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At least 703 records · Page 39
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Pathogenic and Apathogenic Strains of Lymphocytic Choriomeningitis Virus Have Distinct Entry and Innate Immune Activation Pathways

Lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV) share many genetic and biological features including subtle differences between pathogenic and apathogenic strains. Despite remarkable genetic similarity, the viscerotropic WE strain of LCMV causes a fatal LASV fever-like hepatitis in non-human primates (NHPs) while the mouse-adapted Armstrong (ARM) strain of LCMV is deeply attenuated in NHPs and can vaccinate against LCMV-WE challenge. Here, we demonstrate that internalization of WE is more sensitive to the depletion of membrane cholesterol than ARM infection while ARM infection is more reliant on endosomal acidification. LCMV-ARM induces robust NF-κB and interferon response factor (IRF) activation while LCMV-WE seems to avoid early innate sensing and failed to induce strong NF-κB and IRF responses in dual-reporter monocyte and epithelial cells. Toll-like receptor 2 (TLR-2) signaling appears to play a critical role in NF-κB activation and the silencing of TLR-2 shuts down IL-6 production in ARM but not in WE-infected cells. Pathogenic LCMV-WE infection is poorly recognized in early endosomes and failed to induce TLR-2/Mal-dependent pro-inflammatory cytokines. Following infection, Interleukin-1 receptor-associated kinase 1 (IRAK-1) expression is diminished in LCMV-ARM- but not LCMV-WE-infected cells, which indicates it is likely involved in the LCMV-ARM NF-κB activation. By confocal microscopy, ARM and WE strains have similar intracellular trafficking although LCMV-ARM infection appears to coincide with greater co-localization of early endosome marker EEA1 with TLR-2. Both strains co-localize with Rab-7, a late endosome marker, but the interaction with LCMV-WE seems to be more prolonged. These findings suggest that LCMV-ARM’s intracellular trafficking pathway may facilitate interaction with innate immune sensors, which promotes the induction of effective innate and adaptive immune responses.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Impact of Selenium and Vitamin E Deficiency on Zika Virus Pathogenesis and Immune Response in Mice

Micronutrient status is recognized to influence host susceptibility to viral infections, yet its impact on Zika virus (ZIKV) pathogenesis remains incompletely understood. We investigated the effects of dietary selenium and combined selenium plus vitamin E deficiency on ZIKV infection outcomes in a type I interferon α/β receptor knockout (Ifnar1 −/− ) murine model. Mice maintained on deficient diets exhibited significantly lower neutralizing antibody titers and reduced levels of key antiviral cytokines (IFN-γ, TNF-α, IFN-α, IFN-β, IL-12p70, CCL5) compared to controls. Correspondingly, higher viral RNA loads were detected in the brains of double-deficient mice, which also experienced greater weight loss and increased mortality. Deep sequencing revealed no major differences in overall viral genome diversity across diet groups; however, specific mutations, including V330L and D67E in the E gene, and V360I in the NS3 gene, were enriched or detected in nutritionally deficient animals. These findings suggest that antioxidant micronutrient deficiency impairs both humoral and cellular immune responses to ZIKV, potentially facilitating enhanced neuroinvasion. While the functional consequences of the identified mutations warrant further investigation, our results underscore the importance of adequate micronutrient intake for optimal antiviral defense. Further studies are needed to clarify the epidemiological significance of these observations.

