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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 91 records · Page 5
All sourcesNASA NTRSDOE OSTI
NASA NTRS1995

Advanced in Visualization of 3D Time-Dependent CFD Solutions

Numerical simulations of complex 3D time-dependent (unsteady) flows are becoming increasingly feasible because of the progress in computing systems. Unfortunately, many existing flow visualization systems were developed for time-independent (steady) solutions and do not adequately depict solutions from unsteady flow simulations. Furthermore, most systems only handle one time step of the solutions individually and do not consider the time-dependent nature of the solutions. For example, instantaneous streamlines are computed by tracking the particles using one time step of the solution. However, for streaklines and timelines, particles need to be tracked through all time steps. Streaklines can reveal quite different information about the flow than those revealed by instantaneous streamlines. Comparisons of instantaneous streamlines with dynamic streaklines are shown. For a complex 3D flow simulation, it is common to generate a grid system with several millions of grid points and to have tens of thousands of time steps. The disk requirement for storing the flow data can easily be tens of gigabytes. Visualizing solutions of this magnitude is a challenging problem with today's computer hardware technology. Even interactive visualization of one time step of the flow data can be a problem for some existing flow visualization systems because of the size of the grid. Current approaches for visualizing complex 3D time-dependent CFD solutions are described. The flow visualization system developed at NASA Ames Research Center to compute time-dependent particle traces from unsteady CFD solutions is described. The system computes particle traces (streaklines) by integrating through the time steps. This system has been used by several NASA scientists to visualize their CFD time-dependent solutions. The flow visualization capabilities of this system are described, and visualization results are shown.

Lane, David A.↗
NASA NTRS1990

Partial purification and characterization of a Ca(2+)-dependent protein kinase from the green alga, Dunaliella salina

A calcium-dependent protein kinase was partially purified and characterized from the green alga Dunaliella salina. The enzyme was activated at free Ca2+ concentrations above 10(-7) molar. and half-maximal activation was at about 3 x 10(-7) molar. The optimum pH for its Ca(2+)-dependent activity was 7.5. The addition of various phospholipids and diolein had no effects on enzyme activity and did not alter the sensitivity of the enzyme toward Ca2+. The enzyme was inhibited by calmodulin antagonists, N-(6-aminohexyl)-1-naphthalene sulfonamide and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide in a dose-dependent manner while the protein kinase C inhibitor, sphingosine, had little effect on enzyme activity up to 800 micromolar. Immunoassay showed some calmodulin was present in the kinase preparations. However, it is unlikely the kinase was calmodulin regulated, since it still showed stimulation by Ca2+ in gel assays after being electrophoretically separated from calmodulin by two different methods. This gel method of detection of the enzyme indicated that a protein band with an apparent molecular weight of 40,000 showed protein kinase activity at each one of the several steps in the purification procedure. Gel assay analysis also showed that after native gel isoelectric focusing the partially purified kinase preparations had two bands with calcium-dependent activity, at isoelectric points 6.7 and 7.1. By molecular weight, by isoelectric point, and by a comparative immunoassay, the Dunaliella kinase appears to differ from at least some of the calcium-dependent, but calmodulin and phospholipid independent kinases described from higher plants.

Non-NASA Center↗
NASA NTRS2004

The Conservation of Structure and Mechanism of Catalytic Action in a Family of Thiamin Pyrophosphate (TPP)-dependent Enzymes

Thiamin pyrophosphate (TPP)-dependent enzymes are a divergent family of TPP and metal ion binding proteins that perform a wide range of functions with the common decarboxylation steps of a -(O=)C-C(OH)- fragment of alpha-ketoacids and alpha- hydroxyaldehydes. To determine how structure and catalytic action are conserved in the context of large sequence differences existing within this family of enzymes, we have carried out an analysis of TPP-dependent enzymes of known structures. The common structure of TPP-dependent enzymes is formed at the interface of four alpha/beta domains from at least two subunits, which provide for two metal and TPP-binding sites. Residues around these catalytic sites are conserved for functional purpose, while those further away from TPP are conserved for structural reasons. Together they provide a network of contacts required for flip-flop catalytic action within TPP-dependent enzymes. Thus our analysis defines a TPP-action motif that is proposed for annotating TPP-dependent enzymes for advancing functional proteomics.

