Radiation-damage-induced phasing: a case study using UV irradiation with light-emitting diodes.

PubMed

de Sanctis, Daniele; Zubieta, Chloe; Felisaz, Franck; Caserotto, Hugo; Nanao, Max H

2016-03-01

Exposure to X-rays, high-intensity visible light or ultraviolet radiation results in alterations to protein structure such as the breakage of disulfide bonds, the loss of electron density at electron-rich centres and the movement of side chains. These specific changes can be exploited in order to obtain phase information. Here, a case study using insulin to illustrate each step of the radiation-damage-induced phasing (RIP) method is presented. Unlike a traditional X-ray-induced damage step, specific damage is introduced via ultraviolet light-emitting diodes (UV-LEDs). In contrast to UV lasers, UV-LEDs have the advantages of small size, low cost and relative ease of use.

Structural Health Monitoring of a Composite Panel Based on PZT Sensors and a Transfer Impedance Framework.

PubMed

Dziendzikowski, Michal; Niedbala, Patryk; Kurnyta, Artur; Kowalczyk, Kamil; Dragan, Krzysztof

2018-05-11

One of the ideas for development of Structural Health Monitoring (SHM) systems is based on excitation of elastic waves by a network of PZT piezoelectric transducers integrated with the structure. In the paper, a variant of the so-called Transfer Impedance (TI) approach to SHM is followed. Signal characteristics, called the Damage Indices (DIs), were proposed for data presentation and analysis. The idea underlying the definition of DIs was to maintain most of the information carried by the voltage induced on PZT sensors by elastic waves. In particular, the DIs proposed in the paper should be sensitive to all types of damage which can influence the amplitude or the phase of the voltage induced on the sensor. Properties of the proposed DIs were investigated experimentally using a GFRP composite panel equipped with PZT networks attached to its surface and embedded into its internal structure. Repeatability and stability of DI indications under controlled conditions were verified in tests. Also, some performance indicators for surface-attached and structure-embedded sensors were obtained. The DIs' behavior was dependent mostly on the presence of a simulated damage in the structure. Anisotropy of mechanical properties of the specimen, geometrical properties of PZT network as well as, to some extent, the technology of sensor integration with the structure were irrelevant for damage indication. This property enables the method to be used for damage detection and classification.

Track Structure and the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage

NASA Technical Reports Server (NTRS)

George, K.; Hada, M.; Chappell, L.; Cucinotta, F. A.

2011-01-01

Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to195 keV/micron. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons.

Parvovirus infection-induced DNA damage response

PubMed Central

Luo, Yong; Qiu, Jianming

2014-01-01

Parvoviruses are a group of small DNA viruses with ssDNA genomes flanked by two inverted terminal structures. Due to a limited genetic resource they require host cellular factors and sometimes a helper virus for efficient viral replication. Recent studies have shown that parvoviruses interact with the DNA damage machinery, which has a significant impact on the life cycle of the virus as well as the fate of infected cells. In addition, due to special DNA structures of the viral genomes, parvoviruses are useful tools for the study of the molecular mechanisms underlying viral infection-induced DNA damage response (DDR). This review aims to summarize recent advances in parvovirus-induced DDR, with a focus on the diverse DDR pathways triggered by different parvoviruses and the consequences of DDR on the viral life cycle as well as the fate of infected cells. PMID:25429305

Ultrastructural study of mitochondrial damage in CHO cells exposed to hyperthermia.

PubMed

Cole, A; Armour, E P

1988-09-01

A unique direct-view stereo electron microscope technique was used to visualize the structure and three-dimensional distributions of mitochondria in CHO cells in situ following hyperthermic treatments. Aberrations induced by various heating regimens were recorded. The protocol included a trypsin digestion that may have enhanced the expression of the initial heat damage. The developed damage was observed as increasing levels of mitochondrial distortion, swelling, and dissociation. Minimal damage was induced at 42 degrees C for exposures of up to 4 h, while significant damage was induced at 43 degrees C for exposures of more than 30 min and at 45 degrees C for exposures of more than 10 min. For moderate exposures, a partial recovery of mitochondrial integrity was observed when the heat treatment was followed by incubation at 37 degrees C for 24 h. Mitochondrial damage was related to the heat dose in that increasing treatment temperature resulted in greater damage, but when compared to cell survival the damage did not parallel cell killing under all time-temperature conditions.

MAPPING TOXICANT-INDUCED NERVOUS SYSTEM DAMAGE WITH A CUPRIC SILVER STAIN: A QUANTITATIVE ANALYSIS OF NEURAL DEGENERATION INDUCED BY 3,4-METHYLENEDIOXYMETHAMPETHAMINE (MDMA)

EPA Science Inventory

The purpose of structural assessments in neurotoxicology is to provide a convincing picture of the location and extent of damage to the nervous system. ilver stains that selectively reveal neural degeneration hold particular promise in this regard. n this chapter we describe resu...

Laser induced photoreceptor damage and recovery in the high numerical aperture eye of the garter snake.

PubMed

Zwick, H; Edsall, P; Stuck, B E; Wood, E; Elliott, R; Cheramie, R; Hacker, H

2008-02-01

The garter snake provides a unique model for in-vivo imaging of photoreceptor damage induced by laser retinal exposure. Laser thermal/mechanical retinal injury induced alterations in photoreceptor structure and leukocyte cellular behavior. Photoreceptors turned white, lost mode structure, and swelled; leukocyte activity was observed in the vicinity of photoreceptor cells. Non-thermal alterations were identified with a bio-tag for oxidative stress. Mechanisms of photoreceptor recovery and replacement were observed and evaluated for active cytoskeletal systems by using an anti-actin tag that could detect the presence of active cytoskeletal systems resident in photoreceptors as well as other retinal systems.

NAD+ administration significantly attenuates synchrotron radiation X-ray-induced DNA damage and structural alterations of rodent testes

PubMed Central

Sheng, Caibin; Chen, Heyu; Wang, Ban; Liu, Tengyuan; Hong, Yunyi; Shao, Jiaxiang; He, Xin; Ma, Yingxin; Nie, Hui; Liu, Na; Xia, Weiliang; Ying, Weihai

2012-01-01

Synchrotron radiation (SR) X-ray has great potential for its applications in medical imaging and cancer treatment. In order to apply SR X-ray in clinical settings, it is necessary to elucidate the mechanisms underlying the damaging effects of SR X-ray on normal tissues, and to search for the strategies to reduce the detrimental effects of SR X-ray on normal tissues. However, so far there has been little information on these topics. In this study we used the testes of rats as a model to characterize SR X-ray-induced tissue damage, and to test our hypothesis that NAD+ administration can prevent SR X-ray-induced injury of the testes. We first determined the effects of SR X-ray at the doses of 0, 0.5, 1.3, 4 and 40 Gy on the biochemical and structural properties of the testes one day after SR X-ray exposures. We found that 40 Gy of SR X-ray induced a massive increase in double-strand DNA damage, as assessed by both immunostaining and Western blot of phosphorylated H2AX levels, which was significantly decreased by intraperitoneally (i.p.) administered NAD+ at doses of 125 and 625 mg/kg. Forty Gy of SR X-ray can also induce marked increases in abnormal cell nuclei as well as significant decreases in the cell layers of the seminiferous tubules one day after SR X-ray exposures, which were also ameliorated by the NAD+ administration. In summary, our study has shown that SR X-ray can produce both molecular and structural alterations of the testes, which can be significantly attenuated by NAD+ administration. These results have provided not only the first evidence that SR X-ray-induced tissue damage can be ameliorated by certain approaches, but also a valuable basis for elucidating the mechanisms underlying SR X-ray-induced tissue injury. PMID:22518270

Modelling and Holographic Visualization of Space Radiation-Induced DNA Damage

NASA Technical Reports Server (NTRS)

Plante, Ianik

2017-01-01

Space radiation is composed by a mixture of ions of different energies. Among these, heavy inos are of particular importance because their health effects are poorly understood. In. the recent years, a software named RITRACKS (Relativistic Ion Tracks) was developed to simulate the detailed radiation track structure, several DNA models and DNA damage. As the DNA structure is complex due to packing, it is difficult to the damage using a regular computer screen.

Dissecting the Molecular Mechanism of Ionizing Radiation-Induced Tissue Damage in the Feather Follicle

PubMed Central

Chen, Xi; Liao, Chunyan; Chu, Qiqi; Zhou, Guixuan; Lin, Xiang; Li, Xiaobo; Lu, Haijie; Xu, Benhua; Yue, Zhicao

2014-01-01

Ionizing radiation (IR) is a common therapeutic agent in cancer therapy. It damages normal tissue and causes side effects including dermatitis and mucositis. Here we use the feather follicle as a model to investigate the mechanism of IR-induced tissue damage, because any perturbation of feather growth will be clearly recorded in its regular yet complex morphology. We find that IR induces defects in feather formation in a dose-dependent manner. No abnormality was observed at 5 Gy. A transient, reversible perturbation of feather growth was induced at 10 Gy, leading to defects in the feather structure. This perturbation became irreversible at 20 Gy. Molecular and cellular analysis revealed P53 activation, DNA damage and repair, cell cycle arrest and apoptosis in the pathobiology. IR also induces patterning defects in feather formation, with disrupted branching morphogenesis. This perturbation is mediated by cytokine production and Stat1 activation, as manipulation of cytokine levels or ectopic Stat1 over-expression also led to irregular feather branching. Furthermore, AG-490, a chemical inhibitor of Stat1 signaling, can partially rescue IR-induced tissue damage. Our results suggest that the feather follicle could serve as a useful model to address the in vivo impact of the many mechanisms of IR-induced tissue damage. PMID:24586618

Study of RF breakdown and multipacting in accelerator components

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pande, Manjiri; Singh, P., E-mail: manjiri@barc.gov.in, E-mail: psingh@barc.gov.in

2014-07-01

Radio frequency (RF) structures that are part of accelerators and energy sources, operate with sinusoidally varying electromagnetic fields under high RF energy. Here, RF breakdown and multipacting take place in RF structures and limit their performance. Electron field emission processes in a RF structure are precursors for breakdown processes. RF breakdown is a major phenomena affecting and causing the irreversible damage to RF structures. Breakdown rate and the damage induced by the breakdowns are its important properties. The damage is related to power absorbed during breakdown, while the breakdown rate is determined by the amplitudes of surface electric and magneticmore » fields, geometry, metal surface preparation and conditioning history. It limits working power and produces irreversible surface damage. The breakdown limit depends on the RF circuit, structure geometry, RF frequency, input RF power, pulse width, materials used, surface processing technique and surface electric and magnetic fields. Multipactor (MP) is a low power, electron multiplication based resonance breakdown phenomenon in vacuum and is often observed in RF structures. A multipactor discharge is undesirable, as it can create a reactive component that detunes the resonant cavities and components, generates noise in communication system and induces gas desorption from the conductor surfaces. In RF structures, certain conditions are required to generate multipacting. (author)« less

Effect of Shock-Induced Cavitation Bubble Collapse on the damage in the Simulated Perineuronal Net of the Brain.

PubMed

Wu, Yuan-Ting; Adnan, Ashfaq

2017-07-13

The purpose of this study is to conduct modeling and simulation to understand the effect of shock-induced mechanical loading, in the form of cavitation bubble collapse, on damage to the brain's perineuronal nets (PNNs). It is known that high-energy implosion due to cavitation collapse is responsible for corrosion or surface damage in many mechanical devices. In this case, cavitation refers to the bubble created by pressure drop. The presence of a similar damage mechanism in biophysical systems has long being suspected but not well-explored. In this paper, we use reactive molecular dynamics (MD) to simulate the scenario of a shock wave induced cavitation collapse within the perineuronal net (PNN), which is the near-neuron domain of a brain's extracellular matrix (ECM). Our model is focused on the damage in hyaluronan (HA), which is the main structural component of PNN. We have investigated the roles of cavitation bubble location, shockwave intensity and the size of a cavitation bubble on the structural evolution of PNN. Simulation results show that the localized supersonic water hammer created by an asymmetrical bubble collapse may break the hyaluronan. As such, the current study advances current knowledge and understanding of the connection between PNN damage and neurodegenerative disorders.

Electromagnetically induced acoustic emission—novel NDT technique for damage evaluation

NASA Astrophysics Data System (ADS)

Finkel, P.; Godinez, V.; Miller, R.; Finlayson, R.

2001-04-01

A recently developed electromagnetically induced acoustic emission technique (EM AE) which can be used for damage assessment of thin walled conducting structures is described. This technique allows a structure to be loaded locally by applying an electromagnetic field in order to produce an AE response, which may be captured by conventional or fiber optic (FO) AE sensors. The advantage of this technique is that the localized dynamic stresses induced by a short current pulse in the presence of an external magnetic field aid in the detection of cracks. Also, it is shown that electromagnetic stimulation can be applied to enhance conventional ultrasonics by modulation of the scattered signal from the defect (EM UT). Experimental data is presented for the case of a fatigue crack near rivet holes in thin walled aluminum structures.

Radiation damage to macromolecules: kill or cure?

PubMed

Garman, Elspeth F; Weik, Martin

2015-03-01

Radiation damage induced by X-ray beams during macromolecular diffraction experiments remains an issue of concern in structural biology. While advances in our understanding of this phenomenon, driven in part by a series of workshops in this area, undoubtedly have been and are still being made, there are still questions to be answered. Eight papers in this volume give a flavour of ongoing investigations, addressing various issues. These range over: a proposed new metric derived from atomic B-factors for identifying potentially damaged amino acid residues, a study of the relative damage susceptibility of protein and DNA in a DNA/protein complex, a report of an indication of specific radiation damage to a protein determined from data collected using an X-ray free-electron laser (FEL), an account of the challenges in FEL raw diffraction data analysis, an exploration of the possibilities of using radiation damage induced phasing to solve structures using FELs, simulations of radiation damage as a function of FEL temporal pulse profiles, results on the influence of radiation damage during scanning X-ray diffraction measurements and, lastly, consideration of strategies for minimizing radiation damage during SAXS experiments. In this short introduction, these contributions are briefly placed in the context of other current work on radiation damage in the field.

Structural Health Monitoring of a Composite Panel Based on PZT Sensors and a Transfer Impedance Framework

PubMed Central

Dziendzikowski, Michal; Niedbala, Patryk; Kurnyta, Artur; Kowalczyk, Kamil; Dragan, Krzysztof

2018-01-01

One of the ideas for development of Structural Health Monitoring (SHM) systems is based on excitation of elastic waves by a network of PZT piezoelectric transducers integrated with the structure. In the paper, a variant of the so-called Transfer Impedance (TI) approach to SHM is followed. Signal characteristics, called the Damage Indices (DIs), were proposed for data presentation and analysis. The idea underlying the definition of DIs was to maintain most of the information carried by the voltage induced on PZT sensors by elastic waves. In particular, the DIs proposed in the paper should be sensitive to all types of damage which can influence the amplitude or the phase of the voltage induced on the sensor. Properties of the proposed DIs were investigated experimentally using a GFRP composite panel equipped with PZT networks attached to its surface and embedded into its internal structure. Repeatability and stability of DI indications under controlled conditions were verified in tests. Also, some performance indicators for surface-attached and structure-embedded sensors were obtained. The DIs’ behavior was dependent mostly on the presence of a simulated damage in the structure. Anisotropy of mechanical properties of the specimen, geometrical properties of PZT network as well as, to some extent, the technology of sensor integration with the structure were irrelevant for damage indication. This property enables the method to be used for damage detection and classification. PMID:29751664

Resilience of branching and massive corals to wave loading under sea level rise--a coupled computational fluid dynamics-structural analysis.

PubMed

Baldock, Tom E; Karampour, Hassan; Sleep, Rachael; Vyltla, Anisha; Albermani, Faris; Golshani, Aliasghar; Callaghan, David P; Roff, George; Mumby, Peter J

2014-09-15

Measurements of coral structural strength are coupled with a fluid dynamics-structural analysis to investigate the resilience of coral to wave loading under sea level rise and a typical Great Barrier Reef lagoon wave climate. The measured structural properties were used to determine the wave conditions and flow velocities that lead to structural failure. Hydrodynamic modelling was subsequently used to investigate the type of the bathymetry where coral is most vulnerable to breakage under cyclonic wave conditions, and how sea level rise (SLR) changes this vulnerability. Massive corals are determined not to be vulnerable to wave induced structural damage, whereas branching corals are susceptible at wave induced orbital velocities exceeding 0.5m/s. Model results from a large suite of idealised bathymetry suggest that SLR of 1m or a loss of skeleton strength of order 25% significantly increases the area of reef flat where branching corals are exposed to damaging wave induced flows. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Damage-Dependent Finite Element Analysis for Fiber-Reinforced Composite Laminates

NASA Technical Reports Server (NTRS)

Coats, Timothy W.; Harris, Charles E.

1998-01-01

A progressive damage methodology has been developed to predict damage growth and residual strength of fiber-reinforced composite structure with through penetrations such as a slit. The methodology consists of a damage-dependent constitutive relationship based on continuum damage mechanics. Damage is modeled using volume averaged strain-like quantities known as internal state variables and is represented in the equilibrium equations as damage induced force vectors instead of the usual degradation and modification of the global stiffness matrix.

Photoluminescence Study of Plasma-Induced Damage of GaInN Single Quantum Well

NASA Astrophysics Data System (ADS)

Izumi, Shouichiro; Minami, Masaki; Kamada, Michiru; Tatsumi, Tetsuya; Yamaguchi, Atsushi A.; Ishikawa, Kenji; Hori, Masaru; Tomiya, Shigetaka

2013-08-01

Plasma-induced damage (PID) due to Cl2/SiCl4/Ar plasma etching of the GaN capping layer (CAP)/GaInN single quantum well (SQW)/GaN structure was investigated by conventional photoluminescence (PL), transmission electron microscopy (TEM), and time-resolved and temperature-dependent photoluminescence (TRPL). SQW PL intensity remained constant initially, although plasma etching of the CAP layer proceeded, but when the etching thickness reached a certain amount (˜60 nm above the SQW), PL intensity started to decrease sharply. On the other hand, TEM observations show that the physical damage (structural damage) was limited to the topmost surface region. These findings can be explained by the results of TRPL studies, which revealed that there exist two different causes of PID. One is an increase in the number of nonradiative recombination centers, which mainly affects the PL intensity. The other is an increase in the quantum level fluctuation owing mainly to physical damage.

Multi-scale fracture damage associated with underground chemical explosions

NASA Astrophysics Data System (ADS)

Swanson, E. M.; Sussman, A. J.; Wilson, J. E.; Townsend, M. J.; Prothro, L. B.; Gang, H. E.

2018-05-01

Understanding rock damage induced by explosions is critical for a number of applications including the monitoring and verification of underground nuclear explosions, mine safety issues, and modeling fluid flow through fractured rock. We use core observations, televiewer logs, and thin section observations to investigate fracture damage associated with two successive underground chemical explosions (SPE2 and SPE3) in granitic rock at both the mesoscale and microscale. We compare the frequency and orientations of core-scale fractures, and the frequency of microfractures, between a pre-experiment core and three post-experiment cores. Natural fault zones and explosion-induced fractures in the vicinity of the explosive source are readily apparent in recovered core and in thin sections. Damage from faults and explosions is not always apparent in fracture frequency plots from televiewer logs, although orientation data from these logs suggests explosion-induced fracturing may not align with the pre-existing fracture sets. Core-scale observations indicate the extent of explosion-induced damage is 10.0 m after SPE2 and 6.8 m after SPE3, despite both a similar size and location for both explosions. At the microscale, damage is observed to a range distance of 10.2 ± 0.9 m after SPE2, and 16.6 ± 0.9 and 11.2 ± 0.6 in two different cores collected after SPE3. Additional explosion-induced damage, interpreted to be the result of spalling, is readily apparent near the surface, but only in the microfracture data. This depth extent and intensity of damage in the near-surface region also increased after an additional explosion. This study highlights the importance of evaluating structural damage at multiple scales for a more complete characterization of the damage, and particularly shows the importance of microscale observations for identifying spallation-induced damage.

Nonlinear Dynamic Behavior of Impact Damage in a Composite Skin-Stiffener Structure

NASA Technical Reports Server (NTRS)

Ooijevaar, T. H.; Rogge, M. D.; Loendersloot, R.; Warnet, L.; Akkerman, R.; deBoer, A.

2013-01-01

One of the key issues in composite structures for aircraft applications is the early identification of damage. Often, service induced damage does not involve visible plastic deformation, but internal matrix related damage, like delaminations. A wide range of technologies, comprising global vibration and local wave propagation methods can be employed for health monitoring purposes. Traditional low frequency modal analysis based methods are linear methods. The effectiveness of these methods is often limited since they rely on a stationary and linear approximation of the system. The nonlinear interaction between a low frequency wave field and a local impact induced skin-stiffener failure is experimentally demonstrated in this paper. The different mechanisms that are responsible for the nonlinearities (opening, closing and contact) of the distorted harmonic waveforms are separated with the help of phase portraits. A basic analytical model is employed to support the observations.

Ion irradiation-induced crystal structure changes in inverse spinel MgIn 2O 4

DOE PAGES

Tang, Ming; Valdez, James A.; Wang, Yongqiang; ...

2016-07-29

We performed 400 keV Ne and 200 keV He ion irradiations on fully inverse MgIn 2O 4 samples at cryogenic temperature (~ 77 K), in order to examine the influence of radiation-induced cation disordering on crystal structure. In the case of MgIn 2O 4 samples irradiated with Ne ions to a peak displacement damage dose of 4 displacements per atom (dpa), a spinel-to-rocksalt phase transformation was observed. Conversely, for MgIn 2O 4 samples irradiated with He ions to a peak displacement damage dose of 5 dpa, the only observed structural effect involved cation rearrangements from an inverse to a “random”more » spinel structure.« less

Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney.

PubMed

Cano-Europa, Edgar; Blas-Valdivia, Vanessa; Franco-Colin, Margarita; Gallardo-Casas, Carlos Angel; Ortiz-Butrón, Rocio

2011-01-01

It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T₄ injection (20 μg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T₄ showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T₄ completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole. Copyright © 2009 Elsevier GmbH. All rights reserved.

Measurement of changes in impedance of DNA nanowires due to radiation induced structural damage. A novel approach for a DNA-based radiosensitive device

NASA Astrophysics Data System (ADS)

Heimbach, Florian; Arndt, Alexander; Nettelbeck, Heidi; Langner, Frank; Giesen, Ulrich; Rabus, Hans; Sellner, Stefan; Toppari, Jussi; Shen, Boxuan; Baek, Woon Yong

2017-08-01

The ability of DNA to conduct electric current has been the topic of numerous investigations over the past few decades. Those investigations indicate that this ability is dependent on the molecular structure of the DNA. Radiation-induced damages, which lead to an alteration of the molecular structure, should therefore change the electrical impedance of a DNA molecule. In this paper, the damage due to ionising radiation is shown to have a direct effect on the electrical transport properties of DNA. Impedance measurements of DNA samples were carried out by an AC impedance spectrometer before, during and after irradiation. The samples comprised of DNA segments, which were immobilized between gold electrodes with a gap of 12 μm. The impedance of all DNA samples exhibited rising capacitive behaviour with increasing absorbed dose.

Neuroprotective effects of Bacopa monniera whole-plant extract against aluminum-induced hippocampus damage in rats: evidence from electron microscopic images.

PubMed

Nannepaga, John Sushma; Korivi, Mallikarjuna; Tirumanyam, Madhavi; Bommavaram, Mahitha; Kuo, Chia-Hua

2014-10-31

Impaired antioxidant system and structural changes in hippocampus are considered as key instigators of neurodegenerative diseases. The present study aimed to investigate the antioxidant and tissue protective properties of Bacopa monniera whole-plant extract (BME) against aluminum (Al)- induced oxidative stress and hippocampus damage in rats. Male Wistar rats were evenly divided into four groups, nine in each and labeled as control, Al treated (10 mg/kg), BME administered (40 mg/kg) and combination of both Al plus BME (Al+BME) treated groups. After one month of treatment by oral administration, antioxidant status was determined, and structural changes in the hippocampus were evaluated by electron microscopy. Al-induced increased oxidative damage in the hippocampus was revealed by elevated thiobarbituric acid reactive substances (TBARS). This increased lipid peroxidation was associated with significantly decreased antioxidant enzyme activities, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). However, aluminum intoxicated rats treated with BME for 30 days showed significantly restored antioxidant enzyme activities along with decreased TBARS (P < 0.01). Further evidences from electron micrographs clearly indicated that Al-induced vacuolation, lipofuscin deposition and pyramidal cell degeneration in the hippocampus was attenuated with co-administration of the whole-plant extract. Our results demonstrate that structural derangement in hippocampus by aluminum is directly proportionate with increased lipid peroxidation. Nevertheless, B. monniera treatment potentiates the antioxidant status and suppressed the tissue damage induced by Al-intoxication. These findings suggest that B. monniera whole-plant extracts can be considered as a possible remedy to counteract aluminum-associated neurological disorders.

First-Principles Investigation of Radiation Induced Defects in SiC and Si.

NASA Astrophysics Data System (ADS)

Windl, Wolfgang; Lenosky, Thomas J.; Kress, Joel D.; Voter, Arthur F.

1997-03-01

SiC shows promise as a structural material for fusion reactors, partly because of its low activation under neutron irradiation. This radiation, however, can cause damage to its crystal structure, thereby degrading its properties. The focus of this work is the understanding of this neutron-induced radiation damage to SiC. Neutrons interact with matter primarily by scattering off nuclei, an event which suddenly imparts energy and momentum to an atom. If enough energy is transferred, this scattering event creates structural damage, such as displacement of the impacted atom from its original position to an interstitial site. We performed quantum molecular dynamics simulations to determine the displacement energy threshold, i.e., the minimum energy transfer required to create damage. To do this, we used the self-consistent Demkov-Ortega-Grumbach-Sankey (DOGS) extension(A. A. Demkov et al.), Phys. Rev. B 52, 1618 (1995). of the Harris-functional local orbital LDA method of Sankey et al. In order to benchmark the quality of our methodology for studying radiation damage, we compare our results to those of calculations employing classical interatomic potentials; furthermore, we performed similar simulations for Si, where experimental data exist.

Effects of low and high energy ion bombardment on ETFE polymer

NASA Astrophysics Data System (ADS)

Minamisawa, R. A.; De Almeida, A.; Abidzina, V.; Parada, M. A.; Muntele, I.; Ila, D.

2007-04-01

The polymer ethylenetetrafluoroethylene (ETFE) is used as anti-adherent coatings for food packages and radiation dosimeters. In this work, we compare the damage induced in ETFE bombarded with 100 keV Si ions with that induced by 1 MeV proton bombardment. The damage depends on the type, energy and intensity of the irradiation. Irradiated films were analyzed with optical absorption photospectrometry, Raman spectroscopy and Fourier transform infrared (FTIR) spectroscopy to determine the chemical nature of the structural changes caused by ion irradiation. Computer simulations were performed to evaluate the radiation damage.

A life prediction model for laminated composite structural components

NASA Technical Reports Server (NTRS)

Allen, David H.

1990-01-01

A life prediction methodology for laminated continuous fiber composites subjected to fatigue loading conditions was developed. A summary is presented of research completed. A phenomenological damage evolution law was formulated for matrix cracking which is independent of stacking sequence. Mechanistic and physical support was developed for the phenomenological evolution law proposed above. The damage evolution law proposed above was implemented to a finite element computer program. And preliminary predictions were obtained for a structural component undergoing fatigue loading induced damage.

Optical and electrical characterization methods of plasma-induced damage in silicon nitride films

NASA Astrophysics Data System (ADS)

Kuyama, Tomohiro; Eriguchi, Koji

2018-06-01

We proposed evaluation methods of plasma-induced damage (PID) in silicon nitride (SiN) films. The formation of an oxide layer by air exposure was identified for damaged SiN films by X-ray photoelectron spectroscopy (XPS). Bruggeman’s effective medium approximation was employed for an optical model consisting of damaged and undamaged layers, which is applicable to an in-line monitoring by spectroscopic ellipsometry (SE). The optical thickness of the damaged layer — an oxidized layer — extended after plasma exposure, which was consistent with the results obtained by a diluted hydrofluoric acid (DHF) wet etching. The change in the conduction band edge of the damaged SiN films was presumed from two electrical techniques, i.e., current–voltage (I–V) measurement and time-dependent dielectric breakdown (TDDB) test with a constant voltage stress. The proposed techniques can be used for assigning the plasma-induced structural change in an SiN film widely used as an etch-protecting layer.

Few-cycle pulse laser induced damage threshold determination of ultra-broadband optics.

PubMed

Kafka, Kyle R P; Talisa, Noah; Tempea, Gabriel; Austin, Drake R; Neacsu, Catalin; Chowdhury, Enam A

2016-12-12

A systematic study of few-cycle pulse laser induced damage threshold (LIDT) determination was performed for commercially-available ultra-broadband optics, (i.e. chirped mirrors, silver mirrors, beamsplitters, etc.) in vacuum and in air, for single and multi-pulse regime (S-on-1). Multi-pulse damage morphology at fluences below the single-pulse LIDT was studied in order to investigate the mechanisms leading to the onset of damage. Stark morphological contrast was observed between multi-pulse damage sites formed in air versus those in vacuum. One effect of vacuum testing compared to air included suppression of laser-induced periodic surface structures (LIPSS) formation, possibly influenced by a reduced presence of damage debris. Another effect of vacuum was occasional lowering of LIDT, which appears to be due to the stress-strain performance of the coating design during laser irradiation and under the external stress of vacuum ambience. A fused silica substrate is also examined, and a non-LIPSS nanostructuring is observed on the surface. Possible mechanisms are discussed.

Damage of Escherichia coli membrane by bactericidal agent polyhexamethylene guanidine hydrochloride: micrographic evidences.

PubMed

Zhou, Z X; Wei, D F; Guan, Y; Zheng, A N; Zhong, J J

2010-03-01

The purpose of this study was to provide micrographic evidences for the damaged membrane structure and intracellular structure change of Escherichia coli strain 8099, induced by polyhexamethylene guanidine hydrochloride (PHMG). The bactericidal effect of PHMG on E. coli was investigated based on beta-galactosidase activity assay, fluorescein-5-isothiocyanate confocal laser scanning microscopy, field emission scanning electron microscopy and transmission electron microscopy. The results revealed that a low dose (13 microg ml(-1)) of PHMG slightly damaged the outer membrane structure of the treated bacteria and increased the permeability of the cytoplasmic membrane, while no significant damage was observed to the morphological structure of the cells. A high dose (23 microg ml(-1)) of PHMG collapsed the outer membrane structure, led to the formation of a local membrane pore across the membrane and badly damaged the internal structure of the cells. Subsequently, intracellular components were leaked followed by cell inactivation. Dose-dependent membrane disruption was the main bactericidal mechanism of PHMG. The formation of the local membrane pores was probable after exposure to a high dose (23 microg ml(-1)) of PHMG. Micrographic evidences were provided about the damaged membrane structure and intracellular structure change of E. coli. The presented information helps understand the bactericidal mechanism of PHMG by membrane damage.

Monte Carlo approach in assessing damage in higher order structures of DNA

NASA Technical Reports Server (NTRS)

Chatterjee, A.; Schmidt, J. B.; Holley, W. R.

1994-01-01

We have developed a computer monitor of nuclear DNA in the form of chromatin fibre. The fibres are modeled as a ideal solenoid consisting of twenty helical turns with six nucleosomes per turn. The chromatin model, in combination with are Monte Carlo theory of radiation damage induces by charged particles, based on general features of tack structure and stopping power theory, has been used to evaluate the influence of DNA structure on initial damage. An interesting has emerged from our calculations. Our calculated results predict the existence of strong spatial correlations in damage sites associated with the symmetries in the solenoidal model. We have calculated spectra of short fragments of double stranded DNA produced by multiple double strand breaks induced by both high and low LET radiation. The spectra exhibit peaks at multiples of approximately 85 base pairs (the nucleosome periodicity), and approximately 1000 base pairs (solenoid periodicity). Preliminary experiments to investigate the fragment distributions from irradiated DNA, made by B. Rydberg at Lawrence Berkeley Laboratory, confirm the existence of short DNA fragments and are in substantial agreement with the predictions of our theory.

Multicomponent seismic loss estimation on the North Anatolian Fault Zone (Turkey)

NASA Astrophysics Data System (ADS)

karimzadeh Naghshineh, S.; Askan, A.; Erberik, M. A.; Yakut, A.

2015-12-01

Seismic loss estimation is essential to incorporate seismic risk of structures into an efficient decision-making framework. Evaluation of seismic damage of structures requires a multidisciplinary approach including earthquake source characterization, seismological prediction of earthquake-induced ground motions, prediction of structural responses exposed to ground shaking, and finally estimation of induced damage to structures. As the study region, Erzincan, a city on the eastern part of Turkey is selected which is located in the conjunction of three active strike-slip faults as North Anatolian Fault, North East Anatolian Fault and Ovacik fault. Erzincan city center is in a pull-apart basin underlain by soft sediments that has experienced devastating earthquakes such as the 27 December 1939 (Ms=8.0) and the 13 March 1992 (Mw=6.6) events, resulting in extensive amount of physical as well as economical losses. These losses are attributed to not only the high seismicity of the area but also as a result of the seismic vulnerability of the constructed environment. This study focuses on the seismic damage estimation of Erzincan using both regional seismicity and local building information. For this purpose, first, ground motion records are selected from a set of scenario events simulated with the stochastic finite fault methodology using regional seismicity parameters. Then, existing building stock are classified into specified groups represented with equivalent single-degree-of-freedom systems. Through these models, the inelastic dynamic structural responses are investigated with non-linear time history analysis. To assess the potential seismic damage in the study area, fragility curves for the classified structural types are derived. Finally, the estimated damage is compared with the observed damage during the 1992 Erzincan earthquake. The results are observed to have a reasonable match indicating the efficiency of the ground motion simulations and building analyses.

Doxycycline Attenuates Lipopolysaccharide-Induced Microvascular Endothelial Cell Derangements.

PubMed

Wiggins-Dohlvik, Katie; Stagg, Hayden W; Han, Min Suk; Alluri, Himakarnika; Oakley, Ryan P; Anasooya Shaji, Chinchusha; Davis, Matthew L; Tharakan, Binu

2016-06-01

Lipopolysaccharide (LPS) is known to induce vascular derangements. The pathophysiology involved therein is unknown, but matrix metalloproteinases (MMPs) may be an important mediator. We hypothesized that in vitro LPS provokes vascular permeability, damages endothelial structural proteins, and increases MMP activity; that in vivo LPS increases permeability and fluid requirements; and that the MMP inhibitor doxycycline mitigates such changes. Rat lung microvascular endothelial cells were divided into four groups: control, LPS, LPS plus doxycycline, and doxycycline. Permeability, structural proteins β-catenin and Filamentous-actin, and MMP-9 activity were examined. Sprauge Dawley rats were divided into sham, IV LPS, and IV LPS plus IV doxycycline groups. Mesenteric postcapillary venules were observed. Blood pressure was measured as animals were resuscitated and fluid requirements were compared. Statistical analysis was conducted using Student's t-test and ANOVA. In vitro LPS increased permeability, damaged adherens junctions, induced actin stress fiber formation, and increased MMP-9 enzyme activity. In vivo, IV LPS administration induced vascular permeability. During resuscitation, significantly more fluid was necessary to maintain normotension in the IV LPS group. Doxycycline mitigated all derangements observed. We conclude that LPS increases permeability, damages structural proteins, and increases MMP-9 activity in endothelial cells. Additionally, endotoxemia induces hyperpermeability and increases the amount of IV fluid required to maintain normotension in vivo. Doxycycline mitigates such changes both in vitro and in vivo. Our findings illuminate the possible role of matrix metalloproteinases in the pathophysiology of lipopolysaccharide-induced microvascular hyperpermeability and pave the way for better understanding and treatment of this process.

The Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage: Track Structure Effects and Cytogenetic Signatures of High-LET Exposure

NASA Technical Reports Server (NTRS)

George, K.; Hada, M.; Chappell, L.; Cucinotta, F. A.

2012-01-01

Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to 195 keV/micrometers. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons. All energies of protons have a much higher percentage of complex-type chromosome exchanges than gamma rays, signifying a cytogenetic signature for proton exposures.

Remote Sensing of Wildland Fire-Induced Risk Assessment at the Community Level.

PubMed

Ahmed, M Razu; Rahaman, Khan Rubayet; Hassan, Quazi K

2018-05-15

Wildland fires are some of the critical natural hazards that pose a significant threat to the communities located in the vicinity of forested/vegetated areas. In this paper, our overall objective was to study the structural damages due to the 2016 Horse River Fire (HRF) that happened in Fort McMurray (Alberta, Canada) by employing primarily very high spatial resolution optical satellite data, i.e., WorldView-2. Thus, our activities included the: (i) estimation of the structural damages; and (ii) delineation of the wildland-urban interface (WUI) and its associated buffers at certain intervals, and their utilization in assessing potential risks. Our proposed method of remote sensing-based estimates of the number of structural damages was compared with the ground-based information available from the Planning and Development Recovery Committee Task Force of Regional Municipality of Wood Buffalo (RMWB); and found a strong linear relationship (i.e., r² value of 0.97 with a slope of 0.97). Upon delineating the WUI and its associated buffer zones at 10 m, 30 m, 50 m, 70 m and 100 m distances; we found existence of vegetation within the 30 m buffers from the WUI for all of the damaged structures. In addition, we noticed that the relevant authorities had removed vegetation in some areas between 30 m and 70 m buffers from the WUI, which was proven to be effective in order to protect the structures in the adjacent communities. Furthermore, we mapped the wildland fire-induced vulnerable areas upon considering the WUI and its associated buffers. Our analysis revealed that approximately 30% of the areas within the buffer zones of 10 m and 30 m were vulnerable due to the presence of vegetation; in which, approximately 7% were burned during the 2016 HRF event that led the structural damages. Consequently, we suggest to remove the existing vegetation within these critical zones and also monitor the region at a regular interval in order to reduce the wildland fire-induced risk.

Mitigation in Multiple Effects of Graphene Oxide Toxicity in Zebrafish Embryogenesis Driven by Humic Acid.

PubMed

Chen, Yuming; Ren, Chaoxiu; Ouyang, Shaohu; Hu, Xiangang; Zhou, Qixing

2015-08-18

Graphene oxide (GO) is a widely used carbonaceous nanomaterial. To date, the influence of natural organic matter (NOM) on GO toxicity in aquatic vertebrates has not been reported. During zebrafish embryogenesis, GO induced a significant hatching delay and cardiac edema. The intensive interactions of GO with the chorion induces damage to chorion protuberances, excessive generation of (•)OH, and changes in protein secondary structure. In contrast, humic acid (HA), a ubiquitous form of NOM, significantly relieved the above adverse effects. HA reduced the interactions between GO and the chorion and mitigated chorion damage by regulating the morphology, structures, and surface negative charges of GO. HA also altered the uptake and deposition of GO and decreased the aggregation of GO in embryonic yolk cells and deep layer cells. Furthermore, HA mitigated the mitochondrial damage and oxidative stress induced by GO. This work reveals a feasible antidotal mechanism for GO in the presence of NOM and avoids overestimating the risks of GO in the natural environment.

Effects of chronic fructose overload on renal dopaminergic system: alteration of urinary L-dopa/dopamine index correlates to hypertension and precedes kidney structural damage.

PubMed

Rukavina Mikusic, Natalia L; Kouyoumdzian, Nicolás M; Del Mauro, Julieta S; Cao, Gabriel; Trida, Verónica; Gironacci, Mariela M; Puyó, Ana M; Toblli, Jorge E; Fernández, Belisario E; Choi, Marcelo R

2018-01-01

Insulin resistance induced by a high-fructose diet has been associated to hypertension and renal damage. The aim of this work was to assess alterations in the urinary L-dopa/dopamine ratio over three time periods in rats with insulin resistance induced by fructose overload and its correlation with blood pressure levels and the presence of microalbuminuria and reduced nephrin expression as markers of renal structural damage. Male Sprague-Dawley rats were randomly divided into six groups: control (C) (C4, C8 and C12) with tap water to drink and fructose-overloaded (FO) rats (FO4, FO8 and FO12) with a fructose solution (10% w/v) to drink for 4, 8 and 12 weeks. A significant increase of the urinary L-dopa/dopamine ratio was found in FO rats since week 4, which positively correlated to the development of hypertension and preceded in time the onset of microalbuminuria and reduced nephrin expression observed on week 12 of treatment. The alteration of this ratio was associated to an impairment of the renal dopaminergic system, evidenced by a reduction in renal dopamine transporters and dopamine D1 receptor expression, leading to an overexpression and overactivation of the enzyme Na + , K + -ATPase with sodium retention. In conclusion, urinary L-dopa/dopamine ratio alteration in rats with fructose overload positively correlated to the development of hypertension and preceded in time the onset of renal structural damage. This is the first study to propose the use of the urinary L-dopa/dopamine index as marker of renal dysfunction that temporarily precedes kidney structural damage induced by fructose overload. Copyright © 2017 Elsevier Inc. All rights reserved.

Laboratory performance of highway bridge girder anchorages under simulated hurricane-induced wave loading.

DOT National Transportation Integrated Search

2012-07-01

Many bridges along the Gulf Coast of the United States were damaged by recent hurricanes, and many more are susceptible to : similar damage. This research examines the structural performance of common connection details used to anchor prestressed : c...

Calculation on spectrum of direct DNA damage induced by low-energy electrons including dissociative electron attachment.

PubMed

Liu, Wei; Tan, Zhenyu; Zhang, Liming; Champion, Christophe

2017-03-01

In this work, direct DNA damage induced by low-energy electrons (sub-keV) is simulated using a Monte Carlo method. The characteristics of the present simulation are to consider the new mechanism of DNA damage due to dissociative electron attachment (DEA) and to allow determining damage to specific bases (i.e., adenine, thymine, guanine, or cytosine). The electron track structure in liquid water is generated, based on the dielectric response model for describing electron inelastic scattering and on a free-parameter theoretical model and the NIST database for calculating electron elastic scattering. Ionization cross sections of DNA bases are used to generate base radicals, and available DEA cross sections of DNA components are applied for determining DNA-strand breaks and base damage induced by sub-ionization electrons. The electron elastic scattering from DNA components is simulated using cross sections from different theoretical calculations. The resulting yields of various strand breaks and base damage in cellular environment are given. Especially, the contributions of sub-ionization electrons to various strand breaks and base damage are quantitatively presented, and the correlation between complex clustered DNA damage and the corresponding damaged bases is explored. This work shows that the contribution of sub-ionization electrons to strand breaks is substantial, up to about 40-70%, and this contribution is mainly focused on single-strand break. In addition, the base damage induced by sub-ionization electrons contributes to about 20-40% of the total base damage, and there is an evident correlation between single-strand break and damaged base pair A-T.

Genotoxicity analysis of two halonitromethanes, a novel group of disinfection by-products (DBPs), in human cells treated in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liviac, Danae; Creus, Amadeu; Marcos, Ricard

Halonitromethanes (HNMs) constitute an emerging class of disinfection by-products (DBPs) produced when chlorine and/or ozone are used for water treatment. The HNMs are structurally similar to halomethanes, but have a nitro-group in place of hydrogen bonded to the central carbon atom. Since little information exists on the genotoxic potential of HNMs, a study has been carried out with two HNM compounds, namely trichloronitromethane (TCNM) and bromonitromethane (BNM) by using human cells. Primary damage induction has been measured with the Comet assay, which is used to determine both the repair kinetics of the induced damage and the proportion of induced oxidativemore » damage. In addition, the fixed DNA damage has been evaluated by using the micronucleus (MN) assay. The results obtained indicate that both compounds are genotoxic, inducing high levels of DNA breaks in the Comet assay, and that this DNA damage repairs well over time. In addition, oxidized bases constitute a high proportion of DNA-induced damage (50-75%). Contrarily, no positive effects were observed in the frequency of micronucleus, which measures both clastogenic and aneugenic effects, neither using TK6 cells nor peripheral blood lymphocytes. This lack of fixed genetic damage would minimize the potential mutagenic risk associated with HNMs exposure.« less

Detection of Earthquake-Induced Damage in a Framed Structure Using a Finite Element Model Updating Procedure

PubMed Central

Kim, Seung-Nam; Park, Taewon; Lee, Sang-Hyun

2014-01-01

Damage of a 5-story framed structure was identified from two types of measured data, which are frequency response functions (FRF) and natural frequencies, using a finite element (FE) model updating procedure. In this study, a procedure to determine the appropriate weightings for different groups of observations was proposed. In addition, a modified frame element which included rotational springs was used to construct the FE model for updating to represent concentrated damage at the member ends (a formulation for plastic hinges in framed structures subjected to strong earthquakes). The results of the model updating and subsequent damage detection when the rotational springs (RS model) were used were compared with those obtained using the conventional frame elements (FS model). Comparisons indicated that the RS model gave more accurate results than the FS model. That is, the errors in the natural frequencies of the updated models were smaller, and the identified damage showed clearer distinctions between damaged and undamaged members and was more consistent with observed damage. PMID:24574888

Method for detecting damage in carbon-fibre reinforced plastic-steel structures based on eddy current pulsed thermography

NASA Astrophysics Data System (ADS)

Li, Xuan; Liu, Zhiping; Jiang, Xiaoli; Lodewijks, Gabrol

2018-01-01

Eddy current pulsed thermography (ECPT) is well established for non-destructive testing of electrical conductive materials, featuring the advantages of contactless, intuitive detecting and efficient heating. The concept of divergence characterization of the damage rate of carbon fibre-reinforced plastic (CFRP)-steel structures can be extended to ECPT thermal pattern characterization. It was found in this study that the use of ECPT technology on CFRP-steel structures generated a sizeable amount of valuable information for comprehensive material diagnostics. The relationship between divergence and transient thermal patterns can be identified and analysed by deploying mathematical models to analyse the information about fibre texture-like orientations, gaps and undulations in these multi-layered materials. The developed algorithm enabled the removal of information about fibre texture and the extraction of damage features. The model of the CFRP-glue-steel structures with damage was established using COMSOL Multiphysics® software, and quantitative non-destructive damage evaluation from the ECPT image areas was derived. The results of this proposed method illustrate that damaged areas are highly affected by available information about fibre texture. This proposed work can be applied for detection of impact induced damage and quantitative evaluation of CFRP structures.

Laser-induced periodic annular surface structures on fused silica surface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yi; Brelet, Yohann; Forestier, Benjamin

2013-06-24

We report on the formation of laser-induced periodic annular surface structures on fused silica irradiated with multiple femtosecond laser pulses. This surface morphology emerges after the disappearance of the conventional laser induced periodic surface structures, under successive laser pulse irradiation. It is independent of the laser polarization and universally observed for different focusing geometries. We interpret its formation in terms of the interference between the reflected laser field on the surface of the damage crater and the incident laser pulse.

Effects of soft X-ray radiation damage on paraffin-embedded rat tissues supported on ultralene: a chemical perspective.

PubMed

Bedolla, Diana E; Mantuano, Andrea; Pickler, Arissa; Mota, Carla Lemos; Braz, Delson; Salata, Camila; Almeida, Carlos Eduardo; Birarda, Giovanni; Vaccari, Lisa; Barroso, Regina Cély; Gianoncelli, Alessandra

2018-05-01

Radiation damage is an important aspect to be considered when analysing biological samples with X-ray techniques as it can induce chemical and structural changes in the specimens. This work aims to provide new insights into the soft X-ray induced radiation damage of the complete sample, including not only the biological tissue itself but also the substrate and embedding medium, and the tissue fixation procedure. Sample preparation and handling involves an unavoidable interaction with the sample matrix and could play an important role in the radiation-damage mechanism. To understand the influence of sample preparation and handling on radiation damage, the effects of soft X-ray exposure at different doses on ultralene, paraffin and on paraffin-embedded rat tissues were studied using Fourier-transform infrared (FTIR) microspectroscopy and X-ray microscopy. Tissues were preserved with three different commonly used fixatives: formalin, glutaraldehyde and Karnovsky. FTIR results showed that ultralene and paraffin undergo a dose-dependent degradation of their vibrational profiles, consistent with radiation-induced oxidative damage. In addition, formalin fixative has been shown to improve the preservation of the secondary structure of proteins in tissues compared with both glutaraldehyde and Karnovsky fixation. However, conclusive considerations cannot be drawn on the optimal fixation protocol because of the interference introduced by both substrate and embedding medium in the spectral regions specific to tissue lipids, nucleic acids and carbohydrates. Notably, despite the detected alterations affecting the chemical architecture of the sample as a whole, composed of tissue, substrate and embedding medium, the structural morphology of the tissues at the micrometre scale is essentially preserved even at the highest exposure dose.

Nucleus Accumbens Invulnerability to Methamphetamine Neurotoxicity

PubMed Central

Kuhn, Donald M.; Angoa-Pérez, Mariana; Thomas, David M.

2016-01-01

Methamphetamine (Meth) is a neurotoxic drug of abuse that damages neurons and nerve endings throughout the central nervous system. Emerging studies of human Meth addicts using both postmortem analyses of brain tissue and noninvasive imaging studies of intact brains have confirmed that Meth causes persistent structural abnormalities. Animal and human studies have also defined a number of significant functional problems and comorbid psychiatric disorders associated with long-term Meth abuse. This review summarizes the salient features of Meth-induced neurotoxicity with a focus on the dopamine (DA) neuronal system. DA nerve endings in the caudate-putamen (CPu) are damaged by Meth in a highly delimited manner. Even within the CPu, damage is remarkably heterogeneous, with ventral and lateral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared the damage that accompanies binge Meth intoxication, but relatively subtle changes in the disposition of DA in its nerve endings can lead to dramatic increases in Meth-induced toxicity in the CPu and overcome the normal resistance of the NAc to damage. In contrast to the CPu, where DA neuronal deficiencies are persistent, alterations in the NAc show a partial recovery. Animal models have been indispensable in studies of the causes and consequences of Meth neurotoxicity and in the development of new therapies. This research has shown that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of Meth to include brain structures not normally targeted for damage. The resistance of the NAc to Meth-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of Meth neurotoxicity by alterations in DA homeostasis is significant in light of the numerous important roles played by this brain structure. PMID:23382149

Nucleus accumbens invulnerability to methamphetamine neurotoxicity.

PubMed

Kuhn, Donald M; Angoa-Pérez, Mariana; Thomas, David M

2011-01-01

Methamphetamine (Meth) is a neurotoxic drug of abuse that damages neurons and nerve endings throughout the central nervous system. Emerging studies of human Meth addicts using both postmortem analyses of brain tissue and noninvasive imaging studies of intact brains have confirmed that Meth causes persistent structural abnormalities. Animal and human studies have also defined a number of significant functional problems and comorbid psychiatric disorders associated with long-term Meth abuse. This review summarizes the salient features of Meth-induced neurotoxicity with a focus on the dopamine (DA) neuronal system. DA nerve endings in the caudate-putamen (CPu) are damaged by Meth in a highly delimited manner. Even within the CPu, damage is remarkably heterogeneous, with ventral and lateral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared the damage that accompanies binge Meth intoxication, but relatively subtle changes in the disposition of DA in its nerve endings can lead to dramatic increases in Meth-induced toxicity in the CPu and overcome the normal resistance of the NAc to damage. In contrast to the CPu, where DA neuronal deficiencies are persistent, alterations in the NAc show a partial recovery. Animal models have been indispensable in studies of the causes and consequences of Meth neurotoxicity and in the development of new therapies. This research has shown that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of Meth to include brain structures not normally targeted for damage. The resistance of the NAc to Meth-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of Meth neurotoxicity by alterations in DA homeostasis is significant in light of the numerous important roles played by this brain structure.

Damage assessment in reinforced concrete using nonlinear vibration techniques

NASA Astrophysics Data System (ADS)

Van Den Abeele, K.; De Visscher, J.

2000-07-01

Reinforced concrete (RC) structures are subject to microcrack initiation and propagation at load levels far below the actual failure load. In this paper, nonlinear vibration techniques are applied to investigate stages of progressive damage in RC beams induced by static loading tests. At different levels of damage, a modal analysis is carried out, assuming the structure to behave linearly. At the same time, measurement of resonant frequencies and damping ratios as function of vibration amplitude are performed using a frequency domain technique as well as a time domain technique. We compare the results of the linear and nonlinear techniques, and value them against the visual damage evaluation.

Application of Laser Micro-irradiation for Examination of Single and Double Strand Break Repair in Mammalian Cells.

PubMed

Holton, Nathaniel W; Andrews, Joel F; Gassman, Natalie R

2017-09-05

Highly coordinated DNA repair pathways exist to detect, excise and replace damaged DNA bases, and coordinate repair of DNA strand breaks. While molecular biology techniques have clarified structure, enzymatic functions, and kinetics of repair proteins, there is still a need to understand how repair is coordinated within the nucleus. Laser micro-irradiation offers a powerful tool for inducing DNA damage and monitoring the recruitment of repair proteins. Induction of DNA damage by laser micro-irradiation can occur with a range of wavelengths, and users can reliably induce single strand breaks, base lesions and double strand breaks with a range of doses. Here, laser micro-irradiation is used to examine repair of single and double strand breaks induced by two common confocal laser wavelengths, 355 nm and 405 nm. Further, proper characterization of the applied laser dose for inducing specific damage mixtures is described, so users can reproducibly perform laser micro-irradiation data acquisition and analysis.

A-Type Lamins Maintain the Positional Stability of DNA Damage Repair Foci in Mammalian Nuclei

PubMed Central

Mahen, Robert; Hattori, Hiroyoshi; Lee, Miyoung; Sharma, Pooja; Jeyasekharan, Anand D.; Venkitaraman, Ashok R.

2013-01-01

A-type lamins encoded by LMNA form a structural fibrillar meshwork within the mammalian nucleus. How this nuclear organization may influence the execution of biological processes involving DNA transactions remains unclear. Here, we characterize changes in the dynamics and biochemical interactions of lamin A/C after DNA damage. We find that DNA breakage reduces the mobility of nucleoplasmic GFP-lamin A throughout the nucleus as measured by dynamic fluorescence imaging and spectroscopy in living cells, suggestive of incorporation into stable macromolecular complexes, but does not induce the focal accumulation of GFP-lamin A at damage sites. Using a proximity ligation assay and biochemical analyses, we show that lamin A engages chromatin via histone H2AX and its phosphorylated form (γH2AX) induced by DNA damage, and that these interactions are enhanced after DNA damage. Finally, we use three-dimensional time-lapse imaging to show that LMNA inactivation significantly reduces the positional stability of DNA repair foci in living cells. This defect is partially rescued by the stable expression of GFP-lamin A. Thus collectively, our findings suggest that the dynamic structural meshwork formed by A-type lamins anchors sites of DNA repair in mammalian nuclei, providing fresh insight into the control of DNA transactions by nuclear structural organization. PMID:23658700

Multi-scale fracture damage associated with underground chemical explosions

DOE PAGES

Swanson, Erika M.; Sussman, A. J.; Wilson, J. E.; ...

2018-02-22

Understanding rock damage induced by explosions is critical for a number of applications including the monitoring and verification of underground nuclear explosions, mine safety issues, and modeling fluid flow through fractured rock. We use core observations, televiewer logs, and thin section observations to investigate fracture damage associated with two successive underground chemical explosions (SPE2 and SPE3) in granitic rock at both the mesoscale and microscale. We compare the frequency and orientations of core-scale fractures, and the frequency of microfractures, between a pre-experiment core and three post-experiment cores. Natural fault zones and explosion-induced fractures in the vicinity of the explosive sourcemore » are readily apparent in recovered core and in thin sections. Damage from faults and explosions is not always apparent in fracture frequency plots from televiewer logs, although orientation data from these logs suggests explosion-induced fracturing may not align with the pre-existing fracture sets. Core-scale observations indicate the extent of explosion-induced damage is 10.0 m after SPE2 and 6.8 m after SPE3, despite both a similar size and location for both explosions. At the microscale, damage is observed to a range distance of 10.2 ± 0.9 m after SPE2, and 16.6 ± 0.9 and 11.2 ± 0.6 in two different cores collected after SPE3. Additional explosion-induced damage, interpreted to be the result of spalling, is readily apparent near the surface, but only in the microfracture data. This depth extent and intensity of damage in the near-surface region also increased after an additional explosion. This study highlights the importance of evaluating structural damage at multiple scales for a more complete characterization of the damage, and particularly shows the importance of microscale observations for identifying spallation-induced damage.« less

Multi-scale fracture damage associated with underground chemical explosions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swanson, Erika M.; Sussman, A. J.; Wilson, J. E.

Understanding rock damage induced by explosions is critical for a number of applications including the monitoring and verification of underground nuclear explosions, mine safety issues, and modeling fluid flow through fractured rock. We use core observations, televiewer logs, and thin section observations to investigate fracture damage associated with two successive underground chemical explosions (SPE2 and SPE3) in granitic rock at both the mesoscale and microscale. We compare the frequency and orientations of core-scale fractures, and the frequency of microfractures, between a pre-experiment core and three post-experiment cores. Natural fault zones and explosion-induced fractures in the vicinity of the explosive sourcemore » are readily apparent in recovered core and in thin sections. Damage from faults and explosions is not always apparent in fracture frequency plots from televiewer logs, although orientation data from these logs suggests explosion-induced fracturing may not align with the pre-existing fracture sets. Core-scale observations indicate the extent of explosion-induced damage is 10.0 m after SPE2 and 6.8 m after SPE3, despite both a similar size and location for both explosions. At the microscale, damage is observed to a range distance of 10.2 ± 0.9 m after SPE2, and 16.6 ± 0.9 and 11.2 ± 0.6 in two different cores collected after SPE3. Additional explosion-induced damage, interpreted to be the result of spalling, is readily apparent near the surface, but only in the microfracture data. This depth extent and intensity of damage in the near-surface region also increased after an additional explosion. This study highlights the importance of evaluating structural damage at multiple scales for a more complete characterization of the damage, and particularly shows the importance of microscale observations for identifying spallation-induced damage.« less

Limits of performance: CW laser damage

NASA Astrophysics Data System (ADS)

Shah, Rashmi S.; Rey, Justin J.; Stewart, Alan F.

2007-01-01

High performance optical coatings are an enabling technology for many applications - navigation systems, telecom, fusion, advanced measurement systems of many types as well as directed energy weapons. The results of recent testing of superior optical coatings conducted at high flux levels have been presented. Failure of these coatings was rare. However, induced damage was not expected from simple thermal models relating flux loading to induced temperatures. Clearly, other mechanisms must play a role in the occurrence of laser damage. Contamination is an obvious mechanism-both particulate and molecular. Less obvious are structural defects and the role of induced stresses. These mechanisms are examined through simplified models and finite element analysis. The results of the models are compared to experiment, for induced temperatures and observed stress levels. The role of each mechanism is described and limiting performance is determined.

Damage Evaluation of Concrete Column under Impact Load Using a Piezoelectric-Based EMI Technique.

PubMed

Fan, Shuli; Zhao, Shaoyu; Qi, Baoxin; Kong, Qingzhao

2018-05-17

One of the major causes of damage to column-supported concrete structures, such as bridges and highways, are collisions from moving vehicles, such as cars and ships. It is essential to quantify the collision damage of the column so that appropriate actions can be taken to prevent catastrophic events. A widely used method to assess structural damage is through the root-mean-square deviation (RMSD) damage index established by the collected data; however, the RMSD index does not truly provide quantitative information about the structure. Conversely, the damage volume ratio that can only be obtained via simulation provides better detail about the level of damage in a structure. Furthermore, as simulation can also provide the RMSD index relating to that particular damage volume ratio, the empirically obtained RMSD index can thus be related to the structural damage degree through comparison of the empirically obtained RMSD index to numerically-obtained RMSD. Thus, this paper presents a novel method in which the impact-induced damage to a structure is simulated in order to obtain the relationship between the damage volume ratio to the RMSD index, and the relationship can be used to predict the true damage degree by comparison to the empirical RMSD index. In this paper, the collision damage of a bridge column by moving vehicles was simulated by using a concrete beam model subjected to continuous impact loadings by a freefalling steel ball. The variation in admittance signals measured by the surface attached lead zirconate titanate (PZT) patches was used to establish the RMSD index. The results demonstrate that the RMSD index and the damage ratio of concrete have a linear relationship for the particular simulation model.

Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons

PubMed Central

Wang, Wei-Ping; Iyo, Abiye H.; Miguel-Hidalgo, Javier; Regunathan, Soundar; Zhu, Meng-Yang

2010-01-01

Agmatine is a polyamine and has been considered as a novel neurotransmitter or neuromodulator in the central nervous system. In the present study, the neuroprotective effect of agmatine against cell damage caused by N-methyl-d-aspartate (NMDA) and glutamate was investigated in cultured rat hippocampal neurons. Lactate dehydrogenase (LDH) activity assay, β-tubulin III immunocytochemical staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end-labeling (TUNEL) assay were conducted to detect cell damage. Exposure of 12-day neuronal cultures of rat hippocampus to NMDA or glutamate for 1 h caused a concentration-dependent neurotoxicity, as indicated by the significant increase in released LDH activities. Addition of 100 µM agmatine into media ablated the neurotoxicity induced by NMDA or glutamate, an effect also produced by the specific NMDA receptor antagonist dizocilpine hydrogen maleate (MK801). Arcaine, an analog of agmatine with similar structure as agmatine, fully prevented the NMDA- or glutamate-induced neuronal damage. Spermine and putrescine, the endogenous polyamine and metabolic products of agmatine without the guanidine moiety of agmatine, failed to show this effect, indicating a structural relevance for this neuroprotection. Immunocytochemical staining and TUNEL assay confirmed the findings in the LDH measurement. That is, agmatine and MK801 markedly attenuated NMDA-induced neuronal death and significantly reduced TUNEL-positive cell numbers induced by exposure of cultured hippocampal neurons to NMDA. Taken together, these results demonstrate that agmatine can protect cultured hippocampal neurons from NMDA- or glutamate-induced excitotoxicity, through a possible blockade of the NMDA receptor channels or a potential anti-apoptotic property. PMID:16546145

Enhanced light absorption of solar cells and photodetectors by diffraction

DOEpatents

Zaidi, Saleem H.; Gee, James M.

2005-02-22

Enhanced light absorption of solar cells and photodetectors by diffraction is described. Triangular, rectangular, and blazed subwavelength periodic structures are shown to improve performance of solar cells. Surface reflection can be tailored for either broadband, or narrow-band spectral absorption. Enhanced absorption is achieved by efficient optical coupling into obliquely propagating transmitted diffraction orders. Subwavelength one-dimensional structures are designed for polarization-dependent, wavelength-selective absorption in solar cells and photodetectors, while two-dimensional structures are designed for polarization-independent, wavelength-selective absorption therein. Suitable one and two-dimensional subwavelength periodic structures can also be designed for broadband spectral absorption in solar cells and photodetectors. If reactive ion etching (RIE) processes are used to form the grating, RIE-induced surface damage in subwavelength structures can be repaired by forming junctions using ion implantation methods. RIE-induced surface damage can also be removed by post RIE wet-chemical etching treatments.

[Sex difference of functional and structural alterations in the myocardium of rats with hypothyroidism].

PubMed

Khara, M R; Pavlovych, S I; Mykhaĭliuk, V M

2013-01-01

In experiments on sexually mature rats we studied specific cholinergic regulations of the heart and the degree of its structural damage in hypothyroidism, depending on gender and hormone-productive activity of the gonads. Hypothyroidism in sexually mature males and females was modelled with mercazolil intragastric administration (75 mg/kg) daily during 15 days. We also studied the intensity of bradycardia, which occurred in response to electrical stimulation of vagus nerve and intravenous acetylcholine administration. The degree of structural heart damage was assessed by the percentage of damaged cardiomyocytes in the ventricles of myocardium. It was found that one of the mechanisms of bradycardia in merkazolil-induced hypothyroidism is an increase of the sensitivity of sinus node cholinergic receptors and release of more quanta of acetylcholine from stimulated nerves vagus endings, what was more intense in females. The intensity of bradycardia in hypothyroidism was more significant in gonadectomized animals than in individuals with preserved gonads. The mechanisms of its occurrence in males consist of release of greater amount of acetylcholine from the endings of the nerves vagus, and in females it was the result of significant increase of the sensitivity of sinus node cholinergic receptors. Regardless of the gonads activity, structural damage of the myocardium in merkazolil-induced hypothyroidism was more intensive in female rats.

Damage prognosis of adhesively-bonded joints in laminated composite structural components of unmanned aerial vehicles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farrar, Charles R; Gobbato, Maurizio; Conte, Joel

2009-01-01

The extensive use of lightweight advanced composite materials in unmanned aerial vehicles (UAVs) drastically increases the sensitivity to both fatigue- and impact-induced damage of their critical structural components (e.g., wings and tail stabilizers) during service life. The spar-to-skin adhesive joints are considered one of the most fatigue sensitive subcomponents of a lightweight UAV composite wing with damage progressively evolving from the wing root. This paper presents a comprehensive probabilistic methodology for predicting the remaining service life of adhesively-bonded joints in laminated composite structural components of UAVs. Non-destructive evaluation techniques and Bayesian inference are used to (i) assess the current statemore » of damage of the system and, (ii) update the probability distribution of the damage extent at various locations. A probabilistic model for future loads and a mechanics-based damage model are then used to stochastically propagate damage through the joint. Combined local (e.g., exceedance of a critical damage size) and global (e.g.. flutter instability) failure criteria are finally used to compute the probability of component failure at future times. The applicability and the partial validation of the proposed methodology are then briefly discussed by analyzing the debonding propagation, along a pre-defined adhesive interface, in a simply supported laminated composite beam with solid rectangular cross section, subjected to a concentrated load applied at mid-span. A specially developed Eliler-Bernoulli beam finite element with interlaminar slip along the damageable interface is used in combination with a cohesive zone model to study the fatigue-induced degradation in the adhesive material. The preliminary numerical results presented are promising for the future validation of the methodology.« less

RNA protects a nucleoprotein complex against radiation damage.

PubMed

Bury, Charles S; McGeehan, John E; Antson, Alfred A; Carmichael, Ian; Gerstel, Markus; Shevtsov, Mikhail B; Garman, Elspeth F

2016-05-01

Radiation damage during macromolecular X-ray crystallographic data collection is still the main impediment for many macromolecular structure determinations. Even when an eventual model results from the crystallographic pipeline, the manifestations of radiation-induced structural and conformation changes, the so-called specific damage, within crystalline macromolecules can lead to false interpretations of biological mechanisms. Although this has been well characterized within protein crystals, far less is known about specific damage effects within the larger class of nucleoprotein complexes. Here, a methodology has been developed whereby per-atom density changes could be quantified with increasing dose over a wide (1.3-25.0 MGy) range and at higher resolution (1.98 Å) than the previous systematic specific damage study on a protein-DNA complex. Specific damage manifestations were determined within the large trp RNA-binding attenuation protein (TRAP) bound to a single-stranded RNA that forms a belt around the protein. Over a large dose range, the RNA was found to be far less susceptible to radiation-induced chemical changes than the protein. The availability of two TRAP molecules in the asymmetric unit, of which only one contained bound RNA, allowed a controlled investigation into the exact role of RNA binding in protein specific damage susceptibility. The 11-fold symmetry within each TRAP ring permitted statistically significant analysis of the Glu and Asp damage patterns, with RNA binding unexpectedly being observed to protect these otherwise highly sensitive residues within the 11 RNA-binding pockets distributed around the outside of the protein molecule. Additionally, the method enabled a quantification of the reduction in radiation-induced Lys and Phe disordering upon RNA binding directly from the electron density.

RNA protects a nucleoprotein complex against radiation damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bury, Charles S.; McGeehan, John E.; Antson, Alfred A.

Radiation damage during macromolecular X-ray crystallographic data collection is still the main impediment for many macromolecular structure determinations. Even when an eventual model results from the crystallographic pipeline, the manifestations of radiation-induced structural and conformation changes, the so-called specific damage, within crystalline macromolecules can lead to false interpretations of biological mechanisms. Although this has been well characterized within protein crystals, far less is known about specific damage effects within the larger class of nucleoprotein complexes. We developed a methodology whereby per-atom density changes could be quantified with increasing dose over a wide (1.3–25.0 MGy) range and at higher resolution (1.98more » Å) than the previous systematic specific damage study on a protein–DNA complex. Specific damage manifestations were determined within the largetrpRNA-binding attenuation protein (TRAP) bound to a single-stranded RNA that forms a belt around the protein. Over a large dose range, the RNA was found to be far less susceptible to radiation-induced chemical changes than the protein. The availability of two TRAP molecules in the asymmetric unit, of which only one contained bound RNA, allowed a controlled investigation into the exact role of RNA binding in protein specific damage susceptibility. The 11-fold symmetry within each TRAP ring permitted statistically significant analysis of the Glu and Asp damage patterns, with RNA binding unexpectedly being observed to protect these otherwise highly sensitive residues within the 11 RNA-binding pockets distributed around the outside of the protein molecule. In addition, the method enabled a quantification of the reduction in radiation-induced Lys and Phe disordering upon RNA binding directly from the electron density.« less

RNA protects a nucleoprotein complex against radiation damage

DOE PAGES

Bury, Charles S.; McGeehan, John E.; Antson, Alfred A.; ...

2016-04-26

Radiation damage during macromolecular X-ray crystallographic data collection is still the main impediment for many macromolecular structure determinations. Even when an eventual model results from the crystallographic pipeline, the manifestations of radiation-induced structural and conformation changes, the so-called specific damage, within crystalline macromolecules can lead to false interpretations of biological mechanisms. Although this has been well characterized within protein crystals, far less is known about specific damage effects within the larger class of nucleoprotein complexes. We developed a methodology whereby per-atom density changes could be quantified with increasing dose over a wide (1.3–25.0 MGy) range and at higher resolution (1.98more » Å) than the previous systematic specific damage study on a protein–DNA complex. Specific damage manifestations were determined within the largetrpRNA-binding attenuation protein (TRAP) bound to a single-stranded RNA that forms a belt around the protein. Over a large dose range, the RNA was found to be far less susceptible to radiation-induced chemical changes than the protein. The availability of two TRAP molecules in the asymmetric unit, of which only one contained bound RNA, allowed a controlled investigation into the exact role of RNA binding in protein specific damage susceptibility. The 11-fold symmetry within each TRAP ring permitted statistically significant analysis of the Glu and Asp damage patterns, with RNA binding unexpectedly being observed to protect these otherwise highly sensitive residues within the 11 RNA-binding pockets distributed around the outside of the protein molecule. In addition, the method enabled a quantification of the reduction in radiation-induced Lys and Phe disordering upon RNA binding directly from the electron density.« less

Frost induced damages within porous materials - from concrete technology to fuel cells technique

NASA Astrophysics Data System (ADS)

Palecki, Susanne; Gorelkov, Stanislav; Wartmann, Jens; Heinzel, Angelika

2017-12-01

Porous media like concrete or layers of membrane electrode assemblies (MEA) within fuel cells are affected by a cyclic frost exposure due to different damage mechanisms which could lead to essential degradation of the material. In general, frost damages can only occur in case of a specific material moisture content. In fuel cells, residual water is generally available after shut down inside the membrane i.e. the gas diffusion layer (GDL). During subsequent freezing, this could cause various damage phenomena such as frost heaves and delamination effects of the membrane electrode assembly, which depends on the location of pore water and on the pore structure itself. Porous materials possess a pore structure that could range over several orders of magnitudes with different properties and freezing behaviour of the pore water. Latter can be divided into macroscopic, structured and pre-structured water, influenced by surface interactions. Therefore below 0 °C different water modifications can coexist in a wide temperature range, so that during frost exposure a high amount of unfrozen and moveable water inside the pore system is still available. This induces transport mechanisms and shrinkage effects. The physical basics are similar for porous media. While the freezing behaviour of concrete has been studied over decades of years, in order to enhance the durability, the know-how about the influence of a frost attack on fuel cell systems is not fully understood to date. On the basis of frost damage models for concrete structures, an approach to describe the impact of cyclic freezing and thawing on membrane electrode assemblies has been developed within this research work. Major aim is beyond a better understanding of the frost induced mechanisms, the standardization of a suitable test procedure for the assessment of different MEA materials under such kind of attack. Within this contribution first results will be introduced.

Vitamin C prevents stress-induced damage on the heart caused by the death of cardiomyocytes, through down-regulation of the excessive production of catecholamine, TNF-α, and ROS production in Gulo(-/-)Vit C-Insufficient mice.

PubMed

Kim, Hyemin; Bae, Seyeon; Kim, Yejin; Cho, Chung-Hyun; Kim, Sung Joon; Kim, Yong-Jin; Lee, Seung-Pyo; Kim, Hang-Rae; Hwang, Young-Il; Kang, Jae Seung; Lee, Wang Jae

2013-12-01

It is thought that vitamin C has protective roles on stress-induced heart damage and the development of cardiovascular diseases, but its precise role and mechanisms are unclear. In the present study, we investigated the specific mechanisms by which vitamin C leads to protecting the heart from stress-induced damage in the Gulo(-/-) mice which cannot synthesize vitamin C like humans. By exposure to stress (1h/day), the heartbeat and cardiac output in vitamin C-insufficient Gulo(-/-) mice were definitely decreased, despite a significant increase of adrenaline (ADR) and noradrenaline (NA) production. A change of cardiac structure caused by the death of cardiomyocytes and an increased expression of matrix metalloprotease (MMP)-2 and -9 were also found. Moreover, lipid peroxidation and the production of tumor necrosis factor-alpha (TNF-α) in the heart were increased. Finally, all vitamin C-insufficient Gulo(-/-) mice were expired within 2 weeks. Interestingly, all of the findings in vitamin C-insufficient Gulo(-/-) mice were completely prevented by the supplementation of a sufficient amount of vitamin C. Taken together, vitamin C insufficiency increases the risk of stress-induced cardiac damage with structural and functional changes arising from the apoptosis of cardiomyocytes. Crown Copyright © 2013 Published by Elsevier Inc. All rights reserved.

Active sensing of fatigue damage using embedded ultrasonics

NASA Astrophysics Data System (ADS)

Zagrai, Andrei; Kruse, Walter A.; Gigineishvili, Vlasi

2009-03-01

Embedded ultrasonics has demonstrated considerable utility in structural health monitoring of aeronautical vehicle. This active sensing approach has been widely used to detect and monitor cracks, delaminations, and disbonds in a broad spectrum of metallic and composite structures. However, application of the embedded ultrasonics for active sensing of incipient damage before fracture has received limited attention. The aim of this study was to investigate the suitability of embedded ultrasonics and nonlinear acoustic signatures for monitoring pre-crack fatigue damage in aerospace structural material. A harmonic load was applied to structural specimens in order to induce fatigue damage accumulation and growth. Specimens of simple geometry were considered and piezoelectric active sensors were employed for generation and reception of elastic waves. The elastic wave signatures were analyzed in the frequency domain using nonlinear impedance and nonlinear resonance methods. A relationship between fatigue severity and linear as well as nonlinear acoustic signatures was investigated and considered in the damage classification procedure. Practical aspects of the active sensing of the fatigue damage before fracture were discussed and prospective avenues for future research were suggested.

Investigation of contact acoustic nonlinearities on metal and composite airframe structures via intensity based health monitoring.

PubMed

Romano, P Q; Conlon, S C; Smith, E C

2013-01-01

Nonlinear structural intensity (NSI) and nonlinear structural surface intensity (NSSI) based damage detection techniques were improved and extended to metal and composite airframe structures. In this study, the measurement of NSI maps at sub-harmonic frequencies was completed to provide enhanced understanding of the energy flow characteristics associated with the damage induced contact acoustic nonlinearity mechanism. Important results include NSI source localization visualization at ultra-subharmonic (nf/2) frequencies, and damage detection results utilizing structural surface intensity in the nonlinear domain. A detection metric relying on modulated wave spectroscopy was developed and implemented using the NSSI feature. The data fusion of the intensity formulation provided a distinct advantage, as both the single interrogation frequency NSSI and its modulated wave extension (NSSI-MW) exhibited considerably higher sensitivities to damage than using single-sensor (strain or acceleration) nonlinear detection metrics. The active intensity based techniques were also extended to composite materials, and results show both NSSI and NSSI-MW can be used to detect damage in the bond line of an integrally stiffened composite plate structure with high sensitivity. Initial damage detection measurements made on an OH-58 tailboom (Penn State Applied Research Laboratory, State College, PA) indicate the techniques can be transitioned to complex airframe structures achieving high detection sensitivities with minimal sensors and actuators.

A Tensor-Based Structural Damage Identification and Severity Assessment

PubMed Central

Anaissi, Ali; Makki Alamdari, Mehrisadat; Rakotoarivelo, Thierry; Khoa, Nguyen Lu Dang

2018-01-01

Early damage detection is critical for a large set of global ageing infrastructure. Structural Health Monitoring systems provide a sensor-based quantitative and objective approach to continuously monitor these structures, as opposed to traditional engineering visual inspection. Analysing these sensed data is one of the major Structural Health Monitoring (SHM) challenges. This paper presents a novel algorithm to detect and assess damage in structures such as bridges. This method applies tensor analysis for data fusion and feature extraction, and further uses one-class support vector machine on this feature to detect anomalies, i.e., structural damage. To evaluate this approach, we collected acceleration data from a sensor-based SHM system, which we deployed on a real bridge and on a laboratory specimen. The results show that our tensor method outperforms a state-of-the-art approach using the wavelet energy spectrum of the measured data. In the specimen case, our approach succeeded in detecting 92.5% of induced damage cases, as opposed to 61.1% for the wavelet-based approach. While our method was applied to bridges, its algorithm and computation can be used on other structures or sensor-data analysis problems, which involve large series of correlated data from multiple sensors. PMID:29301314

Effects of carotenoids on damage of biological lipids induced by gamma irradiation

NASA Astrophysics Data System (ADS)

Saito, Takeshi; Fujii, Noriko

2014-05-01

Carotenoids are considered to be involved in the radioresistant mechanisms of radioresistant bacteria. In these bacterial cells, carotenoids are present in biological lipids, and therefore may be related to the radiation-induced damage of lipids. However, only limited data are available for the role of carotenoids in such damage. In this study, we irradiated an α-linolenic acid-benzene solution with gamma rays and analyzed the resulting oxidative degradation and peroxidation damage in the presence or absence of two typical carotenoids: β-carotene and astaxanthin. The analyses revealed that oxidative degradation and peroxidation of α-linolenic acid, as evaluated by the amount of malondialdehyde and conjugated diene formed, respectively, increased in a dose-dependent manner. Moreover, 8.5×10-3 M β-carotene inhibited gamma radiation-induced oxidative degradation of α-linolenic acid, whereas 5.0×10-5 and 5.0×10-6 M β-carotene, and 5.0×10-7 and 5.0×10-8 M astaxanthin promoted degradation. In contrast, neither β-carotene nor astaxanthin affected peroxidation of α-linolenic acid. These results suggest that an optimum concentration of carotenoids in radioresistant bacteria protects biological lipid structures from radiation-induced damage.

Structural Basis of Mec1-Ddc2-RPA Assembly and Activation on Single-Stranded DNA at Sites of Damage.

