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At least 865 records · Page 48
All sourcesNASA NTRSDOE OSTI
DOE OSTI2012

Nitrative DNA damage induced by multi-walled carbon nanotube via endocytosis in human lung epithelial cells

Carbon nanotube (CNT) has a promising usage in the field of material science for industrial purposes because of its unique physicochemical property. However, intraperitoneal administration of CNT was reported to cause mesothelioma in experimental animals. Chronic inflammation may contribute to carcinogenesis induced by fibrous materials. 8-Nitroguanine is a mutagenic DNA lesion formed during inflammation and may play a role in CNT-induced carcinogenesis. In this study, we examined 8-nitroguanine formation in A549 human lung alveolar epithelial cells treated with multi-walled CNT (MWCNT) by fluorescent immunocytochemistry. Both MWCNTs with diameter of 20–30 nm (CNT20) and 40–70 nm (CNT40) significantly induced 8-nitroguanine formation at 5 and 10 μg/ml (p < 0.05), which persisted for 24 h, although there was no significant difference in DNA-damaging abilities of these MWCNTs. MWCNTs significantly induced the expression of inducible nitric oxide synthase (iNOS) for 24 h (p < 0.05). MWCNTs also significantly increased the level of nitrite, a hydrolysis product of oxidized NO, in the culture supernatant at 4 and 8 h (p < 0.05). MWCNT-induced 8-nitroguanine formation and iNOS expression were largely suppressed by inhibitors of iNOS (1400 W), nuclear factor-κB (Bay11-7082), actin polymerization (cytochalasin D), caveolae-mediated endocytosis (methyl-β-cyclodextrin, MBCD) and clathrin-mediated endocytosis (monodansylcadaverine, MDC). Electron microscopy revealed that MWCNT was mainly located in vesicular structures in the cytoplasm, and its cellular internalization was reduced by MBCD and MDC. These results suggest that MWCNT is internalized into cells via clathrin- and caveolae-mediated endocytosis, leading to inflammatory reactions including iNOS expression and resulting nitrative DNA damage, which may contribute to carcinogenesis. Highlights: ►Multi-walled carbon nanotube (MWCNT) caused DNA damage in A549 cells. ►MWCNT formed 8-nitroguanine, a DNA lesion associated with inflammatory response. ►MWCNT was internalized into cells via caveolin- and clathrin-mediated endocytosis. ►8-Nitroguanine formation and iNOS expression involved these types of endocytosis. ►Internalized MWCNT plays a key role in inflammatory response and DNA damage.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. In all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti-inflammatory intervention.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Mechanism study of goldenseal-associated DNA damage

Goldenseal has been used for the treatment of a wide variety of ailments including gastrointestinal disturbances, urinary tract disorders, and inflammation. The five major alkaloid constituents in goldenseal are berberine, palmatine, hydrastine, hydrastinine, and canadine. When goldenseal was evaluated by the National Toxicology Program (NTP) in the standard 2-year bioassay, goldenseal induced an increase in liver tumors in rats and mice; however, the mechanism of goldensealassociated liver carcinogenicity remains unknown. In this study, the toxicity of the five goldenseal alkaloid constituents was characterized, and their toxic potencies were compared. As measured by the Comet assay and the expression of γ-H2A.X, berberine, followed by palmatine, appeared to be the most potent DNA damage inducer in human hepatoma HepG2 cells. Berberine and palmatine suppressed the activities of both topoisomerase (Topo) I and II. In berberine-treated cells, DNA damage was shown to be directly associated with the inhibitory effect of Topo II, but not Topo I by silencing gene of Topo I or Topo II. In addition, DNA damage was also observed when cells were treated with commercially available goldenseal extracts and the extent of DNA damage was positively correlated to the berberine content. Our findings suggest that the Topo II inhibitory effect may contribute to berberine- and goldenseal-induced genotoxicity and tumorigenicity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Modeling nuclear waste disposal in crystalline rocks at the Forsmark and Olkiluoto repository sites – Evaluation of potential thermal–mechanical damage to repository excavations

