The study of past damaging hydrogeological events for damage susceptibility zonation

NASA Astrophysics Data System (ADS)

Petrucci, O.; Pasqua, A. A.

2008-08-01

Damaging Hydrogeological Events are defined as periods during which phenomena, such as landslides, floods and secondary floods, cause damage to people and the environment. A Damaging Hydrogeological Event which heavily damaged Calabria (Southern Italy) between December 1972, and January 1973, has been used to test a procedure to be utilised in the zonation of a province according to damage susceptibility during DHEs. In particular, we analyzed the province of Catanzaro (2391 km2), an administrative district composed of 80 municipalities, with about 370 000 inhabitants. Damage, defined in relation to the reimbursement requests sent to the Department of Public Works, has been quantified using a procedure based on a Local Damage Index. The latter, representing classified losses, has been obtained by multiplying the value of the damaged element and the percentage of damage affecting it. Rainfall has been described by the Maximum Return Period of cumulative rainfall, for both short (1, 3, 5, 7, 10 consecutive days) and long duration (30, 60, 90, 180 consecutive days), recorded during the event. Damage index and population density, presumed to represent the location of vulnerable elements, have been referred to Thiessen polygons associated to rain gauges working at the time of the event. The procedure allowed us to carry out a preliminary classification of the polygons composing the province according to their susceptibility to damage during DHEs. In high susceptibility polygons, severe damage occurs during rainfall characterised by low return periods; in medium susceptibility polygons maximum return period rainfall and induced damage show equal levels of exceptionality; in low susceptibility polygons, high return period rainfall induces a low level of damage. The east and west sectors of the province show the highest susceptibility, while polygons of the N-NE sector show the lowest susceptibility levels, on account of both the low population density and high average rainfall characterizing these mountainous areas. The future analysis of further DHEs, using the tested procedure, can strengthen the obtained zonation. Afterwards, the results can prove useful in establishing civil defence plans, emergency management, and prioritizing hazard mitigation measures.

Effects of a fruit-vegetable dietary pattern on oxidative stress and genetic damage in coke oven workers: a cross-sectional study.

PubMed

Xie, Zheng; Lin, Haijiang; Fang, Renfei; Shen, Weiwei; Li, Shuguang; Chen, Bo

2015-05-06

Coke oven workers (COWs) are exposed to high level of genotoxic chemicals that induce oxidative stress and genetic damage. The dietary intake of certain types of foods may reverse these effects. We conducted a cross-sectional study with 51 topside COWs, 79 other COWs, and 67 controls, to assess the effects of dietary patterns on oxidative stress and genetic damage. Compared to the controls, both topside and other COWs had significantly higher urinary 1-hydroxypyrene levels, serum oxidant levels [malondialdehyde, (MDA)], and genetic damage [micronucleus (MN) frequency & 8-oxo-2'-deoxyguanosine (8-OH-dG)], but lower antioxidant levels [superoxide dismutase (SOD) and glutathione peroxidase, (GPx)]. The fruit-vegetable (FV) dietary pattern was positively correlated with serum SOD levels and negative correlated with serum MDA, MN frequency, and urinary 8-OH-dG. COWs with an FV patter in the highest quartile (Q4) had significantly increased antioxidant levels (SOD and GPx) and decreased oxidant levels (MDA) and genetic damage (MN frequency and 8-OH-dG) than those with an FV pattern in the lowest quartile (Q1). Compared to control subjects, COWs had increased oxidative stress and genetic damage. A FV dietary pattern may reverse oxidative stress and genetic damage in COWs.

[The dose-effect relationship of water fluoride levels and renal damage in children].

PubMed

Liu, Jun-Ling; Xia, Tao; Yu, Yao-Yong; Sun, Xian-Zhong; Zhu, Qilong; He, Weihong; Zhang, Ming; Wang, Aiguo

2005-05-01

To explore the dose-effect relationship of water fluoride levels and renal damage in children and observe the difference of renal function between high-loaded fluoride people and dental fluorosis people in the same water fluoride level region. 210 children were divided into seven groups in term of drinking water fluoride levels and whether they suffered from dental fluorosis. Fluoride concentrations in urine and serum and activities of urine NAG and gamma-GT were determined. The urine and serum fluoride of high-loaded fluoride people and dental fluorosis people increased compared with control, moreover fluoride contents in urine and serum increased gradually with the increase of fluoride level in drinking water. Urine NAG and gamma-GT activities significantly increased in dental fluorosis people from area of 2.58 mg/L fluoride in drinking water and in those two groups from area of 4.51 mg/L fluoride in drinking water. Moreover, there existed an obvious dose-effect relationship between the drinking water fluoride concentration and NAG and gamma-GT activity. Over 2.0 mg/L fluoride in drinking water can cause renal damage in children, and the damage degree increases with the drinking water fluoride content. Renal damage degree is not related to whether the children suffered from dental fluorosis and mainly due to water fluoride concentration.

Irradiation effect on mechanical properties in structural materials of fast breeder reactor plant

NASA Astrophysics Data System (ADS)

Nagae, Yuji; Takaya, Shigeru; Wakai, Eiichi; Aoto, Kazumi

2011-07-01

The effects of displacement per atom (dpa) level, helium content, and the ratio of helium content to dpa level on the tensile and creep properties have been investigated in the assumed irradiation damage range of FBR structural materials. The assumed irradiation damage range is up to about 1 dpa and about 30 appm for helium content. Austenitic stainless steel and high-chromium martensitic steel are considered as FBR structural materials. As a result, it is shown that the dpa level is a promising index for evaluating neutron irradiation damage.

Estimate of radiation damage to low-level electronics of the RF system in the LHC cavities arising from beam gas collisions.

PubMed

Butterworth, A; Ferrari, A; Tsoulou, E; Vlachoudis, V; Wijnands, T

2005-01-01

Monte Carlo simulations have been performed to estimate the radiation damage induced by high-energy hadrons in the digital electronics of the RF low-level systems in the LHC cavities. High-energy hadrons are generated when the proton beams interact with the residual gas. The contributions from various elements-vacuum chambers, cryogenic cavities, wideband pickups and cryomodule beam tubes-have been considered individually, with each contribution depending on the gas composition and density. The probability of displacement damage and single event effects (mainly single event upsets) is derived for the LHC start-up conditions.

Protective Effects of Gelam Honey against Oxidative Damage in Young and Aged Rats

PubMed Central

Sahhugi, Zulaikha; Jubri, Zakiah

2014-01-01

Aging is characterized by progressive decline in physiological and body function due to increase in oxidative damage. Gelam honey has been accounted to have high phenolic and nonphenolic content to attenuate oxidative damage. This study was to determine the effect of local gelam honey on oxidative damage of aged rats. Twenty-four male Spraque-Dawley rats were divided into young (2 months) and aged (19 months) groups. Each group was further divided into control (fed with plain water) and supplemented with 2.5 mg/kg body weight of gelam honey for 8 months. DNA damage level was determined by comet assay and plasma malondialdehyde (MDA) by high performance liquid chromatography (HPLC). The activity of blood and cardiac antioxidant enzymes was determined by spectrophotometer. The DNA damage and MDA level were reduced in both gelam honey supplemented groups. Gelam honey increases erythrocytes CAT and cardiac SOD activities in young and cardiac CAT activity in young and aged groups. The DNA damage was increased in the aged group compared to young group, but reduced at the end of the study. The decline of oxidative damage in rats supplemented with gelam honey might be through the modulation of antioxidant enzyme activities. PMID:25505937

Sustained water-level changes caused by damage and compaction induced by teleseismic earthquakes

NASA Astrophysics Data System (ADS)

Shalev, Eyal; Kurzon, Ittai; Doan, Mai-Linh; Lyakhovsky, Vladimir

2016-07-01

Sustained water-level increase and decrease induced by distant earthquakes were observed in two wells, Gomè 1 and Meizar 1 in Israel. The Gomè 1 well is located within a damage zone of a major fault zone, and Meizar 1 is relatively far from a fault. The monitored pressure change in both wells shows significant water-level oscillations and sustained water-level changes in response to the passage of the seismic waves. The sustained water-level changes include short-term (minutes) undrained behavior and longer-period (hours and days) drained behavior associated with groundwater flow. We model the short-term undrained response of water pressure oscillations and sustained change to the distant 2013 Mw 7.7 Balochistan earthquake by nonlinear elastic behavior of damaged rocks, accounting for small wave-induced compaction and damage accumulation. We suggest that the rocks are close to failure in both locations and strain oscillations produced by the passing seismic waves periodically push the rock above the yield cap, creating compaction when volumetric strain increases and damage when shear strain increases. Compaction increases pore pressure, whereas damage accumulation decreases pore pressure by fracture dilation. The dominant process depends on the properties of the rock. For highly damaged rocks, dilatancy is dominant and a sustained pressure decrease is expected. For low-damage rocks, compaction is the dominant process creating sustained water-level increase. We calculate damage and porosity changes associated to the Balochistan earthquake in both wells and quantify damage accumulation and compaction during the passage of the seismic waves.

Association of HSP70 and genotoxic damage in lymphocytes of workers exposed to coke-oven emission

PubMed Central

Xiao, Chengfeng; Chen, Sheng; Li, Jizhao; Hai, Tao; Lu, Qiaofa; Sun, Enling; Wang, Ruibo; Tanguay, Robert M.; Wu, Tangchun

2002-01-01

Heat shock proteins (Hsps) have been reported to protect cells, tissues, and organisms against damage from a wide variety of stressful stimuli. Whether they protect against deoxyribonucleic acid (DNA) damage in individuals exposed to environmental stresses and chemical carcinogens is unknown. In the study, we investigated the association between Hsp70 levels (the most abundant mammalian Hsp) and genotoxic damage in lymphocytes of workers exposed to coke-oven emission using Western dot blot and 2 DNA damage assays, the comet assay and the micronucleus test. The data show that there is a significant increase in Hsp70 levels, DNA damage score, and micronucleus rates in lymphocytes of workers exposed to coke-oven emission as compared with the control subjects. Furthermore, there was a significant negative correlation of Hsp70 levels with DNA damage scores in the comet assay (r = −0.663, P < 0.01) and with micronucleus rates (r = −0.461, P < 0.01) in the exposed group. In the control group, there was also a light negative correlation between Hsp70 with DNA damage and micronuclei rate (r = −0.236 and r = 0.242, respectively), but it did not reach a statistically significant level (P > 0.05). Our results show that individuals who had high Hsp70 levels generally showed lower genotoxic damage than others. These results suggest a role of Hsp70 in the protection of DNA from genotoxic damage induced by coke-oven emission. PMID:12653484

High-throughput genotoxicity assay identifies antioxidants as inducers of DNA damage response and cell death

EPA Science Inventory

Human ATAD5 is an excellent biomarker for identifying genotoxic compounds because ATADS protein levels increase post-transcriptionally following exposure to a variety of DNA damaging agents. Here we report a novel quantitative high-throughput ATAD5-Iuciferase assay that can moni...

Estimation of serum malondialdehyde and assessment of DNA damage using comet assay in patients with oral submucous fibrosis.

PubMed

Paulose, Swetha; Rangdhol, Vishwanath; Ramesh, Ramasamy; Jeelani, Siccandar Ali; Brooklyin, Sivakumar

2016-08-01

To quantify the level of serum malondialdehyde and extent of DNA damage using comet assay in patients with oral submucous fibrosis (SMF) in comparison to normal individuals and to correlate the extent of DNA damage with MDA levels. Study included 30 cases of SMF (n = 30) and equal number of healthy volunteers. Serum malondialdehyde was measured using the thiobarbituric-trichloroacetitic acid (TBA-TCA) method. Comet assay was used to assess the DNA damage. Association between the extent of DNA damage and serum MDA levels was analyzed in SMF statistically. Comet assay results showed that there was an increase in tail length, percentage of tail DNA and tail moment among SMF subjects (P < 0.05). Serum MDA levels were elevated in SMF patients compared with healthy subjects. A significant positive correlation was observed between serum MDA levels and comet tail length in SMF group (r = 0.56; P < 0.05). Patients with SMF have increased DNA damage and elevated levels of lipid peroxidation compared with healthy controls. Evaluation of MDA levels as an oxidative biomarker along with comet assay analysis will serve as a diagnostic tool to identify patients with high risk of malignant potential in SMF. © 2015 Wiley Publishing Asia Pty Ltd.

Development of High Level Electrical Stress Failure Threshold and Prediction Model for Small Scale Junction Integrated Circuits

DTIC Science & Technology

1978-09-01

AWACS EMP Guidelines presents two different models to predict the damage pcwer of the dev-ce and the circuit damage EMP voltage ( VEMP ). Neither of...calculated as K P~ I V BD 6. The damage EMP voltage ( VEMP ) is calculated KZ EMP +IZ =D +BD VBD1F 7. The damage EMP voltage is calculated for collector

Differential responses of juvenile and adult South African abalone (Haliotis midae Linnaeus) to low and high oxygen levels.

PubMed

Vosloo, Andre; Laas, Anél; Vosloo, Dalene

2013-01-01

Marine invertebrates have evolved multiple responses to naturally variable environmental oxygen, all aimed at either maintaining cellular oxygen homeostasis or limiting cellular damage during or after hypoxic or hyperoxic events. We assessed organismal (rates of oxygen consumption and ammonia excretion) and cellular (heat shock protein expression, anti-oxidant enzymes) responses of juvenile and adult abalone exposed to low (~83% of saturation), intermediate (~95% of saturation) and high (~115% of saturation) oxygen levels for one month. Using the Comet assay, we measured DNA damage to determine whether the observed trends in the protective responses were sufficient to prevent oxidative damage to cells. Juveniles were unaffected by moderately hypoxic and hyperoxic conditions. Elevated basal rates of superoxide dismutase, glutathione peroxidase and catalase were sufficient to prevent DNA fragmentation and protein damage. Adults, with their lower basal rate of anti-oxidant enzymes, had increased DNA damage under hypoxic and hyperoxic conditions, indicating that the antioxidant enzymes were unable to prevent oxidative damage under hypoxic and hyperoxic conditions. The apparent insensitivity of juvenile abalone to decreased and increased oxygen might be related to their life history and development in algal and diatom biofilms where they are exposed to extreme diurnal fluctuations in dissolved oxygen levels. Copyright © 2012 Elsevier Inc. All rights reserved.

A junction-level optoelectronic characterization of etching-induced damage for third-generation HgCdTe infrared focal-plane array photodetectors

NASA Astrophysics Data System (ADS)

Wang, Peng; Wang, Yueming; Wu, Mingzai; Ye, Zhenhua

2018-06-01

Third-generation HgCdTe-based infrared focal plane arrays require high aspect ratio trenches with admissible etch induced damage at the surface and sidewalls for effectively isolating the pixels. In this paper, the high-density inductively coupled plasma enhanced reaction ion etching technique has been used for micro-mesa delineation of HgCdTe for third-generation infrared focal-plane array detectors. A nondestructive junction-level optoelectronic characterization method called laser beam induced current (LBIC) is used to evaluate the lateral junction extent of HgCdTe etch-induced damage scanning electron microscopy. It is found that the LBIC profiles exhibit evident double peaks and valleys phenomena. The lateral extent of etch induced mesa damage of ∼2.4 μm is obtained by comparing the LBIC profile and the scanning electron microscopy image of etched sample. This finding will guide us to nondestructively identify the distributions of the etching damages in large scale HgCdTe micro-mesa.

Similarities and differences in global gene expression profiles between herbicide- and pathogen-induced PSII inhibition

USDA-ARS?s Scientific Manuscript database

Plant pathogens, and photosynthesis inhibiting herbicides, can both damage photosystem II (PSII), causing it to be highly sensitive to damage by light energy, and to release high levels of reactive oxygen species (ROS). This photoinhibition of PSII could possibly be the source of the strong oxidativ...

High-cycle fatigue characterization of titanium 5Al-2.5Sn alloy

NASA Technical Reports Server (NTRS)

Mahfuz, H.; Xin, Yu T.; Jeelani, S.

1993-01-01

High-cycle fatigue behavior of titanium 5Al 2.5Sn alloy at room temperature has been studied. S-N curve characterization is performed at different stress ratios ranging from 0 to 0.9 on a subsized fatigue specimen. Both two-stress and three-stress level tests are conducted at different stress ratios to study the cumulative fatigue damage. Life prediction techniques of linear damage rule, double linear damage rule and damage curve approaches are applied, and results are compared with the experimental data. The agreement between prediction and experiment is found to be excellent.

Displacement cascades in a borosilicate glass: Influence of the level of polymerization on the cascade morphology

NASA Astrophysics Data System (ADS)

Delaye, J. M.; Ghaleb, D.

1998-02-01

We have performed some molecular dynamics calculations of displacement cascades in a simplified nuclear glass (SiO 2 + B 2O 3 + Na 2O + Al 2O 3 + ZrO 2). We have observed that the damaged volume at the end of the collision sequence can be divided into a so called highly damaged volume and lightly damaged volume. The aim of this paper is to propose an explanation of this phenomenon by considering that some regions are easy to cross by the projectile and others are difficult to cross by the projectile. Regions which are easy to cross correspond to those containing Na atoms with a low level of polymerisation, and regions which are difficult to cross are areas no containing Na atoms with a high level of polymerisation.

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.

Decreased photosynthetic rate under high temperature in wheat is due to lipid desaturation, oxidation, acylation, and damage of organelles.

PubMed

Djanaguiraman, M; Boyle, D L; Welti, R; Jagadish, S V K; Prasad, P V V

2018-04-05

High temperature is a major abiotic stress that limits wheat (Triticum aestivum L.) productivity. Variation in levels of a wide range of lipids, including stress-related molecular species, oxidative damage, cellular organization and ultrastructural changes were analyzed to provide an integrated view of the factors that underlie decreased photosynthetic rate under high temperature stress. Wheat plants of cultivar Chinese Spring were grown at optimum temperatures (25/15 °C, maximum/minimum) until the onset of the booting stage. Thereafter, plants were exposed to high temperature (35/25 °C) for 16 d. Compared with optimum temperature, a lower photosynthetic rate was observed at high temperature which is an interplay between thylakoid membrane damage, thylakoid membrane lipid composition, oxidative damage of cell organelle, and stomatal and non-stomatal limitations. Triacylglycerol levels were higher under high temperature stress. Polar lipid fatty acyl unsaturation was lower at high temperature, while triacylglycerol unsaturation was the same at high temperature and optimum temperature. The changes in lipid species indicates increases in activities of desaturating, oxidizing, glycosylating and acylating enzymes under high temperature stress. Cumulative effect of high temperature stress led to generation of reactive oxygen species, cell organelle and membrane damage, and reduced antioxidant enzyme activity, and imbalance between reactive oxygen species and antioxidant defense system. Taken together with recent findings demonstrating that reactive oxygen species are formed from and are removed by thylakoid lipids, the data suggest that reactive oxygen species production, reactive oxygen species removal, and changes in lipid metabolism contribute to decreased photosynthetic rate under high temperature stress.

Inhibition of Fried Meat-Induced Colorectal DNA Damage and Altered Systemic Genotoxicity in Humans by Crucifera, Chlorophyllin, and Yogurt

PubMed Central

Shaughnessy, Daniel T.; Gangarosa, Lisa M.; Schliebe, Barbara; Umbach, David M.; Xu, Zongli; MacIntosh, Beth; Knize, Mark G.; Matthews, Peggy P.; Swank, Adam E.; Sandler, Robert S.; DeMarini, David M.; Taylor, Jack A.

2011-01-01

Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 subjects were randomly assigned to dietary regimens containing meat cooked at either low (100°C) or high temperature (250°C), each for 2 weeks in a crossover design. The other 8 subjects were randomly assigned to dietary regimens containing the high-temperature meat diet alone or in combination with 3 putative mutagen inhibitors: cruciferous vegetables, yogurt, and chlorophyllin tablets, also in a crossover design. Subjects were nonsmokers, at least 18 years old, and not currently taking prescription drugs or antibiotics. We used the Salmonella assay to analyze the meat, urine, and feces for mutagenicity, and the comet assay to analyze rectal biopsies and peripheral blood lymphocytes for DNA damage. Low-temperature meat had undetectable levels of heterocyclic amines (HCAs) and was not mutagenic, whereas high-temperature meat had high HCA levels and was highly mutagenic. The high-temperature meat diet increased the mutagenicity of hydrolyzed urine and feces compared to the low-temperature meat diet. The mutagenicity of hydrolyzed urine was increased nearly twofold by the inhibitor diet, indicating that the inhibitors enhanced conjugation. Inhibitors decreased significantly the mutagenicity of un-hydrolyzed and hydrolyzed feces. The diets did not alter the levels of DNA damage in non-target white blood cells, but the inhibitor diet decreased nearly twofold the DNA damage in target colorectal cells. To our knowledge, this is the first demonstration that dietary factors can reduce DNA damage in the target tissue of fried-meat associated carcinogenesis. Trial Registration ClinicalTrials.gov NCT00340743. PMID:21541030

Diurnal variation in bacterioplankton composition and DNA damage in the microbial community from an Andean oligotrophic lake.

PubMed

Fernández-Zenoff, María V; Estévez, María C; Farías, María E

2014-01-01

Laguna Azul is an oligotrophic lake situated at 4,560 m above sea level and subject to a high level of solar radiation. Bacterioplankton community composition (BCC) was analysed by denaturing gradient gel electrophoresis and the impact of solar ultraviolet radiation was assessed by measuring cyclobutane pyrimidine dimers (CPD). Furthermore, pure cultures of Acinetobacter johnsonii A2 and Rhodococcus sp. A5 were exposed simultaneously and CPD accumulation was studied. Gel analyses generated a total of 7 sequences belonging to Alpha-proteobacteria (1 band), Beta-proteobacteria (1 band), Bacteroidetes (2 bands), Actinobacteria (1 band), and Firmicutes (1 band). DGGE profiles showed minimal changes in BCC and no CPD was detected even though a high level of damage was found in biodosimeters. A. johnsonii A2 showed low level of DNA damage while Rhodococcus sp. A5 exhibited high resistance since no CPD were detected under natural UV-B exposure, suggesting that the bacterial community is well adapted to this highly solar irradiated environment. Copyright © 2014 Asociación Argentina de Microbiología. Publicado por Elsevier España. All rights reserved.

Dose-rate effect of ultrashort electron beam radiation on DNA damage and repair in vitro.

PubMed

Babayan, Nelly; Hovhannisyan, Galina; Grigoryan, Bagrat; Grigoryan, Ruzanna; Sarkisyan, Natalia; Tsakanova, Gohar; Haroutiunian, Samvel; Aroutiounian, Rouben

2017-11-01

Laser-generated electron beams are distinguished from conventional accelerated particles by ultrashort beam pulses in the femtoseconds to picoseconds duration range, and their application may elucidate primary radiobiological effects. The aim of the present study was to determine the dose-rate effect of laser-generated ultrashort pulses of 4 MeV electron beam radiation on DNA damage and repair in human cells. The dose rate was increased via changing the pulse repetition frequency, without increasing the electron energy. The human chronic myeloid leukemia K-562 cell line was used to estimate the DNA damage and repair after irradiation, via the comet assay. A distribution analysis of the DNA damage was performed. The same mean level of initial DNA damages was observed at low (3.6 Gy/min) and high (36 Gy/min) dose-rate irradiation. In the case of low-dose-rate irradiation, the detected DNA damages were completely repairable, whereas the high-dose-rate irradiation demonstrated a lower level of reparability. The distribution analysis of initial DNA damages after high-dose-rate irradiation revealed a shift towards higher amounts of damage and a broadening in distribution. Thus, increasing the dose rate via changing the pulse frequency of ultrafast electrons leads to an increase in the complexity of DNA damages, with a consequent decrease in their reparability. Since the application of an ultrashort pulsed electron beam permits us to describe the primary radiobiological effects, it can be assumed that the observed dose-rate effect on DNA damage/repair is mainly caused by primary lesions appearing at the moment of irradiation. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Absence of Peroxiredoxin 6 Amplifies the Effect of Oxidant Stress on Mobility and SCSA/CMA3 Defined Chromatin Quality and Impairs Fertilizing Ability of Mouse Spermatozoa1

PubMed Central

Ozkosem, Burak; Feinstein, Sheldon I.; Fisher, Aron B.; O'Flaherty, Cristian

2016-01-01

Oxidative stress, the imbalance between reactive oxygen species production and antioxidant defenses, is associated with male infertility. Peroxiredoxins (PRDXs) are antioxidant enzymes with a wide distribution in spermatozoa. PRDX6 is highly abundant and located in all subcellular compartments of the spermatozoon. Infertile men have lower levels of sperm PRDX6 associated with low sperm motility and high DNA damage. In order to better understand the role of PRDX6 in male reproduction, the aim of this study was to elucidate the impact of the lack of PRDX6 on male mouse fertility. Spermatozoa lacking PRDX6 showed significantly increased levels of cellular oxidative damage evidenced by high levels of lipid peroxidation, 8-hydroxy-deoxyguanosine (DNA oxidation), and protein oxidation (S-glutathionylation and carbonylation), lower sperm chromatin quality (high DNA fragmentation and low DNA compaction, due to low levels of protamination and a high percentage of free thiols), along with decreased sperm motility and impairment of capacitation as compared with wild-type (WT) spermatozoa. These manifestations of damage are exacerbated by tert-butyl hydroperoxide treatment in vivo. While WT males partially recovered the quality of their spermatozoa (in terms of motility and sperm DNA integrity), Prdx6−/− males showed higher levels of sperm damage (lower motility and chromatin integrity) 6 mo after the end of treatment. In conclusion, Prdx6−/− males are more vulnerable to oxidative stress than WT males, resulting in impairment of sperm quality and ability to fertilize the oocyte, compatible with the subfertility phenotype observed in these knockout mice. PMID:26792942

Absence of Peroxiredoxin 6 Amplifies the Effect of Oxidant Stress on Mobility and SCSA/CMA3 Defined Chromatin Quality and Impairs Fertilizing Ability of Mouse Spermatozoa.

PubMed

Ozkosem, Burak; Feinstein, Sheldon I; Fisher, Aron B; O'Flaherty, Cristian

2016-03-01

Oxidative stress, the imbalance between reactive oxygen species production and antioxidant defenses, is associated with male infertility. Peroxiredoxins (PRDXs) are antioxidant enzymes with a wide distribution in spermatozoa. PRDX6 is highly abundant and located in all subcellular compartments of the spermatozoon. Infertile men have lower levels of sperm PRDX6 associated with low sperm motility and high DNA damage. In order to better understand the role of PRDX6 in male reproduction, the aim of this study was to elucidate the impact of the lack of PRDX6 on male mouse fertility. Spermatozoa lacking PRDX6 showed significantly increased levels of cellular oxidative damage evidenced by high levels of lipid peroxidation, 8-hydroxy-deoxyguanosine (DNA oxidation), and protein oxidation (S-glutathionylation and carbonylation), lower sperm chromatin quality (high DNA fragmentation and low DNA compaction, due to low levels of protamination and a high percentage of free thiols), along with decreased sperm motility and impairment of capacitation as compared with wild-type (WT) spermatozoa. These manifestations of damage are exacerbated by tert-butyl hydroperoxide treatment in vivo. While WT males partially recovered the quality of their spermatozoa (in terms of motility and sperm DNA integrity), Prdx6(-/-) males showed higher levels of sperm damage (lower motility and chromatin integrity) 6 mo after the end of treatment. In conclusion, Prdx6(-/-) males are more vulnerable to oxidative stress than WT males, resulting in impairment of sperm quality and ability to fertilize the oocyte, compatible with the subfertility phenotype observed in these knockout mice. © 2016 by the Society for the Study of Reproduction, Inc.

True memory, false memory, and subjective recollection deficits after focal parietal lobe lesions.

PubMed

Drowos, David B; Berryhill, Marian; André, Jessica M; Olson, Ingrid R

2010-07-01

There is mounting evidence that the posterior parietal cortex (PPC) plays an important role in episodic memory. We previously found that patients with PPC damage exhibit retrieval-related episodic memory deficits. Here we assess whether parietal lobe damage affects episodic memory on a different task: the Deese-Roediger-McDermott (DRM) false-memory paradigm. Two patients with bilateral PPC damage and a group of matched controls were tested. In Experiment 1, the task was to remember words; in Experiment 2 the task was to remember pictures of common objects. Prior studies have shown that normal participants have high levels of false memory to words, low levels to pictures. The patients exhibited significantly lower levels of false memory to words. One patient showed significantly elevated levels of false memory to pictures. The patients' false memories were accompanied by reduced levels of recollection, as tested by a Remember/Know procedure. PPC damage causes decreased levels of false memories and an abnormal Remember/Know profile. Their false memory rate is similar to the rate exhibited by patients with medial temporal lobe damage. These results support the view that portions of the PPC play a critical role in objective and subjective aspects of recollection.

Quantitation of Radiation Induced Deletion and Recombination Events Associated with Repeated DNA Sequences

NASA Technical Reports Server (NTRS)

Sinden, Richard R.

1999-01-01

Manned exploration of space exposes the explorers to a complex and novel radiation environment. The galactic cosmic ray and trapped belt radiation (predominantly proton) components of this environment are relatively constant, and the variations with the solar cycle are well understood and predictable. The level of radiation encountered in low earth orbits is determined by several factors, including altitude, inclination of orbit with respect to the equator, and spacecraft shielding. At higher altitudes, and on a Mars mission, the level of radiation exposure will increase significantly. A significant fraction of the dose may be delivered by solar particle events which vary dramatically in dose rate and incident particle spectrum. High-LET radiation is of particular concern. High-LET radiation, a component of galactic cosmic rays (GCR), is comprised of a variety of charged particles of various energies (10 MeV/n to 10 GeV/n), including about 87% photons, 12% helium ions, and heavy ions (including iron). These high energy particles can cause significant damage to target cells. The different particle types and energies result in different patterns of energy deposition at the molecular and cellular level in a primary target cell. They can also cause significant damage to other, nearby cells as a result of secondary particles. Protons, for instance produce secondaries that include photons, neutrons, pions, heavy particles, as well as gamma rays. Heavy ions deposit energy in a "track" in which the magnitude of the damage varies as the particle loses energy. Heavy ions produce secondary delta rays, or electrons. The distribution of damage through tissue is described by a Bragg curve which will be characteristic for different energies. Needless to say there are differences in the RBE of protons and a particles. High-LET heavy ions are particularly damaging to cells as they do continual damage throughout their track. Differences in these energy deposition patterns can significantly influence the nature of DNA damage and the ability of cellular systems to repair such damage. It has been suspected that these differences also affect the spatial distribution of damage within the DNA of the interphase cell nucleus and produce corresponding differences in endpoints related to health effects. The interaction of a single high-LET particle with chromatin has been suggested to cause multiple double strand breaks within a relatively short distance. In part this is due to the organization of DNA into chromatin fibers in which distant regions of the DNA helix can be physically juxtaposed by the various levels of coiling of the DNA. This prediction was confirmed by the detection of the generation of double strand DNA fragments of 100-2000 bp following exposure to high-LET ions (including iron).

The Causal Relationship between DNA Damage Induction in Bovine Lymphocytes and the Fukushima Nuclear Power Plant Accident

PubMed Central

Nakamura, Asako J.; Suzuki, Masatoshi; Redon, Christophe E.; Kuwahara, Yoshikazu; Yamashiro, Hideaki; Abe, Yasuyuki; Takahashi, Shintaro; Fukuda, Tomokazu; Isogai, Emiko; Bonner, William M.; Fukumoto, Manabu

2017-01-01

The Fukushima Daiichi Nuclear Power Plant (FNPP) accident, the largest nuclear incident since the 1986 Chernobyl disaster, occurred when the plant was hit by a tsunami triggered by the Great East Japan Earthquake on March 11, 2011. The subsequent uncontrolled release of radioactive substances resulted in massive evacuations in a 20-km zone. To better understand the biological consequences of the FNPP accident, we have been measuring DNA damage levels in cattle in the evacuation zone. DNA damage was evaluated by assessing the levels of DNA double-strand breaks in peripheral blood lymphocytes by immunocyto-fluorescence-based quantification of γ-H2AX foci. A greater than two-fold increase in the fraction of damaged lymphocytes was observed in all animal cohorts within the evacuation zone, and the levels of DNA damage decreased slightly over the 700-day sample collection period. While the extent of damage appeared to be independent of the distance from the accident site and the estimated radiation dose from radiocesium, we observed age-dependent accumulation of DNA damage. Thus, this study, which was the first to evaluate the biological impact of the FNPP accident utilizing the γ-H2AX assays, indicated the causal relation between high levels of DNA damage in animals living in the evacuation zone and the FNPP accident. PMID:28240558

The Causal Relationship between DNA Damage Induction in Bovine Lymphocytes and the Fukushima Nuclear Power Plant Accident.

PubMed

Nakamura, Asako J; Suzuki, Masatoshi; Redon, Christophe E; Kuwahara, Yoshikazu; Yamashiro, Hideaki; Abe, Yasuyuki; Takahashi, Shintaro; Fukuda, Tomokazu; Isogai, Emiko; Bonner, William M; Fukumoto, Manabu

2017-05-01

The Fukushima Daiichi Nuclear Power Plant (FNPP) accident, the largest nuclear incident since the 1986 Chernobyl disaster, occurred when the plant was hit by a tsunami triggered by the Great East Japan Earthquake on March 11, 2011. The subsequent uncontrolled release of radioactive substances resulted in massive evacuations in a 20-km zone. To better understand the biological consequences of the FNPP accident, we have been measuring DNA damage levels in cattle in the evacuation zone. DNA damage was evaluated by assessing the levels of DNA double-strand breaks in peripheral blood lymphocytes by immunocytofluorescence-based quantification of γ-H2AX foci. A greater than two-fold increase in the fraction of damaged lymphocytes was observed in all animal cohorts within the evacuation zone, and the levels of DNA damage decreased slightly over the 700-day sample collection period. While the extent of damage appeared to be independent of the distance from the accident site and the estimated radiation dose from radiocesium, we observed age-dependent accumulation of DNA damage. Thus, this study, which was the first to evaluate the biological impact of the FNPP accident utilizing the γ-H2AX assays, indicated the causal relation between high levels of DNA damage in animals living in the evacuation zone and the FNPP accident.

The control of iron-induced oxidative damage in isolated rat-liver mitochondria by respiration state and ascorbate.

PubMed

Burkitt, M J; Gilbert, B C

1989-01-01

The reaction of iron (II) with H2O2 is believed to generate highly reactive species (e.g. .OH) capable of initiating biological damage. This study investigates the possibility that the severity of oxidative damage induced by iron in hepatic mitochondria is determined by the level of mitochondrial-H2O2 generation, which is believed to be particularly prominent in state-4 respiration. Iron-induced damage is found to be greater in state-4 than in state-3 respiration. Experiments using uncoupling agents and Ca++ to mimic state-3 conditions indicate that this effect reflects differences in the steady-state oxidation-level of the electron carriers of the respiratory chain (and hence the level of H2O2-generation), rather than changes in redox potential or transportation of the metal-ion. Evidence is also presented for a mechanism in which Fe(II) and H2O2 react inside the mitochondrial matrix. Ascorbate (vitamin C) is shown to be pro-oxidant in this system, except when present at very high concentration when it becomes antioxidant in nature.

Deep uncertainty and broad heterogeneity in country-level social cost of carbon

NASA Astrophysics Data System (ADS)

Ricke, K.; Drouet, L.; Caldeira, K.; Tavoni, M.

2017-12-01

The social cost of carbon (SCC) is a commonly employed metric of the expected economic damages expected from carbon dioxide (CO2) emissions. Recent estimates of SCC range from approximately 10/tonne of CO2 to as much as 1000/tCO2, but these have been computed at the global level. While useful in an optimal policy context, a world-level approach obscures the heterogeneous geography of climate damages and vast differences in country-level contributions to global SCC, as well as climate and socio-economic uncertainties, which are much larger at the regional level. For the first time, we estimate country-level contributions to SCC using recent climate and carbon-cycle model projections, empirical climate-driven economic damage estimations, and information from the Shared Socio-economic Pathways. Central specifications show high global SCC values (median: 417 /tCO2, 66% confidence intervals: 168 - 793 /tCO2) with country-level contributions ranging from -11 (-8 - -14) /tCO2 to 86 (50 - 158) /tCO2. We quantify climate-, scenario- and economic damage- driven uncertainties associated with the calculated values of SCC. We find that while the magnitude of country-level social cost of carbon is highly uncertain, the relative positioning among countries is consistent. Countries incurring large fractions of the global cost include India, China, and the United States. The share of SCC distributed among countries is robust, indicating climate change winners and losers from a geopolitical perspective.

The co-evolution of microstructure features in self-ion irradiated HT9 at very high damage levels

NASA Astrophysics Data System (ADS)

Getto, E.; Vancoevering, G.; Was, G. S.