Biological and medical sciences↗
DOE OSTI2021

First Muon Neutrino on Argon Cross Section Measurements With an Off-Axis Beam

While over ninety years have passed since neutrinos were first predicted in 1930 by Wolfgang Pauli, much about them is still unknown [20]. How many types of neutrinos there are, how precisely neutrinos change flavor, and how neutrinos interact with various types of matter are largely unanswered questions that have implications for fields beyond particle physics, such as cosmology and astrophysics. The final question can be answered partially by differential cross section measurements, two of which constitute the primary result of this thesis. The NeUtrinos at the Main Injector (NuMI) Beam at Fermilab in Batavia, IL provides a source of muon neutrinos and muon antineutrinos to the MicroBooNE experiment, an 85 ton liquid argon time projection chamber (LArTPC). The technology allows for high precision particle tracking and energy reconstruction that can be used to make cross section measurements. Necessary work for making these measurements for which the author of this thesis made an essential contribution is presented in detail in References [21] [22] [11] [23]. The measurement presented in this thesis is made with 2.187e20 Protons on Target (POT), the standard metric for an amount of beam exposure, of data when the beam was in forward horn current mode. Single-differential cross section measurements in terms of muon candidate kinetic energy and direction are made, and their statistical fits with simulation are 5.8 (12 d.o.f.) and 11.4 (10 d.o.f.), respectively. This indicates that the muon kinematics for muon neutrino and muon antineutrino charged-current (CC) events primarily in the energy range [0-3] GeV can be trusted for oscillation experiments, including DUNE, because of the agreement to within the associated systematic and statistical uncertainties between the measurement and the model in every bin of both single-differential cross sections. This result adds to the corresponding result for the Booster Neutrino Beam (BNB) because it covers a completely different energy region than that measurement, a double-differential cross section in terms of muon momentum and direction [14]. This result contributes to reducing the uncertainty in near-far event rate comparisons in long baseline neutrino experiments and also adds to existing knowledge of the neutrino-nucleus interaction by describing the outgoing muon kinematics in interactions of muon neutrinos and muon antineutrinos. This result is the first-ever measurement of differential cross sections of muon neutrinos and muon antineutrinos in liquid argon made with an off-axis beam.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2021

Quantile-dependent expressivity of serum C-reactive protein concentrations in family sets

“Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., C-reactive protein, CRP) is high or low relative to its distribution. We have previously shown that the heritabilities ( h 2 ) of coffee and alcohol consumption, postprandial lipemia, lipoproteins, leptin, adiponectin, adiposity, and pulmonary function are quantile-specific. Whether CRP heritability is quantile-specific is currently unknown. Methods Serum CRP concentrations from 2,036 sibships and 6,144 offspring-parent pairs were analyzed from the Framingham Heart Study. Quantile-specific heritability from full-sib (β FS , h 2 ={(1 + 8r spouse β FS ) 0.5 - 1}/(2r spouse )) and offspring-parent regression slopes (β OP , h 2 = 2β OP /(1 + r spouse )) were estimated robustly by quantile regression with nonparametric significance determined from 1,000 bootstrap samples. Results Quantile-specific h 2 (±SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted CRP distribution when estimated from β OP ( P trend = 0.0004): 0.02 ± 0.01 at the 10th, 0.04 ± 0.01 at the 25th, 0.10 ± 0.02 at the 50th, 0.20 ± 0.05 at the 75th, and 0.33 ± 0.10 at the 90th percentile, and when estimated from β FS ( P trend = 0.0008): 0.03±0.01 at the 10th, 0.06 ± 0.02 at the 25th, 0.14 ± 0.03 at the 50th, 0.24 ± 0.05 at the 75th, and 0.53 ± 0.21 at the 90th percentile. Conclusion Heritability of serum CRP concentration is quantile-specific, which may explain or contribute to the inflated CRP differences between CRP (rs1130864, rs1205, rs1800947, rs2794521, rs3091244), FGB (rs1800787), IL-6 (rs1800795, rs1800796), IL6R (rs8192284), TNF- α (rs1800629) and APOE genotypes following CABG surgery, stroke, TIA, curative esophagectomy, intensive periodontal therapy, or acute exercise; during acute coronary syndrome or Staphylococcus aureus bacteremia; or in patients with chronic rheumatoid arthritis, diabetes, peripheral arterial disease, ankylosing spondylitis, obesity or inflammatory bowel disease or who smoke.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1966

Theory and Practical Design of Phase-locked Receivers, Volume I

This is Volume I of a two-volume work on the theory, of phase-locked receivers, with pertinent reference material on practical receiver design. Volume I is primarily devoted to the performance of carrier-tracking loops, including a rigorous treatment of narrow-band systems having IF limiters. The bulk of the work is based on a theoretical linear model, but a nonlinear method is also presented to predict behavior near the threshold. The emphasis throughout the work is toward completeness, simplicity, and internal consistency of the material assembled. Part I of this Volume is an exposition of the theory, the resulting equations, and the design philosophy that have enabled the phase-lock concept to evolve into the basic principle underlying the most sensitive receivers il, the world today. Part II is a condensed version of Part I, intended as a quick reference to formulas, definitions, and salient design considerations.

