Search NASA⌕ Search

SEARCH · Search NASA

Results for “ACTIVATE”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19
All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

The Project “Analogs for VENus’s GEologically Recent Surfaces” (AVENGERS): Unveiling Active Volcanism on Venus

The recently selected missions to Venus opened a new era for the exploration of the Earth’s hellish twin sister. One of the key questions that the selected missions to Venus will address is whether the planet is volcanically active. The identification of ongoing volcanic activity on Venus can indeed unveil important clues on the geologic evolution of the planet, also helping us to better understand how volcanic and atmospheric processes work on Earth, especially those related to the climate change produced by greenhouse gases. To fully contextualize the higher resolution datasets to be provided by the future missions to Venus, we need to be able to exploit the wealth of data to be produced in the best possible way. Different types of instruments will indeed perform unprecedent orbiting and in-situ investigations of the surface and subsurface of Venus. To this regard, the Project “Analogs for VENus’s GEologically Recent Surfaces” (AVENGERS) aims to build a comprehensive database of Terrestrial active volcanoes which may act as suitable analogs for identifying ongoing volcanic activity on Venus. To do this, the project AVENGERS will combine the implementation of terrestrial orbiter radar data analysis techniques (i.e., radar interferometry) with infrared and laboratory analyses of lava flow samples from Terrestrial active volcanoes. As a first suitable analog of the Project AVENGERS, we selected Mount Etna in Sicily for a direct comparison with potentially active volcanic structures of Venus, and with Idunn Mons, one of the most promising possibly active volcanoes of Venus. Given its composite nature, Mount Etna offers the opportunity to identify and study multiple types of eruptive products (both effusive and explosive) from the analysis of high-resolution radar images. The frequent eruptions characterizing this volcano will also allow to test techniques of radar interferometry. Moreover, its ease of access facilitates geologic field trips and in-situ investigations with related sample retrieving. Ongoing infrared laboratory analysis on several altered and unaltered samples retrieved by Mount Etna will help to distinguish spectral signatures of fresh vs weathered volcanic deposits.

P. D’Incecco↗
NASA NTRS2017

Analysis of in Vitro Evolution Reveals the Underlying Distribution of Catalytic Activity Among Random Sequences

The emergence of catalytic RNA is believed to have been a key event during the origin of life. Understanding how catalytic activity is distributed across random sequences is fundamental to estimating the probability that catalytic sequences would emerge. Here, we analyze the in vitro evolution of triphosphorylating ribozymes and translate their fitnesses into absolute estimates of catalytic activity for hundreds of ribozyme families. The analysis efficiently identified highly active ribozymes and estimated catalytic activity with good accuracy. The evolutionary dynamics follow Fisher’s Fundamental Theorem of Natural Selection and a corollary, permitting retrospective inference of the distribution of fitness and activity in the random sequence pool for the first time. The frequency distribution of rate constants appears to be log-normal, with a surprisingly steep dropoff at higher activity, consistent with a mechanism for the emergence of activity as the product of many independent contributions.

Abe Pressman↗
DOE OSTI2026

Affinity and Treatment of LDR Organics in Low Activity Waste by Cementitious Materials – 26109