2017-02-01

Understanding the void swelling and phase evolution of reactor structural materials at very high damage levels is essential to maintaining safety and longevity of components in Gen IV fast reactors. A combination of ion irradiation and modeling was utilized to understand the microstructure evolution of ferritic-martensitic alloy HT9 at high dpa. Self-ion irradiation experiments were performed on alloy HT9 to determine the co-evolution of voids, dislocations and precipitates up to 650 dpa at 460 °C. Modeling of microstructure evolution was conducted using the modified Radiation Induced Microstructure Evolution (RIME) model, which utilizes a mean field rate theory approach with grouped cluster dynamics. Irradiations were performed with 5 MeV raster-scanned Fe2+ ions on samples pre-implanted with 10 atom parts per million He. The swelling, dislocation and precipitate evolution at very high dpa was determined using Analytical Electron Microscopy in Scanning Transmission Electron Microscopy (STEM) mode. Experimental results were then interpreted using the RIME model. A microstructure consisting only of dislocations and voids is insufficient to account for the swelling evolution observed experimentally at high damage levels in a complicated microstructure such as irradiated alloy HT9. G phase was found to have a minimal effect on either void or dislocation evolution. M2X played two roles; a variable biased sink for defects, and as a vehicle for removal of carbon from solution, thus promoting void growth. When accounting for all microstructure interactions, swelling at high damage levels is a dynamic process that continues to respond to other changes in the microstructure as long as they occur.

Stiffness degradation-based damage model for RC members and structures using fiber-beam elements

NASA Astrophysics Data System (ADS)

Guo, Zongming; Zhang, Yaoting; Lu, Jiezhi; Fan, Jian

2016-12-01

To meet the demand for an accurate and highly efficient damage model with a distinct physical meaning for performance-based earthquake engineering applications, a stiffness degradation-based damage model for reinforced concrete (RC) members and structures was developed using fiber beam-column elements. In this model, damage indices for concrete and steel fibers were defined by the degradation of the initial reloading modulus and the low-cycle fatigue law. Then, section, member, story and structure damage was evaluated by the degradation of the sectional bending stiffness, rod-end bending stiffness, story lateral stiffness and structure lateral stiffness, respectively. The damage model was realized in Matlab by reading in the outputs of OpenSees. The application of the damage model to RC columns and a RC frame indicates that the damage model is capable of accurately predicting the magnitude, position, and evolutionary process of damage, and estimating story damage more precisely than inter-story drift. Additionally, the damage model establishes a close connection between damage indices at various levels without introducing weighting coefficients or force-displacement relationships. The development of the model has perfected the damage assessment function of OpenSees, laying a solid foundation for damage estimation at various levels of a large-scale structure subjected to seismic loading.

Field and airborne spectral characterization of suspected damage in red spruce (picea rubens) from Vermont

NASA Technical Reports Server (NTRS)

Rock, B. N.; Vogelmann, J. E.; Williams, D. L.

1985-01-01

The utilization of remote sensing to monitor forest damage due to acid deposition is investigated. Spectral and water measurements and aircraft radiance data of red spruce and balsam fir, collected in Camels Hump Mountain and Ripton, Vermont between August 13-20, 1984, are analyzed to evaluate the damage levels of the trees. Variations in reflectance features and canopy moisture content are studied. It is observed that damage correlates with elevation (greater damage at higher elevations); xylem water column tension is greater at higher damage sites; and a 'blue shift' is indicated in the spectral data at high damage sites.

The Levels of Cortisol, Oxidative Stress, and DNA Damage in the Victims of Childhood Sexual Abuse: A Preliminary Study.

PubMed

Şimşek, Şeref; Kaplan, İbrahim; Uysal, Cem; Yüksel, Tuğba; Alaca, Rümeysa

2016-01-01

In this study we aimed to investigate serum cortisol, oxidative stress, and DNA damage in children who are sexual abuse victims. The study included 38 children who sustained child sexual abuse and 38 age- and gender-matched children who did not have a history of trauma. Cortisol levels reflecting the status of the hypothalamic-pituitary-adrenal axis, anti-oxidant enzymes glutathione peroxidase, superoxide dismutase, natural anti-oxidant coenzyme Q, and 8-hydroxy-2-deoxyguanosine as the indicator of DNA damage were analyzed in serum samples using the enzyme linked immunosorbent assay method. Cortisol levels were significantly higher in the child sexual abuse group compared to the control group. There were no significant differences between the groups in terms of oxidative stress and DNA damage. Cortisol and 8-hydroxy-2-deoxyguanosine levels decreased as the time elapsed since the sexual abuse increased. Coenzyme Q level was lower in victims who sustained multiple assaults than in the victims of a single assault. Cortisol and superoxide dismutase levels were lower in the victims of familial sexual abuse. Decreases in cortisol and 8-hydroxy-2-deoxyguanosine levels as time elapsed may be an adaptation to the toxic effects of high cortisol levels over a prolonged period of time. Child sexual abuse did not result in oxidative stress and DNA damage; however, some features of sexual abuse raised the level of oxidative stress.

Activation of EGFR and ERBB2 by Helicobacter pylori results in survival of gastric epithelial cells with DNA damage.

PubMed

Chaturvedi, Rupesh; Asim, Mohammad; Piazuelo, M Blanca; Yan, Fang; Barry, Daniel P; Sierra, Johanna Carolina; Delgado, Alberto G; Hill, Salisha; Casero, Robert A; Bravo, Luis E; Dominguez, Ricardo L; Correa, Pelayo; Polk, D Brent; Washington, M Kay; Rose, Kristie L; Schey, Kevin L; Morgan, Douglas R; Peek, Richard M; Wilson, Keith T

2014-06-01

The gastric cancer-causing pathogen Helicobacter pylori up-regulates spermine oxidase (SMOX) in gastric epithelial cells, causing oxidative stress-induced apoptosis and DNA damage. A subpopulation of SMOX(high) cells are resistant to apoptosis, despite their high levels of DNA damage. Because epidermal growth factor receptor (EGFR) activation can regulate apoptosis, we determined its role in SMOX-mediated effects. SMOX, apoptosis, and DNA damage were measured in gastric epithelial cells from H. pylori-infected Egfr(wa5) mice (which have attenuated EGFR activity), Egfr wild-type mice, or in infected cells incubated with EGFR inhibitors or deficient in EGFR. A phosphoproteomic analysis was performed. Two independent tissue microarrays containing each stage of disease, from gastritis to carcinoma, and gastric biopsy specimens from Colombian and Honduran cohorts were analyzed by immunohistochemistry. SMOX expression and DNA damage were decreased, and apoptosis increased in H. pylori-infected Egfr(wa5) mice. H. pylori-infected cells with deletion or inhibition of EGFR had reduced levels of SMOX, DNA damage, and DNA damage(high) apoptosis(low) cells. Phosphoproteomic analysis showed increased EGFR and erythroblastic leukemia-associated viral oncogene B (ERBB)2 signaling. Immunoblot analysis showed the presence of a phosphorylated (p)EGFR-ERBB2 heterodimer and pERBB2; knockdown of ErbB2 facilitated apoptosis of DNA damage(high) apoptosis(low) cells. SMOX was increased in all stages of gastric disease, peaking in tissues with intestinal metaplasia, whereas pEGFR, pEGFR-ERBB2, and pERBB2 were increased predominantly in tissues showing gastritis or atrophic gastritis. Principal component analysis separated gastritis tissues from patients with cancer vs those without cancer. pEGFR, pEGFR-ERBB2, pERBB2, and SMOX were increased in gastric samples from patients whose disease progressed to intestinal metaplasia or dysplasia, compared with patients whose disease did not progress. In an analysis of gastric tissues from mice and patients, we identified a molecular signature (based on levels of pEGFR, pERBB2, and SMOX) for the initiation of gastric carcinogenesis. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Long-term strength and damage accumulation in laminates

NASA Astrophysics Data System (ADS)

Dzenis, Yuris A.; Joshi, Shiv P.

1993-04-01

A modified version of the probabilistic model developed by authors for damage evolution analysis of laminates subjected to random loading is utilized to predict long-term strength of laminates. The model assumes that each ply in a laminate consists of a large number of mesovolumes. Probabilistic variation functions for mesovolumes stiffnesses as well as strengths are used in the analysis. Stochastic strains are calculated using the lamination theory and random function theory. Deterioration of ply stiffnesses is calculated on the basis of the probabilities of mesovolumes failures using the theory of excursions of random process beyond the limits. Long-term strength and damage accumulation in a Kevlar/epoxy laminate under tension and complex in-plane loading are investigated. Effects of the mean level and stochastic deviation of loading on damage evolution and time-to-failure of laminate are discussed. Long-term cumulative damage at the time of the final failure at low loading levels is more than at high loading levels. The effect of the deviation in loading is more pronounced at lower mean loading levels.

Comparative analysis of rainfall and landslide damage for landslide susceptibility zonation

NASA Astrophysics Data System (ADS)

Petrucci, O.; Pasqua, A. A.

2009-04-01

In the present work we applied a methodology tested in previous works to a regional sector of Calabria (Southern Italy), aiming to obtain a zonation of this area according to the susceptibility to develop landslides, as inferred from the combined analysis of past landslide events and cumulate rainfall which triggered them. The complete series of both historical landslides and daily rainfall have been organised in two databases. For each landslide event, damage, mainly defined in relation to the reimbursement requests sent to the Department of Public Works, has been quantified using a procedure based on a Local Damage Index. Rainfall has been described by the Maximum Return Period of cumulative rainfall recorded during the landslide events. Damage index and population density, presumed to represent the location of vulnerable elements, have been referred to Thiessen polygons associated to rain gauges working at the time of the event. The procedure allowed us to carry out a classification of the polygons composing the study area according to their susceptibility to damage during DHEs. In high susceptibility polygons, severe damage occurs during rainfall characterised by low return periods; in medium susceptibility polygons, maximum return period rainfall and induced damage show equal levels of exceptionality; in low susceptibility polygons, high return period rainfall induces a low level of damage. The results can prove useful in establishing civil defence plans, emergency management, and prioritizing hazard mitigation measures.

House dust mite-induced asthma causes oxidative damage and DNA double-strand breaks in the lungs.

PubMed

Chan, Tze Khee; Loh, Xin Yi; Peh, Hong Yong; Tan, W N Felicia; Tan, W S Daniel; Li, Na; Tay, Ian J J; Wong, W S Fred; Engelward, Bevin P

2016-07-01

Asthma is related to airway inflammation and oxidative stress. High levels of reactive oxygen and nitrogen species can induce cytotoxic DNA damage. Nevertheless, little is known about the possible role of allergen-induced DNA damage and DNA repair as modulators of asthma-associated pathology. We sought to study DNA damage and DNA damage responses induced by house dust mite (HDM) in vivo and in vitro. We measured DNA double-strand breaks (DSBs), DNA repair proteins, and apoptosis in an HDM-induced allergic asthma model and in lung samples from asthmatic patients. To study DNA repair, we treated mice with the DSB repair inhibitor NU7441. To study the direct DNA-damaging effect of HDM on human bronchial epithelial cells, we exposed BEAS-2B cells to HDM and measured DNA damage and reactive oxygen species levels. HDM challenge increased lung levels of oxidative damage to proteins (3-nitrotyrosine), lipids (8-isoprostane), and nucleic acid (8-oxoguanine). Immunohistochemical evidence for HDM-induced DNA DSBs was revealed by increased levels of the DSB marker γ Histone 2AX (H2AX) foci in bronchial epithelium. BEAS-2B cells exposed to HDM showed enhanced DNA damage, as measured by using the comet assay and γH2AX staining. In lung tissue from human patients with asthma, we observed increased levels of DNA repair proteins and apoptosis, as shown by caspase-3 cleavage, caspase-activated DNase levels, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining. Notably, NU7441 augmented DNA damage and cytokine production in the bronchial epithelium and apoptosis in the allergic airway, implicating DSBs as an underlying driver of asthma pathophysiology. This work calls attention to reactive oxygen and nitrogen species and HDM-induced cytotoxicity and to a potential role for DNA repair as a modulator of asthma-associated pathophysiology. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Application of the CometChip platform to assess DNA damage in field-collected blood samples from turtles.

PubMed

Sykora, Peter; Chiari, Ylenia; Heaton, Andrew; Moreno, Nickolas; Glaberman, Scott; Sobol, Robert W

2018-05-01

DNA damage has been linked to genomic instability and the progressive breakdown of cellular and organismal homeostasis, leading to the onset of disease and reduced longevity. Insults to DNA from endogenous sources include base deamination, base hydrolysis, base alkylation, and metabolism-induced oxidative damage that can lead to single-strand and double-strand DNA breaks. Alternatively, exposure to environmental pollutants, radiation or ultra-violet light, can also contribute to exogenously derived DNA damage. We previously validated a novel, high through-put approach to measure levels of DNA damage in cultured mammalian cells. This new CometChip Platform builds on the classical single cell gel electrophoresis or comet methodology used extensively in environmental toxicology and molecular biology. We asked whether the CometChip Platform could be used to measure DNA damage in samples derived from environmental field studies. To this end, we determined that nucleated erythrocytes from multiple species of turtle could be successfully evaluated in the CometChip Platform to quantify levels of DNA damage. In total, we compared levels of DNA damage in 40 animals from two species: the box turtle (Terrapene carolina) and the red-eared slider (Trachemys scripta elegans). Endogenous levels of DNA damage were identical between the two species, yet we did discover some sex-linked differences and changes in DNA damage accumulation. Based on these results, we confirm that the CometChip Platform allows for the measurement of DNA damage in a large number of samples quickly and accurately, and is particularly adaptable to environmental studies using field-collected samples. Environ. Mol. Mutagen. 59:322-333, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Fuselage Versus Subcomponent Panel Response Correlation Based on ABAQUS Explicit Progressive Damage Analysis Tools

NASA Technical Reports Server (NTRS)

Gould, Kevin E.; Satyanarayana, Arunkumar; Bogert, Philip B.

2016-01-01

Analysis performed in this study substantiates the need for high fidelity vehicle level progressive damage analyses (PDA) structural models for use in the verification and validation of proposed sub-scale structural models and to support required full-scale vehicle level testing. PDA results are presented that capture and correlate the responses of sub-scale 3-stringer and 7-stringer panel models and an idealized 8-ft diameter fuselage model, which provides a vehicle level environment for the 7-stringer sub-scale panel model. Two unique skin-stringer attachment assumptions are considered and correlated in the models analyzed: the TIE constraint interface versus the cohesive element (COH3D8) interface. Evaluating different interfaces allows for assessing a range of predicted damage modes, including delamination and crack propagation responses. Damage models considered in this study are the ABAQUS built-in Hashin procedure and the COmplete STress Reduction (COSTR) damage procedure implemented through a VUMAT user subroutine using the ABAQUS/Explicit code.

Effects of a high fat or a balanced omega 3/omega 6 diet on cytokines levels and DNA damage in experimental colitis.

PubMed

Vieira de Barros, Karina; Gomes de Abreu, Gilclay; Xavier, Roberta Araujo Navarro; Real Martinez, Carlos Augusto; Ribeiro, Marcelo Lima; Gambero, Alessandra; de Oliveira Carvalho, Patrícia; Silveira, Vera Lúcia Flor

2011-02-01

High-fat diets have been shown to be a risk factor for ulcerative colitis (UC). Omega-6 polyunsaturated fatty acids are considered to increase lipid peroxidation, while the omega-3 polyunsaturated fatty acid exerts a chemopreventative effect. We evaluated the effect of high-fat diets (20%) enriched with fish or soybean oil on colonic inflammation and DNA damage in dextran sulfate sodium-induced colitis. Male Wistar rats (28-30 days) were fed an American Institute of Nutrition (AIN)-93 diet for 47 days and divided into five groups: control normal fat non-colitic (C) or control colitis (CC), high soybean fat group (HS) colitis, high fish fat group colitis, or high-fat soybean plus fish oil colitis. UC was induced from day 35 until day 41 by 3% dextran sulfate sodium. On day 47, the rats were anesthetized; blood samples collected for corticosterone determination, and the distal colon was excised to quantify interleukin-4 (IL-4), IL-10, and interferon-gamma levels, myeloperoxidase activity, histological analyses, and DNA damage. The disease activity index was recorded daily. The disease activity index, histological analysis, myeloperoxidase activity, IL-4, interferon-gamma, and corticosterone levels did not differ among the colitic groups. IL-10 was significantly increased by the high fish fat group diet in relation to HS, but only the high soybean-fish fat diet increased the IL-10/IL-4 ratio (anti-inflammatory/pro-inflammatory) to levels closer to the C group and reduced DNA damage compared to the HS group (P<0.05). The data show that high-fat diets did not exacerbate UC and suggest that the soybean and fish oil mixture, more than the fish oil alone, could be a complementary therapy to achieve a cytokine balance in UC. Copyright © 2011 Elsevier Inc. All rights reserved.

The effect of predator exposure and reproduction on oxidative stress parameters in the Catarina scallop Argopecten ventricosus.

PubMed

Guerra, C; Zenteno-Savín, T; Maeda-Martínez, A N; Abele, D; Philipp, E E R

2013-05-01

Predation is known to impact growth and reproduction, and the physiological state of the prey, including its susceptibility to oxidative stress. In this study, we investigated how prolonged exposure to predators modulates tissue specific antioxidant defense and oxidative damage in the short-lived epibenthic scallop Argopecten ventricosus (2years maximum lifespan). Scallops that were experimentally exposed to predators had not only lower antioxidant capacities (superoxide dismutase and catalase), but also lower oxidative damage (protein carbonyls and TBARS=thiobarbituric acid reactive substances including lipid peroxides) in gills and mantle compared to individuals not exposed to predators. In contrast, oxidative damage in the swimming muscle was higher in predator-exposed scallops. When predator-exposed scallops were on the verge of spawning, levels of oxidative damage increased in gills and mantle in spite of a parallel increase in antioxidant defense in both tissues. Levels of oxidative damage increased also in the swimming muscle whereas muscle antioxidant capacities decreased. Interestingly, post-spawned scallops restored antioxidant capacities and oxidative damage to immature levels, suggesting they can recover from spawning-related oxidative stress. Our results show that predator exposure and gametogenesis modulate oxidative damage in a tissue specific manner and that high antioxidant capacities do not necessarily coincide with low oxidative damage. Copyright © 2013 Elsevier Inc. All rights reserved.

Age-dependent damage of hair cuticle: contribution of S100A3 protein and its citrullination.

PubMed

Takahashi, Toshie; Mamada, Akira; Kizawa, Kenji; Suzuki, Ryosuke

2016-09-01

There are two types of damage pattern of human hair cuticle: type L, where the cell membrane complex is split and the cuticle lifts up, and type E, where the fragile substructure of the cuticle cell (endocuticle) is broken. In our previous paper, it was reported that the dominant damage pattern shifts from type L to E with the subjects' age around the 40s. Loss of the cuticle due to daily grooming stresses increases with the subjects' age and is related to the level of type E damage. It is supposed that deterioration of endocuticle advances the loss of cuticle. S100A3 protein, located at the endocuticle, was found to be citrullinated and transformed into tetramer to improve its Ca(2+) -binding ability. It is postulated that this biochemical property affects the maturation of cuticle and contributes to its reinforcement. This study aims to elucidate the role that S100A3 plays in age-dependent cuticle damage. Hair fibers collected from Japanese females were evaluated for the content and citrullination rate of S100A3, incidence of type E damage, and resistance of cuticle. In the aged hair, the content of S100A3 was positively correlated with the level of type E damage and low resistance to stress. Hair fibers in which S100A3 is highly citrullinated, however, showed low levels of type E damage and high resistance of cuticle, even in the aged hair as well as at younger ages. S100A3 and its citrullination process are related to rigidity of endocuticle of aged hair. © 2015 Wiley Periodicals, Inc.

Oxidative damage of DNA in subjects occupationally exposed to lead.

PubMed

Pawlas, Natalia; Olewińska, Elżbieta; Markiewicz-Górka, Iwona; Kozłowska, Agnieszka; Januszewska, Lidia; Lundh, Thomas; Januszewska, Ewa; Pawlas, Krystyna

2017-09-01

Exposure to lead (Pb) in environmental and occupational settings continues to be a serious public health problem and may pose an elevated risk of genetic damage. The aim of this study was to assess the level of oxidative stress and DNA damage in subjects occupationally exposed to lead. We studied a population of 78 male workers exposed to lead in a lead and zinc smelter and battery recycling plant and 38 men from a control group. Blood lead levels were detected by graphite furnace atomic absorption spectrophotometry and plasma lead levels by inductively coupled plasma-mass spectrometry. The following assays were performed to assess the DNA damage and oxidative stress: comet assay, determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG), lipid peroxidation and total antioxidant status (TAS). The mean concentration of lead in the blood of the exposed group was 392 ± 103 μg/L and was significantly higher than in the control group (30.3 ± 29.4 μg/L, p < 0.0001). Oxidative DNA damages measured by comet assay showed no significant differences between populations. The concentration of 8-OHdG was about twice as high as in the control group. We found a significant positive correlation between the level of biomarkers of lead exposure [lead in blood, lead in plasma, zinc protoporphyrin (ZPP)] and urine concentration of 8-OHdG. The level of oxidative damage of DNA was positively correlated with the level of lipid peroxidation (TBARS) and negatively with total anti-oxidative status (TAS). Our study suggests that occupational exposure causes an increase in oxidative damage to DNA, even in subjects with relatively short length of service (average length of about 10 years). 8-OHdG concentration in the urine proved to be a sensitive and non-invasive marker of lead induced genotoxic damage.

Analysis of the damage threshold of the GaAs pseudomorphic high electron mobility transistor induced by the electromagnetic pulse

NASA Astrophysics Data System (ADS)

Xi, Xiao-Wen; Chai, Chang-Chun; Liu, Yang; Yang, Yin-Tang; Fan, Qing-Yang; Shi, Chun-Lei

2016-08-01

An electromagnetic pulse (EMP)-induced damage model based on the internal damage mechanism of the GaAs pseudomorphic high electron mobility transistor (PHEMT) is established in this paper. With this model, the relationships among the damage power, damage energy, pulse width and signal amplitude are investigated. Simulation results show that the pulse width index from the damage power formula obtained here is higher than that from the empirical formula due to the hotspot transferring in the damage process of the device. It is observed that the damage energy is not a constant, which decreases with the signal amplitude increasing, and then changes little when the signal amplitude reaches up to a certain level. Project supported by the National Basic Research Program of China (Grant No. 2014CB339900) and the Open Fund of Key Laboratory of Complex Electromagnetic Environment Science and Technology, China Academy of Engineering Physics (CAEP) (Grant No. 2015-0214.XY.K).

Investigation of Cumulative Fatigue Damage Through Sequential Low Cycle Fatigue and High Cycle Fatigue Cycling at High Temperature for a Type 316LN Stainless Steel: Life-Prediction Techniques and Associated Mechanisms

NASA Astrophysics Data System (ADS)

Sarkar, Aritra; Nagesha, A.; Parameswaran, P.; Sandhya, R.; Laha, K.; Okazaki, M.

2017-03-01

Cumulative fatigue damage under sequential low cycle fatigue (LCF) and high cycle fatigue (HCF) cycling was investigated at 923 K (650 °C) by conducting HCF tests on specimens subjected to prior LCF cycling at various strain amplitudes. Remnant HCF lives were found to decrease drastically with increase in prior fatigue exposure as a result of strong LCF-HCF interactions. The rate of decrease in remnant lives varied as a function of the applied strain amplitude. A threshold damage in terms of prior LCF life-fraction was found, below which no significant LCF-HCF interaction takes place. Similarly, a critical damage during the LCF pre-cycling marking the highest degree of LCF-HCF interaction was identified which was found to depend on the applied strain amplitude. In view of the non-linear damage accumulation behavior, Miner's linear damage rule proved to be highly non-conservative. Manson's damage curve approach, suitably modified, was found to be a better alternative for predicting the remnant HCF life. The single constant ( β) employed in the model, which reflects the damage accumulation of the material under two/multi-level loading conditions is derived from the regression analysis of the experimental results and validated further.

Contribution of insurance data to cost assessment of coastal flood damage to residential buildings: insights gained from Johanna (2008) and Xynthia (2010) storm events

NASA Astrophysics Data System (ADS)

André, C.; Monfort, D.; Bouzit, M.; Vinchon, C.

2013-08-01

There are a number of methodological issues involved in assessing damage caused by natural hazards. The first is the lack of data, due to the rarity of events and the widely different circumstances in which they occur. Thus, historical data, albeit scarce, should not be neglected when seeking to build ex-ante risk management models. This article analyses the input of insurance data for two recent severe coastal storm events, to examine what causal relationships may exist between hazard characteristics and the level of damage incurred by residential buildings. To do so, data was collected at two levels: from lists of about 4000 damage records, 358 loss adjustment reports were consulted, constituting a detailed damage database. The results show that for flooded residential buildings, over 75% of reconstruction costs are associated with interior elements, with damage to structural components remaining very localised and negligible. Further analysis revealed a high scatter between costs and water depth, suggesting that uncertainty remains high in drawing up damage functions with insurance data alone. Due to the paper format of the loss adjustment reports, and the lack of harmonisation between their contents, the collection stage called for a considerable amount of work. For future events, establishing a standardised process for archiving damage information could significantly contribute to the production of such empirical damage functions. Nevertheless, complementary sources of data on hazards and asset vulnerability parameters will definitely still be necessary for damage modelling; multivariate approaches, crossing insurance data with external material, should also be investigated more deeply.

Contribution of insurance data to cost assessment of coastal flood damage to residential buildings: insights gained from Johanna (2008) and Xynthia (2010) storm events

NASA Astrophysics Data System (ADS)

André, C.; Monfort, D.; Bouzit, M.; Vinchon, C.

2013-03-01

There are a number of methodological issues involved in assessing damage caused by natural hazards. The first is the lack of data, due to the rarity of events and the widely different circumstances in which they occur. Thus, historical data, albeit scarce, should not be neglected when seeking to build ex-ante risk management models. This article analyses the input of insurance data for two recent severe coastal storm events, to examine what causal relationships may exist between hazard characteristics and the level of damage incurred by residential buildings. To do so, data was collected at two levels: from lists of about 4000 damage records, 358 loss adjustment reports were consulted, constituting a detailed damage database. The results show that for flooded residential buildings, over 75% of reconstruction costs are associated with interior elements, damage to structural components remaining very localised and negligible. Further analysis revealed a high scatter between costs and water depth, suggesting that uncertainty remains high in drawing up damage functions with insurance data alone. Due to the paper format of the loss adjustment reports and the lack of harmonisation between their contents, the collection stage called for a considerable amount of work. For future events, establishing a standardised process for archiving damage information could significantly contribute to the production of such empirical damage functions. Nevertheless, complementary sources of data on hazards and asset vulnerability parameters, will definitely still be necessary for damage modelling and multivariate approaches, crossing insurance data with external material, should also be deeper investigated.

Evaluation of ikonos satellite imagery for detecting ice storm damage to oak forests in Eastern Kentucky

Treesearch

W. Henry McNab; Tracy Roof

2006-01-01

Ice storms are a recurring landscape-scale disturbance in the eastern U.S. where they may cause varying levels of damage to upland hardwood forests. High-resolution Ikonos imagery and semiautomated detection of ice storm damage may be an alternative to manually interpreted aerial photography. We evaluated Ikonos multispectral, winter and summer imagery as a tool for...

UAV-based urban structural damage assessment using object-based image analysis and semantic reasoning

NASA Astrophysics Data System (ADS)

Fernandez Galarreta, J.; Kerle, N.; Gerke, M.

2015-06-01

Structural damage assessment is critical after disasters but remains a challenge. Many studies have explored the potential of remote sensing data, but limitations of vertical data persist. Oblique imagery has been identified as more useful, though the multi-angle imagery also adds a new dimension of complexity. This paper addresses damage assessment based on multi-perspective, overlapping, very high resolution oblique images obtained with unmanned aerial vehicles (UAVs). 3-D point-cloud assessment for the entire building is combined with detailed object-based image analysis (OBIA) of façades and roofs. This research focuses not on automatic damage assessment, but on creating a methodology that supports the often ambiguous classification of intermediate damage levels, aiming at producing comprehensive per-building damage scores. We identify completely damaged structures in the 3-D point cloud, and for all other cases provide the OBIA-based damage indicators to be used as auxiliary information by damage analysts. The results demonstrate the usability of the 3-D point-cloud data to identify major damage features. Also the UAV-derived and OBIA-processed oblique images are shown to be a suitable basis for the identification of detailed damage features on façades and roofs. Finally, we also demonstrate the possibility of aggregating the multi-perspective damage information at building level.

A Review: Some biological effects of high LET radiations

NASA Technical Reports Server (NTRS)

Wiley, A., Jr.

1972-01-01

There are qualitative and quantitative differences in the biological damage observed after exposure to high LET radiation as compared to that caused by low LET radiations. This review is concerned with these differences, which are ultimately reflected at the biochemical, cellular and even whole animal levels. In general, high LET radiations seem to produce biochemical damage which is more severe and possibly less repairable. Experimental data for those effects are presented in terms of biochemical RBE's with consideration of both early and late manifestations. An LET independent process by which significant biochemical damage may result from protons, neutrons and negative pion mesons is discussed.

A cost for high levels of sperm competition in rodents: increased sperm DNA fragmentation

PubMed Central

Roldan, Eduardo R. S.

2016-01-01

Sperm competition, a prevalent evolutionary process in which the spermatozoa of two or more males compete for the fertilization of the same ovum, leads to morphological and physiological adaptations, including increases in energetic metabolism that may serve to propel sperm faster but that may have negative effects on DNA integrity. Sperm DNA damage is associated with reduced rates of fertilization, embryo and fetal loss, offspring mortality, and mutations leading to genetic disease. We tested whether high levels of sperm competition affect sperm DNA integrity. We evaluated sperm DNA integrity in 18 species of rodents that differ in their levels of sperm competition using the sperm chromatin structure assay. DNA integrity was assessed upon sperm collection, in response to incubation under capacitating or non-capacitating conditions, and after exposure to physical and chemical stressors. Sperm DNA was very resistant to physical and chemical stressors, whereas incubation in non-capacitating and capacitating conditions resulted in only a small increase in sperm DNA damage. Importantly, levels of sperm competition were positively associated with sperm DNA fragmentation across rodent species. This is the first evidence showing that high levels of sperm competition lead to an important cost in the form of increased sperm DNA damage. PMID:26936246

Reduction of damage initiation density in fused silica optics via UV laser conditioning

DOEpatents

Peterson, John E.; Maricle, Stephen M.; Brusasco, Raymond M.; Penetrante, Bernardino M.

2004-03-16

The present invention provides a method for reducing the density of sites on the surface of fused silica optics that are prone to the initiation of laser-induced damage, resulting in optics which have far fewer catastrophic defects and are better capable of resisting optical deterioration upon exposure for a long period of time to a high-power laser beam having a wavelength of about 360 nm or less. The initiation of laser-induced damage is reduced by conditioning the optic at low fluences below levels that normally lead to catastrophic growth of damage. When the optic is then irradiated at its high fluence design limit, the concentration of catastrophic damage sites that form on the surface of the optic is greatly reduced.

Damage evaluation in graphene underlying atomic layer deposition dielectrics

PubMed Central

Tang, Xiaohui; Reckinger, Nicolas; Poncelet, Olivier; Louette, Pierre; Ureña, Ferran; Idrissi, Hosni; Turner, Stuart; Cabosart, Damien; Colomer, Jean-François; Raskin, Jean-Pierre; Hackens, Benoit; Francis, Laurent A.

2015-01-01

Based on micro-Raman spectroscopy (μRS) and X-ray photoelectron spectroscopy (XPS), we study the structural damage incurred in monolayer (1L) and few-layer (FL) graphene subjected to atomic-layer deposition of HfO2 and Al2O3 upon different oxygen plasma power levels. We evaluate the damage level and the influence of the HfO2 thickness on graphene. The results indicate that in the case of Al2O3/graphene, whether 1L or FL graphene is strongly damaged under our process conditions. For the case of HfO2/graphene, μRS analysis clearly shows that FL graphene is less disordered than 1L graphene. In addition, the damage levels in FL graphene decrease with the number of layers. Moreover, the FL graphene damage is inversely proportional to the thickness of HfO2 film. Particularly, the bottom layer of twisted bilayer (t-2L) has the salient features of 1L graphene. Therefore, FL graphene allows for controlling/limiting the degree of defect during the PE-ALD HfO2 of dielectrics and could be a good starting material for building field effect transistors, sensors, touch screens and solar cells. Besides, the formation of Hf-C bonds may favor growing high-quality and uniform-coverage dielectric. HfO2 could be a suitable high-K gate dielectric with a scaling capability down to sub-5-nm for graphene-based transistors. PMID:26311131

Correlation of Radiation Dosage With Mechanical Properties of Thin Films

NASA Technical Reports Server (NTRS)

Newton, R. L.

2003-01-01

The objective of this investigation was to examine the relationship between irradiation level (proton dose), microstructure, and stress levels in chemical vapor deposited diamond and polysilicon film using crosssectioned specimens. However, the emphasis was placed on the diamond specimen because diamond holds much promise for use in advanced technologies. The use of protons allows not only the study of the charged particle that may cause the most microstructural damage in Earth-orbit microelectromechanical systems (MEMS) devices, but also allows the study of relatively deeply buried damage inside the diamond material. Using protons allows these studies without having to resort to megaelectronvolt implant energies that may create extensive damage due to the high energy that is needed for the implantation process. Since 1 MEMS devices operating in space will not have an opportunity to reverse radiation damage via annealing, only nonannealed specimens were investigated. The following three high spatial resolution techniques were used to examine these relationships: (I) Scanning electron microscopy, (2) micro-Raman spectroscopy, and (3) micro x-ray diffraction.

Using Lymphocyte and Plasma Hsp70 as Biomarkers for Assessing Coke Oven Exposure among Steel Workers

PubMed Central

Yang, Xiaobo; Zheng, Jinping; Bai, Yun; Tian, Fengjie; Yuan, Jing; Sun, Jianya; Liang, Huashan; Guo, Liang; Tan, Hao; Chen, Weihong; Tanguay, Robert M.; Wu, Tangchun

2007-01-01

Background Hsp70, an early-response protein induced when organisms are confronted with simple or complicated environmental stresses, can act as either a cellular protector or a danger signal. Objectives The goal of this study was to evaluate levels of lymphocyte and/or plasma Hsp70 as biomarkers for assessing exposure response to complex coke oven emissions (COEs). Methods We recruited 101 coke oven workers and determined levels of polycyclic aromatic hydrocarbon (PAH) exposure, urinary 1-hydroxypyrene (1-OHP), genotoxic damage by comet assay and micronuclei test, and other markers of damage, including plasma malondialdehyde (MDA) and lactate dehydrogenase (LDH). These were compared to levels of lymphocyte (intra-cellular) and plasma (extracellular) Hsp70 using Western blots and enzyme-linked immunosorbent assays (ELISA), respectively. Results We observed a COEs-related dose-dependent increase in levels of DNA damage, micronuclei rate, MDA concentration, and LDH activity. Lymphocyte Hsp70 levels increased in the intermediate-exposure group (1.39 ± 0.88) but decreased in the high-exposure group (1.10 ± 0.55), compared with the low-exposure group. In contrast, plasma Hsp70 levels progressively increased as the dose of exposure increased. Negative correlations were seen between lymphocyte Hsp70 levels and olive tail moment and LDH activity in the intermediate- and high-exposure groups. However, we observed positive correlations between plasma Hsp70 levels and LDH activity in the low and intermediate groups. Conclusions In workers exposed to COEs, high lymphocyte Hsp70 levels may provide protection and high plasma Hsp70 levels may serve as a danger marker. Larger validation studies are needed to establish the utility of Hsp70 as a response marker. PMID:18007987

DNA damage in lens epithelium of cataract patients in vivo and ex vivo.

PubMed

Øsnes-Ringen, Oyvind; Azqueta, Amaia O; Moe, Morten C; Zetterström, Charlotta; Røger, Magnus; Nicolaissen, Bjørn; Collins, Andrew R

2013-11-01

DNA damage has been described in the human cataractous lens epithelium, and oxidative stress generated by UV radiation and endogenous metabolic processes has been suggested to play a significant role in the pathogenesis of cataract. In this study, the aim was to explore the quality and relative quantity of DNA damage in lens epithelium of cataract patients in vivo and after incubation in a cell culture system. Capsulotomy specimens were analysed, before and after 1 week of ex vivo cultivation, using the comet assay to measure DNA strand breaks, oxidized purine and pyrimidine bases and UV-induced cyclobutane pyrimidine dimers. DNA strand breaks were barely detectable, oxidized pyrimidines and pyrimidine dimers were present at low levels, whereas there was a relatively high level of oxidized purines, which further increased after cultivation. The observed levels of oxidized purines in cataractous lens epithelium may support a theory consistent with light damage and oxidative stress as mediators of molecular damage to the human lens epithelium. Damage commonly associated with UV-B irradiation was relatively low. The levels of oxidized purines increased further in a commonly used culture system. This is of interest considering the importance and versatility of ex vivo systems in studies exploring the pathogenesis of cataract. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

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.

