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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 955 records · Page 53
All sourcesNASA NTRSDOE OSTI
DOE OSTI2013

A rat retinal damage model predicts for potential clinical visual disturbances induced by Hsp90 inhibitors

In human trials certain heat shock protein 90 (Hsp90) inhibitors, including 17-DMAG and NVP-AUY922, have caused visual disorders indicative of retinal dysfunction; others such as 17-AAG and ganetespib have not. To understand these safety profile differences we evaluated histopathological changes and exposure profiles of four Hsp90 inhibitors, with or without clinical reports of adverse ocular effects, using a rat retinal model. Retinal morphology, Hsp70 expression (a surrogate marker of Hsp90 inhibition), apoptotic induction and pharmacokinetic drug exposure analysis were examined in rats treated with the ansamycins 17-DMAG and 17-AAG, or with the second-generation compounds NVP-AUY922 and ganetespib. Both 17-DMAG and NVP-AUY922 induced strong yet restricted retinal Hsp70 up-regulation and promoted marked photoreceptor cell death 24 h after the final dose. In contrast, neither 17-AAG nor ganetespib elicited photoreceptor injury. When the relationship between drug distribution and photoreceptor degeneration was examined, 17-DMAG and NVP-AUY922 showed substantial retinal accumulation, with high retina/plasma (R/P) ratios and slow elimination rates, such that 51% of 17-DMAG and 65% of NVP-AUY922 present at 30 min post-injection were retained in the retina 6 h post-dose. For 17-AAG and ganetespib, retinal elimination was rapid (90% and 70% of drugs eliminated from the retina at 6 h, respectively) which correlated with lower R/P ratios. These findings indicate that prolonged inhibition of Hsp90 activity in the eye results in photoreceptor cell death. Moreover, the results suggest that the retina/plasma exposure ratio and retinal elimination rate profiles of Hsp90 inhibitors, irrespective of their chemical class, may predict for ocular toxicity potential. - Highlights: • In human trials some Hsp90 inhibitors cause visual disorders, others do not. • Prolonged inhibition of Hsp90 in the rat eye results in photoreceptor cell death. • Retina/plasma ratio and retinal elimination rate are linked to toxicity potential. • Rat retinotoxic responses to individual Hsp90 inhibitors reflect clinical profiles. • Rodent modeling may be used to assess ocular risks of targeted Hsp90 compounds.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Neuron-specific knockdown of Drosophila PDHB induces reduction of lifespan, deficient locomotive ability, abnormal morphology of motor neuron terminals and photoreceptor axon targeting

Highlights: • Drosophila CG11876 (dPDHB) is a homolog of human pyruvate dehydrogenase beta, PDHB. • Neuron-specific knockdown of dPDHB causes locomotive defects and reduced life span. • Neuron-specific knockdown of dPDHB causes structural defects in NMJ. • Neuron-specific knockdown of dPDHB induces mitochondrial fragmentation in brain. • Knockdown of dPDHB induces a rough eye and aberrant photoreceptor axon targeting. Pyruvate dehydrogenase complex deficiency (PDCD) is a common primary cause of defects in mitochondrial function and also can lead to peripheral neuropathy. Pyruvate dehydrogenase E1 component subunit beta (PDHB) is a subunit of pyruvate dehydrogenase E1, which is a well-known component of PDC. In Drosophila melanogaster, the CG11876 (dPDHB) gene is a homolog of human PDHB. In this study, we established a Drosophila model with neuron-specific knockdown of dPDHB to investigate its role in neuropathy pathogenesis. Knockdown of dPDHB in pan-neurons induced locomotor defects in both larval and adult stages, which were consistent with abnormal morphology of the motor neuron terminals at neuromuscular junctions and mitochondrial fragmentation in brains. Moreover, neuron-specific knockdown of dPDHB also shortened the lifespan of adult flies. In addition, flies with knockdown of dPDHB manifested a rough eye phenotype and aberrant photoreceptor axon targeting. These results with the Drosophila model suggest the involvement of PDHB in peripheral neuropathy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Mini-peptide RPL41 attenuated retinal neovascularization by inducing degradation of ATF4 in oxygen-induced retinopathy mice

