mass spectrometer and incorporates a heated ion transfer tube. The preparation of liquid MALDI matrices is similar to positive ion mode analysis but has been adjusted for negative ion mode by changing the chromophore to 3-aminoquinoline and 9-aminoacridine for further improvements. RESULTS: For DNA, liquid AP-MALDI MS analysis benefited from switching to 9-aminoacridine-based MALDI samples and the negative ion mode, increasing the number of charges by up to a factor of 2 and the analyte ion signal intensities by more than ten-fold compared to the positive ion mode. The limit of detection was recorded at around 10fmol for ATGCAT. For lipids, negative ion mode analysis provided a fully orthogonal set of detected lipids. CONCLUSIONS: Negative ion mode is a sensitive alternative to positive ion mode in liquid AP-MALDI MS analysis. In particular, the analysis of lipids and DNA benefited from the complementarity of the detected lipid species and the vastly greater DNA ion signal intensities in negative ion mode

A latent spatial piecewise exponential model for interval-censored disease surveillance data with time-varying covariates and misclassification

Understanding the dynamics of disease spread is critical to achieving effective animal disease surveillance. A major challenge in modeling disease spread is the fact that the true disease status cannot be known with certainty due to the imperfect diagnostic sensitivity and specificity of the tests used to generate the disease surveillance data. Other challenges in modeling such data include interval censoring, relating disease spread to distance between units, and incorporating time-varying covariates, which are the unobserved disease statuses. We propose a latent spatial piecewise exponential model (PEX) with misclassification of events to address the challenges in modeling such disease surveillance data. Specifically, a piecewise exponential model is used to describe the latent disease process, with spatial distance and timevarying covariates incorporated for disease spread. The observed surveillance data with imperfect diagnostic tests are then modeled using a binary misclassification process given the latent disease statuses from the PEX model. Model parameters are estimated through a Bayesian approach utilizing non-informative priors. A simulation study is performed to evaluate the model performance and the results are compared with a candidate model where no misclassification is considered. For further illustration, we discuss an application of this model to a porcine reproductive and respiratory syndrome virus (PRRSV) surveillance data collected from commercial swine farms

Chemically Modified Oligonucleotides Modulate an Epigenetically Varied and Transient Form of Transcription Silencing of HIV-1 in Human Cells

Small noncoding RNAs (ncRNAs) have been shown to guide epigenetic silencing complexes to target loci in human cells. When targeted to gene promoters, these small RNAs can lead to long-term stable epigenetic silencing of gene transcription. To date, small RNAs have been shown to modulate transcriptional gene silencing (TGS) of human immunodeficiency virus type 1 (HIV-1) as well as several other disease-related genes, but it has remained unknown as to what extent particular chemistries can be used to generate single-stranded backbone-modified oligonucleotides that are amenable to this form of gene targeting and regulation. Here, we present data indicating that specific combinations of backbone modifications can be used to generate single-stranded antisense oligonucleotides that can functionally direct TGS of HIV-1 in a manner that is however, independent of epigenetic changes at the target loci. Furthermore, this functionality appears contingent on the absence of a 5′ phosphate in the oligonucleotide. These data suggest that chemically modified oligonucleotide based approaches could be implemented as a means to regulate gene transcription in an epigenetically independent manner