Dominiak, P.↗
NASA NTRS1997

Kinematic principles of primate rotational vestibulo-ocular reflex. II. Gravity-dependent modulation of primary eye position

The kinematic constraints of three-dimensional eye positions were investigated in rhesus monkeys during passive head and body rotations relative to gravity. We studied fast and slow phase components of the vestibulo-ocular reflex (VOR) elicited by constant-velocity yaw rotations and sinusoidal oscillations about an earth-horizontal axis. We found that the spatial orientation of both fast and slow phase eye positions could be described locally by a planar surface with torsional variation of <2.0 +/- 0.4 degrees (displacement planes) that systematically rotated and/or shifted relative to Listing's plane. In supine/prone positions, displacement planes pitched forward/backward; in left/right ear-down positions, displacement planes were parallel shifted along the positive/negative torsional axis. Dynamically changing primary eye positions were computed from displacement planes. Torsional and vertical components of primary eye position modulated as a sinusoidal function of head orientation in space. The torsional component was maximal in ear-down positions and approximately zero in supine/prone orientations. The opposite was observed for the vertical component. Modulation of the horizontal component of primary eye position exhibited a more complex dependence. In contrast to the torsional component, which was relatively independent of rotational speed, modulation of the vertical and horizontal components of primary position depended strongly on the speed of head rotation (i.e., on the frequency of oscillation of the gravity vector component): the faster the head rotated relative to gravity, the larger was the modulation. Corresponding results were obtained when a model based on a sinusoidal dependence of instantaneous displacement planes (and primary eye position) on head orientation relative to gravity was fitted to VOR fast phase positions. When VOR fast phase positions were expressed relative to primary eye position estimated from the model fits, they were confined approximately to a single plane with a small torsional standard deviation ( approximately 1.4-2.6 degrees). This reduced torsional variation was in contrast to the large torsional spread (well >10-15 degrees ) of fast phase positions when expressed relative to Listing's plane. We conclude that primary eye position depends dynamically on head orientation relative to space rather than being fixed to the head. It defines a gravity-dependent coordinate system relative to which the torsional variability of eye positions is minimized even when the head is moved passively and vestibulo-ocular reflexes are evoked. In this general sense, Listing's law is preserved with respect to an otolith-controlled reference system that is defined dynamically by gravity.

NASA Discipline Neuroscience↗
NASA NTRS2006

High Performance, Dependable Multiprocessor

With the ever increasing demand for higher bandwidth and processing capacity of today's space exploration, space science, and defense missions, the ability to efficiently apply commercial-off-the-shelf (COTS) processors for on-board computing is now a critical need. In response to this need, NASA's New Millennium Program office has commissioned the development of Dependable Multiprocessor (DM) technology for use in payload and robotic missions. The Dependable Multiprocessor technology is a COTS-based, power efficient, high performance, highly dependable, fault tolerant cluster computer. To date, Honeywell has successfully demonstrated a TRL4 prototype of the Dependable Multiprocessor [I], and is now working on the development of a TRLS prototype. For the present effort Honeywell has teamed up with the University of Florida's High-performance Computing and Simulation (HCS) Lab, and together the team has demonstrated major elements of the Dependable Multiprocessor TRLS system.

fault tolerant↗
NASA NTRS2011

The Distribution of Chromosomal Aberrations in Human Cells Predicted by a Generalized Time-Dependent Model of Radiation-Induced Formation of Aberrations

New experimental data show how chromosomal aberrations for low- and high-LET radiation are dependent on DSB repair deficiencies in wild-type, AT and NBS cells. We simulated the development of chromosomal aberrations in these cells lines in a stochastic track-structure-dependent model, in which different cells have different kinetics of DSB repair. We updated a previously formulated model of chromosomal aberrations, which was based on a stochastic Monte Carlo approach, to consider the time-dependence of DSB rejoining. The previous version of the model had an assumption that all DSBs would rejoin, and therefore we called it a time-independent model. The chromosomal-aberrations model takes into account the DNA and track structure for low- and high-LET radiations, and provides an explanation and prediction of the statistics of rare and more complex aberrations. We compared the program-simulated kinetics of DSB rejoining to the experimentally-derived bimodal exponential curves of the DSB kinetics. We scored the formation of translocations, dicentrics, acentric and centric rings, deletions, and inversions. The fraction of DSBs participating in aberrations was studied in relation to the rejoining time. Comparisons of simulated dose dependence for simple aberrations to the experimental dose-dependence for HF19, AT and NBS cells will be made.