Circulating AIM as an Indicator of Liver Damage and Hepatocellular Carcinoma in Humans

PubMed Central

Yamazaki, Tomoko; Mori, Mayumi; Arai, Satoko; Tateishi, Ryosuke; Abe, Masanori; Ban, Mihoko; Nishijima, Akemi; Maeda, Maki; Asano, Takeharu; Kai, Toshihiro; Izumino, Kiyohiro; Takahashi, Jun; Aoyama, Kayo; Harada, Sei; Takebayashi, Toru; Gunji, Toshiaki; Ohnishi, Shin; Seto, Shinji; Yoshida, Yukio; Hiasa, Yoichi; Koike, Kazuhiko; Yamamura, Ken-ichi; Inoue, Ken-ichiro; Miyazaki, Toru

2014-01-01

Background Hepatocellular carcinoma (HCC), the fifth most common cancer type and the third highest cause of cancer death worldwide, develops in different types of liver injuries, and is mostly associated with cirrhosis. However, non-alcoholic fatty liver disease often causes HCC with less fibrosis, and the number of patients with this disease is rapidly increasing. The high mortality rate and the pathological complexity of liver diseases and HCC require blood biomarkers that accurately reflect the state of liver damage and presence of HCC. Methods and Findings Here we demonstrate that a circulating protein, apoptosis inhibitor of macrophage (AIM) may meet this requirement. A large-scale analysis of healthy individuals across a wide age range revealed a mean blood AIM of 4.99±1.8 µg/ml in men and 6.06±2.1 µg/ml in women. AIM levels were significantly augmented in the younger generation (20s–40s), particularly in women. Interestingly, AIM levels were markedly higher in patients with advanced liver damage, regardless of disease type, and correlated significantly with multiple parameters representing liver function. In mice, AIM levels increased in response to carbon tetrachloride, confirming that the high AIM observed in humans is the result of liver damage. In addition, carbon tetrachloride caused comparable states of liver damage in AIM-deficient and wild-type mice, indicating no influence of AIM levels on liver injury progression. Intriguingly, certain combinations of AIM indexes normalized to liver marker score significantly distinguished HCC patients from non-HCC patients and thus could be applicable for HCC diagnosis. Conclusion AIM potently reveals both liver damage and HCC. Thus, our results may provide the basis for novel diagnostic strategies for this widespread and fatal disease. PMID:25302503

[Factors associated with the psychological impact of the Great East Japan earthquake on high school students 1 year and 4 months after the disaster].

PubMed

Funakoshi, Shunichi; Ohno, Takashi; Kodaka, Akira; Okuyama, Junko; Honda, Nami; Inoue, Takao; Sato, Yuki; Miyajima, Maki; Tomita, Hiroaki; Denda, Kenzou; Matsuoka, Hiroo

2014-01-01

The purpose of this study was to investigate factors associated with the psychological impact of the Great East Japan Earthquake on high school students 1 year and 4 months after the disaster, and clarify support needs of the students. In the outreach program for students of three high schools in coastal areas of southern Miyagi Prefecture, Japan, 1,973 students were surveyed after obtaining informed consent for participation. Questionnaires included: the Quick Inventory of Depressive Symptomatology (QIDS-J), Self-rating Anxiety Scale (SAS), Impact of Event Scale-revised (IES-R), and Connor-Davidson Resilience Scale (CD-RISC10). All scores were compared using SPSS 20.0 J between school grades, locations of the schools, and extent of damage due to the Great East Japan Earthquake. Our analysis showed a significant positive correlation between school grades and the level of anxiety. PTSR scores, but not anxiety nor depressive scores, of students whose lives have suffered extensive damage were significantly higher than those of students who have not. Students of high schools which have suffered extensive damage and use temporary buildings showed significantly higher levels of depression and anxiety, and significantly lower resilience, compared to students of high schools which were not damaged. Although previous findings demonstrated that younger children have a higher risk of being influenced by disasters, symptoms related to PTSR and depression were found frequently in the high school students as well. Among the high school students, our analysis showed a positive correlation between the level of anxiety and school grades, probably because the disaster has affected an influential and pivotal point in their lives.

DNA damage and glutathione level in children with asthma bronchiale: effect of antiasthmatic therapy.

PubMed

Hasbal, Canan; Aksu, Bagdagul Y; Himmetoglu, Solen; Dincer, Yildiz; Koc, Eylem E; Hatipoglu, Sami; Akcay, Tulay

2010-06-01

When the production of reactive oxygen species (ROS) exceeds the capacity of antioxidant defences, a condition known as oxidative stress occurs and it has been implicated in many pathological conditions including asthma. Interaction of ROS with DNA may result in mutagenic oxidative base modifications such as 8-hydroxydeoxyguanosine (8-oxo-dGuo) and DNA strand breaks. Reduced glutathione (GSH) serves as a powerful antioxidant against harmful effects of ROS. The aim of this study was to describe DNA damage as level of DNA strand breaks and formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites, which reflects oxidative DNA damage and GSH level in children with mild-to-moderate persistent asthma; and to examine the effect of antiasthmatic therapy on these DNA damage parameters and GSH level. Before and after 8 wk of antiasthmatic therapy blood samples were taken, DNA strand breaks and Fpg-sensitive sites in peripheral leukocytes were determined by comet assay, GSH level of whole blood was measured by spectrophotometric method. DNA strand breaks and Fpg-sensitive sites in the asthma group were found to be increased as compared with control group. GSH level in the asthma group was not significantly different from those in the control group. Levels of strand breaks, Fpg-sensitive sites and GSH were found to be decreased in the asthma group after the treatment. In conclusion, oxidative DNA damage (strand breaks and Fpg-sensitive sites) is at a high level in children with asthma. DNA damage parameters and GSH level were found to be decreased after therapy. Our findings imply that antiasthmatic therapy including glucocorticosteroids not only controls asthma but also decreases mutation risk in children with asthma bronchiale.

Counter Electrical Generation and Distribution: An Assessment for Global Strike in 2035

DTIC Science & Technology

2012-02-15

magnetic field . Satellites in low earth orbit (LEO) or high earth orbit (HEO) orbits would be disabled from effects of the ionizing electrons on...of delivery.34 High power microwaves may also offer an ability to “dial down” the electro- magnetic fields being used to fine tune the effects on the...target system and reduce collateral damage. At high levels of electro- magnetic fields , permanent and catastrophic damage to circuitry, power lines

High-quality care improves outcome in recumbent dairy cattle.

PubMed

Poulton, P J; Vizard, A L; Anderson, G A; Pyman, M F

2016-06-01

To investigate the influence of the quality of care on outcome and occurrence of secondary damage in recumbent dairy cows. Recumbent dairy cows were monitored during their recumbency under field conditions in South Gippsland, Victoria, Australia. The cause of the original recumbency of 218 downer cows was determined and any secondary damage, day 7 status, final outcome and the nursing conditions of the cows were recorded. A four-tiered grading system describing nursing quality was developed to allow analysis of its influence on outcome and on the occurrence of secondary damage. Day 7 outcome, final outcome and occurrence of important secondary damage were very strongly associated with the level of overall care provided to the recumbent cows. There was a decrease in the percentage of cows recovering by day 7 from 33% to 0%, a decrease from 45% to 0% of cows eventually recovering and an increase from 68% to 100% of cows with clinically important secondary damage as overall care decreased. Management of recumbent cattle is potentially a significant animal welfare issue for the dairy industry and their care is a very important but often under-appreciated aspect of their management. Recovery is positively influenced by high-quality care by improving the chances of recovery from the initial cause of recumbency and by reducing the occurrence of secondary damage. Recumbent cows must either be nursed at a high level of care or euthanased promptly. © 2016 Australian Veterinary Association.

Dampness and Moisture Problems in Norwegian Homes

PubMed Central

Becher, Rune; Høie, Anja Hortemo; Bakke, Jan Vilhelm; Holøs, Sverre Bjørn; Øvrevik, Johan

2017-01-01

The occurrence of dampness and mold in the indoor environment is associated with respiratory-related disease outcomes. Thus, it is pertinent to know the magnitude of such indoor environment problems to be able to estimate the potential health impact in the population. In the present study, the moisture damage in 10,112 Norwegian dwellings was recorded based on building inspection reports. The levels of moisture damage were graded based on a condition class (CC), where CC0 is immaculate and CC1 acceptable (actions not required), while CC2 and CC3 indicate increased levels of damage that requires action. Of the 10,112 dwellings investigated, 3125 had verified moisture or mold damage. This amounts to 31% of the surveyed dwellings. Of these, 27% had CC2 as the worst grade, whereas 4% had CC3 as the worst grade level. The room types and building structures most prone to moisture damage were (in rank order) crawl spaces, basements, un-insulated attics, cooling rooms, and bathrooms. The high proportion of homes with moisture damage indicate a possible risk for respiratory diseases in a relatively large number of individuals, even if only the more extensive moisture damages and those located in rooms where occupants spend the majority of their time would have a significant influence on adverse health effects. PMID:29039816

Accumulation of senescent cells in mitotic tissue of aging primates.

PubMed

Jeyapalan, Jessie C; Ferreira, Mark; Sedivy, John M; Herbig, Utz

2007-01-01

Cellular senescence, a stress induced growth arrest of somatic cells, was first documented in cell cultures over 40 years ago, however its physiological significance has only recently been demonstrated. Using novel biomarkers of cellular senescence we examined whether senescent cells accumulate in tissues from baboons of ages encompassing the entire lifespan of this species. We show that dermal fibroblasts, displaying markers of senescence such as telomere damage, active checkpoint kinase ATM, high levels of heterochromatin proteins and elevated levels of p16, accumulate in skin biopsies from baboons with advancing age. The number of dermal fibroblasts containing damaged telomeres reaches a value of over 15% of total fibroblasts, whereas 80% of cells contain high levels of the heterochromatin protein HIRA. In skeletal muscle, a postmitotic tissue, only a small percentage of myonuclei containing damaged telomeres were detected regardless of animal age. The presence of senescent cells in mitotic tissues might therefore be a contributing factor to aging and age related pathology and provides further evidence that cellular senescence is a physiological event.

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.

A Maxwell elasto-brittle rheology for sea ice modelling

NASA Astrophysics Data System (ADS)

Dansereau, Véronique; Weiss, Jérôme; Saramito, Pierre; Lattes, Philippe

2016-07-01

A new rheological model is developed that builds on an elasto-brittle (EB) framework used for sea ice and rock mechanics, with the intent of representing both the small elastic deformations associated with fracturing processes and the larger deformations occurring along the faults/leads once the material is highly damaged and fragmented. A viscous-like relaxation term is added to the linear-elastic constitutive law together with an effective viscosity that evolves according to the local level of damage of the material, like its elastic modulus. The coupling between the level of damage and both mechanical parameters is such that within an undamaged ice cover the viscosity is infinitely large and deformations are strictly elastic, while along highly damaged zones the elastic modulus vanishes and most of the stress is dissipated through permanent deformations. A healing mechanism is also introduced, counterbalancing the effects of damaging over large timescales. In this new model, named Maxwell-EB after the Maxwell rheology, the irreversible and reversible deformations are solved for simultaneously; hence drift velocities are defined naturally. First idealized simulations without advection show that the model reproduces the main characteristics of sea ice mechanics and deformation: strain localization, anisotropy, intermittency and associated scaling laws.

ELEVATED LEVELS OF INDUCIBLE HEAT SHOCK PROTEIN (HSP70-1) PROTECT MCF-7 CELLS FROM ARSENITE TOXICITY

EPA Science Inventory

Heat shock proteins (HSPs) belong to the highly conserved family of stress proteins and are induced following exposure to arsenic. Elevated HSPs protect against cellular damage from heat but it is unclear whether HSP induction alters the damaging effects of environmental chemical...

Cumulative fatigue damage behavior of MAR M-247

NASA Technical Reports Server (NTRS)

Mcgaw, Michael A.; Halford, Gary R.; Kalluri, Sreeramesh

1991-01-01

The objective was to examine the room temperature fatigue and nonlinear cumulative fatigue damage behavior of the cast nickel-based superalloy, MAR M-247. The fatigue test matrix consisted of single-level, fully reversed fatigue experiments. Two series of tests were performed: one of the two baseline fatigue LCF (Low-Cycle Fatigue) life levels was used in the first loading block, and the HCF (High-Cycle Fatigue) baseline loading level was used in the second block in each series. For each series, duplicate tests were performed at each applied LCF life fraction.

Evidence of direct cardiac damage following high-intensity exercise in chronic energy restriction: A case report and literature review.

PubMed

Baird, Marianne F; Grace, Fergal; Sculthorpe, Nicholas; Graham, Scott M; Fleming, Audrey; Baker, Julien S

2017-07-01

Following prolonged endurance events such as marathons, elevated levels of cardiospecific biomarkers are commonly reported. Although transiently raised levels are generally not considered to indicate clinical myocardial damage, comprehension of this phenomenon remains incomplete. The popularity of high-intensity interval training highlights a paucity of research measuring cardiac biomarker response to this type of exercise. This a posteriori case report discusses the elevation of cardiac troponins (cTn) associated with short interval, high-intensity exercise. In this case report, an apparently healthy 29-year-old recreationally active female presented clinically raised cardiac troponin I (cTnI) levels (>0.04 ng/mL), after performing high-intensity cycle ergometer sprints. As creatine kinase (CK) is expressed by multiple organs (e.g., skeletal muscle, brain, and myocardium), cTnI assays were performed to determine any changes in total serum CK levels not originating from skeletal muscle damage. A posteriori the individual's daily energy expenditure indicated chronically low-energy availability. Psychometric testing suggested that the individual scored positive for disordered eating, highly for fatigue levels, and low in mental health components. The current case report provides novel evidence of elevated cTnI occurring as a result of performing short duration, high intensity, cycle ergometer exercise in an individual with self-reported chronically depleted energy balance. A schematic to identify potentially "at risk" individuals is presented. Considering this as a case report, results cannot be generalized; however, the main findings suggest that individuals who habitually restrict their calorie intake below their bodies' daily energy requirements, may have elevated biomarkers of exercise induced myocardial stress from performing high-intensity exercise.

Effects of flight activity and age on oxidative damage in the honey bee, Apis mellifera.

PubMed

Margotta, Joseph W; Roberts, Stephen P; Elekonich, Michelle M

2018-05-03

Frequent and highly aerobic behaviors likely contribute to naturally occurring stress, accelerate senescence, and limit lifespan. To understand how the physiological and cellular mechanisms that determine the onset and duration of senescence are shaped by behavioral development and behavioral duration, we exploited the tractability of the honey bee ( Apis mellifera ) model system. First, we determined if a cause-effect relationship exists between honey bee flight and oxidative stress by comparing oxidative damage accrued from intense flight bouts to damage accrued from D-galactose ingestion, which induces oxidative stress and limit lifespan in other insects. Second, we experimentally manipulated the duration of honey bee flight across a range of ages to determine their effects on reactive oxygen species (ROS) accumulation and associated enzymatic antioxidant protective mechanisms. In bees fed D-galactose, lipid peroxidation (MDA) was higher than in bees fed sucrose and age-matched bees with high and low flight experience collected from a colony. Bees with high amounts of flight experience exhibited elevated 8-OHdG, a marker of oxidative DNA damage, relative to bees with less flight experience. Bees with high amounts of flight experience also showed increased levels of pro-oxidants (superoxide and H 2 O 2 ) and decreased or unchanged levels of antioxidants (SOD and catalase). These data implicate an imbalance of pro- to antioxidants in flight-associated oxidative stress and reveal how behavior can damage a cell and consequently limit lifespan. © 2018. Published by The Company of Biologists Ltd.

C/EBPα regulates CRL4Cdt2-mediated degradation of p21 in response to UVB-induced DNA damage to control the G1/S checkpoint

PubMed Central

Hall, Jonathan R; Bereman, Michael S; Nepomuceno, Angelito I; Thompson, Elizabeth A; Muddiman, David C; Smart, Robert C

2014-01-01

The bZIP transcription factor, C/EBPα is highly inducible by UVB and other DNA damaging agents in keratinocytes. C/EBPα-deficient keratinocytes fail to undergo cell cycle arrest in G1 in response to UVB-induced DNA damage and mice lacking epidermal C/EBPα are highly susceptible to UVB-induced skin cancer. The mechanism through which C/EBPα regulates the cell cycle checkpoint in response to DNA damage is unknown. Here we report untreated C/EBPα-deficient keratinocytes have normal levels of the cyclin-dependent kinase inhibitor, p21, however, UVB-treated C/EBPα-deficient keratinocytes fail to up-regulate nuclear p21 protein levels despite normal up-regulation of Cdkn1a mRNA levels. UVB-treated C/EBPα-deficient keratinocytes displayed a 4-fold decrease in nuclear p21 protein half-life due to the increased proteasomal degradation of p21 via the E3 ubiquitin ligase CRL4Cdt2. Cdt2 is the substrate recognition subunit of CRL4Cdt2 and Cdt2 mRNA and protein levels were up-regulated in UVB-treated C/EBPα-deficient keratinocytes. Knockdown of Cdt2 restored p21 protein levels in UVB-treated C/EBPα-deficient keratinocytes. Lastly, the failure to accumulate p21 in response to UVB in C/EBPα-deficient keratinocytes resulted in decreased p21 interactions with critical cell cycle regulatory proteins, increased CDK2 activity, and inappropriate entry into S-phase. These findings reveal C/EBPα regulates G1/S cell cycle arrest in response to DNA damage via the control of CRL4Cdt2 mediated degradation of p21. PMID:25483090

Smoking modify the effects of polycyclic aromatic hydrocarbons exposure on oxidative damage to DNA in coke oven workers.

PubMed

Yang, Jin; Zhang, Hongjie; Zhang, Huitao; Wang, Wubin; Liu, Yanli; Fan, Yanfeng

2017-07-01

Coke oven emissions containing polycyclic aromatic hydrocarbons (PAHs) are predominant toxic constituents of particulate air pollution that have been linked to increased risk of lung cancer. Numerous epidemiological studies have suggested that oxidative DNA damage may play a pivotal role in the carcinogenic mechanism of lung cancer. Little is known about the effect of interaction between PAHs exposure and lifestyle on DNA oxidative damage. The study population is composed by coke oven workers (365) and water treatment workers (144), and their urinary levels of four PAH metabolites and 8-hydroxydeoxyguanosine (8-OHdG) were determined. Airborne samples of exposed sites (4) and control sites (3) were collected, and eight carcinogenic PAHs were detected by high-performance liquid chromatography. The median values of the sum of eight carcinogenic PAHs and BaP in exposed sites were significantly higher than control sites (P < 0.01). The study found that the urinary PAH metabolites were significantly elevated in coke oven workers (P < 0.01). Multivariate logistic regression analysis revealed that the risk of high levels of urinary 8-OHdG will increase with increasing age, cigarette consumption, and levels of urinary 1-hydroxypyrene, and P for trend were all <0.05. Smoking can significantly modify the effects of urinary 1-hydroxypyrene on high concentrations urinary 8-OHdG, during co-exposure to both light or heavy smoking and high 1-hydroxypyrene levels (OR 4.28, 95% CI 1.32-13.86 and OR 5.05, 95% CI 1.63-15.67, respectively). Our findings quantitatively demonstrate that workers exposed to coke oven fumes and smoking will cause more serious DNA oxidative damage.

Leisure noise exposure: participation trends, symptoms of hearing damage, and perception of risk.

PubMed

Beach, Elizabeth Francis; Gilliver, Megan; Williams, Warwick

2013-02-01

Leisure activities that emit high noise levels have the potential to expose participants to excessive noise exposure, which can result in hearing damage. This study investigated young people's participation in high-noise leisure activities and the relationship between their leisure noise exposure, symptoms of hearing damage, and perception of risk. Participants completed an online survey relating to participation in selected high-noise leisure activities, symptoms of hearing damage, and beliefs about the risk posed by these activities. One thousand 18- to 35-year-old Australian adults completed the survey. Annual noise exposure from the five leisure activities ranged from 0-6.77 times the acceptable noise exposure, with nightclubs posing the greatest risk. Those who attended one noisy activity were more likely to attend others, in particular nightclubs, pubs, and live music events. Noise exposure was correlated with early warning signs of hearing damage and perceived risk of damage. Active young adults who engage in noisy activities are showing early signs of hearing damage. Furthermore, they perceive the risk associated with their activities. The challenge for researchers and hearing health practitioners is to convert self-perceived risk into positive hearing health behaviours for long-term hearing health.

High-Intensity Exercise Induced Oxidative Stress and Skeletal Muscle Damage in Postpubertal Boys and Girls: A Comparative Study.

PubMed

Pal, Sangita; Chaki, Biswajit; Chattopadhyay, Sreya; Bandyopadhyay, Amit

2018-04-01

Pal, S, Chaki, B, Chattopadhyay, S, and Bandyopadhyay, A. High-intensity exercise induced oxidative stress and skeletal muscle damage in post-pubertal boys and girls: a comparative study. J Strength Cond Res 32(4): 1045-1052, 2018-The purpose of this study was to examine the sex variation in high-intensity exercise induced oxidative stress and muscle damage among 44 sedentary postpubertal boys and girls through estimation of postexercise release pattern of muscle damage markers like creatine kinase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and oxidative stress markers like extent of lipid peroxidation (thiobarbituric acid-reactive substances) and catalase activity. Muscle damage markers like creatine kinase, LDH, ALT, and AST were measured before, immediately after, and 24 and 48 hours after high-intensity incremental treadmill running. Oxidative stress markers like thiobarbituric acid-reactive substances and catalase activity were estimated before and immediately after the exercise. Lipid peroxidation and serum catalase activity increased significantly in both groups after exercise (p < 0.001) with postexercise values and percentage increase significantly higher in postpubertal boys as compared to girls (p < 0.001). Creatine kinase and LDH activity also increased significantly above pre-exercise level at 24 and 48 hours after exercise in both the sexes, (p < 0.001) with values significantly higher for boys than the girls (p < 0.001). Although ALT and AST increased significantly in both the groups after exercise, the pattern of postexercise release of these markers were found to be similar in both the groups. Accordingly, it has been concluded from the present investigation that high-intensity exercise induces significant oxidative stress and increases indices of skeletal muscle damage in both postpubertal girls and boys. However, postpubertal girls are relatively better protected from oxidative stress and muscle damage as compared to the boys of similar age and physical activity level. It is further evident that sex difference may not be apparent for all the biomarkers of muscle damage in this age group.

Combined assessment of myocardial damage and electrical disturbance in chronic heart failure

PubMed Central

Kadowaki, Shinpei; Watanabe, Tetsu; Otaki, Yoichiro; Narumi, Taro; Honda, Yuki; Takahashi, Hiroki; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Kubota, Isao

2017-01-01

AIM To investigate feasibility of combined assessment of biochemical and electrophysiological myocardial impairment markers risk-stratifying patients with chronic heart failure (CHF). METHODS Serum levels of heart-type fatty acid binding protein (H-FABP) as a marker of ongoing myocardial damage and QRS duration on electrocardiogram were measured at admission in 322 consecutive patients with CHF. A prolonged QRS duration was defined as 120 ms or longer. The cut-off value for H-FABP level (4.5 ng/mL) was determined from a previous study. Patients were prospectively followed during a median follow up period of 534 d. The primary endpoint was cardiac deaths and rehospitalization for worsening CHF. RESULTS There were 117 primary events, including 27 cardiac deaths and 90 rehospitalizations. Patients were stratified into four groups according to H-FABP level and QRS duration (≥ 120 ms). Multivariate analysis demonstrated that high H-FABP levels [hazard ratio (HR) = 1.745, P = 0.021] and QRS prolongation (HR 1.612, P = 0.0258) were independent predictors of cardiac events. Kaplan-Meier analysis demonstrated that the combination of high H-FABP levels and QRS prolongation could be used to reliably stratify patients at high risk for cardiac events (log rank test P < 0.0001). CONCLUSION Combined assessment of myocardial damage and electrical disturbance can be used to risk-stratify patients with CHF. PMID:28603594

Using damage data to estimate the risk from summer convective precipitation extremes

NASA Astrophysics Data System (ADS)

Schroeer, Katharina; Tye, Mari

2017-04-01

This study explores the potential added value from including loss and damage data to understand the risks from high-intensity short-duration convective precipitation events. Projected increases in these events are expected even in regions that are likely to become more arid. Such high intensity precipitation events can trigger hazardous flash floods, debris flows, and landslides that put people and local assets at risk. However, the assessment of local scale precipitation extremes is hampered by its high spatial and temporal variability. In addition to this, not only are extreme events rare, but such small-scale events are likely to be underreported where they do not coincide with the observation network. Reports of private loss and damage on a local administrative unit scale (LAU 2 level) are used to explore the relationship between observed rainfall events and damages reportedly related to hydro-meteorological processes. With 480 Austrian municipalities located within our south-eastern Alpine study region, the damage data are available on a much smaller scale than the available rainfall data. Precipitation is recorded daily at 185 gauges and 52% of these stations additionally deliver sub-hourly rainfall information. To obtain physically plausible information, damage and rainfall data are grouped and analyzed on a catchment scale. The data indicate that rainfall intensities are higher on days that coincide with a damage claim than on days for which no damage was reported. However, approximately one third of the damages related to hydro-meteorological hazards were claimed on days for which no rainfall was recorded at any gauge in the respective catchment. Our goal is to assess whether these events indicate potential extreme events missing in the observations. Damage always is a consequence of an asset being exposed and susceptible to a hazardous process, and naturally, many factors influence whether an extreme rainfall event causes damage. We set up a statistical model to test whether the relationship between extreme rainfall events and damages is robust enough to estimate a potential underrepresentation of high intensity rainfall events in ungauged areas. Risk-relevant factors of socio-economic vulnerability, land cover, streamflow data, and weather type information are included to improve and sharpen the analysis. Within this study, we first aim to identify which rainfall events are most damaging and which factors affect the damages - seen as a proxy for the vulnerability - related to summer convective rainfall extremes in different catchment types. Secondly, we aim to detect potentially unreported damaging rainfall events and estimate the likelihood of such cases. We anticipate this damage perspective on summertime extreme convective precipitation to be beneficial for risk assessment, uncertainty management, and decision making with respect to weather and climate extremes on the regional-to-local level.

Continuous real-time in vivo measurement of cerebral nitric oxide supports theoretical predictions of an irreversible switching in cerebral ROS after sufficient exposure to external toxins.

PubMed

Finnerty, Niall J; O'Riordan, Saidhbhe L; Lowry, John P; Cloutier, Mathieu; Wellstead, Peter

2013-01-01

Mathematical models of the interactions between alphasynuclein (αS) and reactive oxygen species (ROS) predict a systematic and irreversible switching to damagingly high levels of ROS after sufficient exposure to risk factors associated with Parkinson's disease (PD). We tested this prediction by continuously monitoring real-time changes in neurochemical levels over periods of several days in animals exposed to a toxin known to cause Parkinsonian symptoms. Nitric oxide (NO) sensors were implanted in the brains of freely moving rats and the NO levels continuously recorded while the animals were exposed to paraquat (PQ) injections of various amounts and frequencies. Long-term, real-time measurement of NO in a cohort of animals showed systematic switching in levels when PQ injections of sufficient size and frequency were administered. The experimental observations of changes in NO imply a corresponding switching in endogenous ROS levels and support theoretical predictions of an irreversible change to damagingly high levels of endogenous ROS when PD risks are sufficiently large. Our current results only consider one form of PD risk, however, we are sufficiently confident in them to conclude that: (i) continuous long-term measurement of neurochemical dynamics provide a novel way to measure the temporal change and system dynamics which determine Parkinsonian damage, and (ii) the bistable feedback switching predicted by mathematical modelling seems to exist and that a deeper analysis of its characteristics would provide a way of understanding the pathogenic mechanisms that initiate Parkinsonian cell damage.

High-Resolution Characterizations of Grain Boundary Damage and Stress Corrosion Cracks in Cold-Rolled Alloy 690

NASA Astrophysics Data System (ADS)

Bruemmer, S. M.; Olszta, M. J.; Toloczko, M. B.; Thomas, L. E.

Unidirectional cold rolling has been shown to promote intergranular stress corrosion cracking (IGSCC) in alloy 690 tested in PWR primary water. High-resolution scanning (SEM) and transmission electron microscopy (TEM) have been employed to investigate the microstructural reasons for this enhanced susceptibility in two stages, first examining grain boundary damage produced by cold rolling and second by characterization of stress corrosion crack tips. The degree of permanent grain boundary damage from cold rolling was found to depend directly on the initial IG precipitate distribution. Cold rolling to high levels of reduction was discovered to produce small IG voids and cracked carbides in alloys with a high density of grain boundary carbides. For the same degree of cold rolling, alloys with few IG carbides exhibited much less permanent damage. Although this difference in grain boundary damage appears to correlate with measured SCC growth rates, crack tip examinations reveal no interaction between the preexisting voids and cracked carbides with the propagation. In many cases, these features appeared to blunt propagation of IGSCC cracks. High-resolution characterizations are described for cold-rolled alloy 690 CRDM tubing and plate materials to gain insights into IGSCC mechanisms.

Irradiation response of commercial, high-Tc superconducting tapes: Electromagnetic transport properties

DOE PAGES

Gapud, A. A.; Greenwood, N. T.; Alexander, J. A.; ...

2015-07-01

Effects of low dose irradiation on the electrical transport current properties of commercially available high-temperature superconducting, coated-conductor tapes were investigated, in view of potential applications in the irradiative environment of fusion reactors. Three different tapes, each with unique as-grown flux-pinning structures, were irradiated with Au and Ni ions at energies that provide a range of damage effects, with accumulated damage levels near that expected for conductors in a fusion reactor environment. Measurements using transport current determined the pre- and post-irradiation resistivity, critical current density, and pinning force density, yielding critical temperatures, irreversibility lines, and inferred vortex creep rates. Results showmore » that at the irradiation damage levels tested, any detriment to as-grown pre-irradiation properties is modest; indeed in one case already-superior pinning forces are enhanced, leading to higher critical currents.« less

Oxidative stress and DNA damage induced by imidacloprid in zebrafish (Danio rerio).

PubMed

Ge, Weili; Yan, Saihong; Wang, Jinhua; Zhu, Lusheng; Chen, Aimei; Wang, Jun

2015-02-18

Imidacloprid is a neonicotinoid insecticide that can have negative effects on nontarget animals. The present study was conducted to assess the toxicity of various imidacloprid doses (0.3, 1.25, and 5 mg/mL) on zebrafish sampled after 7, 14, 21, and 28 days of exposure. The levels of catalase (CAT), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione-S-transferase (GST), and malondialdehyde (MDA) and the extent of DNA damage were measured to evaluate the toxicity of imidacloprid on zebrafish. SOD and GST activities were noticeably increased during early exposure but were inhibited toward the end of the exposure period. In addition, the CAT levels decreased to the control level following their elevation during early exposure. High concentrations of imidacloprid (1.25 and 5 mg/L) induced excessive ROS production and markedly increased MDA content on the 21st day of exposure. DNA damage was dose- and time-dependent. In conclusion, the present study showed that imidacloprid can induce oxidative stress and DNA damage in zebrafish.

Analysis of the 2011 Mekong flood in Can Tho city

NASA Astrophysics Data System (ADS)

Do, Thi-Chinh; Bubeck, Philip; Nguyen, Viet-Dung; Kreibich, Heidi

2014-05-01

Floods in the Mekong delta occur on a recurring basis during the flood season from July to November, and regular inundations of large areas are a prerequisite for the livelihoods of about 17 million people in the Vietnamese delta. At the same time, large-scale flood events above usual water levels pose a serious hazard that repeatedly caused severe economic damage and losses of life in past decades. The flood event in 2011 in the Mekong Delta heavily impacted Can Tho City and caused substantial damage to various economic sectors. Data from face to face interviews with 480 flood-affected households and 378 small businesses were analysed to gain detailed insights into flood preparedness, early warning, emergency measures, flood impacts and recovery before, during and after the 2011 flood in Can Tho city. Amongst other things, the findings reveal that damage to households is high, often exceeding the amount of several months of income, despite a relatively high level of preparedness. In terms of small businesses, it is found that higher losses indeed occur due to the disruption of production processes compared with direct damage.

Parametric study of irradiation effects on the ductile damage and flow stress behavior in ferritic-martensitic steels

NASA Astrophysics Data System (ADS)

Chakraborty, Pritam; Biner, S. Bulent

2015-10-01

Ferritic-martensitic steels are currently being considered as structural materials in fusion and Gen-IV nuclear reactors. These materials are expected to experience high dose radiation, which can increase their ductile to brittle transition temperature and susceptibility to failure during operation. Hence, to estimate the safe operational life of the reactors, precise evaluation of the ductile to brittle transition temperatures of ferritic-martensitic steels is necessary. Owing to the scarcity of irradiated samples, particularly at high dose levels, micro-mechanistic models are being employed to predict the shifts in the ductile to brittle transition temperatures. These models consider the ductile damage evolution, in the form of nucleation, growth and coalescence of voids; and the brittle fracture, in the form of probabilistic cleavage initiation, to estimate the influence of irradiation on the ductile to brittle transition temperature. However, the assessment of irradiation dependent material parameters is challenging and influences the accuracy of these models. In the present study, the effects of irradiation on the overall flow stress and ductile damage behavior of two ferritic-martensitic steels is parametrically investigated. The results indicate that the ductile damage model parameters are mostly insensitive to irradiation levels at higher dose levels though the resulting flow stress behavior varies significantly.

DNA damage in children with scoliosis following X-ray exposure.

PubMed

Himmetoglu, S; Guven, M F; Bilsel, N; Dincer, Y

2014-10-14

It has been suggested that cancer incidence is high in subjects with scoliosis who are relatively more often exposed to X--ray for diagnosis and follow--up. X--ray is a kind of ionizing radiation and leads to formation of oxygen free radicals which are capable of damage to DNA, thus altered gen expression and mutation. p53 tumor suppressor gene plays a crucial role in the damage response. It controls the checkpoint of cell cycle and redirects the cell metabolism to either repair of damaged DNA or apoptosis as response to DNA damage. The aim of the present study was to examine serum levels of 8--Hydroxydeoxyguanosine (8--OHdG), a strongly mutagenic product of oxidative DNA damage, p53, superoxide dismutase (SOD) and glutathione peroxidase (G--Px), as antioxidant activity, in children with scoliosis who had got whole spine radiograph two times during the last year. A total of 31 children with adolescent idiopathic scoliosis and age--matched 21 healthy children were included in the study. Serum levels of 8--OHdG and p53 were measured with ELISA kits. SOD and G--Px activities were determined with spectrophotometric assays. Serum levels of 8--OHdG and p53 were found to be higher (P<0.001 and P<0.01, respectively), SOD activity was found to be lower (P<0.001) in the children with scoliosis as compared to age--matched controls. There was no significant difference between the groups for G--Px activity. Our data show that X--ray exposure causes increased 8--OHdG level, and decreased SOD activity, which both may reflect a tumor promoting condition. Increased p53 level may be interpreted as a compensatory effort of cell to X--ray mediated DNA damage.

DNA damage in children with scoliosis following X-ray exposure.

PubMed

Himmetoglu, S; Guven, M F; Bilsel, N; Dincer, Y

2015-06-01

It has been suggested that cancer incidence is high in subjects with scoliosis who are relatively more often exposed to X-ray for diagnosis and follow-up. X-ray is a kind of ionizing radiation and leads to formation of oxygen free radicals which are capable of damage to DNA, thus altered gen expression and mutation. p53 tumor suppressor gene plays a crucial role in the damage response. It controls the checkpoint of cell cycle and redirects the cell metabolism to either repair of damaged DNA or apoptosis as response to DNA damage. The aim of the present study was to examine serum levels of 8-Hydroxydeoxyguanosine (8-OHdG), a strongly mutagenic product of oxidative DNA damage, p53, superoxide dismutase (SOD) and glutathione peroxidase (G-Px), as antioxidant activity, in children with scoliosis who had got whole spine radiograph two times during the last year. A total of 31 children with adolescent idiopathic scoliosis and 21 age-matched healthy children were included in the study. Serum levels of 8-OHdG and p53 were measured with ELISA kits. SOD and G-Px activities were determined with spectrophotometric assays. Serum levels of 8-OHdG and p53 were found to be higher (P<0.001 and P<0.01, respectively), SOD activity was found to be lower (P<0.001) in the children with scoliosis as compared to age-matched controls. There was no significant difference between the groups for G-Px activity. Our data show that X-ray exposure causes increased 8-OHdG level, and decreased SOD activity, which both may reflect a tumor promoting condition. Increased p53 level may be interpreted as a compensatory effort of cell to X-ray mediated DNA damage.

Effect of ionizing radiation exposure on Trypanosoma cruzi ubiquitin-proteasome system.

PubMed

Cerqueira, Paula G; Passos-Silva, Danielle G; Vieira-da-Rocha, João P; Mendes, Isabela Cecilia; de Oliveira, Karla A; Oliveira, Camila F B; Vilela, Liza F F; Nagem, Ronaldo A P; Cardoso, Joseane; Nardelli, Sheila C; Krieger, Marco A; Franco, Glória R; Macedo, Andrea M; Pena, Sérgio D J; Schenkman, Sérgio; Gomes, Dawidson A; Guerra-Sá, Renata; Machado, Carlos R

2017-03-01

In recent years, proteasome involvement in the damage response induced by ionizing radiation (IR) became evident. However, whether proteasome plays a direct or indirect role in IR-induced damage response still unclear. Trypanosoma cruzi is a human parasite capable of remarkable high tolerance to IR, suggesting a highly efficient damage response system. Here, we investigate the role of T. cruzi proteasome in the damage response induced by IR. We exposed epimastigotes to high doses of gamma ray and we analyzed the expression and subcellular localization of several components of the ubiquitin-proteasome system. We show that proteasome inhibition increases IR-induced cell growth arrest and proteasome-mediated proteolysis is altered after parasite exposure. We observed nuclear accumulation of 19S and 20S proteasome subunits in response to IR treatments. Intriguingly, the dynamic of 19S particle nuclear accumulation was more similar to the dynamic observed for Rad51 nuclear translocation than the observed for 20S. In the other hand, 20S increase and nuclear translocation could be related with an increase of its regulator PA26 and high levels of proteasome-mediated proteolysis in vitro. The intersection between the opposed peaks of 19S and 20S protein levels was marked by nuclear accumulation of both 20S and 19S together with Ubiquitin, suggesting a role of ubiquitin-proteasome system in the nuclear protein turnover at the time. Our results revealed the importance of proteasome-mediated proteolysis in T. cruzi IR-induced damage response suggesting that proteasome is also involved in T. cruzi IR tolerance. Moreover, our data support the possible direct/signaling role of 19S in DNA damage repair. Based on these results, we speculate that spatial and temporal differences between the 19S particle and 20S proteasome controls proteasome multiple roles in IR damage response. Copyright © 2017 Elsevier B.V. All rights reserved.