PubMed

Deshpande, Ishan; Seeber, Andrew; Shimada, Kenji; Keusch, Jeremy J; Gut, Heinz; Gasser, Susan M

2017-10-19

Mec1-Ddc2 (ATR-ATRIP) is a key DNA-damage-sensing kinase that is recruited through the single-stranded (ss) DNA-binding replication protein A (RPA) to initiate the DNA damage checkpoint response. Activation of ATR-ATRIP in the absence of DNA damage is lethal. Therefore, it is important that damage-specific recruitment precedes kinase activation, which is achieved at least in part by Mec1-Ddc2 homodimerization. Here, we report a structural, biochemical, and functional characterization of the yeast Mec1-Ddc2-RPA assembly. High-resolution co-crystal structures of Ddc2-Rfa1 and Ddc2-Rfa1-t11 (K45E mutant) N termini and of the Ddc2 coiled-coil domain (CCD) provide insight into Mec1-Ddc2 homodimerization and damage-site targeting. Based on our structural and functional findings, we present a Mec1-Ddc2-RPA-ssDNA composite structural model. By way of validation, we show that RPA-dependent recruitment of Mec1-Ddc2 is crucial for maintaining its homodimeric state at ssDNA and that Ddc2's recruitment domain and CCD are important for Mec1-dependent survival of UV-light-induced DNA damage. Copyright © 2017 Elsevier Inc. All rights reserved.

Fatigue Life of Postbuckled Structures with Indentation Damage

NASA Technical Reports Server (NTRS)

Davila, Carlos G.; Bisagni, Chiara

2016-01-01

The fatigue life of composite stiffened panels with indentation damage was investigated experimentally using single stringer compression specimens. Indentation damage was induced on one of the two flanges of the stringer. The experiments were conducted using advanced instrumentation, including digital image correlation, passive thermography, and in-situ ultrasonic scanning. Specimens with initial indentation damage lengths of 37 millimeters to 56 millimeters were tested in fatigue and the effects of cyclic load amplitude and damage size were studied. A means of comparison of the damage propagation rates and collapse loads based on a stress intensity measure and the Paris law is proposed.

Atrophy of spared gray matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke.

PubMed

Gauthier, Lynne V; Taub, Edward; Mark, Victor W; Barghi, Ameen; Uswatte, Gitendra

2012-02-01

Although the motor deficit after stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to constraint-induced movement therapy in patients with chronic stroke may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Voxel-based morphometry analysis was performed on MRI scans from 80 patients with chronic stroke to investigate whether variations in gray matter density were correlated with extent of residual motor impairment or with constraint-induced movement therapy-induced motor recovery. Decreased gray matter density in noninfarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced gray matter density in multiple remote brain regions predicted a lesser extent of motor improvement from constraint-induced movement therapy. Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke.

Quantitative nondestructive evaluation of materials and structures

NASA Technical Reports Server (NTRS)

Smith, Barry T.

1991-01-01

An experimental investigation was undertaken to quantify damage tolerance and resistance in composite materials impacted using the drop-weight method. Tests were conducted on laminates of several different carbon-fiber composite systems, such as epoxies, modified epoxies, and amorphous and semicrystalline thermoplastics. Impacted composite specimens were examined using destructive and non-destructive techniques to establish the characteristic damage states. Specifically, optical microscopy, ultrasonic, and scanning electron microscopy techniques were used to identify impact induced damage mechanisms. Damage propagation during post impact compression was also studied.

Structural modifications induced by ion irradiation and temperature in boron carbide B4C

NASA Astrophysics Data System (ADS)

Victor, G.; Pipon, Y.; Bérerd, N.; Toulhoat, N.; Moncoffre, N.; Djourelov, N.; Miro, S.; Baillet, J.; Pradeilles, N.; Rapaud, O.; Maître, A.; Gosset, D.

2015-12-01

Already used as neutron absorber in the current French nuclear reactors, boron carbide (B4C) is also considered in the future Sodium Fast Reactors of the next generation (Gen IV). Due to severe irradiation conditions occurring in these reactors, it is of primary importance that this material presents a high structural resistance under irradiation, both in the ballistic and electronic damage regimes. Previous works have shown an important structural resistance of boron carbide even at high neutron fluences. Nevertheless, the structural modification mechanisms due to irradiation are not well understood. Therefore the aim of this paper is to study structural modifications induced in B4C samples in different damage regimes. The boron carbide pellets were shaped and sintered by using spark plasma sintering method. They were then irradiated in several conditions at room temperature or 800 °C, either by favoring the creation of ballistic damage (between 1 and 3 dpa), or by favoring the electronic excitations using 100 MeV swift iodine ions (Se ≈ 15 keV/nm). Ex situ micro-Raman spectroscopy and Doppler broadening of annihilation radiation technique with variable energy slow positrons were coupled to follow the evolution of the B4C structure under irradiation.

Sonic-boom-induced building structure responses including damage.

NASA Technical Reports Server (NTRS)

Clarkson, B. L.; Mayes, W. H.

1972-01-01

Concepts of sonic-boom pressure loading of building structures and the associated responses are reviewed, and results of pertinent theoretical and experimental research programs are summarized. The significance of sonic-boom load time histories, including waveshape effects, are illustrated with the aid of simple structural elements such as beams and plates. Also included are discussions of the significance of such other phenomena as three-dimensional loading effects, air cavity coupling, multimodal responses, and structural nonlinearities. Measured deflection, acceleration, and strain data from laboratory models and full-scale building tests are summarized, and these data are compared, where possible, with predicted values. Damage complaint and claim experience due both to controlled and uncontrolled supersonic flights over communities are summarized with particular reference to residential, commercial, and historic buildings. Sonic-boom-induced building responses are compared with those from other impulsive loadings due to natural and cultural events and from laboratory simulation tests.

Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis.

PubMed

Gupta, Indranil; Ganguly, Souradipta; Rozanas, Christine R; Stuehr, Dennis J; Panda, Koustubh

2016-07-19

Cigarette smoking causes emphysema, a fatal disease involving extensive structural and functional damage of the lung. Using a guinea pig model and human lung cells, we show that oxidant(s) present in tobacco smoke not only cause direct oxidative damage of lung proteins, contributing to the major share of lung injury, but also activate Rtp801, a key proinflammatory cellular factor involved in tobacco smoke-induced lung damage. Rtp801 triggers nuclear factor κB and consequent inducible NOS (iNOS)-mediated overproduction of NO, which in combination with excess superoxide produced during Rtp801 activation, contribute to increased oxido-nitrosative stress and lung protein nitration. However, lung-specific inhibition of iNOS with a iNOS-specific inhibitor, N6-(1-iminoethyl)-L-lysine, dihydrochloride (L-NIL) solely restricts lung protein nitration but fails to prevent or reverse the major tobacco smoke-induced oxidative lung injury. In comparison, the dietary antioxidant, ascorbate or vitamin C, can substantially prevent such damage by inhibiting both tobacco smoke-induced lung protein oxidation as well as activation of pulmonary Rtp801 and consequent iNOS/NO-induced nitration of lung proteins, that otherwise lead to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases, resulting in emphysematous lung damage. Vitamin C also restricts the up-regulation of matrix-metalloproteinase-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco smoke-induced emphysema. Overall, our findings implicate tobacco-smoke oxidant(s) as the primary etiopathogenic factor behind both the noncellular and cellular damage mechanisms governing emphysematous lung injury and demonstrate the potential of vitamin C to accomplish holistic prevention of such damage.

Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis

PubMed Central

Gupta, Indranil; Ganguly, Souradipta; Rozanas, Christine R.; Stuehr, Dennis J.

2016-01-01

Cigarette smoking causes emphysema, a fatal disease involving extensive structural and functional damage of the lung. Using a guinea pig model and human lung cells, we show that oxidant(s) present in tobacco smoke not only cause direct oxidative damage of lung proteins, contributing to the major share of lung injury, but also activate Rtp801, a key proinflammatory cellular factor involved in tobacco smoke-induced lung damage. Rtp801 triggers nuclear factor κB and consequent inducible NOS (iNOS)-mediated overproduction of NO, which in combination with excess superoxide produced during Rtp801 activation, contribute to increased oxido-nitrosative stress and lung protein nitration. However, lung-specific inhibition of iNOS with a iNOS-specific inhibitor, N6-(1-iminoethyl)-L-lysine, dihydrochloride (L-NIL) solely restricts lung protein nitration but fails to prevent or reverse the major tobacco smoke-induced oxidative lung injury. In comparison, the dietary antioxidant, ascorbate or vitamin C, can substantially prevent such damage by inhibiting both tobacco smoke-induced lung protein oxidation as well as activation of pulmonary Rtp801 and consequent iNOS/NO-induced nitration of lung proteins, that otherwise lead to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases, resulting in emphysematous lung damage. Vitamin C also restricts the up-regulation of matrix-metalloproteinase-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco smoke-induced emphysema. Overall, our findings implicate tobacco-smoke oxidant(s) as the primary etiopathogenic factor behind both the noncellular and cellular damage mechanisms governing emphysematous lung injury and demonstrate the potential of vitamin C to accomplish holistic prevention of such damage. PMID:27382160

Remote Sensing of Wildland Fire-Induced Risk Assessment at the Community Level

PubMed Central

Hassan, Quazi K.

2018-01-01

Wildland fires are some of the critical natural hazards that pose a significant threat to the communities located in the vicinity of forested/vegetated areas. In this paper, our overall objective was to study the structural damages due to the 2016 Horse River Fire (HRF) that happened in Fort McMurray (Alberta, Canada) by employing primarily very high spatial resolution optical satellite data, i.e., WorldView-2. Thus, our activities included the: (i) estimation of the structural damages; and (ii) delineation of the wildland-urban interface (WUI) and its associated buffers at certain intervals, and their utilization in assessing potential risks. Our proposed method of remote sensing-based estimates of the number of structural damages was compared with the ground-based information available from the Planning and Development Recovery Committee Task Force of Regional Municipality of Wood Buffalo (RMWB); and found a strong linear relationship (i.e., r2 value of 0.97 with a slope of 0.97). Upon delineating the WUI and its associated buffer zones at 10 m, 30 m, 50 m, 70 m and 100 m distances; we found existence of vegetation within the 30 m buffers from the WUI for all of the damaged structures. In addition, we noticed that the relevant authorities had removed vegetation in some areas between 30 m and 70 m buffers from the WUI, which was proven to be effective in order to protect the structures in the adjacent communities. Furthermore, we mapped the wildland fire-induced vulnerable areas upon considering the WUI and its associated buffers. Our analysis revealed that approximately 30% of the areas within the buffer zones of 10 m and 30 m were vulnerable due to the presence of vegetation; in which, approximately 7% were burned during the 2016 HRF event that led the structural damages. Consequently, we suggest to remove the existing vegetation within these critical zones and also monitor the region at a regular interval in order to reduce the wildland fire-induced risk. PMID:29762504

Selenium suppresses glutamate-induced cell death and prevents mitochondrial morphological dynamic alterations in hippocampal HT22 neuronal cells.

PubMed

Ma, Yan-Mei; Ibeanu, Gordon; Wang, Li-Yao; Zhang, Jian-Zhong; Chang, Yue; Dong, Jian-Da; Li, P Andy; Jing, Li

2017-01-19

Previous studies have indicated that selenium supplementation may be beneficial in neuroprotection against glutamate-induced cell damage, in which mitochondrial dysfunction is considered a major pathogenic feature. However, the exact mechanisms by which selenium protects against glutamate-provoked mitochondrial perturbation remain ambiguous. In this study glutamate exposed murine hippocampal neuronal HT22 cell was used as a model to investigate the underlying mechanisms of selenium-dependent protection against mitochondria damage. We find that glutamate-induced cytotoxicity was associated with enhancement of superoxide production, activation of caspase-9 and -3, increases of mitochondrial fission marker and mitochondrial morphological changes. Selenium significantly resolved the glutamate-induced mitochondria structural damage, alleviated oxidative stress, decreased Apaf-1, caspases-9 and -3 contents, and altered the autophagy process as observed by a decline in the ratio of the autophagy markers LC3-I and LC3-II. These findings suggest that the protection of selenium against glutamate stimulated cell damage of HT22 cells is associated with amelioration of mitochondrial dynamic imbalance.

Role of tool marks inside spherical mitigation pit fabricated by micro-milling on repairing quality of damaged KH2PO4 crystal

PubMed Central

Chen, Ming-Jun; Cheng, Jian; Yuan, Xiao-Dong; Liao, Wei; Wang, Hai-Jun; Wang, Jing-He; Xiao, Yong; Li, Ming-Quan

2015-01-01

Repairing initial slight damage site into stable structures by engineering techniques is the leading strategy to mitigate the damage growth on large-size components used in laser-driven fusion facilities. For KH2PO4 crystals, serving as frequency converter and optoelectronic switch-Pockels cell, micro-milling has been proven the most promising method to fabricate these stable structures. However, tool marks inside repairing pit would be unavoidably introduced due to the wearing of milling cutter in actual repairing process. Here we quantitatively investigate the effect of tool marks on repairing quality of damaged crystal components by simulating its induced light intensification and testing the laser-induced damage threshold. We found that due to the formation of focusing hot spots and interference ripples, the light intensity is strongly enhanced with the presence of tool marks, especially for those on rear surfaces. Besides, the negative effect of tool marks is mark density dependent and multiple tool marks would aggravate the light intensification. Laser damage tests verified the role of tool marks as weak points, reducing the repairing quality. This work offers new criterion to comprehensively evaluate the quality of repaired optical surfaces to alleviate the bottleneck issue of low laser damage threshold for optical components in laser-driven fusion facilities. PMID:26399624

Human XPA and RPA DNA repair proteins participate in specific recognition of triplex-induced helical distortions

NASA Astrophysics Data System (ADS)

Vasquez, Karen M.; Christensen, Jesper; Li, Lei; Finch, Rick A.; Glazer, Peter M.

2002-04-01

Nucleotide excision repair (NER) plays a central role in maintaining genomic integrity by detecting and repairing a wide variety of DNA lesions. Xeroderma pigmentosum complementation group A protein (XPA) is an essential component of the repair machinery, and it is thought to be involved in the initial step as a DNA damage recognition and/or confirmation factor. Human replication protein A (RPA) and XPA have been reported to interact to form a DNA damage recognition complex with greater specificity for damaged DNA than XPA alone. The mechanism by which these two proteins recognize such a wide array of structures resulting from different types of DNA damage is not known. One possibility is that they recognize a common feature of the lesions, such as distortions of the helical backbone. We have tested this idea by determining whether human XPA and RPA proteins can recognize the helical distortions induced by a DNA triple helix, a noncanonical DNA structure that has been shown to induce DNA repair, mutagenesis, and recombination. We measured binding of XPA and RPA, together or separately, to substrates containing triplexes with three, two, or no strands covalently linked by psoralen conjugation and photoaddition. We found that RPA alone recognizes all covalent triplex structures, but also forms multivalent nonspecific DNA aggregates at higher concentrations. XPA by itself does not recognize the substrates, but it binds them in the presence of RPA. Addition of XPA decreases the nonspecific DNA aggregate formation. These results support the hypothesis that the NER machinery is targeted to helical distortions and demonstrate that RPA can recognize damaged DNA even without XPA.

Discontinuously Stiffened Composite Panel under Compressive Loading

NASA Technical Reports Server (NTRS)

Minnetyan, Levon; Rivers, James M.; Chamis, Christos C.; Murthy, Pappu L. N.

1995-01-01

The design of composite structures requires an evaluation of their safety and durability under service loads and possible overload conditions. This paper presents a computational tool that has been developed to examine the response of stiffened composite panels via the simulation of damage initiation, growth, accumulation, progression, and propagation to structural fracture or collapse. The structural durability of a composite panel with a discontinuous stiffener is investigated under compressive loading induced by the gradual displacement of an end support. Results indicate damage initiation and progression to have significant effects on structural behavior under loading. Utilization of an integrated computer code for structural durability assessment is demonstrated.

Fabrication of monolithic microfluidic channels in diamond with ion beam lithography

NASA Astrophysics Data System (ADS)

Picollo, F.; Battiato, A.; Boarino, L.; Ditalia Tchernij, S.; Enrico, E.; Forneris, J.; Gilardino, A.; Jakšić, M.; Sardi, F.; Skukan, N.; Tengattini, A.; Olivero, P.; Re, A.; Vittone, E.

2017-08-01

In the present work, we report on the monolithic fabrication by means of ion beam lithography of hollow micro-channels within a diamond substrate, to be employed for microfluidic applications. The fabrication strategy takes advantage of ion beam induced damage to convert diamond into graphite, which is characterized by a higher reactivity to oxidative etching with respect to the chemically inert pristine structure. This phase transition occurs in sub-superficial layers thanks to the peculiar damage profile of MeV ions, which mostly damage the target material at their end of range. The structures were obtained by irradiating commercial CVD diamond samples with a micrometric collimated C+ ion beam at three different energies (4 MeV, 3.5 MeV and 3 MeV) at a total fluence of 2 × 1016 cm-2. The chosen multiple-energy implantation strategy allows to obtain a thick box-like highly damaged region ranging from 1.6 μm to 2.1 μm below the sample surface. High-temperature annealing was performed to both promote the graphitization of the ion-induced amorphous layer and to recover the pristine crystalline structure in the cap layer. Finally, the graphite was removed by ozone etching, obtaining monolithic microfluidic structures. These prototypal microfluidic devices were tested injecting aqueous solutions and the evidence of the passage of fluids through the channels was confirmed by confocal fluorescent microscopy.

Effects of fluoride on synapse morphology and myelin damage in mouse hippocampus.

PubMed

Niu, Ruiyan; Chen, Huijuan; Manthari, Ram Kumar; Sun, Zilong; Wang, Jinming; Zhang, Jianhai; Wang, Jundong

2018-03-01

To investigate the fluoride-induced neurotoxicity on mice hippocampus, healthy adult mice were exposed to 25, 50, and 100 mg NaF/L for 60 days. The results showed that medium and high fluoride administration induced ultrastructural alterations in the structure of neuron synapse, including indistinct and short synaptic cleft, and thickened postsynaptic density (PSD). The significant reduced mRNA expressions of proteolipid protein (PLP) in medium and high fluoride groups suggested that myelin damage occurred in hippocampus. The myelin damage in turn was determined by the increased myelin-associated glycoprotein (MAG) level, which is naturally released by injured myelin, in high fluoride group, compared to the medium fluoride group. In addition, high fluoride exposure also reduced the mRNA and protein levels of cAMP response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF), and neural cell adhesion molecule (NCAM). These findings suggested that the alteration in synaptic structure and myelin damage may partly be due to adverse effects of fluoride on the neurotrophy and neuron adhesion in mice hippocampus. Copyright © 2017 Elsevier Ltd. All rights reserved.

Linking lung function to structural damage of alveolar epithelium in ventilator-induced lung injury.

PubMed

Hamlington, Katharine L; Smith, Bradford J; Dunn, Celia M; Charlebois, Chantel M; Roy, Gregory S; Bates, Jason H T

2018-05-06

Understanding how the mechanisms of ventilator-induced lung injury (VILI), namely atelectrauma and volutrauma, contribute to the failure of the blood-gas barrier and subsequent intrusion of edematous fluid into the airspace is essential for the design of mechanical ventilation strategies that minimize VILI. We ventilated mice with different combinations of tidal volume and positive end-expiratory pressure (PEEP) and linked degradation in lung function measurements to injury of the alveolar epithelium observed via scanning electron microscopy. Ventilating with both high inspiratory plateau pressure and zero PEEP was necessary to cause derangements in lung function as well as visually apparent physical damage to the alveolar epithelium of initially healthy mice. In particular, the epithelial injury was tightly associated with indicators of alveolar collapse. These results support the hypothesis that mechanical damage to the epithelium during VILI is at least partially attributed to atelectrauma-induced damage of alveolar type I epithelial cells. Copyright © 2018. Published by Elsevier B.V.

Study on Wind-induced Vibration and Fatigue Life of Cable-stayed Flexible Antenna

NASA Astrophysics Data System (ADS)

He, Kongde; He, Xuehui; Fang, Zifan; Zheng, Xiaowei; Yu, Hongchang

2018-03-01

The cable-stayed flexible antenna is a large-span space structure composed of flexible multibody, with low frequency of vibration, vortex-induced resonance can occur under the action of Stochastic wind, and a larger amplitude is generated when resonance occurs. To solve this problem, based on the theory of vortex-induced vibration, this paper analyzes the vortex-induced vibration of a cable-stayed flexible antenna under the action of Wind. Based on the sinusoidal force model and Autoregressive Model (AR) method, the vortex-induced force is simulated, then the fatigue analysis of the structure is based on the linear fatigue cumulative damage principle and the rain-flow method. The minimum fatigue life of the structure is calculated to verify the vibration fatigue performance of the structure.

Wireless ultrasonic wavefield imaging via laser for hidden damage detection inside a steel box girder bridge

NASA Astrophysics Data System (ADS)

An, Yun-Kyu; Song, Homin; Sohn, Hoon

2014-09-01

This paper presents a wireless ultrasonic wavefield imaging (WUWI) technique for detecting hidden damage inside a steel box girder bridge. The proposed technique allows (1) complete wireless excitation of piezoelectric transducers and noncontact sensing of the corresponding responses using laser beams, (2) autonomous damage visualization without comparing against baseline data previously accumulated from the pristine condition of a target structure and (3) robust damage diagnosis even for real structures with complex structural geometries. First, a new WUWI hardware system was developed by integrating optoelectronic-based signal transmitting and receiving devices and a scanning laser Doppler vibrometer. Next, a damage visualization algorithm, self-referencing f-k filter (SRF), was introduced to isolate and visualize only crack-induced ultrasonic modes from measured ultrasonic wavefield images. Finally, the performance of the proposed technique was validated through hidden crack visualization at a decommissioned Ramp-G Bridge in South Korea. The experimental results reveal that the proposed technique instantaneously detects and successfully visualizes hidden cracks even in the complex structure of a real bridge.

Fatigue Life of Postbuckled Structures with Indentation Damages

NASA Technical Reports Server (NTRS)

Davila, Carlos G.; Bisagni, Chiara

2016-01-01

The fatigue life of composite stiffened panels with indentation damage was investigated experimentally using single stringer compression specimens. Indentation damage was induced on one of the two flanges of each stringer. The experiments were conducted using advanced instrumentation, including digital image correlation, passive thermography, and in-situ ultrasonic scanning. Specimens with initial indentation damage lengths of 32 millimeters to 56 millimeters were tested quasi-statically and in fatigue, and the effects of cyclic load amplitude and damage size were studied. A means of comparison of the damage propagation rates and collapse loads based on a stress intensity measure and the Paris law is proposed.

Laser-Induced Damage with Femtosecond Pulses

NASA Astrophysics Data System (ADS)

Kafka, Kyle R. P.

The strong electric fields of focused femtosecond laser pulses lead to non-equilibrium dynamics in materials, which, beyond a threshold intensity, causes laser-induced damage (LID). Such a strongly non-linear and non-perturbative process renders important LID observables like fluence and intensity thresholds and damage morphology (crater) extremely difficult to predict quantitatively. However, femtosecond LID carries a high degree of precision, which has been exploited in various micro/nano-machining and surface engineering applications, such as human eye surgery and super-hydrophobic surfaces. This dissertation presents an array of experimental studies which have measured the damage behavior of various materials under femtosecond irradiation. Precision experiments were performed to produce extreme spatio-temporal confinement of the femtosecond laser-solid damage interaction on monocrystalline Cu, which made possible the first successful direct-benchmarking of LID simulation with realistic damage craters. A technique was developed to produce laser-induced periodic surface structures (LIPSS) in a single pulse (typically a multi-pulse phenomenon), and was used to perform a pump-probe study which revealed asynchronous LIPSS formation on copper. Combined with 1-D calculations, this new experimental result suggests more drastic electron heating than expected. Few-cycle pulses were used to study the LID performance and morphology of commercial ultra-broadband optics, which had not been systematically studied before. With extensive surface analysis, various morphologies were observed, including LIPSS, swelling (blisters), simple craters, and even ring-shaped structures, which varied depending on the coating design, number of pulses, and air/vacuum test environment. Mechanisms leading to these morphologies are discussed, many of which are ultrafast in nature. The applied damage behavior of multi-layer dielectric mirrors was measured and compared between long pulse (150 ps) and femtosecond (33 fs) regimes for a large number of optics contributed by manufacturers globally. The damage performance of the mirrors in the 150 ps tests was shown to be uncorrelated with the 33 fs tests, which implies that the two regimes are guided by different mechanisms. In fact, one of the worst-performing mirrors in the long-pulse regime turned out to be the best-performer in the femtosecond regime. The broad array of experimental results presented here all found that LID in the femtosecond regime is distinctly different from long pulse damage, and paves multiple pathways into developing the next stage of theoretical models and applications of femtosecond laser-induced damage.

Irradiation induced modest changes in murine cardiac function despite progressive structural damage to the myocardium and microvasculature.

PubMed

Seemann, Ingar; Gabriels, Karen; Visser, Nils L; Hoving, Saske; te Poele, Johannes A; Pol, Jeffrey F; Gijbels, Marion J; Janssen, Ben J; van Leeuwen, Fijs W; Daemen, Mat J; Heeneman, Sylvia; Stewart, Fiona A

2012-05-01

Radiotherapy of thoracic and chest wall tumors increases the long-term risk of cardiotoxicity, but the underlying mechanisms are unclear. Single doses of 2, 8, or 16 Gy were delivered to the hearts of mice and damage was evaluated at 20, 40, and 60 weeks, relative to age matched controls. Single photon emission computed tomography (SPECT/CT) and ultrasound were used to measure cardiac geometry and function, which was related to histo-morphology and microvascular damage. Gated SPECT/CT and ultrasound demonstrated decreases in end diastolic and systolic volumes, while the ejection fraction was increased at 20 and 40 weeks after 2, 8, and 16 Gy. Cardiac blood volume was decreased at 20 and 60 weeks after irradiation. Histological examination revealed inflammatory changes at 20 and 40 weeks after 8 and 16 Gy. Microvascular density in the left ventricle was decreased at 40 and 60 weeks after 8 and 16 Gy, with functional damage to remaining microvasculature manifest as decreased alkaline phosphatase (2, 8, and 16 Gy), increased von Willebrand Factor and albumin leakage from vessels (8 and 16 Gy), and amyloidosis (16 Gy). 16 Gy lead to sudden death between 30 and 40 weeks in 38% of mice. Irradiation with 2 and 8 Gy induced modest changes in murine cardiac function within 20 weeks but this did not deteriorate further, despite progressive structural and microvascular damage. This indicates that heart function can compensate for significant structural damage, although higher doses, eventually lead to sudden death. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Coupled attenuation and multiscale damage model for composite structures

NASA Astrophysics Data System (ADS)

Moncada, Albert M.; Chattopadhyay, Aditi; Bednarcyk, Brett; Arnold, Steven M.

2011-04-01

Composite materials are widely used in many applications for their high strength, low weight, and tailorability for specific applications. However, the development of robust and reliable methodologies to detect micro level damage in composite structures has been challenging. For composite materials, attenuation of ultrasonic waves propagating through the media can be used to determine damage within the material. Currently available numerical solutions for attenuation induce arbitrary damage, such as fiber-matrix debonding or inclusions, to show variations between healthy and damaged states. This paper addresses this issue by integrating a micromechanics analysis to simulate damage in the form of a fiber-matrix crack and an analytical model for calculating the attenuation of the waves when they pass through the damaged region. The hybrid analysis is validated by comparison with experimental stress-strain curves and piezoelectric sensing results for attenuation measurement. The results showed good agreement between the experimental stress-strain curves and the results from the micromechanics analysis. Wave propagation analysis also showed good correlation between simulation and experiment for the tested frequency range.

Structural damage detection for in-service highway bridge under operational and environmental variability

NASA Astrophysics Data System (ADS)

Jin, Chenhao; Li, Jingcheng; Jang, Shinae; Sun, Xiaorong; Christenson, Richard

2015-03-01

Structural health monitoring has drawn significant attention in the past decades with numerous methodologies and applications for civil structural systems. Although many researchers have developed analytical and experimental damage detection algorithms through vibration-based methods, these methods are not widely accepted for practical structural systems because of their sensitivity to uncertain environmental and operational conditions. The primary environmental factor that influences the structural modal properties is temperature. The goal of this article is to analyze the natural frequency-temperature relationships and detect structural damage in the presence of operational and environmental variations using modal-based method. For this purpose, correlations between natural frequency and temperature are analyzed to select proper independent variables and inputs for the multiple linear regression model and neural network model. In order to capture the changes of natural frequency, confidence intervals to detect the damages for both models are generated. A long-term structural health monitoring system was installed on an in-service highway bridge located in Meriden, Connecticut to obtain vibration and environmental data. Experimental testing results show that the variability of measured natural frequencies due to temperature is captured, and the temperature-induced changes in natural frequencies have been considered prior to the establishment of the threshold in the damage warning system. This novel approach is applicable for structural health monitoring system and helpful to assess the performance of the structure for bridge management and maintenance.

Structural responses of metallic glasses under neutron irradiation.

PubMed

Yang, L; Li, H Y; Wang, P W; Wu, S Y; Guo, G Q; Liao, B; Guo, Q L; Fan, X Q; Huang, P; Lou, H B; Guo, F M; Zeng, Q S; Sun, T; Ren, Y; Chen, L Y

2017-12-01

Seeking nuclear materials that possess a high resistance to particle irradiation damage is a long-standing issue. Permanent defects, induced by irradiation, are primary structural changes, the accumulation of which will lead to structural damage and performance degradation in crystalline materials served in nuclear plants. In this work, structural responses of neutron irradiation in metallic glasses (MGs) have been investigated by making a series of experimental measurements, coupled with simulations in ZrCu amorphous alloys. It is found that, compared with crystalline alloys, MGs have some specific structural responses to neutron irradiation. Although neutron irradiation can induce transient vacancy-like defects in MGs, they are fully annihilated after structural relaxation by rearrangement of free volumes. In addition, the rearrangement of free volumes depends strongly on constituent elements. In particular, the change in free volumes occurs around the Zr atoms, rather than the Cu centers. This implies that there is a feasible strategy for identifying glassy materials with high structural stability against neutron irradiation by tailoring the microstructures, the systems, or the compositions in alloys. This work will shed light on the development of materials with high irradiation resistance.

XPD-dependent activation of apoptosis in response to triplex-induced DNA damage

PubMed Central

Kaushik Tiwari, Meetu; Rogers, Faye A.

2013-01-01

DNA sequences capable of forming triplexes are prevalent in the human genome and have been found to be intrinsically mutagenic. Consequently, a balance between DNA repair and apoptosis is critical to counteract their effect on genomic integrity. Using triplex-forming oligonucleotides to synthetically create altered helical distortions, we have determined that pro-apoptotic pathways are activated by the formation of triplex structures. Moreover, the TFIIH factor, XPD, occupies a central role in triggering apoptosis in response to triplex-induced DNA strand breaks. Here, we show that triplexes are capable of inducing XPD-independent double strand breaks, which result in the formation of γH2AX foci. XPD was subsequently recruited to the triplex-induced double strand breaks and co-localized with γH2AX at the damage site. Furthermore, phosphorylation of H2AX tyrosine 142 was found to stimulate the signaling pathway of XPD-dependent apoptosis. We suggest that this mechanism may play an active role in minimizing genomic instability induced by naturally occurring noncanonical structures, perhaps protecting against cancer initiation. PMID:23913414

Dynamic permeability in fault damage zones induced by repeated coseismic fracturing events

NASA Astrophysics Data System (ADS)

Aben, F. M.; Doan, M. L.; Mitchell, T. M.

2017-12-01

Off-fault fracture damage in upper crustal fault zones change the fault zone properties and affect various co- and interseismic processes. One of these properties is the permeability of the fault damage zone rocks, which is generally higher than the surrounding host rock. This allows large-scale fluid flow through the fault zone that affects fault healing and promotes mineral transformation processes. Moreover, it might play an important role in thermal fluid pressurization during an earthquake rupture. The damage zone permeability is dynamic due to coseismic damaging. It is crucial for earthquake mechanics and for longer-term processes to understand how the dynamic permeability structure of a fault looks like and how it evolves with repeated earthquakes. To better detail coseismically induced permeability, we have performed uniaxial split Hopkinson pressure bar experiments on quartz-monzonite rock samples. Two sample sets were created and analyzed: single-loaded samples subjected to varying loading intensities - with damage varying from apparently intact to pulverized - and samples loaded at a constant intensity but with a varying number of repeated loadings. The first set resembles a dynamic permeability structure created by a single large earthquake. The second set resembles a permeability structure created by several earthquakes. After, the permeability and acoustic velocities were measured as a function of confining pressure. The permeability in both datasets shows a large and non-linear increase over several orders of magnitude (from 10-20 up to 10-14 m2) with an increasing amount of fracture damage. This, combined with microstructural analyses of the varying degrees of damage, suggests a percolation threshold. The percolation threshold does not coincide with the pulverization threshold. With increasing confining pressure, the permeability might drop up to two orders of magnitude, which supports the possibility of large coseismic fluid pulses over relatively large distances along a fault. Also, a relatively small threshold could potentially increase permeability in a large volume of rock, given that previous earthquakes already damaged these rocks.

Effects of substrate on the femtosecond laser-induced damage properties of gold films

NASA Astrophysics Data System (ADS)

Huang, Haopeng; Wang, Leilei; Kong, Fanyu; Xia, Zhilin; Jin, Yunxia; Xu, Jiao; Chen, Junming; Cui, Yun; Shao, Jianda

2018-07-01

In this work, gold films on two different types of substrates were fabricated by electron beam (e-beam) evaporation, and the femtosecond laser-induced damage properties were evaluated. The first sample was gold film deposited on fused silica, whereas the second was gold deposited on photoresist. 1-on-1 damage tests were implemented by an 800 ± 30 nm laser with pulse duration of 30 fs. Different damage thresholds and morphologies were obtained for the two samples. The damage threshold of the gold film on fused silica was 0.64 J/cm2, with the typical damage morphology of thermal ablation and melting; the damage threshold of the gold film on photoresist was 0.30 J/cm2, with the typical damage morphology of blisters or peeling off. In order to better understand the impact of the substrate on the properties of the whole sample, the normalized electric field intensity, temperature, and thermal stress distributions were calculated. The adhesion between the gold film and substrate were measured and the experimental results well agreed with the theoretical analysis. The results indicate that gold films deposited onto grating-structured fused silica will have more powerful laser damage resistance performance.

Next generation control system for reflexive aerostructures

NASA Astrophysics Data System (ADS)

Maddux, Michael R.; Meents, Elizabeth P.; Barnell, Thomas J.; Cable, Kristin M.; Hemmelgarn, Christopher; Margraf, Thomas W.; Havens, Ernie

2010-04-01

Cornerstone Research Group Inc. (CRG) has developed and demonstrated a composite structural solution called reflexive composites for aerospace applications featuring CRG's healable shape memory polymer (SMP) matrix. In reflexive composites, an integrated structural health monitoring (SHM) system autonomously monitors the structural health of composite aerospace structures, while integrated intelligent controls monitor data from the SHM system to characterize damage and initiate healing when damage is detected. Development of next generation intelligent controls for reflexive composites were initiated for the purpose of integrating prognostic health monitoring capabilities into the reflexive composite structural solution. Initial efforts involved data generation through physical inspections and mechanical testing. Compression after impact (CAI) testing was conducted on composite-reinforced shape memory polymer samples to induce damage and investigate the effectiveness of matrix healing on mechanical performance. Non-destructive evaluation (NDE) techniques were employed to observe and characterize material damage. Restoration of mechanical performance was demonstrated through healing, while NDE data showed location and size of damage and verified mitigation of damage post-healing. Data generated was used in the development of next generation reflexive controls software. Data output from the intelligent controls could serve as input to Integrated Vehicle Health Management (IVHM) systems and Integrated Resilient Aircraft Controls (IRAC). Reflexive composite technology has the ability to reduce maintenance required on composite structures through healing, offering potential to significantly extend service life of aerospace vehicles and reduce operating and lifecycle costs.

33 CFR 222.4 - Reporting earthquake effects.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... This indicates the possibility that earthquake induced loads may not have been adequately considered in... misalignment of hydraulic control structures or gates. Induced dynamic loading on earth dams may result in loss... area where the earthquake is felt but causes no or insignificant damage (Modified Mercalli Intensity VI...

33 CFR 222.4 - Reporting earthquake effects.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... This indicates the possibility that earthquake induced loads may not have been adequately considered in... misalignment of hydraulic control structures or gates. Induced dynamic loading on earth dams may result in loss... area where the earthquake is felt but causes no or insignificant damage (Modified Mercalli Intensity VI...

Sensing Applied Load and Damage Effects in Composites with Nondestructive Techniques

DTIC Science & Technology

2017-05-01

evaluation (NDE) techniques. Evaluation using piezoelectrically induced guided waves, acoustic emission, thermography, and X-ray imaging were compared...nondestructive inspection to further understanding of the material itself and the capabilities of various nondestructive evaluation (NDE) techniques...materials because of their inherent differences. NDE techniques exist that can evaluate composite structures for damage including C-Scan

Damage of multilayer optics with varying capping layers induced by focused extreme ultraviolet beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jody Corso, Alain; Nicolosi, Piergiorgio; Nardello, Marco

2013-05-28

Extreme ultraviolet Mo/Si multilayers protected by capping layers of different materials were exposed to 13.5 nm plasma source radiation generated with a table-top laser to study the irradiation damage mechanism. Morphology of single-shot damaged areas has been analyzed by means of atomic force microscopy. Threshold fluences were evaluated for each type of sample in order to determine the capability of the capping layer to protect the structure underneath.

High-speed imaging and small-scale explosive characterization techniques to understand effects of primary blast-induced injury on nerve cell structure and function

NASA Astrophysics Data System (ADS)

Piehler, T.; Banton, R.; Zander, N.; Duckworth, J.; Benjamin, R.; Sparks, R.

2018-01-01

Traumatic brain injury (TBI) is often associated with blast exposure. Even in the absence of penetrating injury or evidence of tissue injury on imaging, blast TBI may trigger a series of neural/glial cellular and functional changes. Unfortunately, the diagnosis and proper treatment of mild traumatic brain injury (mTBI) caused by explosive blast is challenging, as it is not easy to clinically distinguish blast from non-blast TBI on the basis of patient symptoms. Damage to brain tissue, cell, and subcellular structures continues to occur slowly and in a manner undetectable by conventional imaging techniques. The threshold shock impulse levels required to induce damage and the cumulative effects upon multiple exposures are not well characterized. Understanding how functional and structural damage from realistic blast impact at cellular and tissue levels at variable timescales after mTBI events may be vital for understanding this injury phenomenon and for linking mechanically induced structural changes with measurable effects on the nervous system. Our working hypothesis is that there is some transient physiological dysfunction occurring at cellular and subcellular levels within the central nervous system due to primary blast exposure. We have developed a novel in vitro indoor experimental system that uses real military explosive charges to more accurately represent military blast exposure and to probe the effects of primary explosive blast on dissociated neurons. We believe this system offers a controlled experimental method to analyze and characterize primary explosive blast-induced cellular injury and to understand threshold injury phenomenon. This paper will also focus on the modeling aspect of our work and how it relates to the experimental work.

3D-analysis of plant microstructures: advantages and limitations of synchrotron X-ray microtomography

NASA Astrophysics Data System (ADS)

Matsushima, U.; Graf, W.; Zabler, S.; Manke, I.; Dawson, M.; Choinka, G.; Hilger, A.; Herppich, W. B.

2013-01-01

Synchrotron X-ray computer microtomography was used to analyze the microstructure of rose peduncles. Samples from three rose cultivars, differing in anatomy, were scanned to study the relation between tissue structure and peduncles mechanical strength. Additionally, chlorophyll fluorescence imaging and conventional light microscopy was applied to quantify possible irradiation-induced damage to plant physiology and tissue structure. The spatial resolution of synchrotron X-ray computer microtomography was sufficiently high to investigate the complex tissues of intact rose peduncles without the necessity of any preparation. However, synchrotron X-radiation induces two different types of damage on irradiated tissues. First, within a few hours after first X-ray exposure, there is a direct physical destruction of cell walls. In addition, a slow and delayed destruction of chlorophyll and, consequently, of photosynthetic activity occurred within hours/ days after the exposure. The results indicate that synchrotron X-ray computer microtomography is well suited for three-dimensional visualization of the microstructure of rose peduncles. However, in its current technique, synchrotron X-ray computer microtomography is not really non-destructive but induce tissue damage. Hence, this technique needs further optimization before it can be applied for time-series investigations of living plant materials

DDB2 promotes chromatin decondensation at UV-induced DNA damage

PubMed Central

Lindh, Michael; Acs, Klara; Vrouwe, Mischa G.; Pines, Alex; van Attikum, Haico; Mullenders, Leon H.

2012-01-01

Nucleotide excision repair (NER) is the principal pathway that removes helix-distorting deoxyribonucleic acid (DNA) damage from the mammalian genome. Recognition of DNA lesions by xeroderma pigmentosum group C (XPC) protein in chromatin is stimulated by the damaged DNA-binding protein 2 (DDB2), which is part of a CUL4A–RING ubiquitin ligase (CRL4) complex. In this paper, we report a new function of DDB2 in modulating chromatin structure at DNA lesions. We show that DDB2 elicits unfolding of large-scale chromatin structure independently of the CRL4 ubiquitin ligase complex. Our data reveal a marked adenosine triphosphate (ATP)–dependent reduction in the density of core histones in chromatin containing UV-induced DNA lesions, which strictly required functional DDB2 and involved the activity of poly(adenosine diphosphate [ADP]–ribose) polymerase 1. Finally, we show that lesion recognition by XPC, but not DDB2, was strongly reduced in ATP-depleted cells and was regulated by the steady-state levels of poly(ADP-ribose) chains. PMID:22492724

Gamma and Ion-Beam Irradiation of DNA: Free Radical Mechanisms, Electron Effects, and Radiation Chemical Track Structure

PubMed Central

Sevilla, Michael D.; Becker, David; Kumar, Anil; Adhikary, Amitava

2016-01-01

The focus of our laboratory’s investigation is to study the direct-type DNA damage mechanisms resulting from γ-ray and ion-beam radiation-induced free radical processes in DNA which lead to molecular damage important to cellular survival. This work compares the results of low LET (γ−) and high LET (ion-beam) radiation to develop a chemical track structure model for ion-beam radiation damage to DNA. Recent studies on protonation states of cytosine cation radicals in the N1-substituted cytosine derivatives in their ground state and 5-methylcytosine cation radicals in ground as well as in excited state are described. Our results exhibit a radical signature of excitations in 5-methylcytosine cation radical. Moreover, our recent theoretical studies elucidate the role of electron-induced reactions (low energy electrons (LEE), presolvated electrons (epre−), and aqueous (or, solvated) electrons (eaq−)). Finally DFT calculations of the ionization potentials of various sugar radicals show the relative reactivity of these species. PMID:27695205

Gamma and ion-beam irradiation of DNA: Free radical mechanisms, electron effects, and radiation chemical track structure

NASA Astrophysics Data System (ADS)

Sevilla, Michael D.; Becker, David; Kumar, Anil; Adhikary, Amitava

2016-11-01

The focus of our laboratory's investigation is to study the direct-type DNA damage mechanisms resulting from γ-ray and ion-beam radiation-induced free radical processes in DNA which lead to molecular damage important to cellular survival. This work compares the results of low LET (γ-) and high LET (ion-beam) radiation to develop a chemical track structure model for ion-beam radiation damage to DNA. Recent studies on protonation states of cytosine cation radicals in the N1-substituted cytosine derivatives in their ground state and 5-methylcytosine cation radicals in ground as well as in excited state are described. Our results exhibit a radical signature of excitations in 5-methylcytosine cation radical. Moreover, our recent theoretical studies elucidate the role of electron-induced reactions (low energy electrons (LEE), presolvated electrons (epre-), and aqueous (or, solvated) electrons (eaq-)). Finally DFT calculations of the ionization potentials of various sugar radicals show the relative reactivity of these species.

[Redox-potential of blood and consistence of energoproviding defence system in cytomegalovirus infection in pregnancy].

PubMed

Dzhikiia, I V; Rizhvadze, M A; Dzhangidze, M A

2006-05-01

We have studied the relationship between the hypoxic change and mitochondrial redox-potential disturbances in the mechanism of pheto-placental insufficiency in pregnancy with cytomegalovirus infection (CMV), detected by the positive anti-CMV-IgG titer and more then 4-fold increase of low avid anti-CMV-IgG. It was shown, that chronic CMV infection induces production of active forms of oxygen, peroxidation of structures and concurrently damage of mitochondria with essential decrease of ATP level. Results of the study have shown the important diagnostic value of estimation of hypoxic-oxidative damage induced by CMV infection. The results also revealed important relationships between the activity of the CMV infection and intensity of mitochondrial damage. On the basis of our investigations we suggest the additional diagnostic test (the determination of citozol NADH dependent isocitratdehydrogenaze activity) to evaluate the depth of CMV induced metabolic disturbances.

Repair of distortion-induced fatigue damage in bridge no. 135-87 (043SB and 044NB) using newly-developed strengthening schemes : summary.

DOT National Transportation Integrated Search

2016-08-01

A steel girder twin bridge structure located near Park City, Kansas, has experienced : extensive distortion-induced fatigue cracking in its web-gap regions. Due to : the bridges skewed, staggered configuration, the majority of these cracks have : ...

Impact Cratering Physics al Large Planetary Scales

NASA Astrophysics Data System (ADS)

Ahrens, Thomas J.

2007-06-01

Present understanding of the physics controlling formation of ˜10^3 km diameter, multi-ringed impact structures on planets were derived from the ideas of Scripps oceanographer, W. Van Dorn, University of London's, W, Murray, and, Caltech's, D. O'Keefe who modeled the vertical oscillations (gravity and elasticity restoring forces) of shock-induced melt and damaged rock within the transient crater immediately after the downward propagating hemispheric shock has processed rock (both lining, and substantially below, the transient cavity crater). The resulting very large surface wave displacements produce the characteristic concentric, multi-ringed basins, as stored energy is radiated away and also dissipated upon inducing further cracking. Initial calculational description, of the above oscillation scenario, has focused upon on properly predicting the resulting density of cracks, and, their orientations. A new numerical version of the Ashby--Sammis crack damage model is coupled to an existing shock hydrodynamics code to predict impact induced damage distributions in a series of 15--70 cm rock targets from high speed impact experiments for a range of impactor type and velocity. These are compared to results of crack damage distributions induced in crustal rocks with small arms impactors and mapped ultrasonically in recent Caltech experiments (Ai and Ahrens, 2006).

Spatiotemporal dynamics of DNA repair proteins following laser microbeam induced DNA damage – When is a DSB not a DSB?☆

PubMed Central

Reynolds, Pamela; Botchway, Stanley W.; Parker, Anthony W.; O’Neill, Peter

2013-01-01

The formation of DNA lesions poses a constant threat to cellular stability. Repair of endogenously and exogenously produced lesions has therefore been extensively studied, although the spatiotemporal dynamics of the repair processes has yet to be fully understood. One of the most recent advances to study the kinetics of DNA repair has been the development of laser microbeams to induce and visualize recruitment and loss of repair proteins to base damage in live mammalian cells. However, a number of studies have produced contradictory results that are likely caused by the different laser systems used reflecting in part the wavelength dependence of the damage induced. Additionally, the repair kinetics of laser microbeam induced DNA lesions have generally lacked consideration of the structural and chemical complexity of the DNA damage sites, which are known to greatly influence their reparability. In this review, we highlight the key considerations when embarking on laser microbeam experiments and interpreting the real time data from laser microbeam irradiations. We compare the repair kinetics from live cell imaging with biochemical and direct quantitative cellular measurements for DNA repair. PMID:23688615

Chemistry of MOS-LSI radiation hardening

NASA Technical Reports Server (NTRS)

Grunthaner, P.

1985-01-01

The objective of this task was to obtain chemical information on MOS test samples. Toward this end, high resolution X-ray photoemission spectroscopy (XPS) has been the primary techniques used to characterize the chemistry and structure of the SiO2/Si interface for a variety of MOS structures with differing degrees of susceptibility to damage by ionizing radiation. The major accomplishments of this program are: (1) the identification of a structurally distinct region of SiO2 in the near-interfacial region of thermal SiO2 on Si; (2) the identification in the near-interfacial region of SiO2 structural differences between radiation hard and soft gate oxides; (3) the direct observation of radiation-induced damage sites in thermal SiO2 with XPS using in situ electron stress; (4) the correlation of suboxide state distributions at the SiO2/Si interface with processing parameters and radiation susceptibility; (5) the development of a chemical mechanism for radiation-induced interface state generation in SiO2/Si structures; and (6) the development benign chemical profiling techniques which permit the investigation of oxide/semiconductor structures using surface sensitive electron spectroscopic techniques.

The application of data mining and cloud computing techniques in data-driven models for structural health monitoring

NASA Astrophysics Data System (ADS)

Khazaeli, S.; Ravandi, A. G.; Banerji, S.; Bagchi, A.

2016-04-01

Recently, data-driven models for Structural Health Monitoring (SHM) have been of great interest among many researchers. In data-driven models, the sensed data are processed to determine the structural performance and evaluate the damages of an instrumented structure without necessitating the mathematical modeling of the structure. A framework of data-driven models for online assessment of the condition of a structure has been developed here. The developed framework is intended for automated evaluation of the monitoring data and structural performance by the Internet technology and resources. The main challenges in developing such framework include: (a) utilizing the sensor measurements to estimate and localize the induced damage in a structure by means of signal processing and data mining techniques, and (b) optimizing the computing and storage resources with the aid of cloud services. The main focus in this paper is to demonstrate the efficiency of the proposed framework for real-time damage detection of a multi-story shear-building structure in two damage scenarios (change in mass and stiffness) in various locations. Several features are extracted from the sensed data by signal processing techniques and statistical methods. Machine learning algorithms are deployed to select damage-sensitive features as well as classifying the data to trace the anomaly in the response of the structure. Here, the cloud computing resources from Amazon Web Services (AWS) have been used to implement the proposed framework.

Effects of allopurinol on exercise-induced muscle damage: new therapeutic approaches?

PubMed

Sanchis-Gomar, F; Pareja-Galeano, H; Perez-Quilis, C; Santos-Lozano, A; Fiuza-Luces, C; Garatachea, N; Lippi, G; Lucia, A

2015-01-01

Intensive muscular activity can trigger oxidative stress, and free radicals may hence be generated by working skeletal muscle. The role of the enzyme xanthine oxidase as a generating source of free radicals is well documented and therefore is involved in the skeletal muscle damage as well as in the potential transient cardiovascular damage induced by high-intensity physical exercise. Allopurinol is a purine hypoxanthine-based structural analog and a well-known inhibitor of xanthine oxidase. The administration of the xanthine oxidase inhibitor allopurinol may hence be regarded as promising, safe, and an economic strategy to decrease transient skeletal muscle damage (as well as heart damage, when occurring) in top-level athletes when administered before a competition or a particularly high-intensity training session. Although continuous administration of allopurinol in high-level athletes is not recommended due to its possible role in hampering training-induced adaptations, the drug might be useful in non-athletes. Exertional rhabdomyolysis is the most common form of rhabdomyolysis and affects individuals participating in a type of intense exercise to which they are not accustomed. This condition can cause exercise-related myoglobinuria, thus increasing the risk of acute renal failure and is also associated with sickle cell trait. In this manuscript, we have reviewed the recent evidence about the effects of allopurinol on exercise-induced muscle damage. More research is needed to determine whether allopurinol may be useful for preventing not only exertional rhabdomyolysis and acute renal damage but also skeletal muscle wasting in critical illness as well as in immobilized, bedridden, sarcopenic or cachectic patients.

Vision Integrating Strategies in Ophthalmology and Neurochemistry (VISION)

DTIC Science & Technology

2014-02-01

ganglion cells from pressure-induced damage in a rat model of glaucoma . Brn3b also induced optic nerve regeneration in this model (Stankowska et al. 2013...of glaucoma o Gene therapy with Neuritin1 structurally and functionally protected the retina in ONC model o CHOP knockout mice were structurally and...retinocollicular pathway of mice in a novel model of glaucoma . 2013 Annual Meeting of Association for Research in Vision and Ophthalmology, Abstract 421. Liu

Chronic intermittent hypobaric hypoxia attenuates radiation induced heart damage in rats.

PubMed

Wang, Jun; Wu, Yajing; Yuan, Fang; Liu, Yixian; Wang, Xuefeng; Cao, Feng; Zhang, Yi; Wang, Sheng

2016-09-01

Radiation-induced heart damage (RIHD) is becoming an increasing concern for patients and clinicians due to the use of radiotherapy for thoracic tumor. Chronic intermittent hypobaric hypoxia (CIHH) preconditioning has been documented to exert a cardioprotective effect. Here we hypothesized that CIHH was capable of attenuating functional and structural damage in a rat model of RIHD. Male adult Sprague-Dawley rats were randomly divided into 4 groups: control, radiation, CIHH and CIHH plus radiation. Cardiac function was measured using Langendorff perfusion in in vitro rat hearts. Cardiac fibrosis, oxidative stress and endoplasmic reticulum stress (ERS) was assessed by quantitative analysis of protein expression. No significant difference between any two groups was observed in baseline cardiac function as assessed by left ventricular end diastolic pressure (LVEDP), left ventricular developing pressure (LVDP) and the derivative of left ventricular pressure (±LVdp/dt). When challenged by ischemia/reperfusion, LVEDP was increased but LVDP and ±LVdp/dt was decreased significantly in radiation group compared with controls, accompanied by an enlarged infarct size and decreased coronary flow. Importantly, CIHH dramatically improved radiation-induced damage of cardiac function and blunted radiation-induced cardiac fibrosis in the perivascular and interstitial area. Furthermore, CIHH abrogated radiation-induced increase in malondialdehyde and enhanced total superoxide dismutase activity, as well as downregulated expression levels of ERS markers like GRP78 and CHOP. CIHH pretreatment alleviated radiation-induced damage of cardiac function and fibrosis. Such a protective effect was closely associated with suppression of oxidative stress and ERS responses. Copyright © 2016 Elsevier Inc. All rights reserved.

Paraquat-induced ultrastructural changes and DNA damage in the nervous system is mediated via oxidative-stress-induced cytotoxicity in Drosophila melanogaster.

PubMed

Mehdi, Syed Hassan; Qamar, Ayesha

2013-08-01

Paraquat (PQ), a quaternary nitrogen herbicide, is commonly used as a pesticide despite of its high toxicity. Our study evaluated the effect of subchronic PQ exposure on the neuropathology, genotoxicity, and antioxidant activity on the nervous tissue of Drosophila melanogaster. We also explored the behavioral effect of PQ on D. melanogaster. Furthermore, we attempted to validate the mechanism by evaluating PQ-induced cytotoxicity on the D-Mel2 cell lines. The fruit fly D. melanogaster serves as a feasible model to understand the mechanism of neurodegenerative diseases. Our study shows a dose-dependent PQ-induced neuropathology in the brain tissue of D. melanogaster as evidenced by hematoxylin and eosin staining, silver nitrate staining, and transmission electron microscopy. Electron microscopic study of D. melanogaster brain tissue exhibited vacuolar degeneration and significant neuronal damage across the nervous tissue structure in comparison with control. Our findings also indicate a dose-dependent locomotor impairment and decreased superoxide dismutase (SOD) specific activity in PQ-treated D. melanogaster. These PQ-induced neuroanatomical changes and decreased SOD specific activity showed a significant association with oxidative DNA damage as observed by alkaline comet assay. Additionally, we show, for the first time, a dose-dependent PQ-induced cytotoxicity in the D-Mel2 cells suggesting loss of neuronal cell viability via cytotoxic damage. Our data suggest that PQ exposure results in neurodegeneration in D. melanogaster and that fruit fly is a suitable in vivo model for correlating the neuroanatomical changes with neurotoxic damages to nervous system.

UV and ionizing radiations induced DNA damage, differences and similarities

NASA Astrophysics Data System (ADS)

Ravanat, Jean-Luc; Douki, Thierry

2016-11-01

Both UV and ionizing radiations damage DNA. Two main mechanisms, so-called direct and indirect pathways, are involved in the degradation of DNA induced by ionizing radiations. The direct effect of radiation corresponds to direct ionization of DNA (one electron ejection) whereas indirect effects are produced by reactive oxygen species generated through water radiolysis, including the highly reactive hydroxyl radicals, which damage DNA. UV (and visible) light damages DNA by again two distinct mechanisms. UVC and to a lesser extend UVB photons are directly absorbed by DNA bases, generating their excited states that are at the origin of the formation of pyrimidine dimers. UVA (and visible) light by interaction with endogenous or exogenous photosensitizers induce the formation of DNA damage through photosensitization reactions. The excited photosensitizer is able to induce either a one-electron oxidation of DNA (type I) or to produce singlet oxygen (type II) that reacts with DNA. In addition, through an energy transfer from the excited photosensitizer to DNA bases (sometime called type III mechanism) formation of pyrimidine dimers could be produced. Interestingly it has been shown recently that pyrimidine dimers are also produced by direct absorption of UVA light by DNA, even if absorption of DNA bases at these wavelengths is very low. It should be stressed that some excited photosensitizers (such as psoralens) could add directly to DNA bases to generate adducts. The review will described the differences and similarities in terms of damage formation (structure and mechanisms) between these two physical genotoxic agents.

Characterizing single isolated radiation-damage events from molecular dynamics via virtual diffraction methods

DOE PAGES

Stewart, James A.; Brookman, G.; Price, Patrick Michael; ...

2018-04-25

In this study, the evolution and characterization of single-isolated-ion-strikes are investigated by combining atomistic simulations with selected-area electron diffraction (SAED) patterns generated from these simulations. Five molecular dynamics simulations are performed for a single 20 keV primary knock-on atom in bulk crystalline Si. The resulting cascade damage is characterized in two complementary ways. First, the individual cascade events are conventionally quantified through the evolution of the number of defects and the atomic (volumetric) strain associated with these defect structures. These results show that (i) the radiation damage produced is consistent with the Norgett, Robinson, and Torrens model of damage productionmore » and (ii) there is a net positive volumetric strain associated with the cascade structures. Second, virtual SAED patterns are generated for the resulting cascade-damaged structures along several zone axes. The analysis of the corresponding diffraction patterns shows the SAED spots approximately doubling in size, on average, due to broadening induced by the defect structures. Furthermore, the SAED spots are observed to exhibit an average radial outward shift between 0.33% and 0.87% depending on the zone axis. Finally, this characterization approach, as utilized here, is a preliminary investigation in developing methodologies and opportunities to link experimental observations with atomistic simulations to elucidate microstructural damage states.« less

Characterizing single isolated radiation-damage events from molecular dynamics via virtual diffraction methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stewart, James A.; Brookman, G.; Price, Patrick Michael

In this study, the evolution and characterization of single-isolated-ion-strikes are investigated by combining atomistic simulations with selected-area electron diffraction (SAED) patterns generated from these simulations. Five molecular dynamics simulations are performed for a single 20 keV primary knock-on atom in bulk crystalline Si. The resulting cascade damage is characterized in two complementary ways. First, the individual cascade events are conventionally quantified through the evolution of the number of defects and the atomic (volumetric) strain associated with these defect structures. These results show that (i) the radiation damage produced is consistent with the Norgett, Robinson, and Torrens model of damage productionmore » and (ii) there is a net positive volumetric strain associated with the cascade structures. Second, virtual SAED patterns are generated for the resulting cascade-damaged structures along several zone axes. The analysis of the corresponding diffraction patterns shows the SAED spots approximately doubling in size, on average, due to broadening induced by the defect structures. Furthermore, the SAED spots are observed to exhibit an average radial outward shift between 0.33% and 0.87% depending on the zone axis. Finally, this characterization approach, as utilized here, is a preliminary investigation in developing methodologies and opportunities to link experimental observations with atomistic simulations to elucidate microstructural damage states.« less

Characterizing single isolated radiation-damage events from molecular dynamics via virtual diffraction methods

NASA Astrophysics Data System (ADS)

Stewart, J. A.; Brookman, G.; Price, P.; Franco, M.; Ji, W.; Hattar, K.; Dingreville, R.

2018-04-01

The evolution and characterization of single-isolated-ion-strikes are investigated by combining atomistic simulations with selected-area electron diffraction (SAED) patterns generated from these simulations. Five molecular dynamics simulations are performed for a single 20 keV primary knock-on atom in bulk crystalline Si. The resulting cascade damage is characterized in two complementary ways. First, the individual cascade events are conventionally quantified through the evolution of the number of defects and the atomic (volumetric) strain associated with these defect structures. These results show that (i) the radiation damage produced is consistent with the Norgett, Robinson, and Torrens model of damage production and (ii) there is a net positive volumetric strain associated with the cascade structures. Second, virtual SAED patterns are generated for the resulting cascade-damaged structures along several zone axes. The analysis of the corresponding diffraction patterns shows the SAED spots approximately doubling in size, on average, due to broadening induced by the defect structures. Furthermore, the SAED spots are observed to exhibit an average radial outward shift between 0.33% and 0.87% depending on the zone axis. This characterization approach, as utilized here, is a preliminary investigation in developing methodologies and opportunities to link experimental observations with atomistic simulations to elucidate microstructural damage states.

Calculation of femtosecond pulse laser induced damage threshold for broadband antireflective microstructure arrays.

PubMed

Jing, Xufeng; Shao, Jianda; Zhang, Junchao; Jin, Yunxia; He, Hongbo; Fan, Zhengxiu

2009-12-21

In order to more exactly predict femtosecond pulse laser induced damage threshold, an accurate theoretical model taking into account photoionization, avalanche ionization and decay of electrons is proposed by comparing respectively several combined ionization models with the published experimental measurements. In addition, the transmittance property and the near-field distribution of the 'moth eye' broadband antireflective microstructure directly patterned into the substrate material as a function of the surface structure period and groove depth are performed by a rigorous Fourier model method. It is found that the near-field distribution is strongly dependent on the periodicity of surface structure for TE polarization, but for TM wave it is insensitive to the period. What's more, the femtosecond pulse laser damage threshold of the surface microstructure on the pulse duration taking into account the local maximum electric field enhancement was calculated using the proposed relatively accurate theoretical ionization model. For the longer incident wavelength of 1064 nm, the weak linear damage threshold on the pulse duration is shown, but there is a surprising oscillation peak of breakdown threshold as a function of the pulse duration for the shorter incident wavelength of 532 nm.

Structural changes of Ti3SiC2 induced by helium irradiation with different doses

NASA Astrophysics Data System (ADS)

Zhang, Hongliang; Su, Ranran; Shi, Liqun; O'Connor, Daryl J.; Wen, Haiming

2018-03-01

In this study, the microstructure changes of Ti3SiC2 MAX phase material induced by helium irradiation and evolution with a sequence of different helium irradiation doses of 5 × 1015, 1 × 1016, 5 × 1016 and 1 × 1017 cm-2 at room temperature (RT) were characterized with grazing incidence X-ray diffraction (GIXRD) and Raman spectra analysis. The irradiation damage process of Ti3SiC2 can be roughly divided into three stages according to the level of helium irradiation dose: (1) for a low damage dose, only crystal and damaged Ti3SiC2 exit; (2) at a higher irradiation dose, there is some damaged TiC phase additionally; (3) with a much higher irradiation dose, crystal TiC phase could be found inside the samples as well. Moreover, the 450 °C 5 × 1016 cm-2 helium irradiation on Ti3SiC2 has confirmed that Ti3SiC2 has much higher irradiation tolerance at higher temperature, which implies that Ti3SiC2 could be a potential future structural and fuel coating material working at high temperature environments.

Lattice damage assessment and optical waveguide properties in LaAlO3 single crystal irradiated with swift Si ions

NASA Astrophysics Data System (ADS)

Liu, Y.; Crespillo, M. L.; Huang, Q.; Wang, T. J.; Liu, P.; Wang, X. L.

2017-02-01

As one of the representative ABO3 perovskite-structured oxides, lanthanum aluminate (LaAlO3) crystal has emerged as one of the most valuable functional-materials, and has attracted plenty of fundamental research and promising applications in recent years. Electronic, magnetic, optical and other properties of LaAlO3 strongly depend on its crystal structure, which could be strongly modified owing to the nuclear or electronic energy loss deposited in an ion irradiation environment and, therefore, significantly affecting the performance of LaAlO3-based devices. In this work, utilizing swift (tens of MeV) Si-ion irradiation, the damage behavior of LaAlO3 crystal induced by nuclear or electronic energy loss has been studied in detail utilizing complementary characterization techniques. Differing from other perovskite-structured crystals in which the electronic energy loss could lead to the formation of an amorphous region based on the thermal spike mechanism, in this case, intense electronic energy loss in LaAlO3 will not induce any obvious structural damage. The effects of ion irradiation on the mechanical properties, including hardness increase and elastic modulus decrease, have been confirmed. On the other hand, considering the potential applications of LaAlO3 in the field of integrated optoelectronics, the optical-waveguide properties of the irradiation region have been studied. The significant correspondence (symmetrical inversion) between the iWKB-reconstructed refractive-index profile and SRIM-simulated dpa profile further proves the effects (irradiation-damage production and refractive-index decrease) of nuclear energy loss during the swift-ion penetration process in LaAlO3 crystal. In the case of the rather-thick damage layer produced by swift-ion irradiation, obtaining a damage profile will be constrained owing to the analysis-depth limitation of the characterization techniques (RBS/channeling), and our analysis process (optical guided-mode measurement and subsequent refractive-index-profile reconstruction) also provides a new approach to study the damage behavior (damage profile) once the functional relationship between the refractive index and lattice disorder for the specific material could be determined.

Rainfall-induced landslide vulnerability Assessment in urban area reflecting Urban structure and building characteristics

NASA Astrophysics Data System (ADS)

Park, C.; Cho, M.; Lee, D.

2017-12-01

Landslide vulnerability assessment methodology of urban area is proposed with urban structure and building charateristics which can consider total damage cost of climate impacts. We used probabilistic analysis method for modeling rainfall-induced shallow landslide susceptibility by slope stability analysis and Monte Carlo simulations. And We combined debris flows with considering spatial movements under topographical condition and built environmental condition. Urban vulnerability of landslide is assessed by two categories: physical demages and urban structure aspect. Physical vulnerability is related to buildings, road, other ubran infra. Urban structure vulnerability is considered a function of the socio-economic factors, trigger factor of secondary damage, and preparedness level of the local government. An index-based model is developed to evaluate the life and indirect damage under landslide as well as the resilience ability against disasters. The analysis was performed in a geographic information system (GIS) environment because GIS can deal efficiently with a large volume of spatial data. The results of the landslide susceptibility assessment were compared with the landslide inventory, and the proposed approach demonstrated good predictive performance. The general trend found in this study indicates that the higher population density areas under a weaker fiscal condition that are located at the downstream of mountainous areas are more vulnerable than the areas in opposite conditions.

Using a cover layer to improve the damage resistance of gold-coated gratings induced by a picosecond pulsed laser

NASA Astrophysics Data System (ADS)

Xia, Zhilin; Wu, Yihan; Kong, Fanyu; Jin, Yunxia

2018-04-01

The chirped pulse amplification (CPA) technology is the main approach to achieve high-intensity short-pulse laser. Diffraction gratings are good candidates for stretching and compressing laser pulses in CPA. In this paper, a kind of gold-coated grating has been prepared and its laser damage experiment has been performed. The results reflect that the gratings laser damage was dominated by thermal ablation due to gold films or inclusions absorption and involved the deformation or eruption of the gold film. Based on these damage phenomena, a method of using a cover layer to prevent gold films from deforming and erupting has been adopted to improve the gold-coated gratings laser damage threshold. Since the addition of a cover layer changes the gratings diffraction efficiency, the gratings structure has been re-optimized. Furthermore, according to the calculated thermal stress distributions in gratings with optimized structures, the cover layer was demonstrated to be helpful for improving the gratings laser damage resistance if it is thick enough.

A model for the progressive failure of laminated composite structural components

NASA Technical Reports Server (NTRS)

Allen, D. H.; Lo, D. C.

1991-01-01

Laminated continuous fiber polymeric composites are capable of sustaining substantial load induced microstructural damage prior to component failure. Because this damage eventually leads to catastrophic failure, it is essential to capture the mechanics of progressive damage in any cogent life prediction model. For the past several years the authors have been developing one solution approach to this problem. In this approach the mechanics of matrix cracking and delamination are accounted for via locally averaged internal variables which account for the kinematics of microcracking. Damage progression is predicted by using phenomenologically based damage evolution laws which depend on the load history. The result is a nonlinear and path dependent constitutive model which has previously been implemented to a finite element computer code for analysis of structural components. Using an appropriate failure model, this algorithm can be used to predict component life. In this paper the model will be utilized to demonstrate the ability to predict the load path dependence of the damage and stresses in plates subjected to fatigue loading.

Phase space interrogation of the empirical response modes for seismically excited structures

NASA Astrophysics Data System (ADS)

Paul, Bibhas; George, Riya C.; Mishra, Sudib K.

2017-07-01

Conventional Phase Space Interrogation (PSI) for structural damage assessment relies on exciting the structure with low dimensional chaotic waveform, thereby, significantly limiting their applicability to large structures. The PSI technique is presently extended for structure subjected to seismic excitations. The high dimensionality of the phase space for seismic response(s) are overcome by the Empirical Mode Decomposition (EMD), decomposing the responses to a number of intrinsic low dimensional oscillatory modes, referred as Intrinsic Mode Functions (IMFs). Along with their low dimensionality, a few IMFs, retain sufficient information of the system dynamics to reflect the damage induced changes. The mutually conflicting nature of low-dimensionality and the sufficiency of dynamic information are taken care by the optimal choice of the IMF(s), which is shown to be the third/fourth IMFs. The optimal IMF(s) are employed for the reconstruction of the Phase space attractor following Taken's embedding theorem. The widely referred Changes in Phase Space Topology (CPST) feature is then employed on these Phase portrait(s) to derive the damage sensitive feature, referred as the CPST of the IMFs (CPST-IMF). The legitimacy of the CPST-IMF is established as a damage sensitive feature by assessing its variation with a number of damage scenarios benchmarked in the IASC-ASCE building. The damage localization capability, remarkable tolerance to noise contamination and the robustness under different seismic excitations of the feature are demonstrated.

Study on Damage Evaluation and Machinability of UD-CFRP for the Orthogonal Cutting Operation Using Scanning Acoustic Microscopy and the Finite Element Method.

PubMed

Wang, Dongyao; He, Xiaodong; Xu, Zhonghai; Jiao, Weicheng; Yang, Fan; Jiang, Long; Li, Linlin; Liu, Wenbo; Wang, Rongguo

2017-02-20

Owing to high specific strength and designability, unidirectional carbon fiber reinforced polymer (UD-CFRP) has been utilized in numerous fields to replace conventional metal materials. Post machining processes are always required for UD-CFRP to achieve dimensional tolerance and assembly specifications. Due to inhomogeneity and anisotropy, UD-CFRP differs greatly from metal materials in machining and failure mechanism. To improve the efficiency and avoid machining-induced damage, this paper undertook to study the correlations between cutting parameters, fiber orientation angle, cutting forces, and cutting-induced damage for UD-CFRP laminate. Scanning acoustic microscopy (SAM) was employed and one-/two-dimensional damage factors were then created to quantitatively characterize the damage of the laminate workpieces. According to the 3D Hashin's criteria a numerical model was further proposed in terms of the finite element method (FEM). A good agreement between simulation and experimental results was validated for the prediction and structural optimization of the UD-CFRP.

Study on Damage Evaluation and Machinability of UD-CFRP for the Orthogonal Cutting Operation Using Scanning Acoustic Microscopy and the Finite Element Method

PubMed Central

Wang, Dongyao; He, Xiaodong; Xu, Zhonghai; Jiao, Weicheng; Yang, Fan; Jiang, Long; Li, Linlin; Liu, Wenbo; Wang, Rongguo

2017-01-01

Owing to high specific strength and designability, unidirectional carbon fiber reinforced polymer (UD-CFRP) has been utilized in numerous fields to replace conventional metal materials. Post machining processes are always required for UD-CFRP to achieve dimensional tolerance and assembly specifications. Due to inhomogeneity and anisotropy, UD-CFRP differs greatly from metal materials in machining and failure mechanism. To improve the efficiency and avoid machining-induced damage, this paper undertook to study the correlations between cutting parameters, fiber orientation angle, cutting forces, and cutting-induced damage for UD-CFRP laminate. Scanning acoustic microscopy (SAM) was employed and one-/two-dimensional damage factors were then created to quantitatively characterize the damage of the laminate workpieces. According to the 3D Hashin’s criteria a numerical model was further proposed in terms of the finite element method (FEM). A good agreement between simulation and experimental results was validated for the prediction and structural optimization of the UD-CFRP. PMID:28772565

Neuronal and BBB damage induced by sera from patients with secondary progressive multiple sclerosis.

PubMed

Proia, Patrizia; Schiera, Gabriella; Salemi, Giuseppe; Ragonese, Paolo; Savettieri, Giovanni; Di Liegro, Italia

2009-12-01

An important component of the pathogenic process of multiple sclerosis (MS) is the blood-brain barrier (BBB) damage. We recently set an in vitro model of BBB, based on a three-cell-type co-culture system, in which rat neurons and astrocytes synergistically induce brain capillary endothelial cells to form a monolayer with permeability properties resembling those of the physiological BBB. Herein we report that the serum from patients with secondary progressive multiple sclerosis (SPMS) has a damaging effect on isolated neurons. This finding suggests that neuronal damaging in MS could be a primary event and not only secondary to myelin damage, as generally assumed. SPMS serum affects the permeability of the BBB model, as indicated by the decrease of the transendothelial electrical resistance (TEER). Moreover, as shown by both immunofluorescence and Western blot analyses, BBB breaking is accompanied by a decrease of the synthesis as well as the peripheral localization of occludin, a structural protein of the tight junctions that are responsible for BBB properties.

Neuroprotective effect of ginger in the brain of streptozotocin-induced diabetic rats.

PubMed

El-Akabawy, Gehan; El-Kholy, Wael

2014-05-01

Diabetes mellitus results in neuronal damage caused by increased intracellular glucose leading to oxidative stress. Recent evidence revealed the potential of ginger for reducing diabetes-induced oxidative stress markers. The aim of this study is to investigate, for the first time, whether the antioxidant properties of ginger has beneficial effects on the structural brain damage associated with diabetes. We investigated the observable neurodegenerative changes in the frontal cortex, dentate gyrus, and cerebellum after 4, 6, and 8 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of ginger (500 mg/kg/day). Sections of frontal cortex, dentate gyrus, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, quantitative immunohistochemical assessments of the expression of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-α, caspase-3, glial fibrillary acidic protein (GFAP), acetylcholinesterase (AChE), and Ki67 were performed. Our results revealed a protective role of ginger on the diabetic brain via reducing oxidative stress, apoptosis, and inflammation. In addition, this study revealed that the beneficial effect of ginger was also mediated by modulating the astroglial response to the injury, reducing AChE expression, and improving neurogenesis. These results represent a new insight into the beneficial effects of ginger on the structural alterations of diabetic brain and suggest that ginger might be a potential therapeutic strategy for the treatment of diabetic-induced damage in brain. Copyright © 2014 Elsevier GmbH. All rights reserved.

Monitoring of corrosion damage using high-frequency guided ultrasonic waves

NASA Astrophysics Data System (ADS)

Chew, D.; Fromme, P.

2014-03-01

Due to adverse environmental conditions corrosion can develop during the life cycle of industrial structures, e.g., offshore oil platforms, ships, and desalination plants. Both pitting corrosion and generalized corrosion leading to wall thickness loss can cause the degradation of the integrity and load bearing capacity of the structure. Structural health monitoring of corrosion damage in difficult to access areas can in principle be achieved using high frequency guided waves propagating along the structure from accessible areas. Using standard ultrasonic transducers with single sided access to the structure, high frequency guided wave modes were generated that penetrate through the complete thickness of the structure. Wall thickness reduction was induced using accelerated corrosion in a salt water bath. The corrosion damage was monitored based on the effect on the wave propagation and interference of the different modes. The change in the wave interference was quantified based on an analysis in the frequency domain (Fourier transform) and was found to match well with theoretical predictions for the wall thickness loss. High frequency guided waves have the potential for corrosion damage monitoring at critical and difficult to access locations from a stand-off distance.

Monitoring of corrosion damage using high-frequency guided ultrasonic waves

NASA Astrophysics Data System (ADS)

Chew, D.; Fromme, P.

2015-03-01

Due to adverse environmental conditions corrosion can develop during the life cycle of industrial structures, e.g., offshore oil platforms, ships, and desalination plants. Both pitting corrosion and generalized corrosion leading to wall thickness loss can cause the degradation of the integrity and load bearing capacity of the structure. Structural health monitoring of corrosion damage in difficult to access areas can in principle be achieved using high frequency guided waves propagating along the structure from accessible areas. Using standard ultrasonic transducers with single sided access to the structure, high frequency guided wave modes were generated that penetrate through the complete thickness of the structure. Wall thickness reduction was induced using accelerated corrosion in a salt water bath. The corrosion damage was monitored based on the effect on the wave propagation and interference of the different modes. The change in the wave interference was quantified based on an analysis in the frequency domain (Fourier transform) and was found to match well with theoretical predictions for the wall thickness loss. High frequency guided waves have the potential for corrosion damage monitoring at critical and difficult to access locations from a stand-off distance.

Fe model predicting the increase in seismic resistance induced by the progressive FRP strengthening on already damaged masonry arches subjected to settlement

NASA Astrophysics Data System (ADS)

Stockdale, G.; Milani, G.

2017-11-01

In seismic regions, the retrofitting of masonry structures subjected to differential foundation settlements is of the upmost importance. This practice however poses significant challenges, most notably in the consideration of historical monuments where the integrity of the original structure must be weighted alongside public safety. Fiber reinforced polymers (FRPs), when appropriately applied, provide the potential to balance this duality of heritage preservation and modern safety. Using an advanced FE point of view, this work studies the seismic response of a progressive reinforcement strategy aimed at strengthening and controlling the failure mechanism for masonry arches that exist in a damaged state induced through a differential abutment settlement. A heterogeneous FE approach of a semi-circular block and mortar arch on continuously spreading supports is examined. In this model hinge formation is obtained by assigning a damage plasticity behavior to the mortar joints. Strategically placed FRPs, designed through the utilization of the Italian CNR recommendations for externally bonded FRP systems, are applied through the Abaqus birth and death approach and introduced to the spreading support model after settlement. Finally, the structural behavior of the reinforced and unreinforced models are examined for a seismic response.

Swift heavy ion-induced radiation damage in isotropic graphite studied by micro-indentation and in-situ electrical resistivity

NASA Astrophysics Data System (ADS)

Hubert, Christian; Voss, Kay Obbe; Bender, Markus; Kupka, Katharina; Romanenko, Anton; Severin, Daniel; Trautmann, Christina; Tomut, Marilena

2015-12-01

Due to its excellent thermo-physical properties and radiation hardness, isotropic graphite is presently the most promising material candidate for new high-power ion accelerators which will provide highest beam intensities and energies. Under these extreme conditions, specific accelerator components including production targets and beam protection modules are facing the risk of degradation due to radiation damage. Ion-beam induced damage effects were tested by irradiating polycrystalline, isotropic graphite samples at the UNILAC (GSI, Darmstadt) with 4.8 MeV per nucleon 132Xe, 150Sm, 197Au, and 238U ions applying fluences between 1 × 1011 and 1 × 1014 ions/cm2. The overall damage accumulation and its dependence on energy loss of the ions were studied by in situ 4-point resistivity measurements. With increasing fluence, the electric resistivity increases due to disordering of the graphitic structure. Irradiated samples were also analyzed off-line by means of micro-indentation in order to characterize mesoscale effects such as beam-induced hardening and stress fields within the specimen. With increasing fluence and energy loss, hardening becomes more pronounced.