The physiochemical interactions between organic contaminants, minerals, and polymer additives in grout/cementitious materials are being identified. This research supports a proposed Resource Conservation and Recovery Act (RCRA) treatment variance relevant to the Land Disposal Restriction (LDR) organics present in Hanford tank waste. It provides the technical basis to address the aspects documented by the Environmental Protection Agency in a draft memo necessary to establish that organics can be immobilized/stabilized in a cementitious matrix. The organic species may interact with cementitious minerals, including slag, fly ash, cement, and other components/dopants like activated carbon. A list of 132 reasonably expected LDR organics associated with Hanford tank waste (RPP-RPT-63493, Rev 1a) was screened by functional groups, octanol-water partitioning coefficients, and detection frequency in Hanford tank waste samples. A subset of 15 compounds spanning the identified properties was tested using sorption and leachate tests. These compounds were subjected to traditional batch sorption tests and leaching tests on/from Cast Stone cementitious material with and without activated carbon (a potential organic adsorption additive). The interactions between organic compounds were observed in traditional batch sorption and modified TCLP leachate tests for surrogate Cast Stone material with and without activated carbon addition. Specifically, phthalic acid (negatively charged) and 4-chloroaniline (polar) sorbed strongly to unmodified Cast Stone, while a group of three phenolic compounds (2,4,6-Trichlorophenol, Pentachlorophenol, o-Cresol) sorbed to and were retained by Cast Stone with a 1% activated carbon amendment. Mixtures of these compounds demonstrated visible retention of the organics within the matrix with a quantifiable affinity of the organics to the cement. This novel testing supports the notion that organics within Hanford tank waste would be retained onto the cement phase with the addition of simple materials easily added to the formulation as part of the treatment process. To further provide additional support to this claim, models employing Flory-Huggins theory in conjunction with macromolecular and organic molecule solubility parameters and species activity coefficients are being utilized to better understand these interactions. Within this context, Van Krevelen (VK) and Hansen organic and polymer solubility parameters were used to inform the Flory-Huggins interaction parameter, allowing for a quantifiable method of evaluating polymer-solvent compatibility and, by extension, interactions with proposed binding additives (e.g., activated carbon). These models and measurement should test the hypothesis for our systems understanding and applicability of Flory-Huggins theory, and whether the prediction of organics in the polymer phase versus the aqueous phase can be confidently made using this strategy. The estimation of the organic molecular activity coefficient in these high salt-saturated aqueous systems is another factor that will be assessed. This project aims to predict and understand complicated organic interactions in these heterogenous systems, guiding optimal treatment and stabilization methodologies.

Jolin, Will [Savannah River National Laboratory (S↗
NASA NTRS2000

Integrin activation and focal complex formation in cardiac hypertrophy

Cardiac hypertrophy is characterized by both remodeling of the extracellular matrix (ECM) and hypertrophic growth of the cardiocytes. Here we show increased expression and cytoskeletal association of the ECM proteins fibronectin and vitronectin in pressure-overloaded feline myocardium. These changes are accompanied by cytoskeletal binding and phosphorylation of focal adhesion kinase (FAK) at Tyr-397 and Tyr-925, c-Src at Tyr-416, recruitment of the adapter proteins p130(Cas), Shc, and Nck, and activation of the extracellular-regulated kinases ERK1/2. A synthetic peptide containing the Arg-Gly-Asp (RGD) motif of fibronectin and vitronectin was used to stimulate adult feline cardiomyocytes cultured on laminin or within a type-I collagen matrix. Whereas cardiocytes under both conditions showed RGD-stimulated ERK1/2 activation, only collagen-embedded cells exhibited cytoskeletal assembly of FAK, c-Src, Nck, and Shc. In RGD-stimulated collagen-embedded cells, FAK was phosphorylated only at Tyr-397 and c-Src association occurred without Tyr-416 phosphorylation and p130(Cas) association. Therefore, c-Src activation is not required for its cytoskeletal binding but may be important for additional phosphorylation of FAK. Overall, our study suggests that multiple signaling pathways originate in pressure-overloaded heart following integrin engagement with ECM proteins, including focal complex formation and ERK1/2 activation, and many of these pathways can be activated in cardiomyocytes via RGD-stimulated integrin activation.

NASA Discipline Cardiopulmonary↗
NASA NTRS1998

Calcium-independent activation of extracellular signal-regulated kinases 1 and 2 by cyclic strain