RECEIVER↗
NASA NTRS1967

Problems of astrometry

Construction of reliable inertial coordinate system - star catalogs from Ukrainian observatories, ILS materials analysis and increasing accuracy of astrometric observations

STELLAR MOTION↗
NASA NTRS1969

Literal readout of identification signals in Morse code

Instrument, designed for mounting in aircraft instrument panels, decodes identification signals received in Morse from VOR or ILS transmitters as they are received and displays the literal equivalent. Without elaboration it cannot decode numbers.

Meissner, C. W., Jr.↗
NASA NTRS1972

Pilot dynamics for instrument approach tasks: Full panel multiloop and flight director operations

Measurements and interpretations of single and mutiloop pilot response properties during simulated instrument approach are presented. Pilot subjects flew Category 2-like ILS approaches in a fixed base DC-8 simulaton. A conventional instrument panel and controls were used, with simulated vertical gust and glide slope beam bend forcing functions. Reduced and interpreted pilot describing functions and remmant are given for pitch attitude, flight director, and multiloop (longitudinal) control tasks. The response data are correlated with simultaneously recorded eye scanning statistics, previously reported in NASA CR-1535. The resulting combined response and scanning data and their interpretations provide a basis for validating and extending the theory of manual control displays.

Weir, D. H.↗
NASA NTRS1972

Flight evaluations of the effect of advanced control systems and displays on the handling qualities of a general aviation airplane.

Flight tests have shown that, by means of improved displays and advanced control systems, it is possible to transform a typical light airplane into a flying machine that borders on being perfect from a handling-qualities standpoint. A flight-director display and an attitude-command control system used in combination transformed a vehicle with poor handling qualities during ILS approaches in turbulent air into a vehicle with extremely good handling qualities. The attitude-command control system also improved the ride qualities of the airplane. A rate-command control system was less beneficial than an attitude-command control system. Although this paper deals primarily with general aviation aircraft, the results presented pertain to other types of aircraft. Short-takeoff-and-landing (STOL) aircraft would be a natural application of the control systems because, as a result of their low speeds, they encounter many of the handling-qualities problems noted on light aircraft. The improved ride qualities should be of interest to all airline operations, and for STOL aircraft in particular, because of their prolonged exposure to low-altitude turbulence.

Loschke, P. C.↗
NASA NTRS1973

Flight test results from the CV990 simulated space shuttle during unpowered automatic approaches and landings

Unpowered automatic approaches and landings with a CV990 aircraft were conducted to study navigation, guidance, and control problems associated with terminal area approach and landing for the space shuttle. The flight tests were designed to study from 11,300 m to touchdown the performance of a navigation and guidance concept which utilized blended radio/inertial navigation using VOR, DME, and ILS as the ground navigation aids. In excess of fifty automatic approaches and landings were conducted. Preliminary results indicate that this concept may provide sufficient accuracy to accomplish automatic landing of the shuttle orbiter without air-breathing engines on a conventional size runway.

Edwards, F. G.↗
NASA NTRS1974

Noise measurements at Stockton airport obtained during engineering evaluation of two-segment approaches in a DC-8-61 aircraft

A series of noise measurements were made during engineering evaluation tests of the two segment approach using a DC-8-61. The two approaches evaluated were: (1) ILS, 2.9 deg glide slope using 50 deg flaps; and (2) two segment 5.5 deg/2.9 deg glide slope, using 50 deg flaps and lower segment intercept altitude of 575 feet. Measurements were made at twelve sites underneath and to the side of the flight path.

Glass, R. E.↗
NASA NTRS1974

Flight investigation of the VFR and IFR landing approach characteristics and terminal area airspace requirements for a light STOL airplane

A flight research program was conducted to determine the terminal area instrument flight capabilities of a light STOL airplane. Simulated (hooded) instrument landing approaches were made using steep single-segment and two-segment glide slopes. A brief investigation was also made of the visual flight terminal area capabilities of the aircraft. The results indicated that the airplane could be flown on a 7 deg glide-slope ILS-type approach in still air with an adequate 3 deg margin for downward correction.

Crane, H. L.↗