DNA damage in buccal mucosa cells of pre-school children exposed to high levels of urban air pollutants.

PubMed

Ceretti, Elisabetta; Feretti, Donatella; Viola, Gaia C V; Zerbini, Ilaria; Limina, Rosa M; Zani, Claudia; Capelli, Michela; Lamera, Rossella; Donato, Francesco; Gelatti, Umberto

2014-01-01

Air pollution has been recognized as a human carcinogen. Children living in urban areas are a high-risk group, because genetic damage occurring early in life is considered able to increase the risk of carcinogenesis in adulthood. This study aimed to investigate micronuclei (MN) frequency, as a biomarker of DNA damage, in exfoliated buccal cells of pre-school children living in a town with high levels of air pollution. A sample of healthy 3-6-year-old children living in Brescia, Northern Italy, was investigated. A sample of the children's buccal mucosa cells was collected during the winter months in 2012 and 2013. DNA damage was investigated using the MN test. Children's exposure to urban air pollution was evaluated by means of a questionnaire filled in by their parents that included items on various possible sources of indoor and outdoor pollution, and the concentration of fine particulate matter (PM10, PM2.5) and NO2 in the 1-3 weeks preceding biological sample collection. 181 children (mean age ± SD: 4.3 ± 0.9 years) were investigated. The mean ± SD MN frequency was 0.29 ± 0.13%. A weak, though statistically significant, association of MN with concentration of air pollutants (PM10, PM2.5 and NO2) was found, whereas no association was apparent between MN frequency and the indoor and outdoor exposure variables investigated via the questionnaire. This study showed a high MN frequency in children living in a town with heavy air pollution in winter, higher than usually found among children living in areas with low or medium-high levels of air pollution.

Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

PubMed Central

Millán, Mónica; Sobrino, Tomás; Arenillas, Juan Francisco; Rodríguez-Yáñez, Manuel; García, María; Nombela, Florentino; Castellanos, Mar; de la Ossa, Natalia Pérez; Cuadras, Patricia; Serena, Joaquín; Castillo, José; Dávalos, Antoni

2008-01-01

Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. Results: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p <0.001) levels at baseline, and with glutamate (r = 0.57,p <0.001), interleukin-6 (r = 0.49,p <0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research. PMID:19096131

Is UV-induced DNA damage greater at higher elevation?

PubMed

Wang, Qing-Wei; Hidema, Jun; Hikosaka, Kouki

2014-05-01

• Although ultraviolet radiation (UV) is known to have negative effects on plant growth, there has been no direct evidence that plants growing at higher elevations are more severely affected by ultraviolet-B (UV-B) radiation, which is known to increase with elevation. We examined damage to DNA, a primary target of UV-B, in the widespread species Polygonum sachalinense (Fallopia sachalinensis) and Plantago asiatica at two elevations.• We sampled leaves of both species at 300 and 1700 m above sea level every 2 h for 11 d across the growing season and determined the level of cyclobutane pyrimidine dimer (CPD), a major product of UV damage to DNA.• The CPD level was significantly influenced by the time of day, date, elevation, and their interactions in both species. The CPD level tended to be higher at noon or on sunny days. DNA damage was more severe at 1700 m than at 300 m: on average, 8.7% greater at high elevation in P. asiatica and 7.8% greater in P. sachalinense Stepwise multiple regression analysis indicated that the CPD level was explained mainly by UV-B and had no significant relationship with other environmental factors such as temperature and photosynthetically active radiation.• UV-induced DNA damage in plants is greater at higher elevations. © 2014 Botanical Society of America, Inc.

Paternal levels of DNA damage in spermatozoa and maternal parity influence offspring mortality in an endangered ungulate.

PubMed

Ruiz-López, María José; Espeso, Gerardo; Evenson, Donald P; Roldan, Eduardo R S; Gomendio, Montserrat

2010-08-22

Understanding which factors influence offspring mortality rates is a major challenge since it influences population dynamics and may constrain the chances of recovery among endangered species. Most studies have focused on the effects of maternal and environmental factors, but little is known about paternal factors. Among most polygynous mammals, males only contribute the haploid genome to their offspring, but the possibility that sperm DNA integrity may influence offspring survival has not been explored. We examined several maternal, paternal and individual factors that may influence offspring survival in an endangered species (Gazella cuvieri). Levels of sperm DNA damage had the largest impact upon offspring mortality rates, followed by maternal parity. In addition, there was a significant interaction between these two variables, so that offspring born to primiparous mothers were more likely to die if their father had high levels of sperm DNA damage, but this was not the case among multiparous mothers. Thus, multiparous mothers seem to protect their offspring from the deleterious effects of sperm DNA damage. Since levels of sperm DNA damage seem to be higher among endangered species, more attention should be paid to the impact of this largely ignored factor among the viability of endangered species.

Protective effects of folic acid on DNA damage and DNA methylation levels induced by N-methyl- N'-nitro- N-nitrosoguanidine in Kazakh esophageal epithelial cells.

PubMed

Chen, Y; Feng, H; Chen, D; Abuduwaili, K; Li, X; Zhang, H

2018-01-01

The protective effects of folic acid on DNA damage and DNA methylation induced by N-methyl- N'-nitro- N-nitrosoguanidine (MNNG) in Kazakh esophageal epithelial cells were investigated using a 3 × 3 factorial design trial. The cells were cultured in vitro and exposed to media containing different concentrations of folic acid and MNNG, after which growth indices were detected. DNA damage levels were measured using comet assays, and genome-wide DNA methylation levels (MLs) were measured using high-performance liquid chromatography. The DNA methylation of methylenetetrahydrofolate reductase (MTHFR) and folate receptor- α (FR α) genes was detected by bisulfite sequencing polymerase chain reaction (PCR). The results showed significant increases in tail DNA concentration, tail length, and Olive tail moment ( p < 0.01); a significant reduction of genome-wide DNA MLs ( p < 0.01); and an increase in the methylation frequencies of MTHFR and FR α genes. In particular, significant differences were observed in the promoter regions of both genes ( p < 0.01). Our study indicated that a reduction in folic acid concentration promotes DNA damage and DNA methylation in Kazakh esophageal epithelial cells upon MNNG exposure. Thus, sufficient folic acid levels could play a protective role against the damage induced by this compound.

Evaluation of various glyphosate concentrations on DNA damage in human Raji cells and its impact on cytotoxicity.

PubMed

Townsend, Michelle; Peck, Connor; Meng, Wei; Heaton, Matthew; Robison, Richard; O'Neill, Kim

2017-04-01

Glyphosate is a highly used active compound in agriculturally based pesticides. The literature regarding the toxicity of glyphosate to human cells has been highly inconsistent. We studied the resulting DNA damage and cytotoxicity of various glyphosate concentrations on human cells to evaluate DNA damaging potential. Utilizing human Raji cells, DNA damage was quantified using the comet assay, while cytotoxicity was further analyzed using MTT viability assays. Several glyphosate concentrations were assessed, ranging from 15 mM to 0.1 μM. We found that glyphosate treatment is lethal to Raji cells at concentrations above 10 mM, yet has no cytotoxic effects at concentrations at or below 100 μM. Treatment concentrations of 1 mM and 5 mM induce statistically significant DNA damage to Raji cells following 30-60 min of treatment, however, cells show a slow recovery from initial damage and cell viability is unaffected after 2 h. At these same concentrations, cells treated with additional compound did not recover and maintained high levels of DNA damage. While the cytotoxicity of glyphosate appears to be minimal for physiologically relevant concentrations, the compound has a definitive cytotoxic nature in human cells at high concentrations. Our data also suggests a mammalian metabolic pathway for the degradation of glyphosate may be present. Copyright © 2017 Elsevier Inc. All rights reserved.

Damage of actively cooled plasma facing components of magnetic confinement controlled fusion machines

NASA Astrophysics Data System (ADS)

Chevet, G.; Schlosser, J.; Martin, E.; Herb, V.; Camus, G.

2009-03-01

Plasma facing components (PFCs) of magnetic fusion machines have high manufactured residual stresses and have to withstand important stress ranges during operation. These actively cooled PFCs have a carbon fibre composite (CFC) armour and a copper alloy heat sink. Cracks mainly appear in the CFC near the composite/copper interface. In order to analyse damage mechanisms, it is important to well simulate the damage mechanisms both of the CFC and the CFC/Cu interface. This study focuses on the mechanical behaviour of the N11 material for which the scalar ONERA damage model was used. The damage parameters of this model were identified by similarity to a neighbour material, which was extensively analysed, according to the few characterization test results available for the N11. The finite elements calculations predict a high level of damage of the CFC at the interface zone explaining the encountered difficulties in the PFCs fabrication. These results suggest that the damage state of the CFC cells is correlated with a conductivity decrease to explain the temperature increase of the armour surface under fatigue heat load.

CFTR expression and organ damage in cystic fibrosis

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

Tizzano, E.; Chitayat, D.; Buchwald, M.

1994-09-01

To assist our understanding of the origin of organ damage caused by cystic fibrosis (CF) disease, we have analyzed the pattern of expression of the CF gene (CFTR). mRNA in situ hybridization analysis was carried out in human fetal, newborn, infant and adult tissues and the abundance of the mRNA was correlated with the known pathology at the various stages of human development. Analysis of the pattern of expression indicates a constitutive level of mRNA in gastrointestinal tissues starting during early development and maintained throughout life. Prenatal respiratory tissues show qualitative and quantitative major differences in comparison to postnatal lungmore » samples. Male reproductive tissues show high levels of expression in the head of the epididymis compared with the rest of the male ducts. Female reproductive tissues show a variable pattern of expression at different stages during fetal development and during puberty probably due to changes in hormonal levels. Gastrointestinal and male reproductive tissues have a consistent pathology at birth, whereas no lung abnormalities have been described in newborns affected by CF. Our results show that there is no exact correlations between organ damage present at birth and the degree of CFTR expression. To explain these observations, we hypothesize that the pathogenesis of organ damage in CF depend on at least three factors: the rate of CFTR-mediated fluid secretion, differences in genotype and environmental factors, such as the amount of macromolecules in the lumen of the ducts. This last element predicts that damage will occur in tissues with high protein loads and low flow rates (e.g. pancreas, epididymis), where the absence of CFTR function leads to obstruction and pathology. Organs that express CFTR but with no significant damage (e.g. prenatal lung, female reproductive tissues), will have a low protein load and a high flow rates.« less

Continuum damage modeling and simulation of hierarchical dental enamel

NASA Astrophysics Data System (ADS)

Ma, Songyun; Scheider, Ingo; Bargmann, Swantje

2016-05-01

Dental enamel exhibits high fracture toughness and stiffness due to a complex hierarchical and graded microstructure, optimally organized from nano- to macro-scale. In this study, a 3D representative volume element (RVE) model is adopted to study the deformation and damage behavior of the fibrous microstructure. A continuum damage mechanics model coupled to hyperelasticity is developed for modeling the initiation and evolution of damage in the mineral fibers as well as protein matrix. Moreover, debonding of the interface between mineral fiber and protein is captured by employing a cohesive zone model. The dependence of the failure mechanism on the aspect ratio of the mineral fibers is investigated. In addition, the effect of the interface strength on the damage behavior is studied with respect to geometric features of enamel. Further, the effect of an initial flaw on the overall mechanical properties is analyzed to understand the superior damage tolerance of dental enamel. The simulation results are validated by comparison to experimental data from micro-cantilever beam testing at two hierarchical levels. The transition of the failure mechanism at different hierarchical levels is also well reproduced in the simulations.

Coconut water vinegar ameliorates recovery of acetaminophen induced liver damage in mice.

PubMed

Mohamad, Nurul Elyani; Yeap, Swee Keong; Beh, Boon-Kee; Ky, Huynh; Lim, Kian Lam; Ho, Wan Yong; Sharifuddin, Shaiful Adzni; Long, Kamariah; Alitheen, Noorjahan Banu

2018-06-25

Coconut water has been commonly consumed as a beverage for its multiple health benefits while vinegar has been used as common seasoning and a traditional Chinese medicine. The present study investigates the potential of coconut water vinegar in promoting recovery on acetaminophen induced liver damage. Mice were injected with 250 mg/kg body weight acetaminophen for 7 days and were treated with distilled water (untreated), Silybin (positive control) and coconut water vinegar (0.08 mL/kg and 2 mL/kg body weight). Level of oxidation stress and inflammation among treated and untreated mice were compared. Untreated mice oral administrated with acetaminophen were observed with elevation of serum liver profiles, liver histological changes, high level of cytochrome P450 2E1, reduced level of liver antioxidant and increased level of inflammatory related markers indicating liver damage. On the other hand, acetaminophen challenged mice treated with 14 days of coconut water vinegar were recorded with reduction of serum liver profiles, improved liver histology, restored liver antioxidant, reduction of liver inflammation and decreased level of liver cytochrome P450 2E1 in dosage dependent level. Coconut water vinegar has helped to attenuate acetaminophen-induced liver damage by restoring antioxidant activity and suppression of inflammation.

Defect formation in MeV H+ implanted GaN and 4H-SiC investigated by cross-sectional Raman spectroscopy

NASA Astrophysics Data System (ADS)

Huang, Kai; Jia, Qi; You, Tiangui; Zhang, Shibin; Lin, Jiajie; Zhang, Runchun; Zhou, Min; Yu, Wenjie; Zhang, Bo; Ou, Xin; Wang, Xi

2017-09-01

Cross-sectional Raman spectroscopy is used to characterize the defect formation and the defect recovery in MeV H+ implanted bulk GaN and 4H-SiC in the high energy MeV ion-cut process. The Raman intensity decreases but the forbidden modes are activated at the damage region, and the intensity decrease is proportional to the damage level. The Raman spectrum is quite sensitive to detect the damage recovery after annealing. The main peak intensity increases and the forbidden mode disappears in both annealed GaN and 4H-SiC samples. The Raman spectra of GaN samples annealed at different temperatures suggest that higher annealing temperature is more efficient for damage recovery. While, the Raman spectra of SiC indicate that higher implantation temperature results in heavier lattice damage and other polytype clusters might be generated by high annealing temperature in the annealed SiC samples. The cross-sectional Raman spectroscopy is a straightforward method to characterize lattice damage and damage recovery in high energy ion-cut process. It can serve as a fast supplementary measurement technique to Rutherford backscattering spectrometry (RBS), nuclear reaction analysis (NRA) and transmission electron microscope (TEM) for the defect characterizations.

Spermine oxidase, a polyamine catabolic enzyme that links Helicobacter pylori CagA and gastric cancer risk

PubMed Central

Chaturvedi, Rupesh; de Sablet, Thibaut; Peek, Richard M.; Wilson, Keith T.

2012-01-01

We have recently reported that Helicobacter pylori strains expressing the virulence factor cytotoxin-associated gene A (CagA) stimulate increased levels of spermine oxidase (SMO) in gastric epithelial cells, while cagA– strains did not. SMO catabolizes the polyamine spermine and produces H2O2 that results in both apoptosis and DNA damage. Exogenous overexpression of CagA confirmed these findings, and knockdown or inhibition of SMO blocked CagA-mediated apoptosis and DNA damage. The strong association of SMO, apoptosis, and DNA damage was also demonstrated in humans infected with cagA+, but not cagA– strains. In infected gerbils and mice, DNA damage was CagA-dependent and only present in epithelial cells that expressed SMO. We also discovered SMOhigh gastric epithelial cells from infected animals with dysplasia that are resistant to apoptosis despite high levels of DNA damage. Inhibition of polyamine synthesis or SMO could abrogate the development of this cell population that may represent precursors for neoplastic transformation. PMID:22555547

Mitochondrial DNA Damage and its Consequences for Mitochondrial Gene Expression

PubMed Central

Cline, Susan D.

2012-01-01

How mitochondria process DNA damage and whether a change in the steady-state level of mitochondrial DNA damage (mtDNA) contributes to mitochondrial dysfunction are questions that fuel burgeoning areas of research into aging and disease pathogenesis. Over the past decade, researchers have identified and measured various forms of endogenous and environmental mtDNA damage and have elucidated mtDNA repair pathways. Interestingly, mitochondria do not appear to contain the full range of DNA repair mechanisms that operate in the nucleus, although mtDNA contains types of damage that are targets of each nuclear DNA repair pathway. The reduced repair capacity may, in part, explain the high mutation frequency of the mitochondrial chromosome. Since mtDNA replication is dependent on transcription, mtDNA damage may alter mitochondrial gene expression at three levels: by causing DNA polymerase γ nucleotide incorporation errors leading to mutations, by interfering with the priming of mtDNA replication by the mitochondrial RNA polymerase, or by inducing transcriptional mutagenesis or premature transcript termination. This review summarizes our current knowledge of mtDNA damage, its repair, and its effects on mtDNA integrity and gene expression. PMID:22728831

Assessment of DNA damage in car spray painters exposed to organic solvents by the high-throughput comet assay.

PubMed

Londoño-Velasco, Elizabeth; Martínez-Perafán, Fabián; Carvajal-Varona, Silvio; García-Vallejo, Felipe; Hoyos-Giraldo, Luz Stella

2016-05-01

Occupational exposure as a painter is associated with DNA damage and development of cancer. Comet assay has been widely adopted as a sensitive and quantitative tool for DNA damage assessment at the individual cell level in populations exposed to genotoxics. The aim of this study was to assess the application of the high-throughput comet assay, to determine the DNA damage in car spray painters. The study population included 52 car spray painters and 52 unexposed subjects. A significant increase in the %TDNA median (p <  0.001) was observed in the exposed group in comparison to the unexposed group. Neither age (%TDNA: p =  0.913) nor time of exposure (%TDNA: p = 0.398) were significantly correlated with DNA damage. The car spray painters who consumed alcohol did not show a significant increase in DNA damage compared to nonalcohol consumers (p  > 0.05). The results showed an increase in DNA breaks in car spray painters exposed to organic solvents and paints; furthermore, they demonstrated the application of high-throughput comet assay in an occupational exposure study to genotoxic agents.

Ion irradiation induced defect evolution in Ni and Ni-based FCC equiatomic binary alloys

DOE PAGES

Jin, Ke; Zhang, Yanwen; Bei, Hongbin

2015-09-09

In order to explore the chemical effects on radiation response of alloys with multi-principal elements, defect evolution under Au ion irradiation was investigated in the elemental Ni, equiatomic NiCo and NiFe alloys. Single crystals were successfully grown in an optical floating zone furnace and their (100) surfaces were irradiated with 3 MeV Au ions at fluences ranging from 1 × 10 13 to 5 × 10 15 ions cm –2 at room temperature. The irradiation-induced defect evolution was analyzed by using ion channeling technique. Experiment shows that NiFe is more irradiation-resistant than NiCo and pure Ni at low fluences. Withmore » continuously increasing the ion fluences, damage level is eventually saturated for all materials but at different dose levels. The saturation level in pure Ni appears at relatively lower irradiation fluence than the alloys, suggesting that damage accumulation slows down in the alloys. Here, under high-fluence irradiations, pure Ni has wider damage ranges than the alloys, indicating that defects in pure Ni have high mobility.« less

Accumulation of Senescent Cells in Mitotic Tissue of Aging Primates

PubMed Central

Jeyapalan, Jessie C.; Ferreira, Mark; Sedivy, John M.; Herbig, Utz

2013-01-01

Cellular senescence, a stress induced growth arrest of somatic cells, was first documented in cell cultures over forty years ago, however its physiological significance has only recently been demonstrated. Using novel biomarkers of cellular senescence we examined whether senescent cells accumulate in tissues from baboons of ages encompassing the entire lifespan of this species. We show that dermal fibroblasts, displaying markers of senescence such as telomere damage, active checkpoint kinase ATM, high levels of heterochromatin proteins and elevated levels of p16, accumulate in skin biopsies from baboons with advancing age. The number of dermal fibroblasts containing damaged telomeres reaches a value of over 15% of total fibroblasts, whereas 80% of cells contain high levels of the heterochromatin protein HIRA. In skeletal muscle, a postmitotic tissue, only a small percentage of myonuclei containing damaged telomeres were detected regardless of animal age. The presence of senescent cells in mitotic tissues might therefore be a contributing factor to aging and age related pathology and provides further evidence that cellular senescence is a physiological event. PMID:17116315

Damage and protection cost curves for coastal floods within the 600 largest European cities

NASA Astrophysics Data System (ADS)

Prahl, Boris F.; Boettle, Markus; Costa, Luís; Kropp, Jürgen P.; Rybski, Diego

2018-03-01

The economic assessment of the impacts of storm surges and sea-level rise in coastal cities requires high-level information on the damage and protection costs associated with varying flood heights. We provide a systematically and consistently calculated dataset of macroscale damage and protection cost curves for the 600 largest European coastal cities opening the perspective for a wide range of applications. Offering the first comprehensive dataset to include the costs of dike protection, we provide the underpinning information to run comparative assessments of costs and benefits of coastal adaptation. Aggregate cost curves for coastal flooding at the city-level are commonly regarded as by-products of impact assessments and are generally not published as a standalone dataset. Hence, our work also aims at initiating a more critical discussion on the availability and derivation of cost curves.

Damage and protection cost curves for coastal floods within the 600 largest European cities.

PubMed

Prahl, Boris F; Boettle, Markus; Costa, Luís; Kropp, Jürgen P; Rybski, Diego

2018-03-20

The economic assessment of the impacts of storm surges and sea-level rise in coastal cities requires high-level information on the damage and protection costs associated with varying flood heights. We provide a systematically and consistently calculated dataset of macroscale damage and protection cost curves for the 600 largest European coastal cities opening the perspective for a wide range of applications. Offering the first comprehensive dataset to include the costs of dike protection, we provide the underpinning information to run comparative assessments of costs and benefits of coastal adaptation. Aggregate cost curves for coastal flooding at the city-level are commonly regarded as by-products of impact assessments and are generally not published as a standalone dataset. Hence, our work also aims at initiating a more critical discussion on the availability and derivation of cost curves.

Electromagnetic pulse (EMP), Part I: Effects on field medical equipment.

PubMed

Vandre, R H; Klebers, J; Tesche, F M; Blanchard, J P

1993-04-01

The electromagnetic pulse (EMP) from a high-altitude nuclear detonation has the potential to cover an area as large as the continental United States with damaging levels of EMP radiation. In this study, two of seven items of medical equipment were damaged by an EMP simulator. Computer circuit analysis of 17 different items showed that 11 of the 17 items would be damaged by current surges on the power cords, while two would be damaged by current surges on external leads. This research showed that a field commander can expect approximately 65% of his electronic medical equipment to be damaged by a single nuclear detonation as far as 2,200 km away.

Enemy release and plant invasion: patterns of defensive traits and leaf damage in Hawaii.

PubMed

Funk, Jennifer L; Throop, Heather L

2010-04-01

Invasive species may be released from consumption by their native herbivores in novel habitats and thereby experience higher fitness relative to native species. However, few studies have examined release from herbivory as a mechanism of invasion in oceanic island systems, which have experienced particularly high loss of native species due to the invasion of non-native animal and plant species. We surveyed putative defensive traits and leaf damage rates in 19 pairs of taxonomically related invasive and native species in Hawaii, representing a broad taxonomic diversity. Leaf damage by insects and pathogens was monitored in both wet and dry seasons. We found that native species had higher leaf damage rates than invasive species, but only during the dry season. However, damage rates across native and invasive species averaged only 2% of leaf area. Native species generally displayed high levels of structural defense (leaf toughness and leaf thickness, but not leaf trichome density) while native and invasive species displayed similar levels of chemical defenses (total phenolics). A defense index, which integrated all putative defense traits, was significantly higher for native species, suggesting that native species may allocate fewer resources to growth and reproduction than do invasive species. Thus, our data support the idea that invasive species allocate fewer resources to defense traits, allowing them to outperform native species through increased growth and reproduction. While strong impacts of herbivores on invasion are not supported by the low damage rates we observed on mature plants, population-level studies that monitor how herbivores influence recruitment, mortality, and competitive outcomes are needed to accurately address how herbivores influence invasion in Hawaii.

Hyperhomocysteinemia and protein damage in chronic renal failure and kidney transplant pediatric patients--Italian initiative on uremic hyperhomocysteinemia (IIUH).

PubMed

Perna, Alessandra F; Ingrosso, Diego; Molino, Daniela; Galletti, Patrizia; Montini, Giovanni; Zacchello, Graziella; Bellantuono, Rosa; Caringella, Angela; Fede, Carmelo; Chimenz, Roberto; De Santo, Natale G

2003-01-01

Plasma homocysteine, a new cardiovascular risk factor in both children and adults, is higher in chronic renal failure or kidney transplant patients. This alteration has been linked, in chronic renal failure, to plasma protein damage, represented by increased L-isoaspartyl residues. We measured plasma homocysteine levels and plasma protein damage in pediatric patients from four different Italian regions with conservatively treated renal failure; hemodialysis, continuous ambulatory peritoneal dialysis (CAPD), or transplants, to establish the presence of protein damage and the relative role of hyperhomocysteinemia. High performance liquid chromatography (HPLC) separation measured total plasma homocysteine levels, using precolumn derivatization with ammonium 7-fluorobenzo-2-oxa-1, 3-diazole-4-sulphonate (SBD-F). Plasma protein L-isoaspartyl residues were quantitated using human recombinant protein carboxyl methyl transferase (PCMT). In all patient groups, homocysteine levels were significantly higher with respect to the control (Control: 6.87 +/- 0.73 microM) conservatively treated, 14.19 +/- 1.73 microM; hemodialysis, 27.03 +/- 4.32 microM; CAPD, 22.38 +/- 3.73 microM; transplanted, 20.22 +/- 2.27 microM, p < 0.001 vs. control]. Plasma protein damage was significantly higher in conservatively treated, hemodialysis (HD) and CAPD patients, while in transplant patients it was no different from the control. We concluded that in pediatric patients of different Italian geographical origin, plasma homocysteine levels were significantly higher in all groups with respect to healthy children; therefore contributing to the elevated cardiovascular risk present in these patients. Plasma protein L-isoaspartyl content was higher in renal failure patients, but kidney transplant patients had normal levels, indicating that this kind of protein damage relates more to the toxic action of uremic retention solutes, than to plasma homocysteine levels.

Modeling of beam-induced damage of the LHC tertiary collimators

NASA Astrophysics Data System (ADS)

Quaranta, E.; Bertarelli, A.; Bruce, R.; Carra, F.; Cerutti, F.; Lechner, A.; Redaelli, S.; Skordis, E.; Gradassi, P.

2017-09-01

Modern hadron machines with high beam intensity may suffer from material damage in the case of large beam losses and even beam-intercepting devices, such as collimators, can be harmed. A systematic method to evaluate thresholds of damage owing to the impact of high energy particles is therefore crucial for safe operation and for predicting possible limitations in the overall machine performance. For this, a three-step simulation approach is presented, based on tracking simulations followed by calculations of energy deposited in the impacted material and hydrodynamic simulations to predict the thermomechanical effect of the impact. This approach is applied to metallic collimators at the CERN Large Hadron Collider (LHC), which in standard operation intercept halo protons, but risk to be damaged in the case of extraction kicker malfunction. In particular, tertiary collimators protect the aperture bottlenecks, their settings constrain the reach in β* and hence the achievable luminosity at the LHC experiments. Our calculated damage levels provide a very important input on how close to the beam these collimators can be operated without risk of damage. The results of this approach have been used already to push further the performance of the present machine. The risk of damage is even higher in the upgraded high-luminosity LHC with higher beam intensity, for which we quantify existing margins before equipment damage for the proposed baseline settings.

Antioxidant defense parameters as predictive biomarkers for fermentative capacity of active dried wine yeast.

PubMed

Gamero-Sandemetrio, Esther; Gómez-Pastor, Rocío; Matallana, Emilia

2014-08-01

The production of active dried yeast (ADY) is a common practice in industry for the maintenance of yeast starters and as a means of long term storage. The process, however, causes multiple cell injuries, with oxidative damage being one of the most important stresses. Consequentially, dehydration tolerance is a highly appreciated property in yeast for ADY production. In this study we analyzed the cellular redox environment in three Saccharomyces cerevisiae wine strains, which show markedly different fermentative capacities after dehydration. To measure/quantify the effect of dehydration on the S. cerevisiae strains, we used: (i) fluorescent probes; (ii) antioxidant enzyme activities; (ii) intracellular damage; (iii) antioxidant metabolites; and (iv) gene expression, to select a minimal set of biochemical parameters capable of predicting desiccation tolerance in wine yeasts. Our results show that naturally enhanced antioxidant defenses prevent oxidative damage after wine yeast biomass dehydration and improve fermentative capacity. Based on these results we chose four easily assayable parameters/biomarkers for the selection of industrial yeast strains of interest for ADY production: trehalose and glutathione levels, and glutathione reductase and catalase enzymatic activities. Yeast strains selected in accordance with this process display high levels of trehalose, low levels of oxidized glutathione, a high induction of glutathione reductase activity, as well as a high basal level and sufficient induction of catalase activity, which are properties inherent in superior ADY strains. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression

PubMed Central

Barr, Alexis R.; Cooper, Samuel; Heldt, Frank S.; Butera, Francesca; Stoy, Henriette; Mansfeld, Jörg; Novák, Béla; Bakal, Chris

2017-01-01

Following DNA damage caused by exogenous sources, such as ionizing radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21. However, the role of p21 in maintaining genomic stability in the absence of exogenous DNA-damaging agents is unclear. Here, using live single-cell measurements of p21 protein in proliferating cultures, we show that naturally occurring DNA damage incurred over S-phase causes p53-dependent accumulation of p21 during mother G2- and daughter G1-phases. High p21 levels mediate G1 arrest via CDK inhibition, yet lower levels have no impact on G1 progression, and the ubiquitin ligases CRL4Cdt2 and SCFSkp2 couple to degrade p21 prior to the G1/S transition. Mathematical modelling reveals that a bistable switch, created by CRL4Cdt2, promotes irreversible S-phase entry by keeping p21 levels low, preventing premature S-phase exit upon DNA damage. Thus, we characterize how p21 regulates the proliferation-quiescence decision to maintain genomic stability. PMID:28317845

Multiscale modelling of Flow-Induced Blood Cell Damage

NASA Astrophysics Data System (ADS)

Liu, Yaling; Sohrabi, Salman

2017-11-01

We study red blood cell (RBC) damage and hemolysis at cellular level. Under high shear rates, pores form on RBC membranes through which hemoglobin (Hb) leaks out and increases free Hb content of plasma leading to hemolysis. By coupling lattice Boltzmann and spring connected network models through immersed boundary method, we estimate hemolysis of a single RBC under various shear rates. The developed cellular damage model can be used as a predictive tool for hydrodynamic and hematologic design optimization of blood-wetting medical devices.

Statistical study of single and multiple pulse laser-induced damage in glasses.

PubMed

Gallais, L; Natoli, J; Amra, C

2002-12-16

Single and multiple pulse laser damage studies are performed in Suprasil silica and BK-7 borosilicate glasses. Experiments are made in the bulk of materials at 1.064microm with nanosecond pulses, using an accurate and reliable measurement system. By means of a statistical study on laser damage probabilities, we demonstrate that the same nano-precursors could be involved in the multiple shot and single shot damage process. A damage mechanism with two stages is then proposed to explain the results. Firstly, a pre-damage process, corresponding to material changes at a microscopic level, leads the precursor to a state that can induce a one-pulse damage. And secondly a final damage occurs, with a mechanism identical to the single shot case. For each material, a law is found to predict the precursor life-time. We can then deduce the long term life of optical elements in high-power laser systems submitted to multipulse irradiation.

Polygenic Profile and Exercise-Induced Muscle Damage by a Competitive Half-Ironman.

PubMed

Del Coso, Juan; Salinero, Juan J; Lara, Beatriz; Gallo-Salazar, César; Areces, Francisco; Herrero, David; Puente, Carlos

2017-11-14

Del Coso, J, Salinero, JJ, Lara, B, Gallo-Salazar, C, Areces, F, Herrero, D, and Puente, C. Polygenic profile and exercise-induced muscle damage by a competitive half-ironman. J Strength Cond Res XX(X): 000-000, 2017-To date, it is still unknown why some individuals develop higher levels of muscle damage than other individuals, despite participating in exercise with comparable levels of physical intensity. The aim of this investigation was to analyze 7 single-nucleotide polymorphisms (SNPs) that are candidates to explain individual variations in the level of muscle damage attained during a half-ironman competition. Using the model of Williams and Folland (2, 1, and 0 points for optimal, intermediate, and suboptimal genotype), we determined the total genotype score from the accumulated combination of 7 SNPs (ACE = 287bp Ins/Del; ACTN3 = p.R577X; creatine kinase, muscle type = NcoI; insulin-like growth factor 2 = C13790G; interleukin-6 = 174G>C; myosin light chain kinase = C37885A; and tumor necrosis factor-α = 308G>A) in 22 experienced triathletes. Before and after the race, a sample of venous blood was obtained to measure serum markers of muscle damage. Two groups of triathletes were established according to their postcompetition serum CK concentration: low CK responders (n = 10; 377 ± 86 U·L) vs. high CK responders (n = 12; 709 ± 136 U·L). At the end of the race, low CK responders had lower serum myoglobin concentrations (384 ± 243 vs. 597 ± 293 ng·ml, p = 0.04). Although the groups were similar in age, anthropometric characteristics, and training habits, total genotype score was higher in low CK responders than in high CK responders (7.7 ± 1.1 vs. 5.5 ± 1.1 point, p < 0.01). A favorable polygenic profile can contribute to reducing the level of muscle damage developed during endurance exercise.

Use of waveform lidar and hyperspectral sensors to assess selected spatial and structural patterns associated with recent and repeat disturbance and the abundance of sugar maple (Acer saccharum Marsh.) in a temperate mixed hardwood and conifer forest

USGS Publications Warehouse

Anderson, J.E.; Ducey, Mark J.; Fast, A.; Martin, M.E.; Lepine, L.; Smith, M.-L.; Lee, T.D.; Dubayah, R.O.; Hofton, M.A.; Hyde, P.; Peterson, Birgit; Blair, J.B.

2011-01-01

Waveform lidar imagery was acquired on September 26, 1999 over the Bartlett Experimental Forest (BEF) in New Hampshire (USA) using NASA's Laser Vegetation Imaging Sensor (LVIS). This flight occurred 20 months after an ice storm damaged millions of hectares of forestland in northeastern North America. Lidar measurements of the amplitude and intensity of ground energy returns appeared to readily detect areas of moderate to severe ice storm damage associated with the worst damage. Southern through eastern aspects on side slopes were particularly susceptible to higher levels of damage, in large part overlapping tracts of forest that had suffered the highest levels of wind damage from the 1938 hurricane and containing the highest levels of sugar maple basal area and biomass. The levels of sugar maple abundance were determined through analysis of the 1997 Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) high resolution spectral imagery and inventory of USFS Northern Research Station field plots. We found a relationship between field measurements of stem volume losses and the LVIS metric of mean canopy height (r2 = 0.66; root mean square errors = 5.7 m3/ha, p < 0.0001) in areas that had been subjected to moderate-to-severe ice storm damage, accurately documenting the short-term outcome of a single disturbance event.

An experimental study of non-destructive testing on glass fibre reinforced polymer composites after high velocity impact event

NASA Astrophysics Data System (ADS)

Razali, N.; Sultan, M. T. H.; Cardona, F.

2016-10-01

A non-destructive testing method on Glass Fibre Reinforced Polymer (GFRP) after high velocity impact event using single stage gas gun (SSGG) is presented. Specimens of C- type and E-type fibreglass reinforcement, which were fabricated with 6mm, 8mm, 10mm and 12mm thicknesses and size 100 mm x 100 mm, were subjected to a high velocity impact with three types of bullets: conical, hemispherical and blunt at various gas gun pressure levels from 6 bar to 60 bar. Visual observation techniques using a lab microscope were used to determine the infringed damage by looking at the crack zone. Dye penetrants were used to inspect the area of damage, and to evaluate internal and external damages on the specimens after impact. The results from visual analysis of the impacted test laminates were discussed and presented. It was found that the impact damage started with induced delamination, fibre cracking and then failure, simultaneously with matrix cracking and breakage, and finally followed by the fibres pulled out. C-type experienced more damaged areas compared to E-type of GFRP.