We have previously demonstrated that cyclic strain induces extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation in endothelial cells (EC). The aim of this study was to investigate the effect of Ca2+ on the activation of ERK1/2. Bovine aortic EC were pretreated with a chelator of extracellular Ca2+, ethylaneglycol-bis(aminoethylether)-tetra-acetate (EGTA), a depleter of Ca2+ pools, 2,5-Di-(tert-butyl)-1,4-benzohydroquinone (BHQ), or a Ca2+ channel blocker, GdCl3, and subjected to an average 10 % strain at a rate of 60 cycles/min for 10 min. BHQ and GdCl3 did not inhibit the strain-induced ERK1/2 activation. Chelation of normal extracellular Ca2+ (1.8 mM) medium with EGTA (3 mM) acutely stimulated baseline phosphorylation and activation of ERK1/2, thereby obscuring any strain-induced activation of ERK1/2. However, in EC preincubated for 24 hours in Ca2+-free medium, elevated baseline phosphorylation was minimally activated by EGTA (200 microM) such that cyclic strain stimulated ERK1/2 in the presence or absence of BHQ. These results suggest a Ca2+ independence of the ERK1/2 signaling pathway by cyclic strain. Copyright 1998 Academic Press.

NASA Discipline Cell Biology↗
DOE OSTI2024

Non-Reciprocity, Metastability, and Dynamic Reconfiguration in Co-Assembly of Active and Passive Particles

Living organisms often exhibit non-reciprocal interactions where the forces acting on the objects are not equal in magnitude or opposite in direction. The combination of reciprocal and non-reciprocal interactions between synthetic building blocks remains largely unexplored. Here, out-of-equilibrium assemblies of non-motile isotropic passive and metal-patched motile active particles are formed by overlapping bulk interactions with directed self-propulsion. An external alternating current (AC) electric field generates concurrent dipolar and induced-charge electrophoretic forces between the particles which are evaluated using microscopy. The interaction force measurements allow to determine the degree of reciprocity in interactions, which is tunable by designing the active particle and its trajectory. While linearly-propelled active particles evade assembly with passive particles, helically propelled active particles form active-passive clusters with dynamic reconfiguration and long-lived metastability. Large clusters display programmable fluctuations and reconfigurability by controlling the fraction of active particles. The study establishes principles of integrating reciprocal and non-reciprocal interactions in guided colloidal assembly of reconfigurable metastable structures.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Free-Energy Landscapes and Surface Dynamics in Methane Activation on Ni(511) via Machine Learning and Enhanced Sampling

Methane activation on stepped Ni(511) surfaces involves the rearrangement of surface atoms as the chemical reaction proceeds. This process is particularly sensitive to temperature. Using machine-learned interatomic potentials (MLIPs) coupled with enhanced sampling techniques, we investigate the activation of methane under realistic operando conditions. Our analysis reveals that methane dissociation occurs predominantly at step-edge nickel atoms. As CH x (where x = 3 or 4) species bind to additional surface nickel atoms, their reduced mobility leads to entropic penalties that suppress certain configurations and transition states. This is reflected in the underlying free energy surfaces, where configurations such as methyl binding to hollow sites and activation routes involving two nickel atoms become unfavorable as temperature increases. At elevated temperatures, methane activation extends from step-edge sites to terrace regions because of reduced free-energy barriers and enhanced surface dynamics. By decomposing the free-energy into enthalpic and entropic contributions, we uncover temperature-dependent shifts in the preferences of methane for the relevant active sites and arrive at a detailed molecular picture of methane activation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2026

Composition, Activity, and Stability of IrO x Oxygen Evolution Reaction Electrocatalysts