Protective Effect of Fucoxanthin Isolated from Laminaria japonica against Visible Light-Induced Retinal Damage Both in Vitro and in Vivo.

PubMed

Liu, Yixiang; Liu, Meng; Zhang, Xichun; Chen, Qingchou; Chen, Haixiu; Sun, Lechang; Liu, Guangming

2016-01-20

With increasingly serious eye exposure to light stresses, such as light-emitting diodes, computers, and widescreen mobile phones, efficient natural compounds for preventing visible light-induced retinal damages are becoming compelling needs in the modern society. Fucoxanthin, as the main light absorption system in marine algae, may possess an outstanding bioactivity in vision protection because of its filtration of blue light and excellent antioxidative activity. In this work, both in vitro and in vivo simulated visible light-induced retinal damage models were employed. The in vitro results revealed that fucoxanthin exhibited better bioactivities than lutein, zeaxanthin, and blueberry anthocyanins in inhibiting overexpression of vascular endothelial growth factor, resisting senescence, improving phagocytic function, and clearing intracellular reactive oxygen species in retinal pigment epithelium cells. The in vivo experiment also confirmed the superiority of fucoxanthin than lutein in protecting retina against photoinduced damage. This excellent bioactivity may be attributed to its unique structural features, including allenic, epoxide, and acetyl groups. Fucoxanthin is expected to be an important ocular nutrient in the future.

The structural damages of lens crystallins induced by peroxynitrite and methylglyoxal, two causative players in diabetic complications and preventive role of lens antioxidant components.

PubMed

Moghadam, Sogand Sasan; Oryan, Ahmad; Kurganov, Boris I; Tamaddon, Ali-Mohammad; Alavianehr, Mohammad Mehdi; Moosavi-Movahedi, Ali Akbar; Yousefi, Reza

2017-10-01

Peroxynitrite (PON) and methylglyoxal (MGO), two diabetes-associated compounds, are believed to be important causative players in development of diabetic cataracts. In the current study, different spectroscopic methods, gel electrophoresis, lens culture and microscopic assessments were applied to examine the impact of individual, subsequent or simultaneous modification of lens crystallins with MGO and PON on their structure, oligomerization and aggregation. The protein modifications were confirmed with detection of the significantly increased quantity of carbonyl groups and decreased levels of sulfhydryl, tyrosine and tryptophan. Also, lens proteins modification with these chemical agents was accompanied with important structural alteration, oligomerization, disulfide/chromophore mediated protein crosslinking and important proteolytic instability. All these structural damages were more pronounced when the lens proteins were modified in the presence of both mentioned chemical agents, either in sequential or simultaneous manner. Ascorbic acid and glutathione, as the main components of lens antioxidant defense mechanism, were also capable to markedly prevent the damaging effects of PON and MGO on lens crystallins, as indicated by gel electrophoresis. The results of this study may highlight the importance of lens antioxidant defense system in protection of crystallins against the structural insults induced by PON and MGO during chronic hyperglycemia in the diabetic patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Radiation-induced amorphization resistance and radiation tolerance in structurally related oxides.

PubMed

Sickafus, Kurt E; Grimes, Robin W; Valdez, James A; Cleave, Antony; Tang, Ming; Ishimaru, Manabu; Corish, Siobhan M; Stanek, Christopher R; Uberuaga, Blas P

2007-03-01

Ceramics destined for use in hostile environments such as nuclear reactors or waste immobilization must be highly durable and especially resistant to radiation damage effects. In particular, they must not be prone to amorphization or swelling. Few ceramics meet these criteria and much work has been devoted in recent years to identifying radiation-tolerant ceramics and the characteristics that promote radiation tolerance. Here, we examine trends in radiation damage behaviour for families of compounds related by crystal structure. Specifically, we consider oxides with structures related to the fluorite crystal structure. We demonstrate that improved amorphization resistance characteristics are to be found in compounds that have a natural tendency to accommodate lattice disorder.

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

NASA Technical Reports Server (NTRS)

Naghipour, P.; Pineda, E. J.; Arnold, S.

2014-01-01

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

Ordered Conformational Changes in Damaged DNA Induced by Nucleotide Excision Repair Factors*

PubMed Central

Tapias, Angels; Auriol, Jerome; Forget, Diane; Enzlin, Jacqueline H.; Schärer, Orlando D; Coin, Frederic; Coulombe, Benoit; Egly, Jean-Marc

2015-01-01

In response to genotoxic attacks, cells activate sophisticated DNA repair pathways such as nucleotide excision repair (NER), which consists of damage removal via dual incision and DNA resynthesis. Using permanganate footprinting as well as highly purified factors, we show that NER is a dynamic process that takes place in a number of successive steps during which the DNA is remodeled around the lesion in response to the various NER factors. XPC/HR23B first recognizes the damaged structure and initiates the opening of the helix from position −3 to +6. TFIIH is then recruited and, in the presence of ATP, extends the opening from position −6 to +6; it also displaces XPC downstream from the lesion, thereby providing the topological structure for recruiting XPA and RPA, which will enlarge the opening. Once targeted by XPG, the damaged DNA is further melted from position −19 to +8. XPG and XPF/ERCC1 endo-nucleases then cut the damaged DNA at the limit of the opened structure that was previously “labeled” by the positioning of XPC/HR23B and TFIIH. PMID:14981083

Applications of a damage tolerance analysis methodology in aircraft design and production

NASA Technical Reports Server (NTRS)

Woodward, M. R.; Owens, S. D.; Law, G. E.; Mignery, L. A.

1992-01-01

Objectives of customer mandated aircraft structural integrity initiatives in design are to guide material selection, to incorporate fracture resistant concepts in the design, to utilize damage tolerance based allowables and planned inspection procedures necessary to enhance the safety and reliability of manned flight vehicles. However, validated fracture analysis tools for composite structures are needed to accomplish these objectives in a timely and economical manner. This paper briefly describes the development, validation, and application of a damage tolerance methodology for composite airframe structures. A closed-form analysis code, entitled SUBLAM was developed to predict the critical biaxial strain state necessary to cause sublaminate buckling-induced delamination extension in an impact damaged composite laminate. An embedded elliptical delamination separating a thin sublaminate from a thick parent laminate is modelled. Predicted failure strains were correlated against a variety of experimental data that included results from compression after impact coupon and element tests. An integrated analysis package was developed to predict damage tolerance based margin-of-safety (MS) using NASTRAN generated loads and element information. Damage tolerance aspects of new concepts are quickly and cost-effectively determined without the need for excessive testing.

Irradiation creep due to SIPA under cascade damage conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woo, C.H.; Garner, F.A.; Holt, R.A.

1992-12-31

This paper derives the relationships between void swelling and irradiation creep due to Stress-Induced Preferred Absorption (SIPA) and SIPA-Induced Growth (SIG) under cascade damage conditions in an irradiated pressurized tube. It is found that at low swelling rates irradiation creep is a major contribution to the total diametral strain rate of the tube, whereas at high swelling rates the creep becomes a minor contribution. The anisotropy of the corresponding dislocation structure is also predicted to decline as the swelling rate increases. The theoretical predictions are found to agree very well with experimental results.

Regimes of laser-induced periodic surface structure on germanium: radiation remnants and surface plasmons.

PubMed

Young, J F; Sipe, J E; van Driel, H M

1983-08-01

We present experimental evidence showing that the period of the rippled surface structure induced on germanium by 1.06-microm laser pulses undergoes a discontinuous shift above a certain threshold intensity. The measured shift, as a angle of incidence of the damaging beam, is quantitatively interpreted as a transition between a regime of inhomogeneous melting controlled by radiation-remnant field structures and a regime of ripple formation surface plasmons in an optically thick layer of liquid, metallic germanium formed at the surface.

Biologically inspired autonomous structural materials with controlled toughening and healing

NASA Astrophysics Data System (ADS)

Garcia, Michael E.; Sodano, Henry A.

2010-04-01

The field of structural health monitoring (SHM) has made significant contributions in the field of prognosis and damage detection in the past decade. The advantageous use of this technology has not been integrated into operational structures to prevent damage from propagating or to heal injured regions under real time loading conditions. Rather, current systems relay this information to a central processor or human operator, who then determines a course of action such as altering the mission or scheduling repair maintenance. Biological systems exhibit advanced sensory and healing traits that can be applied to the design of material systems. For instance, bone is the major structural component in vertebrates; however, unlike modern structural materials, bone has many properties that make it effective for arresting the propagation of cracks and subsequent healing of the fractured area. The foremost goal for the development of future adaptive structures is to mimic biological systems, similar to bone, such that the material system can detect damage and deploy defensive traits to impede damage from propagating, thus preventing catastrophic failure while in operation. After sensing and stalling the propagation of damage, the structure must then be repaired autonomously using self healing mechanisms motivated by biological systems. Here a novel autonomous system is developed using shape memory polymers (SMPs), that employs an optical fiber network as both a damage detection sensor and a network to deliver stimulus to the damage site initiating adaptation and healing. In the presence of damage the fiber optic fractures allowing a high power laser diode to deposit a controlled level of thermal energy at the fractured sight locally reducing the modulus and blunting the crack tip, which significantly slows the crack growth rate. By applying a pre-induced strain field and utilizing the shape memory recovery effect, thermal energy can be deployed to close the crack and return the system to its original operating state. The entire system will effectively detect, self toughen, and subsequently heal damage as biological materials such as bone does.

EFFECTS OF CYCLIC FLEXURAL FATIGUE ON PORCINE BIOPROSTHETIC HEART VALVE HETEROGRAFT BIOMATERIALS

PubMed Central

Mirnajafi, Ali; Zubiate, Brett; Sacks, Michael S.

2009-01-01

While bioprosthetic heart valves (BHV) remain the primary treatment modality for adult heart valve replacement, continued problems with durability remain. Several studies have implicated flexure as a major damage mode in porcine-derived heterograft biomaterials used in BHV fabrication. While conventional accelerated wear testing can provide valuable insights into BHV damage phenomena, the constituent tissues are subjected to complex, time-varying deformation modes (i.e. tension and flexure), that do not allow for the control of the amount, direction, and location of flexure. Thus, in the present study customized fatigue testing devices were developed to subject circumferentially oriented porcine BHV tissue strips to controlled cyclic flexural loading. By using this approach, we were able to study layer-specific structural damage induced by cyclic flexural tensile and compressive stresses alone. 10×106, 25×106 and 50×106 cycle levels were used, with resulting changes in flexural stiffness and collagen structure assessed. Results indicated that flexural rigidity was markedly reduced after only 10×106 cycles, and progressively decayed at a lower rate with cycle number thereafter. Moreover, the against-curvature fatigue direction induced the most damage, suggesting that the ventricularis and fibrosa layers have low resistance to cyclic flexural compressive and tensile loads, respectively. The histological analyses indicated progressive collagen fiber delamination as early as 10×106 cycles, but otherwise no change in gross collagen orientation. Our results underscore that porcine-derived heterograft biomaterials are very sensitive to flexural fatigue, with delamination of the tissue layers the primary underlying mechanism. This appears to be in contrast to pericardial BHV, wherein high tensile stresses are considered to be the major cause of structural failure. These findings point towards the need for the development of chemical fixation technologies that minimize flexure induced damage to extend porcine heterograft biomaterial durability. PMID:20166221

In vitro mechanistic study of endosulfan-induced spermatogenic cell apoptosis in the mouse.

PubMed

Xu, Ying; Wang, Na; Shi, Zhi-Xiong; Li, Yan-Bo; Zhou, Xian-Qing; Sun, Zhi-Wei

2016-09-01

To investigate the mechanisms of endosulfan-induced reproductive toxicity, the spermatogenic cell lines (GC-1 spg) of mice were treated with 0, 6, 12, and 24 μg/ml endosulfan for 24 h in vitro The results showed that endosulfan induced apoptosis as well as oxidative stress and mitochondrial dysfunction. Reactive oxygen species and damage of mitochondrial structure were considered as major factors to GC-1 spg cells apoptosis. We further examined the expression of apoptosis-related proteins in mitochondria pathway by Western blot and immunohistochemistry analysis as well as activities. The results showed that endosulfan significantly improved the expressions of cytochrome c and B-cell lymphoma 2 (Bcl-2)-associated X protein and increased the activities of caspases 9 and 3 as well as the downregulation of the expression of Bcl-2 in GC-1 spg cells. The results suggested that exposure to endosulfan might induce the apoptosis of spermatogenic cells via mitochondria-dependent pathway mediated by oxidative stress resulting in the damage of mitochondrial structure and mitochondrial dysfunction. © The Author(s) 2015.

Track structure based modelling of light ion radiation effects on nuclear and mitochondrial DNA

NASA Astrophysics Data System (ADS)

Schmitt, Elke; Ottolenghi, Andrea; Dingfelder, Michael; Friedland, Werner; Kundrat, Pavel; Baiocco, Giorgio

2016-07-01

Space radiation risk assessment is of great importance for manned spaceflights in order to estimate risks and to develop counter-measures to reduce them. Biophysical simulations with PARTRAC can help greatly to improve the understanding of initial biological response to ionizing radiation. Results from modelling radiation quality dependent DNA damage and repair mechanisms up to chromosomal aberrations (e.g. dicentrics) can be used to predict radiation effects depending on the kind of mixed radiation field exposure. Especially dicentric yields can serve as a biomarker for an increased risk due to radiation and hence as an indicator for the effectiveness of the used shielding. PARTRAC [1] is a multi-scale biophysical research MC code for track structure based initial DNA damage and damage response modelling. It integrates physics, radiochemistry, detailed nuclear DNA structure and molecular biology of DNA repair by NHEJ-pathway to assess radiation effects on cellular level [2]. Ongoing experiments with quasi-homogeneously distributed compared to sub-micrometre focused bunches of protons, lithium and carbon ions allow a separation of effects due to DNA damage complexity on nanometre scale from damage clustering on (sub-) micrometre scale [3, 4]. These data provide an unprecedented benchmark for the DNA damage response model in PARTRAC and help understand the mechanisms leading to cell killing and chromosomal aberrations (e.g. dicentrics) induction. A large part of space radiation is due to a mixed ion field of high energy protons and few heavier ions that can be only partly absorbed by the shielding. Radiation damage induced by low-energy ions significantly contributes to the high relative biological efficiency (RBE) of ion beams around Bragg peak regions. For slow light ions the physical cross section data basis in PARTRAC has been extended to investigate radiation quality effects in the Bragg peak region [5]. The resulting range and LET values agree with ICRU data and SRIM calculations. Preliminary studies regarding the biological endpoints DSB (cluster) and chromosomal aberrations have been performed for selected light ions up to neon. Validation with experimental data as well as further calculations are underway and final results will be presented at the meeting. Mitochondrial alterations have been implicated in radiation-induced cardiovascular effects. To extend the applicability of PARTRAC biophysical tool towards effects on mitochondria, the nuclear DNA and chromatin as the primary target of radiation has been complemented by a model of mitochondrial DNA (mtDNA) to mimic a coronary cell with thousand mitochondria contained in the cytoplasm. Induced mtDNA damage (SSB, DSB) has been scored for 60Co photons and 5 MeV alpha-particle irradiation, assuming alternative radical scavenging capacities within the mitochondria. While direct radiation effects in mtDNA are identical to nuclear DNA, indirect effects in mtDNA are in general larger due to lower scavenging and the lack of DNA-protecting histones. These simulations complement the scarce experimental data on radiation-induced mtDNA damage and help elucidate the relative roles of initial mtDNA versus nuclear DNA damage and of pathways that amplify their respective effects. Ongoing and planned developments of PARTRAC include coupling with a radiation transport code and track-structure based calculations of cell killing for RBE studies on macroscopic scales within a mixed ion field. [1] Friedland, Dingfelder et al. (2011): "Track structures, DNA targets and radiation effects in the biophysical Monte Carlo simulation code PARTRAC", Mutat. Res. 711, 28-40 [2] Friedland et al. (2013): "Track structure based modelling of chromosome aberrations after photon and alpha-particle irradiation", Mutat. Res. 756, 213-223 [3] Schmid, Friedland et al. (2015): "Sub-micrometer 20 MeV protons or 45 MeV lithium spot irradiation enhances yields of dicentric chromosomes due to clustering of DNA double-strand breaks", Mutat. Res. 793, 30-40 [4] Friedland, Schmitt, Kundrat (2015): "Modelling Proton bunches focussed to submicrometre scales: Low-LET Radiation damage in high-LET-like spatial structure", Radiat. Prot. Dosim. 166, 34-37 [5] Schmitt, Friedland, Kundrat, Dingfelder, Ottolenghi (2015): "Cross section scaling for track structure simulations of low-energy ions in liquid water", Radiat. Prot. Dosim. 166, 15-18} Supported by the European Atomic Energy Community's Seventh Framework Programme (FP7/2007-2011) under grant agreement no 249689 "DoReMi" and the German Federal Ministry on Education and Research (KVSF-Projekt "LET-Verbund").

Monitoring of self-healing composites: a nonlinear ultrasound approach

NASA Astrophysics Data System (ADS)

Malfense Fierro, Gian-Piero; Pinto, Fulvio; Dello Iacono, Stefania; Martone, Alfonso; Amendola, Eugenio; Meo, Michele

2017-11-01

Self-healing composites using a thermally mendable polymer, based on Diels-Alder reaction were fabricated and subjected to various multiple damage loads. Unlike traditional destructive methods, this work presents a nonlinear ultrasound technique to evaluate the structural recovery of the proposed self-healing laminate structures. The results were compared to computer tomography and linear ultrasound methods. The laminates were subjected to multiple loading and healing cycles and the induced damage and recovery at each stage was evaluated. The results highlight the benefit and added advantage of using a nonlinear based methodology to monitor the structural recovery of reversibly cross-linked epoxy with efficient recycling and multiple self-healing capability.

Pharmacological inhibition of NADPH oxidase protects against cisplatin induced nephrotoxicity in mice by two step mechanism.

PubMed

Wang, Yimin; Luo, Xiao; Pan, Hao; Huang, Wei; Wang, Xueping; Wen, Huali; Shen, Kezhen; Jin, Baiye

2015-09-01

Cisplatin induced nephrotoxicity is primarily caused by ROS (Reactive Oxygen Species) induced proximal tubular cell death. NADPH oxidase is major source of ROS production by cisplatin. Here, we reported that pharmacological inhibition of NADPH oxidase by acetovanillone (obtained from medicinal herb Picrorhiza kurroa) led to reduced cisplatin nephrotoxicity in mice. In this study we used various molecular biology and biochemistry methods a clinically relevant model of nephropathy, induced by an important chemotherapeutic drug cisplatin. Cisplatin-induced nephrotoxicity was evident by histological damage from loss of the tubular structure. The damage was also marked by the increase in blood urea nitrogen, creatinine, protein nitration as well as cell death markers such as caspase 3/7 activity and DNA fragmentation. Tubular cell death by cisplatin led to pro-inflammatory response by production of TNFα and IL1β followed by leukocyte/neutrophil infiltration which resulted in new wave of ROS involving more NADPH oxidases. Cisplatin-induced markers of kidney damage such as oxidative stress, cell death, inflammatory cytokine production and nephrotoxicity were attenuated by acetovanillone. In addition to that, acetovanillone enhanced cancer cell killing efficacy of cisplatin. Thus, pharmacological inhibition of NADPH oxidase can be protective for cisplatin-induced nephrotoxicity in mice. Copyright © 2015. Published by Elsevier Ltd.

Structural and biochemical changes in dermis of sea cucumber (Stichopus japonicus) during autolysis in response to cutting the body wall.

PubMed

Liu, Yu-Xin; Zhou, Da-Yong; Liu, Zi-Qiang; Lu, Ting; Song, Liang; Li, Dong-Mei; Dong, Xiu-Ping; Qi, Hang; Zhu, Bei-Wei; Shahidi, Fereidoon

2018-02-01

The autolysis of sea cucumber body wall is caused by endogenous proteolysis of its structural elements. However, changes in collagen fibrils, collagen fibres and microfibrils, the major structural elements in sea cucumber body wall during autolysis are less clear. Autolysis of sea cucumber (S. japonicus) was induced by cutting the body wall, and the structural and biochemical changes in its dermis were investigated using electron microscopy, differential scanning calorimetry, infrared spectroscopy, electrophoresis, and chemical analysis. During autolysis, both collagen fibres and microfibrils gradually degraded. In contrast, damage to microfibrils was more pronounced. Upon massive autolysis, collagen fibres disaggregated into collagen fibril bundles and individual fibrils due to the fracture of interfibrillar bridges. Meanwhile, excessive unfolding of collagen fibrils occurred. However, there was only slight damage to collagen monomers. Therefore, structural damage in collagen fibres, collagen fibrils and microfibrils rather than monomeric collagen accounts for autolysis of S. japonicus dermis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Numerical analysis of laser ablation and damage in glass with multiple picosecond laser pulses.

PubMed

Sun, Mingying; Eppelt, Urs; Russ, Simone; Hartmann, Claudia; Siebert, Christof; Zhu, Jianqiang; Schulz, Wolfgang

2013-04-08

This study presents a novel numerical model for laser ablation and laser damage in glass including beam propagation and nonlinear absorption of multiple incident ultrashort laser pulses. The laser ablation and damage in the glass cutting process with a picosecond pulsed laser was studied. The numerical results were in good agreement with our experimental observations, thereby revealing the damage mechanism induced by laser ablation. Beam propagation effects such as interference, diffraction and refraction, play a major role in the evolution of the crater structure and the damage region. There are three different damage regions, a thin layer and two different kinds of spikes. Moreover, the electronic damage mechanism was verified and distinguished from heat modification using the experimental results with different pulse spatial overlaps.

A new compound, withangulatin A, promotes type II DNA topoisomerase-mediated DNA damage.

PubMed

Juang, J K; Huang, H W; Chen, C M; Liu, H J

1989-03-31

Withangulatin A, a new compound with a known chemical structure and from the antitumor Chinese herb Physalis angulata L, was found to act on topoisomerase II to induce topoisomerase II-mediated DNA damage in vitro. It has two effective dosage ranges of approximate 0.5 and 20 microM, with about one-third the activity of 20 microM VM-26.

Inhibition of NA+/H+ Exchanger 1 Attenuates Renal Dysfunction Induced by Advanced Glycation End Products in Rats

PubMed Central

Li, Peng; Chen, Geng-Rong; Wang, Fu; Xu, Ping; Liu, Li-Ying; Yin, Ya-Ling; Wang, Shuang-Xi

2016-01-01

It has been recognized that sodium hydrogen exchanger 1 (NHE1) is involved in the development of diabetic nephropathy. The role of NHE1 in kidney dysfunction induced by advanced glycation end products (AGEs) remains unknown. Renal damage was induced by AGEs via tail vein injections in rats. Function and morphology of kidney were determined. Compared to vehicle- or BSA-treated rats, AGEs caused abnormalities of kidney structures and functions in rats, accompanied with higher MDA level and lower GSH content. Gene expressions of NHE1 gene and TGF-β1 in the renal cortex and urine were also increased in AGEs-injected rats. Importantly, all these detrimental effects induced by AGEs were reversed by inhibition of NHE1 or suppression of oxidative stress. These pieces of data demonstrated that AGEs may activate NHE1 to induce renal damage, which is related to TGF-β1. PMID:26697498

Segmenting data sets for RIP.

PubMed

de Sanctis, Daniele; Nanao, Max H

2012-09-01

Specific radiation damage can be used for the phasing of macromolecular crystal structures. In practice, however, the optimization of the X-ray dose used to `burn' the crystal to induce specific damage can be difficult. Here, a method is presented in which a single large data set that has not been optimized in any way for radiation-damage-induced phasing (RIP) is segmented into multiple sub-data sets, which can then be used for RIP. The efficacy of this method is demonstrated using two model systems and two test systems. A method to improve the success of this type of phasing experiment by varying the composition of the two sub-data sets with respect to their separation by image number, and hence by absorbed dose, as well as their individual completeness is illustrated.

Insights into the mechanism of X-ray-induced disulfide-bond cleavage in lysozyme crystals based on EPR, optical absorption and X-ray diffraction studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sutton, Kristin A.; Black, Paul J.; Mercer, Kermit R.

2013-12-01

Electron paramagnetic resonance (EPR) and online UV–visible absorption microspectrophotometry with X-ray crystallography have been used in a complementary manner to follow X-ray-induced disulfide-bond cleavage, to confirm a multi-track radiation-damage process and to develop a model of that process. Electron paramagnetic resonance (EPR) and online UV–visible absorption microspectrophotometry with X-ray crystallography have been used in a complementary manner to follow X-ray-induced disulfide-bond cleavage. Online UV–visible spectroscopy showed that upon X-irradiation, disulfide radicalization appeared to saturate at an absorbed dose of approximately 0.5–0.8 MGy, in contrast to the saturating dose of ∼0.2 MGy observed using EPR at much lower dose rates. Themore » observations suggest that a multi-track model involving product formation owing to the interaction of two separate tracks is a valid model for radiation damage in protein crystals. The saturation levels are remarkably consistent given the widely different experimental parameters and the range of total absorbed doses studied. The results indicate that even at the lowest doses used for structural investigations disulfide bonds are already radicalized. Multi-track considerations offer the first step in a comprehensive model of radiation damage that could potentially lead to a combined computational and experimental approach to identifying when damage is likely to be present, to quantitate it and to provide the ability to recover the native unperturbed structure.« less

Low molecular weight guluronate prevents TNF-α-induced oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells.

PubMed

Dun, Yun-lou; Zhou, Xiao-lin; Guan, Hua-shi; Yu, Guang-li; Li, Chun-xia; Hu, Ting; Zhao, Xia; Cheng, Xiao-lei; He, Xiao-xi; Hao, Jie-jie

2015-09-01

Muscle wasting is associated with a variety of chronic or inflammatory disorders. Evidence suggests that inflammatory cytokines play a vital role in muscle inflammatory pathology and this may result in oxidative damage and mitochondrial dysfunction in skeletal muscle. In our study, we used microwave degradation to prepare a water-soluble low molecular weight guluronate (LMG) of 3000 Da from Fucus vesiculosus obtained from Canada, the Atlantic Ocean. We demonstrated the structural characteristics, using HPLC, FTIR and NMR of LMG and investigated its effects on oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells induced by tumor necrosis factor alpha (TNF-α), a cell inflammatory cytokine. The results indicated that LMG could alleviate mitochondrial reactive oxygen species (ROS) production, increase the activities of antioxidant enzymes (GSH and SOD), promote mitochondrial membrane potential (MMP) and upregulate the expression of mitochondrial respiratory chain protein in TNF-α-induced C2C12 cells. LMG supplement also increased the mitochondrial DNA copy number and mitochondrial biogenesis related genes in TNF-α-induced C2C12 cells. LMG may exert these protective effects through the nuclear factor kappa B (NF-κB) signaling pathway. These suggest that LMG is capable of protecting TNF-α-induced C2C12 cells against oxidative damage and mitochondrial dysfunction.

Radiation Damage in XFEL: Case study from the oxygen-evolving complex of Photosystem II

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amin, Muhamed; Badawi, Ashraf; Obayya, S. S.

Structural changes induced by radiation damage in X-ray crystallography hinder the ability to understand the structure/function relationship in chemical reactions. Serial femtosecond crystallography overcomes this problem by exposing the sample to very short and intense laser pulse leading to measurement before destruction. Here we use molecular modeling to map the radiation damage during the 10–50 fs to the intensity, the energy and the time duration of the laser pulse on the oxygen-evolving complex (OEC) of photosystem II. In the model, the nuclei move classically in a fully quantum potential created by electron density under the effect of strong laser pulsemore » in the Ehrenfest dynamics regime. The results show that the Mn-Mn and Mn-Ca distances are less affected by radiation damage due to the their heavy masses, while one μ-oxo bridge (O5) moves significantly. The radiation damage may induce conformational changes of the water ligands but only bond elongation for the amino acids ligands. These effects are relatively intensity independent from 10 16 to 10 17 W/cm 2, but changes increase dramatically if the beam intensity is increased to 10 18 W/cm 2. Finally, in addition, the self amplified spontaneous emission (SASE) nature of the laser beam does not affect the dynamics of the ions.« less

Radiation Damage in XFEL: Case study from the oxygen-evolving complex of Photosystem II

DOE PAGES

Amin, Muhamed; Badawi, Ashraf; Obayya, S. S.

2016-11-09

Structural changes induced by radiation damage in X-ray crystallography hinder the ability to understand the structure/function relationship in chemical reactions. Serial femtosecond crystallography overcomes this problem by exposing the sample to very short and intense laser pulse leading to measurement before destruction. Here we use molecular modeling to map the radiation damage during the 10–50 fs to the intensity, the energy and the time duration of the laser pulse on the oxygen-evolving complex (OEC) of photosystem II. In the model, the nuclei move classically in a fully quantum potential created by electron density under the effect of strong laser pulsemore » in the Ehrenfest dynamics regime. The results show that the Mn-Mn and Mn-Ca distances are less affected by radiation damage due to the their heavy masses, while one μ-oxo bridge (O5) moves significantly. The radiation damage may induce conformational changes of the water ligands but only bond elongation for the amino acids ligands. These effects are relatively intensity independent from 10 16 to 10 17 W/cm 2, but changes increase dramatically if the beam intensity is increased to 10 18 W/cm 2. Finally, in addition, the self amplified spontaneous emission (SASE) nature of the laser beam does not affect the dynamics of the ions.« less

Xeroderma Pigmentosum Group C Deficiency Alters Cigarette Smoke DNA Damage Cell Fate and Accelerates Emphysema Development.

PubMed

Sears, Catherine R; Zhou, Huaxin; Justice, Matthew J; Fisher, Amanda J; Saliba, Jacob; Lamb, Isaac; Wicker, Jessica; Schweitzer, Kelly S; Petrache, Irina

2018-03-01

Cigarette smoke (CS) exposure is a major risk factor for the development of emphysema, a common disease characterized by loss of cells comprising the lung parenchyma. The mechanisms of cell injury leading to emphysema are not completely understood but are thought to involve persistent cytotoxic or mutagenic DNA damage induced by CS. Using complementary cell culture and mouse models of CS exposure, we investigated the role of the DNA repair protein, xeroderma pigmentosum group C (XPC), on CS-induced DNA damage repair and emphysema. Expression of XPC was decreased in mouse lungs after chronic CS exposure and XPC knockdown in cultured human lung epithelial cells decreased their survival after CS exposure due to activation of the intrinsic apoptosis pathway. Similarly, cell autophagy and apoptosis were increased in XPC-deficient mouse lungs and were further increased by CS exposure. XPC deficiency was associated with structural and functional changes characteristic of emphysema, which were worsened by age, similar to levels observed with chronic CS exposure. Taken together, these findings suggest that repair of DNA damage by XPC plays an important and previously unrecognized role in the maintenance of alveolar structures. These findings support that loss of XPC, possibly due to chronic CS exposure, promotes emphysema development and further supports a link between DNA damage, impaired DNA repair, and development of emphysema.

Dynamic modeling of injection-induced fault reactivation and ground motion and impact on surface structures and human perception

DOE PAGES

Rutqvist, Jonny; Cappa, Frederic; Rinaldi, Antonio P.; ...

2014-12-31

We summarize recent modeling studies of injection-induced fault reactivation, seismicity, and its potential impact on surface structures and nuisance to the local human population. We used coupled multiphase fluid flow and geomechanical numerical modeling, dynamic wave propagation modeling, seismology theories, and empirical vibration criteria from mining and construction industries. We first simulated injection-induced fault reactivation, including dynamic fault slip, seismic source, wave propagation, and ground vibrations. From co-seismic average shear displacement and rupture area, we determined the moment magnitude to about M w = 3 for an injection-induced fault reactivation at a depth of about 1000 m. We then analyzedmore » the ground vibration results in terms of peak ground acceleration (PGA), peak ground velocity (PGV), and frequency content, with comparison to the U.S. Bureau of Mines’ vibration criteria for cosmetic damage to buildings, as well as human-perception vibration limits. For the considered synthetic M w = 3 event, our analysis showed that the short duration, high frequency ground motion may not cause any significant damage to surface structures, and would not cause, in this particular case, upward CO 2 leakage, but would certainly be felt by the local population.« less

In-situ structural integrity evaluation for high-power pulsed spallation neutron source - Effects of cavitation damage on structural vibration

NASA Astrophysics Data System (ADS)

Wan, Tao; Naoe, Takashi; Futakawa, Masatoshi

2016-01-01

A double-wall structure mercury target will be installed at the high-power pulsed spallation neutron source in the Japan Proton Accelerator Research Complex (J-PARC). Cavitation damage on the inner wall is an important factor governing the lifetime of the target-vessel. To monitor the structural integrity of the target vessel, displacement velocity at a point on the outer surface of the target vessel is measured using a laser Doppler vibrometer (LDV). The measured signals can be used for evaluating the damage inside the target vessel because of cyclic loading and cavitation bubble collapse caused by pulsed-beam induced pressure waves. The wavelet differential analysis (WDA) was applied to reveal the effects of the damage on vibrational cycling. To reduce the effects of noise superimposed on the vibration signals on the WDA results, analysis of variance (ANOVA) and analysis of covariance (ANCOVA), statistical methods were applied. Results from laboratory experiments, numerical simulation results with random noise added, and target vessel field data were analyzed by the WDA and the statistical methods. The analyses demonstrated that the established in-situ diagnostic technique can be used to effectively evaluate the structural response of the target vessel.

Subclinical chronic kidney disease modifies the diagnosis of experimental acute kidney injury.

PubMed

Succar, Lena; Pianta, Timothy J; Davidson, Trent; Pickering, John W; Endre, Zoltán H

2017-09-01

Extensive structural damage within the kidney must be present before serum creatinine increases. However, a subclinical phase of chronic kidney disease (CKD) usually goes undetected. Here we tested whether experimental subclinical CKD would modify functional and damage biomarker profiles of acute kidney injury (AKI). Subclinical CKD was induced in rats by adenine or aristolochic acid models but without increasing serum creatinine. After prolonged recovery (three to six weeks), AKI was induced with a subnephrotoxic dose of cisplatin. Urinary levels of kidney injury molecule-1 (KIM-1), cytochrome C, monocyte chemotactic protein-1 (MCP-1), clusterin, and interleukin-18 increased during CKD induction, without an increase in serum creatinine. After AKI in adenine-induced CKD, serum creatinine increased more rapidly, while increased urinary KIM-1, clusterin, and MCP-1 were delayed and reduced. Increased serum creatinine and biomarker excretion were associated with diffuse tubulointerstitial injury in the outer stripe of outer medulla coupled with over 50% cortical damage. Following AKI in aristolochic acid-induced CKD, increased serum creatinine, urinary KIM-1, clusterin, MCP-1, cytochrome C, and interleukin-18 concentrations and excretion were greater at day 21 than day 42 and inversely correlated with cortical injury. Subclinical CKD modified functional and damage biomarker profiles in diametrically opposite ways. Functional biomarker profiles were more sensitive, while damage biomarker diagnostic thresholds and increases were diminished and delayed. Damage biomarker concentrations and excretion were inversely linked to the extent of prior cortical damage. Thus, thresholds for AKI biomarkers may need to be lower or sampling delayed in the known presence of CKD. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Impact of TLR4 on behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage.

PubMed

Pascual, María; Baliño, Pablo; Alfonso-Loeches, Silvia; Aragón, Carlos M G; Guerri, Consuelo

2011-06-01

Toll-like receptors (TLRs) play an important role in the innate immune response, and emerging evidence indicates their role in brain injury and neurodegeneration. Our recent results have demonstrated that ethanol is capable of activating glial TLR4 receptors and that the elimination of these receptors in mice protects against ethanol-induced glial activation, induction of inflammatory mediators and apoptosis. This study was designed to assess whether ethanol-induced inflammatory damage causes behavioral and cognitive consequences, and if behavioral alterations are dependent of TLR4 functions. Here we show in mice drinking alcohol for 5months, followed by a 15-day withdrawal period, that activation of the astroglial and microglial cells in frontal cortex and striatum is maintained and that these events are associated with cognitive and anxiety-related behavioral impairments in wild-type (WT) mice, as demonstrated by testing the animals with object memory recognition, conditioned taste aversion and dark and light box anxiety tasks. Mice lacking TLR4 receptors are protected against ethanol-induced inflammatory damage, and behavioral associated effects. We further assess the possibility of the epigenetic modifications participating in short- or long-term behavioral effects associated with neuroinflammatory damage. We show that chronic alcohol treatment decreases H4 histone acetylation and histone acetyltransferases activity in frontal cortex, striatum and hippocampus of WT mice. Alterations in chromatin structure were not observed in TLR4(-/-) mice. These results provide the first evidence of the role that TLR4 functions play in the behavioral consequences of alcohol-induced inflammatory damage and suggest that the epigenetic modifications mediated by TLR4 could contribute to short- or long-term alcohol-induced behavioral or cognitive dysfunctions. Copyright © 2011 Elsevier Inc. All rights reserved.

Hot-carrier-induced current capability degradation and optimization for lateral IGBT on thick SOI substrate

NASA Astrophysics Data System (ADS)

Zhang, Chunwei; Li, Yang; Yue, Wenjing; Fu, Xiaoqian; Li, Zhiming

2018-07-01

In this paper, the hot-carrier-induced current capability degradation of a 600 V lateral insulated gate bipolar transistor (LIGBT) on thick silicon on insulator (SOI) substrate is investigated. Our experiments found that, for the SOI-LIGBT, the worst stress condition is the maximum gate voltage (Vgmax) condition and the current degradation is dominated by the damages in the channel region under the Vgmax stress condition. However, further analyses show that the influence of channel region damages on the collector current degradation increases with the increase of measured collector voltage and is maximum in the current saturation region. Therefore, in our opinion, the hot-carrier-induced current capability degradation of the SOI-LIGBT should be evaluated by the degradation of saturation current under the Vgmax stress condition. In addition, a novel SOI-LIGBT structure with an external p-type region was also proposed, which can alleviate the damage in the channel region by reducing the lateral electric field peak. Our experimental results demonstrate that the proposed structure could optimize the hot-carrier reliability effectively with the other characteristics maintained. He is currently a lecturer at the University of Jinan, Jinan, China. His research interests include power electronics, high voltage devices and the electronics reliability.

Luminescence in the fluoride-containing phosphate-based glasses: A possible origin of their high resistance to nanosecond pulse laser-induced damage

PubMed Central

Wang, Pengfei; Lu, Min; Gao, Fei; Guo, Haitao; Xu, Yantao; Hou, Chaoqi; Zhou, Zhiwei; Peng, Bo

2015-01-01

Fusion power offers the prospect of an almost inexhaustible source of energy for future generations. It was reported that fusion fuel gains exceeding unity on the National Ignition Facility (NIF) were achieved, but so far great deal of scientific and engineering challenges have to be overcome for realizing fusion power generation. There is a bottleneck for color-separation gratings in NIF and other similar inertial confinement fusion (ICF) lasers. Here we show a series of high performance phosphate-based glasses that can transmit the third harmonic frequency (3ω) laser light with high efficiency meanwhile filter the fundamental (1ω) and the second harmonic frequency (2ω) laser lights through direct absorption, and especially they exhibit excellent damage threshold induced by nanosecond pulse laser compared with that of the fused silica used in NIF. Yellowish-orange fluorescence emits during the laser-material interaction process, and it can be tailored through regulating the glass structure. Study on its structural origin suggests that the fluorescence emission is a key factor that conduces to the high laser-induced damage resistance of these glasses. The results also indicated the feasibility of utilizing these high performance glasses in novel color separation optics, allowing novel design for the final optics assembly in ICF lasers. PMID:25716328

Luminescence in the fluoride-containing phosphate-based glasses: a possible origin of their high resistance to nanosecond pulse laser-induced damage.

PubMed

Wang, Pengfei; Lu, Min; Gao, Fei; Guo, Haitao; Xu, Yantao; Hou, Chaoqi; Zhou, Zhiwei; Peng, Bo

2015-02-26

Fusion power offers the prospect of an almost inexhaustible source of energy for future generations. It was reported that fusion fuel gains exceeding unity on the National Ignition Facility (NIF) were achieved, but so far great deal of scientific and engineering challenges have to be overcome for realizing fusion power generation. There is a bottleneck for color-separation gratings in NIF and other similar inertial confinement fusion (ICF) lasers. Here we show a series of high performance phosphate-based glasses that can transmit the third harmonic frequency (3ω) laser light with high efficiency meanwhile filter the fundamental (1ω) and the second harmonic frequency (2ω) laser lights through direct absorption, and especially they exhibit excellent damage threshold induced by nanosecond pulse laser compared with that of the fused silica used in NIF. Yellowish-orange fluorescence emits during the laser-material interaction process, and it can be tailored through regulating the glass structure. Study on its structural origin suggests that the fluorescence emission is a key factor that conduces to the high laser-induced damage resistance of these glasses. The results also indicated the feasibility of utilizing these high performance glasses in novel color separation optics, allowing novel design for the final optics assembly in ICF lasers.

Memory retrieval-induced activation of adult-born neurons generated in response to damage to the dentate gyrus.

PubMed

Aguilar-Arredondo, Andrea; Zepeda, Angélica

2018-07-01

The dentate gyrus (DG) is a neurogenic structure that exhibits functional and structural reorganization after injury. Neurogenesis and functional recovery occur after brain damage, and the possible relation between both processes is a matter of study. We explored whether neurogenesis and the activation of new neurons correlated with DG recovery over time. We induced a DG lesion in young adult rats through the intrahippocampal injection of kainic acid and analyzed functional recovery and the activation of new neurons after animals performed a contextual fear memory task (CFM) or a control spatial exploratory task. We analyzed the number of BrdU+ cells that co-localized with doublecortin (DCX) or with NeuN within the damaged DG and evaluated the number of cells in each population that were labelled with the activity marker c-fos after either task. At 10 days post-lesion (dpl), a region of the granular cell layer was devoid of cells, evidencing the damaged area, whereas at 30 dpl this region was significantly smaller. At 10 dpl, the number of BrdU+/DCX+/c-fos positive cells was increased compared to the sham-lesion group, but CFM was impaired. At 30 dpl, a significantly greater number of BrdU+/NeuN+/c-fos positive cells was observed than at 10 dpl, and activation correlated with CFM recovery. Performance in the spatial exploratory task induced marginal c-fos immunoreactivity in the BrdU+/NeuN+ population. We demonstrate that neurons born after the DG was damaged survive and are activated in a time- and task-dependent manner and that activation of new neurons occurs along functional recovery.

FEM modeling and histological analyses on thermal damage induced in facial skin resurfacing procedure with different CO2 laser pulse duration

NASA Astrophysics Data System (ADS)

Rossi, Francesca; Zingoni, Tiziano; Di Cicco, Emiliano; Manetti, Leonardo; Pini, Roberto; Fortuna, Damiano

2011-07-01

Laser light is nowadays routinely used in the aesthetic treatments of facial skin, such as in laser rejuvenation, scar removal etc. The induced thermal damage may be varied by setting different laser parameters, in order to obtain a particular aesthetic result. In this work, it is proposed a theoretical study on the induced thermal damage in the deep tissue, by considering different laser pulse duration. The study is based on the Finite Element Method (FEM): a bidimensional model of the facial skin is depicted in axial symmetry, considering the different skin structures and their different optical and thermal parameters; the conversion of laser light into thermal energy is modeled by the bio-heat equation. The light source is a CO2 laser, with different pulse durations. The model enabled to study the thermal damage induced into the skin, by calculating the Arrhenius integral. The post-processing results enabled to study in space and time the temperature dynamics induced in the facial skin, to study the eventual cumulative effects of subsequent laser pulses and to optimize the procedure for applications in dermatological surgery. The calculated data where then validated in an experimental measurement session, performed in a sheep animal model. Histological analyses were performed on the treated tissues, evidencing the spatial distribution and the entity of the thermal damage in the collageneous tissue. Modeling and experimental results were in good agreement, and they were used to design a new optimized laser based skin resurfacing procedure.

Radiation-induced effects on the mechanical properties of natural ZrSiO4: double cascade-overlap damage accumulation

NASA Astrophysics Data System (ADS)

Beirau, Tobias; Nix, William D.; Pöllmann, Herbert; Ewing, Rodney C.

2018-05-01

Several different models are known to describe the structure-dependent radiation-induced damage accumulation process in materials (e.g. Gibbons Proc IEEE 60:1062-1096, 1972; Weber Nuc Instr Met Phys Res B 166-167:98-106, 2000). In the literature, two different models of damage accumulation due to α-decay events in natural ZrSiO4 (zircon) have been described. The direct impact damage accumulation model is based on amorphization occurring directly within the collision cascade. However, the double cascade-overlap damage accumulation model predicts that amorphization will only occur due to the overlap of disordered domains within the cascade. By analyzing the dose-dependent evolution of mechanical properties (i.e., Poisson's ratios, compliance constants, elastic modulus, and hardness) as a measure of the increasing amorphization, we provide support for the double cascade-overlap damage accumulation model. We found no evidence to support the direct impact damage accumulation model. Additionally, the amount of radiation damage could be related to an anisotropic-to-isotropic transition of the Poisson's ratio for stress along and perpendicular to the four-fold c-axis and of the related compliance constants of natural U- and Th-bearing zircon. The isotropification occurs in the dose range between 3.1 × and 6.3 × 1018 α-decays/g.

Radiation-induced effects on the mechanical properties of natural ZrSiO4: double cascade-overlap damage accumulation

NASA Astrophysics Data System (ADS)

Beirau, Tobias; Nix, William D.; Pöllmann, Herbert; Ewing, Rodney C.

2017-11-01

Several different models are known to describe the structure-dependent radiation-induced damage accumulation process in materials (e.g. Gibbons Proc IEEE 60:1062-1096, 1972; Weber Nuc Instr Met Phys Res B 166-167:98-106, 2000). In the literature, two different models of damage accumulation due to α-decay events in natural ZrSiO4 (zircon) have been described. The direct impact damage accumulation model is based on amorphization occurring directly within the collision cascade. However, the double cascade-overlap damage accumulation model predicts that amorphization will only occur due to the overlap of disordered domains within the cascade. By analyzing the dose-dependent evolution of mechanical properties (i.e., Poisson's ratios, compliance constants, elastic modulus, and hardness) as a measure of the increasing amorphization, we provide support for the double cascade-overlap damage accumulation model. We found no evidence to support the direct impact damage accumulation model. Additionally, the amount of radiation damage could be related to an anisotropic-to-isotropic transition of the Poisson's ratio for stress along and perpendicular to the four-fold c-axis and of the related compliance constants of natural U- and Th-bearing zircon. The isotropification occurs in the dose range between 3.1 × and 6.3 × 1018 α-decays/g.

Melatonin Role in Ameliorating Radiation-induced Skin Damage: From Theory to Practice (A Review of Literature).

PubMed

Abbaszadeh, A; Haddadi, G H; Haddadi, Z

2017-06-01

Normal skin is composed of epidermis and dermis. Skin is susceptible to radiation damage because it is a continuously renewing organ containing rapidly proliferating mature cells. Radiation burn is a damage to the skin or other biological tissues caused by exposure to radiofrequency energy or ionizing radiation. Acute skin reaction is the most frequently occurring side effect of radiation therapy. Generally, any chemical/biological agent given before or at the time of irradiation to prevent or ameliorate damage to normal tissues is called a radioprotector. Melatonin is a highly lipophilic substance that easily penetrates organic membranes and therefore is able to protect important intracellular structures including mitochondria and DNA against oxidative damage directly at the sites where such a kind of damage would occur. Melatonin leads to an increase in the molecular level of some important antioxidative enzymes such as superoxide, dismotase and glutation-peroxidase, and also a reduction in synthetic activity of nitric oxide. There is a large body of evidence which proves the efficacy of Melatonin in ameliorating UV and X ray-induced skin damage. We propose that, in the future, Melatonin would improve the therapeutic ratio in radiation oncology and ameliorate skin damage more effectively when administered in optimal and non-toxic doses.

Melatonin Role in Ameliorating Radiation-induced Skin Damage: From Theory to Practice (A Review of Literature)

PubMed Central

Abbaszadeh, A.; Haddadi, G.H.; Haddadi, Z.

2017-01-01

Normal skin is composed of epidermis and dermis. Skin is susceptible to radiation damage because it is a continuously renewing organ containing rapidly proliferating mature cells. Radiation burn is a damage to the skin or other biological tissues caused by exposure to radiofrequency energy or ionizing radiation. Acute skin reaction is the most frequently occurring side effect of radiation therapy. Generally, any chemical/biological agent given before or at the time of irradiation to prevent or ameliorate damage to normal tissues is called a radioprotector. Melatonin is a highly lipophilic substance that easily penetrates organic membranes and therefore is able to protect important intracellular structures including mitochondria and DNA against oxidative damage directly at the sites where such a kind of damage would occur. Melatonin leads to an increase in the molecular level of some important antioxidative enzymes such as superoxide, dismotase and glutation-peroxidase, and also a reduction in synthetic activity of nitric oxide. There is a large body of evidence which proves the efficacy of Melatonin in ameliorating UV and X ray-induced skin damage. We propose that, in the future, Melatonin would improve the therapeutic ratio in radiation oncology and ameliorate skin damage more effectively when administered in optimal and non-toxic doses. PMID:28580334

Nonlinear Ultrasonic Diagnosis and Prognosis of ASR Damage in Dry Cask Storage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qu, Jianmin; Bazant, Zdenek; Jacobs, Laurence

Alkali-silica reaction (ASR) is a deleterious chemical process that may occur in cement-based materials such as mortars and concretes, where the hydroxyl ions in the highly alkaline pore solution attack the siloxane groups in the siliceous minerals in the aggregates. The reaction produces a cross-linked alkali-silica gel. The ASR gel swells in the presence of water. Expansion of the gel results in cracking when the swelling-induced stress exceeds the fracture toughness of the concrete. As the ASR continues, cracks may grow and eventually coalesce, which results in reduced service life and a decrease safety of concrete structures. Since concrete ismore » widely used as a critical structural component in dry cask storage of used nuclear fuels, ASR damage poses a significant threat to the sustainability of long term dry cask storage systems. Therefore, techniques for effectively detecting, managing and mitigating ASR damage are needed. Currently, there are no nondestructive methods to accurately detect ASR damage in existing concrete structures. The only current way of accurately assessing ASR damage is to drill a core from an existing structure, and conduct microscopy on this drilled cylindrical core. Clearly, such a practice is not applicable to dry cask storage systems. To meet these needs, this research is aimed at developing (1) a suite of nonlinear ultrasonic quantitative nondestructive evaluation (QNDE) techniques to characterize ASR damage, and (2) a physics-based model for ASR damage evolution using the QNDE data. Outcomes of this research will provide a nondestructive diagnostic tool to evaluate the extent of the ASR damage, and a prognostic tool to estimate the future reliability and safety of the concrete structures in dry cask storage systems« less

Evaluation of Ultrasound-Induced Damage to Escherichia coli and Staphylococcus aureus by Flow Cytometry and Transmission Electron Microscopy

PubMed Central

Li, Jiao; Ahn, Juhee; Liu, Donghong; Chen, Shiguo; Ye, Xingqian

2016-01-01

As a nonthermal sterilization technique, ultrasound has attracted great interest in the field of food preservation. In this study, flow cytometry and transmission electron microscopy were employed to investigate ultrasound-induced damage to Escherichia coli and Staphylococcus aureus. For flow cytometry studies, single staining with propidium iodide (PI) or carboxyfluorescein diacetate (cFDA) revealed that ultrasound treatment caused cell death by compromising membrane integrity, inactivating intracellular esterases, and inhibiting metabolic performance. The results showed that ultrasound damage was independent of initial bacterial concentrations, while the mechanism of cellular damage differed according to the bacterial species. For the Gram-negative bacterium E. coli, ultrasound worked first on the outer membrane rather than the cytoplasmic membrane. Based on the double-staining results, we inferred that ultrasound treatment might be an all-or-nothing process: cells ruptured and disintegrated by ultrasound cannot be revived, which can be considered an advantage of ultrasound over other nonthermal techniques. Transmission electron microscopy studies revealed that the mechanism of ultrasound-induced damage was multitarget inactivation, involving the cell wall, cytoplasmic membrane, and inner structure. Understanding of the irreversible antibacterial action of ultrasound has great significance for its further utilization in the food industry. PMID:26746712

Explaining the heterogeneity of functional connectivity findings in multiple sclerosis: An empirically informed modeling study.

PubMed

Tewarie, Prejaas; Steenwijk, Martijn D; Brookes, Matthew J; Uitdehaag, Bernard M J; Geurts, Jeroen J G; Stam, Cornelis J; Schoonheim, Menno M

2018-06-01

To understand the heterogeneity of functional connectivity results reported in the literature, we analyzed the separate effects of grey and white matter damage on functional connectivity and networks in multiple sclerosis. For this, we employed a biophysical thalamo-cortical model consisting of interconnected cortical and thalamic neuronal populations, informed and amended by empirical diffusion MRI tractography data, to simulate functional data that mimic neurophysiological signals. Grey matter degeneration was simulated by decreasing within population connections and white matter degeneration by lowering between population connections, based on lesion predilection sites in multiple sclerosis. For all simulations, functional connectivity and functional network organization are quantified by phase synchronization and network integration, respectively. Modeling results showed that both cortical and thalamic grey matter damage induced a global increase in functional connectivity, whereas white matter damage induced an initially increased connectivity followed by a global decrease. Both white and especially grey matter damage, however, induced a decrease in network integration. These empirically informed simulations show that specific topology and timing of structural damage are nontrivial aspects in explaining functional abnormalities in MS. Insufficient attention to these aspects likely explains contradictory findings in multiple sclerosis functional imaging studies so far. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Damage threshold in adult rabbit eyes after scleral cross-linking by riboflavin/blue light application.

PubMed

Iseli, Hans Peter; Körber, Nicole; Karl, Anett; Koch, Christian; Schuldt, Carsten; Penk, Anja; Liu, Qing; Huster, Daniel; Käs, Josef; Reichenbach, Andreas; Wiedemann, Peter; Francke, Mike

2015-10-01

Several scleral cross-linking (SXL) methods were suggested to increase the biomechanical stiffness of scleral tissue and therefore, to inhibit axial eye elongation in progressive myopia. In addition to scleral cross-linking and biomechanical effects caused by riboflavin and light irradiation such a treatment might induce tissue damage, dependent on the light intensity used. Therefore, we characterized the damage threshold and mechanical stiffening effect in rabbit eyes after application of riboflavin combined with various blue light intensities. Adult pigmented and albino rabbits were treated with riboflavin (0.5 %) and varying blue light (450 ± 50 nm) dosages from 18 to 780 J/cm(2) (15 to 650 mW/cm(2) for 20 min). Scleral, choroidal and retinal tissue alterations were detected by means of light microscopy, electron microscopy and immunohistochemistry. Biomechanical changes were measured by shear rheology. Blue light dosages of 480 J/cm(2) (400 mW/cm(2)) and beyond induced pathological changes in ocular tissues; the damage threshold was defined by the light intensities which induced cellular degeneration and/or massive collagen structure changes. At such high dosages, we observed alterations of the collagen structure in scleral tissue, as well as pigment aggregation, internal hemorrhages, and collapsed blood vessels. Additionally, photoreceptor degenerations associated with microglia activation and macroglia cell reactivity in the retina were detected. These pathological alterations were locally restricted to the treated areas. Pigmentation of rabbit eyes did not change the damage threshold after a treatment with riboflavin and blue light but seems to influence the vulnerability for blue light irradiations. Increased biomechanical stiffness of scleral tissue could be achieved with blue light intensities below the characterized damage threshold. We conclude that riboflavin and blue light application increased the biomechanical stiffness of scleral tissue at blue light energy levels below the damage threshold. Therefore, applied blue light intensities below the characterized damage threshold might define a therapeutic blue light tolerance range. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exercise-Induced Skeletal Muscle Damage.

PubMed

Evans, W J

1987-01-01

In brief: Delayed-onset muscle soreness is most likely caused by structural damage in skeletal muscle after eccentric exercise, in which muscles produce force while lengthening, as in running downhill. This damage may take as long as 12 weeks to repair. Therefore, athletes should allow plenty of time for recovery after events that cause extreme muscle soreness. Because prostaglandin E2 may be important in muscle repair, prostaglandin blockers, such as aspirin, may be useless or even detrimental in the treatment of delayed-onset muscle soreness. Eccentric exercise training may help prevent soreness.

Study of Impact Damage in PVA-ECC Beam under Low-Velocity Impact Loading Using Piezoceramic Transducers and PVDF Thin-Film Transducers.

PubMed

Qi, Baoxin; Kong, Qingzhao; Qian, Hui; Patil, Devendra; Lim, Ing; Li, Mo; Liu, Dong; Song, Gangbing

2018-02-24

Compared to conventional concrete, polyvinyl alcohol fiber reinforced engineering cementitious composite (PVA-ECC) offers high-strength, ductility, formability, and excellent fatigue resistance. However, impact-induced structural damage is a major concern and has not been previously characterized in PVA-ECC structures. We investigate the damage of PVA-ECC beams under low-velocity impact loading. A series of ball-drop impact tests were performed at different drop weights and heights to simulate various impact energies. The impact results of PVA-ECC beams were compared with mortar beams. A combination of polyvinylidene fluoride (PVDF) thin-film sensors and piezoceramic-based smart aggregate were used for impact monitoring, which included impact initiation and crack evolution. Short-time Fourier transform (STFT) of the signal received by PVDF thin-film sensors was performed to identify impact events, while active-sensing approach was utilized to detect impact-induced crack evolution by the attenuation of a propagated guided wave. Wavelet packet-based energy analysis was performed to quantify failure development under repeated impact tests.

Study of Impact Damage in PVA-ECC Beam under Low-Velocity Impact Loading Using Piezoceramic Transducers and PVDF Thin-Film Transducers

PubMed Central

Qian, Hui; Li, Mo; Liu, Dong; Song, Gangbing

2018-01-01

Compared to conventional concrete, polyvinyl alcohol fiber reinforced engineering cementitious composite (PVA-ECC) offers high-strength, ductility, formability, and excellent fatigue resistance. However, impact-induced structural damage is a major concern and has not been previously characterized in PVA-ECC structures. We investigate the damage of PVA-ECC beams under low-velocity impact loading. A series of ball-drop impact tests were performed at different drop weights and heights to simulate various impact energies. The impact results of PVA-ECC beams were compared with mortar beams. A combination of polyvinylidene fluoride (PVDF) thin-film sensors and piezoceramic-based smart aggregate were used for impact monitoring, which included impact initiation and crack evolution. Short-time Fourier transform (STFT) of the signal received by PVDF thin-film sensors was performed to identify impact events, while active-sensing approach was utilized to detect impact-induced crack evolution by the attenuation of a propagated guided wave. Wavelet packet-based energy analysis was performed to quantify failure development under repeated impact tests. PMID:29495277

Structural defect accumulation in tungsten and tungsten-5wt.% tantalum under incremental proton damage

NASA Astrophysics Data System (ADS)

Ipatova, I.; Harrison, R. W.; Wady, P. T.; Shubeita, S. M.; Terentyev, D.; Donnelly, S. E.; Jimenez-Melero, E.

2018-04-01

We have performed proton irradiation of W and W-5wt.%Ta materials at 350 °C with a step-wise damage level increase up to 0.7 dpa and using two beam energies, namely 40 keV and 3 MeV, in order to probe the accumulation of radiation-induced lattice damage in these materials. Interstitial-type a/2 <111> dislocation loops are formed under irradiation, and their size increases in W-5Ta up to a loop width of 21 ± 4 nm at 0.3 dpa, where loop saturation takes place. In contrast, the loop length in W increases progressively up to 183 ± 50 nm at 0.7 dpa, whereas the loop width remains relatively constant at 29 ± 7 nm at >0.3 dpa, giving rise to dislocation strings. The dislocation loops and tangles are observed in both materials examined after a 3 MeV proton irradiation at 350 °C. Ta doping delays the evolution of radiation-induced dislocation structures in W, and can consequently impact the hydrogen isotope retention under plasma exposure.

Transcription-induced DNA supercoiling: New roles of intranucleosomal DNA loops in DNA repair and transcription.

PubMed

Gerasimova, N S; Pestov, N A; Kulaeva, O I; Clark, D J; Studitsky, V M

2016-05-26

RNA polymerase II (Pol II) transcription through chromatin is accompanied by formation of small intranucleosomal DNA loops. Pol II captured within a small loop drives accumulation of DNA supercoiling, facilitating further transcription. DNA breaks relieve supercoiling and induce Pol II arrest, allowing detection of DNA damage hidden in chromatin structure.

A vibro-haptic human-machine interface for structural health monitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mascarenas, David; Plont, Crystal; Brown, Christina

The structural health monitoring (SHM) community’s goal has been to endow physical systems with a nervous system not unlike those commonly found in living organisms. Typically the SHM community has attempted to do this by instrumenting structures with a variety of sensors, and then applying various signal processing and classification procedures to the data in order to detect the presence of damage, the location of damage, the severity of damage, and to estimate the remaining useful life of the structure. This procedure has had some success, but we are still a long way from achieving the performance of nervous systemsmore » found in biology. This is primarily because contemporary classification algorithms do not have the performance required. In many cases expert judgment is superior to automated classification. This work introduces a new paradigm. We propose interfacing the human nervous system to the distributed sensor network located on the structure and developing new techniques to enable human-machine cooperation. Results from the field of sensory substitution suggest this should be possible. This study investigates a vibro-haptic human-machine interface for SHM. The investigation was performed using a surrogate three-story structure. The structure features three nonlinearity-inducing bumpers to simulate damage. Accelerometers are placed on each floor to measure the response of the structure to a harmonic base excitation. The accelerometer measurements are preprocessed. As a result, the preprocessed data is then encoded encoded as a vibro-tactile stimulus. Human subjects were then subjected to the vibro-tactile stimulus and asked to characterize the damage in the structure.« less

A vibro-haptic human-machine interface for structural health monitoring

DOE PAGES

Mascarenas, David; Plont, Crystal; Brown, Christina; ...

2014-11-01

The structural health monitoring (SHM) community’s goal has been to endow physical systems with a nervous system not unlike those commonly found in living organisms. Typically the SHM community has attempted to do this by instrumenting structures with a variety of sensors, and then applying various signal processing and classification procedures to the data in order to detect the presence of damage, the location of damage, the severity of damage, and to estimate the remaining useful life of the structure. This procedure has had some success, but we are still a long way from achieving the performance of nervous systemsmore » found in biology. This is primarily because contemporary classification algorithms do not have the performance required. In many cases expert judgment is superior to automated classification. This work introduces a new paradigm. We propose interfacing the human nervous system to the distributed sensor network located on the structure and developing new techniques to enable human-machine cooperation. Results from the field of sensory substitution suggest this should be possible. This study investigates a vibro-haptic human-machine interface for SHM. The investigation was performed using a surrogate three-story structure. The structure features three nonlinearity-inducing bumpers to simulate damage. Accelerometers are placed on each floor to measure the response of the structure to a harmonic base excitation. The accelerometer measurements are preprocessed. As a result, the preprocessed data is then encoded encoded as a vibro-tactile stimulus. Human subjects were then subjected to the vibro-tactile stimulus and asked to characterize the damage in the structure.« less

Helium vs. Proton Induced Displacement Damage in Electronic Materials

NASA Technical Reports Server (NTRS)

Ringo, Sawnese; Barghouty, A. F.

2010-01-01

In this project, the specific effects of displacement damage due to the passage of protons and helium nuclei on some typical electronic materials will be evaluated and contrasted. As the electronic material absorbs the energetic proton and helium momentum, degradation of performance occurs, eventually leading to overall failure. Helium nuclei traveling at the same speed as protons are expected to impart more to the material displacement damage; due to the larger mass, and thus momentum, of helium nuclei compared to protons. Damage due to displacement of atoms in their crystalline structure can change the physical properties and hence performance of the electronic materials.

1H NMR-based metabolomics study of liver damage induced by ginkgolic acid (15:1) in mice.

PubMed

Jiang, Lei; Si, Zhi-Hong; Li, Ming-Hui; Zhao, He; Fu, Yong-Hong; Xing, Yue-Xiao; Hong, Wei; Ruan, Ling-Yu; Li, Pu-Min; Wang, Jun-Song

2017-03-20

Ginkgolic acid (15:1) is a major toxic component in extracts obtained from Ginkgo biloba (EGb) that has allergic and genotoxic effects. This study is the first to explore the hepatotoxicity of ginkgolic acid (15:1) using a NMR (nuclear magnetic resonance)-based metabolomics approach in combination with biochemistry assays. Mice were orally administered two doses of ginkgolic acid (15:1), and mouse livers and serum were then collected for NMR recordings and biochemical assays. The levels of activity of alanine aminotransferase (ALT) and glutamic aspartate transaminase (AST) observed in the ginkgolic acid (15:1)-treated mice suggested that it had induced severe liver damage. An orthogonal signal correction partial least-squares discriminant analysis (OSC-PLSDA) performed to determine the metabolomic profile of mouse liver tissues indicated that many metabolic disturbances, especially oxidative stress and purine metabolism, were induced by ginkgolic acid (15:1). A correlation network analysis combined with information related to structural similarities further confirmed that purine metabolism was disturbed by ginkgolic acid (15:1). This mechanism might represent the link between the antitumour activity and the liver injury-inducing effect of ginkgolic acid (15:1). A SUS (Shared and Unique Structure) plot suggested that a two-dose treatment of ginkgolic acid (15:1) had generally the same effect on metabolic variations but that its effects were dose-dependent, revealing some of the common features of ginkgolic acid (15:1) dosing. This integrated metabolomics approach helped us to characterise ginkgolic acid (15:1)-induced liver damage in mice. Copyright © 2016 Elsevier B.V. All rights reserved.

Degradation of CMOS image sensors in deep-submicron technology due to γ-irradiation

NASA Astrophysics Data System (ADS)

Rao, Padmakumar R.; Wang, Xinyang; Theuwissen, Albert J. P.

2008-09-01

In this work, radiation induced damage mechanisms in deep submicron technology is resolved using finger gated-diodes (FGDs) as a radiation sensitive tool. It is found that these structures are simple yet efficient structures to resolve radiation induced damage in advanced CMOS processes. The degradation of the CMOS image sensors in deep-submicron technology due to γ-ray irradiation is studied by developing a model for the spectral response of the sensor and also by the dark-signal degradation as a function of STI (shallow-trench isolation) parameters. It is found that threshold shifts in the gate-oxide/silicon interface as well as minority carrier life-time variations in the silicon bulk are minimal. The top-layer material properties and the photodiode Si-SiO2 interface quality are degraded due to γ-ray irradiation. Results further suggest that p-well passivated structures are inevitable for radiation-hard designs. It was found that high electrical fields in submicron technologies pose a threat to high quality imaging in harsh environments.

Trifluoroacetylated tyrosine-rich D-tetrapeptides have potent antioxidant activity.

PubMed

Sandomenico, Annamaria; Severino, Valeria; Apone, Fabio; De Lucia, Adriana; Caporale, Andrea; Doti, Nunzianna; Russo, Anna; Russo, Rosita; Rega, Camilla; Del Giacco, Tiziana; Falcigno, Lucia; Ruvo, Menotti; Chambery, Angela

2017-03-01

The term "oxidative stress" indicates a set of chemical reactions unleashed by a disparate number of events inducing DNA damage, lipid peroxidation, protein modification and other effects, which are responsible of altering the physiological status of cells or tissues. Excessive Reactive Oxygen Species (ROS) levels may accelerate ageing of tissues or induce damage of biomolecules thus promoting cell death or proliferation in dependence of cell status and of targeted molecules. In this context, new antioxidants preventing such effects may have a relevant role as modulators of cell homeostasis and as therapeutic agents. Following an approach of peptide libraries synthesis and screening by an ORAC FL assay, we have isolated potent anti-oxidant compounds with well-defined structures. Most effective peptides are N-terminally trifluoroacetylated (CF 3 ) and have the sequence tyr-tyr-his-pro or tyr-tyr-pro-his. Slight changes in the sequence or removal of the CF 3 group strongly reduced antioxidant ability, suggesting an active role of both the fluorine atoms and of peptide structure. We have determined the NMR solution structures of the active peptides and found a common structural motif that could underpin the radical scavenging activity. The peptides protect keratinocytes from exogenous oxidation, thereby from potential external damaging cues, suggesting their use as skin ageing protectant and as cell surviving agents. Copyright © 2017 Elsevier Inc. All rights reserved.

Preventive role of lens antioxidant defense mechanism against riboflavin-mediated sunlight damaging of lens crystallins.

PubMed

Anbaraki, Afrooz; Khoshaman, Kazem; Ghasemi, Younes; Yousefi, Reza

2016-10-01

The main components of sunlight reaching the eye lens are UVA and visible light exerting their photo-damaging effects indirectly by the aid of endogenous photosensitizer molecules such as riboflavin (RF). In this study, lens proteins solutions were incubated with RF and exposed to the sunlight. Then, gel mobility shift analysis and different spectroscopic assessments were applied to examine the structural damaging effects of solar radiation on these proteins. Exposure of lens proteins to direct sunlight, in the presence of RF, leads to marked structural crosslinking, oligomerization and proteolytic instability. These structural damages were also accompanied with reduction in the emission fluorescence of Trp and Tyr and appearance of a new absorption peak between 300 and 400nm which can be related to formation of new chromophores. Also, photo-oxidation of lens crystallins increases their oligomeric size distribution as examined by dynamic light scattering analysis. The above mentioned structural insults, as potential sources of sunlight-induced senile cataract and blindness, were significantly attenuated in the presence of ascorbic acid and glutathione which are two important components of lens antioxidant defense system. Therefore, the powerful antioxidant defense mechanism of eye lens is an important barrier against molecular photo-damaging effects of solar radiations during the life span. Copyright © 2016 Elsevier B.V. All rights reserved.

Structural damage to periodontal tissues at varying rate of anesthetic injection.

PubMed

Sarapultseva, Maria; Sarapultsev, Alexey; Medvedeva, Svetlana; Danilova, Irina

2018-04-01

Incorrect administration of an anesthetic during local anesthesia is one of the most important causes of pain symptoms in patients scheduled for dental procedures. The current study assessed the severity of damage to periodontal tissue following different rates of anesthetic administration. The research was conducted on 50 outbred male rats with a body mass of 180-240 g. The anesthetic used was 1% articaine. The results showed that administration of the anesthetic at a rapid pace caused structural damage to the periodontal tissue. Further, signs of impaired microcirculation were noted at all rates of administration. Biochemical studies demonstrated changes in the level of glucose and enzymes with the rapid introduction of the anesthetic, indicating severe systemic stress response of the body. Injection of local anesthetic at any rate of introduction induces vascular congestion in the microcirculatory bloodstream and exudative reactions. Rapid introduction of an anesthetic causes progression of structural changes in the gingival tissue.

Damage detection methodology under variable load conditions based on strain field pattern recognition using FBGs, nonlinear principal component analysis, and clustering techniques

NASA Astrophysics Data System (ADS)

Sierra-Pérez, Julián; Torres-Arredondo, M.-A.; Alvarez-Montoya, Joham

2018-01-01

Structural health monitoring consists of using sensors integrated within structures together with algorithms to perform load monitoring, damage detection, damage location, damage size and severity, and prognosis. One possibility is to use strain sensors to infer structural integrity by comparing patterns in the strain field between the pristine and damaged conditions. In previous works, the authors have demonstrated that it is possible to detect small defects based on strain field pattern recognition by using robust machine learning techniques. They have focused on methodologies based on principal component analysis (PCA) and on the development of several unfolding and standardization techniques, which allow dealing with multiple load conditions. However, before a real implementation of this approach in engineering structures, changes in the strain field due to conditions different from damage occurrence need to be isolated. Since load conditions may vary in most engineering structures and promote significant changes in the strain field, it is necessary to implement novel techniques for uncoupling such changes from those produced by damage occurrence. A damage detection methodology based on optimal baseline selection (OBS) by means of clustering techniques is presented. The methodology includes the use of hierarchical nonlinear PCA as a nonlinear modeling technique in conjunction with Q and nonlinear-T 2 damage indices. The methodology is experimentally validated using strain measurements obtained by 32 fiber Bragg grating sensors bonded to an aluminum beam under dynamic bending loads and simultaneously submitted to variations in its pitch angle. The results demonstrated the capability of the methodology for clustering data according to 13 different load conditions (pitch angles), performing the OBS and detecting six different damages induced in a cumulative way. The proposed methodology showed a true positive rate of 100% and a false positive rate of 1.28% for a 99% of confidence.

A study of oxidative stress induced by non-thermal plasma-activated water for bacterial damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Qian; Ma, Ruonan; Tian, Ying

2013-05-20

Ar/O{sub 2} (2%) cold plasma microjet was used to create plasma-activated water (PAW). The disinfection efficacy of PAW against Staphylococcus aureus showed that PAW can effectively disinfect bacteria. Optical emission spectra and oxidation reduction potential results demonstrated the inactivation is attributed to oxidative stress induced by reactive oxygen species in PAW. Moreover, the results of X-ray photoelectron spectroscopy, atomic absorption spectrometry, and transmission electron microscopy suggested that the chemical state of cell surface, the integrity of cell membrane, as well as the cell internal components and structure were damaged by the oxidative stress.

Quinacrine pretreatment reduces microwave-induced neuronal damage by stabilizing the cell membrane

PubMed Central

Ding, Xue-feng; Wu, Yan; Qu, Wen-rui; Fan, Ming; Zhao, Yong-qi

2018-01-01

Quinacrine, widely used to treat parasitic diseases, binds to cell membranes. We previously found that quinacrine pretreatment reduced microwave radiation damage in rat hippocampal neurons, but the molecular mechanism remains poorly understood. Considering the thermal effects of microwave radiation and the protective effects of quinacrine on heat damage in cells, we hypothesized that quinacrine would prevent microwave radiation damage to cells in a mechanism associated with cell membrane stability. To test this, we used retinoic acid to induce PC12 cells to differentiate into neuron-like cells. We then pretreated the neurons with quinacrine (20 and 40 mM) and irradiated them with 50 mW/cm2 microwaves for 3 or 6 hours. Flow cytometry, atomic force microscopy and western blot assays revealed that irradiated cells pretreated with quinacrine showed markedly less apoptosis, necrosis, and membrane damage, and greater expression of heat shock protein 70, than cells exposed to microwave irradiation alone. These results suggest that quinacrine stabilizes the neuronal membrane structure by upregulating the expression of heat shock protein 70, thus reducing neuronal injury caused by microwave radiation. PMID:29623929

Effect of saffron (Crocus sativus L.) on sodium valporate induced cytogenetic and testicular alterations in albino rats.

PubMed

Sakr, Saber A; Zowail, Mohamed E; Marzouk, Amera M

2014-09-01

The present study investigated the cytogenetic and testicular damage induced by the antiepileptic drug, sodium valporate (SVP) in albino rats and the effect of saffron aqueous extracts. Treating rats with SVP caused a significant increase in the chromosomal aberrations either structural or numerical and decreased the mitotic index. Besides, animals administered SVP showed DNA damage appeared in the single strand breaks (comet assay). Testis of SVP-treated rats showed many histopathological changes. A significant decrease in seminiferous tubules and their epithelial heights diameters and inhibition of spermatogenesis was recorded. In addition, the number of sperm head abnormalities was increased. Biochemical results revealed an increase in malondialdhyde (MDA) which is lipid peroxidation marker and a significant decrease in the level of serum antioxidant enzyme, catalase (CAT) and reducing antioxidant power (RAP). Animals given SVP and saffron showed an improvement in chromosomal aberrations, mitotic index, DNA damage and testicular alterations caused by SVP. Moreover, MDA decreased and CAT and RAP increased. It is concluded from the present results that the ameliorative effects of saffron extract against SVP-induced cytogenetic and testicular damage in albino rats may be due to the presence of one or more antioxidant components of saffron.

Curcumin protects neuronal cells against status-epilepticus-induced hippocampal damage through induction of autophagy and inhibition of necroptosis.

PubMed

Wang, Jin; Liu, Yuan; Li, Xiao-Hui; Zeng, Xiang-Chang; Li, Jian; Zhou, Jun; Xiao, Bo; Hu, Kai

2017-05-01

Status epilepticus, the most severe form of epilepsy, is characterized by progressive functional and structural damage in the hippocampus, ultimately leading to the development and clinical appearance of spontaneous, recurrent seizures. Although the pathogenesis underlying epileptogenesis processes remains unclear, a substantial body of evidence has shown that status epilepticus acts as an important initial factor in triggering epileptogenesis. Notably, besides classical cell death mechanisms such as apoptosis and necrosis, 2 novel regulators of cell fate known as necroptosis and autophagy, are demonstrated to be involved in neuronal damage in various neurodegenerative and neuropsychiatric disorders. However, whether necroptosis and autophagy play a role in post-status-epilepticus rat hippocampus and other epilepsy mechanisms deserves further research effort. In addition, research is needed to determine whether compounds from traditional Chinese herbs possess antiepileptic effects through the modulation of necroptosis and autophagy. In this study, we found that curcumin, a polyphenolic phytochemical extracted from the Curcuma longa plant, protects neuronal cells against status-epilepticus-induced hippocampal neuronal damage in the lithium-pilocarpine-induced status epilepticus rat model through induction of autophagy and inhibition of necroptosis.

Tailoring rice flour structure by rubbery milling for improved gluten-free baked goods.

PubMed

Brütsch, Linda; Tribolet, Liliane; Isabettini, Stéphane; Soltermann, Patrick; Baumann, Andreas; Windhab, Erich J

2018-05-10

Ever-growing demand for gluten-free products calls for the development of novel food processing techniques to widen the range of existing baked goods. Extensive research has been targeted towards recipe optimization, widely neglecting the tailoring potential of process-induced structuring of gluten-free raw materials. Herein, we address this shortcoming by demonstrating the potential of rubbery milling for the generation of structure and techno-functionality in breads obtained from a variety of rice flour types. Moisture and temperature induced state transitions during milling were exploited to tailor the physicochemical properties of the flour. Moisture addition during conditioning of the different rice varieties and milling in the rubbery state considerably decreased starch damage due to more gentle disintegration. The degree of starch damage dictated the water absorption capacity of the rice flour types. Flour types with reduced starch damage upon milling offered lower dough densities, yielding bread loafs with a higher volume and better appearance. The choice of rice variety enables fine-tuning of the final product quality by influencing the dough viscoelasticity, which defines the final loaf volume. Whole grain rice flour dramatically increased the loaf volume, whilst simultaneously offering nutritional benefits. Combining the proposed functionalised flour types with current and future advances in product recipes paves the way towards optimised gluten-free goods.

Cancer cells recovering from damage exhibit mitochondrial restructuring and increased aerobic glycolysis.

PubMed

Akakura, Shin; Ostrakhovitch, Elena; Sanokawa-Akakura, Reiko; Tabibzadeh, Siamak

2014-06-13

Instead of relying on mitochondrial oxidative phosphorylation, most cancer cells rely heavily on aerobic glycolysis, a phenomenon termed as "the Warburg effect". We considered that this effect is a direct consequence of damage which persists in cancer cells that recover from damage. To this end, we studied glycolysis and rate of cell proliferation in cancer cells that recovered from severe damage. We show that in vitro Damage-Recovered (DR) cells exhibit mitochondrial structural remodeling, display Warburg effect, and show increased in vitro and in vivo proliferation and tolerance to damage. To test whether cancer cells derived from tumor microenvironment can show similar properties, we isolated Damage-Recovered (T(DR)) cells from tumors. We demonstrate that T(DR) cells also show increased aerobic glycolysis and a high proliferation rate. These findings show that Warburg effect and its consequences are induced in cancer cells that survive severe damage. Copyright © 2014 Elsevier Inc. All rights reserved.