We conduct coupled thermo-hydro-mechanical modeling of a KBS-3V repository design in crystalline rocks, using data and conditions from the Forsmark in Olkiluoto repository sites in Sweden and Finland. The study focuses on repository performance related to the impact of thermal and hydraulic evolution on the potential for thermal–mechanical damage to underground repository excavations. For the designs and conditions considered at the Forsmark and Olkiluoto repository sites, the simulations show a peak temperature well under the adopted performance target of a 100°C maximum temperature, whereas there is still a high potential for thermal–mechanical damage to the KBS-3V waste deposition holes. The thermal–mechanical damage is much more likely if rock permeability is so low that it delays saturation and swelling of bentonite-clay-based backfill beyond the time for the thermal–mechanical peak, which occurs 50 to 100 years after nuclear waste deposition. We also found that sidewalls of the KBS-3V emplacement tunnels are vulnerable to tensile fracturing due to the combined effect of thermal stressing and backfill swelling. The study highlights a strong interaction between bentonite-based backfill and host rock through capillary suction along with induced rock desaturation. A careful design and selection of the bentonite-clay-based backfill materials for KBS-3V tunnels and deposition holes can facilitate a timely saturation and backfill swelling that in turn can minimize thermal–mechanical damage.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2015

DNA damage checkpoint recovery and cancer development

Cell cycle checkpoints were initially presumed to function as a regulator of cell cycle machinery in response to different genotoxic stresses, and later found to play an important role in the process of tumorigenesis by acting as a guard against DNA over-replication. As a counterpart of checkpoint activation, the checkpoint recovery machinery is working in opposition, aiming to reverse the checkpoint activation and resume the normal cell cycle. The DNA damage response (DDR) and oncogene induced senescence (OIS) are frequently found in precancerous lesions, and believed to constitute a barrier to tumorigenesis, however, the DDR and OIS have been observed to be diminished in advanced cancers of most tissue origins. These findings suggest that when progressing from pre-neoplastic lesions to cancer, DNA damage checkpoint barriers are overridden. How the DDR checkpoint is bypassed in this process remains largely unknown. Activated cytokine and growth factor-signaling pathways were very recently shown to suppress the DDR and to promote uncontrolled cell proliferation in the context of oncovirus infection. In recent decades, data from cell line and tumor models showed that a group of checkpoint recovery proteins function in promoting tumor progression; data from patient samples also showed overexpression of checkpoint recovery proteins in human cancer tissues and a correlation with patients' poor prognosis. In this review, the known cell cycle checkpoint recovery proteins and their roles in DNA damage checkpoint recovery are reviewed, as well as their implications in cancer development. This review also provides insight into the mechanism by which the DDR suppresses oncogene-driven tumorigenesis and tumor progression. - Highlights: • DNA damage checkpoint works as a barrier to cancer initiation. • DDR machinary response to genotoxic and oncogenic stress in similar way. • Checkpoint recovery pathways provide active signaling in cell cycle control. • Checkpoint recovery pathway plays a role in overriding tumor barrier in tumorigenesis. • Recovery protein dysregulation and human cancer development is correlated.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Pulse-length dependence of the laser-induced damage behavior of a fused-silica antireflective metasurface

A broadband, antireflective metasurface optic on a silica substrate is subjected to laser-induced damage-threshold measurements to quantify its performance under exposure to high-intensity/fluence laser pulses in the near-infrared at four pulse durations, ranging from 20 fs to 1.4 ns. The performance of the metasurface is benchmarked against that obtained from an equivalent bare fused-silica substrate that did not receive reactive-ion-etching metasurface treatment. Results showed that the damage threshold of the antireflective metasurface was always lower than the input-surface damage threshold of the untreated substrate. The damage initiations with nanosecond and picosecond pulses resulted in localized modification and removal of the nanostructures, whereas the onset of laser-induced modification with 20-fs pulses in a vacuum environment manifested as changes in the optical and electronic properties without significant material removal. The broader goal of this work is to develop a preliminary understanding of the laser-induced failure mechanisms of silica-based metasurface optics.

antireflection↗
DOE OSTI2020

Proteomic Characterization of Damaged Single Hairs Recovered after an Explosion for Protein-Based Human Identification