The oxygen evolution reaction (OER) is integral to several electrochemical energy conversion and storage technologies, including carbon dioxide reduction to value added fuels, nitrogen reduction to ammonia, reversible fuel cells, rechargeable metal−air batteries, and water electrolysis to produce hydrogen. Iridium oxide (IrO x ) is widely recognized as the benchmark OER catalyst for acidic environments. Despite widespread use of IrO x catalysts, most notably in proton-exchange membrane water electrolyzers (PEMWEs), a comprehensive understanding of the physicochemical properties of commercial catalysts and the impact of these properties on both the activity and stability of these catalysts is lacking. Here, we study commercial IrO x catalysts with different physicochemical properties, three nominally considered amorphous and three rutile, to elucidate how structural and compositional variations affect OER activity and stability. Utilizing standardized aqueous electrochemical protocols, time-resolved dissolution quantification using inductively-coupled plasma mass spectrometry, and physicochemical characterization, including multiple synchrotron X-ray techniques, we systematically correlate catalyst properties with OER performance and degradation behavior aided by principal component analysis (PCA). Our results demonstrate the general trend of amorphous IrO x having higher intrinsic activity but limited stability and crystalline rutile IrO 2 having lower activity but enhanced stability against dissolution. The trends within the amorphous and rutile catalyst groups correlate with inherent material properties, including phase composition and structure, crystallinity, particle size, surface area, and surface structure/chemistry. Notably, we identify a rutile catalyst with the largest crystallite/ domain sizes, moderate surface area, a small fraction of hydrous phase, and a favorable pore structure (trimodal distributions of pore sizes ranging from 2−5 nm) that exhibits the best balance between activity and stability among the six catalysts studied here. These findings illustrate a fundamental structure-governed trade-off between activity and stability and highlight the critical role of surface chemistry modification and structure engineering in IrO x catalyst optimization.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Dynamics and activation of membrane-bound B cell receptor assembly

B-cell receptor (BCR) complexes are expressed on the surface of a B-cell and are critical in antigen recognition and modulating the adaptive immune response. Even though the relevance of antibodies has been known for almost a hundred years, the antigen-dependent activation mechanism of B-cells has remained elusive. Several models have been proposed for BCR activation, including cross-linking, conformation-induced oligomerization, and dissociation activation models. Recently, the first cryo-EM structures of the human B-cell antigen receptor of the IgM and IgG isotypes have been published that validates the asymmetric organization of the BCR complex. Here, we carry out extensive molecular dynamics simulations to probe the conformational changes upon antigen binding and the influence of the membrane lipids. We identify two critical dynamical events that could be associated with antigen-dependent activation of BCR. First, antigen binding causes increased flexibility in regions distal to the antigen binding site. Second, antigen binding alters the rearrangement of IgM transmembrane helices, including the relative interaction of Igα/Igβ that mediates intracellular signaling. Furthermore, these transmembrane rearrangements lead to changes in localized lipid composition. Our work indirectly supports the conformational-change induced models of BCR activation and contributes to the understanding of the antigen-dependent activation mechanism of BCRs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Microscopic origin of tunable assembly forces in chiral active environments

Across a variety of spatial scales, from nanoscale biological systems to micron-scale colloidal systems, equilibrium self-assembly is entirely dictated by—and therefore limited by—the thermodynamic properties of the constituent materials. In contrast, nonequilibrium materials, such as self-propelled active matter, expand the possibilities for driving the assemblies that are inaccessible in equilibrium conditions. Recently, a number of works have suggested that active matter drives or accelerates self-organization, but the emergent interactions that arise between solutes immersed in actively driven environments are complex and poorly understood. Here, we analyze and resolve two crucial questions concerning actively driven self-assembly: (i) how, mechanistically, do active environments drive self-assembly of passive solutes? (ii) Under which conditions is this assembly robust? We employ the framework of odd hydrodynamics to theoretically explain numerical and experimental observations that chiral active matter, i.e., particles driven with a directional torque, produces robust and long-ranged assembly forces. Overall, these developments constitute an important step towards a comprehensive theoretical framework for controlling self-assembly in nonequilibrium environments.

36 MATERIALS SCIENCE↗
DOE OSTI2024

Asymmetric fluctuations and self-folding of active interfaces

We study the structure and dynamics of the interface separating a passive fluid from a microtubule-based active fluid. Turbulent-like active flows power giant interfacial fluctuations, which exhibit pronounced asymmetry between regions of positive and negative curvature. Experiments, numerical simulations, and theoretical arguments reveal how the interface breaks up the spatial symmetry of the fundamental bend instability to generate local vortical flows that lead to asymmetric interface fluctuations. The magnitude of interface deformations increases with activity: In the high activity limit, the interface self-folds invaginating passive droplets and generating a foam-like phase, where active fluid is perforated with passive droplets. These results demonstrate how active stresses control the structure, dynamics, and break-up of soft, deformable, and reconfigurable liquid–liquid interfaces.