Ponomarev, Artem L.↗
NASA NTRS2024

Time-dependent Photoionization Modeling of Warm Absorbers: High-resolution Spectra and Response to Flaring Light Curves

Time-dependent photoionization modeling of warm absorber (WA) outflows in active galactic nuclei can play an important role in understanding the interaction between WAs and the central black hole. The WA may be out of the equilibrium state because of the variable nature of the central continuum. In this paper, with the help of time dependent photoionization modeling, we study how the WA gas properties change with time and how it reacts to changing radiation fields. Incorporating a flaring incident light curve, we investigate the behavior of WAs using a photoionization code that simultaneously and consistently solves the time-dependent equations of level population, heating and cooling, and radiative transfer. We simulate the physical processes in the gas clouds, such as ionization, recombination, heating, cooling, and the transfer of ionizing radiation through the cloud and present high-resolution time-resolved absorption spectra. We demonstrate that time-dependent radiative transfer is important and the calculations that omit this effect quantitatively and systematically underestimate the absorption. Time-dependent photoionization models provide crucial insights into the characteristics of WAs and can be used to constrain their density and spatial distribution.

Astrophysicists↗
NASA NTRS2024

Time-Dependent Photoionization Modeling of Warm Absorbers: High-Resolution Spectra and Response to Flaring Light Curves

Time-dependent photoionization modeling of warm absorber (WA) outflows in active galactic nuclei can play an important role in understanding the interaction between WAs and the central black hole. The WA may be out of the equilibrium state because of the variable nature of the central continuum. In this paper, with the help of time dependent photoionization modeling, we study how the WA gas properties change with time and how it reacts to changing radiation fields. Incorporating a flaring incident light curve, we investigate the behavior of WAs using a photoionization code that simultaneously and consistently solves the time-dependent equations of level population, heating and cooling, and radiative transfer. We simulate the physical processes in the gas clouds, such as ionization, recombination, heating, cooling, and the transfer of ionizing radiation through the cloud and present high-resolution time-resolved absorption spectra. We demonstrate that time-dependent radiative transfer is important and the calculations that omit this effect quantitatively and systematically underestimate the absorption. Time-dependent photoionization models provide crucial insights into the characteristics of WAs and can be used to constrain their density and spatial distribution.

Dev R. Sadaula↗
NASA NTRSDate not supplied

Design Under Uncertainty with Design-Dependent Uncertain Variables

Uncertainty quantification (UQ) can provide a more robust understanding of a system, leading to better informed decisions earlier in the design process. The additional information that UQ provides can be leveraged during a design optimization process known as design under uncertainty that, when incorporated with multidisciplinary design and optimization, can become computationally infeasible due to the large number of responses required for meaningful results. Previous work addressed reducing the computational expense in design under uncertainty by incorporating analytic derivatives throughout polynomial chaos expansion. Although this allows design under uncertainty to be feasible for more systems, some multidisciplinary systems have design-dependent uncertain variables. This paper details an implementation of design dependent uncertain variables in a manner than preserves derivatives required for efficient gradient-based optimization throughout the process. Two analytic examples of design-dependent uncertain variables are given: the first transforms a uniform uncertain variable with one design variable and the second transforms a normal uncertain variable with two design variables. The polynomial chaos expansion (PCE) results are comparable to both the Monte Carlo (MC) results and the analytic results for the two examples. A case study that maximizes the lift-to-drag ratio with a design-dependence between the wing leading edge sweep angle and uncertain parameter percentage of laminar flow is compared to a MC and alternative optimization formulations. This paper demonstrates that design-dependent uncertain variables are valid and hold throughout PCE.

Joanna N Schmidt↗
NASA NTRSDate not supplied

Design Under Uncertainty with Design-Dependent Uncertain Variables

Uncertainty quantification (UQ) can provide a more robust understanding of a system, leading to better informed decisions earlier in the design process. The additional information that UQ provides can be leveraged during a design optimization process known as design under uncertainty that, when incorporated with multidisciplinary design and optimization, can become computationally infeasible due to the large number of responses required for meaningful results. Previous work addressed reducing the computational expense in design under uncertainty by incorporating analytic derivatives throughout polynomial chaos expansion. Although this allows design under uncertainty to be feasible for more systems, some multidisciplinary systems have design-dependent uncertain variables. This paper details an implementation of design dependent uncertain variables in a manner than preserves derivatives required for efficient gradient-based optimization throughout the process. Two analytic examples of design-dependent uncertain variables are given: the first transforms a uniform uncertain variable with one design variable and the second transforms a normal uncertain variable with two design variables. The polynomial chaos expansion (PCE) results are comparable to both the Monte Carlo (MC) results and the analytic results for the two examples. A case study that maximizes the lift-to-drag ratio with a design-dependence between the wing leading edge sweep angle and uncertain parameter percentage of laminar flow is compared to a MC and alternative optimization formulations. This paper demonstrates that design-dependent uncertain variables are valid and hold throughout PCE.