Modeling of induced seismicity and ground vibrations associated with geologic CO 2 storage, and assessing their effects on surface structures and human perception

DOE PAGES

Rutqvist, Jonny; Cappa, Frédéric; Rinaldi, Antonio P.; ...

2014-05-01

In this paper, we present model simulations of ground motions caused by CO 2 -injection-induced fault reactivation and analyze the results in terms of the potential for damage to ground surface structures and nuisance to the local human population. It is an integrated analysis from cause to consequence, including the whole chain of processes starting from earthquake inception in the subsurface, wave propagation toward the ground surface, and assessment of the consequences of ground vibration. For a small magnitude (M w =3) event at a hypocenter depth of about 1000m, we first used the simulated ground-motion wave train in anmore » inverse analysis to estimate source parameters (moment magnitude, rupture dimensions and stress drop), achieving good agreement and thereby verifying the modeling of the chain of processes from earthquake inception to ground vibration. We then analyzed the ground vibration results in terms of peak ground acceleration (PGA), peak ground velocity (PGV) and frequency content, with comparison to U.S. Geological Survey's instrumental intensity scales for earthquakes and the U.S. Bureau of Mines' vibration criteria for cosmetic damage to buildings, as well as human-perception vibration limits. Our results confirm the appropriateness of using PGV (rather than PGA) and frequency for the evaluation of potential ground-vibration effects on structures and humans from shallow injection-induced seismic events. For the considered synthetic M w =3 event, our analysis showed that the short duration, high frequency ground motion may not cause any significant damage to surface structures, but would certainly be felt by the local population.« less

Pharmacological Activation of the EDA/EDAR Signaling Pathway Restores Salivary Gland Function following Radiation-Induced Damage

PubMed Central

Hill, Grace; Headon, Denis; Harris, Zoey I.; Huttner, Kenneth; Limesand, Kirsten H.

2014-01-01

Radiotherapy of head and neck cancers often results in collateral damage to adjacent salivary glands associated with clinically significant hyposalivation and xerostomia. Due to the reduced capacity of salivary glands to regenerate, hyposalivation is treated by substitution with artificial saliva, rather than through functional restoration of the glands. During embryogenesis, the ectodysplasin/ectodysplasin receptor (EDA/EDAR) signaling pathway is a critical element in the development and growth of salivary glands. We have assessed the effects of pharmacological activation of this pathway in a mouse model of radiation-induced salivary gland dysfunction. We report that post-irradiation administration of an EDAR-agonist monoclonal antibody (mAbEDAR1) normalizes function of radiation damaged adult salivary glands as determined by stimulated salivary flow rates. In addition, salivary gland structure and homeostasis is restored to pre-irradiation levels. These results suggest that transient activation of pathways involved in salivary gland development could facilitate regeneration and restoration of function following damage. PMID:25409170

The aggregation and inheritance of damaged proteins determines cell fate during mitosis

PubMed Central

Bufalino, Mary Rose; van der Kooy, Derek

2014-01-01

Recent evidence suggests that proliferating cells polarize damaged proteins during mitosis to protect one cell from aging, and that the structural conformation of damaged proteins mediates their toxicity. We report that the growth, resistance to stress, and differentiation characteristics of a cancer cell line (PC12) with an inducible Huntingtin (Htt) fused to enhanced green fluorescent protein (GFP) are dependent on the conformation of Htt. Cell progeny containing inclusion bodies have a longer cell cycle and increased resistance to stress than those with diffuse Htt. Using live imaging, we demonstrate that asymmetric division resulting from a cell containing a single inclusion body produces sister cells with different fates. The cell that receives the inclusion body has decreased proliferation and increased differentiation compared with its sister cell without Htt. This is the first report that reveals a functional consequence of the asymmetric division of damaged proteins in mammalian cells, and we suggest that this is a result of inclusion body-induced proteasome impairment. PMID:24553116

Slope topography-induced spatial variation correlation with observed building damages in Corso during the May 21, 2003, M w 6.8, Boumerdes earthquake (Algeria)

NASA Astrophysics Data System (ADS)

Messaoudi, Akila; Laouami, Nasser; Mezouar, Nourredine

2017-07-01

During the May 21, 2003 M w 6.8 Boumerdes earthquake, in the "Cité des 102 Logements" built on a hilltop, in Corso, heavy damages were observed: near the crest, a four-story RC building collapsed while others experienced severe structural damage and far from the crest, slight damage was observed. In the present paper, we perform a 2D slope topography seismic analysis and investigate its effects on the response at the plateau as well as the correlation with the observed damage distribution. A site-specific seismic scenario is used involving seismological, geological, and geotechnical data. 2D finite element numerical seismic study of the idealized Corso site subjected to vertical SV wave propagation is carried out by the universal code FLUSH. The results highlighted the main factors that explain the causes of block collapse, located 8-26 m far from the crest. These are as follows: (i) a significant spatial variation of ground response along the plateau due to the topographic effect, (ii) this spatial variation presents high loss of coherence, (iii) the seismic ground responses (PGA and response spectra) reach their maxima, and (iv) the fundamental frequency of the collapsed blocks coincides with the frequency content of the topographic component. For distances far from the crest where slight damages were observed, the topographic contribution is found negligible. On the basis of these results, it is important to take into account the topographic effect and the induced spatial variability in the seismic design of structures sited near the crest of slope.

Specific reaction of alpha,beta-unsaturated carbonyl compounds such as 6-shogaol with sulfhydryl groups in tubulin leading to microtubule damage.

PubMed

Ishiguro, Kazuhiro; Ando, Takafumi; Watanabe, Osamu; Goto, Hidemi

2008-10-15

6-Shogaol and 6-gingerol are ginger components with similar chemical structures. However, while 6-shogaol damages microtubules, 6-gingerol does not. We have investigated the molecular mechanism of 6-shogaol-induced microtubule damage and found that the action of 6-shogaol results from the structure of alpha,beta-unsaturated carbonyl compounds. alpha,beta-Unsaturated carbonyl compounds such as 6-shogaol react with sulfhydryl groups of cysteine residues in tubulin, and impair tubulin polymerization. The reaction with sulfhydryl groups depends on the chain length of alpha,beta-unsaturated carbonyl compounds. In addition, alpha,beta-unsaturated carbonyl compounds are more reactive with sulfhydryl groups in tubulin than in 2-mercaptoethanol, dithiothreitol, glutathione and papain, a cysteine protease.

Structure, chaperone-like activity and allergenicity profile of bovine caseins upon peroxynitrite modification: New evidences underlying mastitis pathomechanisms.

PubMed

Sadeghian, Tanaz; Tavaf, Zohreh; Oryan, Ahmad; Shokouhi, Raheleh; Pourpak, Zahra; Moosavi-Movahedi, Ali Akbar; Yousefi, Reza

2018-01-01

Mastitis, an inflammatory reaction frequently develops in response to intra-mammary bacterial infection‌‌, may induce the generation of peroxynitrite (PON)‌ which is a highly potent reactive oxygen and nitrogen species. Caseins as the intrinsically unfolded proteins seem feasible substrates to react with PON. Therefore, in the current study, structural and functional aspects of both β-casein (β-CN) and whole casein fraction (WCF) were evaluated after PON modification, using a variety of techniques. Modification of the bovine caseins with PON results in an important enhancement in the carbonyl, nitrotryptophan, nitrotyrosine and dityrosine content of these proteins‌. The results of fluorescence and far UV-CD assessments suggested significant structural alteration of caseins upon PON-modification. The chaperone-like activity of β-casein was significantly altered after PON modification. The results of scanning electron microscopy suggest that bovine caseins display unique morphological features after treatment with PON. Also, the PON-modified caseins preserved their allergenicity profile and displayed partial resistance against digestion by the pancreatic proteases. Ascorbic acid, an important antioxidant component of milk, was also capable to significantly prevent the PON-induced structural damages in bovine milk caseins. In conclusion, our results suggest that PON may have significant role in the structural and functional alteration of milk caseins. Also, the PON-induced structural damaging effects of caseins might be effectively prevented by a sufficient level of milk antioxidant components particularly by ascorbic acid. Copyright © 2017 Elsevier B.V. All rights reserved.

An Analysis of Nondestructive Evaluation Techniques for Polymer Matrix Composite Sandwich Materials

NASA Technical Reports Server (NTRS)

Cosgriff, Laura M.; Roberts, Gary D.; Binienda, Wieslaw K.; Zheng, Diahua; Averbeck, Timothy; Roth, Donald J.; Jeanneau, Philippe

2006-01-01

Structural sandwich materials composed of triaxially braided polymer matrix composite material face sheets sandwiching a foam core are being utilized for applications including aerospace components and recreational equipment. Since full scale components are being made from these sandwich materials, it is necessary to develop proper inspection practices for their manufacture and in-field use. Specifically, nondestructive evaluation (NDE) techniques need to be investigated for analysis of components made from these materials. Hockey blades made from sandwich materials and a flat sandwich sample were examined with multiple NDE techniques including thermographic, radiographic, and shearographic methods to investigate damage induced in the blades and flat panel components. Hockey blades used during actual play and a flat polymer matrix composite sandwich sample with damage inserted into the foam core were investigated with each technique. NDE images from the samples were presented and discussed. Structural elements within each blade were observed with radiographic imaging. Damaged regions and some structural elements of the hockey blades were identified with thermographic imaging. Structural elements, damaged regions, and other material variations were detected in the hockey blades with shearography. Each technique s advantages and disadvantages were considered in making recommendations for inspection of components made from these types of materials.

Transcription-induced DNA supercoiling: New roles of intranucleosomal DNA loops in DNA repair and transcription

PubMed Central

Gerasimova, N. S.; Pestov, N. A.; Kulaeva, O. I.; Clark, D. J.; Studitsky, V. M.

2016-01-01

ABSTRACT RNA polymerase II (Pol II) transcription through chromatin is accompanied by formation of small intranucleosomal DNA loops. Pol II captured within a small loop drives accumulation of DNA supercoiling, facilitating further transcription. DNA breaks relieve supercoiling and induce Pol II arrest, allowing detection of DNA damage hidden in chromatin structure. PMID:27115204

Molecular adaptations of neuromuscular disease-associated proteins in response to eccentric exercise in human skeletal muscle

PubMed Central

Féasson, L; Stockholm, D; Freyssenet, D; Richard, I; Duguez, S; Beckmann, J S; Denis, C

2002-01-01

The molecular events by which eccentric muscle contractions induce muscle damage and remodelling remain largely unknown. We assessed whether eccentric exercise modulates the expression of proteinases (calpains 1, 2 and 3, proteasome, cathepsin B+L), muscle structural proteins (α-sarcoglycan and desmin), and the expression of the heat shock proteins Hsp27 and αB-crystallin. Vastus lateralis muscle biopsies from twelve healthy male volunteers were obtained before, immediately after, and 1 and 14 days after a 30 min downhill treadmill running exercise. Eccentric exercise induced muscle damage as evidenced by the analysis of muscle pain and weakness, creatine kinase serum activity, myoglobinaemia and ultrastructural analysis of muscle biopsies. The calpain 3 mRNA level was decreased immediately after exercise whereas calpain 2 mRNA level was increased at day 1. Both mRNA levels returned to control values by day 14. By contrast, cathepsin B+L and proteasome enzyme activities were increased at day 14. The α-sarcoglycan protein level was decreased immediately after exercise and at day 1, whereas the desmin level peaked at day 14. αB-crystallin and Hsp27 protein levels were increased at days 1 and 14. Our results suggest that the differential expression of calpain 2 and 3 mRNA levels may be important in the process of exercise-induced muscle damage, whereas expression of α-sarcoglycan, desmin, αB-crystallin and Hsp27 may be essentially involved in the subsequent remodelling of myofibrillar structure. This remodelling response may limit the extent of muscle damage upon a subsequent mechanical stress. PMID:12181300

Substance-P alleviates dextran sulfate sodium-induced intestinal damage by suppressing inflammation through enrichment of M2 macrophages and regulatory T cells.

PubMed

Hong, Hyun Sook; Hwang, Dae Yeon; Park, Ju Hyeong; Kim, Suna; Seo, Eun Jung; Son, Youngsook

2017-02-01

Intestinal inflammation alters immune responses in the mucosa and destroys colon architecture, leading to serious diseases such as inflammatory bowel disease (IBD). Thus, regulation of inflammation is regarded as the ultimate therapy for intestinal disease. Substance-P (SP) is known to mediate proliferation, migration, and cellular senescence in a variety of cells. SP was found to mobilize stem cells from bone marrow to the site of injury and to suppress inflammatory responses by inducing regulatory T cells (Tregs) and M2 macrophages. In this study, we explored the effects of SP in a dextran sodium sulfate (DSS)-induced intestine damage model. The effects of SP were evaluated by analyzing crypt structures, proliferating cells within the colon, cytokine secretion profiles, and immune cells population in the spleen/mesenteric lymph nodes in vivo. DSS treatment provoked an inflammatory response with loss of crypts in the intestines of experimental mice. This response was associated with high levels of inflammatory cytokines such as TNF-α and IL-17, and low levels of Tregs and M2 macrophages, leading to severely damaged tissue structure. However, SP treatment inhibited inflammatory responses by modulating cytokine production as well as the balance of Tregs/Th 17 cells and the M1/M2 transition in lymphoid organs, leading to accelerated tissue repair. Collectively, our data indicate that SP can promote the regeneration of tissue following damage by DSS treatment, possibly by modulating immune response. Our results propose SP as a candidate therapeutic for intestine-related inflammatory diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Protective effect of alpha glucosyl hesperidin (G-hesperidin) on chronic vanadium induced testicular toxicity and sperm nuclear DNA damage in male Sprague Dawley rats.

PubMed

Vijaya Bharathi, B; Jaya Prakash, G; Krishna, K M; Ravi Krishna, C H; Sivanarayana, T; Madan, K; Rama Raju, G A; Annapurna, A

2015-06-01

The study was conducted to evaluate the vanadium-induced testicular toxicity and its effect on sperm parameters, sperm nuclear DNA damage and histological alterations in Sprague Dawley rats and to assess the protective effect of G-hesperidin against this damage. Treatment of rats with vanadium at a dose of 1 mg kg bw(-1) for 90 days resulted in significant reduction in serum testosterone levels, sperm count and motility. Further, a parallel increase in abnormal sperm morphology and adverse histopathological changes in testis was also associated with vanadium administration when compared to normal control. Moreover, sperm chromatin dispersion assay revealed that vanadium induces sperm nuclear DNA fragmentation. A marked increase in testicular malondialdehyde levels and decreased activity of antioxidant enzymes such as superoxide dismutase and catalase indicates vanadium-induced oxidative stress. Co-administration of G-hesperidin at a dose of 25 and 50 mg kg bw(-1) significantly attenuated the sperm parameters and histological changes by restoring the antioxidant levels in rat testis. These results suggested that vanadium exposure caused reduced bioavailability of androgens to the tissue and increased free radical formation, thereby causing structural and functional changes in spermatozoa. G-hesperidin exhibited antioxidant effect by protecting the rat testis against vanadium-induced oxidative damage, further ensures antioxidant potential of bioflavonoids. © 2014 Blackwell Verlag GmbH.

Antioxidant activity and protective effect of Clitoria ternatea flower extract on testicular damage induced by ketoconazole in rats.

PubMed

Iamsaard, Sitthichai; Burawat, Jaturon; Kanla, Pipatpong; Arun, Supatcharee; Sukhorum, Wannisa; Sripanidkulchai, Bungorn; Uabundit, Nongnut; Wattathorn, Jintanaporn; Hipkaeo, Wiphawi; Fongmoon, Duriya; Kondo, Hisatake

2014-06-01

Ketoconazole (KET), an antifungal drug, has adverse effects on the male reproductive system. Pre-treatments with antioxidant plant against testicular damage induced by KET are required. The flowers of Clitoria ternatea (CT) are proven to have hepatoprotective potential. However, the protective effect on KET-induced testicular damage has not been reported. To investigate the protective effect of CT flower extracts with antioxidant activity on male reproductive parameters including sperm concentration, serum testosterone level, histopathology of the testis, and testicular tyrosine phosphorylation levels in rats induced with KET. The antioxidant activity of CT flower extracts was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Male rats were treated with CT flower extracts (10, 50, or 100 mg/kg BW) or distilled water via a gastric tube for 28 d (preventive period: Days 1-21) and induced by KET (100 mg/kg BW) via intraperitoneal injection for 7 d (induction period: Days 22-28). After the experiment, all animals were examined for the weights of the testis, epididymis plus vas deferens and seminal vesicle, serum testosterone levels, sperm concentration, histological structures and diameter of testis, and testicular tyrosine phosphorylation levels by immunoblotting. The CT flower extracts had capabilities for DPPH scavenging and high reducing power. At 100 mg/kg BW, the extract had no toxic effects on the male reproductive system. Significantly, in CT+KET groups, CT flower extracts (50 and 100 mg/kg BW) alleviated the reduction of reproductive organ weight parameters, testosterone levels, and sperm concentration. In addition, CT flower extracts gave protection from testicular damage in KET-induced rats. Moreover, in the CT100+KET group, CT flower extracts significantly enhanced the expression of a testicular 50-kDa tyrosine phosphorylated protein compared with that of other groups. C. ternatea flower extracts possessing antioxidant activity are not harmful to the male reproductive system and can protect against testicular damage in KET-induced rats.

Damage Tolerance Testing of a NASA TransHab Derivative Woven Inflatable Module

NASA Technical Reports Server (NTRS)

Edgecombe, John; delaFuente, Horacio; Valle, Gerard

2009-01-01

Current options for Lunar habitat architecture include inflatable habitats and airlocks. Inflatable structures can have mass and volume advantages over conventional structures. However, inflatable structures carry different inherent risks and are at a lower Technical Readiness Level (TRL) than more conventional metallic structures. One of the risks associated with inflatable structures is in understanding the tolerance to induced damage. The Damage Tolerance Test (DTT) is designed to study the structural integrity of an expandable structure. TransHab (Figure 1) was an experimental inflatable module developed at the NASA/Johnson Space Center in the 1990 s. The TransHab design was originally envisioned for use in Mars Transits but was also studied as a potential habitat for the International Space Station (ISS). The design of the TransHab module was based on a woven design using an Aramid fabric. Testing of this design demonstrated a high level of predictability and repeatability with analytical predictions of stresses and deflections. Based on JSC s experience with the design and analysis of woven inflatable structures, the Damage Tolerance Test article was designed and fabricated using a woven design. The DTT article was inflated to 45 psig, representing 25% of the ultimate burst pressure, and one of the one-inch wide longitudinal structural members was severed by initiating a Linear Shaped Charge (LSC). Strain gage measurements, at the interface between the expandable elements (straps) and the nonexpandable metallic elements for pre-selected longitudinal straps, were taken throughout pressurization of the module and strap separation. Strain gage measurements show no change in longitudinal strap loading at the bulkhead interface after strap separation indicating loads in the restraint layer were re-distributed local to the damaged area due to the effects of friction under high internal pressure loading. The test completed all primary objectives with better than expected results. This paper will discuss space inflatable structures, damage tolerance analysis, test results, and applicability to the Lunar architecture.

Structural correlates of imbibitional injury in Typha pollen

NASA Technical Reports Server (NTRS)

Sack, F. D.; Leopold, A. C.; Hoekstra, F. A.

1988-01-01

The ultrastructure of Typha latifolia pollen was examined as a function of pollen moisture content and incubation temperature, in order to identify possible lesions induced by imbibitional chilling. A syndrome of structural traits was found which characterizes damaged grains. Compared to viable grains, the protoplast of damaged pollen has a higher proportion of its volume occupied by vesicles, and less volume occupied by cytoplasm. Damaged grains also tend to have dilated cisternae of endoplasmic reticulum, larger starch grains and lipid bodies, poorly preserved mitochondria and membranes, and, sometimes, numerous electron-dense globules associated with membranes. The percentage of grains exhibiting this damage syndrome correlates closely with the number of ungerminated grains in most samples, regardless of moisture content or incubation temperature. Injury due to rapid imbibition from the dry state or to imbibitional chilling appear to be similar structurally, regardless of whether the stresses are imposed singly or together. The injury is not confined to one cell component (e.g., mitochondria), but may involve a generalized disruption of membranes. These results suggest that similar stress responses are elicited by imbibition from the dry state and by imbibitional chilling.

Compensating temperature-induced ultrasonic phase and amplitude changes

NASA Astrophysics Data System (ADS)

Gong, Peng; Hay, Thomas R.; Greve, David W.; Junker, Warren R.; Oppenheim, Irving J.

2016-04-01

In ultrasonic structural health monitoring (SHM), environmental and operational conditions, especially temperature, can significantly affect the propagation of ultrasonic waves and thus degrade damage detection. Typically, temperature effects are compensated using optimal baseline selection (OBS) or optimal signal stretch (OSS). The OSS method achieves compensation by adjusting phase shifts caused by temperature, but it does not fully compensate phase shifts and it does not compensate for accompanying signal amplitude changes. In this paper, we develop a new temperature compensation strategy to address both phase shifts and amplitude changes. In this strategy, OSS is first used to compensate some of the phase shifts and to quantify the temperature effects by stretching factors. Based on stretching factors, empirical adjusting factors for a damage indicator are then applied to compensate for the temperature induced remaining phase shifts and amplitude changes. The empirical adjusting factors can be trained from baseline data with temperature variations in the absence of incremental damage. We applied this temperature compensation approach to detect volume loss in a thick wall aluminum tube with multiple damage levels and temperature variations. Our specimen is a thick-walled short tube, with dimensions closely comparable to the outlet region of a frac iron elbow where flow-induced erosion produces the volume loss that governs the service life of that component, and our experimental sequence simulates the erosion process by removing material in small damage steps. Our results show that damage detection is greatly improved when this new temperature compensation strategy, termed modified-OSS, is implemented.

Treatment of hypertension and metabolic syndrome: lowering blood pressure is not enough for organ protection, new approach-arterial destiffening.

PubMed

Zimlichman, Reuven

2014-10-01

Cardiovascular risk factors (CVRFs) have been shown to induce end organ damage. Until now, the main approach to reduce CVRF-induced end organ damage was by normalization of CVRFs; this approach was found effective to reduce damage and cardiovascular (CV) events. However, a residual risk always remained even when CVRFs were optimally balanced. An additional risk factor which has an immense effect on the progression of end organ damage is aging. Aging is accompanied by gradual stiffening of the arteries which finally leads to CV events. Until recently, the process of arterial aging was considered as unmodifiable, but this has changed. Arterial stiffening caused by the aging process is similar to the changes seen as a result of CVRF-induced arterial damage. Actually, the presence of CVRFs causes faster arterial stiffening, and the extent of damage is proportional to the severity of the CVRF, the length of its existence, the patient's genetic factors, etc. Conventional treatments of osteoporosis and of hormonal decline at menopause are potential additional approaches to positively affect progression of arterial stiffening. The new approach to further decrease progression of arteriosclerosis, thus preventing events, is the prevention of age-associated arterial structural changes. This approach should further decrease age-associated arterial stiffening. A totally new promising approach is to study the possibility of affecting collagen, elastin, and other components of connective tissue that participate in the process of arterial stiffening. Reduction of pulse pressure by intervention in arterial stiffening process by novel methods as breaking collagen cross-links or preventing their formation is an example of future directions in treatment. This field is of enormous potential that might be revolutionary in inducing further significant reduction of cardiovascular events.

Fatigue damage prognosis of internal delamination in composite plates under cyclic compression loadings using affine arithmetic as uncertainty propagation tool

NASA Astrophysics Data System (ADS)

Gbaguidi, Audrey J.-M.

Structural health monitoring (SHM) has become indispensable for reducing maintenance costs and increasing the in-service capacity of a structure. The increased use of lightweight composite materials in aircraft structures drastically increased the effects of fatigue induced damage on their critical structural components and thus the necessity to predict the remaining life of those components. Damage prognosis, one of the least investigated fields in SHM, uses the current damage state of the system to forecast its future performance by estimating the expected loading environments. A successful damage prediction model requires the integration of technologies in areas like measurements, materials science, mechanics of materials, and probability theories, but most importantly the quantification of uncertainty in all these areas. In this study, Affine Arithmetic is used as a method for incorporating the uncertainties due to the material properties into the fatigue life prognosis of composite plates subjected to cyclic compressive loadings. When loadings are compressive in nature, the composite plates undergo repeated buckling-unloading of the delaminated layer which induces mixed modes I and II states of stress at the tip of the delamination in the plates. The Kardomateas model-based prediction law is used to predict the growth of the delamination, while the integration of the effects of the uncertainties for modes I and II coefficients in the fatigue life prediction model is handled using Affine arithmetic. The Mode I and Mode II interlaminar fracture toughness and fatigue characterization of the composite plates are first experimentally studied to obtain the material coefficients and fracture toughness, respectively. Next, these obtained coefficients are used in the Kardomateas law to predict the delamination lengths in the composite plates while using Affine Arithmetic to handle their uncertainties. At last, the fatigue characterization of the composite plates during compressive-buckling loadings is experimentally studied, and the delamination lengths obtained are compared with the predicted values to check the performance of Affine Arithmetic as an uncertainty propagation tool.

Escin-induced DNA damage promotes escin-induced apoptosis in human colorectal cancer cells via p62 regulation of the ATM/γH2AX pathway.

PubMed

Wang, Zhong; Chen, Qiang; Li, Bin; Xie, Jia-Ming; Yang, Xiao-Dong; Zhao, Kui; Wu, Yong; Ye, Zhen-Yu; Chen, Zheng-Rong; Qin, Zheng-Hong; Xing, Chun-Gen

2018-05-31

Escin, a triterpene saponin isolated from horse chestnut seed, has been used to treat encephaledema, tissue swelling and chronic venous insufficiency. Recent studies show that escin induces cell cycle arrest, tumor proliferation inhibition and tumor cell apoptosis. But the relationship between escin-induced DNA damage and cell apoptosis in tumor cells remains unclear. In this study, we investigated whether and how escin-induced DNA damage contributed to escin-induced apoptosis in human colorectal cancer cells. Escin (5-80 μg/mL) dose-dependently inhibited the cell viability and colony formation in HCT116 and HCT8 cells. Escin treatment induced DNA damage, leading to p-ATM and γH2AX upregulation. Meanwhile, escin treatment increased the expression of p62, an adaptor protein, which played a crucial role in controlling cell survival and tumorigenesis, and had a protective effect against escin-induced DNA damage: knockdown of p62 apparently enhanced escin-induced DNA damage, whereas overexpression of p62 reduced escin-induced DNA damage. In addition, escin treatment induced concentration- and time-dependent apoptosis. Similarly, knockdown of p62 significantly increased escin-induced apoptosis in vitro and produced en escin-like antitumor effect in vivo. Overexpression of p62 decreased the rate of apoptosis. Further studies revealed that the functions of p62 in escin-induced DNA damage were associated with escin-induced apoptosis, and p62 knockdown combined with the ATM inhibitor KU55933 augmented escin-induced DNA damage and further increased escin-induced apoptosis. In conclusion, our results demonstrate that p62 regulates ATM/γH2AX pathway-mediated escin-induced DNA damage and apoptosis.

Determination of the season-acclimation of photosynthetic apparatus by heat-induced changes in chlorophyll fluorescence

Treesearch

Nicolay Alexandrovich Gaevsky

2002-01-01

Resistance to damage from freezing temperatures is one of the most adaptive properties of "evergreen" (shoot bark, felloderma, needles) woody and bush plant tissues. Species-specific processes accompanying transition of chloroplasts to a frost resistant state (reduction of photochemical activity, the change of chemical structure and structural organization of...

Protective effect of bacoside A on cigarette smoking-induced brain mitochondrial dysfunction in rats.

PubMed

Anbarasi, Kothandapani; Vani, Ganapathy; Devi, Chennam Srinivasulu Shyamala

2005-01-01

Chronic exposure to cigarette smoke affects the structure and function of mitochondria, which may account for the pathogenesis of smoking-related diseases. Bacopa monniera Linn., used in traditional Indian medicine for various neurological disorders, was shown to possess mitrochondrial membrane-stabilizing properties in the rat brain during exposure to morphine. We investigated the protective effect of bacoside A, the active principle of Bacopa monniera, against mitochondrial dysfunction in rat brain induced by cigarette smoke. Male Wistar albino rats were exposed to cigarette smoke and administered bacoside A for a period of 12 weeks. The mitochondrial damage in the brain was assessed by examining the levels of lipid peroxides, cholesterol, phospholipid, cholesterol/phospholipid (C/P) ratio, and the activities of isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase, and cytochrome C oxidase. The oxidative phosphorylation (rate of succinate oxidation, respiratory control ratio and ADP/O ratio, and the levels of ATP) was evaluated for the assessment of mitochondrial functional capacity. We found significantly elevated levels of lipid peroxides, cholesterol, and C/P ratio, and decreased levels of phospholipids and mitochondrial enzymes in the rats exposed to cigarette smoke. Measurement of oxidative phosphorylation revealed a marked depletion in all the variables studied. Administration of bacoside A prevented the structural and functional impairment of mitochondria upon exposure to cigarette smoke. From the results, we suggest that chronic cigarette smoke exposure induces damage to the mitochondria and that bacoside A protects the brain from this damage by maintaining the structural and functional integrity of the mitochondrial membrane.

Low-damage high-throughput grazing-angle sputter deposition on graphene

NASA Astrophysics Data System (ADS)

Chen, C.-T.; Casu, E. A.; Gajek, M.; Raoux, S.

2013-07-01

Despite the prevalence of sputter deposition in the microelectronics industry, it has seen very limited applications for graphene electronics. In this letter, we report systematic investigation of the sputtering induced damages in graphene and identify the energetic sputtering gas neutrals as the primary cause of graphene disorder. We further demonstrate a grazing-incidence sputtering configuration that strongly suppresses fast neutral bombardment and retains graphene structure integrity, creating considerably lower damage than electron-beam evaporation. Such sputtering technique yields fully covered, smooth thin dielectric films, highlighting its potential for contact metals, gate oxides, and tunnel barriers fabrication in graphene device applications.

Analytical cytology applied to detection of induced cytogenetic abnormalities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gray, J.W.; Lucas, J.; Straume, T.

1987-08-06

Radiation-induced biological damage results in formation of a broad spectrum of cytogenetic changes such as translocations, dicentrics, ring chromosomes, and acentric fragments. A battery of analytical cytologic techniques are now emerging that promise to significantly improve the precision and ease with which these radiation induced cytogenetic changes can be quantified. This report summarizes techniques to facilitate analysis of the frequency of occurrence of structural and numerical aberrations in control and irradiated human cells. 14 refs., 2 figs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rutqvist, Jonny; Cappa, Frederic; Rinaldi, Antonio P.

We summarize recent modeling studies of injection-induced fault reactivation, seismicity, and its potential impact on surface structures and nuisance to the local human population. We used coupled multiphase fluid flow and geomechanical numerical modeling, dynamic wave propagation modeling, seismology theories, and empirical vibration criteria from mining and construction industries. We first simulated injection-induced fault reactivation, including dynamic fault slip, seismic source, wave propagation, and ground vibrations. From co-seismic average shear displacement and rupture area, we determined the moment magnitude to about M w = 3 for an injection-induced fault reactivation at a depth of about 1000 m. We then analyzedmore » the ground vibration results in terms of peak ground acceleration (PGA), peak ground velocity (PGV), and frequency content, with comparison to the U.S. Bureau of Mines’ vibration criteria for cosmetic damage to buildings, as well as human-perception vibration limits. For the considered synthetic M w = 3 event, our analysis showed that the short duration, high frequency ground motion may not cause any significant damage to surface structures, and would not cause, in this particular case, upward CO 2 leakage, but would certainly be felt by the local population.« less

Assessment of Stone Columns as a Mitigation Technique of Liquefaction-Induced Effects during Italian Earthquakes (May 2012)

PubMed Central

Forcellini, Davide; Tarantino, Angelo Marcello

2014-01-01

Soil liquefaction has been observed worldwide during recent major earthquakes with induced effects responsible for much of the damage, disruption of function, and considerable replacement expenses for structures. The phenomenon has not been documented in recent time with such damage in Italian context before the recent Emilia-Romagna Earthquake (May 2012). The main lateral spreading and vertical deformations affected the stability of many buildings and impacted social life inducing valuable lessons on liquefaction risk assessment and remediation. This paper aims first of all to reproduce soil response to liquefaction-induced lateral effects and thus to evaluate stone column mitigation technique effectiveness by gradually increasing the extension of remediation, in order to achieve a satisfactory lower level of permanent deformations. The study is based on the use of a FE computational interface able to analyse the earthquake-induced three-dimensional pore pressure generation adopting one of the most credited nonlinear theories in order to assess realistically the displacements connected to lateral spreading. PMID:24592148

Assessment of stone columns as a mitigation technique of liquefaction-induced effects during Italian earthquakes (May 2012).

PubMed

Forcellini, Davide; Tarantino, Angelo Marcello

2014-01-01

Soil liquefaction has been observed worldwide during recent major earthquakes with induced effects responsible for much of the damage, disruption of function, and considerable replacement expenses for structures. The phenomenon has not been documented in recent time with such damage in Italian context before the recent Emilia-Romagna Earthquake (May 2012). The main lateral spreading and vertical deformations affected the stability of many buildings and impacted social life inducing valuable lessons on liquefaction risk assessment and remediation. This paper aims first of all to reproduce soil response to liquefaction-induced lateral effects and thus to evaluate stone column mitigation technique effectiveness by gradually increasing the extension of remediation, in order to achieve a satisfactory lower level of permanent deformations. The study is based on the use of a FE computational interface able to analyse the earthquake-induced three-dimensional pore pressure generation adopting one of the most credited nonlinear theories in order to assess realistically the displacements connected to lateral spreading.

Study of ion-irradiated tungsten in deuterium plasma

NASA Astrophysics Data System (ADS)

Khripunov, B. I.; Gureev, V. M.; Koidan, V. S.; Kornienko, S. N.; Latushkin, S. T.; Petrov, V. B.; Ryazanov, A. I.; Semenov, E. V.; Stolyarova, V. G.; Danelyan, L. S.; Kulikauskas, V. S.; Zatekin, V. V.; Unezhev, V. N.

2013-07-01

Experimental study aimed at investigation of neutron induced damage influence on fusion reactor plasma facing materials is reported. Displacement damage was produced in tungsten by high-energy helium and carbon ions at 3-10 MeV. The reached level of displacement damage ranged from several dpa to 600 dpa. The properties of the irradiated tungsten were studied in steady-state deuterium plasma on the LENTA linear divertor simulator. Plasma exposures were made at 250 eV of ion energy to fluence 1021-1022 ion/сm2. Erosion dynamics of the damaged layer and deuterium retention were observed. Surface microstructure modifications and important damage of the 5 μm layer shown. Deuterium retention in helium-damaged tungsten (ERD) showed its complex behavior (increase or decrease) depending on implanted helium quantity and the structure of the surface layer.

Brain heating induced by near-infrared lasers during multiphoton microscopy

PubMed Central

Ranganathan, Gayathri

2016-01-01

Two-photon imaging and optogenetic stimulation rely on high illumination powers, particularly for state-of-the-art applications that target deeper structures, achieve faster measurements, or probe larger brain areas. However, little information is available on heating and resulting damage induced by high-power illumination in the brain. In the current study we used thermocouple probes and quantum dot nanothermometers to measure temperature changes induced by two-photon microscopy in the neocortex of awake and anaesthetized mice. We characterized heating as a function of wavelength, exposure time, and distance from the center of illumination. Although total power is highest near the surface of the brain, heating was most severe hundreds of micrometers below the focal plane, due to heat dissipation through the cranial window. Continuous illumination of a 1-mm2 area produced a peak temperature increase of ∼1.8°C/100 mW. Continuous illumination with powers above 250 mW induced lasting damage, detected with immunohistochemistry against Iba1, glial fibrillary acidic protein, heat shock proteins, and activated caspase-3. Higher powers were usable in experiments with limited duty ratios, suggesting an approach to mitigate damage in high-power microscopy experiments. PMID:27281749

Appendix : liquefaction damage to bridges and approach embankment : catalog of selected case histories.

DOT National Transportation Integrated Search

2002-11-01

The catalog documents the seismic performance of bridges and ancillary components in the presence of liquefaction-induced ground displacements. Data pertaining to seismological, geotechnical, and structural aspects of numerous case studies are presen...

Engineered biosealant producing inorganic and organic biopolymers

USDA-ARS?s Scientific Manuscript database

Microbiologically induced calcium carbonate precipitation (MICCP) is a naturally occurring biological process that has shown its potential in remediation of a wide range of structural damages including concrete cracks. MICCP involves sequential microbiological and chemical reactions, such as urea h...

RNA-Mediated cis Regulation in Acinetobacter baumannii Modulates Stress-Induced Phenotypic Variation

PubMed Central

Ching, Carly; Gozzi, Kevin; Heinemann, Björn; Chai, Yunrong

2017-01-01

ABSTRACT In the nosocomial opportunistic pathogen Acinetobacter baumannii, RecA-dependent mutagenesis, which causes antibiotic resistance acquisition, is linked to the DNA damage response (DDR). Notably, unlike the Escherichia coli paradigm, recA and DDR gene expression in A. baumannii is bimodal. Namely, there is phenotypic variation upon DNA damage, which may provide a bet-hedging strategy for survival. Thus, understanding recA gene regulation is key to elucidate the yet unknown DDR regulation in A. baumannii. Here, we identify a structured 5′ untranslated region (UTR) in the recA transcript which serves as a cis-regulatory element. We show that a predicted stem-loop structure in this 5′ UTR affects mRNA half-life and underlies bimodal gene expression and thus phenotypic variation in response to ciprofloxacin treatment. We furthermore show that the stem-loop structure of the recA 5′ UTR influences intracellular RecA protein levels and, in vivo, impairing the formation of the stem-loop structure of the recA 5′ UTR lowers cell survival of UV treatment and decreases rifampin resistance acquisition from DNA damage-induced mutagenesis. We hypothesize that the 5′ UTR allows for stable recA transcripts during stress, including antibiotic treatment, enabling cells to maintain suitable RecA levels for survival. This innovative strategy to regulate the DDR in A. baumannii may contribute to its success as a pathogen. IMPORTANCE Acinetobacter baumannii is an opportunistic pathogen quickly gaining antibiotic resistances. Mutagenesis and antibiotic resistance acquisition are linked to the DNA damage response (DDR). However, how the DDR is regulated in A. baumannii remains unknown, since unlike most bacteria, A. baumannii does not follow the regulation of the Escherichia coli paradigm. In this study, we have started to uncover the mechanisms regulating the novel A. baumannii DDR. We have found that a cis-acting 5′ UTR regulates recA transcript stability, RecA protein levels, and DNA damage-induced phenotypic variation. Though 5′ UTRs are known to provide stability to transcripts in bacteria, this is the first example in which it regulates a bimodal DDR response through recA transcript stabilization, potentially enabling cells to have enough RecA for survival and genetic variability. PMID:28320880

Heat-Stress and Light-Stress Induce Different Cellular Pathologies in the Symbiotic Dinoflagellate during Coral Bleaching

PubMed Central

Downs, C. A.; McDougall, Kathleen E.; Woodley, Cheryl M.; Fauth, John E.; Richmond, Robert H.; Kushmaro, Ariel; Gibb, Stuart W.; Loya, Yossi; Ostrander, Gary K.; Kramarsky-Winter, Esti

2013-01-01

Coral bleaching is a significant contributor to the worldwide degradation of coral reefs and is indicative of the termination of symbiosis between the coral host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex), usually by expulsion or xenophagy (symbiophagy) of its dinoflagellates. Herein, we provide evidence that during the earliest stages of environmentally induced bleaching, heat stress and light stress generate distinctly different pathomorphological changes in the chloroplasts, while a combined heat- and light-stress exposure induces both pathomorphologies; suggesting that these stressors act on the dinoflagellate by different mechanisms. Within the first 48 hours of a heat stress (32°C) under low-light conditions, heat stress induced decomposition of thylakoid structures before observation of extensive oxidative damage; thus it is the disorganization of the thylakoids that creates the conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours of a light stress (2007 µmoles m−2 s−1 PAR) at 25°C, condensation or fusion of multiple thylakoid lamellae occurred coincidently with levels of oxidative damage products, implying that photo-oxidative stress causes the structural membrane damage within the chloroplasts. Exposure to combined heat- and light-stresses induced both pathomorphologies, confirming that these stressors acted on the dinoflagellate via different mechanisms. Within 72 hours of exposure to heat and/or light stresses, homeostatic processes (e.g., heat-shock protein and anti-oxidant enzyme response) were evident in the remaining intact dinoflagellates, regardless of the initiating stressor. Understanding the sequence of events during bleaching when triggered by different environmental stressors is important for predicting both severity and consequences of coral bleaching. PMID:24324575

Reservoir Structure and Wastewater-Induced Seismicity at the Val d'Agri Oilfield (Italy) Shown by Three-Dimensional Vp and Vp/Vs Local Earthquake Tomography

NASA Astrophysics Data System (ADS)

Improta, L.; Bagh, S.; De Gori, P.; Valoroso, L.; Pastori, M.; Piccinini, D.; Chiarabba, C.; Anselmi, M.; Buttinelli, M.

2017-11-01

Wastewater injection into a high-rate well in the Val d'Agri oilfield, the largest in onshore Europe, has induced swarm microseismicity since the initiation of disposal in 2006. To investigate the reservoir structure and to track seismicity, we performed a high-spatial resolution local earthquake tomography using 1,281 natural and induced earthquakes recorded by local networks. The properties of the carbonate reservoir (rock fracturing, pore fluid pressure) and inherited faults control the occurrence and spatiotemporal distribution of seismicity. A low-Vp, high-Vp/Vs region under the well represents a fluid saturated fault zone ruptured by induced seismicity. High-Vp, high-Vp/Vs bumps match reservoir culminations indicating saturated liquid-bearing zones, whereas a very low Vp, low Vp/Vs anomaly might represent a strongly fractured and depleted zone of the hydrocarbon reservoir characterized by significant fluid withdrawal. The comprehensive picture of the injection-linked seismicity obtained by integrating reservoir-scale tomography, high-precision earthquake locations, and geophysical and injection data suggests that the driving mechanism is the channeling of pore pressure perturbations through a high permeable fault damage zone within the reservoir. The damage zone surrounds a Pliocene reverse fault optimally oriented in the current extensional stress field. The ruptured damage zone measures 2 km along strike and 3 km along dip and is confined between low permeability ductile formations. Injection pressure is the primary parameter controlling seismicity rate. Our study underlines that local earthquake tomography also using wastewater-induced seismicity can give useful insights into the physical mechanism leading to these earthquakes.

Heat-stress and light-stress induce different cellular pathologies in the symbiotic dinoflagellate during coral bleaching.

PubMed

Downs, C A; McDougall, Kathleen E; Woodley, Cheryl M; Fauth, John E; Richmond, Robert H; Kushmaro, Ariel; Gibb, Stuart W; Loya, Yossi; Ostrander, Gary K; Kramarsky-Winter, Esti

2013-01-01

Coral bleaching is a significant contributor to the worldwide degradation of coral reefs and is indicative of the termination of symbiosis between the coral host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex), usually by expulsion or xenophagy (symbiophagy) of its dinoflagellates. Herein, we provide evidence that during the earliest stages of environmentally induced bleaching, heat stress and light stress generate distinctly different pathomorphological changes in the chloroplasts, while a combined heat- and light-stress exposure induces both pathomorphologies; suggesting that these stressors act on the dinoflagellate by different mechanisms. Within the first 48 hours of a heat stress (32°C) under low-light conditions, heat stress induced decomposition of thylakoid structures before observation of extensive oxidative damage; thus it is the disorganization of the thylakoids that creates the conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours of a light stress (2007 µmoles m(-2) s(-1) PAR) at 25°C, condensation or fusion of multiple thylakoid lamellae occurred coincidently with levels of oxidative damage products, implying that photo-oxidative stress causes the structural membrane damage within the chloroplasts. Exposure to combined heat- and light-stresses induced both pathomorphologies, confirming that these stressors acted on the dinoflagellate via different mechanisms. Within 72 hours of exposure to heat and/or light stresses, homeostatic processes (e.g., heat-shock protein and anti-oxidant enzyme response) were evident in the remaining intact dinoflagellates, regardless of the initiating stressor. Understanding the sequence of events during bleaching when triggered by different environmental stressors is important for predicting both severity and consequences of coral bleaching.

Vibration-based damage detection in wind turbine blades using Phase-based Motion Estimation and motion magnification

NASA Astrophysics Data System (ADS)

Sarrafi, Aral; Mao, Zhu; Niezrecki, Christopher; Poozesh, Peyman

2018-05-01

Vibration-based Structural Health Monitoring (SHM) techniques are among the most common approaches for structural damage identification. The presence of damage in structures may be identified by monitoring the changes in dynamic behavior subject to external loading, and is typically performed by using experimental modal analysis (EMA) or operational modal analysis (OMA). These tools for SHM normally require a limited number of physically attached transducers (e.g. accelerometers) in order to record the response of the structure for further analysis. Signal conditioners, wires, wireless receivers and a data acquisition system (DAQ) are also typical components of traditional sensing systems used in vibration-based SHM. However, instrumentation of lightweight structures with contact sensors such as accelerometers may induce mass-loading effects, and for large-scale structures, the instrumentation is labor intensive and time consuming. Achieving high spatial measurement resolution for a large-scale structure is not always feasible while working with traditional contact sensors, and there is also the potential for a lack of reliability associated with fixed contact sensors in outliving the life-span of the host structure. Among the state-of-the-art non-contact measurements, digital video cameras are able to rapidly collect high-density spatial information from structures remotely. In this paper, the subtle motions from recorded video (i.e. a sequence of images) are extracted by means of Phase-based Motion Estimation (PME) and the extracted information is used to conduct damage identification on a 2.3-m long Skystream® wind turbine blade (WTB). The PME and phased-based motion magnification approach estimates the structural motion from the captured sequence of images for both a baseline and damaged test cases on a wind turbine blade. Operational deflection shapes of the test articles are also quantified and compared for the baseline and damaged states. In addition, having proper lighting while working with high-speed cameras can be an issue, therefore image enhancement and contrast manipulation has also been performed to enhance the raw images. Ultimately, the extracted resonant frequencies and operational deflection shapes are used to detect the presence of damage, demonstrating the feasibility of implementing non-contact video measurements to perform realistic structural damage detection.

Both Complexity and Location of DNA Damage Contribute to Cellular Senescence Induced by Ionizing Radiation

PubMed Central

Zhang, Xurui; Ye, Caiyong; Sun, Fang; Wei, Wenjun; Hu, Burong; Wang, Jufang

2016-01-01

Persistent DNA damage is considered as a main cause of cellular senescence induced by ionizing radiation. However, the molecular bases of the DNA damage and their contribution to cellular senescence are not completely clear. In this study, we found that both heavy ions and X-rays induced senescence in human uveal melanoma 92–1 cells. By measuring senescence associated-β-galactosidase and cell proliferation, we identified that heavy ions were more effective at inducing senescence than X-rays. We observed less efficient repair when DNA damage was induced by heavy ions compared with X-rays and most of the irreparable damage was complex of single strand breaks and double strand breaks, while DNA damage induced by X-rays was mostly repaired in 24 hours and the remained damage was preferentially associated with telomeric DNA. Our results suggest that DNA damage induced by heavy ion is often complex and difficult to repair, thus presents as persistent DNA damage and pushes the cell into senescence. In contrast, persistent DNA damage induced by X-rays is preferentially associated with telomeric DNA and the telomere-favored persistent DNA damage contributes to X-rays induced cellular senescence. These findings provide new insight into the understanding of high relative biological effectiveness of heavy ions relevant to cancer therapy and space radiation research. PMID:27187621

Enhancement of IUdR Radiosensitization by Low-Energy Photons Results from Increased and Persistent DNA Damage.

PubMed

Bayart, Emilie; Pouzoulet, Frédéric; Calmels, Lucie; Dadoun, Jonathan; Allot, Fabien; Plagnard, Johann; Ravanat, Jean-Luc; Bridier, André; Denozière, Marc; Bourhis, Jean; Deutsch, Eric

2017-01-01

Low-energy X-rays induce Auger cascades by photoelectric absorption in iodine present in the DNA of cells labeled with 5-iodo-2'-deoxyuridine (IUdR). This photoactivation therapy results in enhanced cellular sensitivity to radiation which reaches its maximum with 50 keV photons. Synchrotron core facilities are the only way to generate such monochromatic beams. However, these structures are not adapted for the routine treatment of patients. In this study, we generated two beams emitting photon energy means of 42 and 50 keV respectively, from a conventional 225 kV X-ray source. Viability assays performed after pre-exposure to 10 μM of IUdR for 48h suggest that complex lethal damage is generated after low energy photons irradiation compared to 137Cs irradiation (662KeV). To further decipher the molecular mechanisms leading to IUdR-mediated radiosensitization, we analyzed the content of DNA damage-induced foci in two glioblastoma cell lines and showed that the decrease in survival under these conditions was correlated with an increase in the content of DNA damage-induced foci in cell lines. Moreover, the follow-up of repair kinetics of the induced double-strand breaks showed the maximum delay in cells labeled with IUdR and exposed to X-ray irradiation. Thus, there appears to be a direct relationship between the reduction of radiation survival parameters and the production of DNA damage with impaired repair of these breaks. These results further support the clinical potential use of a halogenated pyrimidine analog combined with low-energy X-ray therapy.

TATA Binding Protein Discriminates between Different Lesions on DNA, Resulting in a Transcription Decrease

PubMed Central

Coin, Frédéric; Frit, Philippe; Viollet, Benoit; Salles, Bernard; Egly, Jean-Marc

1998-01-01

DNA damage recognition by basal transcription factors follows different mechanisms. Using transcription-competition, nitrocellulose filter binding, and DNase I footprinting assays, we show that, although the general transcription factor TFIIH is able to target any kind of lesion which can be repaired by the nucleotide excision repair pathway, TATA binding protein (TBP)-TFIID is more selective in damage recognition. Only genotoxic agents which are able to induce kinked DNA structures similar to the one for the TATA box in its TBP complex are recognized. Indeed, DNase I footprinting patterns reveal that TBP protects equally 4 nucleotides upstream and 6 nucleotides downstream from the A-T (at position −29 of the noncoding strand) of the adenovirus major late promoter and from the G-G of a cisplatin-induced 1,2-d(GpG) cross-link. Together, our results may partially explain differences in transcription inhibition rates following DNA damage. PMID:9632775

Genotoxic effect of ethacrynic acid and impact of antioxidants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ward, William M.; Hoffman, Jared D.; Loo, George, E-mail: g_loo@uncg.edu

It is known that ethacrynic acid (EA) decreases the intracellular levels of glutathione. Whether the anticipated oxidative stress affects the structural integrity of DNA is unknown. Therefore, DNA damage was assessed in EA-treated HCT116 cells, and the impact of several antioxidants was also determined. EA caused both concentration-dependent and time-dependent DNA damage that eventually resulted in cell death. Unexpectedly, the DNA damage caused by EA was intensified by either ascorbic acid or trolox. In contrast, EA-induced DNA damage was reduced by N-acetylcysteine and by the iron chelator, deferoxamine. In elucidating the DNA damage, it was determined that EA increased themore » production of reactive oxygen species, which was inhibited by N-acetylcysteine and deferoxamine but not by ascorbic acid and trolox. Also, EA decreased glutathione levels, which were inhibited by N-acetylcysteine. But, ascorbic acid, trolox, and deferoxamine neither inhibited nor enhanced the capacity of EA to decrease glutathione. Interestingly, the glutathione synthesis inhibitor, buthionine sulfoxime, lowered glutathione to a similar degree as EA, but no noticeable DNA damage was found. Nevertheless, buthionine sulfoxime potentiated the glutathione-lowering effect of EA and intensified the DNA damage caused by EA. Additionally, in examining redox-sensitive stress gene expression, it was found that EA increased HO-1, GADD153, and p21mRNA expression, in association with increased nuclear localization of Nrf-2 and p53 proteins. In contrast to ascorbic acid, trolox, and deferoxamine, N-acetylcysteine suppressed the EA-induced upregulation of GADD153, although not of HO-1. Overall, it is concluded that EA has genotoxic properties that can be amplified by certain antioxidants. - Highlights: • Ethacrynic acid (EA) caused cellular DNA damage. • EA-induced DNA damage was potentiated by ascorbic acid or trolox. • EA increased ROS production, not inhibited by ascorbic acid or trolox. • EA decreased glutathione levels, not prevented by ascorbic acid or trolox. • Buthionine sulfoxime intensified the DNA damage caused by EA.« less

Subsurface defects of fused silica optics and laser induced damage at 351 nm.

PubMed

Hongjie, Liu; Jin, Huang; Fengrui, Wang; Xinda, Zhou; Xin, Ye; Xiaoyan, Zhou; Laixi, Sun; Xiaodong, Jiang; Zhan, Sui; Wanguo, Zheng

2013-05-20

Many kinds of subsurface defects are always present together in the subsurface of fused silica optics. It is imperfect that only one kind of defects is isolated to investigate its impact on laser damage. Therefore it is necessary to investigate the impact of subsurface defects on laser induced damage of fused silica optics with a comprehensive vision. In this work, we choose the fused silica samples manufactured by different vendors to characterize subsurface defects and measure laser induced damage. Contamination defects, subsurface damage (SSD), optical-thermal absorption and hardness of fused silica surface are characterized with time-of-flight secondary ion mass spectrometry (TOF-SIMS), fluorescence microscopy, photo-thermal common-path interferometer and fully automatic micro-hardness tester respectively. Laser induced damage threshold and damage density are measured by 351 nm nanosecond pulse laser. The correlations existing between defects and laser induced damage are analyzed. The results show that Cerium element and SSD both have a good correlation with laser-induced damage thresholds and damage density. Research results evaluate process technology of fused silica optics in China at present. Furthermore, the results can provide technique support for improving laser induced damage performance of fused silica.

Local-based damage detection of cyclically loaded bridge piers using wireless sensing units

NASA Astrophysics Data System (ADS)

Hou, Tsung-Chin; Lynch, Jerome P.; Parra-Montesinos, Gustavo

2005-05-01

Concrete bridge piers are a common structural element employed in the design of bridges and elevated roadways. In order to ensure adequate behavior under earthquake-induced displacements, extensive reinforcement detailing in the form of closely spaced ties or spirals is necessary, leading to congestion problems and difficulties during concrete casting. Further, costly repairs are often necessary in bridge piers after a major earthquake which in some cases involve the total or partial shutdown of the bridge. In order to increase the damage tolerance while relaxing the transverse reinforcement requirements of bridge piers, the use of high-performance fiber reinforced cementitious composites (HPFRCC) in earthquake-resistant bridge piers is explored. HPFRCCs are a relatively new class of cementitious material for civil structures with tensile strain-hardening behavior and high damage tolerance. To monitor the behavior of this new class of material in the field, low-cost wireless monitoring technologies will be adopted to provide HPFRCC structural elements the capability to accurately monitor their performance and health. In particular, the computational core of a wireless sensing unit can be harnessed to screen HPFRCC components for damage in real-time. A seismic damage index initially proposed for flexure dominated reinforced concrete elements is modified to serve as an algorithmic tool for the rapid assessment of damage (due to flexure and shear) in HPFRCC bridge piers subjected to large shear reversals. Traditional and non-traditional sensor strategies of an HPFRCC bridge pier are proposed to optimize the correlation between the proposed damage index model and the damage observed in a circular pier test specimen. Damage index models are shown to be a sufficiently accurate rough measure of the degree of local-area damage that can then be wirelessly communicated to bridge officials.

Insights into the mechanism of X-ray-induced disulfide-bond cleavage in lysozyme crystals based on EPR, optical absorption and X-ray diffraction studies.

PubMed

Sutton, Kristin A; Black, Paul J; Mercer, Kermit R; Garman, Elspeth F; Owen, Robin L; Snell, Edward H; Bernhard, William A

2013-12-01

Electron paramagnetic resonance (EPR) and online UV-visible absorption microspectrophotometry with X-ray crystallography have been used in a complementary manner to follow X-ray-induced disulfide-bond cleavage. Online UV-visible spectroscopy showed that upon X-irradiation, disulfide radicalization appeared to saturate at an absorbed dose of approximately 0.5-0.8 MGy, in contrast to the saturating dose of ∼0.2 MGy observed using EPR at much lower dose rates. The observations suggest that a multi-track model involving product formation owing to the interaction of two separate tracks is a valid model for radiation damage in protein crystals. The saturation levels are remarkably consistent given the widely different experimental parameters and the range of total absorbed doses studied. The results indicate that even at the lowest doses used for structural investigations disulfide bonds are already radicalized. Multi-track considerations offer the first step in a comprehensive model of radiation damage that could potentially lead to a combined computational and experimental approach to identifying when damage is likely to be present, to quantitate it and to provide the ability to recover the native unperturbed structure.

Damage detection methodology on beam-like structures based on combined modal Wavelet Transform strategy

NASA Astrophysics Data System (ADS)

Serra, Roger; Lopez, Lautaro

2018-05-01

Different approaches on the detection of damages based on dynamic measurement of structures have appeared in the last decades. They were based, amongst others, on changes in natural frequencies, modal curvatures, strain energy or flexibility. Wavelet analysis has also been used to detect the abnormalities on modal shapes induced by damages. However the majority of previous work was made with non-corrupted by noise signals. Moreover, the damage influence for each mode shape was studied separately. This paper proposes a new methodology based on combined modal wavelet transform strategy to cope with noisy signals, while at the same time, able to extract the relevant information from each mode shape. The proposed methodology will be then compared with the most frequently used and wide-studied methods from the bibliography. To evaluate the performance of each method, their capacity to detect and localize damage will be analyzed in different cases. The comparison will be done by simulating the oscillations of a cantilever steel beam with and without defect as a numerical case. The proposed methodology proved to outperform classical methods in terms of noisy signals.

Impact of the track structure of heavy charged particles on cytogenetic damage in human blood lymphocytes

NASA Astrophysics Data System (ADS)

Lee, Ryonfa; Nasonova, Elena; Sommer, Sylwetster; Hartel, Carola; Durante, Marco; Ritter, Sylvia

In space, astronauts are unavoidably exposed to charged particles from protons to irons. For a better estimate of the health risks of astronauts, further knowledge on the biological effects of charged particles, in particular the induction of cytogenetic damage is required. One im-portant factor that determines the biological response is the track structure of particles, i.e. their microscopic dose deposition in cells. The aim of the present study was to assess the influence of track structure of heavy ions on the yield and the quality of cytogenetic damage in human peripheral blood lymphocytes representing normal tissue. Cells were irradiated with 9.5 MeV/u C-ions or 990 MeV/u Fe-ions which have a comparable LET (175 keV/µm and 155 keV/µm, respectively) but a different track radius (2.3 and 6200 µm, respectively). When aberrations were analyzed in first cycle metaphases collected at different post-irradiation times (48-84 h) following fluorescence plus Giemsa staining, an increase in the aberration yield with sampling time was observed for both radiation qualities reflecting a damage dependent cell cycle progression delay to mitosis. The pronounced differences in the aberration frequency per cell are attributable to the stochastic distribution of particle traversals per cell nucleus (radius: 2.8 µm). Following C-ion exposure we found a high fraction of non-aberrant cells in samples collected at 48 h which represent cells not directly hit by a particle and slightly damaged cells that successfully repaired the induced lesions. In addition, at higher C-ion fluences the aberra-tion yield saturated, suggesting that a fraction of lymphocytes receiving multiple particle hits is not able to reach mitosis. On the other hand, at 48 h after Fe-ion exposure the proportion of non-aberrant cells is lower than after C-ion irradiation clearly reflecting the track structure of high energy particles (i.e. more homogeneous dose deposition compared to low energy C-ions). Furthermore, the aberration yield increased linearly with Fe-ion fluence. When aberrations were analyzed in first cycle G2 -PCC cells to account for the prolonged G2 arrest of damaged cells, the same trend was detected. However, the increase in the aberration yield with time and the saturation effect were less pronounced compared to metaphase samples. Altogether, these data show that the aberration analysis with multiple samplings is necessary for a reliable estimate of cytogenetic damage induced by charged particles. In particular, when damage is measured at one early time-point the effectiveness of low energy particles will be considerably underestimated. When the aberration spectrum induced by low energy C-ions and high en-ergy Fe-ions was compared, we did not find a difference. Preliminary data obtained with the high resolution mFISH-technique confirm this observation. (Work supported by BMBF, Bonn, under contract 02S8497)

Microwave detection of fatigue cracks in specially prepared steel specimens.

DOT National Transportation Integrated Search

1998-01-01

In the aging highway systems the problems of fatigue-induced damage and cracking in metal structures are very severe. Many such systems are operating even beyond their design lifetime, which requires more than the originally prescribed inspection cyc...

Electronmicroscopic observations on the effects of orally administered aspirin and aspirin-bicarbonate mixtures on the development of gastric mucosal damage in the rat.

PubMed Central

Rainsford, K D

1975-01-01

The effects of administering a single dose of (200 mg to 50 mg/kg body weight) aspirin or an equimolar mixture of aspirin (200 mg/kg body wt) with sodium bicarbonate on the fine structure of the rat gastric mucosa were investigated in order to establish the role of particles of the drug in the development of gastric damage. The sequence of cellular events involved in the development of a lesion and the influence of short-term starvation were also investigated. Aspirin-bicarbonate solutions produced much less damage in starved rats than aspirin suspensions given at low (50 mg/kg body weight) or high therapeutic doses (200 mg/kg body weight). Also, when non-starved rats were given 200 mg/kg aspirin, only slight damage was observed. The presence of particles of the drug in intimate contact with the mucosa is thus important in the development of gastric damage. A sequence of events with time involving direct physical exfoliation of mucosal cells and selective structural damage to parietal cells followed by structural damage indicative of a disturbance to oxidative and biosynthetic functions in cells near the developing erosion was observed. The implications of these results on the development of aspirin-induced lesions are discussed. Images Fig 3a Fig 3b Fig 1a Fig 1b Fig 1c Fig 2a Fig 2b Fig 4 Fig 5 PMID:1158188

Camptosorus sibiricus rupr aqueous extract prevents lung tumorigenesis via dual effects against ROS and DNA damage.

PubMed

He, Shugui; Ou, Rilan; Wang, Wensheng; Ji, Liyan; Gao, Hui; Zhu, Yuanfeng; Liu, Xiaomin; Zheng, Hongming; Liu, Zhongqiu; Wu, Peng; Lu, Linlin

2018-06-28

Camptosorus sibiricus Rupr (CSR) is a widely used herbal medicine with antivasculitis, antitrauma, and antitumor effects. However, the effect of CSR aqueous extract on B[a]P-initiated tumorigenesis and the underlying mechanism remain unclear. Moreover, the compounds in CSR aqueous extract need to be identified and structurally characterized. We aim to investigate the chemopreventive effect of CSR and the underlying molecular mechanism. A B[a]P-stimulated normal cell model (BEAS.2B) and lung adenocarcinoma animal model were established on A/J mice. In B[a]P-treated BEAS.2B cells, the protective effects of CSR aqueous extract on B[a]P-induced DNA damage and ROS production were evaluated through flow cytometry, Western blot, real-time quantitative PCR, single-cell gel electrophoresis, and immunofluorescence. Moreover, a model of B[a]P-initiated lung adenocarcinoma was established on A/J mice to determine the chemopreventive effect of CSR in vivo. The underlying mechanism was analyzed via immunohistochemistry and microscopy. Furthermore, the new compounds in CSR aqueous extract were isolated and structurally characterized using IR, HR-ESI-MS, and 1D and 2D NMR spectroscopy. CSR effectively suppressed ROS production by re-activating Nrf2-mediated reductases HO-1 and NQO-1. Simultaneously, CSR attenuated the DNA damage of BEAS.2B cells in the presence of B[a]P. Moreover, CSR at 1.5 and 3 g/kg significantly suppressed tumorigenesis with tumor inhibition ratios of 36.65% and 65.80%, respectively. The tumor volume, tumor size, and multiplicity of B[a]P-induced lung adenocarcinoma were effectively decreased by CSR in vivo. After extracting and identifying the compounds in CSR aqueous extract, three new triterpene saponins were isolated and characterized structurally. CSR aqueous extract prevents lung tumorigenesis by exerting dual effects against ROS and DNA damage, suggesting that CSR is a novel and effective agent for B[a]P-induced carcinogenesis. Moreover, by isolating and structurally characterizing three new triterpene saponins, our study further standardized the quality of CSR aqueous extract, which could widen CSR clinical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanistic study of plasma damage to porous low-k: Process development and dielectric recovery

NASA Astrophysics Data System (ADS)

Shi, Hualiang

Low-k dielectrics with porosity are being introduced to reduce the RC delay of Cu/low-k interconnect. However, during the O2 plasma ashing process, the porous low-k dielectrics tend to degrade due to methyl depletion, moisture uptake, and densification, increasing the dielectric constant and leakage current. This dissertation presents a study of the mechanisms of plasma damage and dielectric recovery. The kinetics of plasma interaction with low-k dielectrics was investigated both experimentally and theoretically. By using a gap structure, the roles of ion, photon, and radical in producing damage on low-k dielectrics were differentiated. Oxidative plasma induced damage was proportional to the oxygen radical density, enhanced by VUV photon, and increased with substrate temperature. Ion bombardment induced surface densification, blocking radical diffusion. Two analytical models were derived to quantify the plasma damage. Based on the radical diffusion, reaction, and recombination inside porous low-k dielectrics, a plasma altered layer model was derived to interpret the chemical effect in the low ion energy region. It predicted that oxidative plasma induced damage can be reduced by decreasing pore radius, substrate temperature, and oxygen radical density and increasing carbon concentration and surface recombination rate inside low-k dielectrics. The model validity was verified by experiments and Monte-Carlo simulations. This model was also extended to the patterned low-k structure. Based on the ion collision cascade process, a sputtering yield model was introduced to interpret the physical effect in the high ion energy region. The model validity was verified by checking the ion angular and energy dependences of sputtering yield using O2/He/Ar plasma, low-k dielectrics with different k values, and a Faraday cage. Low-k dielectrics and plasma process were optimized to reduce plasma damage, including increasing carbon concentration in low-k dielectrics, switching plasma generator from ICP to RIE, increasing hard mask thickness, replacing O2 by CO2 plasma, increasing CO addition in CO/O 2 plasma, and increasing N2 addition in CO2/N 2 plasma. By combining analytical techniques with the Kramers-Kronig dispersion relation and quantum chemistry calculation, the origin of dielectric loss was ascribed to the physisorbed water molecules. Post-ash CH4 plasma treatment, vapor silylation process, and UV radiation were developed to repair plasma damage.

Optimization of a low noise detection circuit for probing the structure of damage cascades with IBIC

DOE PAGES

Auden, Elizabeth C.; Doyle, Barney L.; Bielejec, Edward; ...

2015-06-18

Optimal detector / pre-amplifier combinations have been identified for the use of light ion IBIC (ion beam induced charge) to probe the physical structure of electrically active defects in damage cascades caused by heavy ion implantation. The ideal detector must have a sufficiently thin dead layer that incident ions will produce the majority of damage cascades in the depletion region of the detector rather than the dead layer. Detector and circuit noise must be low enough to detect the implantation of a single heavy ion as well as the decrease in the light ion IBIC signal caused by Shockley-Read-Hall recombinationmore » when the beam scans regions of the detector damaged by the heavy ion. The IBIC signals from three detectors irradiated with 750 keV He⁺ ions are measured with commercial and bespoke charge sensitive pre-amplifiers to identify the combination with the lowest noise.« less

A quantitative and non-contact technique to characterise microstructural variations of skin tissues during photo-damaging process based on Mueller matrix polarimetry.

PubMed

Dong, Yang; He, Honghui; Sheng, Wei; Wu, Jian; Ma, Hui

2017-10-31

Skin tissue consists of collagen and elastic fibres, which are highly susceptible to damage when exposed to ultraviolet radiation (UVR), leading to skin aging and cancer. However, a lack of non-invasive detection methods makes determining the degree of UVR damage to skin in real time difficult. As one of the fundamental features of light, polarization can be used to develop imaging techniques capable of providing structural information about tissues. In particular, Mueller matrix polarimetry is suitable for detecting changes in collagen and elastic fibres. Here, we demonstrate a novel, quantitative, non-contact and in situ technique based on Mueller matrix polarimetry for monitoring the microstructural changes of skin tissues during UVR-induced photo-damaging. We measured the Mueller matrices of nude mouse skin samples, then analysed the transformed parameters to characterise microstructural changes during the skin photo-damaging and self-repairing processes. Comparisons between samples with and without the application of a sunscreen showed that the Mueller matrix-derived parameters are potential indicators for fibrous microstructure in skin tissues. Histological examination and Monte Carlo simulations confirmed the relationship between the Mueller matrix parameters and changes to fibrous structures. This technique paves the way for non-contact evaluation of skin structure in cosmetics and dermatological health.

Characterization of photoactivated singlet oxygen damage in single-molecule optical trap experiments.

PubMed

Landry, Markita P; McCall, Patrick M; Qi, Zhi; Chemla, Yann R

2009-10-21

Optical traps or "tweezers" use high-power, near-infrared laser beams to manipulate and apply forces to biological systems, ranging from individual molecules to cells. Although previous studies have established that optical tweezers induce photodamage in live cells, the effects of trap irradiation have yet to be examined in vitro, at the single-molecule level. In this study, we investigate trap-induced damage in a simple system consisting of DNA molecules tethered between optically trapped polystyrene microspheres. We show that exposure to the trapping light affects the lifetime of the tethers, the efficiency with which they can be formed, and their structure. Moreover, we establish that these irreversible effects are caused by oxidative damage from singlet oxygen. This reactive state of molecular oxygen is generated locally by the optical traps in the presence of a sensitizer, which we identify as the trapped polystyrene microspheres. Trap-induced oxidative damage can be reduced greatly by working under anaerobic conditions, using additives that quench singlet oxygen, or trapping microspheres lacking the sensitizers necessary for singlet state photoexcitation. Our findings are relevant to a broad range of trap-based single-molecule experiments-the most common biological application of optical tweezers-and may guide the development of more robust experimental protocols.

Characterization of Photoactivated Singlet Oxygen Damage in Single-Molecule Optical Trap Experiments

PubMed Central

Landry, Markita P.; McCall, Patrick M.; Qi, Zhi; Chemla, Yann R.

2009-01-01

Abstract Optical traps or “tweezers” use high-power, near-infrared laser beams to manipulate and apply forces to biological systems, ranging from individual molecules to cells. Although previous studies have established that optical tweezers induce photodamage in live cells, the effects of trap irradiation have yet to be examined in vitro, at the single-molecule level. In this study, we investigate trap-induced damage in a simple system consisting of DNA molecules tethered between optically trapped polystyrene microspheres. We show that exposure to the trapping light affects the lifetime of the tethers, the efficiency with which they can be formed, and their structure. Moreover, we establish that these irreversible effects are caused by oxidative damage from singlet oxygen. This reactive state of molecular oxygen is generated locally by the optical traps in the presence of a sensitizer, which we identify as the trapped polystyrene microspheres. Trap-induced oxidative damage can be reduced greatly by working under anaerobic conditions, using additives that quench singlet oxygen, or trapping microspheres lacking the sensitizers necessary for singlet state photoexcitation. Our findings are relevant to a broad range of trap-based single-molecule experiments—the most common biological application of optical tweezers—and may guide the development of more robust experimental protocols. PMID:19843445

Effect of saffron (Crocus sativus L.) on sodium valporate induced cytogenetic and testicular alterations in albino rats

PubMed Central

Zowail, Mohamed E.; Marzouk, Amera M.

2014-01-01

The present study investigated the cytogenetic and testicular damage induced by the antiepileptic drug, sodium valporate (SVP) in albino rats and the effect of saffron aqueous extracts. Treating rats with SVP caused a significant increase in the chromosomal aberrations either structural or numerical and decreased the mitotic index. Besides, animals administered SVP showed DNA damage appeared in the single strand breaks (comet assay). Testis of SVP-treated rats showed many histopathological changes. A significant decrease in seminiferous tubules and their epithelial heights diameters and inhibition of spermatogenesis was recorded. In addition, the number of sperm head abnormalities was increased. Biochemical results revealed an increase in malondialdhyde (MDA) which is lipid peroxidation marker and a significant decrease in the level of serum antioxidant enzyme, catalase (CAT) and reducing antioxidant power (RAP). Animals given SVP and saffron showed an improvement in chromosomal aberrations, mitotic index, DNA damage and testicular alterations caused by SVP. Moreover, MDA decreased and CAT and RAP increased. It is concluded from the present results that the ameliorative effects of saffron extract against SVP-induced cytogenetic and testicular damage in albino rats may be due to the presence of one or more antioxidant components of saffron. PMID:25276476

A behavioural analysis of spatial localization following electrolytic, kainate- or colchicine-induced damage to the hippocampal formation in the rat.

PubMed

Sutherland, R J; Whishaw, I Q; Kolb, B

1983-02-01

This experiment examines the notion that in the rat the hippocampal formation is an essential structure in the neurological representation of spatial abilities. Spatial localization by rats with different types of hippocampal damage, including bilateral electrolytic lesions, unilateral and bilateral kainic acid-induced CA3-CA4 lesions, and unilateral and bilateral colchicine-induced dentate gyrus lesions, was compared with vehicle-injected and normal control groups in the Morris water task. The task required the rats to escape from cold water by finding a submerged and hidden platform located at a fixed place within the room. The start point was varied randomly from trial to trial and there were no local cues available to indicate the position of the hidden platform. After training, the platform was moved. Escape latencies and the initial swimming headings revealed that all lesion groups, except the unilateral CA3-damaged group, were impaired at finding the platform: the dentate-damaged rats exhibited the greatest deficit. When the platform was moved the control rats swam mainly in the part of the pool that had previously contained the platform and, on finding it in the new location, they showed a marked dishabituation of rearing. None of the bilateral lesion groups showed these effects.

Atrophy of spared grey matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke

PubMed Central

Gauthier, Lynne V.; Taub, Edward; Mark, Victor W.; Barghi, Ameen; Uswatte, Gitendra

2011-01-01

Background and Purpose Although the motor deficit following stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to Constraint-Induced Movement therapy (CI therapy) in chronic stroke patients may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Methods Voxel-based morphometry (VBM) analysis was performed on MRI scans from 80 chronic stroke patients to investigate whether variations in grey matter density were correlated with extent of residual motor impairment or with CI therapy-induced motor recovery. Results Decreased grey matter density in non-infarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced grey matter density in multiple remote brain regions predicted a lesser extent of motor improvement from CI therapy. Conclusions Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke. PMID:22096036

The role of defects in laser-induced modifications of silica coatings and fused silica using picosecond pulses at 1053 nm: I Damage morphology

DOE PAGES

Laurence, T. A.; Ly, S.; Shen, N.; ...

2017-06-22

Laser-induced damage with ps pulse widths straddles the transition from intrinsic, multi-photon ionization and avalanche ionization-based ablation with fs pulses to defect-dominated, thermal-based damage with ns pulses. We investigated the morphology of damage for fused silica and silica coatings between 1 ps and 60 ps at 1053 nm. Using calibrated laser-induced damage experiments, in situ imaging, and high-resolution optical microscopy, atomic force microscopy, and scanning electron microscopy, we show that defects play an important role in laser-induced damage down to 1 ps. Three types of damage are observed: ablation craters, ultra-high density pits, and smooth, circular depressions with central pits.more » For 10 ps and longer, the smooth, circular depressions limit the damage performance of fused silica and silica coatings. The observed high-density pits and material removal down to 3 ps indicate that variations in surface properties limit the laser-induced damage onset to a greater extent than expected below 60 ps. Below 3 ps, damage craters are smoother although there is still evidence as seen by AFM of inhomogeneous laser-induced damage response very near the damage onset. These results show that modeling the damage onset only as a function of pulse width does not capture the convoluted processes leading to laser induced damage with ps pulses. It is necessary to account for the effects of defects on the processes leading to laser-induced damage. In conclusion, the effects of isolated defects or inhomogeneities are most pronounced above 3 ps but are still discernible and possibly important down to the shortest pulse width investigated here.« less

The role of defects in laser-induced modifications of silica coatings and fused silica using picosecond pulses at 1053 nm: I Damage morphology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laurence, T. A.; Ly, S.; Shen, N.

Laser-induced damage with ps pulse widths straddles the transition from intrinsic, multi-photon ionization and avalanche ionization-based ablation with fs pulses to defect-dominated, thermal-based damage with ns pulses. We investigated the morphology of damage for fused silica and silica coatings between 1 ps and 60 ps at 1053 nm. Using calibrated laser-induced damage experiments, in situ imaging, and high-resolution optical microscopy, atomic force microscopy, and scanning electron microscopy, we show that defects play an important role in laser-induced damage down to 1 ps. Three types of damage are observed: ablation craters, ultra-high density pits, and smooth, circular depressions with central pits.more » For 10 ps and longer, the smooth, circular depressions limit the damage performance of fused silica and silica coatings. The observed high-density pits and material removal down to 3 ps indicate that variations in surface properties limit the laser-induced damage onset to a greater extent than expected below 60 ps. Below 3 ps, damage craters are smoother although there is still evidence as seen by AFM of inhomogeneous laser-induced damage response very near the damage onset. These results show that modeling the damage onset only as a function of pulse width does not capture the convoluted processes leading to laser induced damage with ps pulses. It is necessary to account for the effects of defects on the processes leading to laser-induced damage. In conclusion, the effects of isolated defects or inhomogeneities are most pronounced above 3 ps but are still discernible and possibly important down to the shortest pulse width investigated here.« less

Effect of diet induced obesity or type 1 or type 2 diabetes on corneal nerves and peripheral neuropathy in C57Bl/6J mice

PubMed Central

Yorek, Matthew S.; Obrosov, Alexander; Shevalye, Hanna; Holmes, Amey; Harper, Matthew M.; Kardon, Randy H.; Yorek, Mark A.

2015-01-01

We determined the impact diet induced obesity (DIO) and types 1 and 2 diabetes has on peripheral neuropathy with emphasis on corneal nerve structural changes in C57Bl/6J mice. Endpoints examined included nerve conduction velocity, response to thermal and mechanical stimuli and innervation of the skin and cornea. DIO mice and to a greater extent type 2 diabetic mice were insulin resistant. DIO and both types 1 and 2 diabetic mice developed motor and sensory nerve conduction deficits. In the cornea of DIO and type 2 diabetic mice there was a decrease in sub-epithelial corneal nerves, innervation of the corneal epithelium and corneal sensitivity. Type 1 diabetic mice did not present with any significant changes in corneal nerve structure until after 20 weeks of hyperglycemia. DIO and type 2 diabetic mice developed corneal structural damage more rapidly than type 1 diabetic mice even though hemoglobin A1C values were significantly higher in type 1 diabetic mice. This suggests that DIO with or without hyperglycemia contributes to development and progression of peripheral neuropathy and nerve structural damage in the cornea. PMID:25858759

Effectiveness of human spermatozoa biomarkers as indicators of structural damage during cryopreservation.