active fluid↗
NASA NTRS1987

Correlation between calmodulin activity and gravitropic sensitivity in primary roots of maize

Recent evidence indicates a role for calcium and calmodulin in the gravitropic response of primary roots of maize (Zea mays, L.). We examined this possibility by testing the relationship between calmodulin activity and gravitropic sensitivity in roots of the maize cultivars Merit and B73 x Missouri 17. Roots of the Merit cultivar require light to the gravitropically competent. The gravitropic response of the Missouri cultivar is independent of light. The occurrence of calmodulin in primary roots of these maize cultivars was tested by affinity gel chromatography followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with bovine brain calmodulin as standard. The distribution of calmodulin activity was measured using both the phosphodiesterase and NAD kinase assays for calmodulin. These assays were performed on whole tissue segments, crude extracts, and purified extracts. In light-grown seedlings of the Merit cultivar or in either dark- or light-grown seedlings of the Missouri cultivar, calmodulin activity per millimeter of root tissue was about 4-fold higher in the apical millimeter than in the subtending 3 millimeters. Calmodulin activity was very low in the apical millimeter of roots of dark-grown (gravitropically nonresponsive) seedlings of the Merit cultivar. Upon illumination, the calmodulin activity in the apical millimeter increased to a level comparable to that of light-grown seedlings and the roots became gravitropically competent. The time course of the development of gravitropic sensitivity following illumination paralleled the time course of the increase in calmodulin activity in the apical millimeter of the root. The results are consistent with the suggestion that calmodulin plays an important role in the gravitropic response of roots.

NASA Program Space Biology↗
NASA NTRS2001

NADH oxidase activity (NOX) and enlargement of HeLa cells oscillate with two different temperature-compensated period lengths of 22 and 24 minutes corresponding to different NOX forms

NOX proteins are cell surface-associated and growth-related hydroquinone (NADH) oxidases with protein disulfide-thiol interchange activity. A defining characteristic of NOX proteins is that the two enzymatic activities alternate to generate a regular period length of about 24 min. HeLa cells exhibit at least two forms of NOX. One is tumor-associated (tNOX) and is inhibited by putative quinone site inhibitors (e.g., capsaicin or the antitumor sulfonylurea, LY181984). Another is constitutive (CNOX) and refractory to inhibition. The periodic alternation of activities and drug sensitivity of the NADH oxidase activity observed with intact HeLa cells was retained in isolated plasma membranes and with the solubilized and partially purified enzyme. At least two activities were present. One had a period length of 24 min and the other had a period length of 22 min. The lengths of both the 22 and the 24 min periods were temperature compensated (approximately the same when measured at 17, 27 or 37 degrees C) whereas the rate of NADH oxidation approximately doubled with each 10 degrees C rise in temperature. The rate of increase in cell area of HeLa cells when measured by video-enhanced light microscopy also exhibited a complex period of oscillations reflective of both 22 and 24 min period lengths. The findings demonstrate the presence of a novel oscillating NOX activity at the surface of cancer cells with a period length of 22 min in addition to the constitutive NOX of non-cancer cells and tissues with a period length of 24 min.

Non-NASA Center↗
NASA NTRS2000

TAK1 is activated in the myocardium after pressure overload and is sufficient to provoke heart failure in transgenic mice

The transforming-growth-factor-beta-activated kinase TAK1 is a member of the mitogen-activated protein kinase kinase kinase family, which couples extracellular stimuli to gene transcription. The in vivo function of TAK1 is not understood. Here, we investigated the potential involvement of TAK1 in cardiac hypertrophy. In adult mouse myocardium, TAK1 kinase activity was upregulated 7 days after aortic banding, a mechanical load that induces hypertrophy and expression of transforming growth factor beta. An activating mutation of TAK1 expressed in myocardium of transgenic mice was sufficient to produce p38 mitogen-activated protein kinase phosphorylation in vivo, cardiac hypertrophy, interstitial fibrosis, severe myocardial dysfunction, 'fetal' gene induction, apoptosis and early lethality. Thus, TAK1 activity is induced as a delayed response to mechanical stress, and can suffice to elicit myocardial hypertrophy and fulminant heart failure.