robust design↗
DOE OSTI2025

Sensitivities of time-dependent temperature profile predictions for NSTX with the multi-mode model

The Multi-Mode Model (MMM) for turbulent transport was applied to a large set of well-analyzed discharges from the National Spherical Torus Experiment (NSTX) in order to evaluate its sensitivities to a wide range of plasma conditions. MMM calculations were performed for hundreds of milliseconds in each discharge by performing time-dependent predictive simulations with the 1.5D tokamak integrated modeling code TRANSP. A closely related study (Lestz et al 2025 Plasma Phys. Control. Fusion 67 105029) concluded that MMM predicted electron and ion temperature profiles that were in reasonable agreement with NSTX observations, generally outperforming a different reduced transport model, TGLF. This finding motivates the more thorough investigation of the characteristics of the MMM predictions conducted in this work. The simulations with MMM have electron energy transport dominated by electron temperature gradient modes in the examined discharges with relatively low plasma β (ratio of kinetic plasma pressure to magnetic field pressure) and high collisionality, transitioning to a mixture of different modes for higher β and lower collisionality. The thermal ion diffusivity predicted by MMM is much smaller than the neoclassical contribution, in line with previous experimental analysis of NSTX. Nonetheless, the electron and ion temperature profiles are coupled via collisional energy exchange and thus sensitive to which transport channels are predicted. The time-dependent simulations with MMM are robust to the simulation start time, converging to remarkably similar temperature profiles later during the discharge. MMM typically overpredicts confinement relative to NSTX observations, leading to the prediction of overly steep temperature profiles. Plasmas with spatially broader temperature profiles, higher plasma β, and longer energy confinement times tend to be predicted by MMM with better agreement with the experiment. As a result, these findings provide useful context for understanding the regime-dependent tendencies of MMM in anticipation of self-consistent, time-dependent predictive simulations of NSTX-U discharges with these same modeling tools.

MMM↗
DOE OSTI2025

Transverse-momentum-dependent pion structures from lattice QCD: Collins-Soper kernel, soft factor, TMDWF, and TMDPDF

We present the first lattice quantum chromodynamics (QCD) calculation of the pion valence-quark transverse-momentum-dependent parton distribution function (TMDPDF) within the framework of large-momentum effective theory (LaMET). Using correlators fixed in the Coulomb gauge (CG), we computed the quasi-TMD beam function for a pion with a mass of 300 MeV, a fine lattice spacing of 𝑎 =0.06 fm, and multiple large momenta up to 3 GeV. The intrinsic soft functions in the CG approach are extracted from form factors with large momentum transfer, and as a byproduct, we also obtain the corresponding Collins-Soper (CS) kernel. Our determinations of both the soft function and the CS kernel agree with perturbation theory at small transverse separations (𝑏 ⊥ ) between the quarks. At larger 𝑏 ⊥ , the CS kernel remains consistent with recent results obtained using both CG and gauge-invariant TMD correlators in the literature. By combining next-to-leading logarithmic factorization of the quasi-TMD beam function and the soft function, we obtain an 𝑥-dependent pion valence-quark TMDPDF for transverse separations 𝑏 ⊥ ≳1 fm. Interestingly, we find that the 𝑏 ⊥ dependence of the phenomenological parametrizations of TMDPDF for moderate values of 𝑥 are in reasonable agreement with our QCD determinations. In addition, we present results for the transverse-momentum-dependent wave function for a heavier pion with 670 MeV mass.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2025

Dependable classical-quantum computing systems engineering

Increasing evidence suggests quantum computing (QC) complements traditional High-Performance Computing (HPC) by leveraging its unique capabilities, leading to the emergence of a new, hybrid paradigm, QHPC. However, this integration introduces new challenges, with dependability–defined by reproducibility, resiliency, and security and privacy–emerging as a central concern for building trustworthy systems that provide an advantage to the users. This paper proposes a framework for dependable QHPC system design, organized around these three pillars. We identify integration challenges, anticipate roadblocks, and highlight productive synergies across QC, HPC, cloud platforms, and network security. Drawing from both classical computing principles and quantum-specific insights, we present a roadmap for co-design that supports robust hybrid architectures. Our approach offers concrete metrics for assessing dependability, provides design guidance for engineers working at the QC-HPC interface, and surfaces new engineering questions around complexity, scale, and fault tolerance. Ultimately, designing for dependability is key to realizing practical, scalable QHPC systems and accelerating the broader quantum ecosystem capable of translating quantum promises into actual application delivery.