PubMed

Gómez-Torres, María José; Medrano, Llanos; Romero, Alejandro; Fernández-Colom, Pedro José; Aizpurúa, Jon

2017-10-01

Human spermatozoa cryopreservation techniques are used to maintain and protect male fertility in cases such as infertility and malignancy treatments. However, during cryopreservation, the spermatozoa's metabolic rate is reduced and they undergo dramatic functional and structural changes owing to exposure to cryoprotectants and freezing-thawing procedures. While the effects of cryopreservation on cells are documented, to date the induced cryodamage on structural and/or functional sperm biomarkers is not well established at multivariate scale. To address this question, we performed basic sperm analysis, sperm DNA fragmentation assessment, spontaneous acrosome reaction measurement, and cytoskeleton evaluation after thawing samples from subjects with normal and low-quality semen. A cryodamage rate was used to determine the effects of the freeze-thaw process on spermatozoa. In addition, a Principal Component Analysis (PCA) was used for data reduction and to evaluate sperm-specific patterns during the cryopreservation process. We found that the vitality, progressive motility and sperm count from low-quality samples after cryopreservation show higher damage rates (≥40%) than in normal sperm samples. However, cytoskeleton, DNA, tail and mid-piece and acrosome display the highest cryodamage rates (∼50-99%) and are equally susceptible to cryopreservation-induced damage in both low- and normal-quality semen samples. Overall, the evaluation of these parameters provides meaningful information about different aspects of sperm functionality after cryopreservation. Copyright © 2017 Elsevier Inc. All rights reserved.

Regulation of photochemical energy transfer accompanied by structural changes in thylakoid membranes of heat-stressed wheat.

PubMed

Marutani, Yoko; Yamauchi, Yasuo; Miyoshi, Akihito; Inoue, Kanako; Ikeda, Ken-ichi; Mizutani, Masaharu; Sugimoto, Yukihiro

2014-12-11

Photosystems of higher plants alleviate heat-induced damage in the presence of light under moderate stressed conditions; however, in the absence of light (i.e., in the dark), the same plants are damaged more easily. (Yamauchi and Kimura, 2011) We demonstrate that regulating photochemical energy transfer in heat-treated wheat at 40 °C with light contributed to heat tolerance of the photosystem. Chlorophyll fluorescence analysis using heat-stressed wheat seedlings in light showed increased non-photochemical quenching (NPQ) of chlorophyll fluorescence, which was due to thermal dissipation that was increased by state 1 to state 2 transition. Transmission electron microscopy revealed structural changes in thylakoid membranes, including unstacking of grana regions under heat stress in light. It was accompanied by the phosphorylation of thylakoid proteins such as D1 and D2 proteins and the light harvesting complex II proteins Lhcb1 and Lhcb2. These results suggest that heat stress at 40 °C in light induces state 1 to state 2 transition for the preferential excitation of photosystem I (PSI) by phosphorylating thylakoid proteins more strongly. Structural changes of thylakoid membrane also assist the remodeling of photosystems and regulation of energy distribution by transition toward state 2 probably contributes to plastoquione oxidation; thus, light-driven electrons flowing through PSI play a protective role against PSII damage under heat stress.

Cadmium-induced oxidative stress and histological damage in the myocardium. Effects of a soy-based diet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferramola, Mariana L.; Pérez Díaz, Matías F.F.; Honoré, Stella M.

Cd exposure has been associated to an augmented risk for cardiovascular disease. We investigated the effects of 15 and 100 ppm of Cd on redox status as well as histological changes in the rat heart and the putative protective effect of a soy-based diet. Male Wistar rats were separated into 6 groups and treated during 60 days as follows: groups (1), (2) and (3) were fed a casein-based diet; groups (4), (5) and (6), a soy-based diet; (1) and (4) were given tap water; (2) and (5) tap water containing 15 ppm of Cd{sup 2+}; and (3) and (6) tapmore » water containing 100 ppm of Cd{sup 2+}. Serum lipid peroxides increased and PON-1 activity decreased in group (3). Lipoperoxidation also increased in the heart of all intoxicated groups; however protein oxidation only augmented in (3) and reduced glutathione levels diminished in (2) and (3). Catalase activity increased in groups (3) and (6) while superoxide dismutase activity increased only in (6). Glutathione peroxidase activity decreased in groups (3) and (6). Nrf2 expression was higher in groups (3) and (6), and MTI expression augmented in (3). Histological examination of the heart tissue showed the development of hypertrophic and fusion of cardiomyocytes along with foci of myocardial fiber necrosis. The transmission electron microscopy analysis showed profound ultra-structural damages. No protection against tissue degeneration was observed in animals fed the soy-based diet. Our findings indicate that even though the intake of a soy-based diet is capable of ameliorating Cd induced oxidative stress, it failed in preventing cardiac damage. -- Highlights: ► Cd intoxication produces extracellular and ultrastructural damage in the myocardium. ► The intake of a soy-based diet ameliorated Cd-induced oxidative stress. ► Cd-induced myocardial damage wasn't prevented by the intake of a soy-based diet. ► Cd-induced myocardial degeneration may not be caused by oxidative stress generation. ► Histology evaluation is needed to establish the extent of Cd-induced cardiac damage.« less

A new surface fractal dimension for displacement mode shape-based damage identification of plate-type structures

NASA Astrophysics Data System (ADS)

Shi, Binkai; Qiao, Pizhong

2018-03-01

Vibration-based nondestructive testing is an area of growing interest and worthy of exploring new and innovative approaches. The displacement mode shape is often chosen to identify damage due to its local detailed characteristic and less sensitivity to surrounding noise. Requirement for baseline mode shape in most vibration-based damage identification limits application of such a strategy. In this study, a new surface fractal dimension called edge perimeter dimension (EPD) is formulated, from which an EPD-based window dimension locus (EPD-WDL) algorithm for irregularity or damage identification of plate-type structures is established. An analytical notch-type damage model of simply-supported plates is proposed to evaluate notch effect on plate vibration performance; while a sub-domain of notch cases with less effect is selected to investigate robustness of the proposed damage identification algorithm. Then, fundamental aspects of EPD-WDL algorithm in term of notch localization, notch quantification, and noise immunity are assessed. A mathematical solution called isomorphism is implemented to remove false peaks caused by inflexions of mode shapes when applying the EPD-WDL algorithm to higher mode shapes. The effectiveness and practicability of the EPD-WDL algorithm are demonstrated by an experimental procedure on damage identification of an artificially-induced notched aluminum cantilever plate using a measurement system of piezoelectric lead-zirconate (PZT) actuator and scanning laser Doppler vibrometer (SLDV). As demonstrated in both the analytical and experimental evaluations, the new surface fractal dimension technique developed is capable of effectively identifying damage in plate-type structures.

Atrial fibrillation in the elderly: the potential contribution of reactive oxygen species

PubMed Central

Schillinger, Kurt J.; Patel, Vickas V.

2012-01-01

Atrial fibrillation (AF) is the most commonly encountered cardiac arrhythmia, and is a significant source of healthcare expenditures throughout the world. It is an arrhythmia with a very clearly defined predisposition for individuals of advanced age, and this fact has led to intense study of the mechanistic links between aging and AF. By promoting oxidative damage to multiple subcellular and cellular structures, reactive oxygen species (ROS) have been shown to induce the intra- and extra-cellular changes necessary to promote the pathogenesis of AF. In addition, the generation and accumulation of ROS have been intimately linked to the cellular processes which underlie aging. This review begins with an overview of AF pathophysiology, and introduces the critical structures which, when damaged, predispose an otherwise healthy atrium to AF. The available evidence that ROS can lead to damage of these critical structures is then reviewed. Finally, the evidence linking the process of aging to the pathogenesis of AF is discussed. PMID:23341843

Characterization of subsets of human spermatozoa at different stages of maturation: implications in the diagnosis and treatment of male infertility.

PubMed

Ollero, M; Gil-Guzman, E; Lopez, M C; Sharma, R K; Agarwal, A; Larson, K; Evenson, D; Thomas, A J; Alvarez, J G

2001-09-01

Reactive oxygen species (ROS)-induced damage of membrane phospholipids and DNA in human spermatozoa has been implicated in the pathogenesis of male infertility. In this study, variations in ROS production, DNA structure (as measured by the sperm chromatin structure assay) and lipid composition, were studied in human spermatozoa at different stages of maturation. Sperm subsets were isolated by discontinuous density gradient centrifugation of semen samples obtained from healthy donors and from infertility patients. DNA damage and ROS production were highest in immature spermatozoa with cytoplasmic retention and abnormal head morphology, and lowest in mature spermatozoa. Docosahexaenoic acid and sterol content were highest in immature germ cells and immature spermatozoa, and lowest in mature spermatozoa. The relative proportion of ROS-producing immature spermatozoa in the sample was directly correlated with DNA damage in mature spermatozoa, and inversely correlated with the recovery of motile spermatozoa. There was no correlation between DNA damage and sperm morphology in mature spermatozoa. The high levels of ROS production and DNA damage observed in immature spermatozoa may be indicative of derangements in the regulation of spermiogenesis. DNA damage in mature spermatozoa may be the result of oxidative damage by ROS-producing immature spermatozoa during sperm migration from the seminiferous tubules to the epididymis.

Characterization of plasma processing induced charging damage to MOS devices

NASA Astrophysics Data System (ADS)

Ma, Shawming

1997-12-01

Plasma processing has become an integral part of the fabrication of integrated circuits and takes at least 30% of whole process steps since it offers advantages in terms of directionality, low temperature and process convenience. However, wafer charging during plasma processes is a significant concern for both thin oxide damage and profile distortion. In this work, the factors affecting this damage will be explained by plasma issues, device structure and oxide quality. The SPORT (Stanford Plasma On-wafer Real Time) charging probe was developed to investigate the charging mechanism of different plasma processes including poly-Si etching, resist ashing and PECVD. The basic idea of this probe is that it simulates a real device structure in the plasma environment and allows measurement of plasma induced charging voltages and currents directly in real time. This measurement is fully compatible with other charging voltage measurement but it is the only one to do in real-time. Effect of magnetic field induced plasma nonuniformity on spatial dependent charging is well understood by this measurement. In addition, the plasma parameters including ion current density and electron temperature can also be extracted from the probe's plasma I-V characteristics using a dc Langmuir probe like theory. It will be shown that the MOS device tunneling current from charging, the dependence on antenna ratio and the etch uniformity can all be predicted by using this measurement. Moreover, the real-time measurement reveals transient and electrode edge effect during processing. Furthermore, high aspect ratio pattern induced electron shading effects can also be characterized by the probe. On the oxide quality issue, wafer temperature during plasma processing has been experimentally shown to be critical to charging damage. Finally, different MOS capacitor testing methods including breakdown voltage, charge-to-breakdown, gate leakage current and voltage-time at constant current bias were compared to find the optimum method for charging device reliability testing.

Behavior-associated Neuronal Activation After Kainic Acid-induced Hippocampal Neurotoxicity is Modulated in Time.

PubMed

Aguilar-Arredondo, Andrea; López-Hernández, Fernanda; García-Velázquez, Lizbeth; Arias, Clorinda; Zepeda, Angélica

2017-02-01

Kainic acid-induced (KA) hippocampal damage leads to neuronal death and further synaptic plasticity. Formation of aberrant as well as of functional connections after such procedure has been documented. However, the impact of such structural plasticity on cell activation along time after damage and in face of a behavioral demand has not been explored. We evaluated if the mRNA and protein levels of plasticity-related protein synaptophysin (Syp and SYP, respectively) and activity-regulated cytoskeleton-associated protein mRNA and protein levels (Arc and Arc, respectively) in the dentate gyrus were differentially modulated in time in response to a spatial-exploratory task after KA-induced hippocampal damage. In addition, we analyzed Arc+/NeuN+ immunopositive cells in the different experimental conditions. We infused KA intrahippocampally to young-adult rats and 10 or 30 days post-lesion (dpl) animals performed a hippocampus-activating spatial-exploratory task. Our results show that Syp mRNA levels significantly increase at 10dpl and return to control levels after 30dpl, whereas SYP protein levels are diminished at 10dpl, but significantly increase at 30dpl, as compared to 10dpl. Arc mRNA and protein levels are both increased at 30dpl as compared to sham. Also the number of NeuN+/Arc+ cells significantly increases at 30dpl in the group with a spatial-exploratory demand. These results provide information on the long-term modifications associated to structural plasticity and neuronal activation in the dentate gyrus after excitotoxic damage and in face of a spatial-exploratory behavior. Anat Rec, 300:425-432, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Methamphetamine induces autophagy and apoptosis in a mesencephalic dopaminergic neuronal culture model: role of cathepsin-D in methamphetamine-induced apoptotic cell death.

PubMed

Kanthasamy, Arthi; Anantharam, V; Ali, Syed F; Kanthasamy, A G

2006-08-01

Autophagy is a phylogenetically conserved process that plays a critical role in the degradation of oxidatively damaged proteins and organelle turnover. The role of oxidative stress and apoptosis in methamphetamine (METH)-induced neurotoxicity is well known; however, the potential contribution of autophagy to METH-induced oxidative damage in dopaminergic neuronal systems remains unclear. The goals of the present article were twofold: (a) to develop an in vitro dopaminergic cell culture model to study cellular and molecular mechanisms underlying METH-induced autophagy and apoptosis, and (b) to determine whether lysosomal protease cathepsin-D activation, resulting from the loss of lysosomal membrane integrity, contributes to METH-induced apoptosis. To accomplish these goals, we characterized morphological and biochemical changes in an immortalized mesencephalic dopaminergic neuronal cell line (N27 cells) following treatment with METH. Exposure of METH (2 mM) to N27 cells resulted in the appearance of cytoplasmic vacuolar structures reminiscent of autophagic vacuoles within 3 h. In order to ascertain the identity of the vacuolar structures that are formed following METH exposure, immunohistochemical staining for markers of autophagy were performed. LAMP 2, a classical marker of autophagolysosomes, revealed an extensive punctuate pattern of distribution on the vacuolar membrane surface, with exclusive localization in the cytoplasm. Additionally, using DNA fragmentation analysis we showed a dose-dependent increase in fragmented DNA in METH treated N27 cells. Since METH-induced autophagy preceded DNA fragmentation, we tested whether dysfunction of the autophagolysosomal system contributes to nuclear damage. Immunofluorescence studies with cathepsin-d demonstrated a granular pattern of staining in untreated cells, whereas an increased cathepsin- D immunoreactivity with a globular pattern of staining was observed in METH-treated cells. Nevertheless, blockade of cathepsin-D activation by pepstatin-A, cathepsin-D inhibitor, failed to alter METH-induced DNA fragmentation. Collectively, these results demonstrate that N27 dopaminergic neuronal cell model may serve as an excellent in vitro model to study the mechanisms of METH-induced autophagy and apoptosis. Furthermore, it is less likely that cathepsin-D may serve as a trigger for the induction of apoptosis subsequent to exposure of N27 dopaminergic neuronal cells to METH.

Experimental Analysis of Dynamic Effects of FRP Reinforced Masonry Vaults.

PubMed

Corradi, Marco; Borri, Antonio; Castori, Giulio; Coventry, Kathryn

2015-11-27

An increasing interest in the preservation of historic structures has produced a need for new methods for reinforcing curved masonry structures, such as arches and vaults. These structures are generally very ancient, have geometries and materials which are poorly defined and have been exposed to long-term historical movements and actions. Consequently, they are often in need of repair or reinforcement. This article presents the results of an experimental study carried out in the laboratory and during on-site testing to investigate the behaviour of brick masonry vaults under dynamic loading strengthened with FRPs (Fiber Reinforced Polymers). For the laboratory tests, the brick vaults were built with solid sanded clay bricks and weak mortar and were tested under dynamic loading. The experimental tests were designed to facilitate analysis of the dynamic behaviour of undamaged, damaged and reinforced vaulted structures. On-site tests were carried out on an earthquake-damaged thin brick vault of an 18th century aristocratic residence in the city of L'Aquila, Italy. The provision of FRP reinforcement is shown to re-establish elastic behavior previously compromised by time induced damage in the vaults.

Experimental Analysis of Dynamic Effects of FRP Reinforced Masonry Vaults

PubMed Central

Corradi, Marco; Borri, Antonio; Castori, Giulio; Coventry, Kathryn

2015-01-01

An increasing interest in the preservation of historic structures has produced a need for new methods for reinforcing curved masonry structures, such as arches and vaults. These structures are generally very ancient, have geometries and materials which are poorly defined and have been exposed to long-term historical movements and actions. Consequently, they are often in need of repair or reinforcement. This article presents the results of an experimental study carried out in the laboratory and during on-site testing to investigate the behaviour of brick masonry vaults under dynamic loading strengthened with FRPs (Fiber Reinforced Polymers). For the laboratory tests, the brick vaults were built with solid sanded clay bricks and weak mortar and were tested under dynamic loading. The experimental tests were designed to facilitate analysis of the dynamic behaviour of undamaged, damaged and reinforced vaulted structures. On-site tests were carried out on an earthquake-damaged thin brick vault of an 18th century aristocratic residence in the city of L’Aquila, Italy. The provision of FRP reinforcement is shown to re-establish elastic behavior previously compromised by time induced damage in the vaults. PMID:28793697

Radiofrequency ablation of the pancreas with and without intraluminal duodenal cooling in a porcine model.

PubMed

Fegrachi, Samira; Molenaar, I Quintus; Klaessens, John H; Besselink, Marc G; Offerhaus, Johan A; van Hillegersberg, Richard

2013-10-01

To determine the short-term outcome of radiofrequency ablation (RFA) of pancreatic tissue near the duodenum and portomesenteric vessels (PMV) in a porcine model with and without intraluminal duodenal cooling. RFA has been proposed as a new treatment strategy in patients with unresectable locally advanced pancreatic cancer. RFA may cause thermal damage to the duodenum and vascular structures, but these risks and potential protective measures have never been systematically addressed. Intraluminal duodenal cooling during RFA could prevent thermal damage to the duodenum. RFA was performed in 11 pigs during laparotomy with a bipolar probe of 30 mm active length at a power of 30 W until a total energy of 15 kJ was administered. The RFA probe was inserted in the pancreas at 5 or 15 mm from the duodenum, PMV, and in the pancreatic tail. RFA near the duodenum was performed with and without intraluminal duodenal cooling using 100 mL/min saline of 5°C. Histopathologic assessment was performed. The maximum RFA-induced temperature was 92°C. RFA with one single probe induced adequate ablation lesions with a diameter of 20 mm over a length of 30 mm. Without duodenal cooling, RFA induced duodenal thermal damage, whereas with duodenal cooling, no damage was observed. RFA at 15 mm from the PMV resulted in minimal superficial focal vascular damage, without thrombosis or hemorrhage. RFA provides adequate ablation zones in the pancreas of the porcine. Thermal damage to the duodenum can be prevented by intraluminal duodenal cooling without loss of ablation effectivity. Copyright © 2013 Elsevier Inc. All rights reserved.

Damage detection in rotating machinery by means of entropy-based parameters

NASA Astrophysics Data System (ADS)

Tocarciuc, Alexandru; Bereteu, Liviu; ǎgǎnescu, Gheorghe Eugen, Dr

2014-11-01

The paper is proposing two new entropy-based parameters, namely Renyi Entropy Index (REI) and Sharma-Mittal Entropy Index (SMEI), for detecting the presence of failures (or damages) in rotating machinery, namely: belt structural damage, belt wheels misalignment, failure of the fixing bolt of the machine to its baseplate and eccentricities (i.e.: due to detaching a small piece of material or bad mounting of the rotating components of the machine). The algorithms to obtain the proposed entropy-based parameters are described and test data is used in order to assess their sensitivity. A vibration test bench is used for measuring the levels of vibration while artificially inducing damage. The deviation of the two entropy-based parameters is compared in two states of the vibration test bench: not damaged and damaged. At the end of the study, their sensitivity is compared to Shannon Entropic Index.

Understanding a reference-free impedance method using collocated piezoelectric transducers

NASA Astrophysics Data System (ADS)

Kim, Eun Jin; Kim, Min Koo; Sohn, Hoon; Park, Hyun Woo

2010-03-01

A new concept of a reference-free impedance method, which does not require direct comparison with a baseline impedance signal, is proposed for damage detection in a plate-like structure. A single pair of piezoelectric (PZT) wafers collocated on both surfaces of a plate are utilized for extracting electro-mechanical signatures (EMS) associated with mode conversion due to damage. A numerical simulation is conducted to investigate the EMS of collocated PZT wafers in the frequency domain at the presence of damage through spectral element analysis. Then, the EMS due to mode conversion induced by damage are extracted using the signal decomposition technique based on the polarization characteristics of the collocated PZT wafers. The effects of the size and the location of damage on the decomposed EMS are investigated as well. Finally, the applicability of the decomposed EMS to the reference-free damage diagnosis is discussed.

Transcriptional upregulation of p19INK4d upon diverse genotoxic stress is critical for optimal DNA damage response.

PubMed

Ceruti, Julieta M; Scassa, María E; Marazita, Mariela C; Carcagno, Abel C; Sirkin, Pablo F; Cánepa, Eduardo T

2009-06-01

p19INK4d promotes survival of several cell lines after UV irradiation due to enhanced DNA repair, independently of CDK4 inhibition. To further understand the action of p19INK4d in the cellular response to DNA damage, we aimed to elucidate whether this novel regulator plays a role only in mechanisms triggered by UV or participates in diverse mechanisms initiated by different genotoxics. We found that p19INK4d is induced in cells injured with cisplatin or beta-amyloid peptide as robustly as with UV. The mentioned genotoxics transcriptionally activate p19INK4d expression as demonstrated by run-on assay without influencing its mRNA stability and with partial requirement of protein synthesis. It is not currently known whether DNA damage-inducible genes are turned on by the DNA damage itself or by the consequences of that damage. Experiments carried out in cells transfected with distinct damaged DNA structures revealed that the damage itself is not responsible for the observed up-regulation. It is also not known whether the increased expression of DNA-damage-inducible genes is related to immediate protective responses such as DNA repair or to more delayed responses such as cell cycle arrest or apoptosis. We found that ectopic expression of p19INK4d improves DNA repair ability and protects neuroblastoma cells from apoptosis caused by cisplatin or beta-amyloid peptide. Using clonal cell lines where p19INK4d levels can be modified at will, we show that p19INK4d expression correlates with increased survival and clonogenicity. The results presented here, prompted us to suggest that p19INK4d displays an important role in an early stage of cellular DNA damage response.

Shock-Induced Turbulence and Acoustic Loading on Aerospace Structures

DTIC Science & Technology

2015-08-22

aerospace structures. Pulsating flows featuring unsteadiness attributed to SWTBLI can lead to fatigue and structural damages1. Advancing our understanding...transformed system of coordinates in order to minimize scaling effects that appear in stencils consisting of elements of different sizes, as well as to...preceding the separation bubble as the 5th-order MUSCL. An integral length scale of 2Δx in the streamwise direction was chosen for the digital filter

Genotoxicity and Cytotoxicity Evaluation of the Neolignan Analogue 2-(4-Nitrophenoxy)-1Phenylethanone and its Protective Effect Against DNA Damage

PubMed Central

Hanusch, Alex Lucas; de Oliveira, Guilherme Roberto; de Sabóia-Morais, Simone Maria Teixeira; Machado, Rafael Cosme; dos Anjos, Murilo Machado; Chen Chen, Lee

2015-01-01

Neolignans are secondary metabolites found in various groups of Angiosperms. They belong to a class of natural compounds with great diversity of chemical structures and pharmacological activities. These compounds are formed by linking two phenylpropanoid units. Several compounds that have ability to prevent genetic damage have been isolated from plants, and can be used to prevent or delay the development of tumor cells. Genetic toxicology evaluation is widely used in risk assessment of new drugs in preclinical screening tests. In this study, we evaluated the genotoxicity and cytotoxicity of the neolignan analogue 2-(4-nitrophenoxy)-1-phenylethanone (4NF) and its protective effect against DNA damage using the mouse bone marrow micronucleus test and the comet assay in mouse peripheral blood. Our results showed that this neolignan analogue had no genotoxic activity and was able to reduce induced damage both in mouse bone marrow and peripheral blood. Although the neolignan analogue 4NF was cytotoxic, it reduced cyclophosphamide-induced cytotoxicity. In conclusion, it showed no genotoxic action, but exhibited cytotoxic, antigenotoxic, and anticytotoxic activities. PMID:26554835

The KnowRISK project - Know your city, Reduce seISmic risK through non-structural elements

NASA Astrophysics Data System (ADS)

Sousa Oliveria, Carlos; Amaral Ferreira, Mónica; Lopez, Mário; Sousa Silva, Delta; Musacchio, Gemma; Rupakhety, Rajesh; Falsaperla, Susanna; Meroni, Fabrizio; Langer, Horst

2016-04-01

Historically, there is a tendency to focus on seismic structural performance of buildings, neglecting the potential for damage of non-structural elements. In particular, non-structural elements of buildings are their architectural parts (i.e. partitions, ceilings, cladding), electrical and mechanical components (i.e., distribution panels, piping, plumbing), and contents (e.g., furniture, bookcases, computers and desktop equipment). Damage of these elements often contributes significantly to earthquake impacts. In the 1999 Izmit Earthquake, Turkey, 50% of the injuries and 3% of human losses were caused by non-structural failures. In the 2010-2011 Christchurch Earthquakes (New Zealand), 40% of building damage was induced by non-structural malfunctions. Around 70%-85% of construction cost goes into these elements, and their damage can strongly influence the ability of communities to cope with and recover from earthquakes. The project Know your city, Reduce seISmic risK through non-structural elements (KnowRISK) aims at facilitating local communities' access to expert knowledge on non-structural seismic protection solutions. The project will study seismic scenarios critical for non-structural damage, produce a portfolio of non-structural protection measures and investigate the level of awareness in specific communities. We will implement risk communication strategies that will take into account the social and cultural background and a participatory approach to raise awareness in local communities. The paradox between the progress of scientific knowledge and the ongoing increase of losses from natural disasters worldwide is a well-identified gap in the UN Hyogo Framework for Action 2005-2015, in which one of the main priorities is the investment on "knowledge use, innovation and education to build a culture of safety and resilience". The KnowRISK is well aligned with these priorities and will contribute to participatory action aimed at: i) transferring expert knowledge on seismic risk and non-structural protective solutions into practical knowledge and ii) communication tools designed to engage communities in disaster risk reduction

Smartphone imagery to analyze animal-induced erosion in riverbanks

NASA Astrophysics Data System (ADS)

Sofia, Giulia; Masin, Roberta; Tarolli, Paolo

2016-04-01

Among the most invasive species, the Coypu (Myocastor coypus) best exemplifies the widespread damage caused by alien species to ecosystems, with effects on crops, riverine systems, and hydraulic structures. The extent of the latter impact is still rarely quantified, despite the increasing economic and social importance. In northern Italy, Coypu damages to the drainage network have multiple aspects. One main issue is related to the weakening of earthen structures: burrows significantly reduce the integrity of the banks, and potentially contribute to the bank failure. A second concern is related to the agricultural activities nearby the channels. When burrows are present, soil may collapse when subjected to the weight of heavy objects on the surface (such as vehicles and farm machinery). A third issue is connected on the impact of burrowing activities on riparian buffer zones. Coypu burrows create specific flowing paths for the water, delivering water and sediment from the fields directly to the drainage system, thus possibly reducing the efficiency of these zones, and improving the risk of surface water contamination. The purpose of this research is to provide a new perspective, from a geoscience point of view, on Coypu damages to riverbanks, showing the effectiveness of a low-cost approach to model surface burrowing damages and to quantify the related erosion. The work is based on the Structure-from-Motion (SfM) photogrammetric method. To quantify the damages, high-resolution 3D models of the riverbanks were reconstructed from imagery acquired with a smartphone (Prosdocimi et al. 2015). From these models, it was possible to determine the volume of the animal-induced erosion. Proven its effectiveness, the proposed method could allow the creation of a database of damages. Researchers could test the flexibility of the approach to determine the distribution of erosion along the whole drainage system as an index of damage region wide, and to determine the severity of damage as classified according to Coypu relative abundance ratings when available. This would offer the basis to compare biomes, identifying those suffering the most. The quantification of eroded sediment would also provide a scientific basis to improve the analysis of the impacts of burrowing animals on riparian habitats and native species as well as on the efficiency of buffer zones. Prosdocimi, M., Sofia, G., Dalla Fontana, G., Tarolli, P. (2015). Bank erosion in agricultural drainage networks: effectiveness of Structure-from-Motion photogrammetry for post-event analysis, Earth Surface Processes and Landforms, 40: 1891-1906. doi: 10.1002/esp.3767.

Radiation damage in a micron-sized protein crystal studied via reciprocal space mapping and Bragg coherent diffractive imaging.

PubMed

Coughlan, H D; Darmanin, C; Phillips, N W; Hofmann, F; Clark, J N; Harder, R J; Vine, D J; Abbey, B

2015-07-01

For laboratory and synchrotron based X-ray sources, radiation damage has posed a significant barrier to obtaining high-resolution structural data from biological macromolecules. The problem is particularly acute for micron-sized crystals where the weaker signal often necessitates the use of higher intensity beams to obtain the relevant data. Here, we employ a combination of techniques, including Bragg coherent diffractive imaging to characterise the radiation induced damage in a micron-sized protein crystal over time. The approach we adopt here could help screen for potential protein crystal candidates for measurement at X-ray free election laser sources.

Radiation damage in a micron-sized protein crystal studied via reciprocal space mapping and Bragg coherent diffractive imaging

PubMed Central

Coughlan, H. D.; Darmanin, C.; Phillips, N. W.; Hofmann, F.; Clark, J. N.; Harder, R. J.; Vine, D. J.; Abbey, B.

2015-01-01

For laboratory and synchrotron based X-ray sources, radiation damage has posed a significant barrier to obtaining high-resolution structural data from biological macromolecules. The problem is particularly acute for micron-sized crystals where the weaker signal often necessitates the use of higher intensity beams to obtain the relevant data. Here, we employ a combination of techniques, including Bragg coherent diffractive imaging to characterise the radiation induced damage in a micron-sized protein crystal over time. The approach we adopt here could help screen for potential protein crystal candidates for measurement at X-ray free election laser sources. PMID:26798804

Radiation damage in a micron-sized protein crystal studied via reciprocal space mapping and Bragg coherent diffractive imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coughlan, H. D.; Darmanin, C.; Phillips, N. W.

For laboratory and synchrotron based X-ray sources, radiation damage has posed a significant barrier to obtaining high-resolution structural data from biological macromolecules. The problem is particularly acute for micron-sized crystals where the weaker signal often necessitates the use of higher intensity beams to obtain the relevant data. Here, we employ a combination of techniques, including Bragg coherent diffractive imaging to characterise the radiation induced damage in a micron-sized protein crystal over time. The approach we adopt here could help screen for potential protein crystal candidates for measurement at X-ray free election laser sources.

Radiation damage in a micron-sized protein crystal studied via reciprocal space mapping and Bragg coherent diffractive imaging

DOE PAGES

Coughlan, H. D.; Darmanin, C.; Phillips, N. W.; ...

2015-04-29

For laboratory and synchrotron based X-ray sources, radiation damage has posed a significant barrier to obtaining high-resolution structural data from biological macromolecules. The problem is particularly acute for micron-sized crystals where the weaker signal often necessitates the use of higher intensity beams to obtain the relevant data. Here, we employ a combination of techniques, including Bragg coherent diffractive imaging to characterise the radiation induced damage in a micron-sized protein crystal over time. The approach we adopt here could help screen for potential protein crystal candidates for measurement at X-ray free election laser sources.

Hyperoxia Causes Mitochondrial Fragmentation in Pulmonary Endothelial Cells by Increasing Expression of Pro-Fission Proteins.

PubMed

Ma, Cui; Beyer, Andreas M; Durand, Matthew; Clough, Anne V; Zhu, Daling; Norwood Toro, Laura; Terashvili, Maia; Ebben, Johnathan D; Hill, R Blake; Audi, Said H; Medhora, Meetha; Jacobs, Elizabeth R

2018-03-01

We explored mechanisms that alter mitochondrial structure and function in pulmonary endothelial cells (PEC) function after hyperoxia. Mitochondrial structures of PECs exposed to hyperoxia or normoxia were visualized and mitochondrial fragmentation quantified. Expression of pro-fission or fusion proteins or autophagy-related proteins were assessed by Western blot. Mitochondrial oxidative state was determined using mito-roGFP. Tetramethylrhodamine methyl ester estimated mitochondrial polarization in treatment groups. The role of mitochondrially derived reactive oxygen species in mt-fragmentation was investigated with mito-TEMPOL and mitochondrial DNA (mtDNA) damage studied by using ENDO III (mt-tat-endonuclease III), a protein that repairs mDNA damage. Drp-1 (dynamin-related protein 1) was overexpressed or silenced to test the role of this protein in cell survival or transwell resistance. Hyperoxia increased fragmentation of PEC mitochondria in a time-dependent manner through 48 hours of exposure. Hyperoxic PECs exhibited increased phosphorylation of Drp-1 (serine 616), decreases in Mfn1 (mitofusion protein 1), but increases in OPA-1 (optic atrophy 1). Pro-autophagy proteins p62 (LC3 adapter-binding protein SQSTM1/p62), PINK-1 (PTEN-induced putative kinase 1), and LC3B (microtubule-associated protein 1A/1B-light chain 3) were increased. Returning cells to normoxia for 24 hours reversed the increased mt-fragmentation and changes in expression of pro-fission proteins. Hyperoxia-induced changes in mitochondrial structure or cell survival were mitigated by antioxidants mito-TEMPOL, Drp-1 silencing, or inhibition or protection by the mitochondrial endonuclease ENDO III. Hyperoxia induced oxidation and mitochondrial depolarization and impaired transwell resistance. Decrease in resistance was mitigated by mito-TEMPOL or ENDO III and reproduced by overexpression of Drp-1. Because hyperoxia evoked mt-fragmentation, cell survival and transwell resistance are prevented by ENDO III and mito-TEMPOL and Drp-1 silencing, and these data link hyperoxia-induced mt-DNA damage, Drp-1 expression, mt-fragmentation, and PEC dysfunction. © 2018 American Heart Association, Inc.

The use of the SRIM code for calculation of radiation damage induced by neutrons

NASA Astrophysics Data System (ADS)

Mohammadi, A.; Hamidi, S.; Asadabad, Mohsen Asadi

2017-12-01

Materials subjected to neutron irradiation will being evolve to structural changes by the displacement cascades initiated by nuclear reaction. This study discusses a methodology to compute primary knock-on atoms or PKAs information that lead to radiation damage. A program AMTRACK has been developed for assessing of the PKAs information. This software determines the specifications of recoil atoms (using PTRAC card of MCNPX code) and also the kinematics of interactions. The deterministic method was used for verification of the results of (MCNPX+AMTRACK). The SRIM (formely TRIM) code is capable to compute neutron radiation damage. The PKAs information was extracted by AMTRACK program, which can be used as an input of SRIM codes for systematic analysis of primary radiation damage. Then the Bushehr Nuclear Power Plant (BNPP) radiation damage on reactor pressure vessel is calculated.

Structural health monitoring for DOT using magnetic shape memory alloy cables in concrete

NASA Astrophysics Data System (ADS)

Davis, Allen; Mirsayar, Mirmilad; Sheahan, Emery; Hartl, Darren

2018-03-01

Embedding shape memory alloy (SMA) wires in concrete components offers the potential to monitor their structural health via external magnetic field sensing. Currently, structural health monitoring (SHM) is dominated by acoustic emission and vibration-based methods. Thus, it is attractive to pursue alternative damage sensing techniques that may lower the cost or increase the accuracy of SHM. In this work, SHM via magnetic field detection applied to embedded magnetic shape memory alloy (MSMA) is demonstrated both experimentally and using computational models. A concrete beam containing iron-based MSMA wire is subjected to a 3-point bend test where structural damage is induced, thereby resulting in a localized phase change of the MSMA wire. Magnetic field lines passing through the embedded MSMA domain are altered by this phase change and can thus be used to detect damage within the structure. A good correlation is observed between the computational and experimental results. Additionally, the implementation of stranded MSMA cables in place of the MSMA wire is assessed through similar computational models. The combination of these computational models and their subsequent experimental validation provide sufficient support for the feasibility of SHM using magnetic field sensing via MSMA embedded components.

Lycium barbarum polysaccharide protects human keratinocytes against UVB-induced photo-damage.

PubMed

Li, Huaping; Li, Zhenjie; Peng, Liqian; Jiang, Na; Liu, Qing; Zhang, Erting; Liang, Bihua; Li, Runxiang; Zhu, Huilan

2017-02-01

Ultraviolet B (UVB) irradiation plays a key role in skin damage, which induces oxidative and inflammatory damages, thereby causing photoaging or photocarcinogenesis. Lycium barbarum polysaccharide (LBP), the most biologically active fraction of wolfberry, possesses significant antioxidative and anti-inflammatory effects on multiple tissues. In the present study, the photoprotective effects and potential underlying molecular mechanisms of LBP against UVB-induced photo-damage were investigated in immortalized human keratinocytes (HaCaT cells). The data indicated that pretreatment with LBP significantly attenuated UVB-induced decrease in cell viability, increase in ROS production and DNA damage. LBP also significantly suppressed UVB-induced p38 MAPK activation, and subsequently reversed caspase-3 activation and MMP-9 expression. Notably, LBP was found to induce Nrf2 nuclear translocation and increase the expression of Nrf2-dependent ARE target genes. Furthermore, the protective effects of LBP were abolished by siRNA-mediated Nrf2 silencing. These results showed that the antioxidant LBP could partially protect against UVB irradiation-induced photo-damage through activation of Nrf2/ARE pathway, thereby scavenging ROS and reducing DNA damage, and subsequently suppressing UVB-induced p38 MAP pathway. Thus, LBP can be potentially used for skincare against oxidative damage from environmental insults.

Online damage inspection of optics for ATP system

NASA Astrophysics Data System (ADS)

Chen, Jing; Jiang, Yu; Mao, Yao; Gan, Xun; Liu, Qiong

2016-09-01

In the Electro-Optical acquisition-tracking-pointing system (ATP), the optical components will be damaged with the several influencing factors. In this situation, the rate will increase sharply when the arrival of damage to some extent. As the complex processing techniques and long processing cycle of optical components, the damage will cause the great increase of the system development cost and cycle. Therefore, it is significant to detect the laser-induced damage in the ATP system. At present, the major research on the on-line damage detection technology of optical components is for the large optical system in the international. The relevant detection systems have complicated structures and many of components, and require enough installation space reserved, which do not apply for ATP system. To solve the problem mentioned before, This paper use a method based on machine vision to detect the damage on-line for the present ATP system. To start with, CCD and PC are used for image acquisition. Secondly, smoothing filters are used to restrain false damage points produced by noise. Then, with the shape feature included in the damage image, the OTSU Method which can define the best segmentation threshold automatically is used to achieve the goal to locate the damage regions. At last, we can supply some opinions for the lifetime of the optical components by analyzing the damage data, such as damage area, damage position. The method has the characteristics of few-detectors and simple-structures which can be installed without any changes of the original light path. With the method, experimental results show that it is stable and effective to achieve the goal of detecting the damage of optical components on-line in the ATP system.

The effects of metal ions on the DNA damage induced by hydrogen peroxide.

PubMed

Kobayashi, S; Ueda, K; Komano, T

1990-01-01

The effects of metal ions on DNA damage induced by hydrogen peroxide were investigated using two methods, agarose-gel electrophoretic analysis of supercoiled DNA and sequencing-gel analysis of single end-labeled DNA fragments of defined sequences. Hydrogen peroxide induced DNA damage when iron or copper ion was present. At least two classes of DNA damage were induced, one being direct DNA-strand cleavage, and the other being base modification labile to hot piperidine. The investigation of the damaged sites and the inhibitory effects of radical scavengers revealed that hydroxyl radical was the species which attacked DNA in the reaction of H2O2/Fe(II). On the other hand, two types of DNA damage were induced by H2O2/Cu(II). Type I damage was predominant and inhibited by potassium iodide, but type II was not. The sites of the base-modification induced by type I damage were similar to those by lipid peroxidation products and by ascorbate in the presence of Cu(II), suggesting the involvement of radical species other than free hydroxyl radical in the damaging reactions.

Finite element analysis when orthogonal cutting of hybrid composite CFRP/Ti

NASA Astrophysics Data System (ADS)

Xu, Jinyang; El Mansori, Mohamed

2015-07-01

Hybrid composite, especially CFRP/Ti stack, is usually considered as an innovative structural configuration for manufacturing the key load-bearing components in modern aerospace industry. This paper originally proposed an FE model to simulate the total chip formation process dominated the hybrid cutting operation. The hybrid composite model was established based on three physical constituents, i.e., Ti constituent, interface and CFRP constituent. Different constitutive models and damage criteria were introduced to replicate the interrelated cutting behaviour of the stack material. The CFRP/Ti interface was modelled as a third phase through the concept of cohesive zone (CZ). Particular attention was made on the comparative studies of the influence of different cutting-sequence strategies on the machining responses induced in hybrid stack cutting. The numerical results emphasized the pivotal role of cutting-sequence strategy on the various machining induced responses including cutting-force generation, machined surface quality and induced interface damage.

RNF168 forms a functional complex with RAD6 during the DNA damage response

PubMed Central

Liu, Chao; Wang, Degui; Wu, Jiaxue; Keller, Jennifer; Ma, Teng; Yu, Xiaochun

2013-01-01

Summary Protein ubiquitination plays an important role in initiating the DNA damage response. Following DNA damage, E2 ubiquitin conjugating enzymes are crucial for catalyzing substrate ubiquitination that recruits downstream DNA repair factors to DNA lesions. To identify novel E2 conjugating enzymes important for initiating the DNA-damage-induced ubiquitination cascade, we screened most of the known E2 enzymes and found that RAD6A and RAD6B function together with RNF168 in the ionizing radiation (IR)-induced DNA damage response. Similarly to RNF168-deficient cells, RAD6A- or RAD6B-deficient cells exhibit a reduction in DNA-damage-induced protein ubiquitination. Correspondingly, DNA-damage-induced foci formation of DNA damage repair proteins, such as BRCA1 and 53BP1, is impaired in the absence of RAD6A or RAD6B. Moreover, the RNF168–RAD6 complex targeted histone H1.2 for ubiquitination in vitro and regulated DNA-damage-induced histone H1.2 ubiquitination in vivo. Collectively, these data demonstrate that RNF168, in complex with RAD6A or RAD6B, is activated in the DNA-damage-induced protein ubiquitination cascade. PMID:23525009

The thermal and mechanical stability of composite materials for space structures

NASA Technical Reports Server (NTRS)

Tompkins, S. S.; Sykes, G. F.; Bowles, D. E.

1985-01-01

A continuing research objective of the National Aeronautical and Space Administration (NASA) is to develop advanced composite materials for space structures. The thrust of this research is to gain fundamental understanding of the performance of advanced composites in the space environment. The emphasis has been to identify and model changes in the thermal-physical properties due to induced damage and develop improved materials.

Brain tissues atrophy is not always the best structural biomarker of physiological aging: A multimodal cross-sectional study.

PubMed

Cherubini, Andrea; Caligiuri, Maria Eugenia; Péran, Patrice; Sabatini, Umberto; Cosentino, Carlo; Amato, Francesco

2015-01-01

This study presents a voxel-based multiple regression analysis of different magnetic resonance image modalities, including anatomical T1-weighted, T2* relaxometry, and diffusion tensor imaging. Quantitative parameters sensitive to complementary brain tissue alterations, including morphometric atrophy, mineralization, microstructural damage, and anisotropy loss, were compared in a linear physiological aging model in 140 healthy subjects (range 20-74 years). The performance of different predictors and the identification of the best biomarker of age-induced structural variation were compared without a priori anatomical knowledge. The best quantitative predictors in several brain regions were iron deposition and microstructural damage, rather than macroscopic tissue atrophy. Age variations were best resolved with a combination of markers, suggesting that multiple predictors better capture age-induced tissue alterations. These findings highlight the importance of a combined evaluation of multimodal biomarkers for the study of aging and point to a number of novel applications for the method described.

Fatigue-Induced Damage in Zr-Based Bulk Metallic Glasses

PubMed Central

Chuang, Chih-Pin; Yuan, Tao; Dmowski, Wojciech; Wang, Gong-Yao; Freels, Matt; Liaw, Peter K.; Li, Ran; Zhang, Tao

2013-01-01

In the present work, we investigate the effect of “fatigue” on the fatigue behavior and atomic structure of Zr-based BMGs. Fatigue experiments on the failed-by-fatigue samples indicate that the remnants generally have similar or longer fatigue life than the as-cast samples. Meanwhile, the pair-distribution-function (PDF) analysis of the as-cast and post-fatigue samples showed very small changes of local atomic structures. These observations suggest that the fatigue life of the 6-mm in-diameter Zr-based BMG is dominated by the number of pre-existing crack-initiation sites in the sample. Once the crack initiates in the specimen, the fatigue-induced damage is accumulated locally on these initiated sites, while the rest of the region deforms elastically. The results suggest that the fatigue failure of BMGs under compression-compression fatigue experiments is a defect-controlled process. The present work indicates the significance of the improved fatigue resistance with decreasing the sample size. PMID:23999496

The hazard map of ML6.6 0206 Meinong earthquake near Guanmiao and its Neotectonic implication

NASA Astrophysics Data System (ADS)

Chung, L. H.; Shyu, J. B. H.; Huang, M. H.; Yang, K. M.; Le Beon, M.; Lee, Y. H.; Chuang, R.; Yi, D.

2016-12-01

The serious damage was occurred in SW Taiwan by ML 6.6 0206 Meinong earthquake. Based on InSAR result, 10 cm oval-raised surface deformation is 15 km away from its epicenter, and two obviously N-S trend sharp phase change nearby Guanmiao area. Our field investigation shows bulling damage and surface fracture are high related with the two sharp phase change. Here, we perform the detailed shallow underground geometry by using reflection seismic data, geologic data, and field hazard investigation. This N-S trend surface deformation may be induced by local shallow folding, while the huge uplift west of Guanmiao may be related with pure shear deformation of thick clayey Gutingkeng (GTK) Formation. Our results imply that not only a moderate lower crustal earthquake can trigger active structure at shallower depth, but also those minor shallow active structures are occurred serious damage and surface deformation.

High-Frequency, High-Temperature Fretting Experiments

NASA Technical Reports Server (NTRS)

Matlik, J. F.; Farris, T. N.; Haake, F. K.; Swanson, G. R.; Duke, G. C.

2005-01-01

Fretting is a structural damage mechanism observed when two nominally clamped surfaces are subjected to an oscillatory loading. A critical location for fretting induced damage has been identified at the blade/disk and blade/damper interfaces of gas turbine engine turbomachinery and space propulsion components. The high-temperature, high-frequency loading environment seen by these components lead to severe stress gradients at the edge-of-contact. These contact stresses drive crack nucleation and propagation in fretting and are very sensitive to the geometry of the contacting bodies, the contact loads, materials, temperature, and contact surface tribology (friction). To diagnose the threat that small and relatively undetectable fretting cracks pose to damage tolerance and structural integrity of in-service components, the objective of this work is to develop a well-characterized experimental fretting rig capable of investigating fretting behavior of advanced aerospace alloys subjected to load and temperature conditions representative of such turbomachinery components.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Feiye, E-mail: zhizi0269@doc.medic.mie-u.ac.jp; Ma, Ning, E-mail: maning@suzuka-u.ac.jp; Horibe, Yoshiteru, E-mail: violinteru@yahoo.co.jp

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 formationmore » 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.« less

Bi-Metallic Composite Structures With Designed Internal Residual Stress Field

NASA Technical Reports Server (NTRS)

Brice, Craig A.

2014-01-01

Shape memory alloys (SMA) have a unique ability to recover small amounts of plastic strain through a temperature induced phase change. For these materials, mechanical displacement can be accomplished by heating the structure to induce a phase change, through which some of the plastic strain previously introduced to the structure can be reversed. This paper introduces a concept whereby an SMA phase is incorporated into a conventional alloy matrix in a co-continuous reticulated arrangement forming a bi-metallic composite structure. Through memory activation of the mechanically constrained SMA phase, a controlled residual stress field is developed in the interior of the structure. The presented experimental data show that the memory activation of the SMA composite component significantly changes the residual stress distribution in the overall structure. Designing the structural arrangement of the two phases to produce a controlled residual stress field could be used to create structures that have much improved durability and damage tolerance properties.

Coenzyme Q10 Protects Human Endothelial Cells from β-Amyloid Uptake and Oxidative Stress-Induced Injury

PubMed Central

Durán-Prado, Mario; Frontiñán, Javier; Santiago-Mora, Raquel; Peinado, Juan Ramón; Parrado-Fernández, Cristina; Gómez-Almagro, María Victoria; Moreno, María; López-Domínguez, José Alberto; Villalba, José Manuel; Alcaín, Francisco J.

2014-01-01

Neuropathological symptoms of Alzheimer's disease appear in advances stages, once neuronal damage arises. Nevertheless, recent studies demonstrate that in early asymptomatic stages, ß-amyloid peptide damages the cerebral microvasculature through mechanisms that involve an increase in reactive oxygen species and calcium, which induces necrosis and apoptosis of endothelial cells, leading to cerebrovascular dysfunction. The goal of our work is to study the potential preventive effect of the lipophilic antioxidant coenzyme Q (CoQ) against ß-amyloid-induced damage on human endothelial cells. We analyzed the protective effect of CoQ against Aβ-induced injury in human umbilical vein endothelial cells (HUVECs) using fluorescence and confocal microscopy, biochemical techniques and RMN-based metabolomics. Our results show that CoQ pretreatment of HUVECs delayed Aβ incorporation into the plasma membrane and mitochondria. Moreover, CoQ reduced the influx of extracellular Ca2+, and Ca2+ release from mitochondria due to opening the mitochondrial transition pore after β-amyloid administration, in addition to decreasing O2 .− and H2O2 levels. Pretreatment with CoQ also prevented ß-amyloid-induced HUVECs necrosis and apoptosis, restored their ability to proliferate, migrate and form tube-like structures in vitro, which is mirrored by a restoration of the cell metabolic profile to control levels. CoQ protected endothelial cells from Aβ-induced injury at physiological concentrations in human plasma after oral CoQ supplementation and thus could be a promising molecule to protect endothelial cells against amyloid angiopathy. PMID:25272163

Freezing-induced deformation of biomaterials in cryomedicine

NASA Astrophysics Data System (ADS)

Ozcelikkale, Altug

Cryomedicine utilizes low temperature treatments of biological proteins, cells and tissues for cryopreservation, materials processing and cryotherapy. Lack of proper understanding of cryodamage that occurs during these applications remains to be the primary bottleneck for development of successful tissue cryopreservation and cryosurgery procedures. An engineering approach based on a view of biological systems as functional biomaterials can help identify, predict and control the primary cryodamage mechanisms by developing an understanding of underlying freezing-induced biophysical processes. In particular, freezing constitutes the main structural/mechanical origin of cryodamage and results in significant deformation of biomaterials at multiple length scales. Understanding of these freezing-induced deformation processes and their effects on post-thaw biomaterial functionality is currently lacking but will be critical to engineer improved cryomedicine procedures. This dissertation addresses this problem by presenting three separate but related studies of freezing-induced deformation at multiple length scales including nanometer-scale protein fibrils, single cells and whole tissues. A combination of rigorous experimentation and computational modeling is used to characterize post-thaw biomaterial structure and properties, predict biomaterial behavior and assess its post-thaw biological functionality. Firstly, freezing-induced damage on hierarchical extracellular matrix structure of collagen is investigated at molecular, fibril and matrix levels. Results indicate to a specific kind of fibril damage due to freezing-induced expansion of intrafibrillar fluid. This is followed by a study of freezing-induced cell and tissue deformation coupled to osmotically driven cellular water transport. Computational and semi empirical modeling of these processes indicate that intracellular deformation of the cell during freezing is heterogeneous and can interfere with cellular water transport, thereby leading to previously unconsidered mechanisms of cell freezing response. In addition, cellular water transport is identified as the critical limiting factor on the amount of freezing-induced tissue deformation, particularly in native tissues with high cell densities. Finally, effects of cryopreservation on post-thaw biological functionality of collagen engineered tissue constructs is investigated where cell-matrix interactions during fibroblast migration are considered as the functional response. Simultaneous cell migration and extracellular matrix deformation are characterized. Results show diminished cell-matrix coupling by freeze/thaw accompanied by a subtle decrease in cell migration. A connection between these results and freezing-induced collagen fibril damage is also suggested. Overall, this dissertation provides new fundamental knowledge on cryodamage mechanisms and a collection of novel multi-purpose engineering tools that will open the way for rational design of cryomedicine technologies.

Chromosome territories reposition during DNA damage-repair response

PubMed Central

2013-01-01

Background Local higher-order chromatin structure, dynamics and composition of the DNA are known to determine double-strand break frequencies and the efficiency of repair. However, how DNA damage response affects the spatial organization of chromosome territories is still unexplored. Results Our report investigates the effect of DNA damage on the spatial organization of chromosome territories within interphase nuclei of human cells. We show that DNA damage induces a large-scale spatial repositioning of chromosome territories that are relatively gene dense. This response is dose dependent, and involves territories moving from the nuclear interior to the periphery and vice versa. Furthermore, we have found that chromosome territory repositioning is contingent upon double-strand break recognition and damage sensing. Importantly, our results suggest that this is a reversible process where, following repair, chromosome territories re-occupy positions similar to those in undamaged control cells. Conclusions Thus, our report for the first time highlights DNA damage-dependent spatial reorganization of whole chromosomes, which might be an integral aspect of cellular damage response. PMID:24330859

Phospho-Bcl-x(L)(Ser62) plays a key role at DNA damage-induced G(2) checkpoint.

PubMed

Wang, Jianfang; Beauchemin, Myriam; Bertrand, Richard

2012-06-01

Accumulating evidence suggests that Bcl-xL, an anti-apoptotic member of the Bcl-2 family, also functions in cell cycle progression and cell cycle checkpoints. Analysis of a series of phosphorylation site mutants reveals that cells expressing Bcl-xL(Ser62Ala) mutant are less stable at the G 2 checkpoint and enter mitosis more rapidly than cells expressing wild-type Bcl-xL or Bcl-xL phosphorylation site mutants, including Thr41Ala, Ser43Ala, Thr47Ala, Ser56Ala and Thr115Ala. Analysis of the dynamic phosphorylation and location of phospho-Bcl-xL(Ser62) in unperturbed, synchronized cells and during DNA damage-induced G 2 arrest discloses that a pool of phospho-Bcl-xL(Ser62) accumulates into nucleolar structures in etoposide-exposed cells during G 2 arrest. In a series of in vitro kinase assays, pharmacological inhibitors and specific siRNAs experiments, we found that Polo kinase 1 and MAPK9/JNK2 are major protein kinases involved in Bcl-xL(Ser62) phosphorylation and accumulation into nucleolar structures during the G 2 checkpoint. In nucleoli, phospho-Bcl-xL(Ser62) binds to and co-localizes with Cdk1(cdc2), the key cyclin-dependent kinase required for entry into mitosis. These data indicate that during G 2 checkpoint, phospho-Bcl-xL(Ser62) stabilizes G 2 arrest by timely trapping of Cdk1(cdc2) in nucleolar structures to slow mitotic entry. It also highlights that DNA damage affects the dynamic composition of the nucleolus, which now emerges as a piece of the DNA damage response.

Mechanical reliability of porous low-k dielectrics for advanced interconnect: Study of the instability mechanisms in porous low-k dielectrics and their mediation through inert plasma induced re-polymerization of the backbone structure

NASA Astrophysics Data System (ADS)

Sa, Yoonki

Continuous scaling down of critical dimensions in interconnect structures requires the use of ultralow dielectric constant (k) films as interlayer dielectrics to reduce resistance-capacitance delays. Porous carbon-doped silicon oxide (p-SiCOH) dielectrics have been the leading approach to produce these ultralow-k materials. However, embedding of porosity into dielectric layer necessarily decreases the mechanical reliability and increases its susceptibility to adsorption of potentially deleterious chemical species during device fabrication process. Among those, exposure of porous-SiCOH low-k (PLK) dielectrics to oxidizing plasma environment causes the increase in dielectric constant and their vulnerability to mechanical instability of PLKs due to the loss of methyl species and increase in moisture uptake. These changes in PLK properties and physical stability have been persisting challenges for next-generation interconnects because they are the sources of failure in interconnect integration as well as functional and physical failures appearing later in IC device manufacturing. It is therefore essential to study the fundamentals of the interactions on p-SiCOH matrix induced by plasma exposure and find an effective and easy-to-implement way to reverse such changes by repairing damage in PLK structure. From these perspectives, the present dissertation proposes 1) a fundamental understanding of structural transformation occurring during oxidative plasma exposure in PLK matrix structure and 2) its restoration by using silylating treatment, soft x-ray and inert Ar-plasma radiation, respectively. Equally important, 3) as an alternative way of increasing the thermo-mechanical reliability, PLK dielectric film with an intrinsically robust structure by controlling pore morphology is fabricated and investigated. Based on the investigations, stability of PLK films studied by time-dependent ball indentation tester under the elevated temperature, variation in film thickness and dielectric constant, shows striking difference with small change in the chemical bond structure. Comparison of peak extracted by using FTIR (Fourier transform infrared spectroscopy) reveals that viscoplastic deformation and dielectric constant change correctly reflect the evolution in morphological structure of Si-O-Si peak. It is also found that hydrophilic nature of PLK matrix induced by silanol group is more involved with viscoplastic deformation rate and cage-like crosslinking in Si-O-Si peak is responsible for dielectric constant change. However, the level of instability driven by plasma exposure in PLK matrix is found to recover and desired mechanical and electrical properties are obtained by modifying the chemical bond configuration. Silylation process by HMDS (hexamethyldisilazane) works on recovery of hydrophobicity because it replenishes -C while removing -OH bonds. Contact angle is restored by controlling process temperature, however, the silylating agent cannot penetrate deep into PLK matrix without an adequate medium such as supercritical CO2, making it difficult to implement. As a way of overcoming the limitation of UV cure, soft x-ray cure with Al Kalpha target is applied to induce gentle reconfiguration of chemical bond. It is possible to break bond links selectively by controlling x-ray energy level and also reduce thermal curing temperature due to the increased penetration depth. As a result of soft x-ray cure, film thickness loss almost not occurred. However, influence of x-ray radiation on the moisture removal is limited. Basically, oxidative plasma damage appears in two extensive areas. The first is the loss of -C from PLK matrix, and the second is the increase in hydrophilic nature involved with the formation of Si-OH terminal bonds and H2O. Both alternations cause the dielectric constant to degrade because of increased density and/or loss of free volume, but the second causes PLK to lose thermal and mechanical stability because Si-OH and H2O act as catalysts for reactions that break the cross-linked backbone. Clearly, both changes in PLK chemistry and bond structure must be addressed in order for any repair method to be favorable. For this reason, Ar plasma treatment with low energy ions is employed to repair the plasma induced damage by creating the desired changes in the film matrix without a significant loss of other properties. Our approach of using inert plasma as a way for damage recovery is motivated by the realization that there is no possibility of chemical reaction with any organic species, driving the energy transfer only from the plasma species towards the respective film matrix. As results, after applying Ar plasma beam treatment followed by annealing on damaged PLK films, the resistance against thermal instability and viscoplastic deformation is found to be improved. Ball indentation depth of the films with Ar plasma process is drastically reduced at the identical condition. More noticeable is the fact that such alternation is converted towards a dehydration reaction under hydrostatic thermal pressure, which causes dielectric constant to decrease and films shrinkage to restore during reconstruction of polymer chains. It is suggested that the immediate event of an Ar plasma beam radiation is to deposit energy from the plasma species (ions, electrons) and this energy input produces the excited state species because Ar cannot chemically react with the film matrix. As a consequence, the radical sites are generated at the less stable area such as colony boundary or pore surface with the decay of the excited species, leading to the production of free radicals by an energy transfer to the bonds which are to be broken. Then, the activated sites experience chemical bond rearrangement by chain-scission, branching, or cross-linking. In our case, crosslink with C is involved with silylmethylene (Si-(CH 2)x-Si) groups and it is turned out that some of these groups are converted to methyl groups terminally bonded to siloxane backbone structure under 300˜400°C by reaction with -OH, and simultaneously creating a new Si-O-Si crosslink. As an alternative way of increasing the thermo-mechanical reliability, PLK dielectric film with an intrinsically robust structure by controlling pore morphology is fabricated. Since pore surface is susceptible to be damaged by BEOL integration damage, pore morphology in terms of size, distribution, and connectivity should be controlled in order to increase the robustness of PLK dielectrics. Generally, pores in PLK matrix are created by depositing organic fragment (called 'porogen') into the film and removed later by thermal and electron beam cure to form porous PLK layer (; Subtractive deposition). However, during the curing Si-O-Si backbone crosslink is broken and pores are easily interconnected, leading to vulnerable structure to the extrinsic damage. Constitutive deposition approach is feasible for the introduction of smaller nano-pores with little or no interconnectivity by steric hindrance. Due to the closed pore system, thermally-induced stress and plasma-induced damage is restricted merely to the surface of the dielectric film. This is attributed to the stable siloxane (Si-O-Si) backbone and the terminally bonded methyl group attached to silicon (Si-CH3), inducing steric hindrance that lowers the density of the films. The low dielectric constant and mechanical stability are closely involved with the formation of the Si-O-Si cage-like structure and an appropriate combination of stable Si-O-Si, Si-CH3 groups. Based on the FTIR and XPS spectra, it is concluded that the formation of the Si-O-Si cage-like structure was enhanced by structural method. It is believed that all these changes are beneficial for improving PLK stability as will be detailed in this dissertation. Especially, the originality and particular advantage of this study regarding plasma-induced damage repair will be highlighted.

Chronic intermittent ethanol induced axon and myelin degeneration is attenuated by calpain inhibition

PubMed Central

Samantaray, Supriti; Knaryan, Varduhi H.; Patel, Kaushal S.; Mulholland, Patrick J.; Becker, Howard C.; Banik, Naren L.

2015-01-01

Chronic alcohol consumption causes multifaceted damage to the central nervous system (CNS), underlying mechanisms of which are gradually being unraveled. In our previous studies, activation of calpain, a calcium-activated neutral protease has been found to cause detrimental alterations in spinal motor neurons following ethanol (EtOH) exposure in vitro. However, it is not known whether calpain plays a pivotal role in chronic EtOH exposure-induced structural damage to CNS in vivo. To test the possible involvement of calpain in EtOH-associated neurodegenerative mechanisms the present investigation was conducted in a well-established mouse model of alcohol dependence - chronic intermittent EtOH (CIE) exposure and withdrawal. Our studies indicated significant loss of axonal proteins (neurofilament light and heavy, 50-60 %), myelin proteins (myelin basic protein, 20-40 % proteolipid protein, 25 %) and enzyme (2′, 3′-cyclic-nucleotide 3′-phosphodiesterase, 21-55 %) following CIE in multiple regions of brain including hippocampus, corpus callosum, cerebellum, and importantly in spinal cord. These CIE-induced deleterious effects escalated after withdrawal in each CNS region tested. Increased expression and activity of calpain along with enhanced ratio of active calpain to calpastatin (sole endogenous inhibitor) was observed after withdrawal compared to EtOH exposure. Pharmacological inhibition of calpain with calpeptin (25 μg/kg) prior to each EtOH vapor inhalation significantly attenuated damage to axons and myelin as demonstrated by immuno-profiles of axonal and myelin proteins, and Luxol Fast Blue staining. Calpain inhibition significantly protected the ultrastructural integrity of axons and myelin compared to control as confirmed by electron microscopy. Together, these findings confirm CIE exposure and withdrawal induced structural alterations in axons and myelin, predominantly after withdrawal and corroborate calpain inhibition as a potential protective strategy against EtOH associated CNS degeneration. PMID:26100335

Example Building Damage Caused by Mining Exploitation in Disturbed Rock Mass

NASA Astrophysics Data System (ADS)

Florkowska, Lucyna

2013-06-01

Issues concerning protection of buildings against the impact of underground coal mining pose significant scientific and engineering challenges. In Poland, where mining is a potent and prominent industry assuring domestic energy security, regions within reach of mining influences are plenty. Moreover, due to their industrial character they are also densely built-up areas. Because minerals have been extracted on an industrial scale in majority of those areas for many years, the rock mass structure has been significantly disturbed. Hence, exploitation of successive layers of multi-seam deposits might cause considerable damage - both in terms of surface and existing infrastructure networks. In the light of those facts, the means of mining and building prevention have to be improved on a regular basis. Moreover, they have to be underpinned by reliable analyses holistically capturing the comprehensive picture of the mining, geotechnical and constructional situation of structures. Scientific research conducted based on observations and measurements of mining-induced strain in buildings is deployed to do just that. Presented in this paper examples of damage sustained by buildings armed with protection against mining influences give an account of impact the mining exploitation in disturbed rock mass can have. This paper is based on analyses of mining damage to church and Nursing Home owned by Evangelical Augsburg Parish in Bytom-Miechowice. Neighbouring buildings differ in the date they were built, construction, building technology, geometry of the building body and fitted protection against mining damage. Both the buildings, however, have sustained lately significant deformation and damage caused by repeated mining exploitation. Selected damage has been discussed hereunder. The structures have been characterised, their current situation and mining history have been outlined, which have taken their toll on character and magnitude of damage. Description has been supplemented with photographic documentation.

Mutagenic effect of accelerated heavy ions on bacterial cells

NASA Astrophysics Data System (ADS)

Boreyko, A. V.; Krasavin, E. A.

2011-11-01

The heavy ion accelerators of the Joint Institute for Nuclear Research were used to study the regularities and mechanisms of formation of different types of mutations in prokaryote cells. The induction of direct (lac-, ton B-, col B) mutations for Esherichia coli cells and reverse his- → His+ mutations of Salmonella typhimurium, Bacillus subtilis cells under the action of radiation in a wide range of linear energy transfer (LET) was studied. The regularities of formation of gene and structural (tonB trp-) mutations for Esherichia coli bacteria under the action of accelerated heavy ions were studied. It was demonstrated that the rate of gene mutations as a function of the dose under the action of Γ rays and accelerated heavy ions is described by linear-quadratic functions. For structural mutations, linear "dose-effect" dependences are typical. The quadratic character of mutagenesis dose curves is determined by the "interaction" of two independent "hitting" events in the course of SOS repair of genetic structures. The conclusion made was that gene mutations under the action of accelerated heavy ions are induced by δ electron regions of charged particle tracks. The methods of SOS chromotest, SOS lux test, and λ prophage induction were used to study the regularities of SOS response of cells under the action of radiations in a wide LET range. The following proposition was substantiated: the molecular basis for formation of gene mutations are cluster single-strand DNA breaks, and that for structural mutations, double-strand DNA breaks. It was found out that the LET dependence of the relative biological efficiency of accelerated ions is described by curves with a local maximum. It was demonstrated that the biological efficiency of ionizing radiations with different physical characteristics on cells with different genotype, estimated by the lethal action, induction of gene and deletion mutations, precision excision of transposons, is determined by the specific features of energy transfer of the radiations that affect the character of induced DNA damage, and the efficiency inducible and constitutive cell repair systems. The growth of relative biological efficiency of heavy charged particles is determined by the growth of the damage yield of the DNA participating in the formation of radiation-induced effects, and higher efficiency of inducible repair systems. It was established that the LET value ( L max) for which the maximum (according to the applied irradiation criteria) coefficients of relative biological efficiency are observed varies depending on the character of the registered radiation induced effect. It was demonstrated that for gene mutations and induction of precision excision of mobile elements the values of L max are realized in a LET range of ≈20 keV/μm. For lethal effects of irradiation and induction of deletion mutations the value of L max is ≈ 100 and 50 keV/μm, respectively. The differences in the L max for the studied radiation gene effectis are determined by the different type of DNA damage participating in the mutation process. A molecular model of the formation of gene mutations in Escherichia coli cells under the action of ionizing radiation was proposed. Basic DNA radiation damage and main repair ways were considered in the framework of this model. The basis is the idea of the decisive role of mutagenic, error-prone, branch of SOS repair in fixing premutation DNA damage into point mutations. It was demonstrated that the central mechanism in this process is the formation of an inducible multi-enzymatic complex including the DNA polymerase V (Umu C), RecA-protease, SSB proteins, subunits of DNA polymerase III, performing erroneous DNA synthesis on the damaged matrix. A mathematical model of induction of gene mutations under ultraviolet cell irradiation was developed based on the molecular model.

Recruitment of TRF2 to laser-induced DNA damage sites.

PubMed

Huda, Nazmul; Abe, Satoshi; Gu, Ling; Mendonca, Marc S; Mohanty, Samarendra; Gilley, David

2012-09-01

Several lines of evidence suggest that the telomere-associated protein TRF2 plays critical roles in the DNA damage response. TRF2 is rapidly and transiently phosphorylated by an ATM-dependent pathway in response to DNA damage and this DNA damage-induced phosphoryation is essential for the DNA-PK-dependent pathway of DNA double-strand break repair (DSB). However, the type of DNA damage that induces TRF2 localization to the damage sites, the requirement for DNA damage-induced phosphorylation of TRF2 for its recruitment, as well as the detailed kinetics of TRF2 accumulation at DNA damage sites have not been fully investigated. In order to address these questions, we used an ultrafast femtosecond multiphoton laser and a continuous wave 405-nm single photon laser to induce DNA damage at defined nuclear locations. Our results showed that DNA damage produced by a femtosecond multiphoton laser was sufficient for localization of TRF2 to these DNA damage sites. We also demonstrate that ectopically expressed TRF2 was recruited to DNA lesions created by a 405-nm laser. Our data suggest that ATM and DNA-PKcs kinases are not required for TRF2 localization to DNA damage sites. Furthermore, we found that phosphorylation of TRF2 at residue T188 was not essential for its recruitment to laser-induced DNA damage sites. Thus, we provide further evidence that a protein known to function in telomere maintenance, TRF2, is recruited to sites of DNA damage and plays critical roles in the DNA damage response. Copyright © 2012 Elsevier Inc. All rights reserved.

Gamma radiation effects on siloxane-based additive manufactured structures

NASA Astrophysics Data System (ADS)

Schmalzer, Andrew M.; Cady, Carl M.; Geller, Drew; Ortiz-Acosta, Denisse; Zocco, Adam T.; Stull, Jamie; Labouriau, Andrea

2017-01-01

Siloxane-basedadditive manufactured structures prepared by the direct ink write (DIW) technology were exposed to ionizing irradiation in order to gauge radiolysis effects on structure-property relationships. These well-defined 3-D structures were subjected to moderate doses of gamma irradiation in an inert atmosphere and characterized by a suite of experimental methods. Changes in thermal, chemical, microstructure, and mechanical properties were evaluated by DSC, TGA, FT-IR, mass spectroscopy, EPR, solvent swelling, SEM, and uniaxial compressive load techniques. Our results demonstrated that 3-D structures made from aromatic-free siloxane resins exhibited hardening after being exposed to gamma radiation. This effect was accompanied by gas evolution, decreasing in crystallization levels, decreasing in solvent swelling and damage to the microstructure. Furthermore, long-lived radiation-induced radicals were not detected by EPR methods. Our results are consistent with cross-link formation being the dominant degradation mechanism over chain scission reactions. On the other hand, 3-D structures made from high phenyl content siloxane resins showed little radiation damage as evidenced by low off gassing.

Qualitative and quantitative changes in phospholipids and proteins investigated by spectroscopic techniques in animal depression model.

PubMed

Depciuch, J; Sowa-Kucma, M; Nowak, G; Papp, M; Gruca, P; Misztak, P; Parlinska-Wojtan, M

2017-04-05

Depression becomes nowadays a high mortality civilization disease with one of the major causes being chronic stress. Raman, Fourier Transform Infra Red (FTIR) and Ultraviolet-Visible (UV-vis) spectroscopies were used to determine the changes in the quantity and structure of phospholipids and proteins in the blood serum of rats subjected to chronic mild stress, which is a common animal depression model. Moreover, the efficiency of the imipramine treatment was evaluated. It was found that chronic mild stress not only damages the structure of the phospholipids and proteins, but also decreases their level in the blood serum. A 5weeks imipramine treatment did increase slightly the quantity of proteins, leaving the damaged phospholipids unchanged. Structural information from phospholipids and proteins was obtained by UV-vis spectroscopy combined with the second derivative of the FTIR spectra. Indeed, the structure of proteins in blood serum of stressed rats was normalized after imipramine therapy, while the impaired structure of phospholipids remained unaffected. These findings strongly suggest that the depression factor, which is chronic mild stress, may induce permanent (irreversible) damages into the phospholipid structure identified as shortened carbon chains. This study shows a possible new application of spectroscopic techniques in the diagnosis and therapy monitoring of depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Qualitative and quantitative changes in phospholipids and proteins investigated by spectroscopic techniques in animal depression model

NASA Astrophysics Data System (ADS)

Depciuch, J.; Sowa-Kucma, M.; Nowak, G.; Papp, M.; Gruca, P.; Misztak, P.; Parlinska-Wojtan, M.

2017-04-01

Depression becomes nowadays a high mortality civilization disease with one of the major causes being chronic stress. Raman, Fourier Transform Infra Red (FTIR) and Ultraviolet-Visible (UV-vis) spectroscopies were used to determine the changes in the quantity and structure of phospholipids and proteins in the blood serum of rats subjected to chronic mild stress, which is a common animal depression model. Moreover, the efficiency of the imipramine treatment was evaluated. It was found that chronic mild stress not only damages the structure of the phospholipids and proteins, but also decreases their level in the blood serum. A 5 weeks imipramine treatment did increase slightly the quantity of proteins, leaving the damaged phospholipids unchanged. Structural information from phospholipids and proteins was obtained by UV-vis spectroscopy combined with the second derivative of the FTIR spectra. Indeed, the structure of proteins in blood serum of stressed rats was normalized after imipramine therapy, while the impaired structure of phospholipids remained unaffected. These findings strongly suggest that the depression factor, which is chronic mild stress, may induce permanent (irreversible) damages into the phospholipid structure identified as shortened carbon chains. This study shows a possible new application of spectroscopic techniques in the diagnosis and therapy monitoring of depression.

Lightning Strike Induced Damage Mechanisms of Carbon Fiber Composites

NASA Astrophysics Data System (ADS)

Kawakami, Hirohide

Composite materials have a wide application in aerospace, automotive, and other transportation industries, because of the superior structural and weight performances. Since carbon fiber reinforced polymer composites possess a much lower electrical conductivity as compared to traditional metallic materials utilized for aircraft structures, serious concern about damage resistance/tolerance against lightning has been rising. Main task of this study is to clarify the lightning damage mechanism of carbon fiber reinforced epoxy polymer composites to help further development of lightning strike protection. The research on lightning damage to carbon fiber reinforced polymer composites is quite challenging, and there has been little study available until now. In order to tackle this issue, building block approach was employed. The research was started with the development of supporting technologies such as a current impulse generator to simulate a lightning strike in a laboratory. Then, fundamental electrical properties and fracture behavior of CFRPs exposed to high and low level current impulse were investigated using simple coupon specimens, followed by extensive parametric investigations in terms of different prepreg materials frequently used in aerospace industry, various stacking sequences, different lightning intensity, and lightning current waveforms. It revealed that the thermal resistance capability of polymer matrix was one of the most influential parameters on lightning damage resistance of CFRPs. Based on the experimental findings, the semi-empirical analysis model for predicting the extent of lightning damage was established. The model was fitted through experimental data to determine empirical parameters and, then, showed a good capability to provide reliable predictions for other test conditions and materials. Finally, structural element level lightning tests were performed to explore more practical situations. Specifically, filled-hole CFRP plates and patch-repaired CFRP plates were selected as structural elements likely to be susceptible to lightning event. This study forms a solid foundation for the understanding of lightning damage mechanism of CFRPs, and become an important first step toward building a practical damage prediction tool of lighting event.

Thermal conductivity measurements via time-domain thermoreflectance for the characterization of radiation induced damage

DOE PAGES

Cheaito, Ramez; Gorham, Caroline S.; Carnegie Mellon Univ., Pittsburgh, PA; ...

2015-05-01

The progressive build up of displacement damage and fission products inside different systems and components of a nuclear reactor can lead to significant defect formation, degradation, and damage of the constituent materials. This structural modification can highly influence the thermal transport mechanisms and various mechanical properties of solids. In this paper we demonstrate the use of time-domain thermoreflectance (TDTR), a non-destructive method capable of measuring the thermal transport in material systems from nano to bulk scales, to study the effect of radiation damage and the subsequent changes in the thermal properties of materials. We use TDTR to show that displacementmore » damage from ion irradiation can significantly reduce the thermal conductivity of Optimized ZIRLO, a material used as fuel cladding in several current nuclear reactors. We find that the thermal conductivity of copper-niobium nanostructured multilayers does not change with helium ion irradiation doses of up to 10 15 cm -2 and ion energy of 200 keV suggesting that these structures can be used and radiation tolerant materials in nuclear reactors. We compare the effect of ion doses and ion beam energies on the measured thermal conductivity of bulk silicon. Results demonstrate that TDTR thermal measurements can be used to quantify depth dependent damage.« less

Changes in optical properties during heating of ex vivo liver tissues

NASA Astrophysics Data System (ADS)

Nagarajan, Vivek Krishna; Gogineni, Venkateshwara R.; White, Sarah B.; Yu, Bing

2017-02-01

Thermal ablation is the use of heat to induce cell death through coagulative necrosis. Ideally, complete ablation of tumor cells with no damage to surrounding critical structures such as blood vessels, nerves or even organs is desired. Ablation monitoring techniques are often employed to ensure optimal tumor ablation. In thermal tissue ablation, tissue damage is known to be dependent on the temperature and time of exposure. Aptly, current methods for monitoring ablation rely profoundly on local tissue temperature and duration of heating to predict the degree of tissue damage. However, such methods do not take into account the microstructural and physiological changes in tissues as a result of thermocoagulation. Light propagation within biological tissues is known to be dependent on the tissue microstructure and physiology. During tissue denaturation, changes in tissue structure alter light propagations in tissue which could be used to directly assess the extent of thermal tissue damage. We report the use of a spectroscopic system for monitoring the tissue optical properties during heating of ex vivo liver tissues. We observed that during tissue denaturation, continuous changes in wavelength-averaged μa(λ) and μ's(λ) followed a sigmoidal trend and are correlated with damage predicted by Arrhenius model.

Structural basis for inhibition of the histone chaperone activity of SET/TAF-Iβ by cytochrome c.

PubMed

González-Arzola, Katiuska; Díaz-Moreno, Irene; Cano-González, Ana; Díaz-Quintana, Antonio; Velázquez-Campoy, Adrián; Moreno-Beltrán, Blas; López-Rivas, Abelardo; De la Rosa, Miguel A

2015-08-11

Chromatin is pivotal for regulation of the DNA damage process insofar as it influences access to DNA and serves as a DNA repair docking site. Recent works identify histone chaperones as key regulators of damaged chromatin's transcriptional activity. However, understanding how chaperones are modulated during DNA damage response is still challenging. This study reveals that the histone chaperone SET/TAF-Iβ interacts with cytochrome c following DNA damage. Specifically, cytochrome c is shown to be translocated into cell nuclei upon induction of DNA damage, but not upon stimulation of the death receptor or stress-induced pathways. Cytochrome c was found to competitively hinder binding of SET/TAF-Iβ to core histones, thereby locking its histone-binding domains and inhibiting its nucleosome assembly activity. In addition, we have used NMR spectroscopy, calorimetry, mutagenesis, and molecular docking to provide an insight into the structural features of the formation of the complex between cytochrome c and SET/TAF-Iβ. Overall, these findings establish a framework for understanding the molecular basis of cytochrome c-mediated blocking of SET/TAF-Iβ, which subsequently may facilitate the development of new drugs to silence the oncogenic effect of SET/TAF-Iβ's histone chaperone activity.