NASA Discipline Cardiopulmonary↗
NASA NTRS2000

Caveolin-1 regulates shear stress-dependent activation of extracellular signal-regulated kinase

Fluid shear stress activates a member of the mitogen-activated protein (MAP) kinase family, extracellular signal-regulated kinase (ERK), by mechanisms dependent on cholesterol in the plasma membrane in bovine aortic endothelial cells (BAEC). Caveolae are microdomains of the plasma membrane that are enriched with cholesterol, caveolin, and signaling molecules. We hypothesized that caveolin-1 regulates shear activation of ERK. Because caveolin-1 is not exposed to the outside, cells were minimally permeabilized by Triton X-100 (0.01%) to deliver a neutralizing, polyclonal caveolin-1 antibody (pCav-1) inside the cells. pCav-1 then bound to caveolin-1 and inhibited shear activation of ERK but not c-Jun NH(2)-terminal kinase. Epitope mapping studies showed that pCav-1 binds to caveolin-1 at two regions (residues 1-21 and 61-101). When the recombinant proteins containing the epitopes fused to glutathione-S-transferase (GST-Cav(1-21) or GST-Cav(61-101)) were preincubated with pCav-1, only GST-Cav(61-101) reversed the inhibitory effect of the antibody on shear activation of ERK. Other antibodies, including m2234, which binds to caveolin-1 residues 1-21, had no effect on shear activation of ERK. Caveolin-1 residues 61-101 contain the scaffolding and oligomerization domains, suggesting that binding of pCav-1 to these regions likely disrupts the clustering of caveolin-1 or its interaction with signaling molecules involved in the shear-sensitive ERK pathway. We suggest that caveolae-like domains play a critical role in the mechanosensing and/or mechanosignal transduction of the ERK pathway.

Non-NASA Center↗
NASA NTRS1999

T cell activation responses are differentially regulated during clinorotation and in spaceflight

Studies of T lymphocyte activation with mitogenic lectins during spaceflight have shown a dramatic inhibition of activation as measured by DNA synthesis at 72 h, but the mechanism of this inhibition is unknown. We have investigated the progression of cellular events during the first 24 h of activation using both spaceflight microgravity culture and a ground-based model system that relies on the low shear culture environment of a rotating clinostat (clinorotation). Stimulation of human peripheral blood mononuclear cells (PBMCs) with soluble anti-CD3 (Leu4) in clinorotation and in microgravity culture shows a dramatic reduction in surface expression of the receptor for IL-2 (CD25) and CD69. An absence of bulk RNA synthesis in clinorotation indicates that stimulation with soluble Leu4 does not induce transition of T cells from G0 to the G1 stage of the cell cycle. However, internalization of the TCR by T cells and normal levels of IL-1 synthesis by monocytes indicate that intercellular interactions that are required for activation occur during clinorotation. Complementation of TCR-mediated signaling by phorbol ester restores the ability of PBMCs to express CD25 in clinorotation, indicating that a PKC-associated pathway may be compromised under these conditions. Bypassing the TCR by direct activation of intracellular pathways with a combination of phorbol ester and calcium ionophore in clinorotation resulted in full expression of CD25; however, only partial expression of CD25 occurred in microgravity culture. Though stimulation of purified T cells with Bead-Leu4 in microgravity culture resulted in the engagement and internalization of the TCR, the cells still failed to express CD25. When T cells were stimulated with Bead-Leu4 in microgravity culture, they were able to partially express CD69, a receptor that is constitutively stored in intracellular pools and can be expressed in the absence of new gene expression. Our results suggest that the inhibition of T cell proliferative response in microgravity culture is a result of alterations in signaling events within the first few hours of activation, which are required for the expression of important regulatory molecules.

