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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 793 records · Page 44
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

DOCK1 inhibition suppresses cancer cell invasion and macropinocytosis induced by self-activating Rac1P29S mutation

Highlights: • A guanine nucleotide exchange factor DOCK1 promotes GDP/GTP exchange of Rac1{sup P29S}. • DOCK1 deficiency cancels Rac1{sup P29S}-mediated invasion and macropinocytosis. • A DOCK1 inhibitor suppresses Rac1{sup P29S}-mediated invasion and macropinocytosis. Rac1 is a member of the Rho family of small GTPases that regulates cytoskeletal reorganization, membrane polarization, cell migration and proliferation. Recently, a self-activating mutation of Rac1, Rac1{sup P29S}, has been identified as a recurrent somatic mutation frequently found in sun-exposed melanomas, which possesses increased inherent GDP/GTP exchange activity and cell transforming ability. However, the role of cellular Rac1-interacting proteins in the transforming potential of Rac1{sup P29S} remains unclear. We found that the catalytic domain of DOCK1, a Rac-specific guanine nucleotide exchange factor (GEF) implicated in malignancy of a variety of cancers, can greatly accelerate the GDP/GTP exchange of Rac1{sup P29S}. Enforced expression of Rac1{sup P29S} induced matrix invasion and macropinocytosis in wild-type (WT) mouse embryonic fibroblasts (MEFs), but not in DOCK1-deficient MEFs. Consistently, a selective inhibitor of DOCK1 that blocks its GEF function suppressed the invasion and macropinocytosis in WT MEFs expressing Rac1{sup P29S}. Human melanoma IGR-1 and breast cancer MDA-MB-157 cells harbor Rac1{sup P29S} mutation and express DOCK1 endogenously. Genetic inactivation and pharmacological inhibition of DOCK1 suppressed their invasion and macropinocytosis. Taken together, these results indicate that DOCK1 is a critical regulator of the malignant phenotypes induced by Rac1{sup P29S}, and suggest that targeting DOCK1 might be an effective approach to treat cancers associated with Rac1{sup P29S} mutation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Toxicokinetics of benzo[a]pyrene in humans: Extensive metabolism as determined by UPLC-accelerator mass spectrometry following oral micro-dosing

Benzo[a]pyrene (BaP), produces tumors of skin, lung, liver, kidney and stomach in animals, enhances lung cancer in epidemiological studies and is a known human carcinogen. The EPA cancer slope risk factor for oral BaP exposure is 1 per mg/kg-day. The remarkable sensitivity (attomole 14C; precision 0.5-2% in biological samples) of accelerator mass spectrometry (AMS) makes possible [14C]-BaP dosing of humans with de minimus risk. A micro-dose of 46 ng (5 nCi), was given in 3 separate cycles to 5 human volunteers with a minimum 2 weeks between dosing. Blood was collected over 72 hours and BaP and BaP metabolites ([14C]-BaPeq) measured using AMS. [14C]-BaPeq appeared in plasma with an average Tmax of 75 minutes and Cmax 116-326 fM (29-82 fg/mL). Non-compartmental half-lives in plasma ranged from 30.7-114.2 hours and area under the curve values (AUC0-72 hr) 649-2060 fg x hr x mL-1. A two compartmental model yielded first-order rate constants (Ka, K12, K21, Kela and Kelß) of 0.92, 0.49, 0.12, 0.05 and 0.01 fg/hr, respectively. The T1/2a and T1/2ß were 1.14 and 89 hours, respectively. The actual interval between dosing was 20-420 days with no impact on a low intra-individual variation. No covalent [14C]-BaPeq-DNA adducts from peripheral blood mononuclear cells (PBMCs) were detected (LLOD of 10 fg [14C]-BaPeq adducts/mg DNA) 12-72 hours post-dosing negating the use of this cancer biomarker in risk assessment. We assert that the most relevant model for humans is humans. AMS and micro-dosing could be used to enhance the accuracy of pharmacokinetics and potentially risk assessments.

pharmacokinetcs, Polycyclic aromatic hydrocarbons↗
DOE OSTI2013

Growth rate of a shocked mixing layer with known initial perturbations [Mixing at shocked interfaces with known perturbations]