Highlights: • ER stress actively participates in RNV in OIR mice, in which ATF4 plays a vital role. • RPL41 inhibits the PERK/eIF2α/ATF4 pathway by phosphorylating and degrading ATF4 in mice retinas. • RPL41 is therapeutic implications for treating neovascular eye diseases. Endoplasmic reticulum (ER) stress signaling is activated in retinal degeneration disease. Activating transcription factor 4 (ATF4), an important mediator of the unfolded protein response (UPR), is a key element that maintains cell survival and proliferation in hypoxic conditions. Our previous studies showed that a small ribosomal protein L41 (RPL41) inhibits ATF4 by inducing its phosphorylation and degradation. In the present study, the effects of mini-peptide RPL41 on retinal neovascularization (RNV) in oxygen-induced retinopathy (OIR) mice was investigated. We induced OIR in C57BL/6 mice and obtained retinas from normoxia, OIR, OIR control (treated with PBS), and OIR treated (treated with RPL41) mice. Our results showed that ER stress signaling was activated and ATF4 was overexpressed in the retinas of OIR mice. After intravitreal injection of RPL41, the size of RNV and vaso-obliteration, and the number of preretinal neovascular cell nuclei in the retinas of OIR mice were significantly decreased. Western blot analysis and quantitative real-time polymerase chain reaction (qPCR) showed ATF4 and VEGF expression decreased after intravitreal injection of RPL41. Furthermore, the expression levels of inflammatory genes including TNF-α, IL-1β, and IL-6 were significantly decreased compared with the OIR control mice. In conclusion, RPL41 prevented pathologic neovascularization and exerted anti-inflammatory effects by degrading the important ER stress factor ATF4, thus, RPL41 could be a promising therapeutic agent for the treatment of neovascular eye diseases, especially retinopathy of prematurity (ROP).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

NF-κB activation in retinal microglia is involved in the inflammatory and neovascularization signaling in laser-induced choroidal neovascularization in mice

Highlights: • IMD0354 treatment reduced the microglia infiltration, fluorescein leakage and size of the laser CNV spots. • IKK2 inhibition suppressed phospho-IκBα, VEGF-A, and COX-2 in the Laser CNV mouse eyes. • IMD-0354 treated eyes demonstrated reduced microglial migration to the laser injury site. • In vitro, IKK2 inhibition reduced NF-κB activation, COX-2, Actin-F presence, and the microglia cells' migration capacity. To evaluate Nuclear Factor NF-κB (NF-κB) signaling on microglia activation, migration, and angiogenesis in laser-induced choroidal neovascularization (CNV).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Rationally Designed, Short-Acting RPE65 Inhibitors for Visual Cycle-Associated Retinopathies

Abstract The visual cycle is a metabolic pathway essential for visual function. The bisretinoid byproducts of this pathway can induce retinal toxicity, as occurs in Stargardt disease type 1 (STGD1). Emixustat, which inhibits bisretinoid production, is a visual cycle modulator (VCM) that targets RPE65. However, it causes visual impairment due to its unfavorable duration of action. Here, we report ester-containing analogs of emixustat that are susceptible to hydrolytic clearance and function as short-acting VCMs. We show that the esterase-mediated metabolism of these compounds can be tuned while maintaining high-affinity RPE65 targeting. Compounds 6 (EYE-002) and 7 (EYE-003) containing diethyl acetate and valproate esters, respectively, allowed faster recovery of visual cycle function compared to emixustat. These molecules protected against retinal degeneration in mouse models of photic retinopathy and STGD1. These data demonstrate that shorter attenuation of the visual cycle can therapeutically intervene in retinal diseases with fewer visual side effects compared to emixustat.

Pharmacology & Pharmacy↗
DOE OSTI2014

Mobile Interfaces: Liquids as a Perfect Structural Material for Multifunctional, Antifouling Surfaces

Life creates some of its most robust, extreme surface materials not from solids but from liquids: a purely liquid interface, stabilized by underlying nanotexture, makes carnivorous plant leaves ultraslippery, the eye optically perfect and dirt-resistant, our knees lubricated and pressure-tolerant, and insect feet reversibly adhesive and shape-adaptive. Novel liquid surfaces based on this idea have recently been shown to display unprecedented omniphobic, self-healing, anti-ice, antifouling, optical, and adaptive properties. In this Perspective, we present a framework and a path forward for developing and designing such liquid surfaces into sophisticated, versatile multifunctional materials. Drawing on concepts from solid materials design and fluid dynamics, we outline how the continuous dynamics, responsiveness, and multiscale patternability of a liquid surface layer can be harnessed to create a wide range of unique, active interfacial functions able to operate in harsh, changing environments not achievable with static solids. We discuss how, in partnership with the underlying substrate, the liquid surface can be programmed to adaptively and reversibly reconfigure from a defect-free, molecularly smooth, transparent interface through a range of finely tuned liquid topographies in response to environmental stimuli. With nearly unlimited design possibilities and unmatched interfacial properties, liquid materials as long-term stable interfaces yet in their fully liquid state may potentially transform surface design everywhere from medicine to architecture to energy infrastructure.

