123 research outputs found

    Simulation of a High Stability Reference Clock for Small Satellites with Modeled GPS Timing Errors

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    Small satellites have become capable platforms for a wide range of commercial, scientific and defense missions. Improved onboard clocks would make small satellites a viable option for even more missions, enabling radio aperture interferometry, improved radio occultation measurements, high altitude GPS navigation, and GPS augmentation missions, among others. Previous research by the authors investigated methods for creating a high stability reference clock for small satellites by combining a heterogeneous group of oscillators including multiple CSACs, a GPS receiver and an EMXO. This work predicted that time error standard deviations of ~500 ps were possible with GPS timing errors modeled as AWGN. This paper builds on previous work by developing a high-fidelity model for the GPS receiver timing error onboard a LEO spacecraft. Signal-In-Space Ranging Errors (SISRE) are modeled using post-fit GPS orbit and clock data, and ionospheric delays are approximated using IONEX maps and ionosphere models. GPS point solutions are then calculated over several days of LEO orbits to generate realistic receiver timing errors, which were then used in simulations of the high-stability heterogeneous clock ensemble. Simulations show degraded clock system performance compared to the prior model, with standard deviations of time errors increasing to 1.3 ns 1-σ. The results provide insight into the nature of GPS receiver clock errors for LEOs, as well as practical limitations that should be expected when implementing advanced clock systems on small satellites

    Incorporation Of Quantification Uncertainty Into Bulk and Single-Cell RNA-seq Analysis

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    In the first part of the dissertation, we propose a new method, CompDTU, that applies an isometric log-ratio transform to the vector of transcript-level relative abundance proportions that are of interest in differential transcript usage (DTU) analyses and assumes the resulting transformed data follow a multivariate normal distribution. This procedure does not suffer from computational speed and scalability issues that are present in many methods, making it ideally suited for DTU analysis with large sample sizes. Additionally, we extend CompDTU to incorporate quantification uncertainty using bootstrap replicates of abundance estimates and term this method CompDTUme. We show that CompDTU improves sensitivity and reduces false positive results relative to existing methods. Additionally, CompDTUme results in further improvements in performance over CompDTU while maintaining favorable speed and scalability. In the second part of the dissertation, we examine properties of bootstrap replicates of gene-level quantification estimates for single-cell RNA-seq (scRNA-seq) data. Specifically, we investigate the coverage of various intervals constructed using the bootstrap replicates and demonstrate that storage of mean and variance values from the set of bootstrap replicates ("compression") is sufficient to capture gene-level quantification uncertainty. Pseudo-replicates can then be simulated from a negative binomial distribution as needed, resulting in significant decreases in memory and storage space required to conduct uncertainty-aware analyses. We additionally extend the Swish method to use compression and show improvements in computation time and memory consumption without losses in performance. In the third part of the dissertation, we propose a general framework for incorporating simulated pseudo-replicates into statistical analyses. These approaches involve combining results across different pseudo-replicates using either the mean test statistic or specific quantiles of all p-values across replicates. We apply our framework to trajectory-based differential expression analysis of scRNA-seq data and show reductions in false positives relative to only incorporating the standard point-estimates of expression. Lastly, we demonstrate that discarding multi-mapping reads can result in significant underestimation of counts for functionally important genes using scRNA-seq data from developing mice embryos.Doctor of Philosoph

    Longitudinal T1 relaxation rate (R1) captures changes in short-term Mn exposure in welders

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    We demonstrated recently that the T1 relaxation rate (R1) captured short-term Mn exposure in welders with chronic, relatively low exposure levels in a cross-sectional study. In the current study, we used a longitudinal design to examine whether R1 values reflect the short-term dynamics of Mn exposure

    Increased R2* in the Caudate Nucleus of Asymptomatic Welders

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    Welding has been associated with neurobehavioral disorders. Welding fumes contain several metals including copper (Cu), manganese (Mn), and iron (Fe) that may interact to influence welding-related neurotoxicity. Although welding-related airborne Fe levels are about 10-fold higher than Mn, previous studies have focused on Mn and its accumulation in the basal ganglia. This study examined differences in the apparent transverse relaxation rates [R2* (1/T2*), estimate of Fe accumulation] in the basal ganglia (caudate nucleus, putamen, and globus pallidus) between welders and controls, and the dose–response relationship between estimated Fe exposure and R2* values. Occupational questionnaires estimated recent and lifetime Fe exposure, and blood Fe levels and brain magnetic resonance imaging (MRI) were obtained. Complete exposure and MRI R2* and R1 (1/T1: measure to estimate Mn accumulation) data from 42 subjects with welding exposure and 29 controls were analyzed. Welders had significantly greater exposure metrics and higher whole-blood Fe levels compared with controls. R2* in the caudate nucleus was significantly higher in welders after controlling for age, body mass index, respirator use, caudate R1, and blood metals of Cu and Mn, whereas there was no difference in R1 values in the basal ganglia between groups. The R2* in the caudate nucleus was positively correlated with whole-blood Fe concentration. This study provides the first evidence of higher R2* in the caudate nucleus of welders, which is suggestive of increased Fe accumulation in this area. Further studies are needed to replicate the findings and determine the neurobehavioral relevance