Here we derive a growth-rate model for the Richtmyer–Meshkov mixing layer, given arbitrary but known initial conditions. The initial growth rate is determined by the net mass flux through the centre plane of the perturbed interface immediately after shock passage. The net mass flux is determined by the correlation between the post-shock density and streamwise velocity. The post-shock density field is computed from the known initial perturbations and the shock jump conditions. The streamwise velocity is computed via Biot–Savart integration of the vorticity field. The vorticity deposited by the shock is obtained from the baroclinic torque with an impulsive acceleration. Using the initial growth rate and characteristic perturbation wavelength as scaling factors, the model collapses the growth-rate curves and, in most cases, predicts the peak growth rate over a range of Mach numbers (1.1 ≤M i ≤1.9), Atwood numbers (₋0.73 ≤ A ≤ ₋0.35 and 0.22 ≤ A ≤ 0.73), adiabatic indices (1.40/1.67≤γ 1 /γ 2 ≤1.67/1.09) and narrow-band perturbation spectra. Lastly, the mixing layer at late times exhibits a power-law growth with an average exponent of θ=0.24.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2016

ePix100 camera: Use and applications at LCLS

The ePix100 x-ray camera is a new system designed and built at SLAC for experiments at the Linac Coherent Light Source (LCLS). The camera is the first member of a family of detectors built around a single hardware and software platform, supporting a variety of front-end chips. With a readout speed of 120 Hz, matching the LCLS repetition rate, a noise lower than 80 e-rms and pixels of 50 µm × 50 µm, this camera offers a viable alternative to fast readout, direct conversion, scientific CCDs in imaging mode. The detector, designed for applications such as X-ray Photon Correlation Spectroscopy (XPCS) and wavelength dispersive X-ray Emission Spectroscopy (XES) in the energy range from 2 to 10 keV and above, comprises up to 0.5 Mpixels in a very compact form factor. In this paper, we report the performance of the camera during its first use at LCLS.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2013

RAYLEIGH-TAYLOR INSTABILITY IN A RELATIVISTIC FIREBALL ON A MOVING COMPUTATIONAL GRID

We numerically calculate the growth and saturation of the Rayleigh-Taylor (RT) instability caused by the deceleration of relativistic outflows with Lorentz factor Γ = 10, 30, and 100. The instability generates turbulence whose scale exhibits strong dependence on Lorentz factor, as only modes with angular size smaller than 1/Γ can grow. We develop a simple diagnostic to measure the kinetic energy in turbulent fluctuations, and calculate a ratio of turbulent kinetic energy to thermal energy of ε{sub RT} = .03 in the region affected by the instability. Although our numerical calculation does not include magnetic fields, we argue that small-scale turbulent dynamo amplifies magnetic fields to nearly this same fraction, giving a ratio of magnetic to thermal energy of ε{sub B} ∼ 10{sup –2}, to within a factor of two. The instability completely disrupts the contact discontinuity between the ejecta and the swept up circumburst medium. The reverse shock is stable, but is impacted by the RT instability, which strengthens the reverse shock and pushes it away from the forward shock. The forward shock front is unaffected by the instability, but RT fingers can penetrate of the order of 10% of the way into the energetic region behind the shock during the two-shock phase of the explosion. We calculate afterglow emission from the explosion and find the reverse shock emission peaks at a later time due to its reduced Lorentz factor and modified density and pressure at the shock front. These calculations are performed using a novel numerical technique that includes a moving computational grid. The moving grid is essential as it maintains contact discontinuities to high precision and can easily evolve flows with extremely large Lorentz factors.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2026

Measurement of the near-threshold 𝐽/𝜓 photoproduction cross section with the CLAS12 experiment

We present measurements of the total and differential cross sections for near-threshold 𝐽/𝜓 photoproduction obtained with the CLAS12 detector at the Thomas Jefferson National Accelerator Facility. The results are based on data collected during the fall 2018 and spring 2019 running periods, using electron beams with energies of 10.6 and 10.2 GeV, respectively, scattered off a liquid-hydrogen target. Near-threshold 𝐽/𝜓 photoproduction offers a unique sensitivity to the strong interaction in the nonperturbative regime of quantum chromodynamics (QCD). The energy dependence of the cross section constrains the underlying 𝐽/𝜓 production mechanisms, including multigluon exchange and potential baryonic excitations. Additionally, the 𝑡 dependence of the differential cross section can be related to the transverse spatial distribution of gluons in the proton, providing critical input for theoretical descriptions of the gluonic structure of the proton. An interpretation of the results in terms of the gluon content of the proton is presented, providing new experimental constraints on QCD-inspired models of the proton structure and the role of gluonic degrees of freedom in hadronic mass generation.