HPC↗
NASA NTRS2014

Time-Dependent Response Versus Scan Angle for MODIS Reflective Solar Bands

The Moderate Resolution Imaging Spectroradiometer (MODIS) instruments currently operate onboard the National Aeronautics and Space Administration (NASA's) Terra and Aqua spacecraft, launched on December 18, 1999 and May 4, 2002, respectively. MODIS has 36 spectral bands, among which 20 are reflective solar bands (RSBs) covering a spectral range from 0.412 to 2.13 μm. The RSBs are calibrated on orbit using a solar diffuser (SD) and an SD stability monitor and with additional measurements from lunar observations via a space view (SV) port. Selected pseudo-invariant desert sites are also used to track the RSB on-orbit gain change, particularly for short-wavelength bands. MODIS views the Earth surface, SV, and the onboard calibrators using a two-sided scan mirror. The response versus scan angle (RVS) of the scan mirror was characterized prior to launch, and its changes are tracked using observations made at different angles of incidence from onboard SD, lunar, and Earth view (EV) measurements. These observations show that the optical properties of the scan mirror have experienced large wavelength-dependent degradation in both the visible and near infrared spectral regions. Algorithms have been developed to track the on-orbit RVS change using the calibrators and the selected desert sites. These algorithms have been applied to both Terra and Aqua MODIS Level 1B (L1B) to improve the EV data accuracy since L1B Collection 4, refined in Collection 5, and further improved in the latest Collection 6 (C6). In C6, two approaches have been used to derive the time-dependent RVS for MODIS RSB. The first approach relies on data collected from sensor onboard calibrators and mirror side ratios from EV observations. The second approach uses onboard calibrators and EV response trending from selected desert sites. This approach is mainly used for the bands with much larger changes in their time-dependent RVS, such as the Terra MODIS bands 1-4, 8, and 9 and the Aqua MODIS bands 8- and 9. In this paper, the algorithms of these approaches are described, their performance is demonstrated, and their impact on L1B products is discussed. In general, the shorter wavelength bands have experienced a larger on-orbit RVS change, which, in general, are mirror side and detector dependent. The on-orbit RVS change due to the degradation of band 8 can be as large as 35 percent for Terra MODIS and 20 percent for Aqua MODIS. Vital to maintaining the accuracy of the MODIS L1B products is an accurate characterization of the on-orbit RVS change. The derived time-independent RVS, implemented in C6, makes an important improvement to the quality of the MODIS L1B products.

MODIS↗
NASA NTRS2014

Challenges in Modelling of Lightning-Induced Delamination; Effect of Temperature-Dependent Interfacial Properties

Lightning is a major cause of damage in laminated composite aerospace structures during flight. Due to the dielectric nature of Carbon fiber reinforced polymers (CFRPs), the high energy induced by lightning strike transforms into extreme, localized surface temperature accompanied with a high-pressure shockwave resulting in extensive damage. It is crucial to develop a numerical tool capable of predicting the damage induced from a lightning strike to supplement extremely expensive lightning experiments. Delamination is one of the most significant failure modes resulting from a lightning strike. It can be extended well beyond the visible damage zone, and requires sophisticated techniques and equipment to detect. A popular technique used to model delamination is the cohesive zone approach. Since the loading induced from a lightning strike event is assumed to consist of extreme localized heating, the cohesive zone formulation should additionally account for temperature effects. However, the sensitivity to this dependency remains unknown. Therefore, the major focus point of this work is to investigate the importance of this dependency via defining various temperature dependency profiles for the cohesive zone properties, and analyzing the corresponding delamination area. Thus, a detailed numerical model consisting of multidirectional composite plies with temperature-dependent cohesive elements in between is subjected to lightning (excessive amount of heat and pressure) and delamination/damage expansion is studied under specified conditions.

interlaminar damage↗
NASA NTRS2018

Initial Investigation of the Angular Dependence of the NOAA-20 VIIRS Solar Diffuser BRDF Change Factor