Manuka honey protects middle-aged rats from oxidative damage

PubMed Central

Jubri, Zakiah; Rahim, Noor Baitee Abdul; Aan, Goon Jo

2013-01-01

OBJECTIVE: This study aimed to determine the effect of manuka honey on the oxidative status of middle-aged rats. METHOD: Twenty-four male Sprague-Dawley rats were divided into young (2 months) and middle-aged (9 months) groups. They were further divided into two groups each, which were either fed with plain water (control) or supplemented with 2.5 g/kg body weight of manuka honey for 30 days. The DNA damage level was determined via the comet assay, the plasma malondialdehyde level was determined using high performance liquid chromatography, and the antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione peroxidase and catalase) were determined spectrophotometrically in the erythrocytes and liver. The antioxidant activities were measured using 1,1-diphenyl-2-picrylhydrazyl and ferric reducing/antioxidant power assays, and the total phenolic content of the manuka was analyzed using UV spectrophotometry and the Folin-Ciocalteu method, respectively. RESULTS: Supplementation with manuka honey reduced the level of DNA damage, the malondialdehyde level and the glutathione peroxidase activity in the liver of both the young and middle-aged groups. However, the glutathione peroxidase activity was increased in the erythrocytes of middle-aged rats given manuka honey supplementation. The catalase activity was reduced in the liver and erythrocytes of both young and middle-aged rats given supplementation. Manuka honey was found to have antioxidant activity and to have a high total phenolic content. These findings showed a strong correlation between the total phenolic content and antioxidant activity. CONCLUSIONS: Manuka honey reduces oxidative damage in young and middle-aged rats; this effect could be mediated through the modulation of its antioxidant enzyme activities and its high total phenolic content. Manuka honey can be used as an alternative supplement at an early age to improve the oxidative status. PMID:24270958

Manuka honey protects middle-aged rats from oxidative damage.

PubMed

Jubri, Zakiah; Rahim, Noor Baitee Abdul; Aan, Goon Jo

2013-11-01

This study aimed to determine the effect of manuka honey on the oxidative status of middle-aged rats. Twenty-four male Sprague-Dawley rats were divided into young (2 months) and middle-aged (9 months) groups. They were further divided into two groups each, which were either fed with plain water (control) or supplemented with 2.5 g/kg body weight of manuka honey for 30 days. The DNA damage level was determined via the comet assay, the plasma malondialdehyde level was determined using high performance liquid chromatography, and the antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione peroxidase and catalase) were determined spectrophotometrically in the erythrocytes and liver. The antioxidant activities were measured using 1,1-diphenyl-2-picrylhydrazyl and ferric reducing/antioxidant power assays, and the total phenolic content of the manuka was analyzed using UV spectrophotometry and the Folin-Ciocalteu method, respectively. Supplementation with manuka honey reduced the level of DNA damage, the malondialdehyde level and the glutathione peroxidase activity in the liver of both the young and middle-aged groups. However, the glutathione peroxidase activity was increased in the erythrocytes of middle-aged rats given manuka honey supplementation. The catalase activity was reduced in the liver and erythrocytes of both young and middle-aged rats given supplementation. Manuka honey was found to have antioxidant activity and to have a high total phenolic content. These findings showed a strong correlation between the total phenolic content and antioxidant activity. Manuka honey reduces oxidative damage in young and middle-aged rats; this effect could be mediated through the modulation of its antioxidant enzyme activities and its high total phenolic content. Manuka honey can be used as an alternative supplement at an early age to improve the oxidative status.

Special Section Guest Editorial: Laser Damage

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

Gruzdev, Vitaly E.; Shinn, Michelle D.

2012-11-09

Laser damage of optical materials, first reported in 1964, continues to limit the output energy and power of pulsed and continuous-wave laser systems. In spite of some 48 years of research in this area, interest from the international laser community to laser damage issues remains at a very high level and does not show any sign of decreasing. Moreover, it grows with the development of novel laser systems, for example, ultrafast and short-wavelength lasers that involve new damage effects and specific mechanisms not studied before. This interest is evident from the high level of attendance and presentations at the annualmore » SPIE Laser Damage Symposium (aka, Boulder Damage Symposium) that has been held in Boulder, Colorado, since 1969. This special section of Optical Engineering is the first one devoted to the entire field of laser damage rather than to a specific part. It is prepared in response to growing interest from the international laser-damage community. Some papers in this special section were presented at the Laser Damage Symposium; others were submitted in response to the general call for papers for this special section. The 18 papers compiled into this special section represent many sides of the broad field of laser-damage research. They consider theoretical studies of the fundamental mechanisms of laser damage including laser-driven electron dynamics in solids (O. Brenk and B. Rethfeld; A. Nikiforov, A. Epifanov, and S. Garnov; T. Apostolova et al.), modeling of propagation effects for ultrashort high-intensity laser pulses (J. Gulley), an overview of mechanisms of inclusion-induced damage (M. Koldunov and A. Manenkov), the formation of specific periodic ripples on a metal surface by femtosecond laser pulses (M. Ahsan and M. Lee), and the laser-plasma effects on damage in glass (Y. Li et al). Material characterization is represented by the papers devoted to accurate and reliable measurements of absorption with special emphasis on thin films (C. Mühlig and S. Bublitz; B. Cho, E. Danielewicz, and J. Rudisill; W. Palm et al; and J. Lu et al.). Statistical treatment of measurements of the laser-damage threshold (J. Arenberg) and the relationship to damage mechanisms (F. Wagner et al.) represent the large subfield of laser-damage measurements. Various aspects of multilayer coating and thin-film characterization are considered in papers by B. Cho, J. Rudisill, and E. Danielewicz (spectral shift in multilayer mirrors) and R. Weber et al. (novel approach to damage studies based on third-harmonic generation microscopy). Of special interest for readers is the paper by C. Stolz that summarizes the results of four “thin-film damage competitions” organized as a part of the Laser Damage Symposium. Another paper is devoted to thermal annealing of damage precursors (N. Shen et al.). Finally, the influence of nano-size contamination on initiation of laser damage by ultrashort pulses is considered in paper of V. Komolov et al.« less

Differential responses to acoustic damage and furosemide in auditory brainstem and otoacoustic emission measures

NASA Astrophysics Data System (ADS)

Mills, David M.

2003-02-01

Characteristics of distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs) were measured in Mongolian gerbil before and after the introduction of two different auditory dysfunctions: (1) acoustic damage with a high-intensity tone, or (2) furosemide intoxication. The goal was to find emission parameters and measures that best differentiated between the two dysfunctions, e.g., at a given ABR threshold elevation. Emission input-output or ``growth'' functions were used (frequencies f1 and f2, f2/f1=1.21) with equal levels, L1=L2, and unequal levels, with L1=L2+20 dB. The best parametric choice was found to be unequal stimulus levels, and the best measure was found to be the change in the emission threshold level, Δx. The emission threshold was defined as the stimulus level required to reach a criterion emission amplitude, in this case -10 dB SPL. (The next best measure was the change in emission amplitude at high stimulus levels, specifically that measured at L1×L2=90×70 dB SPL.) For an ABR threshold shift of 20 dB or more, there was essentially no overlap in the emission threshold measures for the two conditions, sound damage or furosemide. The dividing line between the two distributions increased slowly with the change in ABR threshold, ΔABR, and was given by Δxt=0.6 ΔABR+8 dB. For a given ΔABR, if the shift in emission threshold was more than the calculated dividing line value, Δxt, the auditory dysfunction was due to acoustic damage, if less, it was due to furosemide.

Oxidative DNA damage during sleep periods among nightshift workers.

PubMed

Bhatti, Parveen; Mirick, Dana K; Randolph, Timothy W; Gong, Jicheng; Buchanan, Diana Taibi; Zhang, Junfeng Jim; Davis, Scott

2016-08-01

Oxidative DNA damage may be increased among nightshift workers because of suppression of melatonin, a cellular antioxidant, and/or inflammation related to sleep disruption. However, oxidative DNA damage has received limited attention in previous studies of nightshift work. From two previous cross-sectional studies, urine samples collected during a night sleep period for 217 dayshift workers and during day and night sleep (on their first day off) periods for 223 nightshift workers were assayed for 8-hydroxydeoxyguanosine (8-OH-dG), a marker of oxidative DNA damage, using high-performance liquid chromatography with electrochemical detection. Urinary measures of 6-sulfatoxymelatonin (aMT6s), a marker of circulating melatonin levels, and actigraphy-based sleep quality data were also available. Nightshift workers during their day sleep periods excreted 83% (p=0.2) and 77% (p=0.03) of the 8-OH-dG that dayshift workers and they themselves, respectively, excreted during their night sleep periods. Among nightshift workers, higher aMT6s levels were associated with higher urinary 8-OH-dG levels, and an inverse U-shaped trend was observed between 8-OH-dG levels and sleep efficiency and sleep duration. Reduced excretion of 8-OH-dG among nightshift workers during day sleep may reflect reduced functioning of DNA repair machinery, which could potentially lead to increased cellular levels of oxidative DNA damage. Melatonin disruption among nightshift workers may be responsible for the observed effect, as melatonin is known to enhance repair of oxidative DNA damage. Quality of sleep may similarly impact DNA repair. Cellular levels of DNA damage will need to be evaluated in future studies to help interpret these findings. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Smoking in combination with antibodies to cyclic citrullinated peptides is associated with persistently high levels of survivin in early rheumatoid arthritis: a prospective cohort study

PubMed Central

2014-01-01

Introduction High levels of the oncoprotein survivin may be detected in the majority of patients with early rheumatoid arthritis (RA). Survivin is a sensitive predictor of joint damage and persistent disease activity. Survivin-positive patients are often poor responders to antirheumatic and biological treatment. The aim of this study was to investigate the reproducibility of survivin status and its significance for clinical and immunological assessment of RA patients. Methods Survivin levels were measured in 339 patients from the Better Anti-Rheumatic FarmacOTherapy (BARFOT) cohort of early RA at baseline and after 24 months. The association of survivin status with joint damage (total Sharp-van der Heijde score), disease activity (Disease Activity Score based on evaluation of 28 joints (DAS28)), functional disability (Health Assessment Questionnaire (HAQ)), and pain perception (Visual Analogue Scale (VAS)) was calculated in the groups positive and negative for survivin on both occasions, and for the positive-negative and negative-positive groups. Results In 268 patients (79%) the levels of survivin were similar at baseline and after 24 months, 15% converted from survivin-positive to survivin-negative, and 5% from survivin-negative to survivin-positive. A combination of smoking and antibodies against cyclic citrullinated peptides (aCCP) predicted persistently (baseline and 24 months) high levels of survivin (odds ratio 4.36 (95% CI: 2.64 to 7.20), P < 0.001), positive predictive value 0.66 and specificity 0.83). The independent nature of survivin and aCCP was demonstrated by statistical and laboratory analysis. Survivin positivity on both test occasions was associated with the progression of joint damage, significantly higher DAS28 and lower rate of remission at 24 and 60 months compared to negative-negative patients. Survivin status was less associated with changes in HAQ and VAS. Conclusions Survivin is a relevant and reproducible marker of severe RA. Persistently high levels of survivin were associated with smoking and the presence of aCCP and/or RF antibodies and predicted persistent disease activity and joint damage. PMID:24428870

Responses of CO2 Fluxes to Arctic Browning Events in a Range of High Latitude, Shrub-Dominated Ecosystems

NASA Astrophysics Data System (ADS)

Phoenix, G. K.; Treharne, R.; Emberson, L.; Tømmervik, H. A.; Bjerke, J. W.

2017-12-01

Climatic and biotic extreme events can result in considerable damage to arctic vegetation, often at landscape and larger scale. These acute events therefore contribute to the browning observed in some arctic regions. It is of considerable concern, therefore, that such extreme events are increasing in frequency as part of climate change. However, despite the increasing importance of browning events, and the considerable impact they can have on ecosystems, to date there is little understanding of their impacts on ecosystem carbon fluxes. To address this, the impacts of a number of different, commonly occurring, extreme events and their subsequent browning (vegetation damage) on key ecosystem CO2 fluxes were assessed during the growing season at a range of event damaged sites of shrub dominated vegetation. Sites were located from the boreal to High Arctic (64˚N-79˚N) and had been previously been damaged by events of frost-drought, extreme winter warming, ground icing and caterpillar (Epirrita autumnata) outbreaks. Plot-level CO2 fluxes of Ecosystem Exchange (NEE), Gross Primary Productivity (GPP) and Ecosystem Respiration (Reco) were assessed using vegetation chambers. At a sub-set of sites, NDVI (greenness) in flux plots was also assessed by hand-held proximal sensor, allowing the relationship between NDVI of damage plots to CO2 flux to be calculated. Despite the contrasting sites and drivers, damage had consistent, major impacts on all fluxes. All sites showed reductions in GPP and NEE with increasing damage, despite efflux from Reco also declining with damage. When scaled to site-level, reductions of up to 81% of NEE, 51% of GPP and 37% of Reco were observed. In the plot-level NDVI-flux relationship, NDVI was shown to explain up to 91% of variation in GPP, and therefore supports the use of NDVI for estimating changes in ecosystem CO2 flux at larger scales in regions where browning has been driven by extreme events. This work is the first attempt to quantify the impacts of different event drivers of arctic browning on the main ecosystem CO2 fluxes at a range of sites. These insights provide an important step towards incorporating extreme events into our understanding of how ecosystem CO2 balance at high latitudes will respond to continuing climate change.

Paraheliotropic leaf movement in Siratro as a protective mechanism against drought-induced damage to primary photosynthetic reactions: damage by excessive light and heat.

PubMed

Ludlow, M M; Björkman, O

1984-11-01

Damage to primary photosynthetic reactions by drought, excess light and heat in leaves of Macroptilium atropurpureum Dc. cv. Siratro was assessed by measurements of chlorophyll fluorescence emission kinetics at 77 K (-196°C). Paraheliotropic leaf movement protected waterstressed Siratro leaves from damage by excess light (photoinhibition), by heat, and by the interactive effects of excess light and high leaf temperatures. When the leaves were restrained to a horizontal position, photoinhibition occurred and the degree of photoinhibitory damage increased with the time of exposure to high levels of solar radiation. Severe inhibition was followed by leaf death, but leaves gradually recovered from moderate damage. This drought-induced photoinhibitory damage seemed more closely related to low leaf water potential than to low leaf conductance. Exposure to leaf temperatures above 42°C caused damage to the photosynthetic system even in the dark and leaves died at 48°C. Between 42 and 48°C the degree of heat damage increased with the time of exposure, but recovery from moderate heat damage occurred over several days. The threshold temperature for direct heat damage increased with the growth temperature regime, but was unaffected by water-stress history or by current leaf water status. No direct heat damage occurred below 42°C, but in water-stressed plants photoinhibition increased with increasing leaf temperature in the range 31-42°C and with increasing photon flux density up to full sunglight values. Thus, water stress evidently predisposes the photosynthetic system to photoinhibition and high leaf temperature exacerbates this photoinhibitory damage. It seems probable that, under the climatic conditions where Siratro occurs in nature, but in the absence of paraheliotropic leaf movement, photoinhibitory damage would occur more frequently during drought than would direct heat damage.

Particle damage sources for fused silica optics and their mitigation on high energy laser systems.

PubMed

Bude, J; Carr, C W; Miller, P E; Parham, T; Whitman, P; Monticelli, M; Raman, R; Cross, D; Welday, B; Ravizza, F; Suratwala, T; Davis, J; Fischer, M; Hawley, R; Lee, H; Matthews, M; Norton, M; Nostrand, M; VanBlarcom, D; Sommer, S

2017-05-15

High energy laser systems are ultimately limited by laser-induced damage to their critical components. This is especially true of damage to critical fused silica optics, which grows rapidly upon exposure to additional laser pulses. Much progress has been made in eliminating damage precursors in as-processed fused silica optics (the advanced mitigation process, AMP3), and very high damage resistance has been demonstrated in laboratory studies. However, the full potential of these improvements has not yet been realized in actual laser systems. In this work, we explore the importance of additional damage sources-in particular, particle contamination-for fused silica optics fielded in a high-performance laser environment, the National Ignition Facility (NIF) laser system. We demonstrate that the most dangerous sources of particle contamination in a system-level environment are laser-driven particle sources. In the specific case of the NIF laser, we have identified the two important particle sources which account for nearly all the damage observed on AMP3 optics during full laser operation and present mitigations for these particle sources. Finally, with the elimination of these laser-driven particle sources, we demonstrate essentially damage free operation of AMP3 fused silica for ten large optics (a total of 12,000 cm 2 of beam area) for shots from 8.6 J/cm 2 to 9.5 J/cm 2 of 351 nm light (3 ns Gaussian pulse shapes). Potentially many other pulsed high energy laser systems have similar particle sources, and given the insight provided by this study, their identification and elimination should be possible. The mitigations demonstrated here are currently being employed for all large UV silica optics on the National Ignition Facility.

Investigation of high-energy ion-irradiated MA957 using synchrotron radiation under in-situ tension

DOE PAGES

Mo, Kun; Yun, Di; Miao, Yinbin; ...

2016-01-02

In this paper, an MA957 oxide dispersion-strengthened (ODS) alloy was irradiated with high-energy ions in the Argonne Tandem Linac Accelerator System. Fe ions at an energy of 84 MeV bombarded MA957 tensile specimens, creating a damage region similar to 7.5 μm in depth; the peak damage (similar to 40 dpa) was estimated to be at similar to 7 μm from the surface. Following the irradiation, in-situ high-energy X-ray diffraction measurements were performed at the Advanced Photon Source in order to study the dynamic deformation behavior of the specimens after ion irradiation damage. In-situ X-ray measurements taken during tensile testing ofmore » the ion-irradiated MA957 revealed a difference in loading behavior between the irradiated and un-irradiated regions of the specimen. At equivalent applied stresses, lower lattice strains were found in the radiation-damaged region than those in the un-irradiated region. This might be associated with a higher level of Type II stresses as a result of radiation hardening. The study has demonstrated the feasibility of combining high-energy ion radiation and high-energy synchrotron X-ray diffraction to study materials' radiation damage in a dynamic manner.« less

Effects of acetaldehyde and L-carnitine on morphology and enzyme activity of myocardial mitochondria in rats.

PubMed

Jin, Yuan-Zhe; Wang, Guo-Feng; Wang, Qi; Zhang, Xue-Ying; Yan, Bin; Hu, Wei-Na

2014-12-01

This study aimed to investigate the effects of acetaldehyde (AA) and L-carnitine (LC) on morphology and enzyme activity of myocardial mitochondria in rats. Sixty-five Wistar rats were randomly divided into 4 groups: the control group (n = 20), the AA low-dose group (n = 15), the AA high-dose group (n = 15) and the AA + LC group (n = 15). Different doses (110 mg/kg and 220 mg/kg) AA was injected intraperitoneally once a day for 4 weeks. After 4 weeks administration, transmission electron microscope (TEM) observation of morphology of rat myocardial mitochondria was performed. Serum levels of succinate dehydrogenase (SDH), superoxide dismutase (SOD), malondialdehyde (MDA) and cardiac troponin I (cTnI) were detected to evaluate mitochondrial enzymes activities. Light micrograph of rat myocardiocytes in the control group showing normal architecture of myocytes. The numerical density and number of mitochondria in both low-dose and high-dose AA groups were lower than that of the control group. After administration of LC, the rats in the AA + LC group showed an obvious increase in the numerical density and number of mitochondria. TEM showed that both low-dose and high-dose AA could induce myocardial mitochondrial damage in rats in a dose-dependent manner, such as mitochondrial swelling, disruptions of crest and membrane, mitochondrial deficiency. The degree of mitochondrial damage of the AA + LC group was significantly decreased after administration of LC. Our results showed that serum levels of SDH and SOD in the AA + LC and control groups were also higher than those of the low-dose and high-dose AA groups; while the MDA level in the AA + LC and control groups were lower than that of the low-dose and high-dose AA groups. The low-dose AA, high-dose AA and AA + LC groups exhibited a higher level of serum cTnI than that of the control group. However, there was no significant difference in serum cTnI level among the low-dose AA, high-dose AA and AA + LC groups. Our findings indicate that AA may lead to myocardial mitochondrial damage and the induction of enzyme activity in rats, while administration of LC could alleviate AA-related damage of rat myocardial mitochondria.

An anthocyanin/polyphenolic-rich fruit juice reduces oxidative DNA damage and increases glutathione level in healthy probands.

PubMed

Weisel, Tamara; Baum, Matthias; Eisenbrand, Gerhard; Dietrich, Helmut; Will, Frank; Stockis, Jean-Pierre; Kulling, Sabine; Rüfer, Corinna; Johannes, Christian; Janzowski, Christine

2006-04-01

Oxidative cell damage is involved in the pathogenesis of atherosclerosis, cancer, diabetes and other diseases. Uptake of fruit juice with especially high content of antioxidant flavonoids/polyphenols, might reduce oxidative cell damage. Therefore, an intervention study was performed with a red mixed berry juice [trolox equivalent antioxidative capacity (TEAC): 19.1 mmol/L trolox] and a corresponding polyphenol-depleted juice (polyphenols largely removed, TEAC 2.4 mmol/L trolox), serving as control. After a 3-week run-in period, 18 male probands daily consumed 700 mL juice, and 9 consumed control juice, in a 4-week intervention, followed by a 3-week wash-out. Samples were collected weekly to analyze DNA damage (comet assay), lipid peroxidation (plasma malondialdehyde: HPLC/fluorescence; urinary isoprostanes: GC-MS), blood glutathione (photometrically), DNA-binding activity of nuclear factor-kappaB (ELISA) and plasma carotenoid/alpha-tocopherol levels (HPLC-DAD). During intervention with the fruit juice, a decrease of oxidative DNA damage (p<5x10(-4)) and an increase of reduced glutathione (p<5x10(-4)) and of glutathione status (p<0.05) were observed, which returned to the run-in levels in the subsequent wash-out phase. The other biomarkers were not significantly modulated by the juice supplement. Intervention with the control juice did not result in reduction of oxidative damage. In conclusion, the fruit juice clearly reduces oxidative cell damage in healthy probands.

Preventive Effect of the Korean Traditional Health Drink (Taemyeongcheong) on Acetaminophen-Induced Hepatic Damage in ICR Mice

PubMed Central

Yi, Ruo-Kun; Song, Jia-Le; Lim, Yaung-Iee; Kim, Yong-Kyu; Park, Kun-Young

2015-01-01

This study was to investigate the preventive effect of taemyeongcheong (TMC, a Korean traditional health drink) on acetaminophen (APAP, 800 mg/kg BW)-induced hepatic damage in ICR mice. TMC is prepared from Saururus chinensis, Taraxacum officinale, Zingiber officinale, Cirsium setidens, Salicornia herbacea, and Glycyrrhizae. A high dose of TMC (500 mg/kg BW) was found to decrease APAP-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase. TMC pretreatment also increased the hepatic levels of hepatic catalase, superoxide dismutase, glutathione peroxidase, and glutathione, and reduced serum levels of the inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 in mice administered APAP (P<0.05). TMC (500 mg/kg BW) reduced hepatic mRNA levels of TNF-α, IL-1β, IL-6, COX-2, and iNOS by 87%, 84%, 89%, 85%, and 88%, respectively, in mice treated with APAP (P<0.05). Furthermore, histological observations suggested TMC pretreatment dose-dependently prevented APAP-induced hepatocyte damage. These results suggest that TMC could be used as a functional health drink to prevent hepatic damage. PMID:25866750

Preventive Effect of the Korean Traditional Health Drink (Taemyeongcheong) on Acetaminophen-Induced Hepatic Damage in ICR Mice.

PubMed

Yi, Ruo-Kun; Song, Jia-Le; Lim, Yaung-Iee; Kim, Yong-Kyu; Park, Kun-Young

2015-03-01

This study was to investigate the preventive effect of taemyeongcheong (TMC, a Korean traditional health drink) on acetaminophen (APAP, 800 mg/kg BW)-induced hepatic damage in ICR mice. TMC is prepared from Saururus chinensis, Taraxacum officinale, Zingiber officinale, Cirsium setidens, Salicornia herbacea, and Glycyrrhizae. A high dose of TMC (500 mg/kg BW) was found to decrease APAP-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase. TMC pretreatment also increased the hepatic levels of hepatic catalase, superoxide dismutase, glutathione peroxidase, and glutathione, and reduced serum levels of the inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 in mice administered APAP (P<0.05). TMC (500 mg/kg BW) reduced hepatic mRNA levels of TNF-α, IL-1β, IL-6, COX-2, and iNOS by 87%, 84%, 89%, 85%, and 88%, respectively, in mice treated with APAP (P<0.05). Furthermore, histological observations suggested TMC pretreatment dose-dependently prevented APAP-induced hepatocyte damage. These results suggest that TMC could be used as a functional health drink to prevent hepatic damage.

Predisposition to Cancer Caused by Genetic and Functional Defects of Mammalian Atad5

PubMed Central

Bell, Daphne W.; Chatterjee, Raghunath; Park, Hee-Dong; Fox, Jennifer; Ishiai, Masamichi; Rudd, Meghan L.; Pollock, Lana M.; Fogoros, Sarah K.; Mohamed, Hassan; Hanigan, Christin L.; Zhang, Suiyuan; Cruz, Pedro; Renaud, Gabriel; Hansen, Nancy F.; Cherukuri, Praveen F.; Borate, Bhavesh; McManus, Kirk J.; Stoepel, Jan; Sipahimalani, Payal; Godwin, Andrew K.; Sgroi, Dennis C.; Merino, Maria J.; Elliot, Gene; Elkahloun, Abdel; Vinson, Charles; Takata, Minoru; Mullikin, James C.; Wolfsberg, Tyra G.; Hieter, Philip; Lim, Dae-Sik; Myung, Kyungjae

2011-01-01

ATAD5, the human ortholog of yeast Elg1, plays a role in PCNA deubiquitination. Since PCNA modification is important to regulate DNA damage bypass, ATAD5 may be important for suppression of genomic instability in mammals in vivo. To test this hypothesis, we generated heterozygous (Atad5+/m) mice that were haploinsuffficient for Atad5. Atad5+/m mice displayed high levels of genomic instability in vivo, and Atad5+/m mouse embryonic fibroblasts (MEFs) exhibited molecular defects in PCNA deubiquitination in response to DNA damage, as well as DNA damage hypersensitivity and high levels of genomic instability, apoptosis, and aneuploidy. Importantly, 90% of haploinsufficient Atad5+/m mice developed tumors, including sarcomas, carcinomas, and adenocarcinomas, between 11 and 20 months of age. High levels of genomic alterations were evident in tumors that arose in the Atad5+/m mice. Consistent with a role for Atad5 in suppressing tumorigenesis, we also identified somatic mutations of ATAD5 in 4.6% of sporadic human endometrial tumors, including two nonsense mutations that resulted in loss of proper ATAD5 function. Taken together, our findings indicate that loss-of-function mutations in mammalian Atad5 are sufficient to cause genomic instability and tumorigenesis. PMID:21901109

Walking the Oxidative Stress Tightrope: A Perspective from the Naked Mole-Rat, the Longest-Living Rodent

PubMed Central

Rodriguez, Karl A.; Wywial, Ewa; Perez, Viviana I.; Lambert, Adrian J.; Edrey, Yael H.; Lewis, Kaitlyn N.; Grimes, Kelly; Lindsey, Merry L.; Brand, Martin D.; Buffenstein, Rochelle

2014-01-01

Reactive oxygen species (ROS), by-products of aerobic metabolism, cause oxidative damage to cells and tissue and not surprisingly many theories have arisen to link ROS-induced oxidative stress to aging and health. While studies clearly link ROS to a plethora of divergent diseases, their role in aging is still debatable. Genetic knock-down manipulations of antioxidants alter the levels of accrued oxidative damage, however, the resultant effect of increased oxidative stress on lifespan are equivocal. Similarly the impact of elevating antioxidant levels through transgenic manipulations yield inconsistent effects on longevity. Furthermore, comparative data from a wide range of endotherms with disparate longevity remain inconclusive. Many long-living species such as birds, bats and mole-rats exhibit high-levels of oxidative damage, evident already at young ages. Clearly, neither the amount of ROS per se nor the sensitivity in neutralizing ROS are as important as whether or not the accrued oxidative stress leads to oxidative-damage-linked age-associated diseases. In this review we examine the literature on ROS, its relation to disease and the lessons gleaned from a comparative approach based upon species with widely divergent responses. We specifically focus on the longest lived rodent, the naked mole-rat, which maintains good health and provides novel insights into the paradox of maintaining both an extended healthspan and lifespan despite high oxidative stress from a young age. PMID:21736541

Characteristics and oxidative stress on rats and traffic policemen of ambient fine particulate matter from Shenyang.

PubMed

Ma, Mingyue; Li, Shuyin; Jin, Huanrong; Zhang, Yumin; Xu, Jia; Chen, Dongmei; Kuimin, Chen; Yuan, Zhou; Xiao, Chunling

2015-09-01

Fine particulate matter (PM2.5) pollution is becoming serious in China. This study aimed to investigate the impact of PM2.5 on DNA damage in Shenyang city. The concentration and composition of PM2.5 in traffic policemen's working sites including fields and indoor offices were obtained. Blood samples of field and office policemen were collected to detect DNA damage by Comet assay. Rats were used to further analyzing the oxidative DNA damage. The average concentration of PM2.5 in exposed group was significantly higher than that in control group. Composition analysis revealed that toxic heavy metal and polycyclic aromatic hydrocarbon substances were main elements of this PM2.5. DNA damage in field policemen was significantly higher than those in non-field group. Moreover, animal studies confirmed the oxidative DNA damage induced by PM2.5. Taken together, high DNA damages are found in the Shenyang traffic policemen and rats exposed to high level of airborne PM2.5. Copyright © 2015 Elsevier B.V. All rights reserved.

Hepatoprotective activity of sea cucumber Phyllophorus sp. extract in carp (Cyprinus carpio)

NASA Astrophysics Data System (ADS)

Sulmartiwi, Laksmi; Triastuti, Juni; Andriyono, Sapto; Umami, Mardiah Rahma

2017-02-01

Many procedures continuously in aquaculture and scientific research like tagging and vaccinating cause pain, involving damaging tissue and also cause stress responses in fish. Stress responses in fish influence liver because liver have vital role to supply energy and metabolism. Histology alteration in liver is caused by stress response like changes of vacuolation hepatocyte and characteristic colour. Triterpenoid was known had hepatoprotective activity. One of marine organism contained triterpenoid was sea cucumber. Result of research showed that liver tissue in fish with injected acetic acid 5 % (in upper lip) as pain stimulus have histopathology damages such as pyknosis (medium damage level) and oedema (heavy damage level) after 8 hour injection. Injected Lidocaine 1mg/fish as analgesic drug have histopathology damages such as oedema (heavy damages level), necrosis and pyknosis (low damages level). Injected acetic acid 5 % (in upper lip) and ethanolic extract of sea cucumber Phyllophorus sp. dose 5 mg/50 gr body weight shown histopathology damages such as necrosis, edema (medium damage level) and pyknosis (low damage level).

Experimental Study on Damage Detection in Timber Specimens Based on an Electromechanical Impedance Technique and RMSD-Based Mahalanobis Distance

PubMed Central

Wang, Dansheng; Wang, Qinghua; Wang, Hao; Zhu, Hongping

2016-01-01

In the electromechanical impedance (EMI) method, the PZT patch performs the functions of both sensor and exciter. Due to the high frequency actuation and non-model based characteristics, the EMI method can be utilized to detect incipient structural damage. In recent years EMI techniques have been widely applied to monitor the health status of concrete and steel materials, however, studies on application to timber are limited. This paper will explore the feasibility of using the EMI technique for damage detection in timber specimens. In addition, the conventional damage index, namely root mean square deviation (RMSD) is employed to evaluate the level of damage. On that basis, a new damage index, Mahalanobis distance based on RMSD, is proposed to evaluate the damage severity of timber specimens. Experimental studies are implemented to detect notch and hole damage in the timber specimens. Experimental results verify the availability and robustness of the proposed damage index and its superiority over the RMSD indexes. PMID:27782088

Experimental Study on Damage Detection in Timber Specimens Based on an Electromechanical Impedance Technique and RMSD-Based Mahalanobis Distance.

PubMed

Wang, Dansheng; Wang, Qinghua; Wang, Hao; Zhu, Hongping

2016-10-22

In the electromechanical impedance (EMI) method, the PZT patch performs the functions of both sensor and exciter. Due to the high frequency actuation and non-model based characteristics, the EMI method can be utilized to detect incipient structural damage. In recent years EMI techniques have been widely applied to monitor the health status of concrete and steel materials, however, studies on application to timber are limited. This paper will explore the feasibility of using the EMI technique for damage detection in timber specimens. In addition, the conventional damage index, namely root mean square deviation (RMSD) is employed to evaluate the level of damage. On that basis, a new damage index, Mahalanobis distance based on RMSD, is proposed to evaluate the damage severity of timber specimens. Experimental studies are implemented to detect notch and hole damage in the timber specimens. Experimental results verify the availability and robustness of the proposed damage index and its superiority over the RMSD indexes.

Unexpected effect of dry olive leaf extract on the level of DNA damage in lymphocytes of lead intoxicated workers, before and after CaNa2EDTA chelation therapy.

PubMed

Čabarkapa, Andrea; Dekanski, Dragana; Živković, Lada; Milanović-Čabarkapa, Mirjana; Bajić, Vladan; Topalović, Dijana; Giampieri, Francesca; Gasparrini, Massimiliano; Battino, Maurizio; Spremo-Potparević, Biljana

2017-08-01

The CaNa 2 EDTA chelation therapy is often practiced with antioxidant supplementation. Dry olive leaf extract (DOLE) is natural product with antioxidant and DNA protective properties. The effects of DOLE on the levels of DNA damage were investigated ex vivo in peripheral blood lymphocytes (PBLs) of 19 workers occupationally exposed to lead (Pb), before and after CaNa 2 EDTA chelation therapy. DOLE demonstrated pronounced radical scavenging activity in concentrations ≥1 mg/mL, and showed no genotoxicity per se, in concentrations 0.125-1 mg/mL. The level of DNA damage in PBLs of workers before chelation therapy was elevated (24.21 ± 14.26) compared to controls (6.0 ± 3.37). The incubation of PBLs before chelation therapy with selected concentration of DOLE lead to a severe increase of DNA damage (64.03 ± 20.96), exhibiting prooxidant rather than antioxidant effect. After the five-day CaNa 2 EDTA chelation regimen, DNA damage in PBLs of workers decreased (8.26 ± 4.62) significantly compared to baseline. Treatment of PBLs with DOLE after chelation, again produced high level of damage (41.82 ± 23.17) and the acute prooxidant effects of DOLE remained, but, DNA damage was less severe than before chelation. The DOLE exhibits prooxidant effect in presence of Pb in lymphocytes of exposed workers, and its effect is less pronounced following the removal of Pb after standard chelation therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Damage and protection cost curves for coastal floods within the 600 largest European cities

PubMed Central

Prahl, Boris F.; Boettle, Markus; Costa, Luís; Kropp, Jürgen P.; Rybski, Diego

2018-01-01

The economic assessment of the impacts of storm surges and sea-level rise in coastal cities requires high-level information on the damage and protection costs associated with varying flood heights. We provide a systematically and consistently calculated dataset of macroscale damage and protection cost curves for the 600 largest European coastal cities opening the perspective for a wide range of applications. Offering the first comprehensive dataset to include the costs of dike protection, we provide the underpinning information to run comparative assessments of costs and benefits of coastal adaptation. Aggregate cost curves for coastal flooding at the city-level are commonly regarded as by-products of impact assessments and are generally not published as a standalone dataset. Hence, our work also aims at initiating a more critical discussion on the availability and derivation of cost curves. PMID:29557944

Oxidative Stress, Bone Marrow Failure, and Genome Instability in Hematopoietic Stem Cells

PubMed Central

Richardson, Christine; Yan, Shan; Vestal, C. Greer

2015-01-01

Reactive oxygen species (ROS) can be generated by defective endogenous reduction of oxygen by cellular enzymes or in the mitochondrial respiratory pathway, as well as by exogenous exposure to UV or environmental damaging agents. Regulation of intracellular ROS levels is critical since increases above normal concentrations lead to oxidative stress and DNA damage. A growing body of evidence indicates that the inability to regulate high levels of ROS leading to alteration of cellular homeostasis or defective repair of ROS-induced damage lies at the root of diseases characterized by both neurodegeneration and bone marrow failure as well as cancer. That these diseases may be reflective of the dynamic ability of cells to respond to ROS through developmental stages and aging lies in the similarities between phenotypes at the cellular level. This review summarizes work linking the ability to regulate intracellular ROS to the hematopoietic stem cell phenotype, aging, and disease. PMID:25622253

High basal metabolic rate does not elevate oxidative stress during reproduction in laboratory mice.

PubMed

Brzęk, Paweł; Książek, Aneta; Ołdakowski, Łukasz; Konarzewski, Marek

2014-05-01

Increased oxidative stress (OS) has been suggested as a physiological cost of reproduction. However, previous studies reported ambiguous results, with some even showing a reduction of oxidative damage during reproduction. We tested whether the link between reproduction and OS is mediated by basal metabolic rate (BMR), which has been hypothesized to affect both the rate of radical oxygen species production and antioxidative capacity. We studied the effect of reproduction on OS in females of laboratory mice divergently selected for high (H-BMR) and low (L-BMR) BMR, previously shown to differ with respect to parental investment. Non-reproducing L-BMR females showed higher oxidative damage to lipids (quantified as the level of malondialdehyde in internal organ tissues) and DNA (quantified as the level of 8-oxodG in blood serum) than H-BMR females. Reproduction did not affect oxidative damage to lipids in either line; however, it reduced damage to DNA in L-BMR females. Reproduction increased catalase activity in liver (significantly stronger in L-BMR females) and decreased it in kidneys. We conclude that the effect of reproduction on OS depends on the initial variation in BMR and varies between studied internal organs and markers of OS.

The impact of plant chemical diversity on plant-herbivore interactions at the community level.