Grinthal, A↗
DOE OSTI2014

Flow Evaporimeter To Assess Evaporative Resistance of Human Tear-Film Lipid Layer

A novel in vivo flow evaporimeter is developed to measure human tear-evaporation rates. The flow evaporimeter relies on a well-defined flow field to the eye with known and adjustable flow rates and relative humidities, and quantitatively reproduces evaporation rates for pure water. Mass-transfer analysis of the evaporimeter data elucidates, for the first time, the resistance of the human tear-film lipid layer (TFLL) toward minimizing tear loss to the environment. A pilot study on human subjects validates the feasibility of the flow evaporimeter to obtain the tear-film evaporation rates in vivo. Resistance of the TFLL against tear evaporation is found subject specific. Our flow evaporimeter offers an accurate, safe, and convenient diagnostic tool for clinical evaluation of dry-eye-related maladies.

atmospheric chemistry↗
DOE OSTI2017

Antifogging abilities of model nanotextures

Nanometre-scale features with special shapes impart a broad spectrum of unique properties to the surface of insects. These properties are essential for the animal’s survival, and include the low light reflectance of moth eyes, the oil repellency of springtail carapaces and the ultra-adhesive nature of palmtree bugs. Antireflective mosquito eyes and cicada wings are also known to exhibit some antifogging and self-cleaning properties. In all cases, the combination of small feature size and optimal shape provides exceptional surface properties. In this work, we investigate the underlying antifogging mechanism in model materials designed to mimic natural systems, and explain the importance of the texture’s feature size and shape. While exposure to fog strongly compromises the water-repellency of hydrophobic structures, this failure can be minimized by scaling the texture down to nanosize. Furthermore, this undesired effect even becomes non-measurable if the hydrophobic surface consists of nanocones, which generate antifogging efficiency close to unity and water departure of droplets smaller than 2 μm.

77 NANOSCIENCE AND NANOTECHNOLOGY↗
DOE OSTI2022

Smart soft contact lenses for continuous 24-hour monitoring of intraocular pressure in glaucoma care

Continuous monitoring of intraocular pressure, particularly during sleep, remains a grand challenge in glaucoma care. Here we introduce a class of smart soft contact lenses, enabling the continuous 24-hour monitoring of intraocular pressure, even during sleep. Uniquely, the smart soft contact lenses are built upon various commercial brands of soft contact lenses without altering their intrinsic properties such as lens power, biocompatibility, softness, transparency, wettability, oxygen transmissibility, and overnight wearability. We show that the smart soft contact lenses can seamlessly fit across different corneal curvatures and thicknesses in human eyes and therefore accurately measure absolute intraocular pressure under ambulatory conditions. We perform a comprehensive set of in vivo evaluations in rabbit, dog, and human eyes from normal to hypertension to confirm the superior measurement accuracy, within-subject repeatability, and user comfort of the smart soft contact lenses beyond current wearable ocular tonometers. We envision that the smart soft contact lenses will be effective in glaucoma care.

36 MATERIALS SCIENCE↗
DOE OSTI2019

Prospects for Bioinspired Single-Photon Detection Using Nanotube-Chromophore Hybrids

The human eye is an exquisite photodetection system with the ability to detect single photons. The process of vision is initiated by single-photon absorption in the molecule retinal, triggering a cascade of complex chemical processes that eventually lead to the generation of an electrical impulse. Here, we analyze the single-photon detection prospects for an architecture inspired by the human eye: field-effect transistors employing carbon nanotubes functionalized with chromophores. We employ non-equilibrium quantum transport simulations of realistic devices to reveal device response upon absorption of a single photon. We establish the parameters that determine the strength of the response such as the magnitude and orientation of molecular dipole(s), as well as the arrangements of chromophores on carbon nanotubes. Moreover, we show that functionalization of a single nanotube with multiple chromophores allows for number resolution, whereby the number of photons in an incoming light packet can be determined. Finally, we assess the performance prospects by calculating the dark count rate, and we identify the most promising architectures and regimes of operation.