The NOAA-20 (formerly the Joint Polar Satellite System-1) satellite was launched on November 18, 2017. One of the five scientific instruments aboard the NOAA-20 satellite (N20) is the Visible Infrared Imaging Radiometer Suite (VIIRS). The VIIRS scans the earth surface in 22 spectral bands, of which 14 are denoted as the reflective solar bands (RSBs) with design band central wavelengths from 412 to 2250 nm. The VIIRS regularly performs on-orbit radiometric calibration of its RSBs, primarily through observations of an onboard sunlit solar diffuser (SD). The on-orbit change of the SD bidirectional reflectance distribution function (BRDF) value, denoted as the H-factor, is determined by an onboard solar diffuser stability monitor (SDSM). We have shown that the H-factor for the SD on the VIIRS instrument on the Suomi National Polar-orbiting Partnership (SNPP) satellite is both incident and outgoing sunlight direction dependent. This angular dependence profoundly affects the on-orbit radiometric calibration process and results. Here, we give preliminary results for the angular dependence for the N20 VIIRS SD H-factor, and compare the dependence with that for the SNPP VIIRS.

radiometric calibration↗
NASA NTRS2021

Positional Dependence of SNPP VIIRS Solar Diffuser BRDF Change Factor: An Empirical Approach

The Earth-observing Visible Infrared Imaging Radiometer Suite (VIIRS) on the Suomi National Polar-orbiting Partnership satellite regularly performs on-orbit radiometric calibration of its reflective solar bands (RSBs), primarily through observations of an onboard sunlit solar diffuser (SD). The on-orbit change of the SD bidirectional reflectance distribution function (BRDF) value, quantified by a numerical factor called the H-factor, is determined by the onboard SD stability monitor. Our previous study showed that the H-factor is solar angle and view direction dependent. In this study, we determine the dependence of the H-factor on the detector SD view footprint location. We fit an empirical model to the NASA Collection 1 SNPP VIIRS Level 1B (L1B) spectral reflectance difference across the detectors in an RSB over uniform Earth scenes of the Libya 4 desert and deep convective clouds. We apply the model predicted SD positional dependent H-factor to calibrate the RSBs. Under this new calibration scheme, the original unreal striping is removed from the homogeneous Libya 4 desert and the deep convective cloud images, as well as the original unreal striping from the Dunhuang desert image. The SD positional dependent H-factor has been used to calculate the SNPP VIIRS RSB radiometric correction factor for the NASA Collection 2.0 SNPP VIIRS L1B products.

SNPP VIIRS↗
DOE OSTI2024

Submicron immunoglobulin particles exhibit FcγRII-dependent toxicity linked to autophagy in TNFα-stimulated endothelial cells

In intravenous immunoglobulins (IVIG), and some other immunoglobulin products, protein particles have been implicated in adverse events. Role and mechanisms of immunoglobulin particles in vascular adverse effects of blood components and manufactured biologics have not been elucidated. We have developed a model of spherical silica microparticles (SiMPs) of distinct sizes 200–2000 nm coated with different IVIG- or albumin (HSA)-coronas and investigated their effects on cultured human umbilical vein endothelial cells (HUVEC). IVIG products (1–20 mg/mL), bare SiMPs or SiMPs with IVIG-corona, did not display significant toxicity to unstimulated HUVEC. In contrast, in TNFα-stimulated HUVEC, IVIG-SiMPs induced decrease of HUVEC viability compared to HSA-SiMPs, while no toxicity of soluble IVIG was observed. 200 nm IVIG-SiMPs after 24 h treatment further increased ICAM1 (intercellular adhesion molecule 1) and tissue factor surface expression, apoptosis, mammalian target of rapamacin (mTOR)-dependent activation of autophagy, and release of extracellular vesicles, positive for mitophagy markers. Toxic effects of IVIG-SiMPs were most prominent for 200 nm SiMPs and decreased with larger SiMP size. Using blocking antibodies, toxicity of IVIG-SiMPs was found dependent on FcγRII receptor expression on HUVEC, which increased after TNFα-stimulation. Similar results were observed with different IVIG products and research grade IgG preparations. In conclusion, submicron particles with immunoglobulin corona induced size-dependent toxicity in TNFα-stimulated HUVEC via FcγRII receptors, associated with apoptosis and mTOR-dependent activation of autophagy. Testing of IVIG toxicity in endothelial cells prestimulated with proinflammatory cytokines is relevant to clinical conditions. Our results warrant further studies on endothelial toxicity of sub-visible immunoglobulin particles.

59 BASIC BIOLOGICAL SCIENCES↗