    Editor’s Highlight: Lower Fractional Anisotropy in the Globus Pallidus of Asymptomatic Welders, a Marker for Long-Term Welding Exposure

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    Introduction: Welding fumes contain several metals including manganese (Mn), iron (Fe), and copper (Cu) that at high exposure may co-influence welding-related neurotoxicity. The relationship between brain accumulation of these metals and neuropathology, especially in welders with subclinical exposure levels, is unclear. This study examined the microstructural integrity of basal ganglia (BG) regions in asymptomatic welders using diffusion tensor imaging (DTI). Methods: Subjects with (n = 43) and without (age- and gender-matched controls; n = 31) history of welding were studied. Occupational questionnaires estimated short-term (HrsW; welding hours and E90; cumulative exposure, past 90 days) and long-term (YrsW; total years welding and ELT; cumulative exposure, lifetime) exposure. Whole blood metal levels (Mn, Fe, and Cu) were obtained. Brain MRI pallidal index (PI), R1 (1/T1), and R2* (1/T2*) were measured to estimate Mn and Fe accumulation in BG [caudate, putamen, and globus pallidus (GP)]. DTI was used to assess BG microstructural differences, and related with exposure measurements. Results: When compared with controls, welders had significantly lower fractional anisotropy (FA) in the GP. In welders, GP FA values showed non-linear relationships to YrsW, blood Mn, and PI. GP FA decreased after a critical level of YrsW or Mn was reached, whereas it decreased with increasing PI values until plateauing at the highest PI values. GP FA, however, did not show any relationship with short-term exposure measurements (HrsW, E90), blood Cu and Fe, or R2* values. Conclusion: GP FA captured microstructural changes associated with chronic low-level Mn exposure, and may serve as a biomarker for neurotoxicity in asymptomatic welders

    Radiative transition rates and collision strengths for Si II

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    Aims. This work reports radiative transition rates and electron impact excitation collision strengths for levels of the 3s23p, 3s3p2, 3s24s, and 3s23d configurations of Siii. Methods. The radiative data were computed using the Thomas-Fermi-Dirac-Amaldi central potential, but with the modifications introduced by Bautista (2008) that account for the effects of electron-electron interactions. We also introduce new schemes for the optimization of the variational parameters of the potential. Additional calculations were carried out with the Relativistic Hartree-Fock and the multiconfiguration Dirac-Fock methods. Collision strengths in LS-coupling were calculated in the close coupling approximation with the R-matrix method. Then, fine structure collision strengths were obtained by means of the intermediate-coupling frame transformation (ICFT) method which accounts for spin-orbit coupling effects. Results. We present extensive comparisons between the results of different approximations and with the most recent calculations and experiment available in the literature. From these comparisons we derive a recommended set of gf- values and radiative transition rates with their corresponding estimated uncertainties. We also study the effects of different approximations in the representation of the target ion on the electron-impact collision strengths. Our most accurate set of collision strengths were integrated over a Maxwellian distribution of electron energies and the resulting effective collision strengths are given for a wide range of temperatures. Our results present significant differences from recent calculations with the B-spline non-orthogonal R-matrix method. We discuss the sources of the differences.Comment: 6 figures, 5 tables within text, 2 electronic table

    T1 Relaxation Rate (R1) Indicates Nonlinear Mn Accumulation in Brain Tissue of Welders With Low-Level Exposure