form factors↗
DOE OSTI2019

High Precision Detection of Change in Intermediate Range Order of Amorphous Zirconia-Doped Tantala Thin Films Due to Annealing

Understanding the local atomic order in amorphous thin film coatings and how it relates to macroscopic performance factors, such as mechanical loss, provides an important path towards enabling the accelerated discovery and development of improved coatings. High precision x-ray scattering measurements of thin films of amorphous zirconia-doped tantala (ZrO 2 -Ta 2 O 5 ) show systematic changes in intermediate range order (IRO) as a function of postdeposition heat treatment (annealing). Atomic modeling captures and explains these changes, and shows that the material has building blocks of metal-centered polyhedra and the effect of annealing is to alter the connections between the polyhedra. The observed changes in IRO are associated with a shift in the ratio of corner-sharing to edge-sharing polyhedra. These changes correlate with changes in mechanical loss upon annealing, and suggest that the mechanical loss can be reduced by developing a material with a designed ratio of corner-sharing to edge-sharing polyhedra.

36 MATERIALS SCIENCE↗
DOE OSTI2025

COMSOL Simulation of Optical Whispering Gallery Mode (WGM) Resonator

We simulate whispering-gallery mode coupling in a Si$_3$N$_4$--LiNbO$_3$ waveguide--resonator system using 2D and 3D COMSOL models. Results show that the TM$_{00}$ mode couples far more efficiently than TE$_{00}$ due to weaker confinement and stronger evanescent overlap, with critical coupling reached near a 0.20~µm gap. The study highlights polarization dependence, geometric sensitivity, and birefringence as key factors shaping resonant behavior.

42 ENGINEERING↗
NASA NTRS1971

Performance of a neutralizer for electron bombardment thruster

Results of the SERT II flight indicate that the hollow cathode neutralizer not only represents a power and propellant weight penalty but can be a contributing cause to accelerator grid erosion. Tests with a 30-cm diameter thruster show that a neutralizer position of approximately 9 cm axially downstream of the accelerator grid and approximately 9 cm radially away from the outer edge of the accelerator grid and pointing parallel to the thruster axis provides the best overall performance. The estimated grid wear rate was less than 0.08 mm in 10,000 hours. The coupling voltage was approximately 17 volts at a neutralizer flow rate of 22 equivalent milliamperes of mercury and a beam current of 1.5 amperes. Neutralizer power was 31 watts and the effect of neutralizer flow on overall propellant utilization efficiency is a 1.2 percentage point reduction at a thruster utilization efficiency of 90 percent. The neutralizer position defined in tests with a 30 cm thruster was tested with a 15 cm SERT II thruster. When the neutralizer was relocated further downstream with this different orientation, accelerator impingement current due to neutralizer operation was reduced by approximately a factor of seven and was nearly independent of neutralizer operation.

Bechtel, R. T.↗
NASA NTRS1972

Manufacturing in space.

Space, in contrast to earth, offers total gravity control and unequaled vacuum, temperature, pressure, and radiation characteristics. In zero-g molecular forces such as cohesion and adhesion become controlling factors even in the largest bulk processes. The absence of relative mass accelerations eliminates the need for support of solid matter. Stability in liquid-solid, liquid-liquid, or liquid-gas mixtures, and the absence of thermal convection is obtained because there is no relative motion in fluids due to differences in density. Applications of these characteristics include liquid-matrix preparation of composites, fine-grain castings, supersaturated alloys, combinations which exhibit liquid-phase immiscibility, the containerless free suspension of materials, surface-tension casting, surface-tension drawing, adhesion casting, and controlled density casting.

Wuenscher, H. F.↗
NASA NTRS1974

Brain catechol synthesis - Control by brain tyrosine concentration

Brain catechol synthesis was estimated by measuring the rate at which brain dopa levels rose following decarboxylase inhibition. Dopa accumulation was accelerated by tyrosine administration, and decreased by treatments that lowered brain tyrosine concentrations (for example, intraperitoneal tryptophan, leucine, or parachlorophenylalanine). A low dose of phenylalanine elevated brain tyrosine without accelerating dopa synthesis. Our findings raise the possibility that nutritional and endocrine factors might influence brain catecholamine synthesis by controlling the availability of tyrosine.