PubMed

Salazar, Diego; Jaramillo, Alejandra; Marquis, Robert J

2016-08-01

Understanding the role of diversity in ecosystem processes and species interactions is a central goal of ecology. For plant-herbivore interactions, it has been hypothesized that when plant species diversity is reduced, loss of plant biomass to herbivores increases. Although long-standing, this hypothesis has received mixed support. Increasing plant chemical diversity with increasing plant taxonomic diversity is likely to be important for plant-herbivore interactions at the community level, but the role of chemical diversity is unexplored. Here we assess the effect of volatile chemical diversity on patterns of herbivore damage in naturally occurring patches of Piper (Piperaceae) shrubs in a Costa Rican lowland wet forest. Volatile chemical diversity negatively affected total, specialist, and generalist herbivore damage. Furthermore, there were differences between the effects of high-volatility and low-volatility chemical diversity on herbivore damage. High-volatility diversity reduced specialist herbivory, while low-volatility diversity reduced generalist herbivory. Our data suggest that, although increased plant diversity is expected to reduce average herbivore damage, this pattern is likely mediated by the diversity of defensive compounds and general classes of anti-herbivore traits, as well as the degree of specialization of the herbivores attacking those plants.

Protective Effect of Edaravone Against Aβ25-35-Induced Mitochondrial Oxidative Damage in SH-SY5Y Cells.

PubMed

Zhang, G-L; Zhang, L; Guo, Y-Y; Ma, Z-L; Wang, H-Y; Li, T; Liu, J; Du, Y; Yao, L; Li, T-T; Du, J-M

2017-05-20

Amyloid-β (Aβ)-induced oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). Recent studies show that Aβ accumulation may lead to mitochondrial oxidative damage. In the present study, we investigated the protective effect of edaravone on mitochondrial damage in SH-SY5Y cells treated with Aβ25-35. SH-SY5Y cells were pre-treated with 20, 40 or 80 μM edaravone before treatment with 25 μM Aβ25-35. After 24h cell culture, cellular apoptosis, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), ATP levels and mitochondrial morphology were evaluated. SH-SY5Y cells exposed to Aβ25-35 had high levels of apoptosis and ROS; loss of ΔΨm, decreased ATP levels and presence of mitochondrial swelling. However, these effects were significantly inhibited by edaravone pre-treatment. These results indicate that edaravone prevents mitochondria oxidative damage caused by Aβ in SH-SY5Y cells, which suggests that it may have potential clinical application in AD therapy.

IGF-1 Alleviates High Fat Diet-Induced Myocardial Contractile Dysfunction: Role of Insulin Signaling and Mitochondrial Function

PubMed Central

Zhang, Yingmei; Yuan, Ming; Bradley, Katherine M.; Dong, Feng; Anversa, Piero; Ren, Jun

2012-01-01

Obesity is often associated with reduced plasma IGF-1 levels, oxidative stress, mitochondrial damage and cardiac dysfunction. This study was designed to evaluate the impact of IGF-1 on high fat diet-induced oxidative, myocardial, geometric and mitochondrial responses. FVB and cardiomyocyte-specific IGF-1 overexpression transgenic mice were fed a low (10%) or high fat (45%) diet to induce obesity. High fat diet feeding led to glucose intolerance, elevated plasma levels of leptin, interleukin-6, insulin and triglyceride as well as reduced circulating IGF-1 levels. Echocardiography revealed reduced fractional shortening, increased end systolic and diastolic diameter, increased wall thickness, and cardiac hypertrophy in high fat-fed FVB mice. High fat diet promoted ROS generation, apoptosis, protein and mitochondrial damage, reduced ATP content, cardiomyocyte cross-sectional area, contractile and intracellular Ca2+ dysregulation, including depressed peak shortening and maximal velocity of shortening/relengthening, prolonged duration of relengthening, and dampened intracellular Ca2+ rise and clearance. Western blot analysis revealed disrupted phosphorylation of insulin receptor, post-receptor signaling molecules IRS-1 (tyrosine/serine phosphorylation), Akt, GSK3β, Foxo3a, mTOR, as well as downregulated expression of mitochondrial proteins PPARγ coactivator 1α (PGC1α) and UCP-2. Intriguingly, IGF-1 mitigated high fat diet feeding-induced alterations in ROS, protein and mitochondrial damage, ATP content, apoptosis, myocardial contraction, intracellular Ca2+ handling and insulin signaling, but not whole body glucose intolerance and cardiac hypertrophy. Exogenous IGF-1 treatment also alleviated high fat diet-induced cardiac dysfunction. Our data revealed that IGF-1 alleviates high fat diet-induced cardiac dysfunction despite persistent cardiac remodeling, possibly due to preserved cell survival, mitochondrial function and insulin signaling. PMID:22275536

Development of martensitic steels for high neutron damage applications

NASA Astrophysics Data System (ADS)

Gelles, D. S.

1996-12-01

Martensitic stainless steels have been developed for both in-core applications in advanced liquid metal fast breeder reactors (LMFBR) and for first wall and structural materials applications for commercial fusion reactors. It can now be shown that these steels can be expected to maintain properties to levels as high as 175 or 200 dpa, respectively. The 12Cr1Mo0.5W0.2C alloy HT-9 has been extensively tested for LMFBR applications and shown to resist radiation damage, providing a creep and swelling resistant alternative to austenitic steels. Degradation of fracture toughness and Charpy impact properties have been observed, but properties are sufficient to provide reliable service. In comparison, alloys with lower chromium contents are found to decarburize in contact with liquid sodium and are therefore not recommended. Tungsten stabilized martensitic stainless steels have appropriate properties for fusion applications. Radioactivity levels are benign less than 500 years after service, radiation damage resistance is excellent, including impact properties, and swelling is modest. This report describes the history of the development effort.

Factors that contribute to biomarker responses in humans including a study in individuals taking Vitamin C supplementation.

PubMed

Anderson, D

2001-09-01

It is possible in many situations to identify humans exposed to potentially toxic materials in the workplace and in the environment. As in most human studies, there tends to be a high degree of interindividual variability in response to chemical insults. Some non-exposed control individuals exhibit as high a level of damage as some exposed individuals and some of these have levels of damage as low as many of the controls. Thus, it is only the mean values of the groups that can substantiate an exposure-related problem; the data on an individual basis are still of limited use. While human lymphocytes remain the most popular cell type for monitoring purposes, sperm, buccal, nasal, epithelial and placental cells are also used. However, for interpretation of responses, the issue of confounding factors must be addressed. There are endogenous confounding factors, such as age, gender, and genetic make-up and exogenous ones, including lifestyle habits (smoking, drinking, etc.) There are biomarkers of exposure, effect/response and susceptibility and the last may be influenced by the genotype and polymorphism genes existing in a population. From our own studies, confounding effects on cytogenetic damage and ras oncoproteins will be considered in relation to workers exposed to vinyl chloride and petroleum emissions and to volunteers taking Vitamin C supplementation. Smoking history, exposure and duration of employment affected the worker studies. For petroleum emissions, so did gender and season of exposure. For the non-smoking volunteer Vitamin C supplementation study, cholesterol levels, plasma Vitamin C levels, lipid peroxidation products and DNA damage in the Comet assay were also measured. Gender affected differences in Vitamin C levels, antioxidant capacity and the number of chromosome aberrations induced by bleomycin challenge in vitro. The results were the same for both high and low cholesterol subjects. The relationship between biomarkers and the various factors which affect them is complex. Sometimes the variables are not completely independent of each other.

(p)ppGpp-Dependent Persisters Increase the Fitness of Escherichia coli Bacteria Deficient in Isoaspartyl Protein Repair.

PubMed

VandenBerg, Kelsey E; Ahn, Sarah; Visick, Jonathan E

2016-09-01

The l-isoaspartyl protein carboxyl methyltransferase (PCM) repairs protein damage resulting from spontaneous conversion of aspartyl or asparaginyl residues to isoaspartate and increases long-term stationary-phase survival of Escherichia coli under stress. In the course of studies intended to examine PCM function in metabolically inactive cells, we identified pcm as a gene whose mutation influences the formation of ofloxacin-tolerant persisters. Specifically, a Δpcm mutant produced persisters for an extended period in stationary phase, and a ΔglpD mutation drastically increased persisters in a Δpcm background, reaching 23% of viable cells. The high-persister double mutant showed much higher competitive fitness than the pcm mutant in competition with wild type during long-term stationary phase, suggesting a link between persistence and the mitigation of unrepaired protein damage. We hypothesized that reduced metabolism in the high-persister strain might retard protein damage but observed no gross differences in metabolism relative to wild-type or single-mutant strains. However, methylglyoxal, which accumulates in glpD mutants, also increased fitness, suggesting a possible mechanism. High-level persister formation in the Δpcm ΔglpD mutant was dependent on guanosine pentaphosphate [(p)ppGpp] and polyphosphate. In contrast, persister formation in the Δpcm mutant was (p)ppGpp independent and thus may occur by a distinct pathway. We also observed an increase in conformationally unstable proteins in the high-persister strain and discuss this as a possible trigger for persistence as a response to unrepaired protein damage. Protein damage is an important factor in the survival and function of cells and organisms. One specific form of protein damage, the formation of the abnormal amino acid isoaspartate, can be repaired by a nearly universally conserved enzyme, PCM. PCM-directed repair is associated with stress survival and longevity in bacteria, insects, worms, plants, mice, and humans, but much remains to be learned about the specific effects of protein damage and repair. This paper identifies an unexpected connection between isoaspartyl protein damage and persisters, subpopulations in bacterial cultures showing increased tolerance to antibiotics. In the absence of PCM, the persister population in Escherichia coli bacteria increased, especially if the metabolic gene glpD was also mutated. High levels of persisters in pcm glpD double mutants correlated with increased fitness of the bacteria in a competition assay, and the fitness was dependent on the signal molecule (p)ppGpp; this may represent an alternative pathway for responding to protein damage. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Endogenous melatonin and oxidatively damaged guanine in DNA

PubMed Central

Davanipour, Zoreh; Poulsen, Henrik E; Weimann, Allan; Sobel, Eugene

2009-01-01

Background A significant body of literature indicates that melatonin, a hormone primarily produced nocturnally by the pineal gland, is an important scavenger of hydroxyl radicals and other reactive oxygen species. Melatonin may also lower the rate of DNA base damage resulting from hydroxyl radical attack and increase the rate of repair of that damage. This paper reports the results of a study relating the level of overnight melatonin production to the overnight excretion of the two primary urinary metabolites of the repair of oxidatively damaged guanine in DNA. Methods Mother-father-daughter(s) families (n = 55) were recruited and provided complete overnight urine samples. Total overnight creatinine-adjusted 6-sulphatoxymelatonin (aMT6s/Cr) has been shown to be highly correlated with total overnight melatonin production. Urinary 8-oxo-7,8-dihydro-guanine (8-oxoGua) results from the repair of DNA or RNA guanine via the nucleobase excision repair pathway, while urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) may possibly result from the repair of DNA guanine via the nucleotide excision repair pathway. Total overnight urinary levels of 8-oxodG and 8-oxoGua are therefore a measure of total overnight guanine DNA damage. 8-oxodG and 8-oxoGua were measured using a high-performance liquid chromatography-electrospray ionization tandem mass spectrometry assay. The mother, father, and oldest sampled daughter were used for these analyses. Comparisons between the mothers, fathers, and daughters were calculated for aMT6s/Cr, 8-oxodG, and 8-oxoGua. Regression analyses of 8-oxodG and 8-oxoGua on aMT6s/Cr were conducted for mothers, fathers, and daughters separately, adjusting for age and BMI (or weight). Results Among the mothers, age range 42-80, lower melatonin production (as measured by aMT6s/CR) was associated with significantly higher levels of 8-oxodG (p < 0.05), but not with 8-oxoGua. Among the fathers, age range 46-80, lower melatonin production was associated with marginally higher levels of 8-oxoGua (p < 0.07), but not with 8-oxodG. Among the daughters, no relationship was found between melatonin levels and either 8-oxodG or 8-oxoGua levels. When the mother and father data were further analyzed using only subjects older than the oldest daughter, the associations became somewhat stronger. Conclusion Low levels of endogenous melatonin production among older individuals may lead to higher levels of oxidatively damaged guanine in DNA, thereby possibly increasing the risk of developing cancer. The possible different effects of melatonin in the rates of utilization of pathways for repair of oxidatively damaged guanine in DNA identified between older women and older men are intriguing. PMID:19835624

Endogenous melatonin and oxidatively damaged guanine in DNA.

PubMed

Davanipour, Zoreh; Poulsen, Henrik E; Weimann, Allan; Sobel, Eugene

2009-10-18

A significant body of literature indicates that melatonin, a hormone primarily produced nocturnally by the pineal gland, is an important scavenger of hydroxyl radicals and other reactive oxygen species. Melatonin may also lower the rate of DNA base damage resulting from hydroxyl radical attack and increase the rate of repair of that damage. This paper reports the results of a study relating the level of overnight melatonin production to the overnight excretion of the two primary urinary metabolites of the repair of oxidatively damaged guanine in DNA. Mother-father-daughter(s) families (n = 55) were recruited and provided complete overnight urine samples. Total overnight creatinine-adjusted 6-sulphatoxymelatonin (aMT6s/Cr) has been shown to be highly correlated with total overnight melatonin production. Urinary 8-oxo-7,8-dihydro-guanine (8-oxoGua) results from the repair of DNA or RNA guanine via the nucleobase excision repair pathway, while urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) may possibly result from the repair of DNA guanine via the nucleotide excision repair pathway. Total overnight urinary levels of 8-oxodG and 8-oxoGua are therefore a measure of total overnight guanine DNA damage. 8-oxodG and 8-oxoGua were measured using a high-performance liquid chromatography-electrospray ionization tandem mass spectrometry assay. The mother, father, and oldest sampled daughter were used for these analyses. Comparisons between the mothers, fathers, and daughters were calculated for aMT6s/Cr, 8-oxodG, and 8-oxoGua. Regression analyses of 8-oxodG and 8-oxoGua on aMT6s/Cr were conducted for mothers, fathers, and daughters separately, adjusting for age and BMI (or weight). Among the mothers, age range 42-80, lower melatonin production (as measured by aMT6s/CR) was associated with significantly higher levels of 8-oxodG (p < 0.05), but not with 8-oxoGua. Among the fathers, age range 46-80, lower melatonin production was associated with marginally higher levels of 8-oxoGua (p < 0.07), but not with 8-oxodG. Among the daughters, no relationship was found between melatonin levels and either 8-oxodG or 8-oxoGua levels. When the mother and father data were further analyzed using only subjects older than the oldest daughter, the associations became somewhat stronger. Low levels of endogenous melatonin production among older individuals may lead to higher levels of oxidatively damaged guanine in DNA, thereby possibly increasing the risk of developing cancer. The possible different effects of melatonin in the rates of utilization of pathways for repair of oxidatively damaged guanine in DNA identified between older women and older men are intriguing.

Using Unmanned Aerial Vehicles (UAVs) to Modeling Tornado Impacts

NASA Astrophysics Data System (ADS)

Wagner, M.; Doe, R. K.

2017-12-01

Using Unmanned Aerial Vehicles (UAVs) to assess storm damage is a useful research tool. Benefits include their ability to access remote or impassable areas post-storm, identify unknown damages and assist with more detailed site investigations and rescue efforts. Technological advancement of UAVs mean that they can capture high resolution images often at an affordable price. These images can be used to create 3D environments to better interpret and delineate damages from large areas that would have been difficult in ground surveys. This research presents the results of a rapid response site investigation of the 29 April 2017 Canton, Texas, USA, tornado using low cost UAVs. This was a multiple, high impact tornado event measuring EF4 at maximum. Rural farmland was chosen as a challenging location to test both equipment and methodology. Such locations provide multiple impacts at a variety of scales including structural and vegetation damage and even animal fatalities. The 3D impact models allow for a more comprehensive study prior to clean-up. The results show previously unseen damages and better quantify damage impacts at the local level. 3D digital track swaths were created allowing for a more accurate track width determination. These results demonstrate how effective the use of low cost UAVs can be for rapid response storm damage assessments, the high quality of data they can achieve, and how they can help us better visualize tornado site investigations.

Dynamic Impact Analyses and Tests of Concrete Overpacks - 13638

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

Lee, Sanghoon; Cho, Sang-Soon; Kim, Ki-Young

Concrete cask is an option for spent nuclear fuel interim storage which is prevailingly used in US. A concrete cask usually consists of metallic canister which confines the spent nuclear fuel and concrete overpack. When the overpack undergoes a severe missile impact which might be caused by a tornado or an aircraft crash, it should sustain acceptable level of structural integrity so that its radiation shielding capability and the retrievability of canister are maintained. Missile impact against a concrete overpack involves two damage modes, local damage and global damage. Local damage of concrete is usually evaluated by empirical formulas whilemore » the global damage is evaluated by finite element analysis. In many cases, those two damage modes are evaluated separately. In this research, a series of numerical simulations are performed using finite element analysis to evaluate the global damage of concrete overpack as well as its local damage under high speed missile impact. We consider two types of concrete overpack, one with steel in-cased concrete without reinforcement and the other with partially-confined reinforced concrete. The numerical simulation results are compared with test results and it is shown that appropriate modeling of material failure is crucial in this analysis and the results are highly dependent on the choice of failure parameters. (authors)« less

HSP90 gene expression induced by aspirin is associated with damage remission in a chicken myocardial cell culture exposed to heat stress.

PubMed

Zhang, X; Qian, Z; Zhu, H; Tang, S; Wu, D; Zhang, M; Kemper, N; Hartung, J; Bao, E

2016-08-01

To understand the potential protection of heat shock protein 90 (HSP90) induced by aspirin against heat stress damage in chicken myocardial cells, enzyme activities related to stress damage, cytopathological changes, the expression and distribution of HSP90, and HSP90 mRNA levels in the myocardial cells exposed to heat stress (42°C) for different durations with or without aspirin administration (1 mg/ml, 2 h prior) in vitro were investigated. Significant increase of enzyme levels in the supernatant of heat-stressed myocardial cells and cellular lesions characterised by acute degeneration, karyopyknosis and karyorrhexis were observed, compared to non-treated cells. However, the lesions of cells treated with aspirin were milder, characterised by earlier recovery of enzyme levels to the control levels and no obvious heat stress-related cellular necrosis. Stronger positive signals in the cytoplasm and longer retention of HSP90 signal in nuclei were observed in aspirin-treated myocardial cells than those of only heat-stressed cells. HSP90 level in the aspirin-treated myocardial cells was 11.1-fold higher than that in non-treated cells, and remained at a high level at the early stage of heat stress, whereas it was just 4.1-fold higher in only heat-stressed cells and returned rapidly to a low level. Overexpression of HSP90 mRNA in aspirin-treated cells was observed throughout the experiment, whereas HSP90 mRNA decreased significantly only in heat-stressed cells. The early higher HSP90 expression induced by aspirin during heat stress was accompanied by decreased heat stress damage, suggesting that aspirin might play an important role in preventing myocardial cells from heat stress damage in vitro.

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.

Evaluation of Dicyphus hersperus (Heteroptera: Miridae) for biological control of Frankliniella occidentalis (Thysanoptera: Thripidae) on greenhouse tomato.

PubMed

Shipp, J L; Wang, K

2006-04-01

The effectiveness of inoculative releases of the mirid predator Dicyphus hesperus Knight for control of Frankliniella occidentalis (Pergande) on greenhouse tomatoes was evaluated in terms of suppression of the population densities of F. occidentalis and associated fruit damage in the presence of the predator over two seasonal trials. An inoculative release of one D. hesperus per plant (approximately 0.1:10 predator:prey ratio) at a high F. occidentalis population density (140 thrips per plant) suppressed the thrips population density to a significantly lower level, compared with the nonrelease greenhouse, but not below a thrips level that caused economic fruit damage. As the predator:prey ratio increased to approximately 0.5:10 D. hesperus:F. occidentalis, the mean percentage of the thrips-damaged fruit in the D. hesperus release greenhouse decreased to 1.6%. However, the amount of fruit feeding by D. hesperus was highly correlated to the availability of prey (or predator:prey ratio) under greenhouse conditions. D. hesperus-induced fruit damage occurred when the predator:prey ratio was >1:10 D. hesperus:F. occidentalis. Considering the potential risk of fruit damage by D. hesperus and the need for effective control of F. occidentalis, a 0.5-1:10 D. hesperus:F. occidentalis ratio is recommended when the thrips population density is in the range of 60-150 thrips per plant.

Effects of very low fluences of high-energy protons or iron ions on irradiated and bystander cells.

PubMed

Yang, H; Magpayo, N; Rusek, A; Chiang, I-H; Sivertz, M; Held, K D

2011-12-01

In space, astronauts are exposed to radiation fields consisting of energetic protons and high atomic number, high-energy (HZE) particles at very low dose rates or fluences. Under these conditions, it is likely that, in addition to cells in an astronaut's body being traversed by ionizing radiation particles, unirradiated cells can also receive intercellular bystander signals from irradiated cells. Thus this study was designed to determine the dependence of DNA damage induction on dose at very low fluences of charged particles. Novel techniques to quantify particle fluence have been developed at the NASA Space Radiation Biology Laboratory (NSRL) at Brookhaven National Laboratory (BNL). The approach uses a large ionization chamber to visualize the radiation beam coupled with a scintillation counter to measure fluence. This development has allowed us to irradiate cells with 1 GeV/nucleon protons and iron ions at particle fluences as low as 200 particles/cm(2) and quantify biological responses. Our results show an increased fraction of cells with DNA damage in both the irradiated population and bystander cells sharing medium with irradiated cells after low fluences. The fraction of cells with damage, manifest as micronucleus formation and 53BP1 focus induction, is about 2-fold higher than background at doses as low as ∼0.47 mGy iron ions (∼0.02 iron ions/cell) or ∼70 μGy protons (∼2 protons/cell). In the irradiated population, irrespective of radiation type, the fraction of damaged cells is constant from the lowest damaging fluence to about 1 cGy, above which the fraction of damaged cells increases with dose. In the bystander population, the level of damage is the same as in the irradiated population up to 1 cGy, but it does not increase above that plateau level with increasing dose. The data suggest that at fluences of high-energy protons or iron ions less than about 5 cGy, the response in irradiated cell populations may be dominated by the bystander response.

A Mediterranean nocturnal heavy rainfall and tornadic event. Part I: Overview, damage survey and radar analysis

NASA Astrophysics Data System (ADS)

Bech, Joan; Pineda, Nicolau; Rigo, Tomeu; Aran, Montserrat; Amaro, Jéssica; Gayà, Miquel; Arús, Joan; Montanyà, Joan; der Velde, Oscar van

2011-06-01

This study presents an analysis of a severe weather case that took place during the early morning of the 2nd of November 2008, when intense convective activity associated with a rapidly evolving low pressure system affected the southern coast of Catalonia (NE Spain). The synoptic framework was dominated by an upper level trough and an associated cold front extending from Gibraltar along the Mediterranean coast of the Iberian Peninsula to SE France, which moved north-eastward. South easterly winds in the north of the Balearic Islands and the coast of Catalonia favoured high values of 0-3 km storm relative helicity which combined with moderate MLCAPE values and high shear favoured the conditions for organized convection. A number of multicell storms and others exhibiting supercell features, as indicated by Doppler radar observations, clustered later in a mesoscale convective system, and moved north-eastwards across Catalonia. They produced ground-level strong damaging wind gusts, an F2 tornado, hail and heavy rainfall. Total lightning activity (intra-cloud and cloud to ground flashes) was also relevant, exhibiting several classical features such as a sudden increased rate before ground level severe damage, as discussed in a companion study. Remarkable surface observations of this event include 24 h precipitation accumulations exceeding 100 mm in four different observatories and 30 minute rainfall amounts up to 40 mm which caused local flash floods. As the convective system evolved northward later that day it also affected SE France causing large hail, ground level damaging wind gusts and heavy rainfall.

Fractional sunburn threshold UVR doses generate equivalent vitamin D and DNA damage in skin types I-VI, but with epidermal DNA damage gradient correlated to skin darkness.

PubMed

Shih, Barbara B; Farrar, Mark D; Cooke, Marcus S; Osman, Joanne; Langton, Abigail K; Kift, Richard; Webb, Ann R; Berry, Jacqueline L; Watson, Rachel E B; Vail, Andy; de Gruijl, Frank R; Rhodes, Lesley E

2018-05-03

Public health guidance recommends limiting sun-exposure to sub-sunburn levels, but it's unknown whether these can gain vitamin D (for musculoskeletal health) whilst avoiding epidermal DNA damage (initiates skin cancer). Well-characterised healthy humans of all skin types (I-VI; lightest to darkest skin) were exposed to a low dose-series of solar simulated UVR of 20-80% their individual sunburn threshold dose (minimal erythemal dose, MED). Significant UVR dose-responses were seen for serum 25(OH)D and whole epidermal CPD, with as little as 0.2 MED concurrently producing 25(OH)D and CPD. Notably, fractional MEDs generated equivalent levels of whole epidermal CPD and 25(OH)D across all skin types. Crucially, we demonstrated an epidermal gradient of CPD formation strongly correlated with skin darkness (r=0.74; P<0.0001), which reflected melanin content and revealed increasing protection across the skin types, ranging from darkest skin, where high CPD levels occurred superficially with none in the germinative basal layer, through to lightest skin where CPD were induced evenly across the epidermal depth. Darker skin people can be encouraged to utilise sub-sunburn UVR-exposure to enhance their vitamin D. In lighter skin people, basal cell damage occurs concurrent with vitamin D synthesis at exquisitely low UVR levels, providing an explanation for their high skin cancer incidence; greater caution is required. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Testing the Effects of dl-Alpha-Tocopherol Supplementation on Oxidative Damage, Total Antioxidant Protection and the Sex-Specific Responses of Reproductive Effort and Lifespan to Dietary Manipulation in Australian Field Crickets (Teleogryllus commodus)

PubMed Central

Archer, C. Ruth; Hempenstall, Sarah; Royle, Nick J.; Selman, Colin; Willis, Sheridan; Rapkin, James; Blount, Jon D.; Hunt, John

2015-01-01

The oxidative stress theory predicts that the accumulation of oxidative damage causes aging. More generally, oxidative damage could be a cost of reproduction that reduces survival. Both of these hypotheses have mixed empirical support. To better understand the life-history consequences of oxidative damage, we fed male and female Australian field crickets (Teleogryllus commodus) four diets differing in their protein and carbohydrate content, which have sex-specific effects on reproductive effort and lifespan. We supplemented half of these crickets with the vitamin E isoform dl-alpha-tocopherol and measured the effects of nutrient intake on lifespan, reproduction, oxidative damage and antioxidant protection. We found a clear trade-off between reproductive effort and lifespan in females but not in males. In direct contrast to the oxidative stress theory, crickets fed diets that improved their lifespan had high levels of oxidative damage to proteins. Supplementation with dl-alpha-tocopherol did not significantly improve lifespan or reproductive effort. However, males fed diets that increased their reproductive investment experienced high oxidative damage to proteins. While this suggests that male reproductive effort could elevate oxidative damage, this was not associated with reduced male survival. Overall, these results provide little evidence that oxidative damage plays a central role in mediating life-history trade-offs in T. commodus. PMID:26783958

N-Acetyl-L-cysteine protects thyroid cells against DNA damage induced by external and internal irradiation.

PubMed

Kurashige, Tomomi; Shimamura, Mika; Nagayama, Yuji

2017-11-01

We evaluated the effect of the antioxidant N-acetyl-L-cysteine (NAC) on the levels of reactive oxygen species (ROS), DNA double strand breaks (DSB) and micronuclei (MN) induced by internal and external irradiation using a rat thyroid cell line PCCL3. In internal irradiation experiments, ROS and DSB levels increased immediately after 131 I addition and then gradually declined, resulting in very high levels of MN at 24 and 48 h. NAC administration both pre- and also post- 131 I addition suppressed ROS, DSB and MN. In external irradiation experiments with a low dose (0.5 Gy), ROS and DSB increased shortly and could be prevented by NAC administration pre-, but not post-irradiation. In contrast, external irradiation with a high dose (5 Gy) increased ROS and DSB in a bimodal way: ROS and DSB levels increased immediately after irradiation, quickly returned to the basal levels and gradually rose again after >24 h. The second phase was in parallel with an increase in 4-hydroxy-2-nonenal. The number of MN induced by the second wave of ROS/DSB elevations was much higher than that by the first peak. In this situation, NAC administered pre- and post-irradiation comparably suppressed MN induced by a delayed ROS elevation. In conclusion, a prolonged ROS increase during internal irradiation and a delayed ROS increase after external irradiation with a high dose caused serious DNA damage, which were efficiently prevented by NAC. Thus, NAC administration even both after internal or external irradiation prevents ROS increase and eventual DNA damage.

Role of atomic-level defects and electronic energy loss on amorphization in LiNbO3 single crystals

NASA Astrophysics Data System (ADS)

Sellami, N.; Crespillo, M. L.; Xue, H.; Zhang, Y.; Weber, W. J.

2017-08-01

Understanding complex non-equilibrium defect processes, where multiple irradiation mechanisms may take place simultaneously, is a long standing subject in material science. The separate and combined effects of elastic and inelastic energy loss are a very complicated and challenging topic. In this work, LiNbO3 has been irradiated with 0.9 MeV Si+ and 8 MeV O3+, which are representative of regimes where nuclear (S n) and electronic (S e) energy loss are dominant, respectively. The evolution of damage has been investigated by Rutherford backscattering spectrometry (RBS) in channeling configuration. Pristine samples were irradiated with 0.9 MeV Si+ ions to create different pre-existing damage states. Below the threshold (S e,th  =  5-6 keV nm-1) for amorphous track formation in this material, irradiation of the pristine samples with a highly ionizing beam of 8 MeV O3+ ions, with nearly constant S e of about 3 keV nm-1, induces a crystalline to amorphous phase transition at high ion fluences. In the pre-damaged samples, the electronic energy loss from the 8 MeV O3+ ions interacts synergistically with the pre-existing damage, resulting in a rapid, non-linear increase in damage production. There is a significant reduction in the incubation fluence for rapid amorphization with the increasing amount of pre-existing damage. These results highlight the important role of atomic-level defects on increasing the sensitivity of some oxides to amorphization induced by electronic energy loss. Controlling the nature and amount of pre-damage may provide a new approach to tuning optical properties for photonic device applications.

Role of atomic-level defects and electronic energy loss on amorphization in LiNbO 3 single crystals

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

Sellami, N.; Crespillo, M. L.; Xue, H.

Understanding complex non-equilibrium defect processes, where multiple irradiation mechanisms may take place simultaneously, is a long standing subject in material science. The separate and combined effects of elastic and inelastic energy loss are a very complicated and challenging topic. In this work, LiNbO 3 has been irradiated with 0.9 MeV Si + and 8 MeV O 3+, which are representative of regimes where nuclear (S n) and electronic (S e) energy loss are dominant, respectively. The evolution of damage has been investigated by Rutherford backscattering spectrometry (RBS) in channeling configuration. Pristine samples were irradiated with 0.9 MeV Si + ionsmore » to create different pre-existing damage states. Below the threshold (S e,th = 5–6 keV nm –1) for amorphous track formation in this material, irradiation of the pristine samples with a highly ionizing beam of 8 MeV O 3+ ions, with nearly constant S e of about 3 keV nm –1, induces a crystalline to amorphous phase transition at high ion fluences. In the pre-damaged samples, the electronic energy loss from the 8 MeV O 3+ ions interacts synergistically with the pre-existing damage, resulting in a rapid, non-linear increase in damage production. There is a significant reduction in the incubation fluence for rapid amorphization with the increasing amount of pre-existing damage. Here, these results highlight the important role of atomic-level defects on increasing the sensitivity of some oxides to amorphization induced by electronic energy loss. Controlling the nature and amount of pre-damage may provide a new approach to tuning optical properties for photonic device applications.« less

Role of atomic-level defects and electronic energy loss on amorphization in LiNbO 3 single crystals

DOE PAGES

Sellami, N.; Crespillo, M. L.; Xue, H.; ...

2017-06-20

Understanding complex non-equilibrium defect processes, where multiple irradiation mechanisms may take place simultaneously, is a long standing subject in material science. The separate and combined effects of elastic and inelastic energy loss are a very complicated and challenging topic. In this work, LiNbO 3 has been irradiated with 0.9 MeV Si + and 8 MeV O 3+, which are representative of regimes where nuclear (S n) and electronic (S e) energy loss are dominant, respectively. The evolution of damage has been investigated by Rutherford backscattering spectrometry (RBS) in channeling configuration. Pristine samples were irradiated with 0.9 MeV Si + ionsmore » to create different pre-existing damage states. Below the threshold (S e,th = 5–6 keV nm –1) for amorphous track formation in this material, irradiation of the pristine samples with a highly ionizing beam of 8 MeV O 3+ ions, with nearly constant S e of about 3 keV nm –1, induces a crystalline to amorphous phase transition at high ion fluences. In the pre-damaged samples, the electronic energy loss from the 8 MeV O 3+ ions interacts synergistically with the pre-existing damage, resulting in a rapid, non-linear increase in damage production. There is a significant reduction in the incubation fluence for rapid amorphization with the increasing amount of pre-existing damage. Here, these results highlight the important role of atomic-level defects on increasing the sensitivity of some oxides to amorphization induced by electronic energy loss. Controlling the nature and amount of pre-damage may provide a new approach to tuning optical properties for photonic device applications.« less

NECTARINE PROMOTES LONGEVITY IN DROSOPHILA MELANOGASTER

PubMed Central

Boyd, Olga; Weng, Peter; Sun, Xiaoping; Alberico, Thomas; Laslo, Mara; Obenland, David M.; Kern, Bradley; Zou, Sige

2011-01-01

Fruits containing high antioxidant capacities and other bioactivities are ideal for promoting longevity and healthspan. However, few fruits are known to improve the survival and healthspan in animals, let alone the underlying mechanisms. Here we investigate the effect of nectarine, a globally consumed fruit, on lifespan and healthspan in Drosophila melanogaster. Wild-type flies were fed the standard, dietary restriction (DR) or high fat diets supplemented with 0–4% nectarine extract. We measured lifespan, food intake, locomotor activity, fecundity, gene expression changes, and oxidative damage indicated by the level of 4-Hydroxynonenal-protein adduct in these flies. We also measured lifespan, locomotor activity and oxidative damage of sod1 mutant flies on the standard diet supplemented with 0–4% nectarine. Supplementation of 4% nectarine extended lifespan, increased fecundity and decreased expression of some metabolic genes, including a key gluconeogenesis gene PEPCK, and oxidative stress response genes, including peroxiredoxins, in female wild-type flies fed the standard, DR or high fat diet. Nectarine reduced oxidative damage in wild-type females fed the high fat diet. Moreover, nectarine improved the survival and reduced oxidative damage in female sod1 mutant flies. Together, these findings suggest that nectarine promotes longevity and healthspan partly through modulating glucose metabolism and reducing oxidative damage. PMID:21406223

User’s Guide to Southeast Asia Combat Data

DTIC Science & Technology

1976-06-01

North latitude Binary coded decimal Bomb damage assessment Battle Damage Assessment and Reporting Team Brigade Basic encyclopedia A University of...and movement routes Bomb wing CALCOMP CANDLESTICK CAP CAP CAS CAS CAVD CBU , CBS California Computer Products, Inc. Call sign...Special Studies Group (a high-level Washington committee) WAC WBLC WIA WOLF WSE3 WWDMS WWMCCS W X World Aeronautical Chart Waterborne logistic

Multi-level damage identification with response reconstruction

NASA Astrophysics Data System (ADS)

Zhang, Chao-Dong; Xu, You-Lin

2017-10-01

Damage identification through finite element (FE) model updating usually forms an inverse problem. Solving the inverse identification problem for complex civil structures is very challenging since the dimension of potential damage parameters in a complex civil structure is often very large. Aside from enormous computation efforts needed in iterative updating, the ill-condition and non-global identifiability features of the inverse problem probably hinder the realization of model updating based damage identification for large civil structures. Following a divide-and-conquer strategy, a multi-level damage identification method is proposed in this paper. The entire structure is decomposed into several manageable substructures and each substructure is further condensed as a macro element using the component mode synthesis (CMS) technique. The damage identification is performed at two levels: the first is at macro element level to locate the potentially damaged region and the second is over the suspicious substructures to further locate as well as quantify the damage severity. In each level's identification, the damage searching space over which model updating is performed is notably narrowed down, not only reducing the computation amount but also increasing the damage identifiability. Besides, the Kalman filter-based response reconstruction is performed at the second level to reconstruct the response of the suspicious substructure for exact damage quantification. Numerical studies and laboratory tests are both conducted on a simply supported overhanging steel beam for conceptual verification. The results demonstrate that the proposed multi-level damage identification via response reconstruction does improve the identification accuracy of damage localization and quantization considerably.

Sand smelt ability to cope and recover from ocean's elevated CO2 levels.