Detecting delaminations and disbondings on full-scale wing composite panel by guided waves based SHM system

NASA Astrophysics Data System (ADS)

Monaco, E.; Boffa, N. D.; Memmolo, V.; Ricci, F.; Maio, L.

2016-04-01

A full-scale lower wing panel made of composite material has been designed, manufactured and sensorised within the European Funded research project named SARISTU. The authors contributed to the whole development of the system, from design to implementation as well as to the impacts campaign phase where Barely Visible and Visible Damages (BVID and VID) are to be artificially induced on the panel by a pneumatic impact machine. This work summarise part of the experimental results related to damages production, their assessment by C-SCAN as reference NDT method as well as damage detection of delimitations by a guided waves based SHM. The SHM system is made by customized piezoelectric patches secondary bonded on the wing plate acting both as guided waves sources and receivers. The paper will deal mostly with the experimental impact campaign and the signal analyses carried out to extract the metrics more sensitive to damages induced. Image reconstruction of the damages dimensions and shapes will be also described based mostly on the combination of metrics maps over the plate partial surfaces. Finally a comparison of damages maps obtained by the SHM approach and those obtained by "classic" C-SCAN will be presented analyzing briefly pros and cons of the two different approached as a combination to the most effective structural maintenance scenario of a commercial aircraft.

Insights into the mechanism of X-ray-induced disulfide-bond cleavage in lysozyme crystals based on EPR, optical absorption and X-ray diffraction studies

PubMed Central

Sutton, Kristin A.; Black, Paul J.; Mercer, Kermit R.; Garman, Elspeth F.; Owen, Robin L.; Snell, Edward H.; Bernhard, William A.

2013-01-01

Electron paramagnetic resonance (EPR) and online UV–visible absorption microspectrophotometry with X-ray crystallography have been used in a complementary manner to follow X-ray-induced disulfide-bond cleavage. Online UV–visible spectroscopy showed that upon X-irradiation, disulfide radicalization appeared to saturate at an absorbed dose of approximately 0.5–0.8 MGy, in contrast to the saturating dose of ∼0.2 MGy observed using EPR at much lower dose rates. The observations suggest that a multi-track model involving product formation owing to the interaction of two separate tracks is a valid model for radiation damage in protein crystals. The saturation levels are remarkably consistent given the widely different experimental parameters and the range of total absorbed doses studied. The results indicate that even at the lowest doses used for structural investigations disulfide bonds are already radicalized. Multi-track considerations offer the first step in a comprehensive model of radiation damage that could potentially lead to a combined computational and experimental approach to identifying when damage is likely to be present, to quantitate it and to provide the ability to recover the native unperturbed structure. PMID:24311579

Adeno-associated virus inverted terminal repeats stimulate gene editing.

PubMed

Hirsch, M L

2015-02-01

Advancements in genome editing have relied on technologies to specifically damage DNA which, in turn, stimulates DNA repair including homologous recombination (HR). As off-target concerns complicate the therapeutic translation of site-specific DNA endonucleases, an alternative strategy to stimulate gene editing based on fragile DNA was investigated. To do this, an episomal gene-editing reporter was generated by a disruptive insertion of the adeno-associated virus (AAV) inverted terminal repeat (ITR) into the egfp gene. Compared with a non-structured DNA control sequence, the ITR induced DNA damage as evidenced by increased gamma-H2AX and Mre11 foci formation. As local DNA damage stimulates HR, ITR-mediated gene editing was investigated using DNA oligonucleotides as repair substrates. The AAV ITR stimulated gene editing >1000-fold in a replication-independent manner and was not biased by the polarity of the repair oligonucleotide. Analysis of additional human DNA sequences demonstrated stimulation of gene editing to varying degrees. In particular, inverted yet not direct, Alu repeats induced gene editing, suggesting a role for DNA structure in the repair event. Collectively, the results demonstrate that inverted DNA repeats stimulate gene editing via double-strand break repair in an episomal context and allude to efficient gene editing of the human chromosome using fragile DNA sequences.

HREM study of irradiation damage in human dental enamel crystals.

PubMed

Brès, E F; Hutchison, J L; Senger, B; Voegel, J C; Frank, R M

1991-06-01

Several phenomena have been observed during the examination of human dental enamel crystals (mainly constituted by hydroxyapatite (OHAP] by high-resolution electron microscopy (HREM) at 300 and 400 keV: orientation-dependent damage in the form of mass loss from voids or uniform destruction of crystal structure, beam-induced diffusion creating outgrowths at the crystal surfaces, recrystallization of the bulk crystal and crystallization of the inorganic components of the matrix surrounding the crystals. These beam-induced crystals have the CaO structure. The phenomena observed are most likely due to various electron-crystal interaction mechanisms (ballistic knock-on damage, electronic excitations, temperature rise, etc.). In this paper, the contribution of the ballistic process to the phenomena observed is discussed. The quantitative description of the knock-on collisions rests on the McKinley-Feshbach cross-section formula. The minimum ion displacement energies which appear in this expression have been estimated on the basis of the electrostatic ion binding energies, and the covalent bond energies if required. It is shown that hydroxyl, calcium and oxygen ions can effectively be displaced by the incident 300 and 400 keV electrons. Thus, the formation of CaO crystals by the combination of calcium and oxygen ions diffusing from their initial sites inside the OHAP lattice can tentatively be explained.

Association between occupational exposures to pesticides with heterogeneous chemical structures and farmer health in China.

PubMed

Huang, Xusheng; Zhang, Chao; Hu, Ruifa; Li, Yifan; Yin, Yanhong; Chen, Zhaohui; Cai, Jinyang; Cui, Fang

2016-04-27

This study analyzed the associations of farmers' exposure to organophosphates (OPs), organosulfurs (OSs), organonitrogens (ONs) and pyrethroids (PYRs) with parameters of the blood complete counts (CBC), a blood chemistry panel (BCP) and the conventional nerve conduction studies among 224 farmers in China in 2012. Two health examinations and a series of follow-up field surveys were conducted. Multiple linear regression analyses were used to evaluate the associations. The results show considerable associations between multiple groups of pesticides and several CBC parameters, but it was not enough to provide evidence of hematological disorders. The short- and medium-term OPs exposures were mainly associated with liver damage and peripheral nerve impairment, respectively, while OSs exposure might induce liver damage and renal dysfunction. The neurotoxicity of ONs was second only to OPs in addition to its potential liver damage and the induced alterations in glucose. In comparison, the estimated results show that PYRs would be the least toxic in terms of the low-dose application. In conclusion, occupational exposures to pesticides with heterogeneous chemical structures are associated with farmer health in different patterns, and the association between a specific group of pesticides and farmer health also differs between the short- and medium-term exposures.

Anti-Inflammatory and Antioxidative Stress Effects of Oryzanol in Glaucomatous Rabbits.

PubMed

Panchal, Shital S; Patidar, Rajesh K; Jha, Abhishek B; Allam, Ahmed A; Ajarem, Jamaan; Butani, Shital B

2017-01-01

Purpose . γ -Oryzanol works by anti-inflammatory and radical scavenging activity as a neuroprotective, anticancer, antiulcer, and immunosuppressive agent. The present study was conducted to investigate effect of oryzanol in acute and chronic experimental glaucoma in rabbits. Methods . Effect of oryzanol was evaluated in 5% dextrose induced acute model of ocular hypertension in rabbit eye. Chronic model of glaucoma was induced with subconjunctival injection of 5% of 0.3 ml phenol. Treatment with oryzanol was given for next two weeks after induction of glaucoma. From anterior chamber of rabbit eye aqueous humor was collected to assess various oxidative stress parameters like malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, nitric oxide, and inflammatory parameters like TNF- α and IL-6. Structural damage in eye was examined by histopathological studies. Results . In acute model of ocular hypertension oryzanol did not alter raised intraocular pressure. In chronic model of glaucoma oryzanol exhibited significant reduction in oxidative stress followed by reduction in intraocular pressure. Oryzanol treatment reduced level of TNF- α and IL-6. Histopathological studies revealed decreased structural damage of trabecular meshwork, lamina cribrosa, and retina with oryzanol treatment. Conclusions . Oryzanol showed protective effect against glaucoma by its antioxidative stress and anti-inflammatory property. Treatment with oryzanol can reduce optic nerve damage.

Level 1 Tornado PRA for the High Flux Beam Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bozoki, G.E.; Conrad, C.S.

This report describes a risk analysis primarily directed at providing an estimate for the frequency of tornado induced damage to the core of the High Flux Beam Reactor (HFBR), and thus it constitutes a Level 1 Probabilistic Risk Assessment (PRA) covering tornado induced accident sequences. The basic methodology of the risk analysis was to develop a ``tornado specific`` plant logic model that integrates the internal random hardware failures with failures caused externally by the tornado strike and includes operator errors worsened by the tornado modified environment. The tornado hazard frequency, as well as earlier prepared structural and equipment fragility data,more » were used as input data to the model. To keep modeling/calculational complexity as simple as reasonable a ``bounding`` type, slightly conservative, approach was applied. By a thorough screening process a single dominant initiating event was selected as a representative initiator, defined as: ``Tornado Induced Loss of Offsite Power.`` The frequency of this initiator was determined to be 6.37E-5/year. The safety response of the HFBR facility resulted in a total Conditional Core Damage Probability of .621. Thus, the point estimate of the HFBR`s Tornado Induced Core Damage Frequency (CDF) was found to be: (CDF){sub Tornado} = 3.96E-5/year. This value represents only 7.8% of the internal CDF and thus is considered to be a small contribution to the overall facility risk expressed in terms of total Core Damage Frequency. In addition to providing the estimate of (CDF){sub Tornado}, the report documents, the relative importance of various tornado induced system, component, and operator failures that contribute most to (CDF){sub Tornado}.« less

Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer.

PubMed

King, Suzanne N; Dunlap, Neal E; Tennant, Paul A; Pitts, Teresa

2016-06-01

Oncologic treatments, such as curative radiotherapy and chemoradiation, for head and neck cancer can cause long-term swallowing impairments (dysphagia) that negatively impact quality of life. Radiation-induced dysphagia comprised a broad spectrum of structural, mechanical, and neurologic deficits. An understanding of the biomolecular effects of radiation on the time course of wound healing and underlying morphological tissue responses that precede radiation damage will improve options available for dysphagia treatment. The goal of this review is to discuss the pathophysiology of radiation-induced injury and elucidate areas that need further exploration.

The ovarian DNA damage repair response is induced prior to phosphoramide mustard-induced follicle depletion, and ataxia telangiectasia mutated inhibition prevents PM-induced follicle depletion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

Phosphoramide mustard (PM) is an ovotoxic metabolite of cyclophosphamide and destroys primordial and primary follicles potentially by DNA damage induction. The temporal pattern by which PM induces DNA damage and initiation of the ovarian response to DNA damage has not yet been well characterized. This study investigated DNA damage initiation, the DNA repair response, as well as induction of follicular demise using a neonatal rat ovarian culture system. Additionally, to delineate specific mechanisms involved in the ovarian response to PM exposure, utility was made of PKC delta (PKCδ) deficient mice as well as an ATM inhibitor (KU 55933; AI). Fishermore » 344 PND4 rat ovaries were cultured for 12, 24, 48 or 96 h in medium containing DMSO ± 60 μM PM or KU 55933 (48 h; 10 nM). PM-induced activation of DNA damage repair genes was observed as early as 12 h post-exposure. ATM, PARP1, E2F7, P73 and CASP3 abundance were increased but RAD51 and BCL2 protein decreased after 96 h of PM exposure. PKCδ deficiency reduced numbers of all follicular stages, but did not have an additive impact on PM-induced ovotoxicity. ATM inhibition protected all follicle stages from PM-induced depletion. In conclusion, the ovarian DNA damage repair response is active post-PM exposure, supporting that DNA damage contributes to PM-induced ovotoxicity. - Highlights: • PM exposure induces DNA damage repair gene expression. • Inhibition of ATM prevented PM-induced follicle depletion. • PKCδ deficiency did not impact PM-induced ovotoxicity.« less

Alterations in histone acetylation following exposure to 60Co γ-rays and their relationship with chromosome damage in human lymphoblastoid cells.

PubMed

Tian, Xue-Lei; Lu, Xue; Feng, Jiang-Bin; Cai, Tian-Jing; Li, Shuang; Tian, Mei; Liu, Qing-Jie

2018-05-17

Chromosome damage is related to DNA damage and erroneous repair. It can cause cell dysfunction and ultimately induce carcinogenesis. Histone acetylation is crucial for regulating chromatin structure and DNA damage repair. Ionizing radiation (IR) can alter histone acetylation. However, variations in histone acetylation in response to IR exposure and the relationship between histone acetylation and IR-induced chromosome damage remains unclear. Hence, this study investigated the variation in the total acetylation levels of H3 and H4 in human lymphocytes exposed to 0-2 Gy 60 Co γ-rays. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, was added to modify the histone acetylation state of irradiated cells. Then, the total acetylation level, enzyme activity, dicentric plus centric rings (dic + r) frequencies, and micronucleus (MN) frequencies of the treated cells were analyzed. Results indicated that the acetylation levels of H3 and H4 significantly decreased at 1 and 24 h, respectively, after radiation exposure. The acetylation levels of H3 and H4 in irradiated groups treated with SAHA were significantly higher than those in irradiated groups that were not treated with SAHA. SAHA treatment inhibited HDAC activity in cells exposed to 0-1 Gy 60 Co γ-rays. SAHA treatment significantly decreased dic + r/cell and MN/cell in cells exposed to 0.5 or 1.0 Gy 60 Co γ-rays relative to that in cells that did not receive SAHA treatment. In conclusion, histone acetylation is significantly affected by IR and is involved in chromosome damage induced by 60 Co γ-radiation.

The apoptotic effect and the plausible mechanism of microwave radiation on rat myocardial cells.

PubMed

Zhu, Wenhe; Cui, Yan; Feng, Xianmin; Li, Yan; Zhang, Wei; Xu, Junjie; Wang, Huiyan; Lv, Shijie

2016-08-01

Microwaves may exert adverse biological effects on the cardiovascular system at the integrated system and cellular levels. However, the mechanism underlying such effects remains poorly understood. Here, we report a previously uncharacterized mechanism through which microwaves damage myocardial cells. Rats were treated with 2450 MHz microwave radiation at 50, 100, 150, or 200 mW/cm(2) for 6 min. Microwave treatment significantly enhanced the levels of various enzymes in serum. In addition, it increased the malondialdehyde content while decreasing the levels of antioxidative stress enzymes, activities of enzyme complexes I-IV, and ATP in myocardial tissues. Notably, irradiated myocardial cells exhibited structural damage and underwent apoptosis. Furthermore, Western blot analysis revealed significant changes in expression levels of proteins involved in oxidative stress regulation and apoptotic signaling pathways, indicating that microwave irradiation could induce myocardial cell apoptosis by interfering with oxidative stress and cardiac energy metabolism. Our findings provide useful insights into the mechanism of microwave-induced damage to the cardiovascular system.

A novel methodology for self-healing at the nanoscale in CNT/epoxy composites

NASA Astrophysics Data System (ADS)

Quigley, E.; Datta, S.; Chattopadhyay, A.

2016-04-01

Self-healing materials have the potential to repair induced damage and extend the service life of aerospace or civil components as well as prevent catastrophic failure. A novel technique to provide self-healing capabilities at the nanoscale in carbon nanotube/epoxy nanocomposites is presented in this paper. Carbon nanotubes (CNTs) functionalized with the healing agent (dicyclopentadiene) were used to fabricate self-healing CNT/epoxy nanocomposite films. The structure of CNTs was considered suitable for this application since they are nanosized, hollow, and provide a more consistent size distribution than polymeric nanocapsules. Specimens with different weight fractions of the functionalized CNTs were fabricated to explore the effect of weight fraction of functionalized CNTs on the extent of healing. Optical micrographs with different fluorescent filters showed partial or complete healing of damage approximately two to three weeks after damage was induced. Results indicate that by using CNTs to encapsulate a healing agent, crack growth in self-healing CNT/epoxy nanocomposites can be retarded, leading to safer materials that can autonomously repair itself.

Protection against UVB-induced oxidative stress in human skin cells and skin models by methionine sulfoxide reductase A.

PubMed

Pelle, Edward; Maes, Daniel; Huang, Xi; Frenkel, Krystyna; Pernodet, Nadine; Yarosh, Daniel B; Zhang, Qi

2012-01-01

Environmental trauma to human skin can lead to oxidative damage of proteins and affect their activity and structure. When methionine becomes oxidized to its sulfoxide form, methionine sulfoxide reductase A (MSRA) reduces it back to methionine. We report here the increase in MSRA in normal human epidermal keratinocytes (NHEK) after ultraviolet B (UVB) radiation, as well as the reduction in hydrogen peroxide levels in NHEK pre-treated with MSRA after exposure. Further, when NHEK were pre-treated with a non-cytotoxic pentapeptide containing methionine sulfoxide (metSO), MSRA expression increased by 18.2%. Additionally, when the media of skin models were supplemented with the metSO pentapeptide and then exposed to UVB, a 31.1% reduction in sunburn cells was evident. We conclude that the presence of MSRA or an externally applied peptide reduces oxidative damage in NHEK and skin models and that MSRA contributes to the protection of proteins against UVB-induced damage in skin.

Hybrid molecular dynamics simulation for plasma induced damage analysis

NASA Astrophysics Data System (ADS)

Matsukuma, Masaaki

2016-09-01

In order to enable further device size reduction (also known as Moore's law) and improved power performance, the semiconductor industry is introducing new materials and device structures into the semiconductor fabrication process. Materials now include III-V compounds, germanium, cobalt, ruthenium, hafnium, and others. The device structure in both memory and logic has been evolving from planar to three dimensional (3D). One such device is the FinFET, where the transistor gate is a vertical fin made either of silicon, silicon-germanium or germanium. These changes have brought renewed interests in the structural damages caused by energetic ion bombardment of the fin sidewalls which are exposed to the ion flux from the plasma during the fin-strip off step. Better control of the physical damage of the 3D devices requires a better understanding of the damage formation mechanisms on such new materials and structures. In this study, the damage formation processes by ion bombardment have been simulated for Si and Ge substrate by Quantum Mechanics/Molecular Mechanics (QM/MM) hybrid simulations and compared to the results from the classical molecular dynamics (MD) simulations. In our QM/MM simulations, the highly reactive region in which the structural damage is created is simulated with the Density Functional based Tight Binding (DFTB) method and the region remote from the primary region is simulated using classical MD with the Stillinger-Weber and Moliere potentials. The learn on the fly method is also used to reduce the computational load. Hence our QM/MM simulation is much faster than the full QC-MD simulations and the original QM/MM simulations. The amorphous layers profile simulated with QM/MM have obvious differences in their thickness for silicon and germanium substrate. The profile of damaged structure in the germanium substrate is characterized by a deeper tail then in silicon. These traits are also observed in the results from the mass selected ion beam experiments. This observed damage profile dependence on species and substrate cannot be reproduced using classical MD simulations. While the Moliere potential is convenient to describe the interactions between halogens and other atoms, more accurate interatomic modeling such as DFTB method which takes the molecular orbitals into account should be utilized to make the simulations more realistic. Based on the simulations results, the damage formation scenario will be discussed.

Pushing the envelope: microinjection of Minute virus of mice into Xenopus oocytes causes damage to the nuclear envelope.

PubMed

Cohen, Sarah; Panté, Nelly

2005-12-01

Parvoviruses are small DNA viruses that replicate in the nucleus of their host cells. It has been largely assumed that parvoviruses enter the nucleus through the nuclear pore complex (NPC). However, the details of this mechanism remain undefined. To study this problem, the parvovirus Minute virus of mice (MVM) was microinjected into the cytoplasm of Xenopus oocytes and a transmission electron microscope was used to visualize the effect of the virus on the host cell. It was found that MVM caused damage to the nuclear envelope (NE) in a time- and concentration-dependent manner. Damage was predominantly to the outer nuclear membrane and was often near the NPCs. However, microinjection experiments in which the NPCs were blocked showed that NE damage induced by MVM was independent of the NPC. To address the question of whether this effect of MVM is specific to the NE, purified organelles were incubated with MVM. Visualization by electron microscopy revealed that MVM did not affect all intracellular membranes. These data represent a novel form of virus-induced damage to host cell nuclear structure and suggest that MVM is imported into the nucleus using a unique mechanism that is independent of the NPC, and involves disruption of the NE and import through the resulting breaks.

Mechanisms of carbon nanotube-induced toxicity: Focus on oxidative stress

PubMed Central

Shvedova, Anna A.; Pietroiusti, Antonio; Fadeel, Bengt; Kagan, Valerian E.

2015-01-01

Nanotechnologies are emerging as highly promising technologies in many sectors in the society. However, the increasing use of engineered nanomaterials also raises concerns about inadvertent exposure to these materials and the potential for adverse effects on human health and the environment. Despite several years of intensive investigations, a common paradigm for the understanding of nanoparticle-induced toxicity remains to be firmly established. Here, the so-called oxidative stress paradigm is scrutinized. Does oxidative stress represent a secondary event resulting inevitably from disruption of biochemical processes and the demise of the cell, or a specific, non-random event that plays a role in the induction of cellular damage e.g. apoptosis? The answer to this question will have important ramifications for the development of strategies for mitigation of adverse effects of nanoparticles. Recent examples of global lipidomics studies of nanoparticle-induced tissue damage are discussed along with proteomics and transcriptomics approaches to achieve a comprehensive understanding of the complex and interrelated molecular changes in cells and tissues exposed to nanoparticles. We also discuss instances of non-oxidative stress-mediated cellular damage resulting from direct physical interference of nanomaterials with cellular structures. PMID:22513272

A Coupled Multiphysics Approach for Simulating Induced Seismicity, Ground Acceleration and Structural Damage

NASA Astrophysics Data System (ADS)

Podgorney, Robert; Coleman, Justin; Wilkins, Amdrew; Huang, Hai; Veeraraghavan, Swetha; Xia, Yidong; Permann, Cody

2017-04-01

Numerical modeling has played an important role in understanding the behavior of coupled subsurface thermal-hydro-mechanical (THM) processes associated with a number of energy and environmental applications since as early as the 1970s. While the ability to rigorously describe all key tightly coupled controlling physics still remains a challenge, there have been significant advances in recent decades. These advances are related primarily to the exponential growth of computational power, the development of more accurate equations of state, improvements in the ability to represent heterogeneity and reservoir geometry, and more robust nonlinear solution schemes. The work described in this paper documents the development and linkage of several fully-coupled and fully-implicit modeling tools. These tools simulate: (1) the dynamics of fluid flow, heat transport, and quasi-static rock mechanics; (2) seismic wave propagation from the sources of energy release through heterogeneous material; and (3) the soil-structural damage resulting from ground acceleration. These tools are developed in Idaho National Laboratory's parallel Multiphysics Object Oriented Simulation Environment, and are integrated together using a global implicit approach. The governing equations are presented, the numerical approach for simultaneously solving and coupling the three coupling physics tools is discussed, and the data input and output methodology is outlined. An example is presented to demonstrate the capabilities of the coupled multiphysics approach. The example involves simulating a system conceptually similar to the geothermal development in Basel Switzerland, and the resultant induced seismicity, ground motion and structural damage is predicted.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rutqvist, Jonny; Cappa, Frédéric; Rinaldi, Antonio P.

In this paper, we present model simulations of ground motions caused by CO 2 -injection-induced fault reactivation and analyze the results in terms of the potential for damage to ground surface structures and nuisance to the local human population. It is an integrated analysis from cause to consequence, including the whole chain of processes starting from earthquake inception in the subsurface, wave propagation toward the ground surface, and assessment of the consequences of ground vibration. For a small magnitude (M w =3) event at a hypocenter depth of about 1000m, we first used the simulated ground-motion wave train in anmore » inverse analysis to estimate source parameters (moment magnitude, rupture dimensions and stress drop), achieving good agreement and thereby verifying the modeling of the chain of processes from earthquake inception to ground vibration. We then analyzed the ground vibration results in terms of peak ground acceleration (PGA), peak ground velocity (PGV) and frequency content, with comparison to U.S. Geological Survey's instrumental intensity scales for earthquakes and the U.S. Bureau of Mines' vibration criteria for cosmetic damage to buildings, as well as human-perception vibration limits. Our results confirm the appropriateness of using PGV (rather than PGA) and frequency for the evaluation of potential ground-vibration effects on structures and humans from shallow injection-induced seismic events. For the considered synthetic M w =3 event, our analysis showed that the short duration, high frequency ground motion may not cause any significant damage to surface structures, but would certainly be felt by the local population.« less

Method for detecting moment connection fracture using high-frequency transients in recorded accelerations

USGS Publications Warehouse

Rodgers, J.E.; Elebi, M.

2011-01-01

The 1994 Northridge earthquake caused brittle fractures in steel moment frame building connections, despite causing little visible building damage in most cases. Future strong earthquakes are likely to cause similar damage to the many un-retrofitted pre-Northridge buildings in the western US and elsewhere. Without obvious permanent building deformation, costly intrusive inspections are currently the only way to determine if major fracture damage that compromises building safety has occurred. Building instrumentation has the potential to provide engineers and owners with timely information on fracture occurrence. Structural dynamics theory predicts and scale model experiments have demonstrated that sudden, large changes in structure properties caused by moment connection fractures will cause transient dynamic response. A method is proposed for detecting the building-wide level of connection fracture damage, based on observing high-frequency, fracture-induced transient dynamic responses in strong motion accelerograms. High-frequency transients are short (<1 s), sudden-onset waveforms with frequency content above 25 Hz that are visually apparent in recorded accelerations. Strong motion data and damage information from intrusive inspections collected from 24 sparsely instrumented buildings following the 1994 Northridge earthquake are used to evaluate the proposed method. The method's overall success rate for this data set is 67%, but this rate varies significantly with damage level. The method performs reasonably well in detecting significant fracture damage and in identifying cases with no damage, but fails in cases with few fractures. Combining the method with other damage indicators and removing records with excessive noise improves the ability to detect the level of damage. ?? 2010 Elsevier B.V. All rights reserved.

The effect of magnetic and non-magnetic ion damage on the surface state in SmB 6

DOE PAGES

Wakeham, N.; Wen, J.; Wang, Y. Q.; ...

2015-07-14

SmB 6 is a Kondo insulator with a band structure that is topologically distinct from the vacuum. We theoretically predict this in order to produce metallic topological surface states that are robust to perturbations that do not break time reversal symmetry, such as non-magnetic defects. But, the surface state may be destroyed by an impurity with a sufficiently large magnetic moment. In order to test this prediction we show measurements of the resistance of the surface state of single crystals of SmB 6 with varying levels of damage induced by magnetic and non-magnetic ion irradiation. Finally, we find that atmore » a sufficiently high concentration of damage the surface state reconstructs below an amorphous damaged layer, whether the damage was caused by a magnetic or non-magnetic ion.« less

Health Monitoring System for Composite Structures

NASA Technical Reports Server (NTRS)

Tang, S. S.; Riccardella, P. C.; Andrews, R. J.; Grady, J. E.; Mucciaradi, A. N.

1996-01-01

An automated system was developed to monitor the health status of composites. It uses the vibration characteristics of composites to identify a component's damage condition. The vibration responses are characterized by a set of signal features defined in the time, frequency and spatial domains. The identification of these changes in the vibration characteristics corresponding to different health conditions was performed using pattern recognition principles. This allows efficient data reduction and interpretation of vast amounts of information. Test components were manufactured from isogrid panels to evaluate performance of the monitoring system. The components were damaged by impact to simulate different health conditions. Free vibration response was induced by a tap test on the test components. The monitoring system was trained using these free vibration responses to identify three different health conditions. They are undamaged vs. damaged, damage location and damage zone size. High reliability in identifying the correct component health condition was achieved by the monitoring system.

Multiscale Fatigue Life Prediction for Composite Panels

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Yarrington, Phillip W.; Arnold, Steven M.

2012-01-01

Fatigue life prediction capabilities have been incorporated into the HyperSizer Composite Analysis and Structural Sizing Software. The fatigue damage model is introduced at the fiber/matrix constituent scale through HyperSizer s coupling with NASA s MAC/GMC micromechanics software. This enables prediction of the micro scale damage progression throughout stiffened and sandwich panels as a function of cycles leading ultimately to simulated panel failure. The fatigue model implementation uses a cycle jumping technique such that, rather than applying a specified number of additional cycles, a specified local damage increment is specified and the number of additional cycles to reach this damage increment is calculated. In this way, the effect of stress redistribution due to damage-induced stiffness change is captured, but the fatigue simulations remain computationally efficient. The model is compared to experimental fatigue life data for two composite facesheet/foam core sandwich panels, demonstrating very good agreement.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Preston, Daniel N; Peterson, Paul D; Kien - Yin, Lee

Structural damage in energetic materials plays a significant role in the probability of nonshock initiation events. Damage may occur in the form of voids or cracks either within crystals or in binder-rich regions between crystals. These cracks affect whether hotspots generated by impact will quench or propagate under non-shock insult. For this study, we have separately engineered intracrystalline and inter-crystalline cracks in to the HMX-based PBX 9501. Intra-crystalline cracks were created by subjecting HMX to forward and reverse solid-to-solid phase transformations prior to formulation. Inter-crystalline cracks were induced by compressing formulated samples of PBX 9501 at an average strain ratemore » of 0.00285 S{sup -1}. Both sets of pre-damaged explosives were then impact tested using the LANL Type 12 Drop Weight-Impact Machine and their sensitivities compared to nondamaged PBX 9501. Results of these tests clearly show significant differences in sensitivity between damaged and non-damaged PBX 9501.« less

Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice

PubMed Central

Souza, M H L P; Lemos, H. Paula; Oliveira, R B; Cunha, F Q

2004-01-01

Background: Tumour necrosis factor α (TNF-α) is involved in non-steroidal anti-inflammatory drug induced gastropathy. Nitric oxide (NO) is a mediator of gastrointestinal mucosal defence but, paradoxically, it also contributes to mucosal damage. Aims: We optimised the C57BL/6 mouse model of indomethacin induced gastropathy to evaluate the role of TNF-α and inducible nitric oxide synthase (iNOS) generated NO in gastric damage and granulocyte infiltration using tumour necrosis factor receptor 1 (TNF-R1−/−) or iNOS (iNOS−/−) deficient mice. Methods: Different doses of indomethacin (2.5, 5, 10, 20 mg/kg) were administered and animals were assessed 6, 12, or 24 hours later. Gastric damage was measured by the sum of all erosions in the gastric mucosa, and gastric granulocyte infiltration was determined by myeloperoxidase (MPO) activity. Other groups of wild-type mice received thalidomide, dexamethasone, fucoidin, l-NAME, or 1400W, and then indomethacin was administered. Additionally, indomethacin was administered to TNF-R1−/− or iNOS−/−. Gastric damage and MPO activity were evaluated 12 hours later. Results: Indomethacin induced dose and time dependent gastric damage and increase in MPO activity in wild-type mice, with the greatest effect at a dose of 10 mg/kg and after 12 hours. Treatment with thalidomide, dexamethasone, or fucoidin reduced gastric damage and MPO activity induced by indomethacin. After indomethacin administration, TNF-R1−/− had less gastric damage and MPO activity than controls. Genetic (knockout mice) or pharmacological (1400W and l-NAME) inhibition of iNOS activity reduced indomethacin induced gastric damage, despite no reduction in MPO activity. Conclusion: TNF-α, acting via TNF-R1, is involved in indomethacin induced gastric damage and granulocyte infiltration. Furthermore, iNOS generated NO is involved in gastric damage induced by indomethacin. PMID:15138204

Re-examining the cause of the "Damage Belt" during the 1995 Kobe Earthquake

NASA Astrophysics Data System (ADS)

Matsushima, S.; Miyake, H.

2017-12-01

The 1995 Kobe earthquake caused devastating disaster which killed 6434 people and collapsed more than 1 million houses. The heavy damage was concentrated in a belt-like area, which was called the "Damage Belt". The cause of the "Damage Belt" was investigated by various researchers and it was found that it was a result of "The Basin-Edge Effect", which is the constructive interference of the direct S-wave with the basin-induced diffracted Rayleigh waves (Kawase, 1996). Matsushima and Kawase (2009) estimated the rupture model of the 1995 Kobe Earthquake by using 3-D reciprocal Green's functions and searching for the best fitting case by grid-search technique assuming plural rectangular strong motion generation areas (SMGAs) and succeeded to reproduce the high PGV area that corresponds to the "Damage Belt". In this study, we re-examine the cause of the "Damage Belt" by combining the estimated rupture model with the up-to-date 3-D velocity structure. The velocity structure of whole Japan has been modeled and is being modified occasionally by the Headquarters for Earthquake Research Promotion using the geological surveys conducted thoroughly by local governments as well as by large research projects since 1995. The very detailed velocity structure of the Osaka basin has been modeled by the Geological Survey of Japan, AIST (Horikawa et al., 2003; Sekiguchi et al., 2008). The aim of this study is to take in account of the different amplification characteristics due to the different velocity structure of the sediment from the seismic bedrock to the surface in Kobe, and investigate its effect to the results of the distribution of PGVs of the simulated ground motions.

Impact of different cleaning processes on the laser damage threshold of antireflection coatings for Z-Backlighter optics at Sandia National Laboratories

DOE Office of Scientific and Technical Information (OSTI.GOV)

Field, Ella; Bellum, John; Kletecka, Damon

We have examined how different cleaning processes affect the laser-induced damage threshold of antireflection coatings for large dimension, Z-Backlighter laser optics at Sandia National Laboratories. Laser damage thresholds were measured after the coatings were created, and again 4 months later to determine which cleaning processes were most effective. There is a nearly twofold increase in laser-induced damage threshold between the antireflection coatings that were cleaned and those that were not cleaned. Aging of the coatings after 4 months resulted in even higher laser-induced damage thresholds. Also, the laser-induced damage threshold results revealed that every antireflection coating had a high defectmore » density, despite the cleaning process used, which indicates that improvements to either the cleaning or deposition processes should provide even higher laser-induced damage thresholds.« less

Impact of different cleaning processes on the laser damage threshold of antireflection coatings for Z-Backlighter optics at Sandia National Laboratories

DOE PAGES

Field, Ella; Bellum, John; Kletecka, Damon

2014-11-06

We have examined how different cleaning processes affect the laser-induced damage threshold of antireflection coatings for large dimension, Z-Backlighter laser optics at Sandia National Laboratories. Laser damage thresholds were measured after the coatings were created, and again 4 months later to determine which cleaning processes were most effective. There is a nearly twofold increase in laser-induced damage threshold between the antireflection coatings that were cleaned and those that were not cleaned. Aging of the coatings after 4 months resulted in even higher laser-induced damage thresholds. Also, the laser-induced damage threshold results revealed that every antireflection coating had a high defectmore » density, despite the cleaning process used, which indicates that improvements to either the cleaning or deposition processes should provide even higher laser-induced damage thresholds.« less

Inspection Correlation Study of Ultrasonic-Based In Situ Structural Health Monitoring Monthly Report for December 2014-January 2015

DTIC Science & Technology

2015-05-01

fatigue an induced ultrasonic elastic vibration (via piezoelectric transducers [ PZTs ]) propagates through the dogbone specimen. A receiver PZT picks up...inspection of fatigue crack growth in aluminum 7075-T6 dogbone specimens. Acellent Technologies, Inc., is supporting this project through providing...January 2015. 15. SUBJECT TERMS structural health monitoring, probabilistics, fatigue damage, guided waves, Lamb waves 16. SECURITY CLASSIFICATION OF

Damage of photoreceptor-derived cells in culture induced by light emitting diode-derived blue light

PubMed Central

Kuse, Yoshiki; Ogawa, Kenjiro; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki

2014-01-01

Our eyes are increasingly exposed to light from the emitting diode (LED) light of video display terminals (VDT) which contain much blue light. VDTs are equipped with televisions, personal computers, and smart phones. The present study aims to clarify the mechanism underlying blue LED light-induced photoreceptor cell damage. Murine cone photoreceptor-derived cells (661 W) were exposed to blue, white, or green LED light (0.38 mW/cm2). In the present study, blue LED light increased reactive oxygen species (ROS) production, altered the protein expression level, induced the aggregation of short-wavelength opsins (S-opsin), resulting in severe cell damage. While, blue LED light damaged the primary retinal cells and the damage was photoreceptor specific. N-Acetylcysteine (NAC), an antioxidant, protected against the cellular damage induced by blue LED light. Overall, the LED light induced cell damage was wavelength-, but not energy-dependent and may cause more severe retinal photoreceptor cell damage than the other LED light. PMID:24909301

Detection of vesicant-induced upper airway mucosa damage in the hamster cheek pouch model using optical coherence tomography.

PubMed

Hammer-Wilson, Marie J; Nguyen, Vi; Jung, Woong-Gyu; Ahn, Yehchen; Chen, Zhongping; Wilder-Smith, Petra

2010-01-01

Hamster cheek pouches were exposed to 2-chloroethyl ethyl sulfide [CEES, half-mustard gas (HMG)] at a concentration of 0.4, 2.0, or 5.0 mg/ml for 1 or 5 min. Twenty-four hours post-HMG exposure, tissue damage was assessed by both stereomicrography and optical coherence tomography (OCT). Damage that was not visible on gross visual examination was apparent in the OCT images. Tissue changes were found to be dependent on both HMG concentration and exposure time. The submucosal and muscle layers of the cheek pouch tissue showed the greatest amount of structural alteration. Routine light microscope histology was performed to confirm the OCT observations.

Investigation of high temperature annealing effectiveness for recovery of radiation-induced structural changes and properties of 18Cr-10Ni-Ti austenitic stainless steels

NASA Astrophysics Data System (ADS)

Gurovich, B. A.; Kuleshova, E. A.; Frolov, A. S.; Maltsev, D. A.; Prikhodko, K. E.; Fedotova, S. V.; Margolin, B. Z.; Sorokin, A. A.

2015-10-01

A complex study of structural state and properties of 18Cr-10Ni-Ti austenitic stainless steel after irradiation in BOR-60 fast research reactor (in the temperature range 330-400 °С up to damaging doses of 145 dpa) and in VVER-1000 light water reactor (at temperature ∼320 °С and damaging doses ∼12-14 dpa) was performed. The possibility of recovery of structural-phase state and mechanical properties to the level almost corresponding to the initial state by the recovery annealing was studied. The principal possibility of the recovery annealing of pressurized water reactor internals that ensures almost complete recovery of its mechanical properties and microstructure was shown. The optimal mode of recovery annealing was established: 1000 °C during 120 h.

Using structures of the August 24, 2016 Amatrice earthquake affected area as seismoscopes for assessing ground motion characteristics and parameters of the main shock and its largest aftershocks

NASA Astrophysics Data System (ADS)

Carydis, Panayotis; Lekkas, Efthymios; Mavroulis, Spyridon

2017-04-01

On August 24, 2016 an Mw 6.0 earthquake struck Central Apennines (Italy) resulting in 299 fatalities, 388 injuries and about 3000 homeless in Amatrice wider area. Normal faulting surface ruptures along the western slope of Mt Vettore along with provided focal mechanisms demonstrated a NW-SE striking and SE dipping causative normal fault. The dominant building types in the affected area are unreinforced masonry (URM) and reinforced concrete (RC) buildings. Based on our macroseismic survey in the affected area immediately after the earthquake, RC buildings suffered non-structural damage including horizontal cracking of infill and internal partition walls, detachment of infill walls from the surrounding RC frame and detachment of large plaster pieces from infill walls as well as structural damage comprising soft story failure, symmetrical buckling of rods, compression damage at midheight of columns and bursting of over-stressed columns resulting in partial or total collapse. Damage in RC buildings was due to poor quality of concrete, inadequacy of reinforcement, inappropriate foundation close to the edge of slopes leading to differential settlements, poor workmanship and the destructive effect of vertical ground motions. Damage in URM buildings ranged from cracks and detachment of large plaster pieces from load-bearing walls to destruction due to poor workmanship with randomly placed materials bound by low-strength mortars, the effect of the vertical ground motion, inadequate repair and/or strengthening after previous earthquakes as well as inadequate interventions, additions and extensions to older URM buildings. During field surveying, the authors had the opportunity to observe damage induced not only by the main shock but also by its largest aftershocks (Mw 4.5-5.3) during the first three days of the aftershock sequence (August 24-26). Bearing in mind that: (a) soil conditions in foundations of the affected villages were more or less similar, (b) building damage induced by the studied earthquakes indicated the predominant effect of the vertical ground motion on buildings based on already reported building damage induced by recent destructive events in the Mediterranean region, (c) the conventional dynamic parameters of buildings did not play a significant role in their seismic response against the vertical component, due to its impact type of loading, (d) structures and materials presented similar response to ground motions almost independent from type and existing quality, and carried memories from previous large shocks of this sequence, (e) the main shock and its largest aftershocks caused building damage including spatial homothetic motions that reached statistically significant levels, it is concluded that the main shock and its largest aftershocks had similar focal mechanism parameters (normal faulting), were shallow events and were near-field earthquakes with short duration but high amplitude and the vertical component of the earthquakes' ground motion has prevailed. The aforementioned approach based solely on macroseismic observations was applied in the case of the 1755 Great Lisbon earthquake in order to determine its mechanism and epicenter location. Thus, it is suggested that the aforementioned methodology can be applied either in past historic earthquakes or complementarily in cases when the available seismological data are insufficient.

Mitochondrial Modulation by Epigallocatechin 3-Gallate Ameliorates Cisplatin Induced Renal Injury through Decreasing Oxidative/Nitrative Stress, Inflammation and NF-kB in Mice

PubMed Central

Wang, Xueping; Wang, Ping; Fu, Guanghou; Meng, Hongzhou; Wang, Yimin; Jin, Baiye

2015-01-01

Cancer chemotherapy drug cisplatin is known for its nephrotoxicity. The aim of this study is to investigate whether Epigallocatechin 3-Gallate (EGCG) can reduce cisplatin mediated side effect in kidney and to understand its mechanism of protection against tissue injury. We used a well-established 3-day cisplatin induced nephrotoxicity mice model where EGCG were administered. EGCG is a major active compound in Green Tea and have strong anti-oxidant and anti-inflammatory properties. EGCG protected against cisplatin induced renal dysfunction as measured by serum creatinine and blood urea nitrogen (BUN). EGCG improved cisplatin induced kidney structural damages such as tubular dilatation, cast formation, granulovaculoar degeneration and tubular cell necrosis as evident by PAS staining. Cisplatin induced kidney specific mitochondrial oxidative stress, impaired activities of mitochondrial electron transport chain enzyme complexes, impaired anti-oxidant defense enzyme activities such as glutathione peroxidase (GPX) and manganese superoxide dismutase (MnSOD) in mitochondria, inflammation (tumor necrosis factor α and interleukin 1β), increased accumulation of NF-κB in nuclear fraction, p53 induction, and apoptotic cell death (caspase 3 activity and DNA fragmentation). Treatment of mice with EGCG markedly attenuated cisplatin induced mitochondrial oxidative/nitrative stress, mitochondrial damages to electron transport chain activities and antioxidant defense enzyme activities in mitochondria. These mitochondrial modulations by EGCG led to protection mechanism against cisplatin induced inflammation and apoptotic cell death in mice kidney. As a result, EGCG improved renal function in cisplatin mediated kidney damage. In addition to that, EGCG attenuated cisplatin induced apoptotic cell death and mitochondrial reactive oxygen species (ROS) generation in human kidney tubular cell line HK-2. Thus, our data suggest that EGCG may represent new promising adjunct candidate for cisplatin. PMID:25875356

Effects of oxidative stress-induced changes in the actin cytoskeletal structure on myoblast damage under compressive stress: confocal-based cell-specific finite element analysis.

PubMed

Yao, Yifei; Lacroix, Damien; Mak, Arthur F T

2016-12-01

Muscle cells are frequently subjected to both mechanical and oxidative stresses in various physiological and pathological situations. To explore the mechanical mechanism of muscle cell damage under loading and oxidative stresses, we experimentally studied the effects of extrinsic hydrogen peroxides on the actin cytoskeletal structure in C2C12 myoblasts and presented a finite element (FE) analysis of how such changes in the actin cytoskeletal structure affected a myoblast's capability to resist damage under compression. A confocal-based cell-specific FE model was built to parametrically study the effects of stress fiber density, fiber cross-sectional area, fiber tensile prestrain, as well as the elastic moduli of the stress fibers, actin cortex, nucleus and cytoplasm. The results showed that a decrease in the elastic moduli of both the stress fibers and actin cortex could increase the average tensile strain on the actin cortex-membrane structure and reduce the apparent cell elastic modulus. Assuming the cell would die when a certain percentage of membrane elements were strained beyond a threshold, a lower elastic modulus of actin cytoskeleton would compromise the compressive resistance of a myoblast and lead to cell death more readily. This model was used with a Weibull distribution function to successfully describe the extent of myoblasts damaged in a monolayer under compression.

Molecular mechanisms by which oxidative DNA damage promotes telomerase activity.

PubMed

Lee, Hui-Ting; Bose, Arindam; Lee, Chun-Ying; Opresko, Patricia L; Myong, Sua

2017-11-16

Telomeres are highly susceptible to oxidative DNA damage, which if left unrepaired can lead to dysregulation of telomere length homeostasis. Here we employed single molecule FRET, single molecule pull-down and biochemical analysis to investigate how the most common oxidative DNA lesions, 8-oxoguanine (8oxoG) and thymine glycol (Tg), regulate the structural properties of telomeric DNA and telomerase extension activity. In contrast to 8oxoG which disrupts the telomeric DNA structure, Tg exhibits substantially reduced perturbation of G-quadruplex folding. As a result, 8oxoG induces high accessibility, whereas Tg retains limited accessibility, of telomeric G-quadruplex DNA to complementary single stranded DNA and to telomere binding protein POT1. Surprisingly, the Tg lesion stimulates telomerase loading and activity to a similar degree as an 8oxoG lesion. We demonstrate that this unexpected stimulation arises from Tg-induced conformational alterations and dynamics in telomeric DNA. Despite impacting structure by different mechanisms, both 8oxoG and Tg enhance telomerase binding and extension activity to the same degree, potentially contributing to oncogenesis. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

HYPOTHYRODISM INDUCED BY EARLY POSTNATAL EXPOSURE TO PROPYLTHIOURACIL IMPAIRS SYNAPTIC TRANSMISSION IN VIVO IN THE HIPPOCAMPUS OF THE ADULT RAT.

EPA Science Inventory

Thyroid hormones are essential for maturation and function of the mammalian central nervous system. Severe congenital hypothyroidism results in irreversible structural damage and mental retardation in children. Although a variety of environmental contaminants have been demonstrat...

Reducing seismic risk to highway mobility : assessment and design of pile foundations affected by lateral loading.

DOT National Transportation Integrated Search

2013-04-01

Damage in pile supported structures due to liquefaction and liquefaction induced deformation were reported in past earthquakes around the world (eg, Ansal et al. 1999, Seed et al. 1990, EERI 2010, EERI 2011, GEER 2010a, GEER 2010b, GEER 2011). For ex...

Indirect diagnosis of pavement structural damages using surface GPR reflection techniques

NASA Astrophysics Data System (ADS)

Benedetto, A.; Pensa, S.

2007-06-01

The safety and operability of road networks is, in part, dependent on the quality of the pavement. It is known that pavements suffer from many different structural problems which can lead to damage to the pavement surface. To minimize the effect of these problems programmed policies for pavement management are required. Additionally a given local anomaly on the road surface can affect the safety of the road to various degrees according to the category of the road, so it is possible to set up different programmes of repair according to the different standards of road. Programmed policies for pavement management are required because of the wide structural damage which occurs to pavements during their normal operating life. This has consequences for the safety and operability of road networks. During the last decade, road networks suffered from great structural damage. The damage occurs for different reasons, such as the increasing traffic or the lack of means for routine maintenance. Many forms of damage, originating in the bottom layers are invisible until the pavement cracks. They depend on the infiltration of water and the presence of cohesive soil greatly reduces the bearing capacity of the sub-asphalt layers and underlying soils. On the basis of an in-depth literature review, an experimental survey with Ground Penetrating Radar (GPR) was carried out to calibrate the geophysical parameters and to validate the reliability of an indirect diagnostic method of pavement damage. The experiments were set on a pavement under which water was injected over a period of several hours. GPR travel time data were used to estimate the dielectric constant and the water content in the unbound aggregate layer, the variations in water content with time and particular areas where rate of infiltration decreases. A new methodology has been proposed to extract the hydraulic permittivity fields in sub-asphalt structural layers and soils from the moisture maps observed with GPR. It is effective at diagnosing the presence of clay or cohesive soil that compromises the bearing capacity of sub-base and induces damage.

Functional characterization of two SOS-regulated genes involved in mitomycin C resistance in Caulobacter crescentus.

PubMed

Lopes-Kulishev, Carina O; Alves, Ingrid R; Valencia, Estela Y; Pidhirnyj, María I; Fernández-Silva, Frank S; Rodrigues, Ticiane R; Guzzo, Cristiane R; Galhardo, Rodrigo S

2015-09-01

The SOS response is a universal bacterial regulon involved in the cellular response to DNA damage and other forms of stress. In Caulobacter crescentus, previous work has identified a plethora of genes that are part of the SOS regulon, but the biological roles of several of them remain to be determined. In this study, we report that two genes, hereafter named mmcA and mmcB, are involved in the defense against DNA damage caused by mitomycin C (MMC), but not against lesions induced by other common DNA damaging agents, such as UVC light, methyl methanesulfonate (MMS) and hydrogen peroxide. mmcA is a conserved gene that encodes a member of the glyoxalases/dioxygenases protein family, and acts independently of known DNA repair pathways. On the other hand, epistasis analysis showed that mmcB acts in the same pathway as imuC (dnaE2), and is required specifically for MMC-induced mutagenesis, but not for that induced by UV light, suggesting a role for MmcB in translesion synthesis-dependent repair of MMC damage. We show that the lack of MMC-induced mutability in the mmcB strain is not caused by lack of proper SOS induction of the imuABC operon, involved in translesion synthesis (TLS) in C. crescentus. Based on this data and on structural analysis of a close homolog, we propose that MmcB is an endonuclease which creates substrates for ImuABC-mediated TLS patches. Copyright © 2015 Elsevier B.V. All rights reserved.

Reversible Disruption of Neuronal Mitochondria by Ischemic and Traumatic Injury Revealed by Quantitative Two-Photon Imaging in the Neocortex of Anesthetized Mice

PubMed Central

Kislin, Mikhail; Sword, Jeremy; Fomitcheva, Ioulia V.; Croom, Deborah; Pryazhnikov, Evgeny; Lihavainen, Eero; Toptunov, Dmytro; Rauvala, Heikki; Ribeiro, Andre S.

2017-01-01

Mitochondria play a variety of functional roles in cortical neurons, from metabolic support and neuroprotection to the release of cytokines that trigger apoptosis. In dendrites, mitochondrial structure is closely linked to their function, and fragmentation (fission) of the normally elongated mitochondria indicates loss of their function under pathological conditions, such as stroke and brain trauma. Using in vivo two-photon microscopy in mouse brain, we quantified mitochondrial fragmentation in a full spectrum of cortical injuries, ranging from severe to mild. Severe global ischemic injury was induced by bilateral common carotid artery occlusion, whereas severe focal stroke injury was induced by Rose Bengal photosensitization. The moderate and mild traumatic injury was inflicted by focal laser lesion and by mild photo-damage, respectively. Dendritic and mitochondrial structural changes were tracked longitudinally using transgenic mice expressing fluorescent proteins localized either in cytosol or in mitochondrial matrix. In response to severe injury, mitochondrial fragmentation developed in parallel with dendritic damage signified by dendritic beading. Reconstruction from serial section electron microscopy confirmed mitochondrial fragmentation. Unlike dendritic beading, fragmentation spread beyond the injury core in focal stroke and focal laser lesion models. In moderate and mild injury, mitochondrial fragmentation was reversible with full recovery of structural integrity after 1–2 weeks. The transient fragmentation observed in the mild photo-damage model was associated with changes in dendritic spine density without any signs of dendritic damage. Our findings indicate that alterations in neuronal mitochondria structure are very sensitive to the tissue damage and can be reversible in ischemic and traumatic injuries. SIGNIFICANCE STATEMENT During ischemic stroke or brain trauma, mitochondria can either protect neurons by supplying ATP and adsorbing excessive Ca2+, or kill neurons by releasing proapoptotic factors. Mitochondrial function is tightly linked to their morphology: healthy mitochondria are thin and long; dysfunctional mitochondria are thick (swollen) and short (fragmented). To date, fragmentation of mitochondria was studied either in dissociated cultured neurons or in brain slices, but not in the intact living brain. Using real-time in vivo two-photon microscopy, we quantified mitochondrial fragmentation during acute pathological conditions that mimic severe, moderate, and mild brain injury. We demonstrated that alterations in neuronal mitochondria structural integrity can be reversible in traumatic and ischemic injuries, highlighting mitochondria as a potential target for therapeutic interventions. PMID:28077713

Factors influencing heterogeneity of radiation-induced DNA-damage measured by the alkaline comet assay.

PubMed

Seidel, Clemens; Lautenschläger, Christine; Dunst, Jürgen; Müller, Arndt-Christian

2012-04-20

To investigate whether different conditions of DNA structure and radiation treatment could modify heterogeneity of response. Additionally to study variance as a potential parameter of heterogeneity for radiosensitivity testing. Two-hundred leukocytes per sample of healthy donors were split into four groups. I: Intact chromatin structure; II: Nucleoids of histone-depleted DNA; III: Nucleoids of histone-depleted DNA with 90 mM DMSO as antioxidant. Response to single (I-III) and twice (IV) irradiation with 4 Gy and repair kinetics were evaluated using %Tail-DNA. Heterogeneity of DNA damage was determined by calculation of variance of DNA-damage (V) and mean variance (Mvar), mutual comparisons were done by one-way analysis of variance (ANOVA). Heterogeneity of initial DNA-damage (I, 0 min repair) increased without histones (II). Absence of histones was balanced by addition of antioxidants (III). Repair reduced heterogeneity of all samples (with and without irradiation). However double irradiation plus repair led to a higher level of heterogeneity distinguishable from single irradiation and repair in intact cells. Increase of mean DNA damage was associated with a similarly elevated variance of DNA damage (r = +0.88). Heterogeneity of DNA-damage can be modified by histone level, antioxidant concentration, repair and radiation dose and was positively correlated with DNA damage. Experimental conditions might be optimized by reducing scatter of comet assay data by repair and antioxidants, potentially allowing better discrimination of small differences. Amount of heterogeneity measured by variance might be an additional useful parameter to characterize radiosensitivity.

Spectral algorithm for non-destructive damage localisation: Application to an ancient masonry arch model

NASA Astrophysics Data System (ADS)

Masciotta, Maria-Giovanna; Ramos, Luís F.; Lourenço, Paulo B.; Vasta, Marcello

2017-02-01

Structural monitoring and vibration-based damage identification methods are fundamental tools for condition assessment and early-stage damage identification, especially when dealing with the conservation of historical constructions and the maintenance of strategic civil structures. However, although the substantial advances in the field, several issues must still be addressed to broaden the application range of such tools and to assert their reliability. This study deals with the experimental validation of a novel method for non-destructive damage identification purposes. This method is based on the use of spectral output signals and has been recently validated by the authors through a numerical simulation. After a brief insight into the basic principles of the proposed approach, the spectral-based technique is applied to identify the experimental damage induced on a masonry arch through statically increasing loading. Once the direct and cross spectral density functions of the nodal response processes are estimated, the system's output power spectrum matrix is built and decomposed in eigenvalues and eigenvectors. The present study points out how the extracted spectral eigenparameters contribute to the damage analysis allowing to detect the occurrence of damage and to locate the target points where the cracks appear during the experimental tests. The sensitivity of the spectral formulation to the level of noise in the modal data is investigated and discussed. As a final evaluation criterion, the results from the spectrum-driven method are compared with the ones obtained from existing non-model based damage identification methods.

Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation

NASA Technical Reports Server (NTRS)

Sutherland, B. M.; Bennett, P. V.; Sidorkina, O.; Laval, J.; Lowenstein, D. I. (Principal Investigator)

2000-01-01

Clustered DNA damages-two or more closely spaced damages (strand breaks, abasic sites, or oxidized bases) on opposing strands-are suspects as critical lesions producing lethal and mutagenic effects of ionizing radiation. However, as a result of the lack of methods for measuring damage clusters induced by ionizing radiation in genomic DNA, neither the frequencies of their production by physiological doses of radiation, nor their repairability, nor their biological effects are known. On the basis of methods that we developed for quantitating damages in large DNAs, we have devised and validated a way of measuring ionizing radiation-induced clustered lesions in genomic DNA, including DNA from human cells. DNA is treated with an endonuclease that induces a single-strand cleavage at an oxidized base or abasic site. If there are two closely spaced damages on opposing strands, such cleavage will reduce the size of the DNA on a nondenaturing gel. We show that ionizing radiation does induce clustered DNA damages containing abasic sites, oxidized purines, or oxidized pyrimidines. Further, the frequency of each of these cluster classes is comparable to that of frank double-strand breaks; among all complex damages induced by ionizing radiation, double-strand breaks are only about 20%, with other clustered damage constituting some 80%. We also show that even low doses (0.1-1 Gy) of high linear energy transfer ionizing radiation induce clustered damages in human cells.

Laser-based structural sensing and surface damage detection

NASA Astrophysics Data System (ADS)

Guldur, Burcu

Damage due to age or accumulated damage from hazards on existing structures poses a worldwide problem. In order to evaluate the current status of aging, deteriorating and damaged structures, it is vital to accurately assess the present conditions. It is possible to capture the in situ condition of structures by using laser scanners that create dense three-dimensional point clouds. This research investigates the use of high resolution three-dimensional terrestrial laser scanners with image capturing abilities as tools to capture geometric range data of complex scenes for structural engineering applications. Laser scanning technology is continuously improving, with commonly available scanners now capturing over 1,000,000 texture-mapped points per second with an accuracy of ~2 mm. However, automatically extracting meaningful information from point clouds remains a challenge, and the current state-of-the-art requires significant user interaction. The first objective of this research is to use widely accepted point cloud processing steps such as registration, feature extraction, segmentation, surface fitting and object detection to divide laser scanner data into meaningful object clusters and then apply several damage detection methods to these clusters. This required establishing a process for extracting important information from raw laser-scanned data sets such as the location, orientation and size of objects in a scanned region, and location of damaged regions on a structure. For this purpose, first a methodology for processing range data to identify objects in a scene is presented and then, once the objects from model library are correctly detected and fitted into the captured point cloud, these fitted objects are compared with the as-is point cloud of the investigated object to locate defects on the structure. The algorithms are demonstrated on synthetic scenes and validated on range data collected from test specimens and test-bed bridges. The second objective of this research is to combine useful information extracted from laser scanner data with color information, which provides information in the fourth dimension that enables detection of damage types such as cracks, corrosion, and related surface defects that are generally difficult to detect using only laser scanner data; moreover, the color information also helps to track volumetric changes on structures such as spalling. Although using images with varying resolution to detect cracks is an extensively researched topic, damage detection using laser scanners with and without color images is a new research area that holds many opportunities for enhancing the current practice of visual inspections. The aim is to combine the best features of laser scans and images to create an automatic and effective surface damage detection method, which will reduce the need for skilled labor during visual inspections and allow automatic documentation of related information. This work enables developing surface damage detection strategies that integrate existing condition rating criteria for a wide range damage types that are collected under three main categories: small deformations already existing on the structure (cracks); damage types that induce larger deformations, but where the initial topology of the structure has not changed appreciably (e.g., bent members); and large deformations where localized changes in the topology of the structure have occurred (e.g., rupture, discontinuities and spalling). The effectiveness of the developed damage detection algorithms are validated by comparing the detection results with the measurements taken from test specimens and test-bed bridges.

Numerical modeling of the load effect on PZT-induced guided wave for load compensation of damage detection

NASA Astrophysics Data System (ADS)

Sun, Hu; Zhang, Aijia; Wang, Yishou; Qing, Xinlin P.

2017-04-01

Guided wave-based structural health monitoring (SHM) has been given considerable attention and widely studied for large-scale aircraft structures. Nevertheless, it is difficult to apply SHM systems on board or online, for which one of the most serious reasons is the environmental influence. Load is one fact that affects not only the host structure, in which guided wave propagates, but also the PZT, by which guided wave is transmitted and received. In this paper, numerical analysis using finite element method is used to study the load effect on guided wave acquired by PZT. The static loads with different grades are considered to analyze its effect on guided wave signals that PZT transmits and receives. Based on the variation trend of guided waves versus load, a load compensation method is developed to eliminate effects of load in the process of damage detection. The probabilistic reconstruction algorithm based on the signal variation of transmitter-receiver path is employed to identify the damage. Numerical tests is conducted to verify the feasibility and effectiveness of the given method.

Inflammation-Induced Cell Proliferation Potentiates DNA Damage-Induced Mutations In Vivo

PubMed Central

Kiraly, Orsolya; Gong, Guanyu; Olipitz, Werner; Muthupalani, Sureshkumar; Engelward, Bevin P.

2015-01-01

Mutations are a critical driver of cancer initiation. While extensive studies have focused on exposure-induced mutations, few studies have explored the importance of tissue physiology as a modulator of mutation susceptibility in vivo. Of particular interest is inflammation, a known cancer risk factor relevant to chronic inflammatory diseases and pathogen-induced inflammation. Here, we used the fluorescent yellow direct repeat (FYDR) mice that harbor a reporter to detect misalignments during homologous recombination (HR), an important class of mutations. FYDR mice were exposed to cerulein, a potent inducer of pancreatic inflammation. We show that inflammation induces DSBs (γH2AX foci) and that several days later there is an increase in cell proliferation. While isolated bouts of inflammation did not induce HR, overlap between inflammation-induced DNA damage and inflammation-induced cell proliferation induced HR significantly. To study exogenously-induced DNA damage, animals were exposed to methylnitrosourea, a model alkylating agent that creates DNA lesions relevant to both environmental exposures and cancer chemotherapy. We found that exposure to alkylation damage induces HR, and importantly, that inflammation-induced cell proliferation and alkylation induce HR in a synergistic fashion. Taken together, these results show that, during an acute bout of inflammation, there is a kinetic barrier separating DNA damage from cell proliferation that protects against mutations, and that inflammation-induced cell proliferation greatly potentiates exposure-induced mutations. These studies demonstrate a fundamental mechanism by which inflammation can act synergistically with DNA damage to induce mutations that drive cancer and cancer recurrence. PMID:25647331

Advances in Structural Integrity Analysis Methods for Aging Metallic Airframe Structures with Local Damage

NASA Technical Reports Server (NTRS)

Starnes, James H., Jr.; Newman, James C., Jr.; Harris, Charles E.; Piascik, Robert S.; Young, Richard D.; Rose, Cheryl A.

2003-01-01

Analysis methodologies for predicting fatigue-crack growth from rivet holes in panels subjected to cyclic loads and for predicting the residual strength of aluminum fuselage structures with cracks and subjected to combined internal pressure and mechanical loads are described. The fatigue-crack growth analysis methodology is based on small-crack theory and a plasticity induced crack-closure model, and the effect of a corrosive environment on crack-growth rate is included. The residual strength analysis methodology is based on the critical crack-tip-opening-angle fracture criterion that characterizes the fracture behavior of a material of interest, and a geometric and material nonlinear finite element shell analysis code that performs the structural analysis of the fuselage structure of interest. The methodologies have been verified experimentally for structures ranging from laboratory coupons to full-scale structural components. Analytical and experimental results based on these methodologies are described and compared for laboratory coupons and flat panels, small-scale pressurized shells, and full-scale curved stiffened panels. The residual strength analysis methodology is sufficiently general to include the effects of multiple-site damage on structural behavior.

A tissue phantom for visualization and measurement of ultrasound-induced cavitation damage.

PubMed

Maxwell, Adam D; Wang, Tzu-Yin; Yuan, Lingqian; Duryea, Alexander P; Xu, Zhen; Cain, Charles A

2010-12-01

Many ultrasound studies involve the use of tissue-mimicking materials to research phenomena in vitro and predict in vivo bioeffects. We have developed a tissue phantom to study cavitation-induced damage to tissue. The phantom consists of red blood cells suspended in an agarose hydrogel. The acoustic and mechanical properties of the gel phantom were found to be similar to soft tissue properties. The phantom's response to cavitation was evaluated using histotripsy. Histotripsy causes breakdown of tissue structures by the generation of controlled cavitation using short, focused, high-intensity ultrasound pulses. Histotripsy lesions were generated in the phantom and kidney tissue using a spherically focused 1-MHz transducer generating 15 cycle pulses, at a pulse repetition frequency of 100 Hz with a peak negative pressure of 14 MPa. Damage appeared clearly as increased optical transparency of the phantom due to rupture of individual red blood cells. The morphology of lesions generated in the phantom was very similar to that generated in kidney tissue at both macroscopic and cellular levels. Additionally, lesions in the phantom could be visualized as hypoechoic regions on a B-mode ultrasound image, similar to histotripsy lesions in tissue. High-speed imaging of the optically transparent phantom was used to show that damage coincides with the presence of cavitation. These results indicate that the phantom can accurately mimic the response of soft tissue to cavitation and provide a useful tool for studying damage induced by acoustic cavitation. Copyright © 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Damage Simulation in Composite Materials: Why It Matters and What Is Happening Currently at NASA in This Area

NASA Technical Reports Server (NTRS)

McElroy, Mack; de Carvalho, Nelson; Estes, Ashley; Lin, Shih-yung

2017-01-01

Use of lightweight composite materials in space and aircraft structure designs is often challenging due to high costs associated with structural certification. Of primary concern in the use of composite structures is durability and damage tolerance. This concern is due to the inherent susceptibility of composite materials to both fabrication and service induced flaws. Due to a lack of general industry accepted analysis tools applicable to composites damage simulation, a certification procedure relies almost entirely on testing. It is this reliance on testing, especially compared to structures comprised of legacy metallic materials where damage simulation tools are available, that can drive costs for using composite materials in aerospace structures. The observation that use of composites can be expensive due to testing requirements is not new and as such, research on analysis tools for simulating damage in composite structures has been occurring for several decades. A convenient approach many researchers/model-developers in this area have taken is to select a specific problem relevant to aerospace structural certification and develop a model that is accurate within that scope. Some examples are open hole tension tests, compression after impact tests, low-velocity impact, damage tolerance of an embedded flaw, and fatigue crack growth to name a few. Based on the premise that running analyses is cheaper than running tests, one motivation that many researchers in this area have is that if generally applicable and reliable damage simulation tools were available the dependence on certification testing could be lessened thereby reducing overall design cost. It is generally accepted that simulation tools if applied in this manner would still need to be thoroughly validated and that composite testing will never be completely replaced by analysis. Research and development is currently occurring at NASA to create numerical damage simulation tools applicable to damage in composites. The Advanced Composites Project (ACP) at NASA Langley has supported the development of composites damage simulation tools in a consortium of aerospace companies with a goal of reducing the certification time of a commercial aircraft by 30%. And while the scope of ACP does not include spacecraft, much of the methodology and simulation capabilities can apply to spacecraft certification in the Space Launch System and Orion programs as well. Some specific applications of composite damage simulation models in a certification program are (1) evaluation of damage during service when maintenance may be difficult or impossible, (2) a tool for early design iterations, (3) gaining insight into a particular damage process and applying this insight towards a test coupon or structural design, and (4) analysis of damage scenarios that are difficult or impossible to recreate in a test. As analysis capabilities improve, these applications and more will become realized resulting in a reduction in cost for use of composites in aerospace vehicles. NASA is engaged in this process from both research and application perspectives. In addition to the background information discussed previously, this presentation covers a look at recent research at NASA in this area and some current/potential applications in the Orion program.

Rainstorms able to induce flash floods in a Mediterranean-climate region (Calabria, southern Italy)

NASA Astrophysics Data System (ADS)

Terranova, O. G.; Gariano, S. L.

2014-03-01

Heavy rainstorms often induce flash flooding, one of the natural disasters most responsible for damage to man-made infrastructure and loss of lives, adversely affecting also the opportunities for socio-economic development of Mediterranean Countries. The frequently dramatic damage of flash floods are often detected with sufficient accuracy by post-event surveys, but rainfall causing them are still only roughly characterized. With the aim of improving the understanding of the temporal structure and spatial distribution of heavy rainstorms in the Mediterranean context, a statistical analysis was carried out in Calabria (southern Italy) concerning rainstorms that mainly induced flash floods, but also shallow landslides and debris-flows. Thus a method is proposed - based on the overcoming of heuristically predetermined threshold values of cumulated rainfall, maximum intensity, and kinetic energy of the rainfall event - to select and characterize the rainstorms able to induce flash floods in the Mediterranean-climate Countries. Therefore the obtained (heavy) rainstorms were automatically classified and studied according to their structure in time, localization and extension. Rainfall-runoff watershed models can consequently benefit from the enhanced identification of design storms, with a realistic time structure integrated with the results of the spatial analysis. A survey of flash flood events recorded in the last decades provides a preliminary validation of the method proposed to identify the heavy rainstorms and synthetically describe their characteristics. The notable size of the employed sample, including data with a very detailed resolution in time, that relate to several rain gauges well-distributed throughout the region, give robustness to the obtained results.

Rainstorms able to induce flash floods in a Mediterranean-climate region (Calabria, southern Italy)

NASA Astrophysics Data System (ADS)

Terranova, O. G.; Gariano, S. L.

2014-09-01

Heavy rainstorms often induce flash flooding, one of the natural disasters most responsible for damage to man-made infrastructures and loss of lives, also adversely affecting the opportunities for socio-economic development of Mediterranean countries. The frequently dramatic damage of flash floods are often detected, with sufficient accuracy, by post-event surveys, but rainfall causing them are still only roughly characterized. With the aim of improving the understanding of the temporal structure and spatial distribution of heavy rainstorms in the Mediterranean context, a statistical analysis was carried out in Calabria (southern Italy) concerning rainstorms that mainly induced flash floods, but also shallow landslides and debris flows. Thus, a method is proposed - based on the overcoming of heuristically predetermined threshold values of cumulated rainfall, maximum intensity, and kinetic energy of the rainfall event - to select and characterize the rainstorms able to induce flash floods in the Mediterranean-climate countries. Therefore, the obtained (heavy) rainstorms were automatically classified and studied according to their structure in time, localization, and extension. Rainfall-runoff watershed models can consequently benefit from the enhanced identification of design storms, with a realistic time structure integrated with the results of the spatial analysis. A survey of flash flood events recorded in the last decades provides a preliminary validation of the method proposed to identify the heavy rainstorms and synthetically describe their characteristics. The notable size of the employed sample, including data with a very detailed resolution in time that relate to several rain gauges well-distributed throughout the region, gives robustness to the obtained results.

Monte Carlo simulation of ionizing radiation induced DNA strand breaks utilizing coarse grained high-order chromatin structures.

PubMed

Liang, Ying; Yang, Gen; Liu, Feng; Wang, Yugang

2016-01-07

Ionizing radiation threatens genome integrity by causing DNA damage. Monte Carlo simulation of the interaction of a radiation track structure with DNA provides a powerful tool for investigating the mechanisms of the biological effects. However, the more or less oversimplification of the indirect effect and the inadequate consideration of high-order chromatin structures in current models usually results in discrepancies between simulations and experiments, which undermine the predictive role of the models. Here we present a biophysical model taking into consideration factors that influence indirect effect to simulate radiation-induced DNA strand breaks in eukaryotic cells with high-order chromatin structures. The calculated yields of single-strand breaks and double-strand breaks (DSBs) for photons are in good agreement with the experimental measurements. The calculated yields of DSB for protons and α particles are consistent with simulations by the PARTRAC code, whereas an overestimation is seen compared with the experimental results. The simulated fragment size distributions for (60)Co γ irradiation and α particle irradiation are compared with the measurements accordingly. The excellent agreement with (60)Co irradiation validates our model in simulating photon irradiation. The general agreement found in α particle irradiation encourages model applicability in the high linear energy transfer range. Moreover, we demonstrate the importance of chromatin high-order structures in shaping the spectrum of initial damage.

Quantitative Characterisation of Fracturing Around the Damage Zone Surrounding New Zealand's Alpine Fault Using X-ray CT Scans of DFDP-1 Core

NASA Astrophysics Data System (ADS)

Williams, J. N.; Toy, V.; Massiot, C.; Mcnamara, D. D.; Wang, T.

2015-12-01

X-ray computer tomography (CT) scans of core recovered from the first phase of the Deep Fault Drilling Project (DFDP-1) through the Alpine Fault provide an excellent opportunity to analyse brittle deformation around the fault. In particular, assessment can be made of the heavily fractured protolith constituting the damage zone. Damage zone structures are divided into two types that result from two distinct processes: (1) "off fault damage" formed by stress changes induced by the passage of a seismic rupture and (2) "off fault deformation" that represent structures, which accommodate strain around the fault that was not localised on the principal slip zone (PSZ). The distribution of these damage zones structures within CT scans of the recovered core was measured along a scanline parallel to the core axis and assessed using a weighted moving average technique to account for orientation bias. The results of this analysis reveal that within the part of the fault rocks sampled by DFDP-1 there is no increase in density of these structures towards the PSZ. This is in agreement with independent analysis using Borehole Televiewer Data of the DFDP-1B borehole. Instead, we consider the density of these structures to be controlled to the first order by lithology, which modulates the mechanical properties of the fault rocks such as its frictional strength and cohesion. Comparisons of fracture density to p-wave velocities obtained from wireline logs indicate they are independent of each other, therefore, for the cores sampled in this study fractures impart no influence on the elastic properties of the rock. This is consistent with the observation from core that the majority of fractures are cemented. We consider how this might influence future rupture dynamics.

DNA replication after mutagenic treatment in Hordeum vulgare.

PubMed

Kwasniewska, Jolanta; Kus, Arita; Swoboda, Monika; Braszewska-Zalewska, Agnieszka

2016-12-01

The temporal and spatial properties of DNA replication in plants related to DNA damage and mutagenesis is poorly understood. Experiments were carried out to explore the relationships between DNA replication, chromatin structure and DNA damage in nuclei from barley root tips. We quantitavely analysed the topological organisation of replication foci using pulse EdU labelling during the S phase and its relationship with the DNA damage induced by mutagenic treatment with maleic hydrazide (MH), nitroso-N-methyl-urea (MNU) and gamma ray. Treatment with mutagens did not change the characteristic S-phase patterns in the nuclei; however, the frequencies of the S-phase-labelled cells after treatment differed from those observed in the control cells. The analyses of DNA replication in barley nuclei were extended to the micronuclei induced by mutagens. Replication in the chromatin of the micronuclei was rare. The results of simultanous TUNEL reaction to identify cells with DNA strand breaks and the labelling of the S-phase cells with EdU revealed the possibility of DNA replication occurring in damaged nuclei. For the first time, the intensity of EdU fluorescence to study the rate of DNA replication was analysed. Copyright © 2016 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Bu; Yu, Yingtian; Bauchy, Mathieu, E-mail: bauchy@ucla.edu

Although quartz (α-form) is a mineral used in numerous applications wherein radiation exposure is an issue, the nature of the atomistic defects formed during radiation-induced damage has not been fully clarified. Especially, the extent of oxygen vacancy formation is still debated, which is an issue of primary importance as optical techniques based on charged oxygen vacancies have been utilized to assess the level of radiation damage in quartz. In this paper, molecular dynamics simulations are applied to study the effects of ballistic impacts on the atomic network of quartz. We show that the defects that are formed mainly consist ofmore » over-coordinated Si and O, as well as Si–O connectivity defects, e.g., small Si–O rings and edge-sharing Si tetrahedra. Oxygen vacancies, on the contrary, are found in relatively low abundance, suggesting that characterizations based on E′ centers do not adequately capture radiation-induced structural damage in quartz. Finally, we evaluate the dependence on the incident energy, of the amount of each type of the point defects formed, and quantify unambiguously the threshold displacement energies for both O and Si atoms. These results provide a comprehensive basis to assess the nature and extent of radiation damage in quartz.« less

[Microflora of damaged ferroconcrete structures under the conditions of inhibitory protection].

PubMed

Kopteva, Zh P; Zanina, V V; Purish, L M; Piliashenko-Novokhatnyĭ, A I; Kozlova, I A

2004-01-01

Thionic, sulphate-reducing, denitrifying and ammonifying bacteria widely distributed in the sewer system on various structure elements have been isolated from damaged ferroconcrete samples. Effect of protective materials on microbe-induced corrosion of metal famework of concrete samples has been studied. Selective effect of corrosion inhibitors and coatings on the growth of corrosion-active bacteria of sulphur and nitrogen cycle has been revealed. It is shown that acid medium formed by thionic bacteria is more aggressive than ammonium-hydrosulphide one formed by denitrifying and sulphate-reducing bacteria. It has been established that the corrosion inhibitor--pyrquin, organosilicon coating CO-FMI and epoxyorganosilicon coating 4sk are most effective materials as to the action of thionic bacteria--dangerous agents of ferroconcrete aerobic corrosion.

Cavity evolution at grain boundaries as a function of radiation damage and thermal conditions in nanocrystalline nickel

DOE PAGES

Muntifering, Brittany; Blair, Sarah Jane; Gong, Cajer; ...

2015-12-30

Enhanced radiation tolerance of nanostructured metals is attributed to the high density of interfaces that can absorb radiation-induced defects. Here, cavity evolution mechanisms during cascade damage, helium implantation, and annealing of nanocrystalline nickel are characterized via in situ transmission electron microscopy (TEM). Films subjected to self-ion irradiation followed by helium implantation developed evenly distributed cavity structures, whereas films exposed in the reversed order developed cavities preferentially distributed along grain boundaries. Post-irradiation annealing and orientation mapping demonstrated uniform cavity growth in the nanocrystalline structure, and cavities spanning multiple grains. Furthermore, these mechanisms suggest limited ability to reduce swelling, despite the stabilitymore » of the nanostructure.« less

Restoration of high-resolution AFM images captured with broken probes

NASA Astrophysics Data System (ADS)

Wang, Y. F.; Corrigan, D.; Forman, C.; Jarvis, S.; Kokaram, A.

2012-03-01

A type of artefact is induced by damage of the scanning probe when the Atomic Force Microscope (AFM) captures a material surface structure with nanoscale resolution. This artefact has a dramatic form of distortion rather than the traditional blurring artefacts. Practically, it is not easy to prevent the damage of the scanning probe. However, by using natural image deblurring techniques in image processing domain, a comparatively reliable estimation of the real sample surface structure can be generated. This paper introduces a novel Hough Transform technique as well as a Bayesian deblurring algorithm to remove this type of artefact. The deblurring result is successful at removing blur artefacts in the AFM artefact images. And the details of the fibril surface topography are well preserved.