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    Although the essential element manganese (Mn) is neurotoxic at high doses, the effects of lower exposure are unclear. MRI T1-weighted (TIW) imaging has been used to estimate brain Mn exposure via the pallidal index (PI), defined as the T1W intensity ratio in the globus pallidus (GP) versus frontal white matter (FWM). PI may not, however, be sensitive to Mn in GP because Mn also may accumulate in FWM. This study explored: (1) whether T1 relaxation rate (R1) could quantify brain Mn accumulation more sensitively; and (2) the dose-response relationship between estimated Mn exposure and T1 relaxation rate (R1). Thirty-five active welders and 30 controls were studied. Occupational questionnaires were used to estimate hours welding in the past 90 days (HrsW) and lifetime measures of Mn exposure. T1W imaging and T1-measurement were utilized to generate PI and R1 values in brain regions of interest (ROIs). PI did not show a significant association with any measure of Mn and/or welding-related exposure. Conversely, in several ROIs, R1 showed a nonlinear relationship to HrsW, with R1 signal increasing only after a critical exposure was reached. The GP had the greatest rate of Mn accumulation. Welders with higher exposure showed significantly higher R1 compared either with controls or with welders with lower exposure. Our data are additional evidence that Mn accumulation can be assessed more sensitively by R1 than by PI. Moreover, the nonlinear relationship between welding exposure and Mn brain accumulation should be considered in future studies and policies

    The Grizzly, November 2, 1999

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    Is Safety an Issue on Campus? • Payne Stewart, Golfer, Dies in Plane Crash • A First for National French Week • Summer Business Internship Opportunities • Hobson Hall: Home Sweet Home • Opinion: The Effectiveness of College in the Preparation of Students for the World; Gun Control has to be Enacted for Everyone\u27s Safety: A Response; Paying Back the US Dues to the UN • Always Unique, Ben Folds Five Rocks Philadelphia as Part of 1999 Tour • Vecchio, Duncan Power Bears Offense as Bears Rout Mules • Soccer Splits Pair with Fords, Green Terror • Flag Football: APO Downs 2-Time Champion Delta Pi in Double-OT • Junior Vecchio Awarded CC Offensive Football Player of the Week • Tough End to Tough Hockey Season • Volleyball Finishes Best Season Ever • Bears Defense Roars to Big Winhttps://digitalcommons.ursinus.edu/grizzlynews/1450/thumbnail.jp

    Illumination in symbiotic binary stars: Non-LTE photoionization models. II. Wind case

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    We describe a non-LTE photoionization code to calculate the wind structure and emergent spectrum of a red giant wind illuminated by the hot component of a symbiotic binary system. We consider spherically symmetric winds with several different velocity and temperature laws and derive predicted line fluxes as a function of the red giant mass loss rate, \mdot. Our models generally match observations of the symbiotic stars EG And and AG Peg for \mdot about 10^{-8} \msunyr to 10^{-7} \msunyr. The optically thick cross- section of the red giant wind as viewed from the hot component is a crucial parameter in these models. Winds with cross-sections of 2--3 red giant radii reproduce the observed fluxes, because the wind density is then high, about 10^9 cm^{-3}. Our models favor winds with acceleration regions that either lie far from the red giant photosphere or extend for 2--3 red giant radii.Comment: 51 pages, LaTeX including three tables, requires 15 Encapsulated Postscript figures, to appear in Ap

    Hepatocyte KLF6 expression affects FXR signalling and the clinical course of primary sclerosing cholangitis

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    Background & Aims: Primary sclerosing cholangitis (PSC) is characterized by chronic cholestasis and inflammation, which promotes cirrhosis and an increased risk of cholangiocellular carcinoma (CCA). The transcription factor Krueppel-like-factor-6 (KLF6) is a mediator of liver regeneration, steatosis, and hepatocellular carcinoma (HCC), but no data are yet available on its potential role in cholestasis. Here, we aimed to identify the impact of hepatic KLF6 expression on cholestatic liver injury and PSC and identify potential effects on farnesoid-X-receptor (FXR) signalling. Methods: Hepatocellular KLF6 expression was quantified by immunohistochemistry (IHC) in liver biopsies of PSC patients and correlated with serum parameters and clinical outcome. Liver injury was analysed in hepatocyte-specific Klf6-knockout mice following bile duct ligation (BDL). Chromatin-immunoprecipitation-assays (ChIP) and KLF6-overexpressing HepG2 cells were used to analyse the interaction of KLF6 and FXR target genes such as NR0B2. Results: Based on IHC, PSC patients could be subdivided into two groups showing either low (80%) hepatocellular KLF6 expression. In patients with high KLF6 expression, we observed a superior survival in Kaplan-Meier analysis. Klf6-knockout mice showed reduced hepatic necrosis following BDL when compared to controls. KLF6 suppressed NR0B2 expression in HepG2 cells mediated through binding of KLF6 to the NR0B2 promoter region. Conclusion: Here, we show an association between KLF6 expression and the clinical course and overall survival in PSC patients. Mechanistically, we identified a direct interaction of KLF6 with the FXR target gene NR0B2
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