Evidence recovery is challenging where an explosion has occurred. Though hair evidence may be sufficiently robust to be recovered at the site, forensic analysis underutilizes the matrix by relying on morphological analysis. Where DNA is compromised, particularly in hair, protein-based human identification presents a promising alternative. Detection of amino acid polymorphisms in hair proteins as genetically variant peptides (GVPs) permits the inference of individualizing single nucleotide polymorphisms for identification. However, an explosive blast may damage hair proteins and compromise GVP identification. This work evaluates effects of an explosive blast on the hair proteome and GVP identification, investigates microscopy as a predictor of proteome profiling success in recovered hairs to improve analysis throughput, and quantifies discriminative power in damaged hairs. The proteomics dataset has been deposited into the ProteomeXchange Consortium (PXD017427). With the exception of degradation in keratins K75, K80, K40, and keratin-associated protein KAP10-11 as markers of hair cuticular damage, corroborated by scanning electron microscopic analysis, minimal hair proteome degradation following explosion allowed successful proteome profiling of single hairs regardless of morphological damage. Finally, GVP identification remained independent of explosion conditions, permitting similar discriminative power between exploded and undamaged hairs. These findings lend greater confidence to GVP analysis in one-inch hairs for forensic identification and provide information about hair protein localization.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Earthquake Damage Patterns Resolve Complex Rupture Processes

Fracture damage patterns around faults induced by dynamic earthquake rupture are an invaluable record to clarify the rupture process on complex fault networks. The 2016 M w 7.8 Kaikōura earthquake in New Zealand has been reported as one of the most complex earthquakes ever documented that ruptured at least 15 crustal faults. High-resolution optical satellite image displacement maps provide distinctive profiles of displacement across the faults and help visualize the off-fault damage pattern. They are combined with field observation and coupled with a numerical tool that captures the dynamics of the rupture and simultaneous activation of off-fault damage to allow the determination of the most likely rupture scenario. Lastly, this study demonstrates that complex rupture processes can be explained in a rather simple way via a synergetic combination of state-of-the-art observation and first principle physics-based numerical modeling of off-fault damage.

58 GEOSCIENCES↗
DOE OSTI2011

Quantifying pulsed laser induced damage to graphene

As an emerging optical material, graphene's ultrafast dynamics are often probed using pulsed lasers yet the region in which optical damage takes place is largely uncharted. Here, femtosecond laser pulses induced localized damage in single-layer graphene on sapphire. Raman spatial mapping, SEM, and AFM microscopy quantified the damage. The resulting size of the damaged area has a linear correlation with the optical fluence. These results demonstrate local modification of sp{sup 2}-carbon bonding structures with optical pulse fluences as low as 14 mJ/cm{sup 2}, an order-of-magnitude lower than measured and theoretical ablation thresholds.

36 MATERIALS SCIENCE↗
DOE OSTI2012

Determination of optical damage cross-sections and volumes surrounding ion bombardment tracks in GaAs using coherent acoustic phonon spectroscopy

We report the results of coherent acoustic phonon spectroscopy analysis of band-edge optical modification of GaAs irradiated with 400 keV Ne{sup ++} for doses between 10{sup 11}-10{sup 13} cm{sup -2}. We relate this optical modification to the structural damage density as predicted by simulation and verified by ion channeling analysis. Crystal damage is observed to cause optical modification that reduces the amplitude of the optoacoustic signal. The depth-dependent nature of the optoacoustic measurement allows us to determine optical damage cross-sections along the ion track, which are found to vary as a function of position along the track. Unexpectedly, we find that this optical modification is primarily dependent on the structural damage density and insensitive to the specific defect configuration along the ion track, suggesting that a simple model of defect density along the track is sufficient to characterize the observed optical changes. The extent of optical modification is strongly probe frequency-dependent as the frequency is detuned from the GaAs band edge. As determined from the experimental measurements, the spatial extent of optical modification exceeds the spatial extent of the structural disorder by an order of magnitude.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2012

Laser damage threshold measurements of optical materials for direct laser accelerators

The laser-damage threshold is a fundamental limit for any dielectric laser-driven accelerator and is set by the material of the structure. In this paper, we present a theoretical model of the laser damage mechanism, in comparison with experimental data on the damage threshold of silicon. Additionally, we present damage threshold measurement data of various optical materials, most of which have not been previously characterized in the picosecond-regime.