Wurtman, R. J.↗
NASA NTRS1974

Geomorphic processes active in the Southwestern Louisiana Canal, Lafourche Parish, Louisiana

The geomorphological changes causing the destruction of the banks of the Southwestern Louisiana Canal are studied by means of field work, laboratory analyses, and infrared color imagery interpretation. Turbulence and flow patterns are mapped, and related to erosion and sediment deposition processes. The accelerated erosion rate of the last decade is discussed, with two causative factors cited: (1) development of faster boats, increasing bank and bottom erosion, and (2) a subsequently larger tidal influx, with greater erosive ability. The physical properties of the canal bank materials are also analyzed. It is concluded that channel erosion progressively increases, with no indications of stabilization, until they merge with other waterways and become indistinguishable from natural water bodies.

Doiron, L. N.↗
NASA NTRS1981

Radially propagating shock waves in the outer heliosphere - The evidence from Pioneer 10 energetic particle and plasma observations

At heliocentric distances between 14 and 22 AU, some 14 increases in the flux of 1 MeV protons have been identified over a 3 yr period by the NASA Goddard/University of New Hampshire cosmic-ray experiment on Pioneer 10. These increases appear to be associated with large solar flares. Combining the particle data with the Pioneer 10 plasma observations from the NASA/Ames plasma analyzer reveals that the particle increases are produced by radially propagating shock waves generated by the solar events. While the characteristics of these particle events in the distant heliosphere appear to differ greatly from those observed at 1 AU, they represent the evolution expected as the interplanetary magnetic field becomes almost azimuthal. These long-lived shocks provide a valuable in situ laboratory for directly studying particle acceleration under a variety of conditions. They may also represent a significant factor in producing the long-term modulation of galactic cosmic rays.

Mcdonald, F. B.↗
NASA NTRS1982

Response of rat body composition to simultaneous exercise and centrifugation at 3.14g

A study is described calling into question the hypothesis that an increased physical load during chronic centrifugation contributes to the body composition changes observed in centrifuged rats. Considering fat-free and fat-free dry masses of the total body and carcass, it is seen that centrifugation combined with either wheel running or restraint reduced these masses to approximately 85% of the respective 1-g values, that is, the same result with either sedentary rats or rats running several hundred meters per day. It is pointed out that if an effect of a centrifugation-induced load is present but hidden by opposing factors, an analysis of variance should reveal it as an interaction between acceleration and other variables; however, no such interactions are found here. Tables are included emphasizing the pervasive influence of chronic centrifugation after only 12 days exposure.

Pitts, G. C.↗
NASA NTRS1995

Time-to-Passage Judgments in Nonconstant Optical Flow Fields

The time until an approaching object will pass an observer (time to passage, or TTP) is optically specified by a global flow field even in the absence of local expansion or size cues. Kaiser and Mowafy have demonstrated that observers are in fact sensitive to this global flow information. The present studies investigate two factors that are usually ignored in work related to TTP: (1) non-constant motion functions and (2) concomitant eye rotation. Non-constant velocities violate an assumption of some TTP derivations, and eye rotations may complicate heading extraction. Such factors have practical significance, for example, in the case of a pilot accelerating an aircraft or executing a roll. In our studies, a flow field of constant-sized stars was presented monocularly on a large screen. TIP judgments had to be made on the basis of one target star. The flow field varied in its acceleration pattern and its roll component. Observers did not appear to utilize acceleration information. In particular, TTP with decelerating motion were consistently underestimated. TTP judgments were fairly robust with respect to roll, even when roll axis and track vector were decoupled. However, substantial decoupling between heading and track vector led to a decrement in performance, in both the presence and the absence of roll.

Kaiser, Mary K.↗
NASA NTRS2001

Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy

Muscle wasting is a debilitating consequence of fasting, inactivity, cancer, and other systemic diseases that results primarily from accelerated protein degradation by the ubiquitin-proteasome pathway. To identify key factors in this process, we have used cDNA microarrays to compare normal and atrophying muscles and found a unique gene fragment that is induced more than ninefold in muscles of fasted mice. We cloned this gene, which is expressed specifically in striated muscles. Because this mRNA also markedly increases in muscles atrophying because of diabetes, cancer, and renal failure, we named it atrogin-1. It contains a functional F-box domain that binds to Skp1 and thereby to Roc1 and Cul1, the other components of SCF-type Ub-protein ligases (E3s), as well as a nuclear localization sequence and PDZ-binding domain. On fasting, atrogin-1 mRNA levels increase specifically in skeletal muscle and before atrophy occurs. Atrogin-1 is one of the few examples of an F-box protein or Ub-protein ligase (E3) expressed in a tissue-specific manner and appears to be a critical component in the enhanced proteolysis leading to muscle atrophy in diverse diseases.

NASA Discipline Musculoskeletal↗