PubMed

Silva, Cátia S E; Lemos, Marco F L; Faria, Ana M; Lopes, Ana F; Mendes, Susana; Gonçalves, Emanuel J; Novais, Sara C

2018-06-15

Considered a major environmental concern, ocean acidification has induced a recent research boost into effects on marine biodiversity and possible ecological, physiological, and behavioural impacts. Although the majority of literature indicate negative effects of future acidification scenarios, most studies are conducted for just a few days or weeks, which may be insufficient to detect the capacity of an organism to adjust to environmental changes through phenotypic plasticity. Here, the effects and the capacity of sand smelt larvae Atherina presbyter to cope and recover (through a treatment combination strategy) from short (15 days) and long-term exposure (45 days) to increasing pCO 2 levels (control: ~515 μatm, pH = 8.07; medium: ~940 μatm, pH = 7.84; high: ~1500 μatm, pH = 7.66) were measured, addressing larval development traits, behavioural lateralization, and biochemical biomarkers related with oxidative stress and damage, and energy metabolism and reserves. Although behavioural lateralization was not affected by high pCO 2 exposure, morphometric changes, energetic costs, and oxidative stress damage were impacted differently through different exposures periods. Generally, short-time exposures led to different responses to either medium or high pCO 2 levels (e.g. development, cellular metabolism, or damage), while on the long-term the response patterns tend to become similar between them, with both acidification scenarios inducing DNA damage and tending to lower growth rates. Additionally, when organisms were transferred to lower acidified condition, they were not able to recover from the mentioned DNA damage impacts. Overall, results suggest that exposure to future ocean acidification scenarios can induce sublethal effects on early life-stages of fish, but effects are dependent on duration of exposure, and are likely not reversible. Furthermore, to improve our understanding on species sensitivity and adaptation strategies, results reinforce the need to use multiple biological endpoints when assessing the effects of ocean acidification on marine organisms. Copyright © 2018 Elsevier Inc. All rights reserved.

Repairing the damage to Atlantis' External Tank

NASA Image and Video Library

2007-03-07

On an upper level of high bay 1 of the Vehicle Assembly Building, technicians prepare the area around the nose cone (left) of Atlantis' external tank that will undergo repair for hail damage. A severe thunderstorm with golf ball-sized hail caused visible divots in the giant tank's foam insulation and minor surface damage to about 26 heat shield tiles on the shuttle's left wing. Further evaluation of the tank is necessary to get an accurate accounting of foam damage and determine the type of repair required and the time needed for that work. A new target launch date has not been determined, but teams will focus on preparing Atlantis for liftoff in late April on mission STS-117.

Repairing the damage to Atlantis' External Tank

NASA Image and Video Library

2007-03-07

On an upper level of high bay 1 of the Vehicle Assembly Building, technicians place protective material around the nose cone of Atlantis' external tank. The nose cone will undergo repair for hail damage. A severe thunderstorm with golf ball-sized hail caused visible divots in the giant tank's foam insulation and minor surface damage to about 26 heat shield tiles on the shuttle's left wing. Further evaluation of the tank is necessary to get an accurate accounting of foam damage and determine the type of repair required and the time needed for that work. A new target launch date has not been determined, but teams will focus on preparing Atlantis for liftoff in late April on mission STS-117.

Repairing the damage to Atlantis' External Tank

NASA Image and Video Library

2007-03-07

On an upper level of high bay 1 of the Vehicle Assembly Building, technicians prepare the area around the nose cone (foreground) of Atlantis' external tank that will undergo repair for hail damage. A severe thunderstorm with golf ball-sized hail caused visible divots in the giant tank's foam insulation and minor surface damage to about 26 heat shield tiles on the shuttle's left wing. Further evaluation of the tank is necessary to get an accurate accounting of foam damage and determine the type of repair required and the time needed for that work. A new target launch date has not been determined, but teams will focus on preparing Atlantis for liftoff in late April on mission STS-117.

Mitigation of Crack Damage in Metallic Materials

NASA Technical Reports Server (NTRS)

Leser, Patrick E.; Newman, John A.; Smith, Stephen W.; Leser, William P.; Wincheski, Russell A.; Wallace, Terryl A.; Glaessgen, Edward H.; Piascik, Robert S.

2014-01-01

A system designed to mitigate or heal crack damage in metallic materials has been developed where the protected material or component is coated with a low-melting temperature film. After a crack is formed, the material is heated, melting the film which then infiltrates the crack opening through capillary action. Upon solidification, the healing material inhibits further crack damage in two ways. While the crack healing material is intact, it acts like an adhesive that bonds or bridges the crack faces together. After fatigue loading damages, the healing material in the crack mouth inhibits further crack growth by creating artificially-high crack closure levels. Mechanical test data show that this method sucessfully arrests or retards crack growth in laboratory specimens.

Basic examination of nondestructive and noncontact measurement system for fire damage level of concrete wall by using high-intensity aerial ultrasonic waves

NASA Astrophysics Data System (ADS)

Osumi, Ayumu; Ito, Youichi

2012-05-01

A fire site holds important information about the cause of fire outbreak; for instance, a concrete wall can provide a wealth of information and the distribution of fire damage of the wall is particularly valuable. If the distribution of fire damage on concrete walls can be used to trace the flow of fire, it would be possible to identify the fire origin and to clarify the cause of fire outbreak. In this study, we considered a new method based on aerial ultrasonic waves and developed a system that adopts this method for detecting fire damage of concrete walls at fire sites.

Damage extraction of buildings in the 2015 Gorkha, Nepal earthquake from high-resolution SAR data

NASA Astrophysics Data System (ADS)

Yamazaki, Fumio; Bahri, Rendy; Liu, Wen; Sasagawa, Tadashi

2016-05-01

Satellite remote sensing is recognized as one of the effective tools for detecting and monitoring affected areas due to natural disasters. Since SAR sensors can capture images not only at daytime but also at nighttime and under cloud-cover conditions, they are especially useful at an emergency response period. In this study, multi-temporal high-resolution TerraSAR-X images were used for damage inspection of the Kathmandu area, which was severely affected by the April 25, 2015 Gorkha Earthquake. The SAR images obtained before and after the earthquake were utilized for calculating the difference and correlation coefficient of backscatter. The affected areas were identified by high values of the absolute difference and low values of the correlation coefficient. The post-event high-resolution optical satellite images were employed as ground truth data to verify our results. Although it was difficult to estimate the damage levels for individual buildings, the high resolution SAR images could illustrate their capability in detecting collapsed buildings at emergency response times.

The Impact of Maturity Stage on Cell Membrane Integrity and Enzymatic Browning Reactions in High Pressure Processed Peaches (Prunus persica).

PubMed

Techakanon, Chukwan; Gradziel, Thomas M; Zhang, Lu; Barrett, Diane M

2016-09-28

Fruit maturity is an important factor associated with final product quality, and it may have an effect on the level of browning in peaches that are high pressure processed (HPP). Peaches from three different maturities, as determined by firmness (M1 = 50-55 N, M2 = 35-40 N, and M3 = 15-20 N), were subjected to pressure levels at 0.1, 200, and 400 MPa for 10 min. The damage from HPP treatment results in loss of fruit integrity and the development of browning during storage. Increasing pressure levels of HPP treatment resulted in greater damage, particularly in the more mature peaches, as determined by shifts in transverse relaxation time (T2) of the vacuolar component and by light microscopy. The discoloration of peach slices of different maturities processed at the same pressure was comparable, indicating that the effect of pressure level is greater than that of maturity in the development of browning.

Influence of alpha-lipoic acid on nicotine-induced lung and liver damage in experimental rats.

PubMed

Ateyya, Hayam; Nader, Manar A; Attia, Ghalia M; El-Sherbeeny, Nagla A

2017-05-01

Nicotine mediates some of the injurious effects caused by consuming tobacco products. This work aimed at investigating the defensive role of alpha-lipoic acid (ALA) with its known antioxidant and antiinflammatory effect in nicotine-induced lung and liver damage. Rats were arranged into 4 groups: control, nicotine, ALA, and ALA-nicotine groups. Oxidative stress and antioxidant status were determined by assessing thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione (GSH) levels in lung and liver. Liver enzymes and lipid profiles were measured and pulmonary and hepatic damage were assessed by histopathological examination. Also, serum levels of transforming growth factor beta 1 (TGF-β1) and vascular cell adhesion molecule 1 (VCAM-1) were determined. The results revealed an increase in TBARS in tissues and a reduction in both SOD and GSH activity in the nicotine-treated rats. Nicotine induced high levels of liver enzymes, TGF-β1, VCAM-1, and dyslipidemia with histopathological changes in the lung and liver. ALA administration along with nicotine attenuated oxidative stress and normalized the SOD and GSH levels, ameliorated dyslipidemia, and improved TGF-β1 and VCAM-1 with better histopathology of the lung and liver. The study data revealed that ALA may be beneficial in alleviating nicotine-induced oxidative stress, dyslipidemia, and both lung and liver damage.

Assessing European wild fire vulnerability

NASA Astrophysics Data System (ADS)

Oehler, F.; Oliveira, S.; Barredo, J. I.; Camia, A.; Ayanz, J. San Miguel; Pettenella, D.; Mavsar, R.

2012-04-01

Wild fire vulnerability is a measure of potential socio-economic damage caused by a fire in a specific area. As such it is an important component of long-term fire risk management, helping policy-makers take informed decisions about adequate expenditures for fire prevention and suppression, and to target those regions at highest risk. This paper presents a first approach to assess wild fire vulnerability at the European level. A conservative approach was chosen that assesses the cost of restoring the previous land cover after a potential fire. Based on the CORINE Land Cover, a restoration cost was established for each land cover class at country level, and an average restoration time was assigned according to the recovery capacity of the land cover. The damage caused by fire was then assessed by discounting the cost of restoring the previous land cover over the restoration period. Three different vulnerability scenarios were considered assuming low, medium and high fire severity causing different levels of damage. Over Europe, the potential damage of wild land fires ranges from 10 - 13, 732 Euro*ha-1*yr-1 for low fire severity, 32 - 45,772 Euro*ha-1*yr-1 for medium fire severity and 54 - 77,812 Euro*ha-1*yr-1 for high fire severity. The least vulnerable are natural grasslands, moors and heathland and sclerophyllous vegetation, while the highest cost occurs for restoring broad-leaved forest. Preliminary validation comparing these estimates with official damage assessments for past fires shows reasonable results. The restoration cost approach allows for a straightforward, data extensive assessment of fire vulnerability at European level. A disadvantage is the inherent simplification of the evaluation procedure with the underestimation of non-markets goods and services. Thus, a second approach has been developed, valuing individual wild land goods and services and assessing their annual flow which is lost for a certain period of time in case of a fire event. However, due to limitations in data availability, this approach of environmental accounting is not fully implemented yet. Keywords: fire vulnerability, damage assessment, land cover restoration, long-term fire risk, European scale

Sex-dependent effects of high-fat-diet feeding on rat pancreas oxidative stress.

PubMed

Gómez-Pérez, Yolanda; Gianotti, Magdalena; Lladó, Isabel; Proenza, Ana M

2011-07-01

The objective of the study was to investigate whether sex differences in oxidative stress-associated insulin resistance previously reported in rats could be attributed to a possible sex dimorphism in pancreas redox status. Fifteen-month-old male and female Wistar rats were fed a control diet or a high-fat diet for 14 weeks. Serum glucose, lipids, and hormone levels were measured. Insulin immunohistochemistry and morphometric analysis of islets were performed. Pancreas triglyceride content, oxidative damage, and antioxidant enzymatic activities were determined. Lipoprotein lipase, hormone-sensitive lipase, and uncoupling protein 2 (UCP2) levels were also measured. Male rats showed a more marked insulin resistance profile than females. In control female rats, pancreas Mn-superoxide dismutase activity and UCP2 levels were higher, and oxidative damage was lower compared with males. High-fat-diet feeding decreased pancreas triglyceride content in female rats and UCP2 levels in male rats. High-fat-diet female rats showed larger islets than both their control and sex counterparts. These results confirm the existence of a sex dimorphism in pancreas oxidative status in both control and high-fat-diet feeding situations, with female rats showing higher protection against oxidative stress, thus maintaining pancreatic function and contributing to a lower risk of insulin resistance.

Lead induced oxidative DNA damage in battery-recycling child workers from Bangladesh.

PubMed

Arif, Mohammad; Islam, Mm Towhidul; Shekhar, Hossain Uddin

2018-04-01

Lead exposure can damage cells directly by effecting DNA or indirectly by modifying proteins and enzymes. In Bangladesh, many working children are exposed to a very high level of lead during their early life due to their involvement with lead-oriented professions. This imposes a severe threat to the growth and development of the children. Therefore to study the effect of lead, we enrolled 60 age-matched male children, from an area of old Dhaka city, where battery-recycling shops are located, depending on their blood lead concentration. If the children had a plasma lead concentration above the WHO recommended threshold level of 10 µg/dl, we grouped them as test subjects and others as control subjects to determine the effect of lead on different biochemical parameters of the body. Compared to the controls, acculumlation of the lipid peroxidation product, malondialdehyde, increased significantly in test subjects ( p < 0.01). Lead exposure also increased the protein carbonyl content ( p < 0.05) and significantly decreased the plasma glutathione levels of test subjects compared to the controls ( p < 0.05). While comparing the lead-exposed group against controls, it was found that the percentage of damaged DNA, as measured using the Comet assay, significantly increased in tail ( p < 0.01) and decreased in head regions. All of these results suggest that high-plasma lead content may induce an oxidative stress to the study population, which may lead to DNA damage.

Oxidative stress and pathology in muscular dystrophies: focus on protein thiol oxidation and dysferlinopathies.

PubMed

Terrill, Jessica R; Radley-Crabb, Hannah G; Iwasaki, Tomohito; Lemckert, Frances A; Arthur, Peter G; Grounds, Miranda D

2013-09-01

The muscular dystrophies comprise more than 30 clinical disorders that are characterized by progressive skeletal muscle wasting and degeneration. Although the genetic basis for many of these disorders has been identified, the exact mechanism for pathogenesis generally remains unknown. It is considered that disturbed levels of reactive oxygen species (ROS) contribute to the pathology of many muscular dystrophies. Reactive oxygen species and oxidative stress may cause cellular damage by directly and irreversibly damaging macromolecules such as proteins, membrane lipids and DNA; another major cellular consequence of reactive oxygen species is the reversible modification of protein thiol side chains that may affect many aspects of molecular function. Irreversible oxidative damage of protein and lipids has been widely studied in Duchenne muscular dystrophy, and we have recently identified increased protein thiol oxidation in dystrophic muscles of the mdx mouse model for Duchenne muscular dystrophy. This review evaluates the role of elevated oxidative stress in Duchenne muscular dystrophy and other forms of muscular dystrophies, and presents new data that show significantly increased protein thiol oxidation and high levels of lipofuscin (a measure of cumulative oxidative damage) in dysferlin-deficient muscles of A/J mice at various ages. The significance of this elevated oxidative stress and high levels of reversible thiol oxidation, but minimal myofibre necrosis, is discussed in the context of the disease mechanism for dysferlinopathies, and compared with the situation for dystrophin-deficient mdx mice. © 2013 The Authors Journal compilation © 2013 FEBS.

A comprehensive analysis of earthquake damage patterns using high dimensional model representation feature selection

NASA Astrophysics Data System (ADS)

Taşkin Kaya, Gülşen

2013-10-01

Recently, earthquake damage assessment using satellite images has been a very popular ongoing research direction. Especially with the availability of very high resolution (VHR) satellite images, a quite detailed damage map based on building scale has been produced, and various studies have also been conducted in the literature. As the spatial resolution of satellite images increases, distinguishability of damage patterns becomes more cruel especially in case of using only the spectral information during classification. In order to overcome this difficulty, textural information needs to be involved to the classification to improve the visual quality and reliability of damage map. There are many kinds of textural information which can be derived from VHR satellite images depending on the algorithm used. However, extraction of textural information and evaluation of them have been generally a time consuming process especially for the large areas affected from the earthquake due to the size of VHR image. Therefore, in order to provide a quick damage map, the most useful features describing damage patterns needs to be known in advance as well as the redundant features. In this study, a very high resolution satellite image after Iran, Bam earthquake was used to identify the earthquake damage. Not only the spectral information, textural information was also used during the classification. For textural information, second order Haralick features were extracted from the panchromatic image for the area of interest using gray level co-occurrence matrix with different size of windows and directions. In addition to using spatial features in classification, the most useful features representing the damage characteristic were selected with a novel feature selection method based on high dimensional model representation (HDMR) giving sensitivity of each feature during classification. The method called HDMR was recently proposed as an efficient tool to capture the input-output relationships in high-dimensional systems for many problems in science and engineering. The HDMR method is developed to improve the efficiency of the deducing high dimensional behaviors. The method is formed by a particular organization of low dimensional component functions, in which each function is the contribution of one or more input variables to the output variables.

DNA-protective effects of quercetin or naringenin in alloxan-induced diabetic mice.

PubMed

Oršolić, Nada; Gajski, Goran; Garaj-Vrhovac, Vera; Dikić, Domagoj; Prskalo, Zvjezdana Špacir; Sirovina, Damir

2011-04-10

Diabetes mellitus is associated with a high production of reactive oxygen species, which may cause oxidative DNA damage. High levels of genomic damage have been associated with liver and renal failure as well as immune-system decline. Flavonoids are effective antioxidants and may protect against several chronic diseases including diabetes. This study used the comet assay to assess the levels of DNA damage in the blood, liver and kidney cells in untreated and quercetin (QU) or naringenin treated diabetic mice. In addition, the study was designed to establish whether QU or naringenin might have a biological effect in protecting diabetic mice against oxidative stress by using survival studies to observe total body injury at the level of the organism. QU or naringenin were injected to mice intraperitoneally (i.p.) at a dose of 50mg/kg for 7days starting 2days after a single dose (75mg/kg, i.v.) alloxan injection. These findings suggest that QU or naringenin treatment resulted in a significant increase in the body weight, the haematological and immunological parameters of blood, as well as leading to 100% survival of diabetic mice. The tested flavonoids have protective effects against alloxan-induced DNA-damage in peripheral lymphocytes but not in the liver and kidney cells of diabetic mice. It might be hypothesised that diabetic mice with a high intake of flavonoid-rich foods, and specifically foods rich in quercetin or naringenin, might be relatively protected against long-term complications of diabetes due to decreased oxidative stress. Various co-operative and synergistic action mechanisms of the tested flavonoids may lead to the protection of the whole organism against diabetes. Copyright © 2011 Elsevier B.V. All rights reserved.

Differences in the fatty-acid composition of rodent spermatozoa are associated to levels of sperm competition

PubMed Central

delBarco-Trillo, Javier; Mateo, Rafael; Roldan, Eduardo R. S.

2015-01-01

Sperm competition is a prevalent phenomenon that drives the evolution of sperm function. High levels of sperm competition lead to increased metabolism to fuel higher sperm velocities. This enhanced metabolism can result in oxidative damage (including lipid peroxidation) and damage to the membrane. We hypothesized that in those species experiencing high levels of sperm competition there are changes in the fatty-acid composition of the sperm membrane that makes the membrane more resistant to oxidative damage. Given that polyunsaturated fatty acids (PUFAs) are the most prone to lipid peroxidation, we predicted that higher sperm competition leads to a reduction in the proportion of sperm PUFAs. In contrast, we predicted that levels of sperm competition should not affect the proportion of PUFAs in somatic cells. To test these predictions, we quantified the fatty-acid composition of sperm, testis and liver cells in four mouse species (genus Mus) that differ in their levels of sperm competition. Fatty-acid composition in testis and liver cells was not associated to sperm competition levels. However, in sperm cells, as predicted, an increase in sperm competition levels was associated with an increase in the proportion of saturated fatty-acids (the most resistant to lipid peroxidation) and by a concomitant decrease in the proportion of PUFAs. Two particular fatty acids were most responsible for this pattern (arachidonic acid and palmitic acid). Our findings thus indicate that sperm competition has a pervasive influence in the composition of sperm cells that ultimately may have important effects in sperm function. PMID:25795911

Carcinogenic damage to deoxyribonucleic acid is induced by near-infrared laser pulses in multiphoton microscopy via combination of two- and three-photon absorption

NASA Astrophysics Data System (ADS)

Nadiarnykh, Oleg; Thomas, Giju; Van Voskuilen, Johan; Sterenborg, Henricus J. C. M.; Gerritsen, Hans C.

2012-11-01

Nonlinear optical imaging modalities (multiphoton excited fluorescence, second and third harmonic generation) applied in vivo are increasingly promising for clinical diagnostics and the monitoring of cancer and other disorders, as they can probe tissue with high diffraction-limited resolution at near-infrared (IR) wavelengths. However, high peak intensity of femtosecond laser pulses required for two-photon processes causes formation of cyclobutane-pyrimidine-dimers (CPDs) in cellular deoxyribonucleic acid (DNA) similar to damage from exposure to solar ultraviolet (UV) light. Inaccurate repair of subsequent mutations increases the risk of carcinogenesis. In this study, we investigate CPD damage that results in Chinese hamster ovary cells in vitro from imaging them with two-photon excited autofluorescence. The CPD levels are quantified by immunofluorescent staining. We further evaluate the extent of CPD damage with respect to varied wavelength, pulse width at focal plane, and pixel dwell time as compared with more pronounced damage from UV sources. While CPD damage has been expected to result from three-photon absorption, our results reveal that CPDs are induced by competing two- and three-photon absorption processes, where the former accesses UVA absorption band. This finding is independently confirmed by nonlinear dependencies of damage on laser power, wavelength, and pulse width.

Coefficient of Friction Patterns Can Identify Damage in Native and Engineered Cartilage Subjected to Frictional-Shear Stress

PubMed Central

Whitney, G. A.; Mansour, J. M.; Dennis, J. E.

2015-01-01

The mechanical loading environment encountered by articular cartilage in situ makes frictional-shear testing an invaluable technique for assessing engineered cartilage. Despite the important information that is gained from this testing, it remains under-utilized, especially for determining damage behavior. Currently, extensive visual inspection is required to assess damage; this is cumbersome and subjective. Tools to simplify, automate, and remove subjectivity from the analysis may increase the accessibility and usefulness of frictional-shear testing as an evaluation method. The objective of this study was to determine if the friction signal could be used to detect damage that occurred during the testing. This study proceeded in two phases: first, a simplified model of biphasic lubrication that does not require knowledge of interstitial fluid pressure was developed. In the second phase, frictional-shear tests were performed on 74 cartilage samples, and the simplified model was used to extract characteristic features from the friction signals. Using support vector machine classifiers, the extracted features were able to detect damage with a median accuracy of approximately 90%. The accuracy remained high even in samples with minimal damage. In conclusion, the friction signal acquired during frictional-shear testing can be used to detect resultant damage to a high level of accuracy. PMID:25691395

A 2D Model of Hydraulic Fracturing, Damage and Microseismicity

NASA Astrophysics Data System (ADS)

Wangen, Magnus

2018-03-01

We present a model for hydraulic fracturing and damage of low-permeable rock. It computes the intermittent propagation of rock damage, microseismic event locations, microseismic frequency-magnitude distributions, stimulated rock volume and the injection pressure. The model uses a regular 2D grid and is based on ideas from invasion percolation. All damaged and connected cells during a time step constitute a microseismic event, where the size of the event is the number of cells in the cluster. The magnitude of the event is the log _{10} of the event size. The model produces events with a magnitude-frequency distribution having a b value that is approximately 0.8. The model is studied with respect to the physical parameters: permeability of damaged rock and the rock strength. "High" permeabilities of the damaged rock give the same b value ≈ 0.8, but "moderate" permeabilities give higher b values. Another difference is that "high" permeabilities produce a percolation-like fracture network, while "moderate" permeabilities result in damage zones that expand circularly away from the injection point. In the latter case of "moderate" permeabilities, the injection pressure increases substantially beyond the fracturing level. The rock strength and the time step do not change the observed b value of the model for moderate changes.

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

Infliximab Modulates Cisplatin-Induced Hepatotoxicity in Rats

PubMed Central

Cüre, Medine Cumhur; Cüre, Erkan; Kalkan, Yıldıray; Kırbaş, Aynur; Tümkaya, Levent; Yılmaz, Arif; Türkyılmaz, Ayşegül Küçükali; Şehitoğlu, İbrahim; Yüce, Süleyman

2016-01-01

Background: Cisplatin (Cis) is one of the most commonly used antineoplastic drugs. It is used as chemotherapy for many solid organ malignancies such as brain, neck, male and female urogenital, vesical and pulmonary cancers. Infliximab blocks tumor necrosis factor alpha (TNF-α). Several studies have reported that infliximab ameliorates cell damage by reducing cytokine levels. Aims: We aimed to investigate whether infliximab has a preventive effect against cisplatin-induced hepatotoxicity and whether it has a synergistic effect when combined with Cis. Study Design: Animal experimentation. Methods: Male Wistar albino rats were divided in three groups as follows: Cis group, infliximab + Cis (CIN) group and the control group. Each group comprised 10 animals. Animals in the Cis group received an intraperitoneal single-dose injection of Cis (7 mg/kg). In the CIN group, a single dose of infliximab (7 mg/kg) was administered 72 h prior to the Cis injection. After 72 h, a single dose of Cis (7 mg/kg) was administered. All rats were sacrificed five days after Cis injection. Results: TNF-α levels in the Cis group were significantly higher (345.5±40.0 pg/mg protein) than those of the control (278.7±62.1 pg/mg protein, p=0.003) and CIN groups (239.0±64.2 pg/mg protein, p=0.013). The Cis group was found to have high carbonic anhydrase (CA)-II and low carbamoyl phosphate synthetase-1 (CPS-1) levels. Aspartate transaminase (AST) and alanine transaminase (ALT) levels were lower in the CIN group as compared to the Cis group. Total histological damage was greater in the Cis group as compared to the control and CIN groups. Conclusion: Cis may lead to liver damage by increasing cytokine levels. It may increase oxidative stress-induced tissue damage by increasing carbonic anhydrase II (CA-II) enzyme levels and decreasing CPS-1 enzyme levels. Infliximab decreases Cis-induced hepatic damage by blocking TNF-α and it may also protect against liver damage by regulating CPS-1 and CA-II enzyme levels. PMID:27761277

An adaptive molecular timer in p53-meidated cell fate decision

NASA Astrophysics Data System (ADS)

Zhang, Xiao-Peng; Wang, Ping; Liu, Feng; Wang, Wei

The tumor suppressor p53 decides cellular outcomes in the DNA damage response. It is intriguing to explore the link between p53 dynamics and cell fates. We developed a theoretical model of p53 signaling network to clarify the mechanism of cell fate decision mediated by its dynamics. We found that the interplay between p53-Mdm2 negative feedback loop and p53-PTEN-Mdm2 positive feedback loop shapes p53 dynamics. Depending on the intensity of DNA damage, p53 shows three modes of dynamics: persistent pulses, two-phase dynamics with pulses followed by sustained high levels and straightforward high levels. Especially, p53 shows two-phase dynamics upon moderated damage and the required number of p53 pulses before apoptosis induction decreases with increasing DNA damage. Our results suggested there exists an adaptive molecular timer that determines whether and when the apoptosis switch should be triggered. We clarified the mechanism behind the switching of p53 dynamical modes by bifurcation analysis. Moreover, we reproduced the experimental results that drug additions alter p53 pulses to sustained p53 activation and leads to senescence. Our work may advance the understanding the significance of p53 dynamics in tumor suppression. This work was supported by National Natural Science Foundation of China (Nos. 11175084, 11204126 and 31361163003).

Progressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes

PubMed Central

Naesens, Maarten; Khatri, Purvesh; Li, Li; Sigdel, Tara K.; Vitalone, Matthew J.; Chen, Rong; Butte, Atul J.; Salvatierra, Oscar; Sarwal, Minnie M.

2015-01-01

The degree of progressive chronic histological damage is associated with long-term renal allograft survival. In order to identify promising molecular targets for timely intervention, we examined renal allograft protocol and indication biopsies from 120 low-risk pediatric and adolescent recipients by whole-genome microarray expression profiling. In data-driven analysis, we found a highly regulated pattern of adaptive and innate immune gene expression that correlated with established or ongoing histological chronic injury, and also with development of future chronic histological damage, even in histologically pristine kidneys. Hence, histologically unrecognized immunological injury at a molecular level sets the stage for the development of chronic tissue injury, while the same molecular response is accentuated during established and worsening chronic allograft damage. Irrespective of the hypothesized immune or nonimmune trigger for chronic allograft injury, a highly orchestrated regulation of innate and adaptive immune responses was found in the graft at the molecular level. This occurred months before histologic lesions appear, and quantitatively below the diagnostic threshold of classic T-cell or antibody-mediated rejection. Thus, measurement of specific immune gene expression in protocol biopsies may be warranted to predict the development of subsequent chronic injury in histologically quiescent grafts and as a means to titrate immunosuppressive therapy. PMID:21881554

Progressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes.

PubMed

Naesens, Maarten; Khatri, Purvesh; Li, Li; Sigdel, Tara K; Vitalone, Matthew J; Chen, Rong; Butte, Atul J; Salvatierra, Oscar; Sarwal, Minnie M

2011-12-01

The degree of progressive chronic histological damage is associated with long-term renal allograft survival. In order to identify promising molecular targets for timely intervention, we examined renal allograft protocol and indication biopsies from 120 low-risk pediatric and adolescent recipients by whole-genome microarray expression profiling. In data-driven analysis, we found a highly regulated pattern of adaptive and innate immune gene expression that correlated with established or ongoing histological chronic injury, and also with development of future chronic histological damage, even in histologically pristine kidneys. Hence, histologically unrecognized immunological injury at a molecular level sets the stage for the development of chronic tissue injury, while the same molecular response is accentuated during established and worsening chronic allograft damage. Irrespective of the hypothesized immune or nonimmune trigger for chronic allograft injury, a highly orchestrated regulation of innate and adaptive immune responses was found in the graft at the molecular level. This occurred months before histologic lesions appear, and quantitatively below the diagnostic threshold of classic T-cell or antibody-mediated rejection. Thus, measurement of specific immune gene expression in protocol biopsies may be warranted to predict the development of subsequent chronic injury in histologically quiescent grafts and as a means to titrate immunosuppressive therapy.

Building Change Detection from Harvey using Unmanned Aerial System (UAS)

NASA Astrophysics Data System (ADS)

Chang, A.; Yeom, J.; Jung, J.; Choi, I.

2017-12-01

Unmanned Aerial System (UAS) is getting to be the most important technique in recent days since the fine spatial and high temporal resolution data previously unobtainable from traditional remote sensing platforms. Advanced UAS data can provide a great opportunity for disaster monitoring. Especially, building change detection is the one of the most important topics for damage assessment and recovery from disasters. This study is proposing a method to monitor building change with UAS data for Holiday Beach in Texas, where was directly hit by Harvey on 25 August 2017. This study adopted 3D change detection to monitor building damage and recovery levels with building height as well as natural color information. We used a rotorcraft UAS to collect RGB data twice on 9 September and 18 October 2017 after the hurricane. The UAS data was processed using Agisoft Photoscan Pro Software to generate super high resolution dataset including orthomosaic, DSM (Digital Surface Model), and 3D point cloud. We compared the processed dataset with an airborne image considerable as before-hurricane data, which was acquired on January 2016. Building damage and recovery levels were determined by height and color change. The result will show that UAS data is useful to assess building damage and recovery for affected area by the natural disaster such as Harvey.

Analysis of Serum Interleukin (IL)-1β and IL-18 in Systemic Lupus Erythematosus.

PubMed

Mende, Rachel; Vincent, Fabien B; Kandane-Rathnayake, Rangi; Koelmeyer, Rachel; Lin, Emily; Chang, Janet; Hoi, Alberta Y; Morand, Eric F; Harris, James; Lang, Tali

2018-01-01

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease characterized by biological and clinical heterogeneity. The interleukin (IL)-1 superfamily is a group of innate cytokines that contribute to pathogenesis in many autoimmune diseases. IL-1β and IL-18 are two members that have been shown to play a role in murine lupus-like models, but their role in human SLE remains poorly understood. Here, IL-1β and IL-18 were quantified by enzyme-linked immunosorbent assay in the serum of healthy controls (HCs) and SLE patients from a prospectively followed cohort. Disease activity and organ damage were assessed using SLE disease activity index 2000 (SLEDAI-2K) and SLE damage index scores (SDI), respectively. 184 SLE patients (mean age 44.9 years, 91% female, 56% double-stranded deoxyribonucleic acid positive) were compared to 52 HC. SLE patients had median [IQR] SLEDAI-2K of 4 [2,6], and SDI of 1 [0-2]. Serum IL-18 levels were statistically significantly higher in SLE patients compared to HCs. Univariable linear regression analyses showed that patients with active renal disease or irreversible organ damage had statistically significantly elevated serum IL-18 levels. The association between serum IL-18 and active renal disease was confirmed in multivariable analysis after adjusting for ethnicity and organ damage. High baseline serum IL-18 levels were associated with organ damage at the subsequent visit. Serum IL-1β levels were not significantly elevated in SLE patients when compared to HCs and had no association with overall or organ-specific disease activity or organ damage in cross-sectional and longitudinal analyses. Our data suggest that serum IL-18 and IL-1β have different clinical implications in SLE, with IL-18 being potentially associated with active renal disease.

Molecular mimicry between Mycobacterium leprae proteins (50S ribosomal protein L2 and Lysyl-tRNA synthetase) and myelin basic protein: a possible mechanism of nerve damage in leprosy.

PubMed

Singh, Itu; Yadav, Asha Ram; Mohanty, Keshar Kunja; Katoch, Kiran; Sharma, Prashant; Mishra, Bishal; Bisht, Deepa; Gupta, U D; Sengupta, Utpal

2015-04-01

Autoantibodies against various components of host are known to occur in leprosy. Nerve damage is the primary cause of disability associated with leprosy. The aim of this study was to detect the level of autoantibodies and lympho-proliferative response against myelin basic protein (MBP) in leprosy patients (LPs) and their correlation with clinical phenotypes of LPs. Further, probable role of molecular mimicry in nerve damage of LPs was investigated. We observed significantly high level of anti-MBP antibodies in LPs across the spectrum and a positive significant correlation between the level of anti-MBP antibodies and the number of nerves involved in LPs. We report here that 4 B cell epitopes of myelin A1 and Mycobacterium leprae proteins, 50S ribosomal L2 and lysyl tRNA synthetase are cross-reactive. Further, M. leprae sonicated antigen hyperimmunization was responsible for induction of autoantibody response in mice which could be adoptively transferred to naive mice. For the first time our findings suggest the role of molecular mimicry in nerve damage in leprosy. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Hepatocerebral degeneration

MedlinePlus

... Liver damage can lead to the buildup of ammonia and other toxic materials in the body. This ... Walking instability Laboratory tests may show a high ammonia level in the bloodstream and abnormal liver function. ...

Specific chemical and structural damage to proteins produced by synchrotron radiation.

PubMed

Weik, M; Ravelli, R B; Kryger, G; McSweeney, S; Raves, M L; Harel, M; Gros, P; Silman, I; Kroon, J; Sussman, J L

2000-01-18

Radiation damage is an inherent problem in x-ray crystallography. It usually is presumed to be nonspecific and manifested as a gradual decay in the overall quality of data obtained for a given crystal as data collection proceeds. Based on third-generation synchrotron x-ray data, collected at cryogenic temperatures, we show for the enzymes Torpedo californica acetylcholinesterase and hen egg white lysozyme that synchrotron radiation also can cause highly specific damage. Disulfide bridges break, and carboxyl groups of acidic residues lose their definition. Highly exposed carboxyls, and those in the active site of both enzymes, appear particularly susceptible. The catalytic triad residue, His-440, in acetylcholinesterase, also appears to be much more sensitive to radiation damage than other histidine residues. Our findings have direct practical implications for routine x-ray data collection at high-energy synchrotron sources. Furthermore, they provide a direct approach for studying the radiation chemistry of proteins and nucleic acids at a detailed, structural level and also may yield information concerning putative "weak links" in a given biological macromolecule, which may be of structural and functional significance.

Feral livestock threatens landscapes dominated by columnar cacti

NASA Astrophysics Data System (ADS)

Malo, J. E.; Acebes, P.; Giannoni, S. M.; Traba, J.

2011-05-01

The introduction and naturalization of alien species represents a serious threat to many natural protected areas. One such case of worldwide concern is the impact of feral livestock on arid ecosystems. Damage suffered by Echinopsis (= Trichocereus) terscheckii dominating the landscape of rocky slopes was surveyed in seven locations within the Ischigualasto-Talampaya World Heritage Site (Argentina) by measuring the frequency, position on the plant and extent of damage. At the same time we employed transects to estimate the abundance of autochtonous and feral large herbivores ( Lama guanicoe, Bos taurus, Equus asinus) from their dung. Our results show relatively high damage levels (40-77% of individuals damaged, more than 5 dm 3 removed by plant in some sites), particularly within 0.50-1.75 m above the ground, showing herbivores to be the main responsible for them. We also found significant differences between sites in variables measuring damage level and in the intensity of use by the two feral livestock species but not by guanacos. The frequency of damaged cacti below 1.75 m (but not above) was significantly positively correlated among locations with the frequencies of cattle and donkey dung, and the damage suffered by individual cacti was also correlated with donkey and cattle dung in their surroundings after correcting for spatial effects. However, all correlations were non-significant in the case of guanacos. We conclude that the continued presence of feral livestock, particularly donkeys, leads to damages to columnar cacti with potential effects on their populations and the physiognomy of this protected landscape.

In field damage of high and low cyanogenic cassava due to a generalist insect herbivore Cyrtomenus bergi (Hemiptera: Cydnidae).