36 MATERIALS SCIENCE↗
DOE OSTI2014

Observed damage during Argon gas cluster depth profiles of compound semiconductors

Argon Gas Cluster Ion Beam (GCIB) sources have become very popular in XPS and SIMS in recent years, due to the minimal chemical damage they introduce in the depth-profiling of polymer and other organic materials. These GCIB sources are therefore particularly useful for depth-profiling polymer and organic materials, but also (though more slowly) the surfaces of inorganic materials such as semiconductors, due to the lower roughness expected in cluster ion sputtering compared to that introduced by monatomic ions. We have examined experimentally a set of five compound semiconductors, cadmium telluride (CdTe), gallium arsenide (GaAs), gallium phosphide (GaP), indium arsenide (InAs), and zinc selenide (ZnSe) and a high-κ dielectric material, hafnium oxide (HfO), in their response to argon cluster profiling. An experimentally determined HfO etch rate of 0.025 nm/min (3.95 × 10{sup −2} amu/atom in ion) for 6 keV Ar gas clusters is used in the depth scale conversion for the profiles of the semiconductor materials. The assumption has been that, since the damage introduced into polymer materials is low, even though sputter yields are high, then there is little likelihood of damaging inorganic materials at all with cluster ions. This seems true in most cases; however, in this work, we report for the first time that this damage can in fact be very significant in the case of InAs, causing the formation of metallic indium that is readily visible even to the naked eye.

36 MATERIALS SCIENCE↗
DOE OSTI2015

Fatigue crack damage detection using subharmonic component with nonlinear boundary condition

In recent years, researchers have focused on structural health monitoring (SHM) and damage detection techniques using nonlinear vibration and nonlinear ultrasonic methods. Fatigue cracks may exhibit contact acoustic nonlinearity (CAN) with distinctive features such as superharmonics and subharmonics in the power spectrum of the sensing signals. However, challenges have been noticed in the practical applications of the harmonic methods. For instance, superharmonics can also be generated by the piezoelectric transducers and the electronic equipment; super/subharmonics may also stem from the nonlinear boundary conditions such as structural fixtures and joints. It is hard to tell whether the nonlinear features come from the structural damage or the intrinsic nonlinear boundary conditions. The objective of this paper is to demonstrate the application of nonlinear ultrasonic subharmonic method for detecting fatigue cracks with nonlinear boundary conditions. The fatigue crack was qualitatively modeled as a single-degree-of-freedom (SDOF) system with non-classical hysteretic nonlinear interface forces at both sides of the crack surfaces. The threshold of subharmonic generation was studied, and the influence of crack interface parameters on the subharmonic resonance condition was investigated. The different threshold behaviors between the nonlinear boundary condition and the fatigue crack was found, which can be used to distinguish the source of nonlinear subharmonic features. To evaluate the proposed method, experiments of an aluminum plate with a fatigue crack were conducted to quantitatively verify the subharmonic resonance range. Two surface-bonded piezoelectric transducers were used to generate and receive ultrasonic wave signals. The fatigue damage was characterized in terms of a subharmonic damage index. The experimental results demonstrated that the subharmonic component of the sensing signal can be used to detect the fatigue crack and further distinguish it from inherent nonlinear boundary conditions.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2015

Identification of the formation phases of filamentary damage induced by nanosecond laser pulses in bulk fused silica