Science & Technology - Other Topics↗
DOE OSTI2013

Amplification of interference color by using liquid crystal for protein detection

Micrometer-sized, periodic protein lines printed on a solid surface cause interference color which is invisible to the naked eye. However, the interference color can be amplified by using a thin layer of liquid crystal (LC) covered on the surface to form a phase diffraction grating. Strong interference color can thus be observed under ambient light. By using the LC-amplified interference color, we demonstrate naked-eye detection of a model protein—immunoglobulin G (IgG). Limit of detection can reach 20 μg/ml of IgG without using any instrumentation. This detection method is potentially useful for the development of low-cost and portable biosensors.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2013

Anisotropic strain relaxation and the resulting degree of polarization by one- and two-step growth in nonpolar a-plane GaN grown on r-sapphire substrate

Anisotropic strain relaxation and the resulting degree of polarization of the electronic transition in nonpolar a-plane GaN using one- and two-step growth are studied. By using two-step growth, a slower coalescence and a longer roughening-recovery process lead to larger anisotropic strain relaxation, a less striated surface, and lower densities of basal stacking fault (BSF) and prismatic stacking fault (PSF). It is suggested that anisotropic in-plane strains, surface striation, and BSF and PSF densities in nonpolar a-GaN are consequences of the rate of coalescence, the period of roughening-recovery process, and the degree of anisotropic strain relaxation. In addition, the two-step growth mode can enhance the degree of polarization of the electronic transition. The simulation results of the k⋅p perturbation approach show that the oscillator strength and degree of polarization of the electronic transition strongly depend on the in-plane strains upon anisotropic in-plane strain relaxation. The research results provide important information for optimized growth of nonpolar III-nitrides. By using two-step growth and by fabricating the devices on the high-quality nonpolar free-standing GaN substrates, high-efficiency nonpolar a-plane InGaN LEDs can be realized. Nonpolar a-plane InGaN/GaN LEDs can exhibit a strongly polarized light to improve the contrast, glare, eye discomfort and eye strain, and efficiency in display application.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2014

Patient dose estimation from CT scans at the Mexican National Neurology and Neurosurgery Institute

In the radiology department of the Mexican National Institute of Neurology and Neurosurgery, a dedicated institute in Mexico City, on average 19.3 computed tomography (CT) examinations are performed daily on hospitalized patients for neurological disease diagnosis, control scans and follow-up imaging. The purpose of this work was to estimate the effective dose received by hospitalized patients who underwent a diagnostic CT scan using typical effective dose values for all CT types and to obtain the estimated effective dose distributions received by surgical and non-surgical patients. Effective patient doses were estimated from values per study type reported in the applications guide provided by the scanner manufacturer. This retrospective study included all hospitalized patients who underwent a diagnostic CT scan between 1 January 2011 and 31 December 2012. A total of 8777 CT scans were performed in this two-year period. Simple brain scan was the CT type performed the most (74.3%) followed by contrasted brain scan (6.1%) and head angiotomography (5.7%). The average number of CT scans per patient was 2.83; the average effective dose per patient was 7.9 mSv; the mean estimated radiation dose was significantly higher for surgical (9.1 mSv) than non-surgical patients (6.0 mSv). Three percent of the patients had 10 or more brain CT scans and exceeded the organ radiation dose threshold set by the International Commission on Radiological Protection for deterministic effects of the eye-lens. Although radiation patient doses from CT scans were in general relatively low, 187 patients received a high effective dose (>20 mSv) and 3% might develop cataract from cumulative doses to the eye lens.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Dynamic characteristics of two-state lasing quantum dot lasers under large signal modulation

Large signal modulation characteristics of the simultaneous ground-state (GS) and excited-state (ES) lasing quantum dot lasers are theoretically investigated. Relaxation oscillations of ‘0 → 1’ and ‘1 → 0’ in the GS lasing region (Region I), the transition region from GS lasing to two-state lasing (Region II) and the two-state lasing region (Region III) are compared and analyzed. It is found that the overshooting power and settling time in both Regions I and III decrease as the bias current increases. However, there exist abnormal behaviors of the overshooting power and settling time in Region II owing to the occurrence of ES lasing, which lead to fuzzy eye diagrams of the GS and ES lasing. Moreover, the ES lasing in Region III possesses much better eye diagrams because of its shorter settling time and smaller overshooting power over the GS lasing in Region I.

36 MATERIALS SCIENCE↗
DOE OSTI2016

Flux-driven algebraic damping of m = 1 diocotron mode

Recent experiments with pure electron plasmas in a Malmberg–Penning trap have observed the algebraic damping of m = 1 diocotron modes. Transport due to small field asymmetries produces a low density halo of electrons moving radially outward from the plasma core, and the mode damping begins when the halo reaches the resonant radius r = R{sub w} at the wall of the trap. The damping rate is proportional to the flux of halo particles through the resonant layer. The damping is related to, but distinct from, spatial Landau damping, in which a linear wave-particle resonance produces exponential damping. This paper explains with analytic theory the new algebraic damping due to particle transport by both mobility and diffusion. As electrons are swept around the “cat's eye” orbits of the resonant wave-particle interaction, they form a dipole (m = 1) density distribution. From this distribution, the electric field component perpendicular to the core displacement produces E × B-drift of the core back to the axis, that is, damps the m = 1 mode. The parallel component produces drift in the azimuthal direction, that is, causes a shift in the mode frequency.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2016