NASA Experiment Number 9403079 1/2↗
NASA NTRS1997

CCAAT/enhancer-binding protein delta activates insulin-like growth factor-I gene transcription in osteoblasts. Identification of a novel cyclic AMP signaling pathway in bone

Insulin-like growth factor-I (IGF-I) plays a key role in skeletal growth by stimulating bone cell replication and differentiation. We previously showed that prostaglandin E2 (PGE2) and other cAMP-activating agents enhanced IGF-I gene transcription in cultured primary rat osteoblasts through promoter 1, the major IGF-I promoter, and identified a short segment of the promoter, termed HS3D, that was essential for hormonal regulation of IGF-I gene expression. We now demonstrate that CCAAT/enhancer-binding protein (C/EBP) delta is a major component of a PGE2-stimulated DNA-protein complex involving HS3D and find that C/EBPdelta transactivates IGF-I promoter 1 through this site. Competition gel shift studies first indicated that a core C/EBP half-site (GCAAT) was required for binding of a labeled HS3D oligomer to osteoblast nuclear proteins. Southwestern blotting and UV-cross-linking studies showed that the HS3D probe recognized a approximately 35-kDa nuclear protein, and antibody supershift assays indicated that C/EBPdelta comprised most of the PGE2-activated gel-shifted complex. C/EBPdelta was detected by Western immunoblotting in osteoblast nuclear extracts after treatment of cells with PGE2. An HS3D oligonucleotide competed effectively with a high affinity C/EBP site from the rat albumin gene for binding to osteoblast nuclear proteins. Co-transfection of osteoblast cell cultures with a C/EBPdelta expression plasmid enhanced basal and PGE2-activated IGF-I promoter 1-luciferase activity but did not stimulate a reporter gene lacking an HS3D site. By contrast, an expression plasmid for the related protein, C/EBPbeta, did not alter basal IGF-I gene activity but did increase the response to PGE2. In osteoblasts and in COS-7 cells, C/EBPdelta, but not C/EBPbeta, transactivated a reporter gene containing four tandem copies of HS3D fused to a minimal promoter; neither transcription factor stimulated a gene with four copies of an HS3D mutant that was unable to bind osteoblast nuclear proteins. These results identify C/EBPdelta as a hormonally activated inducer of IGF-I gene transcription in osteoblasts and show that the HS3D element within IGF-I promoter 1 is a high affinity binding site for this protein.

NASA Discipline Musculoskeletal↗
NASA NTRS2018

Discovery of Activities via Statistical Clustering of Fixation Patterns

Human behavior often consists of a series of distinct activities, each characterized by a unique pattern of interaction with the visual environment. This is true even in a restricted domain, such as a piloting an aircraft, where activities with distinct visual signatures might be things like communicating, navigating, and monitoring. We propose a novel analysis method for gaze-tracking data, to perform blind discovery of these hypothetical activities. The method is in some respects similar to recurrence analysis, but here we compare not individual fixations, but groups of fixations aggregated over a fixed time interval. The duration of this interval is a parameter that we will refer to as delta. We assume that the environment has been divided into a set of N different areas-of-interest (AOIs). For a given interval of time of duration delta, we compute the proportion of time spent fixating each AOI, resulting in an N-dimensional vector. These proportions can be converted to integer counts by multiplying by delta divided by the average fixation duration (another parameter that we fix at 280 milliseconds). We compare different intervals by computing the chi-square statistic. The p-value associated with the statistic is the likelihood of observing the data under the hypothesis that the data in the two intervals were generated by a single process with a single set of probabilities governing the fixation of each AOI. The method has been applied to approximately 100 hours of eye movement data collected from pilots in a high-fidelity B747 flight simulator, and the results have been compared to synthetic data in which the each activity is represented as first-order Markov process with random probabilities assigned to the AOIs. Randomly-generated synthetic activities can require thousands of fixations to be discriminated with statistical significance, while the human data can be clustered using averaging windows of some 10's of seconds, suggesting that the actual activities are much more narrowly focused than random Markov models.

activity analysis↗