Employing a pump-probe polarization-based two-frame shadowgraphy setup, the formation of filamentary damage induced in bulk fused silica by a nanosecond pulse at 1064 nm is investigated with a picosecond probe. Three different phases are exhibited in the damage experiments. The first phase is the formation of a micrometric plasma channel along the laser direction during the beginning of the pulse likely caused by multi-photon ionization. This channel exhibits growth during ∼400 ps, and the newly grown plasma is discrete. Then, during the end of the pulse, this channel evolves into a tadpole-like morphology showing an elliptical head upstream the laser flux followed by a thin tail. This observed asymmetry is attributed to shielding effects caused by both the plasma and hot modified silica. Once the damage shows its almost final morphology, a last phase consists in the launch of a pressure wave enlarging it after the laser pulse. The physical mechanisms that might be involved in the formation of plasma channels are discussed. The experimental data are first confronted to the moving breakdown model which overestimates the filamentary damage length. Finally, taking into account the temporal shape of the laser pulses, the coupling between Kerr-induced self-focusing and stimulated Brillouin scattering is discussed to interpret the observations.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2016

Damage threshold of coating materials on x-ray mirror for x-ray free electron laser

We evaluated the damage threshold of coating materials such as Mo, Ru, Rh, W, and Pt on Si substrates, and that of uncoated Si substrate, for mirror optics of X-ray free electron lasers (XFELs). Focused 1 μm (full width at half maximum) XFEL pulses with the energies of 5.5 and 10 keV, generated by the SPring-8 angstrom compact free electron laser (SACLA), were irradiated under the grazing incidence condition. The damage thresholds were evaluated by in situ measurements of X-ray reflectivity degradation during irradiation by multiple pulses. The measured damage fluences below the critical angles were sufficiently high compared with the unfocused SACLA beam fluence. Rh coating was adopted for two mirror systems of SACLA. One system was a beamline transport mirror system that was partially coated with Rh for optional utilization of a pink beam in the photon energy range of more than 20 keV. The other was an improved version of the 1 μm focusing mirror system, and no damage was observed after one year of operation.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2016

Damage-plasticity model of the host rock in a nuclear waste repository

The paper describes damage-plasticity model for the modelling of the host rock environment of a nuclear waste repository. Radioactive Waste Repository Authority in Czech Republic assumes the repository to be in a granite rock mass which exhibit anisotropic behaviour where the strength in tension is lower than in compression. In order to describe this phenomenon, the damage-plasticity model is formulated with the help of the Drucker-Prager yield criterion which can be set to capture the compression behaviour while the tensile stress states is described with the help of scalar isotropic damage model. The concept of damage-plasticity model was implemented in the SIFEL finite element code and consequently, the code was used for the simulation of the Äspö Pillar Stability Experiment (APSE) which was performed in order to determine yielding strength under various conditions in similar granite rocks as in Czech Republic. The results from the performed analysis are presented and discussed in the paper.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2016

Radiation damage limits to XPCS studies of protein dynamics

The limitations to x-ray photon correlation spectroscopy (XPCS) imposed by radiation damage have been evaluated for suspensions of alpha crystallin. We find that the threshold for radiation damage to the measured protein diffusion rate is significantly lower than the threshold for damage to the protein structure. We provide damage thresholds beyond which the measured diffusion coeffcients have been modified using both XPCS and dynamic light scattering (DLS).

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2019

Non-thermal fluence threshold for femtosecond pulsed x-ray radiation damage in perovskite complex oxide epitaxial heterostructures

Intense hard x-ray pulses from a free-electron laser induce irreversible structural damage in a perovskite oxide epitaxial heterostructure when pulse fluences exceed a threshold value. The intensity of x-ray diffraction from a 25-nm thick epitaxial BiFeO 3 layer on a SrTiO 3 (STO) substrate measured using a series of pulses decreases abruptly with a per-pulse fluence of 2.7 x 10(6) photons mu m -2 at a photon energy of 9.7 keV but remains constant for 1.3 x 10 6 photons mu m -2 or less. The damage resulted in the destruction of the BiFeO 3 thin film within the focal spot area and the formation of a deep cavity penetrating into the STO substrate via the removal of tens of nanometers of material per pulse. The damage threshold occurs at a fluence that is insufficient to heat the absorption volume to the melting point. The morphology of the ablated sample is consistent with fracture rather than melting. Together, these results indicate that the damage occurs via a nonthermal process consistent with ultrafast ionization of the absorption volume.

36 MATERIALS SCIENCE↗