Toward the realization of erbium-doped GaN bulk crystals as a gain medium for high energy lasers

Er-doped GaN (Er:GaN) is a promising candidate as a gain medium for solid-state high energy lasers (HELs) at the technologically important and eye-safe 1.54 μm wavelength window, as GaN has superior thermal properties over traditional laser gain materials such as Nd:YAG. However, the attainment of wafer-scale Er:GaN bulk or quasi-bulk crystals is a prerequisite to realize the full potential of Er:GaN as a gain medium for HELs. We report the realization of freestanding Er:GaN wafers of 2-in. in diameter with a thickness on the millimeter scale. These freestanding wafers were obtained via growth by hydride vapor phase epitaxy in conjunction with a laser-lift-off process. An Er doping level of 1.4 × 10{sup 20} atoms/cm{sup 3} has been confirmed by secondary ion mass spectrometry measurements. The freestanding Er:GaN wafers exhibit strong photoluminescent emission at 1.54 μm with its emission intensity increasing dramatically with wafer thickness under 980 nm resonant excitation. A low thermal quenching of 10% was measured for the 1.54 μm emission intensity between 10 K and 300 K. This work represents a significant step in providing a practical approach for producing Er:GaN materials with sufficient thicknesses and dimensions to enable the design of gain media in various geometries, allowing for the production of HELs with improved lasing efficiency, atmosphere transmission, and eye-safety.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2015

NuSTAR AND MULTIFREQUENCY STUDY OF THE TWO HIGH-REDSHIFT BLAZARS S5 0836+710 AND PKS 2149–306

Powerful blazars are flat-spectrum radio quasars whose emission is dominated by a Compton component peaking between a few hundred keV and a few hundred MeV. We observed two bright blazars, PKS 2149–306 at redshift z = 2.345 and S5 0836+710 at z = 2.172, in the hard X-ray band with the Nuclear Spectroscopic Telescope Array satellite. Simultaneous soft-X-rays and UV–optical observations were performed with the Swift satellite, while near-infrared (near-IR) data were obtained with the Rapid Eye Mount telescope. To study their variability, we repeated these observations for both sources on a timescale of a few months. While no fast variability was detected during a single observation, both sources were variable in the X-ray band, up to 50%, between the two observations, with larger variability at higher energies. No variability was detected in the optical/NIR band. These data, together with Fermi-Large Area Telescope, Wide-field Infrared Survey Explorer, and other literature data, are then used to study the overall spectral energy distributions (SEDs) of these blazars. Although the jet nonthermal emission dominates the SED, it leaves the UV band unhidden, allowing us to detect the thermal emission of the disk and to estimate the black hole mass. The nonthermal emission is well reproduced by a one-zone leptonic model by the synchrotron, self-Compton, and external Compton processes. Our data are better reproduced if we assume that the location of the dissipation region of the jet, R{sub diss}, is in between the torus and the broad-line region. The observed variability is explained by changing a minimum number of model parameters by a very small amount.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2015

Generalised form factor dark matter in the Sun

We study the effects of energy transport in the Sun by asymmetric dark matter with momentum and velocity-dependent interactions, with an eye to solving the decade-old Solar Abundance Problem. We study effective theories where the dark matter-nucleon scattering cross-section goes as v{sub rel}{sup 2n} and q{sup 2n} with n=−1,0,1 or 2, where v{sub rel} is the dark matter-nucleon relative velocity and q is the momentum exchanged in the collision. Such cross-sections can arise generically as leading terms from the most basic nonstandard DM-quark operators. We employ a high-precision solar simulation code to study the impact on solar neutrino rates, the sound speed profile, convective zone depth, surface helium abundance and small frequency separations. We find that the majority of models that improve agreement with the observed sound speed profile and depth of the convection zone also reduce neutrino fluxes beyond the level that can be reasonably accommodated by measurement and theory errors. However, a few specific points in parameter space yield a significant overall improvement. A 3–5 GeV DM particle with σ{sub SI}∝q{sup 2} is particularly appealing, yielding more than a 6σ improvement with respect to standard solar models, while being allowed by direct detection and collider limits. We provide full analytical capture expressions for q- and v{sub rel}-dependent scattering, as well as complete likelihood tables for all models.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