Impact load-induced micro-structural damage and micro-structure associated mechanical response of concrete made with different surface roughness and porosity aggregates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erdem, Savas, E-mail: evxse1@nottingham.ac.uk; Dawson, Andrew Robert; Thom, Nicholas Howard

2012-02-15

The relationship between the nature of micro damage under impact loading and changes in mechanical behavior associated with different microstructures is studied for concretes made with two different coarse aggregates having significant differences mainly in roughness and porosity - sintered fly ash and uncrushed gravel. A range of techniques including X-ray diffraction, digital image analysis, mercury porosimetry, X-ray computed tomography, laser surface profilometry and scanning electron microscopy were used to characterize the aggregates and micro-structures. The concrete prepared with lightweight aggregates was stronger in compression than the gravel aggregate concrete due to enhanced hydration as a result of internal curing.more » In the lightweight concrete, it was deduced that an inhomogeneous micro-structure led to strain incompatibilities and consequent localized stress concentrations in the mix, leading to accelerated failure. The pore structure, compressibility, and surface texture of the aggregates are of paramount importance for the micro-cracking growth.« less

Lesion-induced DNA weak structural changes detected by pulsed EPR spectroscopy combined with site-directed spin labelling.

PubMed

Sicoli, Giuseppe; Mathis, Gérald; Aci-Sèche, Samia; Saint-Pierre, Christine; Boulard, Yves; Gasparutto, Didier; Gambarelli, Serge

2009-06-01

Double electron-electron resonance (DEER) was applied to determine nanometre spin-spin distances on DNA duplexes that contain selected structural alterations. The present approach to evaluate the structural features of DNA damages is thus related to the interspin distance changes, as well as to the flexibility of the overall structure deduced from the distance distribution. A set of site-directed nitroxide-labelled double-stranded DNA fragments containing defined lesions, namely an 8-oxoguanine, an abasic site or abasic site analogues, a nick, a gap and a bulge structure were prepared and then analysed by the DEER spectroscopic technique. New insights into the application of 4-pulse DEER sequence are also provided, in particular with respect to the spin probes' positions and the rigidity of selected systems. The lesion-induced conformational changes observed, which were supported by molecular dynamics studies, confirm the results obtained by other, more conventional, spectroscopic techniques. Thus, the experimental approaches described herein provide an efficient method for probing lesion-induced structural changes of nucleic acids.

Unrepaired DNA damage in macrophages causes elevation of particulate matter- induced airway inflammatory response.

PubMed

Luo, Man; Bao, Zhengqiang; Xu, Feng; Wang, Xiaohui; Li, Fei; Li, Wen; Chen, Zhihua; Ying, Songmin; Shen, Huahao

2018-04-14

The inflammatory cascade can be initiated with the recognition of damaged DNA. Macrophages play an essential role in particulate matter (PM)-induced airway inflammation. In this study, we aim to explore the PM induced DNA damage response of macrophages and its function in airway inflammation. The DNA damage response and inflammatory response were assessed using bone marrow-derived macrophages following PM treatment and mouse model instilled intratracheally with PM. We found that PM induced significant DNA damage both in vitro and in vivo and simultaneously triggered a rapid DNA damage response, represented by nuclear RPA, 53BP1 and γH2AX foci formation. Genetic ablation or chemical inhibition of the DNA damage response sensor amplified the production of cytokines including Cxcl1, Cxcl2 and Ifn-γ after PM stimulation in bone marrow-derived macrophages. Similar to that seen in vitro , mice with myeloid-specific deletion of RAD50 showed higher levels of airway inflammation in response to the PM challenge, suggesting a protective role of DNA damage sensor during inflammation. These data demonstrate that PM exposure induces DNA damage and activation of DNA damage response sensor MRN complex in macrophages. Disruption of MRN complex lead to persistent, unrepaired DNA damage that causes elevated inflammatory response.

Noise Induced DNA Damage Within the Auditory Nerve.

PubMed

Guthrie, O'neil W

2017-03-01

An understanding of the molecular pathology that underlies noise induced neurotoxicity is a prerequisite to the design of targeted therapies. The objective of the current experiment was to determine whether or not DNA damage is part of the pathophysiologic sequela of noise induced neurotoxicity. The experiment consisted of 41 hooded Long-Evans rats (2 month old males) that were randomized into control and noise exposed groups. Both the control and the noise group followed the same time schedule and therefore started and ended the experiment together. The noise dose consisted of a 6000 Hz noise band at 105 dB SPL. Temporal bones from both groups were harvested, and immunohistochemistry was used to identify neurons with DNA damage. Quantitative morphometric analyses was then employed to determine the level of DNA damage. Neural action potentials were recorded to assess the functional impact of noise induced DNA damage. Immunohistochemical reactions revealed that the noise exposure precipitated DNA damage within the nucleus of auditory neurons. Quantitative morphometry confirmed the noise induced increase in DNA damage levels and the precipitation of DNA damage was associated with a significant loss of nerve sensitivity. Therefore, DNA damage is part of the molecular pathology that drives noise induced neurotoxicity. Anat Rec, 300:520-526, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

DNA damage induced by ascorbate in the presence of Cu2+.

PubMed

Kobayashi, S; Ueda, K; Morita, J; Sakai, H; Komano, T

1988-01-25

DNA damage induced by ascorbate in the presence of Cu2+ was investigated by use of bacteriophage phi X174 double-stranded supercoiled DNA and linear restriction fragments as substrates. Single-strand cleavage was induced when supercoiled DNA was incubated with 5 microM-10 mM ascorbate and 50 microM Cu2+ at 37 degrees C for 10 min. The induced DNA damage was analyzed by sequencing of fragments singly labeled at their 5'- or 3'-end. DNA was cleaved directly and almost uniformly at every nucleotide by ascorbate and Cu2+. Piperidine treatment after the reaction showed that ascorbate and Cu2+ induced another kind of DNA damage different from the direct cleavage. The damage proceeded to DNA cleavage by piperidine treatment and was sequence-specific rather than random. These results indicate that ascorbate induces two classes of DNA damage in the presence of Cu2+, one being direct strand cleavage, probably via damage to the DNA backbone, and the other being a base modification labile to alkali treatment. These two classes of DNA damage were inhibited by potassium iodide, catalase and metal chelaters, suggesting the involvement of radicals generated from ascorbate hydroperoxide.

International Space Station 2A Array Modal Analysis

NASA Technical Reports Server (NTRS)

Laible, Michael; Fitzpatrick, Kristin; Grygier, Michael

2012-01-01

On December 9th 2009, the International Space Station (ISS) 2A solar array mast experienced prolonged longeron shadowing during a Soyuz undocking. Analytical reconstruction of induced thermal and dynamic structural loads showed an exceedance of the mast buckling limit. Possible structural damage to the solar array mast could have occurred during this event. A Low fidelity video survey of the 2A mast showed no obvious damage of the mast longerons or battens. The decision was made to conduct an on-orbit dynamic test of the 2A array on December 18th, 2009. The test included thruster pluming on the array while photogrammetry data was recorded. The test was similar to other Dedicated Thruster Firings (DTFs) that were performed to measure structural frequency and damping of a solar array. Results of the DTF indicated lower frequency mast modes than model predictions, thus leading to speculation of mast damage. A detailed nonlinear analysis was performed on the 2A array model to assess possible solutions to modal differences. The setup of the parametric nonlinear trade study included the use of a detailed array model and the reduced mass and stiffness matrices of the entire ISS being applied to the array interface. The study revealed that the array attachment structure is nonlinear and thus was the source of error in the model prediction of mast modes. In addition, a detailed study was performed to determine mast mode sensitivity to mast longeron damage. This sensitivity study was performed to assess if the ISS program has sufficient instrumentation for mast damage detection.

The mitochondrial O-linked N-acetylglucosamine transferase (mOGT) in the diabetic patient could be the initial trigger to develop Alzheimer disease.

PubMed

Lozano, Liliana; Lara-Lemus, Roberto; Zenteno, Edgar; Alvarado-Vásquez, Noé

2014-10-01

Diabetes mellitus (DM) is considered a risk factor for the development of Alzheimer disease (AD); however, how DM favors evolution of AD is still insufficiently understood. Hyperglycemia in DM is associated to an increase in mitochondrial reactive oxygen species (ROS) generation, as well as damage of hippocampal cells, reflected by changes in morphological and mitochondrial functionality. Similar mitochondrial damage has been observed when amyloid beta (Aβ) accumulates in the brain of AD patients. In DM, the excess of glucose in the brain induces higher activity of the hexosamine biosynthesis pathway (HBP), it synthesizes UDP-N-acetylglucosamine (UDP-GlcNAc), which is used by O-linked N-acetylglucosamine transferase (OGT) to catalyze O-GlcNAcylation of numerous proteins. Although O-GlcNAcylation plays an important role in maintaining structure and cellular functionality, chronic activity of this pathway has been associated with insulin resistance and hyperglycemia-induced glucose toxicity. Three different forms of OGT are known: nucleocytoplasmic (ncOGT), short (sOGT), and mitochondrial (mOGT). Previous reports showed that overexpression of ncOGT is not toxic to the cell; in contrast, overexpression of mOGT is associated with cellular apoptosis. In this work, we suggest that hyperglycemia in the diabetic patient could induce greater expression and activity of mOGT, modifying the structure and functionality of mitochondria in hippocampal cells, accelerating neuronal damage, and favoring the start of AD. In consequence, mOGT activity could be a key point for AD development in patients with DM. Copyright © 2014 Elsevier Inc. All rights reserved.

Optical diagnosis of the progression and reversal of CCl4-induced liver injury in rodent model using minimally invasive autofluorescence spectroscopy.

PubMed

Nazeer, Shaiju S; Sandhyamani, S; Jayasree, Ramapurath S

2015-06-07

Worldwide, liver cancer is the fifth most common cancer in men and seventh most common cancer in women. Intoxicant-induced liver injury is one of the major causes for severe structural damage with fibrosis and functional derangement of the liver leading to cancer in its later stages. This report focuses on the minimally invasive autofluorescence spectroscopic (AFS) studies on intoxicant, carbon tetrachloride (CCl4)-induced liver damage in a rodent model. Different stages of liver damage, including the reversed stage, on stoppage of the intoxicant are examined. Emission from prominent fluorophores, such as collagen, nicotinamide adenine dinucleotide (NADH), and flavin adenine dinucleotide (FAD), and variations in redox ratio have been studied. A direct correlation between the severity of the disease and the levels of collagen and redox ratio was observed. On withdrawal of the intoxicant, a gradual reversal of the disease to normal conditions was observed as indicated by the decrease in collagen levels and redox ratio. Multivariate statistical techniques and principal component analysis followed by linear discriminant analysis (PC-LDA) were used to develop diagnostic algorithms for distinguishing different stages of the liver disease based on spectral features. The PC-LDA modeling on a minimally invasive AFS dataset yielded diagnostic sensitivities of 93%, 87% and 87% and specificities of 90%, 98% and 98% for pairwise classification among normal, fibrosis, cirrhosis and reversal conditions. We conclude that AFS along with PC-LDA algorithm has the potential for rapid and accurate minimally invasive diagnosis and detection of structural changes due to liver injury resulting from various intoxicants.

Ultrastructural and DNA damaging effects of lead nitrate in the liver.

PubMed

Narayana, K; Al-Bader, Maie

2011-01-01

A ubiquitous environmental toxicant - lead is known to affect several organ systems. This study was designed to investigate the effects of lead nitrate exposure on liver structure and DNA fragmentation. Adult male Wistar rats were treated orally with lead nitrate at the dose levels of 0%, 0.5% and 1% for 60 days and sacrificed on the next day. The liver was processed for thick sections and evaluated after toludine blue staining and by electron microscopy after staining with uranyl acetate and lead citrate. The DNA damage was assessed by DNA fragmentation assay. The liver weight was not significantly affected in the experimental groups. Hepatocyte nuclei were not shrunk, instead lead was mitogenic to hepatocytes as indicated by an increase in the number of binucleated hepatocytes (P<0.05). The number of mitochondria per hepatocyte decreased in a dose-dependent manner (P<0.05). Qualitatively, the necrotic changes such as small to large-sized cytoplasmic vacuoles often displacing the organelles, decrease in hepatocyte microvilli, degeneration of mitochondria, and vacuolar encroachment of nuclei and dilatation of sinusoids were observed. The qualitative changes were induced in a dose-dependent manner. Kupffer cells or Ito cells did not present any notable structural changes. Although the electrophoretic flow of DNA fragments was observed in lead-treated groups, these changes were not significantly different from that in control as evaluated by optical density. In conclusion, lead induces necrotic changes with simultaneous mitogenic activity; however, it does not induce significant DNA damage in the liver. Copyright © 2009 Elsevier GmbH. All rights reserved.

Estimation of fatigue life using electromechanical impedance technique

NASA Astrophysics Data System (ADS)

Lim, Yee Yan; Soh, Chee Kiong

2010-04-01

Fatigue induced damage is often progressive and gradual in nature. Structures subjected to large number of fatigue load cycles will encounter the process of progressive crack initiation, propagation and finally fracture. Monitoring of structural health, especially for the critical components, is therefore essential for early detection of potential harmful crack. Recent advent of smart materials such as piezo-impedance transducer adopting the electromechanical impedance (EMI) technique and wave propagation technique are well proven to be effective in incipient damage detection and characterization. Exceptional advantages such as autonomous, real-time and online, remote monitoring may provide a cost-effective alternative to the conventional structural health monitoring (SHM) techniques. In this study, the main focus is to investigate the feasibility of characterizing a propagating fatigue crack in a structure using the EMI technique as well as estimating its remaining fatigue life using the linear elastic fracture mechanics (LEFM) approach. Uniaxial cyclic tensile load is applied on a lab-sized aluminum beam up to failure. Progressive shift in admittance signatures measured by the piezo-impedance transducer (PZT patch) corresponding to increase of loading cycles reflects effectiveness of the EMI technique in tracing the process of fatigue damage progression. With the use of LEFM, prediction of the remaining life of the structure at different cycles of loading is possible.

The Involvement of the Oxidative Stress in Murine Blue LED Light-Induced Retinal Damage Model.

PubMed

Nakamura, Maho; Kuse, Yoshiki; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki

2017-01-01

The aim of study was to establish a mouse model of blue light emitting diode (LED) light-induced retinal damage and to evaluate the effects of the antioxidant N-acetylcysteine (NAC). Mice were exposed to 400 or 800 lx blue LED light for 2 h, and were evaluated for retinal damage 5 d later by electroretinogram amplitude and outer nuclear layer (ONL) thickness. Additionally, we investigated the effect of blue LED light exposure on shorts-wave-sensitive opsin (S-opsin), and rhodopsin expression by immunohistochemistry. Blue LED light induced light intensity dependent retinal damage and led to collapse of S-opsin and altered rhodopsin localization from inner and outer segments to ONL. Conversely, NAC administered at 100 or 250 mg/kg intraperitoneally twice a day, before dark adaptation and before light exposure. NAC protected the blue LED light-induced retinal damage in a dose-dependent manner. Further, blue LED light-induced decreasing of S-opsin levels and altered rhodopsin localization, which were suppressed by NAC. We established a mouse model of blue LED light-induced retinal damage and these findings indicated that oxidative stress was partially involved in blue LED light-induced retinal damage.

Agmatine protects Müller cells from high-concentration glucose-induced cell damage via N-methyl-D-aspartic acid receptor inhibition

PubMed Central

HAN, NING; YU, LI; SONG, ZHIDU; LUO, LIFU; WU, YAZHEN

2015-01-01

Neural injury is associated with the development of diabetic retinopathy. Müller cells provide structural and metabolic support for retinal neurons. High glucose concentrations are known to induce Müller cell activity. Agmatine is an endogenous polyamine, which is enzymatically formed in the mammalian brain and has exhibited neuroprotective effects in a number of experimental models. The aims of the present study were to investigate whether agmatine protects Müller cells from glucose-induced damage and to explore the mechanisms underlying this process. Lactate dehydrogenase activity and tumor necrosis factor-α mRNA expression were significantly reduced in Müller cells exposed to a high glucose concentration, following agmatine treatment, compared with cells not treated with agmatine. In addition, agmatine treatment inhibited glucose-induced Müller cell apoptosis, which was associated with the regulation of Bax and Bcl-2 expression. Agmatine treatment suppressed glucose-induced phosphorylation of mitogen-activated protein kinase (MAPK) protein in Müller cells. The present study demonstrated that the protective effects of agmatine on Müller cells were inhibited by N-methyl-D-aspartic acid (NMDA). The results of the present study suggested that agmatine treatment protects Müller cells from high-concentration glucose-induced cell damage. The underlying mechanisms may relate to the anti-inflammatory and antiapoptotic effects of agmatine, as well as to the inhibition of the MAPK pathway, via NMDA receptor suppression. Agmatine may be of use in the development of novel therapeutic approaches for patients with diabetic retinopathy. PMID:25816073

Agmatine protects Müller cells from high-concentration glucose-induced cell damage via N-methyl-D-aspartic acid receptor inhibition.

PubMed

Han, Ning; Yu, Li; Song, Zhidu; Luo, Lifu; Wu, Yazhen

2015-07-01

Neural injury is associated with the development of diabetic retinopathy. Müller cells provide structural and metabolic support for retinal neurons. High glucose concentrations are known to induce Müller cell activity. Agmatine is an endogenous polyamine, which is enzymatically formed in the mammalian brain and has exhibited neuroprotective effects in a number of experimental models. The aims of the present study were to investigate whether agmatine protects Müller cells from glucose-induced damage and to explore the mechanisms underlying this process. Lactate dehydrogenase activity and tumor necrosis factor-α mRNA expression were significantly reduced in Müller cells exposed to a high glucose concentration, following agmatine treatment, compared with cells not treated with agmatine. In addition, agmatine treatment inhibited glucose-induced Müller cell apoptosis, which was associated with the regulation of Bax and Bcl-2 expression. Agmatine treatment suppressed glucose-induced phosphorylation of mitogen-activated protein kinase (MAPK) protein in Müller cells. The present study demonstrated that the protective effects of agmatine on Müller cells were inhibited by N-methyl-D-aspartic acid (NMDA). The results of the present study suggested that agmatine treatment protects Müller cells from high-concentration glucose-induced cell damage. The underlying mechanisms may relate to the anti-inflammatory and antiapoptotic effects of agmatine, as well as to the inhibition of the MAPK pathway, via NMDA receptor suppression. Agmatine may be of use in the development of novel therapeutic approaches for patients with diabetic retinopathy.

Gravity-induced rock mass damage related to large en masse rockslides: Evidence from Vajont

NASA Astrophysics Data System (ADS)

Paronuzzi, Paolo; Bolla, Alberto

2015-04-01

The Vajont landslide is a well-known, reservoir-induced slope failure that occurred on 9 October 1963 and was characterized by an 'en masse' sliding motion that triggered various large waves, determining catastrophic consequences for the nearby territory and adjacent villages. During the Vajont dam construction, and especially after the disaster, some researchers identified widespread field evidence of heavy rock mass damage involving the presumed prehistoric rockslide and/or the 1963 failed mass. This paper describes evidence of heavy gravitational damage, including (i) folding, (ii) fracturing, (iii) faulting, and (iv) intact rock disintegration. The gravity-induced rock mass damage (GRMD) characterizes the remnants of the basal shear zone, still resting on the large detachment surface, and the 1963 failed rock mass. The comprehensive geological study of the 1963 Vajont landslide, based on the recently performed geomechanical survey (2006-present) and on the critical analysis of the past photographic documentation (1959-1964), allows us to recognize that most GRMD evidence is related to the prehistoric multistage Mt. Toc rockslide. The 1963 catastrophic en masse remobilization induced an increase to the prehistoric damage, reworking preexisting structures and creating additional gravity-driven features (folds, fractures, faults, and rock fragmentation). The gravity-induced damage was formed during the slope instability phases that preceded the collapse (static or quasi-static GRMD) and also as a consequence of the sliding motion and of the devastating impact between the failed blocks (dynamic GRMD). Gravitational damage originated various types of small drag folds such as flexures, concentric folds, chevron, and kink-box folds, all having a radius of 1-5 m. Large buckle folds (radius of 10-50 m) are related to the dynamic damage and were formed during the en masse motion as a consequence of deceleration and impact processes that involved the sliding mass. Prior to failure, unstable rock slopes can be affected by diffuse newly formed gravity-driven joints that are absent in the surrounding area and within the underlying bedrock, as the Vajont case history demonstrates (joint sets J9 and J10). These fractures, caused by critical tensile and shear stresses, represent an important mechanical clue to recognizing, on a geological basis, the instability condition of a rock slope under investigation. Owing to its complex geological evolution, the Vajont landslide is an outstanding example to help learn about cumulative GRMD effects that can accumulate over time when an ancient rockslide is further remobilized by a sudden en masse sliding motion.

Structure and Inhibition of Microbiome β-Glucuronidases Essential to the Alleviation of Cancer Drug Toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallace, Bret D.; Roberts, Adam B.; Pollet, Rebecca M.

The selective inhibition of bacterial β-glucuronidases was recently shown to alleviate drug-induced gastrointestinal toxicity in mice, including the damage caused by the widely used anticancer drug irinotecan. Here, we report crystal structures of representative β-glucuronidases from the Firmicutes Streptococcus agalactiae and Clostridium perfringens and the Proteobacterium Escherichia coli, and the characterization of a β-glucuronidase from the Bacteroidetes Bacteroides fragilis. While largely similar in structure, these enzymes exhibit marked differences in catalytic properties and propensities for inhibition, indicating that the microbiome maintains functional diversity in orthologous enzymes. Small changes in the structure of designed inhibitors can induce significant conformational changes inmore » the β-glucuronidase active site. Finally, we establish that β-glucuronidase inhibition does not alter the serum pharmacokinetics of irinotecan or its metabolites in mice. Together, the data presented advance our in vitro and in vivo understanding of the microbial β-glucuronidases, a promising new set of targets for controlling drug-induced gastrointestinal toxicity.« less

An Investigation of Laser Induced Surface Damage in glass.

DTIC Science & Technology

1985-06-01

ROA-RI60 669 RN INVESTIGATION OF LASER INDUCED SURFACE DAMAG IN In1 1 6lo GLASS (U) NAVAL POSTGRADUATE SCHOOL MONTEREY CA R D UYAK JUN 85IUNCLASSIFIED...ii -0 NAVAL POSTGRADUATE SCHOOL Monterey, California bor OCT THESIS AN INVESTIGATION OF LASER INDUCED SURFACE DAMAGE IN GLASS by )Richard David Uyak ,L...Subtitle) EPORT 6 PERIOD COVERED %An Investigation of Laser Induced Master’s Thesis Surface Damage in Glass June 1985S. PERFORMING ORG. REPORT MUMMER 7

Cancer cells recovering from damage exhibit mitochondrial restructuring and increased aerobic glycolysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akakura, Shin; Ostrakhovitch, Elena; Sanokawa-Akakura, Reiko

2014-06-13

Highlights: • Some cancer cells recover from severe damage that causes cell death in majority of cells. • Damage-Recovered (DR) cancer cells show reduced mitochondria, mDNA and mitochondrial enzymes. • DR cells show increased aerobic glycolysis, ATP, cell proliferation, and resistance to damage. • DR cells recovered from in vivo damage also show increased glycolysis and proliferation rate. - Abstract: Instead of relying on mitochondrial oxidative phosphorylation, most cancer cells rely heavily on aerobic glycolysis, a phenomenon termed as “the Warburg effect”. We considered that this effect is a direct consequence of damage which persists in cancer cells that recovermore » from damage. To this end, we studied glycolysis and rate of cell proliferation in cancer cells that recovered from severe damage. We show that in vitro Damage-Recovered (DR) cells exhibit mitochondrial structural remodeling, display Warburg effect, and show increased in vitro and in vivo proliferation and tolerance to damage. To test whether cancer cells derived from tumor microenvironment can show similar properties, we isolated Damage-Recovered (T{sup DR}) cells from tumors. We demonstrate that T{sup DR} cells also show increased aerobic glycolysis and a high proliferation rate. These findings show that Warburg effect and its consequences are induced in cancer cells that survive severe damage.« less

Complex damage distribution behaviour in cobalt implanted rutile TiO2 (1 1 0) lattice

NASA Astrophysics Data System (ADS)

Joshi, Shalik Ram; Padmanabhan, B.; Chanda, Anupama; Ojha, Sunil; Kanjilal, D.; Varma, Shikha

2017-11-01

The present work investigates the radiation damage, amorphization and structural modifications that are produced by ion-solid interactions in TiO2 crystals during 200 keV Cobalt ion implantation. RBS/C and GIXRD have been utilized to evaluate the damage in the host lattice as a function of ion fluence. Multiple scattering formalism has been applied to extract the depth dependent damage distributions in TiO2(1 1 0). The results have been compared with the MC simulations performed using SRIM-2013. RBS/C results delineate a buried amorphous layer at a low fluence. Surprisingly, ion induced dynamic activation produces a recovery in this damage at higher fluences. This improvement interestingly occurs only in deep regions (60-300 nm) where a systematic lowering in damage with fluence is observed. Formation of Co-Ti-O phases and generation of stress in TiO2 lattice can also be responsible for this improvement in deep regions. In contrast, surface region (0-60 nm) indicates a gradual increase in damage with fluence. Such a switch in the damage behavior creates a cross point in damage profiles at 60 nm. Surface region is a sink of vacancies whereas deep layers are interstitial rich. However, these regions are far separated from each other resulting in an intermediate (100-150 nm) region with a significant dip (valley) in damage which can be characterized by enhanced recombination of point defects. The damage profiles thus indicate a very complex behavior. MC simulations, however, present very different results. They depict a damage profile that extends to a depth of only 150 nm, which is only about half of the damage- width observed here via RBS/C. Moreover, MC simulations do not indicate presence of any valley like structure in the damage profile. The complex nature of damage distribution observed here via RBS/C may be related to the high ionic nature of the chemical bonds in the TiO2 lattice.

The role of NLRP3-CASP1 in inflammasome-mediated neuroinflammation and autophagy dysfunction in manganese-induced, hippocampal-dependent impairment of learning and memory ability.

PubMed

Wang, Diya; Zhang, Jianbin; Jiang, Wenkai; Cao, Zipeng; Zhao, Fang; Cai, Tongjian; Aschner, Michael; Luo, Wenjing

2017-05-04

Central nervous system (CNS) inflammation and autophagy dysfunction are known to be involved in the pathology of neurodegenerative diseases. Manganese (Mn), a neurotoxic metal, has the potential to induce microglia-mediated neuroinflammation as well as autophagy dysfunction. NLRP3 (NLR family, pyrin domain containing 3)- CASP1 (caspase 1) inflammasome-mediated neuroinflammation in microglia has specific relevance to neurological diseases. However, the mechanism driving these phenomena remains poorly understood. We demonstrate that Mn activates the NLRP3-CASP1 inflammasome pathway in the hippocampus of mice and BV2 cells by triggering autophagy-lysosomal dysfunction. The autophagy-lysosomal dysfunction is induced by lysosomal damage caused by excessive Mn accumulation, damaging the structure and normal function of these organelles. Additionally, we show that the release of lysosomal CTSB (cathepsin B) plays an important role in Mn-induced NLRP3-CASP1 inflammasome activation, and that the increased autophagosomes in the cytoplasm are not the main cause of NLRP3-CASP1 inflammasome activation. The accumulation of proinflammatory cytokines, such as IL1B (interleukin 1 β) and IL18 (interleukin 18), as well as the dysfunctional autophagy pathway may damage hippocampal neuronal cells, thus leading to hippocampal-dependent impairment in learning and memory, which is associated with the pathogenesis of Alzheimer disease (AD).

Dietary supplementation with omega-3 polyunsaturated fatty acid-rich oils protects against visible-light-induced retinal damage in vivo.

PubMed

Deng, Qianchun; Wang, Yong; Wang, Chengtao; Ji, Baoping; Cong, Renhuai; Zhao, Lei; Chen, Peng; Zang, Xixi; Lu, Feng; Han, Fei; Huang, Fenghong

2018-04-25

The effects of administering omega-3 (ω-3) polyunsaturated fatty acid (PUFA)-rich oils on visible-light-induced retinal damage were investigated in rabbits. The mole percentages of α-linolenic acid in sea buckthorn berry oil, sea buckthorn oil (SO), sea buckthorn seed oil and flaxseed oil (FO) were 2.12%, 12.98%, 31.56% and 55.41%, respectively. Algal oil (AO) contains 33.34% docosahexaenoic acid. SO has the highest total phenolic content (63.42 ± 0.59 mg SAE per 100 g) amongst these oils. The administration of SO, FO and AO provided structural and functional protection to the retina. In the retina, we observed a significant increase in the levels of DHA in the AO group compared with the normal group. The mechanism of retinal protection by SO, FO and AO involves up-regulating the expression of nuclear factor erythroid-2 related factor 2 and haem oxygenase-1. The levels of interleukin-1 β, tumour necrosis factor-alpha, interleukin-8, and cyclooxygenase 2 in the retina were significantly reduced with AO treatment. The administration of AO resulted in the down-regulation of nuclear factor kappa B mRNA expression. In addition, the treatment with AO significantly attenuated the light-induced apoptosis and angiogenesis in the retina. These results suggest that dietary ω-3 PUFA-rich oils protect against visible-light-induced retinal damage.

Prediction and experimental observation of damage dependent damping in laminated composite beams

NASA Technical Reports Server (NTRS)

Allen, D. H.; Harris, C. E.; Highsmith, A. L.

1987-01-01

The equations of motion are developed for laminated composite beams with load-induced matrix cracking. The damage is accounted for by utilizing internal state variables. The net result of these variables on the field equations is the introduction of both enhanced damping, and degraded stiffness. Both quantities are history dependent and spatially variable, thus resulting in nonlinear equations of motion. It is explained briefly how these equations may be quasi-linearized for laminated polymeric composites under certain types of structural loading. The coupled heat conduction equation is developed, and it is shown that an enhanced Zener damping effect is produced by the introduction of microstructural damage. The resulting equations are utilized to demonstrate how damage dependent material properties may be obtained from dynamic experiments. Finaly, experimental results are compared to model predictions for several composite layups.

Seismic velocities and geologic logs from boreholes at three downhole arrays in San Francisco, California

USGS Publications Warehouse

Gibbs, James F.; Fumal, Thomas E.; Borcherdt, Roger D.; Warrick, Richard E.; Liu, Hsi-Ping; Westerlund, Robert E.

1994-01-01

The Loma Prieta earthquake of October 17, 1989 (1704 PST), has reinforced observations made by Wood and others (1908) after the 1906 San Francisco earthquake, that poor ground conditions (soft soil) increase the likelihood of shaking damage to structures. Since 1908 many studies (for example Borcherdt, 1970, Borcherdt and Gibbs, 1976, Borcherdt and Glassmoyer, 1992) have shown that soft soils amplify seismic waves at frequencies that can be damaging to structures. Damage in the City of San Francisco from the Loma Prieta earthquake was concentrated in the Marina District, the Embarcadero, and the China Basin areas. Each of these areas, to some degree, is underlain by soft soil deposits. These concentrations of damage raise important questions regarding the amplification effects of such deposits at damaging levels of motion. Unfortunately, no strong-motion recordings were obtained in these areas during the Loma Prieta earthquake and only a limited number (< 10) have been obtained on other soft soil sites in the United States. Consequently, important questions exist regarding the response of such deposits during damaging earthquakes, especially questions regarding the nonlinear soil response. Towards developing a data set to address these important questions, borehole strong-motion arrays have been installed at three locations. These arrays consist of groups of wide-dynamic-range pore-pressure transducers and three-component accelerometers, the outputs of which are recorded digitally. The arrays are designed to provide an integrated set of data on ground shaking, liquifaction-induced ground failure, and structural response. This report describes the detailed geologic, seismic, and material-property determinations derived at each of these sites.

Protective Effect of Pyruvate Against Radiation-Induced Damage in Collagenized Tissues

NASA Technical Reports Server (NTRS)

Griko, Y. V.; Yan, Xiaoli

2016-01-01

Exposure to high doses of ionizing radiation produces both acute and late effects on the collagenized tissues and have profound effects on wound healing. Because of the crucial practical importance for new radioprotective agents, our study has been focused on evaluation of the efficacy of non-toxic naturally occurring compounds to protect tissue integrity against high-dose gamma radiation. Here, we demonstrate that molecular integrity of collagen may serve as a sensitive biological marker for quantitative evaluation of molecular damage to collagenized tissue and efficacy of radioprotective agents. Increasing doses of gamma radiation (0-50kGy) result in progressive destruction of the native collagen fibrils, which provide a structural framework, strength, and proper milieu for the regenerating tissue. The strategy used in this study involved the thermodynamic specification of all structural changes in collagenized matrix of skin, aortic heart valve, and bone tissue induced by different doses and conditions of g-irradiation. This study describes a simple biophysical approach utilizing the Differential Scanning Calorimetry (DSC) to characterize the structural resistance of the aortic valve matrix exposed to different doses of g-irradiation. It allows us to identify the specific response of each constituent as well as to determine the influence of the different treatments on the characteristic parameters of protein structure. We found that pyruvate, a substance that naturally occurs in the body, provide significant protection (up to 80%) from biochemical and biomechanical damage to the collagenized tissue through the effective targeting of reactive oxygen species. The recently discovered role of pyruvate in the cell antioxidant defense to O2 oxidation, and its essential constituency in the daily human diet, indicate that the administration of pyruvate-based radioprotective formulations may provide safe and effective protection from deleterious effects of ionizing radiation.

Characterization of laser induced damage of HR coatings with picosecond pulses

NASA Astrophysics Data System (ADS)

Li, Cheng; Zhao, Yuan'an; Cui, Yun; Wang, Yueliang; Peng, Xiaocong; Shan, Chong; Zhu, Meiping; Wang, Jianguo; Shao, Jianda

2017-11-01

The effect of protective layer on the picosecond laser-induced damage behaviors of HfO2/SiO2 high-reflective (HR) coatings are explored. Two kinds of 1064nm HR coatings with and without protective layer are deposited by electron beam evaporation. Laser-induced damage tests are conducted with 1064nm, 30ps S-polarized and P-polarized pulses with different angle of incidence (AOI) to make the electric fields intensity in the HR coatings discrepantly. Damage morphology and cross section of damage sites were characterized by scanning electron microscope (SEM) and focused ion beam (FIB), respectively. It is found that SiO2 protective layer have a certain degree of improvement on laser induced damage threshold (LIDT) for every AOIs. The onset damage initiated very near to the Max peak of e-field, after which forms ripple-like pits. The damage morphology presents as layer delamination at high fluence. The Laser damage resistance is correspond with the maximum E-intensity in the coating stacks.

Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin.

PubMed

Lai, Yu; Zhong, Wa; Yu, Tao; Xia, Zhong-Sheng; Li, Jie-Yao; Ouyang, Hui; Shan, Ti-Dong; Yang, Hong-Sheng; Chen, Qi-Kui

2015-01-01

The effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage. BALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively. COX expression was significantly down-regulated in aspirin induced SII (P < 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P < 0.05). Rebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin.

Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin

PubMed Central

Yu, Tao; Xia, Zhong-Sheng; Li, Jie-Yao; Ouyang, Hui; Shan, Ti-Dong; Yang, Hong-Sheng; Chen, Qi-Kui

2015-01-01

Background The effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage. Methods BALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively. Results COX expression was significantly down-regulated in aspirin induced SII (P < 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P < 0.05). Conclusion Rebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin. PMID:26135128

Structural Pain Compensating Flight Control

NASA Technical Reports Server (NTRS)

Miller, Chris J.

2014-01-01

The problem of control command and maneuver induced structural loads is an important aspect of any control system design. Designers must design the aircraft structure and the control architecture to achieve desired piloted control responses while limiting the imparted structural loads. The classical approach is to build the structure with high margins, restrict control surface commands to known good combinations, and train pilots to follow procedural maneuvering limitations. With recent advances in structural sensing and the continued desire to improve safety and vehicle fuel efficiency, it is both possible and desirable to develop control architectures that enable lighter vehicle weights while maintaining and improving protection against structural damage.

High-pressure-assisted X-ray-induced damage as a new route for materials synthesis

DOE PAGES

Evlyukhin, Egor; Kim, Eunja; Goldberger, David; ...

2018-01-01

X-ray radiation induced damage has been known for decades and has largely been viewed as a tremendous nuisance; e.g., most X-ray-related studies of organic and inorganic materials suffer X-ray damage to varying degrees. Although, recent theoretical and experimental investigation of the response of simple chemical systems to X-rays offered better understanding of the mechanistic details of X-ray induced damage, the question about useful applicability of this technique is still unclear. Furthermore we experimentally demonstrate that by tuning pressure and X-ray energy, the radiation induced damage can be controlled and used for synthesis of novel materials.

Robust optimization of the laser induced damage threshold of dielectric mirrors for high power lasers.

PubMed

Chorel, Marine; Lanternier, Thomas; Lavastre, Éric; Bonod, Nicolas; Bousquet, Bruno; Néauport, Jérôme

2018-04-30

We report on a numerical optimization of the laser induced damage threshold of multi-dielectric high reflection mirrors in the sub-picosecond regime. We highlight the interplay between the electric field distribution, refractive index and intrinsic laser induced damage threshold of the materials on the overall laser induced damage threshold (LIDT) of the multilayer. We describe an optimization method of the multilayer that minimizes the field enhancement in high refractive index materials while preserving a near perfect reflectivity. This method yields a significant improvement of the damage resistance since a maximum increase of 40% can be achieved on the overall LIDT of the multilayer.

Quantitatively characterizing microstructural variations of skin tissues during ultraviolet radiation damaging process based on Mueller matrix polarimetry

NASA Astrophysics Data System (ADS)

Sheng, Wei; He, Honghui; Dong, Yang; Ma, Hui

2018-02-01

As one of the most fundamental features of light, polarization can be used to develop imaging techniques which can provide insight into the optical and structural properties of tissues. Especially, the Mueller matrix polarimetry is suitable to detect the changes in collagen and elastic fibres, which are the main compositions of skin tissue. Here we demonstrate a novel quantitative, non-contact and in situ technique to monitor the microstructural variations of skin tissue during ultraviolet radiation (UVR) induced photoaging based on Mueller matrix polarimetry. Specifically, we measure the twodimensional (2D) backscattering Mueller matrices of nude mouse skin samples, then calculate and analyze the Mueller matrix derived parameters during the skin photoaging and self-repairing processes. To induce three-day skin photoaging, the back skin of each mouse is irradiated with UVR (0.05J/cm2) for five minutes per day. After UVR, the microstructures of the nude mouse skin are damaged. During the process of UV damage, we measure the backscattering Mueller matrices of the mouse skin samples and examine the relationship between the Mueller matrix parameters and the microstructural variations of skin tissue quantitatively. The comparisons between the UVR damaged groups with and without sunscreens show that the Mueller matrix derived parameters are potential indicators for fibrous microstructure variation in skin tissue. The pathological examinations and Monte Carlo simulations confirm the relationship between the values of Mueller matrix parameters and the changes of fibrous structures. Combined with smart phones or wearable devices, this technique may have a good application prospect in the fields of cosmetics and dermatological health.

Walnut polyphenols prevent liver damage induced by carbon tetrachloride and d-galactosamine: hepatoprotective hydrolyzable tannins in the kernel pellicles of walnut.

PubMed

Shimoda, Hiroshi; Tanaka, Junji; Kikuchi, Mitsunori; Fukuda, Toshiyuji; Ito, Hideyuki; Hatano, Tsutomu; Yoshida, Takashi

2008-06-25

The polyphenol-rich fraction (WP, 45% polyphenol) prepared from the kernel pellicles of walnuts was assessed for its hepatoprotective effect in mice. A single oral administration of WP (200 mg/kg) significantly suppressed serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) elevation in liver injury induced by carbon tetrachloride (CCl 4), while it did not suppress d-galactosamine (GalN)-induced liver injury. In order to identify the active principles in WP, we examined individual constituents for the protective effect on cell damage induced by CCl 4 and d-GalN in primary cultured rat hepatocytes. WP was effective against both CCl 4- and d-GalN-induced hepatocyte damages. Among the constituents, only ellagitannins with a galloylated glucopyranose core, such as tellimagrandins I, II, and rugosin C, suppressed CCl 4-induced hepatocyte damage significantly. Most of the ellagitannins including tellimagrandin I and 2,3- O-hexahydroxydiphenoylglucose exhibited remarkable inhibitory effect against d-GalN-induced damage. Telliamgrandin I especially completely suppressed both CCl 4- and d-GalN-induced cell damage, and thus is likely the principal constituent for the hepatoprotective effect of WP.

AtMMS21, an SMC5/6 complex subunit, is involved in stem cell niche maintenance and DNA damage responses in Arabidopsis roots.

PubMed

Xu, Panglian; Yuan, Dongke; Liu, Ming; Li, Chunxin; Liu, Yiyang; Zhang, Shengchun; Yao, Nan; Yang, Chengwei

2013-04-01

Plants maintain stem cells in meristems to sustain lifelong growth; these stem cells must have effective DNA damage responses to prevent mutations that can propagate to large parts of the plant. However, the molecular links between stem cell functions and DNA damage responses remain largely unexplored. Here, we report that the small ubiquitin-related modifier E3 ligase AtMMS21 (for methyl methanesulfonate sensitivity gene21) acts to maintain the root stem cell niche by mediating DNA damage responses in Arabidopsis (Arabidopsis thaliana). Mutation of AtMMS21 causes defects in the root stem cell niche during embryogenesis and postembryonic stages. AtMMS21 is essential for the proper expression of stem cell niche-defining transcription factors. Moreover, mms21-1 mutants are hypersensitive to DNA-damaging agents, have a constitutively increased DNA damage response, and have more DNA double-strand breaks (DSBs) in the roots. Also, mms21-1 mutants exhibit spontaneous cell death within the root stem cell niche, and treatment with DSB-inducing agents increases this cell death, suggesting that AtMMS21 is required to prevent DSB-induced stem cell death. We further show that AtMMS21 functions as a subunit of the STRUCTURAL MAINTENANCE OF CHROMOSOMES5/6 complex, an evolutionarily conserved chromosomal ATPase required for DNA repair. These data reveal that AtMMS21 acts in DSB amelioration and stem cell niche maintenance during Arabidopsis root development.

Telomere damage induced by the G-quadruplex ligand RHPS4 has an antitumor effect

PubMed Central

Salvati, Erica; Leonetti, Carlo; Rizzo, Angela; Scarsella, Marco; Mottolese, Marcella; Galati, Rossella; Sperduti, Isabella; Stevens, Malcolm F.G.; D’Incalci, Maurizio; Blasco, Maria; Chiorino, Giovanna; Bauwens, Serge; Horard, Béatrice; Gilson, Eric; Stoppacciaro, Antonella; Zupi, Gabriella; Biroccio, Annamaria

2007-01-01

Functional telomeres are required for the replicability of cancer cells. The G-rich strand of telomeric DNA can fold into a 4-stranded structure known as the G-quadruplex (G4), whose stabilization alters telomere function limiting cancer cell growth. Therefore, the G4 ligand RHPS4 may possess antitumor activity. Here, we show that RHPS4 triggers a rapid and potent DNA damage response at telomeres in human transformed fibroblasts and melanoma cells, characterized by the formation of several telomeric foci containing phosphorylated DNA damage response factors γ-H2AX, RAD17, and 53BP1. This was dependent on DNA repair enzyme ATR, correlated with delocalization of the protective telomeric DNA–binding protein POT1, and was antagonized by overexpression of POT1 or TRF2. In mice, RHPS4 exerted its antitumor effect on xenografts of human tumor cells of different histotype by telomere injury and tumor cell apoptosis. Tumor inhibition was accompanied by a strong DNA damage response, and tumors overexpressing POT1 or TRF2 were resistant to RHPS4 treatment. These data provide evidence that RHPS4 is a telomere damage inducer and that telomere disruption selectively triggered in malignant cells results in a high therapeutic index in mice. They also define a functional link between telomere damage and antitumor activity and reveal the key role of telomere-protective factors TRF2 and POT1 in response to this anti-telomere strategy. PMID:17932567

Efficacy of vitamin C against liver and kidney damage induced by paraquat toxicity.

PubMed

Awadalla, Eatemad A

2012-07-01

Paraquat has been demonstrated to be a highly toxic compound for humans and animals and many cases of acute poisoning and death have been reported over the past few decades. The current experiment aimed to examine if vitamin C (ascorbic acid) alleviates the morphological changes induced by paraquat (PQ) administration in the liver and kidney of male albino rats. Male adult rats received paraquat (PQ) (1.5 mg/kg body weight) daily for three weeks. Vitamin C (VC) at a dose of 20 mg/kg body weight was given concomitantly with PQ to rats. Animals were divided into three groups in this experiment (control, PQ and PQ+VC). The morphopathological manifestations were investigated in tissues from liver and kidney. As expected, PQ administration induced marked changes in the morphological structure of the liver and kidney in PQ demonstrated animals. Importantly, vitamin C administration restored PQ-induced changes in the studied organs. Vitamin C administration attenuated the morphological damages induced by PQ in the liver and kidney of experimental animals. Our results suggest an antitoxic effect of vitamin C against paraquat. Copyright © 2010 Elsevier GmbH. All rights reserved.

Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer

PubMed Central

King, Suzanne N.; Dunlap, Neal E.; Tennant, Paul A.; Pitts, Teresa

2017-01-01

Oncologic treatments, such as curative radiotherapy and chemoradiation, for head and neck cancer can cause long-term swallowing impairments (dysphagia) that negatively impact quality of life. Radiation-induced dysphagia is comprised of a broad spectrum of structural, mechanical, and neurologic deficits. An understanding of the biomolecular effects of radiation on the time course of wound healing and underlying morphological tissue responses that precede radiation damage will improve options available for dysphagia treatment. The goal of this review is to discuss the pathophysiology of radiation-induced injury and elucidate areas that need further exploration. PMID:27098922

In vitro Cytotoxicity and Genotoxicity Analysis of Ten Tannery Chemicals Using SOS/umu Tests and High-content In vitro Micronucleus Tests.

PubMed

Huang, Zehao; Li, Na; Rao, Kaifeng; Liu, Cuiting; Wang, Zijian; Ma, Mei

2018-01-01

More than 2,000 chemicals have been used in the tannery industry. Although some tannery chemicals have been reported to have harmful effects on both human health and the environment, only a few have been subjected to genotoxicity and cytotoxicity evaluations. This study focused on cytotoxicity and genotoxicity of ten tannery chemicals widely used in China. DNA-damaging effects were measured using the SOS/umu test with Salmonella typhimurium TA1535/pSK1002. Chromosome-damaging and cytotoxic effects were determined with the high-content in vitro Micronucleus test (MN test) using the human-derived cell lines MGC-803 and A549. The cytotoxicity of the ten tannery chemicals differed somewhat between the two cell assays, with A549 cells being more sensitive than MGC-803 cells. None of the chemicals induced DNA damage before metabolism, but one was found to have DNA-damaging effects on metabolism. Four of the chemicals, DY64, SB1, DB71 and RR120, were found to have chromosome-damaging effects. A Quantitative Structure-Activity Relationship (QSAR) analysis indicated that one structural feature favouring chemical genotoxicity, Hacceptor-path3-Hacceptor, may contribute to the chromosome-damaging effects of the four MN-test-positive chemicals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Molecular dynamics simulations of damage production by thermal spikes in Ge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lopez, Pedro; Pelaz, Lourdes; Santos, Ivan

2012-02-01

Molecular dynamics simulation techniques are used to analyze damage production in Ge by the thermal spike process and to compare the results to those obtained for Si. As simulation results are sensitive to the choice of the inter-atomic potential, several potentials are compared in terms of material properties relevant for damage generation, and the most suitable potentials for this kind of analysis are identified. A simplified simulation scheme is used to characterize, in a controlled way, the damage generation through the local melting of regions in which energy is deposited. Our results show the outstanding role of thermal spikes inmore » Ge, since the lower melting temperature and thermal conductivity of Ge make this process much more efficient in terms of damage generation than in Si. The study is extended to the modeling of full implant cascades, in which both collision events and thermal spikes coexist. Our simulations reveal the existence of bigger damaged or amorphous regions in Ge than in Si, which may be formed by the melting and successive quenching induced by thermal spikes. In the particular case of heavy ion implantation, defect structures in Ge are not only bigger, but they also present a larger net content in vacancies than in Si, which may act as precursors for the growth of voids and the subsequent formation of honeycomb-like structures.« less

Shock wave lithotripsy (SWL) induces significant structural and functional changes in the kidney

NASA Astrophysics Data System (ADS)

Evan, Andrew P.; Willis, Lynn R.; Lingeman, James E.

2003-10-01

The foundation for understanding SWL-injury has been well-controlled renal structural and functional studies in pigs, a model that closely mimics the human kidney. A clinical dose (2000 shocks at 24 kV) of SWL administered by the Dornier HM3 induces a predictable, unique vascular injury at F2 that is associated with transient renal vasoconstriction, seen as a reduction in renal plasma flow, in both treated and untreated kidneys. Unilateral renal denervation studies links the fall in blood flow in untreated kidneys to autonomic nerve activity in the treated kidney. SWL-induced trauma is associated with an acute inflammatory process, termed Lithotripsy Nephritis and tubular damage at the site of damage that leads to a focal region of scar. Lesion size increases with shock number and kV level. In addition, risk factors like kidney size and pre-existing renal disease (e.g., pyelonephritis), can exaggerate the predicted level of renal impairment. Our new protection data show that lesion size can be greatly reduced by a pretreatment session with low kV and shock number. The mechanisms of soft tissue injury probably involves shear stress followed by acoustic cavitation. Because of the perceived enhanced level of bioeffects from 3rd generation lithotripters, these observations are more relevant than ever.

Protective effect of hydroxytyrosol and its metabolite homovanillic alcohol on H(2)O(2) induced lipid peroxidation in renal tubular epithelial cells.

PubMed

Deiana, Monica; Incani, Alessandra; Rosa, Antonella; Corona, Giulia; Atzeri, Angela; Loru, Debora; Paola Melis, M; Assunta Dessì, M

2008-09-01

We investigated the capacity of hydroxytyrosol (HT), 3,4-dihydroxyphenylethanol, and homovanillic alcohol (HVA), 4-hydroxy-3-methoxy-phenylethanol, to inhibit H(2)O(2) induced oxidative damage in LLC-PK1, a porcine kidney epithelial cell line, studying the effect of H(2)O(2) on specific cell membrane lipid targets, unsaturated fatty acids and cholesterol. Exposure to H(2)O(2) induced a significant increase of the level of MDA together with a disruption of the membrane structure, with the loss of unsaturated fatty acids, cholesterol and alpha-tocopherol, and the formation of fatty acids hydroperoxides and 7-ketocholesterol. Pretreatment with HT protected renal cells from oxidative damage: the level of membrane lipids was preserved and there was no significant detection of oxidation products. HVA exerted a comparable activity, thus both HT and HVA were able to prevent in renal cells the lipid peroxidation process that plays a central role in tubular cell injury.

Enthalpy Landscape Dictates the Irradiation-Induced Disordering of Quartz

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krishnan, N. M. Anoop; Wang, Bu; Yu, Yingtian

Here, under irradiation, minerals tend to experience an accumulation of structural defects, ultimately leading to a disordered atomic network. Despite the critical importance of understanding and predicting irradiation-induced damage, the physical origin of the initiation and saturation of defects remains poorly understood. Here, based on molecular dynamics simulations of α-quartz, we show that the topography of the enthalpy landscape governs irradiation-induced disordering. Specifically, we show that such disordering differs from that observed upon vitrification in that, prior to saturation, irradiated quartz accesses forbidden regions of the enthalpy landscape, i.e., those that are inaccessible by simply heating and cooling. Furthermore, wemore » demonstrate that damage saturates when the system accesses a local region of the enthalpy landscape corresponding to the configuration of an allowable liquid. At this stage, a sudden decrease in the heights of the energy barriers enhances relaxation, thereby preventing any further accumulation of defects and resulting in a defect-saturated disordered state.« less

Enthalpy Landscape Dictates the Irradiation-Induced Disordering of Quartz

DOE PAGES

Krishnan, N. M. Anoop; Wang, Bu; Yu, Yingtian; ...

2017-07-28

Here, under irradiation, minerals tend to experience an accumulation of structural defects, ultimately leading to a disordered atomic network. Despite the critical importance of understanding and predicting irradiation-induced damage, the physical origin of the initiation and saturation of defects remains poorly understood. Here, based on molecular dynamics simulations of α-quartz, we show that the topography of the enthalpy landscape governs irradiation-induced disordering. Specifically, we show that such disordering differs from that observed upon vitrification in that, prior to saturation, irradiated quartz accesses forbidden regions of the enthalpy landscape, i.e., those that are inaccessible by simply heating and cooling. Furthermore, wemore » demonstrate that damage saturates when the system accesses a local region of the enthalpy landscape corresponding to the configuration of an allowable liquid. At this stage, a sudden decrease in the heights of the energy barriers enhances relaxation, thereby preventing any further accumulation of defects and resulting in a defect-saturated disordered state.« less

Chemical and Structural Stability of Lithium-Ion Battery Electrode Materials under Electron Beam

DOE PAGES

Lin, Feng; Markus, Isaac M.; Doeff, Marca M.; ...

2014-07-16

Our investigation of chemical and structural dynamics in battery materials is essential to elucidation of structure-property relationships for rational design of advanced battery materials. Spatially resolved techniques, such as scanning/transmission electron microscopy (S/TEM), are widely applied to address this challenge. But, battery materials are susceptible to electron beam damage, complicating the data interpretation. In this study, we demonstrate that, under electron beam irradiation, the surface and bulk of battery materials undergo chemical and structural evolution equivalent to that observed during charge-discharge cycling. In a lithiated NiO nanosheet, a Li2CO3-containing surface reaction layer (SRL) was gradually decomposed during electron energy loss spectroscopy (EELS) acquisition. For cycled LiNi 0.4Mn 0.4Co 0.18Ti 0.02O 2 particles, repeated electron beam irradiation induced a phase transition from an Rmore » $$\\bar{3}$$m layered structure to an rock-salt structure, which is attributed to the stoichiometric lithium and oxygen removal from R$$\\bar{3}$$m 3a and 6c sites, respectively. Nevertheless, it is still feasible to preserve pristine chemical environments by minimizing electron beam damage, for example, in using fast electron imaging and spectroscopy. Finally, the present study provides examples of electron beam damage on lithium-ion battery materials and suggests that special attention is necessary to prevent misinterpretation of experimental results.« less

Strain sensors optimal placement for vibration-based structural health monitoring. The effect of damage on the initially optimal configuration

NASA Astrophysics Data System (ADS)

Loutas, T. H.; Bourikas, A.

2017-12-01

We revisit the optimal sensor placement of engineering structures problem with an emphasis on in-plane dynamic strain measurements and to the direction of modal identification as well as vibration-based damage detection for structural health monitoring purposes. The approach utilized is based on the maximization of a norm of the Fisher Information Matrix built with numerically obtained mode shapes of the structure and at the same time prohibit the sensorization of neighbor degrees of freedom as well as those carrying similar information, in order to obtain a satisfactory coverage. A new convergence criterion of the Fisher Information Matrix (FIM) norm is proposed in order to deal with the issue of choosing an appropriate sensor redundancy threshold, a concept recently introduced but not further investigated concerning its choice. The sensor configurations obtained via a forward sequential placement algorithm are sub-optimal in terms of FIM norm values but the selected sensors are not allowed to be placed in neighbor degrees of freedom providing thus a better coverage of the structure and a subsequent better identification of the experimental mode shapes. The issue of how service induced damage affects the initially nominated as optimal sensor configuration is also investigated and reported. The numerical model of a composite sandwich panel serves as a representative aerospace structure upon which our investigations are based.

Reducing seismic risk to highway mobility : assessment and design examples for pile foundations affected by lateral spreading.

DOT National Transportation Integrated Search

2013-04-01

Damage in pile supported structures due to liquefaction and liquefaction induced deformation were reported in past earthquakes around the world : (e.g., Ansal et al. 1999; Seed et al. 1990; EERI 2010, EERI 2011; GEER 2010a, GEER 2010b, GEER 2011). Fo...

SYNAPTONEMAL COMPLEX DAMAGE IN RELATION TO MEIOTIC CHROMOSOME ABERRATIONS AFTER EXPOSURE OF MALE MICE TO CYCLOPHOSPHAMIDE (JOURNAL VERSION)

EPA Science Inventory

Cyclophosphamide (CP) has been reported to cause structural and numerical chromosome aberrations in mouse spermatocyte metaphase chromosomes. Further, it was concluded to be one of the few chemicals for which there appears to be reliable data suggesting that it can induce germ ce...

Hyperthyroidism causes cardiac dysfunction by mitochondrial impairment and energy depletion.

PubMed

Maity, Sangeeta; Kar, Dipak; De, Kakali; Chander, Vivek; Bandyopadhyay, Arun

2013-05-01

This study elucidates the role of metabolic remodeling in cardiac dysfunction induced by hyperthyroidism. Cardiac hypertrophy, structural remodeling, and expression of the genes associated with fatty acid metabolism were examined in rats treated with triiodothyronine (T3) alone (8 μg/100 g body weight (BW), i.p.) for 15 days or along with a peroxisome proliferator-activated receptor alpha agonist bezafibrate (Bzf; 30 μg/100 g BW, oral) and were found to improve in the Bzf co-treated condition. Ultrastructure of mitochondria was damaged in T3-treated rat heart, which was prevented by Bzf co-administration. Hyperthyroidism-induced oxidative stress, reduction in cytochrome c oxidase activity, and myocardial ATP concentration were also significantly checked by Bzf. Heart function studied at different time points during the course of T3 treatment shows an initial improvement and then a gradual but progressive decline with time, which is prevented by Bzf co-treatment. In summary, the results demonstrate that hyperthyroidism inflicts structural and functional damage to mitochondria, leading to energy depletion and cardiac dysfunction.

Histone H3 Lysine 14 (H3K14) Acetylation Facilitates DNA Repair in a Positioned Nucleosome by Stabilizing the Binding of the Chromatin Remodeler RSC (Remodels Structure of Chromatin)*

PubMed Central

Duan, Ming-Rui; Smerdon, Michael J.

2014-01-01

Histone H3 acetylation is induced by UV damage in yeast and may play an important role in regulating the repair of UV photolesions in nucleosome-loaded genomic loci. However, it remains elusive how H3 acetylation facilitates repair. We generated a strongly positioned nucleosome containing homogeneously acetylated H3 at Lys-14 (H3K14ac) and investigated possible mechanisms by which H3K14 acetylation modulates repair. We show that H3K14ac does not alter nucleosome unfolding dynamics or enhance the repair of UV-induced cyclobutane pyrimidine dimers by UV photolyase. Importantly, however, nucleosomes with H3K14ac have a higher affinity for purified chromatin remodeling complex RSC (Remodels the Structure of Chromatin) and show greater cyclobutane pyrimidine dimer repair compared with unacetylated nucleosomes. Our study indicates that, by anchoring RSC, H3K14 acetylation plays an important role in the unfolding of strongly positioned nucleosomes during repair of UV damage. PMID:24515106

Application of a Subspace-Based Fault Detection Method to Industrial Structures

NASA Astrophysics Data System (ADS)

Mevel, L.; Hermans, L.; van der Auweraer, H.

1999-11-01

Early detection and localization of damage allow increased expectations of reliability, safety and reduction of the maintenance cost. This paper deals with the industrial validation of a technique to monitor the health of a structure in operating conditions (e.g. rotating machinery, civil constructions subject to ambient excitations, etc.) and to detect slight deviations in a modal model derived from in-operation measured data. In this paper, a statistical local approach based on covariance-driven stochastic subspace identification is proposed. The capabilities and limitations of the method with respect to health monitoring and damage detection are discussed and it is explained how the method can be practically used in industrial environments. After the successful validation of the proposed method on a few laboratory structures, its application to a sports car is discussed. The example illustrates that the method allows the early detection of a vibration-induced fatigue problem of a sports car.

Vitamin C mitigates oxidative/nitrosative stress and inflammation in doxorubicin-induced cardiomyopathy.

PubMed

Akolkar, Gauri; da Silva Dias, Danielle; Ayyappan, Prathapan; Bagchi, Ashim K; Jassal, Davinder S; Salemi, Vera Maria Cury; Irigoyen, Maria Claudia; De Angelis, Katia; Singal, Pawan K

2017-10-01

Increase in oxidative/nitrosative stress is one of the mechanisms associated with the development of cardiotoxicity due to doxorubicin (Dox), a potent chemotherapy drug. Previously, we reported mitigation of Dox-induced oxidative/nitrosative stress and apoptosis by vitamin C (Vit C) in isolated cardiomyocytes. In the present in vivo study in rats, we investigated the effect of prophylactic treatment with Vit C on Dox-induced apoptosis, inflammation, oxidative/nitrosative stress, cardiac dysfunction, and Vit C transporter proteins. Dox (cumulative dose: 15 mg/kg) in rats reduced systolic and diastolic cardiac function and caused structural damage. These changes were associated with a myocardial increase in reactive oxygen species, reduction in antioxidant enzyme activities, increased expression of apoptotic proteins, and inflammation. Dox also caused an increase in the expression of proapoptotic proteins Bax, Bnip-3, Bak, and caspase-3. An increase in oxidative/nitrosative stress attributable to Dox was indicated by an increase in superoxide, protein carbonyl formation, lipid peroxidation, nitric oxide (NO), NO synthase (NOS) activity, protein nitrosylation, and inducible NOS protein expression. Dox increased the levels of cardiac proinflammatory cytokines TNF-α, IL-1β, and IL-6, whereas the expression of Vit C transporter proteins (sodium-ascorbate cotransporter 2 and glucose transporter 4) was reduced. Prophylactic and concurrent treatment with Vit C prevented all these changes and improved survival in the Vit C + Dox group. Vit C also improved Dox-mediated systolic and diastolic dysfunctions and structural damage. These results suggest a cardioprotective role of Vit C in Dox-induced cardiomyopathy by reducing oxidative/nitrosative stress, inflammation, and apoptosis, as well as improving Vit C transporter proteins. NEW & NOTEWORTHY This in vivo study provides novel data that vitamin C improves cardiac structure and function in doxorubicin-induced cardiomyopathy by reducing oxidative/nitrosative stress, apoptosis, and inflammation along with upregulation of cardiac vitamin C transporter proteins. The latter may have a crucial role in improving antioxidant status in this cardiomyopathy. Copyright © 2017 the American Physiological Society.

Curcumin-Mediated HDAC Inhibition Suppresses the DNA Damage Response and Contributes to Increased DNA Damage Sensitivity

PubMed Central

Wang, Shu-Huei; Lin, Pei-Ya; Chiu, Ya-Chen; Huang, Ju-Sui; Kuo, Yi-Tsen; Wu, Jen-Chine; Chen, Chin-Chuan

2015-01-01

Chemo- and radiotherapy cause multiple forms of DNA damage and lead to the death of cancer cells. Inhibitors of the DNA damage response are candidate drugs for use in combination therapies to increase the efficacy of such treatments. In this study, we show that curcumin, a plant polyphenol, sensitizes budding yeast to DNA damage by counteracting the DNA damage response. Following DNA damage, the Mec1-dependent DNA damage checkpoint is inactivated and Rad52 recombinase is degraded by curcumin, which results in deficiencies in double-stand break repair. Additive effects on damage-induced apoptosis and the inhibition of damage-induced autophagy by curcumin were observed. Moreover, rpd3 mutants were found to mimic the curcumin-induced suppression of the DNA damage response. In contrast, hat1 mutants were resistant to DNA damage, and Rad52 degradation was impaired following curcumin treatment. These results indicate that the histone deacetylase inhibitor activity of curcumin is critical to DSB repair and DNA damage sensitivity. PMID:26218133

Protective activity of green tea against free radical- and glucose-mediated protein damage.

PubMed

Nakagawa, Takako; Yokozawa, Takako; Terasawa, Katsutoshi; Shu, Seiji; Juneja, Lekh Raj

2002-04-10

Protein oxidation and glycation are posttranslational modifications that are implicated in the pathological development of many age-related disease processes. This study investigated the effects of green tea extract, and a green tea tannin mixture and its components, on protein damage induced by 2,2'-azobis(2-amidinopropane) dihydrochloride (a free radical generator) and glucose in in vitro assay systems. We found that green tea extract can effectively protect against protein damage, and showed that its action is mainly due to tannin. In addition, it was shown that the chemical structures of tannin components are also involved in this activity, suggesting that the presence of the gallate group at the 3 position plays the most important role in the protective activity against protein oxidation and glycation, and that there is also a contribution by the hydroxyl group at the 5' position in the B ring and the sterical structure. These findings demonstrate the mechanisms of the usefulness of green tea in protein oxidation- and glycation-associated diseases.

Theoretical research and experimental validation of elastic dynamic load spectra on bogie frame of high-speed train

NASA Astrophysics Data System (ADS)

Zhu, Ning; Sun, Shouguang; Li, Qiang; Zou, Hua

2016-05-01

When a train runs at high speeds, the external exciting frequencies approach the natural frequencies of bogie critical components, thereby inducing strong elastic vibrations. The present international reliability test evaluation standard and design criteria of bogie frames are all based on the quasi-static deformation hypothesis. Structural fatigue damage generated by structural elastic vibrations has not yet been included. In this paper, theoretical research and experimental validation are done on elastic dynamic load spectra on bogie frame of high-speed train. The construction of the load series that correspond to elastic dynamic deformation modes is studied. The simplified form of the load series is obtained. A theory of simplified dynamic load-time histories is then deduced. Measured data from the Beijing-Shanghai Dedicated Passenger Line are introduced to derive the simplified dynamic load-time histories. The simplified dynamic discrete load spectra of bogie frame are established. Based on the damage consistency criterion and a genetic algorithm, damage consistency calibration of the simplified dynamic load spectra is finally performed. The computed result proves that the simplified load series is reasonable. The calibrated damage that corresponds to the elastic dynamic discrete load spectra can cover the actual damage at the operating conditions. The calibrated damage satisfies the safety requirement of damage consistency criterion for bogie frame. This research is helpful for investigating the standardized load spectra of bogie frame of high-speed train.

Multi-damage identification based on joint approximate diagonalisation and robust distance measure

NASA Astrophysics Data System (ADS)

Cao, S.; Ouyang, H.

2017-05-01

Mode shapes or operational deflection shapes are highly sensitive to damage and can be used for multi-damage identification. Nevertheless, one drawback of this kind of methods is that the extracted spatial shape features tend to be compromised by noise, which degrades their damage identification accuracy, especially for incipient damage. To overcome this, joint approximate diagonalisation (JAD) also known as simultaneous diagonalisation is investigated to estimate mode shapes (MS’s) statistically. The major advantage of JAD method is that it efficiently provides the common Eigen-structure of a set of power spectral density matrices. In this paper, a new criterion in terms of coefficient of variation (CV) is utilised to numerically demonstrate the better noise robustness and accuracy of JAD method over traditional frequency domain decomposition method (FDD). Another original contribution is that a new robust damage index (DI) is proposed, which is comprised of local MS distortions of several modes weighted by their associated vibration participation factors. The advantage of doing this is to include fair contributions from changes of all modes concerned. Moreover, the proposed DI provides a measure of damage-induced changes in ‘modal vibration energy’ in terms of the selected mode shapes. Finally, an experimental study is presented to verify the efficiency and noise robustness of JAD method and the proposed DI. The results show that the proposed DI is effective and robust under random vibration situations, which indicates that it has the potential to be applied to practical engineering structures with ambient excitations.

Towards improved NDE and SHM methodologies incorporating nonlinear structural features

NASA Astrophysics Data System (ADS)

Chillara, Vamshi Krishna

Ultrasound is widely employed in Nondestructive Evaluation (NDE) and Structural Health Monitoring (SHM) applications to detect and characterize damage/defects in materials. In particular, ultrasonic guided waves are considered a foremost candidate for in-situ monitoring applications. Conventional ultrasonic techniques rely on changes/discontinuities in linear elastic material properties, namely the Young's modulus and shear modulus to detect damage. On the other hand, nonlinear ultrasonic techniques that rely on micro-scale nonlinear material/structural behavior are proven to be sensitive to damage induced microstructural changes that precede macro-scale damage and are hence capable of early damage detection. The goal of this thesis is to investigate the capabilities of nonlinear guided waves --- a fusion of nonlinear ultrasonic techniques with the guided wave methodologies for early damage detection. To that end, the thesis focuses on two important aspects of the problem: 1. Wavemechanics - deals with ultrasonic guided wave propagation in nonlinear waveguides; 2. Micromechanics - deals with correlating ultrasonic response with micro-scale nonlinear material behavior. For the development of efficient NDE and SHM methodologies that incorporate nonlinear structural features, a detailed understanding of the above aspects is indispensable. In this thesis, the wavemechanics aspect of the problem is dealt with from both theoretical and numerical standpoints. A generalized theoretical framework is developed to study higher harmonic guided waves in plates. This was employed to study second harmonic guided waves in pipes using a large-radius asymptotic approximation. Second harmonic guided waves in plates are studied from a numerical standpoint. Theoretical predictions are validated and some key aspects of higher harmonic generation in waveguides are outlined. Finally, second harmonic guided waves in plates with inhomogeneous and localized nonlinearities are studied and some important aspects of guided wave mode selection are addressed. The other part of the work focused on developing a micromechanics based understanding of ultrasonic higher harmonic generation. Three important aspects of micro-scale material behavior, namely tension-compression asymmetry, shearnormal coupling and deformation induced asymmetry are identified and their role in ultrasonic higher harmonic generation is discussed. Tension-compression asymmetry is identified to cause second (even) harmonic generation in materials. Then, shearnormal coupling is identified to cause generation of secondary waves of different polarity than the primary waves. In addition, deformation induced anisotropy due to the presence of residual stress/strain and its contribution to ultrasonic higher harmonic generation is qualitatively discussed. Also, the tension-compression asymmetry in the material is quantified using an energy based measure. The above measure is employed to develop a homogenization based approach amenable to multi-scale analysis to correlate microstructure with ultrasonic higher harmonic generation. Finally, experimental investigations concerning third harmonic SH wave generation in plates are carried out and the effect of load and temperature changes on nonlinear ultrasonic measurements are discussed in the context of SHM. It was found that while nonlinear ultrasound is sensitive to micro-scale damage, the relative nonlinearity parameter may not always be the best measure to quantify the nonlinearity as it is subject to spurious effects from changes in environmental factors such as loads and temperature.

Real-space analysis of radiation-induced specific changes with independent component analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borek, Dominika; Bromberg, Raquel; Hattne, Johan

A method of analysis is presented that allows for the separation of specific radiation-induced changes into distinct components in real space. The method relies on independent component analysis (ICA) and can be effectively applied to electron density maps and other types of maps, provided that they can be represented as sets of numbers on a grid. Here, for glucose isomerase crystals, ICA was used in a proof-of-concept analysis to separate temperature-dependent and temperature-independent components of specific radiation-induced changes for data sets acquired from multiple crystals across multiple temperatures. ICA identified two components, with the temperature-independent component being responsible for themore » majority of specific radiation-induced changes at temperatures below 130 K. The patterns of specific temperature-independent radiation-induced changes suggest a contribution from the tunnelling of electron holes as a possible explanation. In the second case, where a group of 22 data sets was collected on a single thaumatin crystal, ICA was used in another type of analysis to separate specific radiation-induced effects happening on different exposure-level scales. Here, ICA identified two components of specific radiation-induced changes that likely result from radiation-induced chemical reactions progressing with different rates at different locations in the structure. In addition, ICA unexpectedly identified the radiation-damage state corresponding to reduced disulfide bridges rather than the zero-dose extrapolated state as the highest contrast structure. The application of ICA to the analysis of specific radiation-induced changes in real space and the data pre-processing for ICA that relies on singular value decomposition, which was used previously in data space to validate a two-component physical model of X-ray radiation-induced changes, are discussed in detail. This work lays a foundation for a better understanding of protein-specific radiation chemistries and provides a framework for analysing effects of specific radiation damage in crystallographic and cryo-EM experiments.« less

Quantitative Evaluation of Hard X-ray Damage to Biological Samples using EUV Ptychography

NASA Astrophysics Data System (ADS)

Baksh, Peter; Odstrcil, Michal; Parsons, Aaron; Bailey, Jo; Deinhardt, Katrin; Chad, John E.; Brocklesby, William S.; Frey, Jeremy G.

2017-06-01

Coherent diffractive imaging (CDI) has become a standard method on a variety of synchrotron beam lines. The high brilliance short wavelength radiation from these sources can be used to reconstruct attenuation and relative phase of a sample with nanometre resolution via CDI methods. However, the interaction between the sample and high energy ionising radiation can cause degradation to sample structure. We demonstrate, using a laboratory based high harmonic generation (HHG) based extreme ultraviolet (EUV) source, imaging a sample of hippocampal neurons using the ptychography method. The significant increase in contrast of the sample in the EUV light allows identification of damage induced from exposure to 7.3 keV photons, without causing any damage to the sample itself.

Mechanisms Underlying Testicular Damage and Dysfunction in Mice With Partial IGF-1 Deficiency and the Effectiveness of IGF-1 Replacement Therapy.

PubMed

Castilla-Cortázar, Inma; Gago, Alberto; Muñoz, Úrsula; Ávila-Gallego, Elena; Guerra-Menéndez, Lucía; Sádaba, María Cruz; García-Magariño, Mariano; Olleros Santos-Ruiz, María; Aguirre, G A; Puche, Juan Enrique

2015-12-01

To determine whether insulin-like growth factor (IGF-1) deficiency can cause testicular damage and to examine changes of the testicular morphology and testicular function-related gene expression caused by IGF-1 deficiency. Therefore, this study aims to determine the benefits of low doses of IGF-1 and to explore the mechanisms underlying the IGF-1 replacement therapy. A murine model of IGF-1 deficiency was used to avoid any factor that could contribute to testicular damage. Testicular weight, score of histopathological damage, and gene expressions were studied in 3 experimental groups of mice: controls (wild-type Igf1(+/+)), heterozygous Igf1(+/-) with partial IGF-1 deficiency, and heterozygous Igf1(+/-) treated with IGF-1. Results show that the partial IGF-1 deficiency induced testicular damage and altered expression of genes involved in IGF-1 and growth hormone signaling and regulation, testicular hormonal function, extracellular matrix establishment and its regulation, angiogenesis, fibrogenesis, inflammation, and cytoprotection. In addition, proteins involved in tight junction expression were found to be reduced. However, low doses of IGF-1 restored the testicular damage and most of these parameters. IGF-1 deficiency caused the damage of the blood-testis barrier and testicular structure and induced the abnormal testicular function-related gene expressions. However, low doses of IGF-1 constitute an effective replacement therapy that restores the described testicular damage. Data herein show that (1) cytoprotective activities of IGF-1 seem to be mediated by heat shock proteins and that (2) connective tissue growth factor could play a relevant role together with IGF-1 in the extracellular matrix establishment. Copyright © 2015 Elsevier Inc. All rights reserved.

A Coupled Thermal–Hydrological–Mechanical Damage Model and Its Numerical Simulations of Damage Evolution in APSE

PubMed Central

Wei, Chenhui; Zhu, Wancheng; Chen, Shikuo; Ranjith, Pathegama Gamage

2016-01-01

This paper proposes a coupled thermal–hydrological–mechanical damage (THMD) model for the failure process of rock, in which coupling effects such as thermally induced rock deformation, water flow-induced thermal convection, and rock deformation-induced water flow are considered. The damage is considered to be the key factor that controls the THM coupling process and the heterogeneity of rock is characterized by the Weibull distribution. Next, numerical simulations on excavation-induced damage zones in Äspö pillar stability experiments (APSE) are carried out and the impact of in situ stress conditions on damage zone distribution is analysed. Then, further numerical simulations of damage evolution at the heating stage in APSE are carried out. The impacts of in situ stress state, swelling pressure and water pressure on damage evolution at the heating stage are simulated and analysed, respectively. The simulation results indicate that (1) the v-shaped notch at the sidewall of the pillar is predominantly controlled by the in situ stress trends and magnitude; (2) at the heating stage, the existence of confining pressure can suppress the occurrence of damage, including shear damage and tensile damage; and (3) the presence of water flow and water pressure can promote the occurrence of damage, especially shear damage. PMID:28774001

Improvement of the functional properties of nanostructured Ti-Ni shape memory alloys by means of thermomechanical processing

NASA Astrophysics Data System (ADS)

Kreitcberg, Alena

Severe plastic deformation (SPD) is commonly used for nanostructure formation in Ti-Ni shape memory alloys (SMAs), but it increases the risk of damage during processing and, consequently, negatively affects functional fatigue resistance of these materials. The principal objective of this project is, therefore, to study the interrelations between the processing conditions, damageability during processing, microstructure and the functional properties of Ti-Ni SMAs with the aim of improving long-term functional performances of these materials by optimizing their processing conditions. First, microstructure and fatigue properties of Ti-Ni SMAs were studied after thermomechanical treatment (TMT) with different combinations of severe cold and warm rolling (CR and WR), as well as intermediate and post-deformation annealing (IA and PDA) technological steps. It was shown that either when WR and IA were introduced into the TMT schedule, or CR intensity was decreased, the fatigue life was improved as a consequence of less processing-induced damage and higher density of the favorable B2-austenite texture. This improvement was reached, however, at a price of a lower multi-cycle functional stability of these materials, the latter being a direct consequence of the microstructure coarsening after higher-temperature lower-intensity processing. At the end of this study, however, it was not possible to distinguish between contributions to the functional performances of Ti-Ni SMAs from different processing-related features: a) grain/subgrain size; b) texture; and c) level of rolling-induced defects. To be capable of separating contributions to the functional properties of Ti-Ni alloys from grain/subgrain size and from texture, the theoretical crystallographic resource of recovery strain after different TMTs and, therefore, different textures, were calculated and compared with the experiment. The comparative analysis showed that the structural factors (grain/subgrain size) strongly dominate the texture contributions, and therefore, there is no real alternative to having nanocrystalline Ti-Ni alloys, if one needs to maximize the Ti-Ni alloys functional properties. Since the creation of such a microstructure requires the use of severe cold deformation techniques and neither of these techniques can be completely exempt from defects, it was deemed necessary to compare the damage tolerance of nanocrystalline Ti-Ni alloys to that of their nanosubgrained and mixed nanocrystalline/nanosubgrained counterparts. With this objective in mind, a detailed analysis of interrelations between the level of the CR/WR-induced damage (edge microcrack size and concentration) and the fatigue life of Ti- Ni SMAs was carried out. It was shown that nanocrystalline structure provides higher tolerance to small-crack propagation than nanosubgrained or mixed nanocrystalline/ nanosubgrained structures, and that low-temperature deformability of these alloys has to be improved to benefit from the property-enhancement potential of nanocrystalline structure. To broaden our knowledge in the field of Ti-Ni alloy deformability, the strain-rate sensitivity of these alloys was studied. Different microstructures, varying from the coarse- to ultrafinegrained, were created by means of equal-channel angular pressing (ECAP) and subjected to strain-rate sensitivity testing. As a result, the material with ultrafine-grained microstructure demonstrated an improved deformability as compared to the coarse-grained structure, at any deformation temperature. Moreover, it was determined that the smaller the grain size, the lower the temperature and the higher the strain-rate at which superplasticity occurs. Based on the results obtained, combined thermomechanical processing (ECAP at elevated temperatures followed by CR) was proposed and validated in terms of structural refinement with reduced level of processing-induced defects. Scientific contributions. This thesis contributes to the advancement of knowledge in the field of Ti-Ni SMAs' processing-structure-properties interactions, and the main conclusions of this study can be summed-up as follows: • Nanocrystalline Ti-Ni alloys significantly outperform nanosubgrain Ti-Ni alloys in terms of the absolute values and stability of their single- and multiple-cycle functional properties (superelasticity and shape memory characteristics). The main factor limiting the number of cycles to failure of the nanocrystalline alloys is the processingrelated damage. • The structure of Ti-Ni alloys plays significantly higher role in the realization of their functional potential that does their texture. • In terms of fatigue life, the nanocrystalline structure has lower small-crack sensitivity than does the nanosubgrained structure. • Grain refinement makes it possible to improve deformability of Ti-Ni alloys at any temperature. • To produce nanocrystalline Ti-Ni SMAs free of processing-induced-defects, a novel three-step processing is proposed (ECAP+CR+PDA): grain-refining severe plastic deformation at elevated temperatures (ECAP), followed-up by amorphizing SPD at low temperatures (CR), and ended-up by nanocrystallizing post-deformation heat treatment (PDA).

Structural basis for inhibition of the histone chaperone activity of SET/TAF-Iβ by cytochrome c

PubMed Central

González-Arzola, Katiuska; Díaz-Moreno, Irene; Cano-González, Ana; Díaz-Quintana, Antonio; Velázquez-Campoy, Adrián; Moreno-Beltrán, Blas; López-Rivas, Abelardo; De la Rosa, Miguel A.

2015-01-01

Chromatin is pivotal for regulation of the DNA damage process insofar as it influences access to DNA and serves as a DNA repair docking site. Recent works identify histone chaperones as key regulators of damaged chromatin’s transcriptional activity. However, understanding how chaperones are modulated during DNA damage response is still challenging. This study reveals that the histone chaperone SET/TAF-Iβ interacts with cytochrome c following DNA damage. Specifically, cytochrome c is shown to be translocated into cell nuclei upon induction of DNA damage, but not upon stimulation of the death receptor or stress-induced pathways. Cytochrome c was found to competitively hinder binding of SET/TAF-Iβ to core histones, thereby locking its histone-binding domains and inhibiting its nucleosome assembly activity. In addition, we have used NMR spectroscopy, calorimetry, mutagenesis, and molecular docking to provide an insight into the structural features of the formation of the complex between cytochrome c and SET/TAF-Iβ. Overall, these findings establish a framework for understanding the molecular basis of cytochrome c-mediated blocking of SET/TAF-Iβ, which subsequently may facilitate the development of new drugs to silence the oncogenic effect of SET/TAF-Iβ’s histone chaperone activity. PMID:26216969

Visualization of complex DNA damage along accelerated ions tracks

NASA Astrophysics Data System (ADS)

Kulikova, Elena; Boreyko, Alla; Bulanova, Tatiana; Ježková, Lucie; Zadneprianetc, Mariia; Smirnova, Elena

2018-04-01

The most deleterious DNA lesions induced by ionizing radiation are clustered DNA double-strand breaks (DSB). Clustered or complex DNA damage is a combination of a few simple lesions (single-strand breaks, base damage etc.) within one or two DNA helix turns. It is known that yield of complex DNA lesions increases with increasing linear energy transfer (LET) of radiation. For investigation of the induction and repair of complex DNA lesions, human fibroblasts were irradiated with high-LET 15N ions (LET = 183.3 keV/μm, E = 13MeV/n) and low-LET 60Co γ-rays (LET ≈ 0.3 keV/μm) radiation. DNA DSBs (γH2AX and 53BP1) and base damage (OGG1) markers were visualized by immunofluorecence staining and high-resolution microscopy. The obtained results showed slower repair kinetics of induced DSBs in cells irradiated with accelerated ions compared to 60Co γ-rays, indicating induction of more complex DNA damage. Confirming previous assumptions, detailed 3D analysis of γH2AX/53BP1 foci in 15N ions tracks revealed more complicated structure of the foci in contrast to γ-rays. It was shown that proteins 53BP1 and OGG1 involved in repair of DNA DSBs and modified bases, respectively, were colocalized in tracks of 15N ions and thus represented clustered DNA DSBs.

Structural and Functional Modifications of Corneal Crystallin ALDH3A1 by UVB Light

PubMed Central

Estey, Tia; Chen, Ying; Carpenter, John F.; Vasiliou, Vasilis

2010-01-01

As one of the most abundantly expressed proteins in the mammalian corneal epithelium, aldehyde dehydrogenase 3A1 (ALDH3A1) plays critical and multifaceted roles in protecting the cornea from oxidative stress. Recent studies have demonstrated that one protective mechanism of ALDH3A1 is the direct absorption of UV-energy, which reduces damage to other corneal proteins such as glucose-6-phosphate dehydrogenase through a competition mechanism. UV-exposure, however, leads to the inactivation of ALDH3A1 in such cases. In the current study, we demonstrate that UV-light caused soluble, non-native aggregation of ALDH3A1 due to both covalent and non-covalent interactions, and that the formation of the aggregates was responsible for the loss of ALDH3A1 enzymatic activity. Spectroscopic studies revealed that as a result of aggregation, the secondary and tertiary structure of ALDH3A1 were perturbed. LysC peptide mapping using MALDI-TOF mass spectrometry shows that UV-induced damage to ALDH3A1 also includes chemical modifications to Trp, Met, and Cys residues. Surprisingly, the conserved active site Cys of ALDH3A1 does not appear to be affected by UV-exposure; this residue remained intact after exposure to UV-light that rendered the enzyme completely inactive. Collectively, our data suggest that the UV-induced inactivation of ALDH3A1 is a result of non-native aggregation and associated structural changes rather than specific damage to the active site Cys. PMID:21203538

Biological effectiveness of accelerated particles for the induction of chromosome damage: track structure effects.

PubMed

George, Kerry A; Hada, Megumi; Chappell, Lori; Cucinotta, Francis A

2013-07-01

We have investigated how radiation quality affects the induction of chromosomal aberrations in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated high charge and energy (HZE) particles including oxygen, neon, silicon, titanium and iron. Chromosome damage was assessed using three-color FISH chromosome painting in chemically induced premature chromosome condensation samples collected at first cell division after irradiation. The LET values for these particles ranged from 30 to 195 keV/μm, and their energies ranged from about 55 MeV/u to more than 1,000 MeV/u. The 89 and 142 MeV/u neon particles produced the most simple-type reciprocal exchanges per unit dose. For complex-type exchanges, 64 MeV/u neon and 450 MeV/u iron were equally effective and induced the greatest amount of complex damage. Track structure models predict that at a fixed value of LET, particles with lower charge number (Z) will have a higher biological effectiveness compared to particles with a higher Z, and that a saturation cross section will be observed for different radiation qualities. Our results are consistent with model expectations within the limitation of experimental error, and provide the most extensive data that have been reported on the radiation quality dependences of chromosomal aberrations. © 2013 by Radiation Research Society

[The diagnostic importance of the new marker KIM-1 in kidney damage].

PubMed

Marchewka, Zofia; Płonka, Joanna

2013-07-24

In recent years, the rapid development of scientific research led to the introduction of strategies based on new markers that allow for estimation of the latent disease period before the clinical symptoms of actual kidney failure are revealed. The experimental tests carried out on animals and cell lines derived from the proximal tubule have made possible the detection of genes that are induced early after hypoxia. The protein products of these genes can be considered as useful markers for the diagnosis of renal failure. The induction of gene KIM-1 (called Kidney Injury Molecule-1) results in the formation of protein that can be considered as a diagnostic marker. This work describes the data on the structure, biological function and importance of determining the concentrations of KIM-1 in the diagnosis of drug-induced toxicity and kidney damage.

Transmission Electron Microscopy of Vacuum Sensitive, Radiation Sensitive, and Structurally Delicate Materials

NASA Astrophysics Data System (ADS)

Levin, Barnaby

The transmission electron microscope (TEM) is a powerful tool for characterizing the nanoscale and atomic structure of materials, offering insights into their fundamental physical properties. However, TEM characterization requires very thin samples of material to be placed in a high vacuum environment, and exposed to electron radiation. The high vacuum will induce some materials to evaporate or sublimate, preventing them from being accurately characterized, radiation may damage the sample, causing mass loss, or altering its structure, and structurally delicate samples may collapse and break apart when they are thinned for TEM imaging. This dissertation discusses three different projects in which each of these three difficulties pose challenges to TEM characterization of samples. Firstly, we outline strategies for minimizing radiation damage when characterizing materials in TEM at atomic resolution. We consider types of radiation damage, such as vacancy enhanced displacement, that are not included in some previous discussions of beam damage, and we consider how to minimize damage when using new imaging techniques such as annular bright-field scanning TEM. Our methodology emphasizes the general principle that variation of both signal strength and damage cross section must be considered when choosing an experimental electron beam voltage to minimize damage. Secondly, we consider samples containing sulfur, which is prone to sublimation in high vacuum. TEM is routinely used to attempt to characterize the sulfur distribution in lithium-sulfur battery electrodes, but sublimation artifacts can give misleading results. We demonstrate that sulfur sublimation can be suppressed by using cryogenic TEM to characterize sulfur at very low temperatures, or by using the recently developed airSEM to characterize sulfur without exposing it to vacuum. Finally, we discuss the characterization of aging cadmium yellow paint from early 20th century art masterpieces. The binding medium holding paint particles together bends and curls as sample thickness is reduced to 100 nm, making high resolution characterization challenging. We acquire lattice resolution images of the pigment particles through the binder using high voltage zero-loss energy filtered TEM, allowing us to measure the pigment particle size and determine the pigment crystal structure, providing insight into why the paint is aging and how it was synthesized.

Radiation-Induced Liver Damage: Correlation of Histopathology with Hepatobiliary Magnetic Resonance Imaging, a Feasibility Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seidensticker, Max, E-mail: max.seidensticker@med.ovgu.de; Burak, Miroslaw; Kalinski, Thomas

PurposeRadiotherapy of liver malignancies shows promising results (radioembolization, stereotactic irradiation, interstitial brachytherapy). Regardless of the route of application, a certain amount of nontumorous liver parenchyma will be collaterally damaged by radiation. The functional reserve may be significantly reduced with an impact on further treatment planning. Monitoring of radiation-induced liver damage by imaging is neither established nor validated. We performed an analysis to correlate the histopathological presence of radiation-induced liver damage with functional magnetic resonance imaging (MRI) utilizing hepatobiliary contrast media (Gd-BOPTA).MethodsPatients undergoing local high-dose-rate brachytherapy for whom a follow-up hepatobiliary MRI within 120 days after radiotherapy as well as an evaluablemore » liver biopsy from radiation-exposed liver tissue within 7 days before MRI were retrospectively identified. Planning computed tomography (CT)/dosimetry was merged to the CT-documentation of the liver biopsy and to the MRI. Presence/absence of radiation-induced liver damage (histopathology) and Gd-BOPTA uptake (MRI) as well as the dose applied during brachytherapy at the site of tissue sampling was determined.ResultsFourteen biopsies from eight patients were evaluated. In all cases with histopathological evidence of radiation-induced liver damage (n = 11), no uptake of Gd-BOPTA was seen. In the remaining three, cases no radiation-induced liver damage but Gd-BOPTA uptake was seen. Presence of radiation-induced liver damage and absence of Gd-BOPTA uptake was correlated with a former high-dose exposition.ConclusionsAbsence of hepatobiliary MRI contrast media uptake in radiation-exposed liver parenchyma may indicate radiation-induced liver damage. Confirmatory studies are warranted.« less

Entire Photodamaged Chloroplasts Are Transported to the Central Vacuole by Autophagy[OPEN

PubMed Central

2017-01-01

Turnover of dysfunctional organelles is vital to maintain homeostasis in eukaryotic cells. As photosynthetic organelles, plant chloroplasts can suffer sunlight-induced damage. However, the process for turnover of entire damaged chloroplasts remains unclear. Here, we demonstrate that autophagy is responsible for the elimination of sunlight-damaged, collapsed chloroplasts in Arabidopsis thaliana. We found that vacuolar transport of entire chloroplasts, termed chlorophagy, was induced by UV-B damage to the chloroplast apparatus. This transport did not occur in autophagy-defective atg mutants, which exhibited UV-B-sensitive phenotypes and accumulated collapsed chloroplasts. Use of a fluorescent protein marker of the autophagosomal membrane allowed us to image autophagosome-mediated transport of entire chloroplasts to the central vacuole. In contrast to sugar starvation, which preferentially induced distinct type of chloroplast-targeted autophagy that transports a part of stroma via the Rubisco-containing body (RCB) pathway, photooxidative damage induced chlorophagy without prior activation of RCB production. We further showed that chlorophagy is induced by chloroplast damage caused by either artificial visible light or natural sunlight. Thus, this report establishes that an autophagic process eliminates entire chloroplasts in response to light-induced damage. PMID:28123106

Factors influencing heterogeneity of radiation-induced DNA-damage measured by the alkaline comet assay

PubMed Central

2012-01-01

Background To investigate whether different conditions of DNA structure and radiation treatment could modify heterogeneity of response. Additionally to study variance as a potential parameter of heterogeneity for radiosensitivity testing. Methods Two-hundred leukocytes per sample of healthy donors were split into four groups. I: Intact chromatin structure; II: Nucleoids of histone-depleted DNA; III: Nucleoids of histone-depleted DNA with 90 mM DMSO as antioxidant. Response to single (I-III) and twice (IV) irradiation with 4 Gy and repair kinetics were evaluated using %Tail-DNA. Heterogeneity of DNA damage was determined by calculation of variance of DNA-damage (V) and mean variance (Mvar), mutual comparisons were done by one-way analysis of variance (ANOVA). Results Heterogeneity of initial DNA-damage (I, 0 min repair) increased without histones (II). Absence of histones was balanced by addition of antioxidants (III). Repair reduced heterogeneity of all samples (with and without irradiation). However double irradiation plus repair led to a higher level of heterogeneity distinguishable from single irradiation and repair in intact cells. Increase of mean DNA damage was associated with a similarly elevated variance of DNA damage (r = +0.88). Conclusions Heterogeneity of DNA-damage can be modified by histone level, antioxidant concentration, repair and radiation dose and was positively correlated with DNA damage. Experimental conditions might be optimized by reducing scatter of comet assay data by repair and antioxidants, potentially allowing better discrimination of small differences. Amount of heterogeneity measured by variance might be an additional useful parameter to characterize radiosensitivity. PMID:22520045

Cytotoxicity and gene induction by some essential oils in the yeast Saccharomyces cerevisiae.

PubMed

Bakkali, F; Averbeck, S; Averbeck, D; Zhiri, A; Idaomar, M

2005-08-01

In order to get an insight into the possible genotoxicity of essential oils (EOs) used in traditional pharmacological applications we tested five different oils extracted from the medicinal plants Origanum compactum, Coriandrum sativum, Artemisia herba alba, Cinnamomum camphora (Ravintsara aromatica) and Helichrysum italicum (Calendula officinalis) for genotoxic effects using the yeast Saccharomyces cerevisiae. Clear cytotoxic effects were observed in the diploid yeast strain D7, with the cells being more sensitive to EOs in exponential than in stationary growth phase. The cytotoxicity decreased in the following order: Origanum compactum>Coriandrum sativum>Artemisia herba alba>Cinnamomum camphora>Helichrysum italicum. In the same order, all EOs, except that derived from Helichrysum italicum, clearly induced cytoplasmic petite mutations indicating damage to mitochondrial DNA. However, no nuclear genetic events such as point mutations or mitotic intragenic or intergenic recombination were induced. The capacity of EOs to induce nuclear DNA damage-responsive genes was tested using suitable Lac-Z fusion strains for RNR3 and RAD51, which are genes involved in DNA metabolism and DNA repair, respectively. At equitoxic doses, all EOs demonstrated significant gene induction, approximately the same as that caused by hydrogen peroxide, but much lower than that caused by methyl methanesulfonate (MMS). EOs affect mitochondrial structure and function and can stimulate the transcriptional expression of DNA damage-responsive genes. The induction of mitochondrial damage by EOs appears to be closely linked to overall cellular cytotoxicity and appears to mask the occurrence of nuclear genetic events. EO-induced cytotoxicity involves oxidative stress, as is evident from the protection observed in the presence of ROS inhibitors such as glutathione, catalase or the iron-chelating agent deferoxamine.

Involvement of lysosomal dysfunction in silver nanoparticle-induced cellular damage in A549 human lung alveolar epithelial cells.

PubMed

Miyayama, Takamitsu; Matsuoka, Masato

2016-01-01

While silver nanoparticles (AgNPs) are widely used in consumer and medical products, the mechanism by which AgNPs cause pulmonary cytotoxicity is not clear. AgNP agglomerates are found in endo-lysosomal structures within the cytoplasm of treated cells. In this study, the functional role of lysosomes in AgNP-induced cellular damage was examined in A549 human lung alveolar epithelial cells. We evaluated the intracellular distribution of AgNPs, lysosomal pH, cellular viability, Ag dissolution, and metallothionein (MT) mRNA levels in AgNP-exposed A549 cells that were treated with bafilomycin A1, the lysosomal acidification inhibitor. Exposure of A549 cells to citrate-coated AgNPs (20 nm diameter) for 24 h induced cellular damage and cell death at 100 and 200 μg Ag/ml, respectively. Confocal laser microscopic examination of LysoTracker-stained cells showed that AgNPs colocalized with lysosomes and their agglomeration increased in a dose-dependent manner (50-200 μg Ag/ml). In addition, the fluorescence signals of LysoTracker were reduced following exposure to AgNPs, suggesting the elevation of lysosomal pH. Treatment of A549 cells with 200 nM bafilomycin A1 and AgNPs (50 μg Ag/ml) further reduced the fluorescence signals of LysoTracker. AgNP-induced cell death was also increased by bafilomycin A1 treatment. Finally, treatment with bafilomycin A1 suppressed the dissolution of Ag and decreased the mRNA expression levels of MT-I and MT-II following exposure to AgNPs. The perturbation of lysosomal pH by AgNP exposure may play a role in AgNP agglomeration and subsequent cellular damage in A549 cells.

Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury

PubMed Central

Fakhruddin, Selim; Alanazi, Wael

2017-01-01

Diabetes induces the onset and progression of renal injury through causing hemodynamic dysregulation along with abnormal morphological and functional nephron changes. The most important event that precedes renal injury is an increase in permeability of plasma proteins such as albumin through a damaged glomerular filtration barrier resulting in excessive urinary albumin excretion (UAE). Moreover, once enhanced UAE begins, it may advance renal injury from progression of abnormal renal hemodynamics, increased glomerular basement membrane (GBM) thickness, mesangial expansion, extracellular matrix accumulation, and glomerulosclerosis to eventual end-stage renal damage. Interestingly, all these pathological changes are predominantly driven by diabetes-induced reactive oxygen species (ROS) and abnormal downstream signaling molecules. In diabetic kidney, NADPH oxidase (enzymatic) and mitochondrial electron transport chain (nonenzymatic) are the prominent sources of ROS, which are believed to cause the onset of albuminuria followed by progression to renal damage through podocyte depletion. Chronic hyperglycemia and consequent ROS production can trigger abnormal signaling pathways involving diverse signaling mediators such as transcription factors, inflammatory cytokines, chemokines, and vasoactive substances. Persistently, increased expression and activation of these signaling molecules contribute to the irreversible functional and structural changes in the kidney resulting in critically decreased glomerular filtration rate leading to eventual renal failure. PMID:28164134

Sex as a response to oxidative stress: a twofold increase in cellular reactive oxygen species activates sex genes.

PubMed

Nedelcu, Aurora M; Marcu, Oana; Michod, Richard E

2004-08-07

Organisms are constantly subjected to factors that can alter the cellular redox balance and result in the formation of a series of highly reactive molecules known as reactive oxygen species (ROS). As ROS can be damaging to biological structures, cells evolved a series of mechanisms (e.g. cell-cycle arrest, programmed cell death) to respond to high levels of ROS (i.e. oxidative stress). Recently, we presented evidence that in a facultatively sexual lineage--the multicellular green alga Volvox carteri--sex is an additional response to increased levels of stress, and probably ROS and DNA damage. Here we show that, in V. carteri, (i) sex is triggered by an approximately twofold increase in the level of cellular ROS (induced either by the natural sex-inducing stress, namely heat, or by blocking the mitochondrial electron transport chain with antimycin A), and (ii) ROS are responsible for the activation of sex genes. As most types of stress result in the overproduction of ROS, we believe that our findings will prove to extend to other facultatively sexual lineages, which could be indicative of the ancestral role of sex as an adaptive response to stress and ROS-induced DNA damage. Copyright 2004 The Royal Society

Raman spectroscopic study of plasma-treated salmon DNA

NASA Astrophysics Data System (ADS)

Joon Lee, Geon; Kwon, Young-Wan; Hee Kim, Yong; Ha Choi, Eun

2013-01-01

In this research, we studied the effect of plasma treatment on the optical/structural properties of the deoxyribonucleic acid (DNA) extracted from salmon sperm. DNA-cetyltrimethylammonium (CTMA) films were obtained by complexation of DNA with CTMA. Circular dichroism (CD) and Raman spectra indicated that DNA retained its double helical structure in the solid film. The Raman spectra exhibited several vibration modes corresponding to the nuclear bases and the deoxyribose-phosphate backbones of the DNA, as well as the alkylchains of CTMA. Dielectric-barrier-discharge (DBD) plasma treatment induced structural modification and damage to the DNA, as observed by changes in the ultraviolet-visible absorption, CD, and Raman spectra. The optical emission spectra of the DBD plasma confirmed that DNA modification was induced by plasma ions such as reactive oxygen species and reactive nitrogen species.

Tailoring the Employment of Offshore Wind Turbine Support Structure Load Mitigation Controllers

NASA Astrophysics Data System (ADS)

Shrestha, Binita; Kühn, Martin

2016-09-01

The currently available control concepts to mitigate aerodynamic and hydrodynamic induced support structure loads reduce either fore-aft or side-to-side damage under certain operational conditions. The load reduction is achieved together with an increase in loads in other components of the turbine e.g. pitch actuators or drive train, increasing the risk of unscheduled maintenance. The main objective of this paper is to demonstrate a methodology for reduction of support structure damage equivalent loads (DEL) in fore-aft and side-to-side directions using already available control concepts. A multi-objective optimization problem is formulated to minimize the DELs, while limiting the collateral effects of the control algorithms for load reduction. The optimization gives trigger values of sea state condition for the activation or deactivation of certain control concepts. As a result, by accepting the consumption of a small fraction of the load reserve in the design load envelope of other turbine components, a considerable reduction of the support structure loads is facilitated.

Kinetic gating mechanism of DNA damage recognition by Rad4/XPC

NASA Astrophysics Data System (ADS)

Chen, Xuejing; Velmurugu, Yogambigai; Zheng, Guanqun; Park, Beomseok; Shim, Yoonjung; Kim, Youngchang; Liu, Lili; van Houten, Bennett; He, Chuan; Ansari, Anjum; Min, Jung-Hyun

2015-01-01

The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformation similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivity arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump perturbation spectroscopy. Kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.

Kinetic gating mechanism of DNA damage recognition by Rad4/XPC

DOE PAGES

Chen, Xuejing; Velmurugu, Yogambigai; Zheng, Guanqun; ...

2015-01-06

The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformation similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivitymore » arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump perturbation spectroscopy. Lastly, kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.« less

Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Juanjuan; Zhang, Yu; Xu, Wentao, E-mail: xuwentaoboy@sina.com

Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did notmore » affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ{sub m}). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by OTA in vitro.« less

Acoustic emission monitoring of low velocity impact damage in graphite/epoxy laminates during tensile loading

NASA Technical Reports Server (NTRS)

Parker, Bradford H.

1992-01-01

An acoustic emission (AE) system was set up in a linear location data acquisition mode to monitor the tensile loading of eight-ply quasi-isotropic graphite/epoxy specimens containing low velocity impact damage. The impact damage was induced using an instrumented drop weight tower. During impact, specimens were supported by either an aluminum plate or a membrane configuration. Cross-sectional examinations revealed that the aluminum plate configuration resulted in primarily matrix cracking and back surface fiber failure. The membrane support resulted in only matrix cracking and delamination damage. Penetrant enhanced radiography and immersion ultrasonics were used in order to assess the amount of impact damage in each tensile specimen. During tensile loading, AE reliably detected and located the damage sites which included fiber failure. All specimens with areas of fiber breakage ultimately failed at the impact site. AE did not reliably locate damage which consisted of only delaminations and matrix cracking. Specimens with this type of damage did not ultimately fail at the impact site. In summary, AE demonstrated the ability to increase the reliability of structural proof tests; however, the successful use of this technique requires extensive baseline testing.

Real-time dynamics of neutrophil clustering in response to phototoxicity-induced cell death and tissue damage in mouse ear dermis.

PubMed

Park, Sang A; Choe, Young Ho; Park, Eunji; Hyun, Young-Min

2018-05-22

Neutrophils are highly motile innate immune cells; they actively migrate in response to inflammatory signals. Using two-photon intravital microscopy, we discovered that neutrophils form stable clusters upon phototoxicity at a certain threshold. Without significant damage to the collagen structure of mouse dermis, neutrophils aggregated together with nearby neutrophils. Surprisingly, this in situ neutrophil clustering resulted in rigorous changes of migratory direction. The density of residing neutrophils was also a critical factor affecting clustering. Additionally, we found that the triggering point of neutrophil aggregation was correlated with the structure of the extracellular matrix in the ear dermis, where autofluorescence was strongly observed. This swarming behavior of neutrophils may reflect an unknown communication mechanism of neutrophils during migration under sterile injury.

Electron beam induced radiation damage in the catalyst layer of a proton exchange membrane fuel cell.

PubMed

He, Qianping; Chen, Jihua; Keffer, David J; Joy, David C

2014-01-01

Electron microscopy is an essential tool for the evaluation of microstructure and properties of the catalyst layer (CL) of proton exchange membrane fuel cells (PEMFCs). However, electron microscopy has one unavoidable drawback, which is radiation damage. Samples suffer temporary or permanent change of the surface or bulk structure under radiation damage, which can cause ambiguity in the characterization of the sample. To better understand the mechanism of radiation damage of CL samples and to be able to separate the morphological features intrinsic to the material from the consequences of electron radiation damage, a series of experiments based on high-angle annular dark-field-scanning transmission scanning microscope (HAADF-STEM), energy filtering transmission scanning microscope (EFTEM), and electron energy loss spectrum (EELS) are conducted. It is observed that for thin samples (0.3-1 times λ), increasing the incident beam energy can mitigate the radiation damage. Platinum nanoparticles in the CL sample facilitate the radiation damage. The radiation damage of the catalyst sample starts from the interface of Pt/C or defective thin edge and primarily occurs in the form of mass loss accompanied by atomic displacement and edge curl. These results provide important insights on the mechanism of CL radiation damage. Possible strategies of mitigating the radiation damage are provided. © 2013 Wiley Periodicals, Inc.

Renal accumulation of pentosidine in non-diabetic proteinuria-induced renal damage in rats.

PubMed

Waanders, Femke; Greven, Wendela L; Baynes, John W; Thorpe, Suzanne R; Kramer, Andrea B; Nagai, Ryoji; Sakata, Noriyuki; van Goor, Harry; Navis, Gerjan

2005-10-01

Advanced glycation end-products (AGEs) contribute to the pathogenesis of diabetic glomerulopathy. The role of AGEs in non-diabetic renal damage is not well characterized. First, we studied whether renal AGE accumulation occurs in non-diabetic proteinuria-induced renal damage and whether this is ameliorated by renoprotective treatment. Secondly, we investigated whether renal AGE accumulation was due to intrarenal effects of local protein trafficking. Pentosidine was measured (by high-performance liquid chromatography) in rats with chronic bilateral adriamycin nephropathy (AN), untreated and treated with lisinopril. Age-matched healthy rats served as negative controls. Secondly, we compared renal pentosidine in mild proteinuric and non-proteinuric kidneys of unilateral AN and in age-matched controls at 12 and 30 weeks. Intrarenal localization of pentosidine was studied by immunohistochemistry. Renal pentosidine was elevated in untreated AN (0.14+/-0.04 micromol/mol valine) vs healthy controls (0.04+/-0.01 micromol/mol valine, P<0.01). In lisinopril-treated AN, pentosidine was lower (0.09+/-0.02 micromol/mol valine) than in untreated AN (P<0.05). In unilateral proteinuria, pentosidine was similar in non-proteinuric and proteinuric kidneys. After 30 weeks of unilateral proteinuria, pentosidine was increased in both kidneys (0.26+/-0.10 micromol/mol valine) compared with controls (0.18+/-0.06 micromol/mol valine, P<0.05). Pentosidine (AN, week 30) was also increased compared with AN at week 12 (0.16+/-0.06 micromol/mol valine, P<0.01). In control and diseased kidneys, pentosidine was present in the collecting ducts. In proteinuric kidneys, in addition, pentosidine was present in the brush border and cytoplasm of dilated tubular structures, i.e. at sites of proteinuria-induced tubular damage. Pentosidine accumulates in non-diabetic proteinuric kidneys in damaged tubules, and renoprotective treatment by angiotensin-converting enzyme (ACE) inhibitors inhibits AGE accumulation, supporting a relationship between abnormal renal protein trafficking, proteinuria-induced tubular damage and tubular pentosidine accumulation. Future studies, applying specific AGE inhibitors, should be conducted to provide insight into the pathophysiological significance of renal AGEs in non-diabetic renal disease.

Atrx deficiency induces telomere dysfunction, endocrine defects, and reduced life span

PubMed Central

Watson, L. Ashley; Solomon, Lauren A.; Li, Jennifer Ruizhe; Jiang, Yan; Edwards, Matthew; Shin-ya, Kazuo; Beier, Frank; Bérubé, Nathalie G.

2013-01-01

Human ATRX mutations are associated with cognitive deficits, developmental abnormalities, and cancer. We show that the Atrx-null embryonic mouse brain accumulates replicative damage at telomeres and pericentromeric heterochromatin, which is exacerbated by loss of p53 and linked to ATM activation. ATRX-deficient neuroprogenitors exhibited higher incidence of telomere fusions and increased sensitivity to replication stress–inducing drugs. Treatment of Atrx-null neuroprogenitors with the G-quadruplex (G4) ligand telomestatin increased DNA damage, indicating that ATRX likely aids in the replication of telomeric G4-DNA structures. Unexpectedly, mutant mice displayed reduced growth, shortened life span, lordokyphosis, cataracts, heart enlargement, and hypoglycemia, as well as reduction of mineral bone density, trabecular bone content, and subcutaneous fat. We show that a subset of these defects can be attributed to loss of ATRX in the embryonic anterior pituitary that resulted in low circulating levels of thyroxine and IGF-1. Our findings suggest that loss of ATRX increases DNA damage locally in the forebrain and anterior pituitary and causes tissue attrition and other systemic defects similar to those seen in aging. PMID:23563309

Failure and recovery in dynamical networks.

PubMed

Böttcher, L; Luković, M; Nagler, J; Havlin, S; Herrmann, H J

2017-02-03

Failure, damage spread and recovery crucially underlie many spatially embedded networked systems ranging from transportation structures to the human body. Here we study the interplay between spontaneous damage, induced failure and recovery in both embedded and non-embedded networks. In our model the network's components follow three realistic processes that capture these features: (i) spontaneous failure of a component independent of the neighborhood (internal failure), (ii) failure induced by failed neighboring nodes (external failure) and (iii) spontaneous recovery of a component. We identify a metastable domain in the global network phase diagram spanned by the model's control parameters where dramatic hysteresis effects and random switching between two coexisting states are observed. This dynamics depends on the characteristic link length of the embedded system. For the Euclidean lattice in particular, hysteresis and switching only occur in an extremely narrow region of the parameter space compared to random networks. We develop a unifying theory which links the dynamics of our model to contact processes. Our unifying framework may help to better understand controllability in spatially embedded and random networks where spontaneous recovery of components can mitigate spontaneous failure and damage spread in dynamical networks.

Association of a Platinum Complex to a G-Quadruplex Ligand Enhances Telomere Disruption.

PubMed

Charif, Razan; Granotier-Beckers, Christine; Bertrand, Hélène Charlotte; Poupon, Joël; Ségal-Bendirdjian, Evelyne; Teulade-Fichou, Marie-Paule; Boussin, François D; Bombard, Sophie

2017-08-21

Telomeres protect the ends of chromosomes against illegitimate recombination and repair. They can be targets for G-quadruplex ligands and platinum complexes due to their repeated G-rich sequences. Protection of telomeres is ensured by a complex of six proteins, including TRF2, which inhibits the DNA damage response pathway. We analyzed telomere modifications induced in cancer cells by the experimental hybrid platinum complex, Pt-MPQ, comprising both an ethylene diamine monofunctional platinum complex and a G-quadruplex recognition moiety (MPQ). Pt-MPQ promotes the displacement of two telomeric proteins (TRF2 and TRF1) from telomeres, as well as the formation of telomere damage and telomere sister losses, whereas the control compound MPQ does not. This suggests that the platinum moiety potentiates the targeting of the G-quadruplex ligand to telomeres, opening a new perspective for telomere biology and anticancer therapy. Interestingly, the chemotherapy drug cisplatin, which has no specific affinity for G-quadruplex structures, partially induces the TRF2 delocalization from telomeres but produces less telomeric DNA damage, suggesting that this TRF2 displacement could be independent of G-quadruplex recognition.

An evaluation method of the profile of plasma-induced defects based on capacitance-voltage measurement

NASA Astrophysics Data System (ADS)

Okada, Yukimasa; Ono, Kouichi; Eriguchi, Koji

2017-06-01

Aggressive shrinkage and geometrical transition to three-dimensional structures in metal-oxide-semiconductor field-effect transistors (MOSFETs) lead to potentially serious problems regarding plasma processing such as plasma-induced physical damage (PPD). For the precise control of material processing and future device designs, it is extremely important to clarify the depth and energy profiles of PPD. Conventional methods to estimate the PPD profile (e.g., wet etching) are time-consuming. In this study, we propose an advanced method using a simple capacitance-voltage (C-V) measurement. The method first assumes the depth and energy profiles of defects in Si substrates, and then optimizes the C-V curves. We applied this methodology to evaluate the defect generation in (100), (111), and (110) Si substrates. No orientation dependence was found regarding the surface-oxide layers, whereas a large number of defects was assigned in the case of (110). The damaged layer thickness and areal density were estimated. This method provides the highly sensitive PPD prediction indispensable for designing future low-damage plasma processes.

Methylmercury chloride damage to the adult rat hippocampus cannot be detected by proton magnetic resonance spectroscopy

PubMed Central

Lu, Zhiyan; Wu, Jinwei; Cheng, Guangyuan; Tian, Jianying; Lu, Zeqing; Bi, Yongyi

2014-01-01

Previous studies have found that methylmercury can damage hippocampal neurons and accordingly cause cognitive dysfunction. However, a non-invasive, safe and accurate detection method for detecting hippocampal injury has yet to be developed. This study aimed to detect methylmercury-induced damage on hippocampal tissue using proton magnetic resonance spectroscopy. Rats were given a subcutaneous injection of 4 and 2 mg/kg methylmercury into the neck for 50 consecutive days. Water maze and pathology tests confirmed that cognitive function had been impaired and that the ultrastructure of hippocampal tissue was altered after injection. The results of proton magnetic resonance spectroscopy revealed that the nitrogen-acetyl aspartate/creatine, choline complex/creatine and myoinositol/creatine ratio in rat hippocampal tissue were unchanged. Therefore, proton magnetic resonance spectroscopy can not be used to determine structural damage in the adult rat hippocampus caused by methylmercury chloride. PMID:25368649

Analysis and reduction of well failures in diatomite reservoirs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyer, L.; Jacobsen, J.; Horsman, J.

1995-12-31

Well damage induced by compactable formation deformation has occurred in oil fields in the Gulf of Mexico, the mid-continent region, the North Sea, on-shore Europe, Asia, and South America. The diatomite reservoirs of California are particularly susceptible to compaction due to the very high porosity of the diatomite. In these reservoirs well replacement, lost production and abandonment costs have exceeded $200 million to date. In 1994 alone about 40 wells were damaged. A study is currently underway involving data analysis and 3-D visualization, laboratory testing, and numerical modelling to improve understanding of casing damage due to reservoir compaction and tomore » develop tools and operating strategies to reduce casing damage. The study is focused on the South Belridge field. Results to date show a consistent correlation between failure and structural markers and apparent influence of local production and injection supporting the need for 3-D simulation.« less

A recursive Bayesian approach for fatigue damage prognosis: An experimental validation at the reliability component level

NASA Astrophysics Data System (ADS)

Gobbato, Maurizio; Kosmatka, John B.; Conte, Joel P.

2014-04-01

Fatigue-induced damage is one of the most uncertain and highly unpredictable failure mechanisms for a large variety of mechanical and structural systems subjected to cyclic and random loads during their service life. A health monitoring system capable of (i) monitoring the critical components of these systems through non-destructive evaluation (NDE) techniques, (ii) assessing their structural integrity, (iii) recursively predicting their remaining fatigue life (RFL), and (iv) providing a cost-efficient reliability-based inspection and maintenance plan (RBIM) is therefore ultimately needed. In contribution to these objectives, the first part of the paper provides an overview and extension of a comprehensive reliability-based fatigue damage prognosis methodology — previously developed by the authors — for recursively predicting and updating the RFL of critical structural components and/or sub-components in aerospace structures. In the second part of the paper, a set of experimental fatigue test data, available in the literature, is used to provide a numerical verification and an experimental validation of the proposed framework at the reliability component level (i.e., single damage mechanism evolving at a single damage location). The results obtained from this study demonstrate (i) the importance and the benefits of a nearly continuous NDE monitoring system, (ii) the efficiency of the recursive Bayesian updating scheme, and (iii) the robustness of the proposed framework in recursively updating and improving the RFL estimations. This study also demonstrates that the proposed methodology can lead to either an extent of the RFL (with a consequent economical gain without compromising the minimum safety requirements) or an increase of safety by detecting a premature fault and therefore avoiding a very costly catastrophic failure.

ALD anti-reflection coatings at 1ω, 2ω, 3ω, and 4ω for high-power ns-laser application

NASA Astrophysics Data System (ADS)

Liu, Hao; Jensen, Lars; Ma, Ping; Ristau, Detlev

2018-04-01

Atomic layer deposition (ALD) facilitates the deposition of coatings with precise thickness, high surface conformity, structural uniformity, and nodular-free structure, which are properties desired in high-power laser coatings. ALD was studied to produce uniform and stable Al2O3 and HfO2 single layers and was employed to produce anti-reflection coatings for the harmonics (1ω, 2ω, 3ω, and 4ω) of the Nd:YAG laser. In order to qualify the ALD films for high-power laser applications, the band gap energy, absorption, and element content of single layers were characterized. The damage tests of anti-reflection coatings were carried out with a laser system operated at 1ω, 2ω, 3ω, and 4ω, respectively. The damage mechanism was discussed by analyzing the damage morphology and electric field intensity difference. ALD coatings exhibit stable growth rates, low absorption, and rather high laser-induced damage threshold (LIDT). The LIDT is limited by HfO2 as the employed high-index material. These properties indicate the high versatility of ALD films for applications in high-power coatings.

[Operating room during natural disaster: lessons from the 2011 Tohoku earthquake].

PubMed

Fukuda, Ikuo; Hashimoto, Hiroshi; Suzuki, Yasuyuki; Satomi, Susumu; Unno, Michiaki; Ohuchi, Noriaki; Nakaji, Shigeyuki

2012-03-01

Objective of this study is to clarify damages in operating rooms after the 2011 Tohoku Earthquake. To survey structural and non-structural damage in operating theaters, we sent questionnaires to 155 acute care hospitals in Tohoku area. Questionnaires were sent back from 105 hospitals (70.3%). Total of 280 patients were undergoing any kinds of operations during the earthquake and severe seismic tremor greater than JMA Seismic Intensity 6 hit 49 hospitals. Operating room staffs experienced life-threatening tremor in 41 hospitals. Blackout occurred but emergency electronic supply unit worked immediately in 81 out of 90 hospitals. However, emergency power plant did not work in 9 hospitals. During earthquake some materials fell from shelves in 44 hospitals and medical instruments fell down in 14 hospitals. In 5 hospitals, they experienced collapse of operating room wall or ceiling causing inability to maintain sterile operative field. Damage in electric power and water supply plus damage in logistics made many operating rooms difficult to perform routine surgery for several days. The 2011 Tohoku earthquake affected medical supply in wide area of Tohoku district and induced dysfunction of operating room. Supply-chain management of medical goods should be reconsidered to prepare severe natural disaster.

Evidence for conformational capture mechanism for damage recognition by NER protein XPC/Rad4.

NASA Astrophysics Data System (ADS)

Chakraborty, Sagnik; Steinbach, Peter J.; Paul, Debamita; Min, Jung-Hyun; Ansari, Anjum

Altered flexibility of damaged DNA sites is considered to play an important role in damage recognition by DNA repair proteins. Characterizing lesion-induced DNA dynamics has remained a challenge. We have combined ps-resolved fluorescence lifetime measurements with cytosine analog FRET pair uniquely sensitive to local unwinding/twisting to analyze DNA conformational distributions. This innovative approach maps out with unprecedented sensitivity the alternative conformations accessible to a series of DNA constructs containing 3-base-pair mismatch, suitable model lesions for the DNA repair protein xeroderma pigmentosum C (XPC) complex. XPC initiates eukaryotic nucleotide excision repair by recognizing various DNA lesions primarily through DNA deformability. Structural studies show that Rad4 (yeast ortholog of XPC) unwinds DNA at the lesion site and flips out two nucleotide pairs. Our results elucidate a broad range of conformations accessible to mismatched DNA even in the absence of the protein. Notably, the most severely distorted conformations share remarkable resemblance to the deformed conformation seen in the crystal structure of the Rad4-bound ``recognition'' complex supporting for the first time a possible ``conformational capture'' mechanism for damage recognition by XPC/Rad4. NSF Univ of Illinois-Chicago.

Nanosecond laser-induced damage at different initial temperatures of Ta{sub 2}O{sub 5} films prepared by dual ion beam sputtering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Cheng, E-mail: xucheng@cumt.edu.cn; Jia, Jiaojiao; Fan, Heliang

2014-08-07

Ta{sub 2}O{sub 5} films were deposited by dual ion beam sputtering method. The nanosecond laser-induced damage threshold (LIDT) at different initial temperatures and time of the films was investigated by an in situ high temperature laser-induced damage testing platform. It was shown that, when the initial temperature increased from 298 K to 383 K, the LIDT at 1064 nm and 12 ns significantly decreased by nearly 14%. Then the LIDT at 1064 nm and 12 ns decreased slower with the same temperature increment. Different damage morphologies were found at different initial temperatures. At low initial temperatures, it was the defects-isolated damage while at high initial temperaturesmore » it was the defects-combined damage. The theoretical calculations based on the defect-induced damage model revealed that both the significant increase of the highest temperature and the duration contributed to the different damage morphologies. With the initial temperature being increased, the thermal-stress coupling damage mechanism transformed gradually to the thermal dominant damage mechanism.« less

Hemorrhage-induced intestinal damage is complement independent in Helicobacter-hepaticus infected mice

PubMed Central

Hylton, Diana J.; Phillips, Lauren M.; Hoffman, Sara M.; Fleming, Sherry D.

2010-01-01

With over half of the world population infected, Helicobacter infection is an important public health issue associated with gastrointestinal cancers and inflammatory bowel disease. Animal studies indicate that complement and oxidative stress play a role in Helicobacter infections. Hemorrhage induces tissue damage which is attenuated by blockade of either complement activation or oxidative stress products. Therefore, we hypothesized that chronic Helicobacter hepaticus infection would modulate hemorrhage-induced intestinal damage and inflammation. To test this hypothesis, we examined hemorrhage-induced jejunal damage and inflammation in uninfected and H. hepaticus infected mice. H. hepaticus infection increased hemorrhage-induced mid-jejunal mucosal damage despite attenuating complement activation. In addition, infection alone increased chemokine secretion, changing the hemorrhage-induced neutrophil infiltration to a macrophage-mediated inflammatory response. The hemorrhage-induced macrophage infiltration correlated with increased secretion of tumor necrosis factor-α (TNF-α3) and nitric oxide (NO) in the infected mice. Together these data indicate that Helicobacter infection modulates the mechanism of hemorrhage-induced intestinal damage and inflammation from a complement-mediated response to a macrophage response with elevated TNF-α and NO. These data indicate that chronic, low level infections change the response to trauma and should be considered when designing and administering therapeutics. PMID:20220569

Noise-Induced Building Vibrations Caused by Concorde and Conventional Aircraft Operations at Dulles and Kennedy International Airports

NASA Technical Reports Server (NTRS)

Mayes, W. H.; Stephens, D. G.; Holmes, H. K.; Lewis, R. B.; Holliday, B. G.; Ward, D. W.; Deloach, R.; Cawthorn, J. M.; Finley, T. D.; Lynch, J. W.

1978-01-01

Outdoor and indoor noise levels resulting from aircraft flyovers and certain nonaircraft events were recorded, as were the associated vibration levels in the walls, windows, and floors at building test sites. In addition, limited subjective tests were conducted to examine the human detection and annoyance thresholds for building vibration and rattle caused by aircraft noise. Representative peak levels of aircraft noise-induced building vibrations are reported and comparisons are made with structural damage criteria and with vibration levels induced by common domestic events. In addition, results of a pilot study are reported which indicate the human detection threshold for noise-induced floor vibrations.

Plastic damage induced fracture behaviors of dental ceramic layer structures subjected to monotonic load.

PubMed

Wang, Raorao; Lu, Chenglin; Arola, Dwayne; Zhang, Dongsheng

2013-08-01

The aim of this study was to compare failure modes and fracture strength of ceramic structures using a combination of experimental and numerical methods. Twelve specimens with flat layer structures were fabricated from two types of ceramic systems (IPS e.max ceram/e.max press-CP and Vita VM9/Lava zirconia-VZ) and subjected to monotonic load to fracture with a tungsten carbide sphere. Digital image correlation (DIC) and fractography technology were used to analyze fracture behaviors of specimens. Numerical simulation was also applied to analyze the stress distribution in these two types of dental ceramics. Quasi-plastic damage occurred beneath the indenter in porcelain in all cases. In general, the fracture strength of VZ specimens was greater than that of CP specimens. The crack initiation loads of VZ and CP were determined as 958 ± 50 N and 724 ± 36 N, respectively. Cracks were induced by plastic damage and were subsequently driven by tensile stress at the elastic/plastic boundary and extended downward toward to the veneer/core interface from the observation of DIC at the specimen surface. Cracks penetrated into e.max press core, which led to a serious bulk fracture in CP crowns, while in VZ specimens, cracks were deflected and extended along the porcelain/zirconia core interface without penetration into the zirconia core. The rupture loads for VZ and CP ceramics were determined as 1150 ± 170 N and 857 ± 66 N, respectively. Quasi-plastic deformation (damage) is responsible for crack initiation within porcelain in both types of crowns. Due to the intrinsic mechanical properties, the fracture behaviors of these two types of ceramics are different. The zirconia core with high strength and high elastic modulus has better resistance to fracture than the e.max core. © 2013 by the American College of Prosthodontists.

Defect interactions with stepped CeO₂/SrTiO₃ interfaces: implications for radiation damage evolution and fast ion conduction.

PubMed

Dholabhai, Pratik P; Aguiar, Jeffery A; Misra, Amit; Uberuaga, Blas P

2014-05-21

Due to reduced dimensions and increased interfacial content, nanocomposite oxides offer improved functionalities in a wide variety of advanced technological applications, including their potential use as radiation tolerant materials. To better understand the role of interface structures in influencing the radiation damage tolerance of oxides, we have conducted atomistic calculations to elucidate the behavior of radiation-induced point defects (vacancies and interstitials) at interface steps in a model CeO2/SrTiO3 system. We find that atomic-scale steps at the interface have substantial influence on the defect behavior, which ultimately dictate the material performance in hostile irradiation environments. Distinctive steps react dissimilarly to cation and anion defects, effectively becoming biased sinks for different types of defects. Steps also attract cation interstitials, leaving behind an excess of immobile vacancies. Further, defects introduce significant structural and chemical distortions primarily at the steps. These two factors are plausible origins for the enhanced amorphization at steps seen in our recent experiments. The present work indicates that comprehensive examination of the interaction of radiation-induced point defects with the atomic-scale topology and defect structure of heterointerfaces is essential to evaluate the radiation tolerance of nanocomposites. Finally, our results have implications for other applications, such as fast ion conduction.

Insulin protects against hepatic damage postburn.

PubMed

Jeschke, Marc G; Kraft, Robert; Song, Juquan; Gauglitz, Gerd G; Cox, Robert A; Brooks, Natasha C; Finnerty, Celeste C; Kulp, Gabriela A; Herndon, David N; Boehning, Darren

2011-01-01

Burn injury causes hepatic dysfunction associated with endoplasmic reticulum (ER) stress and induction of the unfolded protein response (UPR). ER stress/UPR leads to hepatic apoptosis and activation of the Jun-N-terminal kinase (JNK) signaling pathway, leading to vast metabolic alterations. Insulin has been shown to attenuate hepatic damage and to improve liver function. We therefore hypothesized that insulin administration exerts its effects by attenuating postburn hepatic ER stress and subsequent apoptosis. Male Sprague Dawley rats received a 60% total body surface area (TBSA) burn injury. Animals were randomized to receive saline (controls) or insulin (2.5 IU/kg q. 24 h) and euthanized at 24 and 48 h postburn. Burn injury induced dramatic changes in liver structure and function, including induction of the ER stress response, mitochondrial dysfunction, hepatocyte apoptosis, and up-regulation of inflammatory mediators. Insulin decreased hepatocyte caspase-3 activation and apoptosis significantly at 24 and 48 h postburn. Furthermore, insulin administration decreased ER stress significantly and reversed structural and functional changes in hepatocyte mitochondria. Finally, insulin attenuated the expression of inflammatory mediators IL-6, MCP-1, and CINC-1. Insulin alleviates burn-induced ER stress, hepatocyte apoptosis, mitochondrial abnormalities, and inflammation leading to improved hepatic structure and function significantly. These results support the use of insulin therapy after traumatic injury to improve patient outcomes.

Insulin Protects against Hepatic Damage Postburn

PubMed Central

Jeschke, Marc G; Kraft, Robert; Song, Juquan; Gauglitz, Gerd G; Cox, Robert A; Brooks, Natasha C; Finnerty, Celeste C; Kulp, Gabriela A; Herndon, David N; Boehning, Darren

2011-01-01

Burn injury causes hepatic dysfunction associated with endoplasmic reticulum (ER) stress and induction of the unfolded protein response (UPR). ER stress/UPR leads to hepatic apoptosis and activation of the Jun-N-terminal kinase (JNK) signaling pathway, leading to vast metabolic alterations. Insulin has been shown to attenuate hepatic damage and to improve liver function. We therefore hypothesized that insulin administration exerts its effects by attenuating postburn hepatic ER stress and subsequent apoptosis. Male Sprague Dawley rats received a 60% total body surface area (TBSA) burn injury. Animals were randomized to receive saline (controls) or insulin (2.5 IU/kg q. 24 h) and euthanized at 24 and 48 h postburn. Burn injury induced dramatic changes in liver structure and function, including induction of the ER stress response, mitochondrial dysfunction, hepatocyte apoptosis, and up-regulation of inflammatory mediators. Insulin decreased hepatocyte caspase-3 activation and apoptosis significantly at 24 and 48 h postburn. Furthermore, insulin administration decreased ER stress significantly and reversed structural and functional changes in hepatocyte mitochondria. Finally, insulin attenuated the expression of inflammatory mediators IL-6, MCP-1, and CINC-1. Insulin alleviates burn-induced ER stress, hepatocyte apoptosis, mitochondrial abnormalities, and inflammation leading to improved hepatic structure and function significantly. These results support the use of insulin therapy after traumatic injury to improve patient outcomes. PMID:21267509

Surface and structure modification induced by high energy and highly charged uranium ion irradiation in monocrystal spinel

NASA Astrophysics Data System (ADS)

Yang, Yitao; Zhang, Chonghong; Song, Yin; Gou, Jie; Zhang, Liqing; Meng, Yancheng; Zhang, Hengqing; Ma, Yizhun

2014-05-01

Due to its high temperature properties and relatively good behavior under irradiation, magnesium aluminate spinel (MgAl2O4) is considered as a possible material to be used as inert matrix for the minor actinides burning. In this case, irradiation damage is an unavoidable problem. In this study, high energy and highly charged uranium ions (290 MeV U32+) were used to irradiate monocrystal spinel to the fluence of 1.0 × 1013 ions/cm2 to study the modification of surface and structure. Highly charged ions carry large potential energy, when they interact with a surface, the release of potential energy results in the modification of surface. Atomic force microscopy (AFM) results showed the occurrence of etching on surface after uranium ion irradiation. The etching depth reached 540 nm. The surprising efficiency of etching is considered to be induced by the deposition of potential energy with high density. The X-ray diffraction results showed that the (4 4 0) diffraction peak obviously broadened after irradiation, which indicated that the distortion of lattice has occurred. After multi-peak Gaussian fitting, four Gaussian peaks were separated, which implied that a structure with different damage layers could be formed after irradiation.

Nano-Se attenuates cyclophosphamide-induced pulmonary injury through modulation of oxidative stress and DNA damage in Swiss albino mice.

PubMed

Bhattacharjee, Arin; Basu, Abhishek; Biswas, Jaydip; Bhattacharya, Sudin

2015-07-01

Chemotherapy is an integral part of modern day treatment regimen but anticancer drugs fail to demarcate between cancerous and normal cells thereby causing severe form of systemic toxicity. Among which pulmonary toxicity is a dreadful complication developed in cancer patients upon cyclophosphamide (CP) therapy. Oxidative stress, fibrosis, and apoptosis are the major patho-mechanisms involved in CP-induced pulmonary toxicity. In the present study, we have synthesized Nano-Se, nanotechnology-based new form of elemental selenium which has significantly lower toxicity and acceptable bioavailability. In order to meet the need of effective drugs against CP-induced adverse effects, nano selenium (Nano-Se) was tested for its possible protective efficacy on CP-induced pulmonary toxicity and bone marrow toxicity. CP intoxication resulted in structural and functional lung impairment which was revealed by massive histopathological changes. Lung injury was associated with oxidative stress/lipid peroxidation as evident by increased in reactive oxygen species, nitric oxide level, and malondialdehyde (MDA) formation with decreased in level of antioxidants such as reduced glutathione, glutathione-S-transferase, glutathione peroxidase, superoxide dismutase, and catalase. Furthermore, CP at a dose of 25 mg/kg b.w. increased pulmonary DNA damage ('comet tail') and triggered DNA fragmentation and apoptosis in mouse bone marrow cells. On the other hand, Nano-Se at a dose of 2 mg Se/kg b.w., significantly inhibited CP-induced DNA damage in bronchoalveolar lavage cells, and decreased the apoptosis and percentage of DNA fragmentation in bone marrow cells and also antagonized the reduction of the activities of antioxidant enzymes and the increase level of MDA. Thus, our results suggest that Nano-Se in pre- and co-administration may serve as a promising preventive strategy against CP-induced pulmonary toxicity.

The Role of Endogenous Serotonin in Methamphetamine-Induced Neurotoxicity to Dopamine Nerve Endings of the Striatum

PubMed Central

Thomas, David M.; Angoa-Pérez, Mariana; Francescutti-Verbeem, Dina M.; Shah, Mrudang M.; Kuhn, Donald M.

2010-01-01

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the striatum where long-term DA depletion and microglial activation are maximal. Endogenous DA has been implicated as a critical participant in METH-induced neurotoxicity, most likely as a substrate for non-enzymatic oxidation by METH-generated reactive oxygen species (ROS). The striatum is also extensively innervated by serotonin (5HT) nerve endings and this neurochemical system is modified by METH in much the same manner as seen in DA nerve endings (i.e., increased release of 5HT, loss of function in tryptophan hydroxylase and the serotonin transporter, long-term depletion of 5HT stores). 5HT can also be modified by ROS to form highly reactive species that damage neurons but its role in METH neurotoxicity has not been assessed. Increases in 5HT levels with 5HTP do not change METH-induced neurotoxicity to the DA nerve endings as revealed by reductions in DA, tyrosine hydroxylase and dopamine transporter levels. Partial reductions in 5HT with p-chlorophenylalanine (PCPA) are without effect on METH toxicity, despite the fact that PCPA largely prevents METH-induced hyperthermia. Mice lacking the gene for brain tryptophan hydroxylase 2 are devoid of brain 5HT and respond to METH in the same manner as wild-type controls, despite showing enhanced drug-induced hyperthermia. Taken together, the present results indicate that endogenous 5HT does not appear to play a role in METH-induced damage to DA nerve endings of the striatum. PMID:20722968

The role of endogenous serotonin in methamphetamine-induced neurotoxicity to dopamine nerve endings of the striatum.

PubMed

Thomas, David M; Angoa Pérez, Mariana; Francescutti-Verbeem, Dina M; Shah, Mrudang M; Kuhn, Donald M

2010-11-01

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the striatum where long-term DA depletion and microglial activation are maximal. Endogenous DA has been implicated as a critical participant in METH-induced neurotoxicity, most likely as a substrate for non-enzymatic oxidation by METH-generated reactive oxygen species. The striatum is also extensively innervated by serotonin (5HT) nerve endings and this neurochemical system is modified by METH in much the same manner as seen in DA nerve endings (i.e., increased release of 5HT, loss of function in tryptophan hydroxylase and the serotonin transporter, long-term depletion of 5HT stores). 5HT can also be modified by reactive oxygen species to form highly reactive species that damage neurons but its role in METH neurotoxicity has not been assessed. Increases in 5HT levels with 5-hydroxytryptophan do not change METH-induced neurotoxicity to the DA nerve endings as revealed by reductions in DA, tyrosine hydroxylase and dopamine transporter levels. Partial reductions in 5HT with p-chlorophenylalanine are without effect on METH toxicity, despite the fact that p-chlorophenylalanine largely prevents METH-induced hyperthermia. Mice lacking the gene for brain tryptophan hydroxylase 2 are devoid of brain 5HT and respond to METH in the same manner as wild-type controls, despite showing enhanced drug-induced hyperthermia. Taken together, the present results indicate that endogenous 5HT does not appear to play a role in METH-induced damage to DA nerve endings of the striatum. © 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry.

Dose-rate plays a significant role in synchrotron radiation X-ray-induced damage of rodent testes.

PubMed

Chen, Heyu; Wang, Ban; Wang, Caixia; Cao, Wei; Zhang, Jie; Ma, Yingxin; Hong, Yunyi; Fu, Shen; Wu, Fan; Ying, Weihai

2016-01-01

Synchrotron radiation (SR) X-ray has significant potential for applications in medical imaging and cancer treatment. However, the mechanisms underlying SR X-ray-induced tissue damage remain unclear. Previous studies on regular X-ray-induced tissue damage have suggested that dose-rate could affect radiation damage. Because SR X-ray has exceedingly high dose-rate compared to regular X-ray, it remains to be determined if dose-rate may affect SR X-ray-induced tissue damage. We used rodent testes as a model to investigate the role of dose-rate in SR X-ray-induced tissue damage. One day after SR X-ray irradiation, we determined the effects of the irradiation of the same dosage at two different dose-rates, 0.11 Gy/s and 1.1 Gy/s, on TUNEL signals, caspase-3 activation and DNA double-strand breaks (DSBs) of the testes. Compared to those produced by the irradiation at 0.11 Gy/s, irradiation at 1.1 Gy/s produced higher levels of DSBs, TUNEL signals, and caspase-3 activation in the testes. Our study has provided the first evidence suggesting that dose-rate could be a significant factor in SR X-ray-induced tissue damage, which may establish a valuable base for utilizing this factor to manipulate the tissue damage in SR X-ray-based medical applications.

Dose-rate plays a significant role in synchrotron radiation X-ray-induced damage of rodent testes

PubMed Central

Chen, Heyu; Wang, Ban; Wang, Caixia; Cao, Wei; Zhang, Jie; Ma, Yingxin; Hong, Yunyi; Fu, Shen; Wu, Fan; Ying, Weihai

2016-01-01

Synchrotron radiation (SR) X-ray has significant potential for applications in medical imaging and cancer treatment. However, the mechanisms underlying SR X-ray-induced tissue damage remain unclear. Previous studies on regular X-ray-induced tissue damage have suggested that dose-rate could affect radiation damage. Because SR X-ray has exceedingly high dose-rate compared to regular X-ray, it remains to be determined if dose-rate may affect SR X-ray-induced tissue damage. We used rodent testes as a model to investigate the role of dose-rate in SR X-ray-induced tissue damage. One day after SR X-ray irradiation, we determined the effects of the irradiation of the same dosage at two different dose-rates, 0.11 Gy/s and 1.1 Gy/s, on TUNEL signals, caspase-3 activation and DNA double-strand breaks (DSBs) of the testes. Compared to those produced by the irradiation at 0.11 Gy/s, irradiation at 1.1 Gy/s produced higher levels of DSBs, TUNEL signals, and caspase-3 activation in the testes. Our study has provided the first evidence suggesting that dose-rate could be a significant factor in SR X-ray-induced tissue damage, which may establish a valuable base for utilizing this factor to manipulate the tissue damage in SR X-ray-based medical applications. PMID:28078052

Ameliorating Effects of Green Synthesized Silver Nanoparticles on Glycated End Product Induced Reactive Oxygen Species Production and Cellular Toxicity in Osteogenic Saos-2 Cells.

PubMed

Ashe, Sarbani; Nayak, Debasis; Kumari, Manisha; Nayak, Bismita

2016-11-09

Advanced glycation end-products (AGEs) that result from nonenzymatic glycation are one of the major factors involved in diabetes and its secondary complications and diseases. This necessitates our urge to discover new compounds that may be used as potential AGEs inhibitors without affecting the normal structure and function of biomolecules. In the present study, we investigated the inhibitory effects of AgNP (silver nanoparticles) on AGEs formation as well as their inhibitory effects on glycation mediated cell toxicity via reactive oxygen species (ROS) production and DNA damage. The excitation-emission fluorescence spectroscopy was employed to investigate the interaction of AgNP during glycation. The values of conditional stability constant (log K a = 4.44) derived from the Stern-Volmer equation indicate that AgNP have strong binding capacity for glycated protein. UV-vis, fluorescence, and Fourier transform infrared spectral data reveal complexation of AgNP with glycated bovine serum albumin, which significantly inhibits AGEs formation in a concentration-dependent manner. Cytotoxic evaluations suggest that simultaneous administration of AgNP and glycated product reduces cell death (42.82% ± 3.54) as compared to the glycated product alone. Similarly, ROS production in AgNP treated cells is significantly less compared to only glycated product treated cells. Although DNA damage studies show DNA damage in both GP and GP-AgNP treated cells, fluorescence activated cell sorting analysis demonstrates that glycated products induce cell death by necrosis, while AgNP cause cell death via apoptotic pathways. AgNP have a positive effect on restoring native protein structure deduced from spectral studies, and hence, inferences can be drawn that AgNP have ameliorating effects on glycated induced cytotoxicity observed in osteogenic Saos-2 cells.

Understanding DNA under oxidative stress and sensitization: the role of molecular modeling

PubMed Central

Dumont, Elise; Monari, Antonio

2015-01-01

DNA is constantly exposed to damaging threats coming from oxidative stress, i.e., from the presence of free radicals and reactive oxygen species. Sensitization from exogenous and endogenous compounds that strongly enhance the frequency of light-induced lesions also plays an important role. The experimental determination of DNA lesions, though a difficult subject, is somehow well established and allows to elucidate even extremely rare DNA lesions. In parallel, molecular modeling has become fundamental to clearly understand the fine mechanisms related to DNA defects induction. Indeed, it offers an unprecedented possibility to get access to an atomistic or even electronic resolution. Ab initio molecular dynamics may also describe the time-evolution of the molecular system and its reactivity. Yet the modeling of DNA (photo-)reactions does necessitate elaborate multi-scale methodologies to tackle a damage induction reactivity that takes place in a complex environment. The double-stranded DNA environment is first characterized by a very high flexibility, but also a strongly inhomogeneous electrostatic embedding. Additionally, one aims at capturing more subtle effects, such as the sequence selectivity which is of critical important for DNA damage. The structure and dynamics of the DNA/sensitizers complexes, as well as the photo-induced electron- and energy-transfer phenomena taking place upon sensitization, should be carefully modeled. Finally the factors inducing different repair ratios for different lesions should also be rationalized. In this review we will critically analyze the different computational strategies used to model DNA lesions. A clear picture of the complex interplay between reactivity and structural factors will be sketched. The use of proper multi-scale modeling leads to the in-depth comprehension of DNA lesions mechanisms and also to the rational design of new chemo-therapeutic agents. PMID:26236706

Not all boronic acids with a five-membered cycle induce tremor, neuronal damage and decreased dopamine.

PubMed

Pérez-Rodríguez, Maribel; García-Mendoza, Esperanza; Farfán-García, Eunice D; Das, Bhaskar C; Ciprés-Flores, Fabiola J; Trujillo-Ferrara, José G; Tamay-Cach, Feliciano; Soriano-Ursúa, Marvin A

2017-09-01

Several striatal toxins can be used to induce motor disruption. One example is MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), whose toxicity is accepted as a murine model of parkinsonism. Recently, 3-Thienylboronic acid (3TB) was found to produce motor disruption and biased neuronal damage to basal ganglia in mice. The aim of this study was to examine the toxic effects of four boronic acids with a close structural relationship to 3TB (all having a five-membered cycle), as well as boric acid and 3TB. These boron-containing compounds were compared to MPTP regarding brain access, morphological disruption of the CNS, and behavioral manifestations of such disruption. Data was collected through acute toxicity evaluations, motor behavior tests, necropsies, determination of neuronal survival by immunohistochemistry, Raman spectroscopic analysis of brain tissue, and HPLC measurement of dopamine in substantia nigra and striatum tissue. Each compound showed a distinct profile for motor disruption. For example, motor activity was not disrupted by boric acid, but was decreased by two boronic acids (caused by a sedative effect). 3TB, 2-Thienyl and 2-furanyl boronic acid gave rise to shaking behavior. The various manifestations generated by these compounds can be linked, in part, to different levels of dopamine (measured by HPLC) and degrees of neuronal damage in the basal ganglia and cerebellum. Clearly, motor disruption is not induced by all boronic acids with a five-membered cycle as substituent. Possible explanations are given for the diverse chemico-morphological changes and degrees of disruption of the motor system, considering the role of boron and the structure-toxicity relationship. Copyright © 2017 Elsevier B.V. All rights reserved.

Arsenite induced oxidative damage in mouse liver is associated with increased cytokeratin 18 expression.

PubMed

Gonsebatt, M E; Del Razo, L M; Cerbon, M A; Zúñiga, O; Sanchez-Peña, L C; Ramírez, P

2007-09-01

Cytokeratins (CK) constitute a family of cytoskeletal intermediate filament proteins that are typically expressed in epithelial cells. An abnormal structure and function are effects that are clearly related to liver diseases as non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. We have previously observed that sodium arsenite (SA) induced the synthesis of CK18 protein and promotes a dose-related disruption of cytoplasmic CK18 filaments in a human hepatic cell line. Both abnormal gene expression and disturbance of structural organization are toxic effects that are likely to cause liver disease by interfering with normal hepatocyte function. To investigate if a disruption in the CK18 expression pattern is associated with arsenite liver damage, we investigated CK18 mRNA and protein levels in liver slices treated with low levels of SA. Organotypic cultures were incubated with 0.01, 1 and 10 microM of SA in the absence and presence of N-acetyl cysteine (NAC). Cell viability and inorganic arsenic metabolism were determined. Increased expression of CK18 was observed after exposure to SA. The addition of NAC impeded the oxidative effects of SA exposure, decreasing the production of thiobarbituric acid-reactive substances and significantly diminishing the up regulation of CK18 mRNA and protein. Liver arsenic levels correlated with increased levels of mRNA. Mice treated with intragastric single doses of 2.5 and 5 mg/kg of SA showed an increased expression of CK18. Results suggest that CK18 expression may be a sensible early biomarker of oxidative stress and damage induced by arsenite in vitro and in vivo. Then, during SA exposure, altered CK expression may compromise liver function.

Dynamic maps of UV damage formation and repair for the human genome

PubMed Central

Hu, Jinchuan; Adebali, Ogun; Adar, Sheera; Sancar, Aziz

2017-01-01

Formation and repair of UV-induced DNA damage in human cells are affected by cellular context. To study factors influencing damage formation and repair genome-wide, we developed a highly sensitive single-nucleotide resolution damage mapping method [high-sensitivity damage sequencing (HS–Damage-seq)]. Damage maps of both cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts [(6-4)PPs] from UV-irradiated cellular and naked DNA revealed that the effect of transcription factor binding on bulky adducts formation varies, depending on the specific transcription factor, damage type, and strand. We also generated time-resolved UV damage maps of both CPDs and (6-4)PPs by HS–Damage-seq and compared them to the complementary repair maps of the human genome obtained by excision repair sequencing to gain insight into factors that affect UV-induced DNA damage and repair and ultimately UV carcinogenesis. The combination of the two methods revealed that, whereas UV-induced damage is virtually uniform throughout the genome, repair is affected by chromatin states, transcription, and transcription factor binding, in a manner that depends on the type of DNA damage. PMID:28607063

Dynamic maps of UV damage formation and repair for the human genome.

PubMed

Hu, Jinchuan; Adebali, Ogun; Adar, Sheera; Sancar, Aziz

2017-06-27

Formation and repair of UV-induced DNA damage in human cells are affected by cellular context. To study factors influencing damage formation and repair genome-wide, we developed a highly sensitive single-nucleotide resolution damage mapping method [high-sensitivity damage sequencing (HS-Damage-seq)]. Damage maps of both cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts [(6-4)PPs] from UV-irradiated cellular and naked DNA revealed that the effect of transcription factor binding on bulky adducts formation varies, depending on the specific transcription factor, damage type, and strand. We also generated time-resolved UV damage maps of both CPDs and (6-4)PPs by HS-Damage-seq and compared them to the complementary repair maps of the human genome obtained by excision repair sequencing to gain insight into factors that affect UV-induced DNA damage and repair and ultimately UV carcinogenesis. The combination of the two methods revealed that, whereas UV-induced damage is virtually uniform throughout the genome, repair is affected by chromatin states, transcription, and transcription factor binding, in a manner that depends on the type of DNA damage.

Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach.

PubMed

Stampanoni Bassi, Mario; Gilio, Luana; Buttari, Fabio; Maffei, Pierpaolo; Marfia, Girolama A; Restivo, Domenico A; Centonze, Diego; Iezzi, Ennio

2017-01-01

Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the "clinico-radiological paradox." The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

Study of self-ion irradiated nanostructured ferritic alloy (NFA) and silicon carbide-nanostructured ferritic alloy (SiC-NFA) cladding materials

NASA Astrophysics Data System (ADS)

Ning, Kaijie; Bai, Xianming; Lu, Kathy

2018-07-01

Silicon carbide-nanostructured ferritic alloy (SiC-NFA) materials are expected to have the beneficial properties of each component for advanced nuclear claddings. Fabrication of pure NFA (0 vol% SiC-100 vol% NFA) and SiC-NFAs (2.5 vol% SiC-97.5 vol% NFA, 5 vol% SiC-95 vol% NFA) has been reported in our previous work. This paper is focused on the study of radiation damage in these materials under 5 MeV Fe++ ion irradiation with a dose up to ∼264 dpa. It is found that the material surfaces are damaged to high roughness with irregularly shaped ripples, which can be explained by the Bradley-Harper (B-H) model. The NFA matrix shows ion irradiation induced defect clusters and small dislocation loops, while the crystalline structure is maintained. Reaction products of Fe3Si and Cr23C6 are identified in the SiC-NFA materials, with the former having a partially crystalline structure but the latter having a fully amorphous structure upon irradiation. The different radiation damage behaviors of NFA, Fe3Si, and Cr23C6 are explained using the defect reaction rate theory.

Targeting HDAC3, a new partner protein of AKT in the reversal of chemoresistance in acute myeloid leukemia via DNA damage response.

PubMed

Long, J; Fang, W Y; Chang, L; Gao, W H; Shen, Y; Jia, M Y; Zhang, Y X; Wang, Y; Dou, H B; Zhang, W J; Zhu, J; Liang, A B; Li, J M; Hu, Jiong

2017-12-01

Resistance to cytotoxic chemotherapy drugs remains as the major cause of treatment failure in acute myeloid leukemia. Histone deacetylases (HDAC) are important regulators to maintain chromatin structure and control DNA damage; nevertheless, how each HDAC regulates genome stability remains unclear, especially under genome stress conditions. Here, we identified a mechanism by which HDAC3 regulates DNA damage repair and mediates resistance to chemotherapy drugs. In addition to inducing DNA damage, chemotherapy drugs trigger upregulation of HDAC3 expression in leukemia cells. Using genetic and pharmacological approaches, we show that HDAC3 contributes to chemotherapy resistance by regulating the activation of AKT, a well-documented factor in drug resistance development. HDAC3 binds to AKT and deacetylates it at the site Lys20, thereby promoting the phosphorylation of AKT. Chemotherapy drug exposure enhances the interaction between HDAC3 and AKT, resulting in decrease in AKT acetylation and increase in AKT phosphorylation. Whereas HDAC3 depletion or inhibition abrogates these responses and meanwhile sensitizes leukemia cells to chemotoxicity-induced apoptosis. Importantly, in vivo HDAC3 suppression reduces leukemia progression and sensitizes MLL-AF9 + leukemia to chemotherapy. Our findings suggest that combination therapy with HDAC3 inhibitor and genotoxic agents may constitute a successful strategy for overcoming chemotherapy resistance.

α-Lipoic acid attenuates transplacental nicotine-induced germ cell and oxidative DNA damage in adult mice.

PubMed

Anto, Santo K; Koyada, Naresh; Khan, Sabbir; Jena, Gopabandhu

2016-11-01

Smoking during pregnancy is associated with numerous fetal and developmental complications and reproductive dysfunctions in the offspring. Nicotine is one of the key chemicals of tobacco responsible for addiction. The present study was aimed to investigate the protective role of α-lipoic acid (ALA) during the transplacental nicotine-induced germ cell and DNA damage in the offspring of Swiss mice. Pregnant mice were treated with nicotine (20 mg/kg/day) in drinking water from 10 to 20 days of gestation period, and ALA (120 mg/kg/day) was administered orally for the same period. Endpoint of evaluation includes general observations at delivery and throughout the study, litter weight and size, sperm count and sperm head morphology, while structural damages and protein expression were assessed by histology and immunohistochemistry, respectively. Maternal nicotine exposure led to decreased growth rate, litter and testicular weight, testosterone level, 3β-HSD expression and sperm count as well as increased sperm head abnormalities, micronucleus frequency and 8-oxo-dG positive cells, and the effects have been restored by ALA supplementation. The present study clearly demonstrated that ALA ameliorates nicotine-associated oxidative stress, DNA damage and testicular toxicity in the offspring by improving steroidogenesis, spermatogenesis and sperm count.

Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scharpfenecker, Marion, E-mail: m.scharpfenecker@nki.nl; Floot, Ben; Russell, Nicola S.

Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, andmore » 40 weeks after irradiation. Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function.« less

Dynamics of laser-induced damage of spherical nanoparticles by high-intensity ultrashort laser pulses

NASA Astrophysics Data System (ADS)

Komolov, Vladimir L.; Gruzdev, Vitaly E.; Przhibelskii, Sergey G.; Smirnov, Dmitry S.

2012-12-01

Damage of a metal spherical nanoparticle by femtosecond laser pulses is analyzed by splitting the overall process into two steps. The fast step includes electron photoemission from a nanoparticle. It takes place during direct action of a laser pulse and its rate is evaluated as a function of laser and particle parameters by two approaches. Obtained results suggest the formation of significant positive charge of the nanoparticles due to the photoemission. The next step includes ion emission that removes the excessive positive charge and modifies particle structure. It is delayed with respect to the photo-emission and is analyzed by a simple analytical model and modified molecular dynamics. Obtained energy distribution suggests generation of fast ions capable of penetrating into surrounding material and generating defects next to the nanoparticle. The modeling is extended to the case of a nanoparticle on a solid surface to understand the basic mechanism of surface laser damage initiated by nano-contamination. Simulations predict embedding the emitted ions into substrate within a spot with size significantly exceeding the original particle size. We discuss the relation of those effects to the problem of bulk and surface laser-induced damage of optical materials by single and multiple ultrashort laser pulses.

Tissue injury and repair following cutaneous exposure of mice to sulfur mustard

PubMed Central

Joseph, Laurie B.; Composto, Gabriella; Heck, Diane E.

2016-01-01

In mouse skin, sulfur mustard is a potent vesicant, damaging both the epidermis and the dermis. The extent of wounding is dependent on the dose of sulfur mustard and the duration of exposure. Initial responses include erythema, pruritus, edema, and xerosis; this is followed by an accumulation of inflammatory leukocytes in the tissue, activation of mast cells, and the release of mediators, including proinflammatory cytokines and bioactive lipids. These proinflammatory mediators contribute to damaging the epidermis, hair follicles, and sebaceous glands and to disruption of the epidermal basement membrane. This can lead to separation of the epidermis from the dermis, resulting in a blister, which ruptures, leading to the formation of an eschar. The eschar stimulates the formation of a neoepidermis and wound repair and may result in persistent epidermal hyperplasia. Epidermal damage and repair is associated with upregulation of enzymes generating proinflammatory and progrowth/pro–wound healing mediators, including cyclooxygenase-2 (COX-2), which generates prostanoids, inducible nitric oxide synthase (iNOS), which generates nitric oxide, fibroblast growth factor receptor 2 (FGFR2), and galectin-3. Characterization of the mediators regulating structural changes in the skin during sulfur mustard–induced tissue damage and wound healing will aid in the development of therapeutic modalities to mitigate toxicity and stimulate tissue repair processes. PMID:27371823

Tissue injury and repair following cutaneous exposure of mice to sulfur mustard.

PubMed

Joseph, Laurie B; Composto, Gabriella M; Heck, Diane E

2016-08-01

In mouse skin, sulfur mustard (SM) is a potent vesicant, damaging both the epidermis and the dermis. The extent of wounding is dependent on the dose of SM and the duration of exposure. Initial responses include erythema, pruritus, edema, and xerosis; this is followed by an accumulation of inflammatory leukocytes in the tissue, activation of mast cells, and the release of mediators, including proinflammatory cytokines and bioactive lipids. These proinflammatory mediators contribute to damaging the epidermis, hair follicles, and sebaceous glands and to disruption of the epidermal basement membrane. This can lead to separation of the epidermis from the dermis, resulting in a blister, which ruptures, leading to the formation of an eschar. The eschar stimulates the formation of a neoepidermis and wound repair and may result in persistent epidermal hyperplasia. Epidermal damage and repair is associated with upregulation of enzymes generating proinflammatory and pro-growth/pro-wound healing mediators, including cyclooxygenase-2, which generates prostanoids, inducible nitric oxide synthase, which generates nitric oxide, fibroblast growth factor receptor 2, and galectin-3. Characterization of the mediators regulating structural changes in the skin during SM-induced tissue damage and wound healing will aid in the development of therapeutic modalities to mitigate toxicity and stimulate tissue repair processes. © 2016 New York Academy of Sciences.