PubMed

Riis, Lisbeth; Bellotti, Anthony Charles; Castaño, Oscar

2003-12-01

The hypothesis that cyanogenic potential in cassava roots deters polyphagous insects in the field is relevant to current efforts to reduce or eliminate the cyanogenic potential in cassava. To test this hypothesis, experiments were conducted in the field under natural selection pressure of the polyphagous root feeder Cyrtomenus bergi Froeschner (Hemiptera: Cydnidae). A number of cassava varieties (33) as well as 13 cassava siblings and their parental clone, each representing a determined level of cyanogenic potential (CNP), were scored for damage caused by C. bergi and related to CNP and nonglycosidic cyanogens, measured as hydrogen cyanide. Additionally, 161 low-CNP varieties (< 50 ppm hydrogen cyanide, fresh weight) from the cassava germplasm core collection at Centro Internacional de Agricultura Tropical (CIAT) were screened for resistance/tolerance to C. bergi. Low root damage scores were registered at all levels of CNP. Nevertheless, CNP and yield (or root size) partly explained the damage in cassava siblings (r2 = 0.82) and different cassava varieties (r2 = 0.42), but only when mean values of damage scores were used. This relation was only significant in one of two crop cycles. A logistic model describes the underlying negative relation between CNP and damage. An exponential model describes the underlying negative relation between root size and damage. Damage, caused by C. bergi feeding, released nonglycosidic cyanogens, and an exponential model fits the underlying positive relation. Fifteen low-CNP clones were selected for potential resistance/tolerance against C. bergi.

Low Velocity Impact Testing and Nondestructive Evaluation of Transparent Materials

NASA Astrophysics Data System (ADS)

Brennan, R. E.; Green, W. H.

2011-06-01

Advanced transparent materials are used in protective systems for enhancing the survivability of ground vehicles, air vehicles, and personnel in applications such as face shields, riot gear, and vehicle windows. Low velocity impact damage can limit visibility and compromise the structural integrity of a transparent system, increasing the likelihood of further damage or penetration from a high velocity impact strike. For this reason, it is critical to determine damage tolerance levels of transparent systems to indicate whether or not a component should be replaced. In this study, transparent laminate systems will be tested by comparing baseline conditions to experimentally controlled damage states. Destructive testing including air gun and sphere impact testing will be used to replicate low velocity impacts in the field. Characterization of the damaged state will include basic visual inspection as well as nondestructive techniques including cross-polarization, x-ray, and ultrasound. The combination of destructive testing and characterization of the resulting damage can help to establish a damage acceptance criterion for materials used in protective systems.

Mus308 Processes Oxygen and Nitrogen Ethylation DNA Damage in Germ Cells of Drosophila

PubMed Central

Díaz-Valdés, Nancy; Comendador, Miguel A.; Sierra, L. María

2010-01-01

The D. melanogaster mus308 gene, highly conserved among higher eukaryotes, is implicated in the repair of cross-links and of O-ethylpyrimidine DNA damage, working in a DNA damage tolerance mechanism. However, despite its relevance, its possible role on the processing of different DNA ethylation damages is not clear. To obtain data on mutation frequency and on mutation spectra in mus308 deficient (mus308−) conditions, the ethylating agent diethyl sulfate (DES) was analysed in postmeiotic male germ cells. These data were compared with those corresponding to mus308 efficient conditions. Our results indicate that Mus308 is necessary for the processing of oxygen and N-ethylation damage, for the survival of fertilized eggs depending on the level of induced DNA damage, and for an influence of the DNA damage neighbouring sequence. These results support the role of mus308 in a tolerance mechanism linked to a translesion synthesis pathway and also to the alternative end-joinig system. PMID:20936147

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.

High normal post-load plasma glucose, cardiometabolic risk factors and signs of organ damage in obese children.

PubMed

Di Bonito, Procolo; Licenziati, Maria Rosaria; Baroni, Marco Giorgio; Congiu, Tiziana; Incani, Michela; Iannuzzi, Arcangelo; Maffeis, Claudio; Perrone, Laura; Valerio, Giuliana; Del Giudice, Emanuele Miraglia

2014-08-01

To evaluate normoglycemic overweight/obese (Ow/Ob) children whose post-load plasma glucose (2hPG) cut-point may be significantly associated with cardiometabolic risk factors (CMRFs) and whether this cut-point predicts preclinical signs of organ damage. One thousand seven hundred and thrity four normoglycemic Ow/Ob children were stratified into quintiles of 2hPG, the sixth group was constituted by 101 children with impaired glucose tolerance (IGT). Moving from the lower quintiles of 2hPG to IGT, the groups differed for Prepubertal stage, BMI, fasting PG, insulin levels, blood pressure, and lipids. To evaluate the best cut-off of 2hPG related to CMRFs, the area under the receiver operating characteristic curve and the Youden's index was calculated. Insulin resistance, high blood pressure, and high triglyceride/HDL-C ratio were associated with a 2hPG cut-off of 110 mg/dl. Children with 2hPG ≥110 mg/dl showed 1.3-3.2 fold higher risk to have high levels of ALT (as surrogate of nonalcoholic fatty liver disease) or increased carotid intima-media thickness. This study, performed in a large cohort of Ow/Ob children, shows that an atherogenic risk profile and preclinical signs of organ damage are associated with post-challenge elevations in plasma glucose still considered in the high normal range. Copyright © 2014 The Obesity Society.

Safety issues in high speed machining

NASA Astrophysics Data System (ADS)

1994-05-01

There are several risks related to High-Speed Milling, but they have not been systematically determined or studied so far. Increased loads by high centrifugal forces may result in dramatic hazards. Flying tools or fragments from a tool with high kinetic energy may damage surrounding people, machines and devices. In the project, mechanical risks were evaluated, theoretic values for kinetic energies of rotating tools were calculated, possible damages of the flying objects were determined and terms to eliminate the risks were considered. The noise levels of the High-Speed Machining center owned by the Helsinki University of Technology (HUT) and the Technical Research Center of Finland (VTT) in practical machining situation were measured and the results were compared to those after basic preventive measures were taken.

Urinary 8-hydroxy-2'-deoxyguanosine (8-oxodG) level can predict acute renal damage in young children with urinary tract infection.

PubMed

Chien, Jien-Wen; Wang, Lien-Yen; Cheng, Yu-Shan; Tsai, Yi-Giien; Liu, Chin-San

2014-06-01

There are no good biomarkers to predict renal parenchymal involvement in children with urinary tract infection (UTI). Children (N = 73) younger than 5 years with UTI were enrolled. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8-oxodG) and total antioxidant capacity (TAC) were checked as markers of oxidative stress and antioxidant capacity, respectively. Tc99m-dimercaptosuccinic acid (DMSA) renal scintigraphy was used to find evidence of renal involvement. Patients with positive DMSA findings had higher levels of urinary 8-oxodG (p = 0.003) and higher urinary TAC (p = 0.001) than patients with normal DMSA findings. High level of urinary 8-oxodG may be a risk factor of severe renal damage.

Thermal effects in Cs DPAL and alkali cell window damage

NASA Astrophysics Data System (ADS)

Zhdanov, B. V.; Rotondaro, M. D.; Shaffer, M. K.; Knize, R. J.

2016-10-01

Experiments on power scaling of Diode Pumped Alkali Lasers (DPALs) revealed some limiting parasitic effects such as alkali cell windows and gain medium contamination and damage, output power degradation in time and others causing lasing efficiency decrease or even stop lasing1 . These problems can be connected with thermal effects, ionization, chemical interactions between the gain medium components and alkali cells materials. Study of all these and, possibly, other limiting effects and ways to mitigate them is very important for high power DPAL development. In this talk we present results of our experiments on temperature measurements in the gain medium of operating Cs DPAL at different pump power levels in the range from lasing threshold to the levels causing damage of the alkali cell windows. For precise contactless in situ temperature measurements, we used an interferometric technique, developed in our lab2 . In these experiments we demonstrated that damage of the lasing alkali cell starts in the bulk with thermal breakdown of the hydrocarbon buffer gas. The degradation processes start at definite critical temperatures of the gain medium, different for each mixture of buffer gas. At this critical temperature, the hydrocarbon and the excited alkali metal begin to react producing the characteristic black soot and, possibly, some other chemical compounds, which both harm the laser performance and significantly increase the harmful heat deposition within the laser medium. This soot, being highly absorptive, is catastrophically heated to very high temperatures that visually observed as bulk burning. This process quickly spreads to the cell windows and causes their damage. As a result, the whole cell is also contaminated with products of chemical reactions.

Unilateral Punctate Keratitis Secondary to Wallenberg Syndrome

PubMed Central

Boto, Ana; Del Hierro, Almudena; Capote, Maria; Noval, Susana; Garcia, Amanda; Santiago, Susana

2014-01-01

We studied three patients who developed left unilateral punctate keratitis after suffering left-sided Wallenberg Syndrome. A complex evolution occurred in two of them. In all cases, neurophysiological studies showed damage in the trigeminal sensory component at the bulbar level. Corneal involvement secondary to Wallenberg syndrome is a rare cause of unilateral superficial punctate keratitis. The loss of corneal sensitivity caused by trigeminal neuropathy leads to epithelial erosions that are frequently unobserved by the patient, resulting in a high risk of corneal-ulcer development with the possibility of superinfection. Neurophysiological studies can help to locate the anatomical level of damage at the ophthalmic branch of the trigeminal nerve, confirming the suspected etiology of stroke, and demonstrating that prior vascular involvement coincides with the location of trigeminal nerve damage. In some of these patients, oculofacial pain is a distinctive feature. PMID:24882965

Salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA.

PubMed

Gao, Qiuqiang; Liou, Liang-Chun; Ren, Qun; Bao, Xiaoming; Zhang, Zhaojie

2014-03-03

The yeast cell wall plays an important role in maintaining cell morphology, cell integrity and response to environmental stresses. Here, we report that salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA (ρ 0 ). Upon salt treatment, the cell wall is thickened, broken and becomes more sensitive to the cell wall-perturbing agent sodium dodecyl sulfate (SDS). Also, SCW11 mRNA levels are elevated in ρ 0 cells. Deletion of SCW11 significantly decreases the sensitivity of ρ 0 cells to SDS after salt treatment, while overexpression of SCW11 results in higher sensitivity. In addition, salt stress in ρ 0 cells induces high levels of reactive oxygen species (ROS), which further damages the cell wall, causing cells to become more sensitive towards the cell wall-perturbing agent.

Feline Toxoplasmosis: Tumor Necrosis Factor, Nitric Oxide, and Free Radicals in Seropositive Cats.

PubMed

Faria, Joice L M; Couto, Caroline do; Wierzynski, Sheron L; Bottari, Nathieli B; Baldissera, Matheus D; Pereira, Wanderson A B; Da Silva, Aleksandro S

2018-02-01

Toxoplasma gondii is a cosmopolitan protozoan that causes disease in several species, including humans. In cats, these infections are usually asymptomatic, but in other species they can lead to high levels of inflammatory and cell damage markers, causing cellular damage. Therefore, the aim of this study was to measure levels of tumor necrosis factor (TNF-α), reactive oxygen species (ROS), and nitric oxide (nitrite/nitrate-NO x ) in the serum of cats seropositive for T. gondii. Initially, we investigated the presence of antibodies against T. gondii in cats in the city of Concordia, Santa Catarina, Brazil, with the use of indirect immunofluorescence (IFA), and found 30 cats seropositive for T. gondii and 30 seronegative cats. In this study, seropositive cats showed higher levels of TNF-α, ROS, and NO x compared to seronegative cats. Although cats do not show clinical signs of disease, constant inflammatory response can cause cell damage, which over time may adversely affect the animal.

Understanding risks in the light of uncertainty: low-probability, high-impact coastal events in cities

NASA Astrophysics Data System (ADS)

Abadie, Luis Maria; Galarraga, Ibon; Sainz de Murieta, Elisa

2017-01-01

A quantification of present and future mean annual losses due to extreme coastal events can be crucial for adequate decision making on adaptation to climate change in coastal areas around the globe. However, this approach is limited when uncertainty needs to be accounted for. In this paper, we assess coastal flood risk from sea-level rise and extreme events in 120 major cities around the world using an alternative stochastic approach that accounts for uncertainty. Probability distributions of future relative (local) sea-level rise have been used for each city, under three IPPC emission scenarios, RCP 2.6, 4.5 and 8.5. The approach allows a continuous stochastic function to be built to assess yearly evolution of damages from 2030 to 2100. Additionally, we present two risk measures that put low-probability, high-damage events in the spotlight: the Value at Risk (VaR) and the Expected Shortfall (ES), which enable the damages to be estimated when a certain risk level is exceeded. This level of acceptable risk can be defined involving different stakeholders to guide progressive adaptation strategies. The method presented here is new in the field of economics of adaptation and offers a much broader picture of the challenges related to dealing with climate impacts. Furthermore, it can be applied to assess not only adaptation needs but also to put adaptation into a timeframe in each city.

Esculin improves dyslipidemia, inflammation and renal damage in streptozotocin-induced diabetic rats.

PubMed

Wang, Yue-Hua; Liu, Yan-Hong; He, Guo-Rong; Lv, Yang; Du, Guan-Hua

2015-11-09

Increasing studies have shown that dyslipidemia and inflammatory responses play important roles in the progression of microvascular diabetic complications. Esculin (ES), a coumarin derivative, was extracted from Fraxinus rhynchophylla. The present study was to evaluate the potential effects of ES on lipid metabolism, inflammation responses and renal damage in streptozotocin (STZ)-induced experimental diabetic rats and explore the possible mechanism. Diabetic rat model was established by administration high-glucose-fat diet and intraperitoneal injection of STZ 45 mg/kg. ES was administrated to diabetic rats intragastrically at 10, 30 and 90 mg/kg for 10 weeks respectively. The levels of triglycerides (TG), total cholesterol (T-CHO), low density lipoproteins (LDL), and high-density-cholesterol (HDL-C) in serum were measured. IL-1, IL-6, ICAM-1, NO, NAGL, and AGEs level in serum were detected by ELISA assay. The accumulation of AGEs in kidney tissue was examined by immunohistochemistry assay. The results showed that ES could decrease TG, T-CHO, LDL levels in serum of diabetic rats in a dose dependent manner. ES also decreased IL-1, IL-6, ICAM-1, NO and NGAL levels in serum of diabetic rats in a dose dependent manner. Furthermore, ES at 30 and 90 mg/kg significantly decreased AGEs level in serum and alleviated AGEs accumulation in renal in diabetic rats. Our findings indicate that ES could improve dyslipidemia, inflammation responses, renal damage in STZ-induced diabetic rats and the possible mechanism might be associated with the inhibition of AGEs formation.

Sodium fluoride induces apoptosis in the kidney of rats through caspase-mediated pathways and DNA damage.

PubMed

Song, Guo Hua; Gao, Ji Ping; Wang, Chun Fang; Chen, Chao Yang; Yan, Xiao Yan; Guo, Min; Wang, Yu; Huang, Fu Bing

2014-09-01

Long-term excessive sodium fluoride (NaF) intake can cause many bone diseases and nonskeletal fluorosis. The kidneys are the primary organs involved in the excretion and retention of NaF. The objective of the present study was to determine the effects of NaF treatment on renal cell apoptosis, DNA damage, and the protein expression levels of cytosolic cytochrome C (Cyt C) and cleaved caspases 9, 8, and 3 in vivo. Male Sprague-Dawley rats were divided randomly into four groups (control, low fluoride, medium fluoride, and high fluoride) and administered 0, 50, 100, and 200 mg/L of NaF, respectively, via drinking water for 120 days. Histopathological changes in the kidneys were visualized using hematoxylin and eosin staining. Renal cell apoptosis was examined using flow cytometry, and renal cell DNA damage was detected using the comet assay. Cytosolic Cyt C and cleaved caspases 9, 8, and 3 protein expression levels were visualized using immunohistochemistry and Western blotting. The results showed that NaF treatment increased apoptosis and DNA damage. In addition, NaF treatment increased the protein expression levels of cytosolic Cyt C and cleaved caspases 9, 8, and 3. These results indicated that NaF induces apoptosis in the kidney of rats through caspase-mediated pathway, and DNA damage may be involved in this process.

Fuel containment, lightning protection and damage tolerance in large composite primary aircraft structures

NASA Technical Reports Server (NTRS)

Griffin, Charles F.; James, Arthur M.

1985-01-01

The damage-tolerance characteristics of high strain-to-failure graphite fibers and toughened resins were evaluated. Test results show that conventional fuel tank sealing techniques are applicable to composite structures. Techniques were developed to prevent fuel leaks due to low-energy impact damage. For wing panels subjected to swept stroke lightning strikes, a surface protection of graphite/aluminum wire fabric and a fastener treatment proved effective in eliminating internal sparking and reducing structural damage. The technology features developed were incorporated and demonstrated in a test panel designed to meet the strength, stiffness, and damage tolerance requirements of a large commercial transport aircraft. The panel test results exceeded design requirements for all test conditions. Wing surfaces constructed with composites offer large weight savings if design allowable strains for compression can be increased from current levels.

Serum S100B level increases after running but not cycling exercise.

PubMed

Stocchero, Cintia Mussi Alvim; Oses, Jean Pierre; Cunha, Giovani Santos; Martins, Jocelito Bijoldo; Brum, Liz Marina; Zimmer, Eduardo Rigon; Souza, Diogo Onofre; Portela, Luis Valmor; Reischak-Oliveira, Alvaro

2014-03-01

The objective of this study was to investigate the effect of running versus cycling exercises upon serum S100B levels and typical markers of skeletal muscle damage such as creatine kinase (CK), aspartate aminotransferase (AST) and myoglobin (Mb). Although recent work demonstrates that S100B is highly expressed and exerts functional properties in skeletal muscle, there is no previous study that tries to establish a relationship between muscle damage and serum S100B levels after exercise. We conducted a cross-sectional study on 13 male triathletes. They completed 2 submaximal exercise protocols at anaerobic threshold intensity. Running was performed on a treadmill with no inclination (RUN) and cycling (CYC) using a cycle-simulator. Three blood samples were taken before (PRE), immediately after (POST) and 1 h after exercise for CK, AST, Mb and S100B assessments. We found a significant increase in serum S100B levels and muscle damage markers in RUN POST compared with RUN PRE. Comparing groups, POST S100B, CK, AST and Mb serum levels were higher in RUN than CYC. Only in RUN, the area under the curve (AUC) of serum S100B is positively correlated with AUC of CK and Mb. Therefore, immediately after an intense exercise such as running, but not cycling, serum levels of S100B protein increase in parallel with levels of CK, AST and Mb. Additionally, the positive correlation between S100B and CK and Mb points to S100B as an acute biomarker of muscle damage after running exercise.

Damage characterization of E-glass and C-glass fibre polymer composites after high velocity impact

NASA Astrophysics Data System (ADS)

Razali, N.; Sultan, M. T. H.; Cardona, F.; Jawaid, M.

2017-12-01

The purpose of this work is to identify impact damage on glass fibre reinforced polymer composite structures after high velocity impact. In this research, Type C-glass (600 g/m2) and Type E-glass (600 g/m2) were used to fabricate Glass Fibre-Reinforced Polymer composites (GFRP) plates. The panels were fabricated using a vacuum bagging and hot bounder method. Single stage gas gun (SSGG) was used to do the testing and data acquisition system was used to collect the damage data. Different types of bullets and different pressure levels were used for the experiment. The obtained results showed that the C-glass type of GFRP experienced more damage in comparison to E-glass type of materials based on the amount of energy absorbed on impact and the size of the damage area. All specimens underwent a partial fibre breakage but the laminates were not fully penetrated by the bullets. This indicated that both types of materials have high impact resistance even though the applied pressures of the gas gun were on the high range. We concluded that within the material specifications of the laminates including the type of glass fibre reinforcement and the thickness of the panels, those composite materials are safe to be applied in structural and body armour applications as an alternative to more expensive materials such as Kevlar and type S-glass fibre based panels.

Persistence of chromosome aberrations in mice acutely exposed to 56Fe+26 ions.

PubMed

Tucker, James D; Marples, Brian; Ramsey, Marilyn J; Lutze-Mann, Louise H

2004-06-01

Space exploration has the potential to yield exciting and significant discoveries, but it also brings with it many risks for flight crews. Among the less well studied of these are health effects from space radiation, which includes the highly charged, energetic particles of elements with high atomic numbers that constitute the galactic cosmic rays. In this study, we demonstrated that 1 Gy iron ions acutely administered to mice in vivo resulted in highly complex chromosome damage. We found that all types of aberrations, including dicentrics as well as translocations, insertions and acentric fragments, disappear rapidly with time after exposure, probably as a result of the death of heavily damaged cells, i.e. cells with multiple and/or complex aberrations. In addition, numerous cells have apparently simple exchanges as their only aberrations, and these cells appear to survive longer than heavily damaged cells. Eight weeks after exposure, the frequency of cells showing cytogenetic damage was reduced to less than 20% of the levels evident at 1 week, with little further decline apparent over an additional 8 weeks. These results indicate that exposure to 1 Gy iron ions produces heavily damaged cells, a small fraction of which appear to be capable of surviving for relatively long periods. The health effects of exposure to high-LET radiation in humans on prolonged space flights should remain a matter of concern.

Repairing the damage to Atlantis' External Tank

NASA Image and Video Library

2007-03-07

On an upper level of high bay 1 of the Vehicle Assembly Building, technicians secure protective material around the base of the nose cone of Atlantis' external tank. The nose cone will undergo repair for hail damage. A severe thunderstorm with golf ball-sized hail caused visible divots in the giant tank's foam insulation and minor surface damage to about 26 heat shield tiles on the shuttle's left wing. Further evaluation of the tank is necessary to get an accurate accounting of foam damage and determine the type of repair required and the time needed for that work. A new target launch date has not been determined, but teams will focus on preparing Atlantis for liftoff in late April on mission STS-117.

Repairing the damage to Atlantis' External Tank

NASA Image and Video Library

2007-03-07

On an upper level of high bay 1 of the Vehicle Assembly Building, technicians move protective material toward the nose cone (foreground) of Atlantis' external tank. The nose cone will undergo repair for hail damage. A severe thunderstorm with golf ball-sized hail caused visible divots in the giant tank's foam insulation and minor surface damage to about 26 heat shield tiles on the shuttle's left wing. Further evaluation of the tank is necessary to get an accurate accounting of foam damage and determine the type of repair required and the time needed for that work. A new target launch date has not been determined, but teams will focus on preparing Atlantis for liftoff in late April on mission STS-117.

Repairing the damage to Atlantis' External Tank

NASA Image and Video Library

2007-03-07

On an upper level of high bay 1 of the Vehicle Assembly Building, technicians secure protective material around Atlantis' external tank. The preparations are for future repair work of the hail damage that happened Feb. 27. A severe thunderstorm with golf ball-sized hail caused visible divots in the giant tank's foam insulation and minor surface damage to about 26 heat shield tiles on the shuttle's left wing. Further evaluation of the tank is necessary to get an accurate accounting of foam damage and determine the type of repair required and the time needed for that work. A new target launch date has not been determined, but teams will focus on preparing Atlantis for liftoff in late April on mission STS-117.

Estimation of the high-spatial-resolution variability in extreme wind speeds for forestry applications

NASA Astrophysics Data System (ADS)

Venäläinen, Ari; Laapas, Mikko; Pirinen, Pentti; Horttanainen, Matti; Hyvönen, Reijo; Lehtonen, Ilari; Junila, Päivi; Hou, Meiting; Peltola, Heli M.

2017-07-01

The bioeconomy has an increasing role to play in climate change mitigation and the sustainable development of national economies. In Finland, a forested country, over 50 % of the current bioeconomy relies on the sustainable management and utilization of forest resources. Wind storms are a major risk that forests are exposed to and high-spatial-resolution analysis of the most vulnerable locations can produce risk assessment of forest management planning. In this paper, we examine the feasibility of the wind multiplier approach for downscaling of maximum wind speed, using 20 m spatial resolution CORINE land-use dataset and high-resolution digital elevation data. A coarse spatial resolution estimate of the 10-year return level of maximum wind speed was obtained from the ERA-Interim reanalyzed data. Using a geospatial re-mapping technique the data were downscaled to 26 meteorological station locations to represent very diverse environments. Applying a comparison, we find that the downscaled 10-year return levels represent 66 % of the observed variation among the stations examined. In addition, the spatial variation in wind-multiplier-downscaled 10-year return level wind was compared with the WAsP model-simulated wind. The heterogeneous test area was situated in northern Finland, and it was found that the major features of the spatial variation were similar, but in some locations, there were relatively large differences. The results indicate that the wind multiplier method offers a pragmatic and computationally feasible tool for identifying at a high spatial resolution those locations with the highest forest wind damage risks. It can also be used to provide the necessary wind climate information for wind damage risk model calculations, thus making it possible to estimate the probability of predicted threshold wind speeds for wind damage and consequently the probability (and amount) of wind damage for certain forest stand configurations.

Effect of single-session aerobic exercise with varying intensities on lipid peroxidation and muscle-damage markers in sedentary males.

PubMed

Moflehi, Daruosh; Kok, Lian-Yee; Tengku-Kamalden, Tengku-Fadilah; Amri, Saidon

2012-05-23

This study was conducted to evaluate the effect of the different intensity levels of single-session aerobic exercise on serum levels of lipid peroxidation and muscle damage markers in sedentary males. Fifty one sedentary healthy males aged 21.76±1.89 years were randomly divided into four groups, with one control (n=10) and three treatment groups that attended single-session aerobic exercise with low (n=14), moderate (n=14), and high (n=13) intensities. The serum levels of malondialdehyde (MDA) and creatine kinase (CK) were measured. Data analysis revealed a significant effect by the intensity levels of aerobic exercise on MDA (P=0.001) and CK (P=0.003) post-test when the participants in the treatment groups were compared with the control. When the intensity of aerobic exercise was increased, the amount of MDA and CK was also found to be increased. Single-session aerobic exercise can increase the amount of MDA and CK, suggesting that low intensity level of aerobic exercise should be utilized for more adaptation, and to prevent lipid peroxidation and muscle damage in sedentary males.

Infant of diabetic mother

MedlinePlus

... high blood sugar (glucose) levels throughout the pregnancy. Causes There are two forms of diabetes during pregnancy: ... blood sugar may be so low as to cause brain damage. Possible Complications The risk of stillbirth ...

Damage-Resistant Composites Using Electrospun Nanofibers: A Multiscale Analysis of the Toughening Mechanisms.

PubMed

Daelemans, Lode; van der Heijden, Sam; De Baere, Ives; Rahier, Hubert; Van Paepegem, Wim; De Clerck, Karen

2016-05-11

Today, fiber-reinforced polymer composites are a standard material in applications where a high stiffness and strength are required at minimal weight, such as aerospace structures, ultralight vehicles, or even flywheels for highly efficient power storage systems. Although fiber-reinforced polymer composites show many advantages compared to other materials, delamination between reinforcing plies remains a major problem limiting further breakthrough. Traditional solutions that have been proposed to toughen the interlaminar region between reinforcing plies have already reached their limit or have important disadvantages such as a high cost or the need for adapted production processes. Recently, electrospun nanofibers have been suggested as a more viable interlaminar toughening method. Although the expected benefits are numerous, the research on composite laminates enhanced with electrospun nanofibrous veils is still very limited. The work that has been done so far is almost exclusively focused on interlaminar fracture toughness tests with different kinds of nanofibers, where typically a trial and error approach has been used. A thorough understanding of the micromechanical fracture mechanisms and the parameters to obtain toughened composites has not been reported as of yet, but it is crucial to advance the research and design highly damage-resistant composites. This article provides such insight by analyzing the nanofiber toughening effect on three different levels for several nanofiber types. Only by combining the results from different levels, a thorough understanding can be obtained. These levels correspond to the hierarchical nature of a composite: the laminate, the interlaminar region, and the matrix resin. It is found that each level corresponds to certain mechanisms that result in a toughening effect. The bridging of microcracks by electrospun nanofibers is the main toughening mechanism resulting in damage resistance. Nevertheless, the way in which the nanofiber bridging mechanism expresses itself is different for each scale and dependent on parameters linked to a certain scale. The multiscale analysis of the toughening mechanisms reported in this paper is therefore crucial for understanding the behavior of nanofiber toughened composites, and as such allows for designing novel, damage-resistant, nanofiber-toughened materials.

Characterization of Radiation Hardened Bipolar Linear Devices for High Total Dose Missions

NASA Technical Reports Server (NTRS)

McClure, Steven S.; Harris, Richard D.; Rax, Bernard G.; Thorbourn, Dennis O.

2012-01-01

Radiation hardened linear devices are characterized for performance in combined total dose and displacement damage environments for a mission scenario with a high radiation level. Performance at low and high dose rate for both biased and unbiased conditions is compared and the impact to hardness assurance methodology is discussed.

The Naked Mole-Rat Response to Oxidative Stress: Just Deal with It

PubMed Central

Lewis, Kaitlyn N.; Andziak, Blazej; Yang, Ting

2013-01-01

Abstract Significance: The oxidative stress theory of aging has been the most widely accepted theory of aging providing insights into why we age and die for over 50 years, despite mounting evidence from a multitude of species indicating that there is no direct relationship between reactive oxygen species (ROS) and longevity. Here we explore how different species, including the longest lived rodent, the naked mole-rat, have defied the most predominant aging theory. Recent Advances: In the case of extremely long-lived naked mole-rat, levels of ROS production are found to be similar to mice, antioxidant defenses unexceptional, and even under constitutive conditions, naked mole-rats combine a pro-oxidant intracellular milieu with high, steady state levels of oxidative damage. Clearly, naked mole-rats can tolerate this level of oxidative stress and must have mechanisms in place to prevent its translation into potentially lethal diseases. Critical Issues: In addition to the naked mole-rat, other species from across the phylogenetic spectrum and even certain mouse strains do not support this theory. Moreover, overexpressing or knocking down antioxidant levels alters levels of oxidative damage and even cancer incidence, but does not modulate lifespan. Future Directions: Perhaps, it is not oxidative stress that modulates healthspan and longevity, but other cytoprotective mechanisms that allow animals to deal with high levels of oxidative damage and stress, and nevertheless live long, relatively healthy lifespans. Studying these mechanisms in uniquely long-lived species, like the naked mole-rat, may help us tease out the key contributors to aging and longevity. Antioxid. Redox Signal. 19, 1388–1399. PMID:23025341

Doping of two-dimensional MoS2 by high energy ion implantation

NASA Astrophysics Data System (ADS)

Xu, Kang; Zhao, Yuda; Lin, Ziyuan; Long, Yan; Wang, Yi; Chan, Mansun; Chai, Yang

2017-12-01

Two-dimensional (2D) materials have been demonstrated to be promising candidates for next generation electronic circuits. Analogues to conventional Si-based semiconductors, p- and n-doping of 2D materials are essential for building complementary circuits. Controllable and effective doping strategies require large tunability of the doping level and negligible structural damage to ultrathin 2D materials. In this work, we demonstrate a doping method utilizing a conventional high-energy ion-implantation machine. Before the implantation, a Polymethylmethacrylate (PMMA) protective layer is used to decelerate the dopant ions and minimize the structural damage to MoS2, thus aggregating the dopants inside MoS2 flakes. By optimizing the implantation energy and fluence, phosphorus dopants are incorporated into MoS2 flakes. Our Raman and high-resolution transmission electron microscopy (HRTEM) results show that only negligibly structural damage is introduced to the MoS2 lattice during the implantation. P-doping effect by the incorporation of p+ is demonstrated by Photoluminescence (PL) and electrical characterizations. Thin PMMA protection layer leads to large kinetic damage but also a more significant doping effect. Also, MoS2 with large thickness shows less kinetic damage. This doping method makes use of existing infrastructures in the semiconductor industry and can be extended to other 2D materials and dopant species as well.

Influence of dermal exposure to ultraviolet radiation and coal tar (polycyclic aromatic hydrocarbons) on the skin aging process.

PubMed

Borska, Lenka; Andrys, Ctirad; Krejsek, Jan; Palicka, Vladimir; Vorisek, Viktor; Hamakova, Kvetoslava; Kremlacek, Jan; Borsky, Pavel; Fiala, Zdenek

2016-03-01

Ultraviolet radiation (UVR) and crude coal tar (CCT) containing PAHs can accelerate the skin-aging process (SAP). However, UVR induces the formation of an important protective factor in SAP (vitamin D). To determine the relation of SAP to selected risks and benefits of combined dermal exposure to UVR and coal tar (PAHs). The study group consisted of patients with chronic stable plaque psoriasis and treated by Goeckerman therapy (GT; daily dermal application of UVR and 5% CCT ointment). The levels of urinary 1-hydroxypyrene (1-OHP), oxidative stress (DNA and RNA damage), genotoxic damage (chromosomal aberration in peripheral lymphocytes; ABC), 25-hydroxy-vitamin D [25(OH)D] and the PASI score were evaluated before and after GT. Intensive dermal absorption of PAHs was confirmed by increased levels of 1-OHP (p<0.01). After the therapy, we found an increased level of oxidative stress (p<0.05), an increased level of genotoxic damage (ABC; p<0.001), a high efficiency of the treatment (p<0.001) and an elevated production of 25(OH)D (p<0.01). We also found a relationship between the duration of UVR and the genotoxic damage (p<0.01), vitD (p<0.05) and the PASI score (p<0.05). Furthermore, we found a relationship between oxidative stress and 25(OH)D (p<0.05) and between genotoxic damage and the PASI score (p<0.05). Dermal exposure to UVR and coal tar (PAHs) enhances the level of oxidative stress and genotoxic damage and thus contributes to SAP. However, the exposure is very effective as a treatment and elevates the production of 25(OH)D, the protective factor in SAP. According to our results, UVR is probably a more hazardous factor in SAP. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

High glucose-induced excessive reactive oxygen species promote apoptosis through mitochondrial damage in rat cartilage endplate cells.

PubMed

Jiang, Zengxin; Lu, Wei; Zeng, Qingmin; Li, Defang; Ding, Lei; Wu, Jingping

2018-04-16

Diabetes mellitus (DM) is an important factor in intervertebral disc degeneration (IDD). Apoptosis of cartilage endplate (CEP) cells is one of the initiators of IDD. However, the effects of high glucose on CEP cells are still unknown. Therefore, we conducted the present study to evaluate the effects of high glucose on CEP cells and to identify the mechanisms of those effects. Rat CEP cells were isolated and cultured in 10% foetal bovine serum (FBS, normal control) or high-glucose medium (10% FBS + 0.1 M glucose or 10% FBS + 0.2 M glucose, experimental conditions) for 1 or 3 days. In addition, CEP cells were treated with 0.2 M glucose for 3 days in the presence or absence of alpha-lipoic acid (ALA, 0.15 M). Flow cytometry was performed to identify and quantify the degree of apoptosis. The expression of reactive oxygen species (ROS) was assessed by flow cytometry, and mitochondrial damage (mitochondrial membrane potential) was assessed by fluorescence microscopy. Furthermore, the expression levels of cleaved caspase-3, cleaved caspase-9, Bcl-2, Bax, and cytochrome c were evaluated by Western blotting. High glucose significantly increased apoptosis and ROS accumulation in CEP cells in a dose- and time-dependent manner. Meanwhile, a disrupted mitochondrial membrane potential was detected in rat CEP cells cultured in the two high glucose concentrations. Incubating in high glucose enhanced the expression levels of cleaved caspase-3, cleaved caspase-9, Bax, and cytochrome c but decreased the level of the anti-apoptotic protein Bcl-2. ALA inhibited the expression of cleaved caspase-3, cleaved caspase-9, Bax, and cytochrome c but enhanced the expression of Bcl-2. ALA also prevented disruption of the mitochondrial membrane potential in CEP cells. This study demonstrates that high glucose-induced excessive reactive oxygen species promote mitochondrial damage, thus causing apoptosis in rat CEP cells in a dose- and time-dependent manner. ALA could prevent mitochondrial damage and apoptosis caused by high glucose in CEP cells. The results suggest that appropriate blood glucose control may be the key to preventing IDD in diabetic patients. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Increased N7-methyldeoxyguanosine DNA adducts after occupational exposure to pesticides and influence of genetic polymorphisms of paraoxonase-1 and glutathione S-transferase M1 and T1.

PubMed

Gómez-Martín, Antonio; Altakroni, Bashar; Lozano-Paniagua, David; Margison, Geoffrey P; de Vocht, Frank; Povey, Andrew C; Hernández, Antonio F

2015-06-01

There are concerns about genetic risks associated with long-term exposure to pesticides as these compounds may damage DNA, resulting in mutations that eventually lead to cancer, neurological, and reproductive adverse health effects. This study assessed DNA damage in intensive agricultural workers exposed to pesticides by determining the levels of N7-methyldeoxyguanosine (N7-MedG), an adduct known to be a robust biomarker of recent exposure to chemical methylating agents. A cohort of 39 plastic greenhouse workers was assessed for changes in lymphocyte DNA N7-MedG levels between low level and high level exposures during the course of a spraying season. The contributions of genetic polymorphisms of the pesticide-metabolizing enzymes paraoxonase-1 (PON1) and the glutathione S-transferases, GSTM1 and GSTT1, on N7-MedG levels and other potential confounders were also assessed. N7-MedG increased in the period of high pesticide exposure as compared to the low exposure period (0.23 and 0.18 µmol N7-MedG/mol dG for the unadjusted and adjusted linear mixed models, P = 0.02 and 0.08, respectively). Significant decreased levels of erythrocyte acetylcholinesterase and plasma cholinesterase were observed in the high versus low exposure period in both the unadjusted (2.85 U/g hemoglobin and 213.13 U/L, respectively) and adjusted linear mixed models (2.99 U/g hemoglobin and 230.77 U/L, respectively), indicating pesticide intake. In intensive agriculture workers, higher pesticide exposure increased DNA alkylation levels, further demonstrating the genotoxicity of pesticides in man. In addition, pesticide-exposed individuals with inherited susceptible metabolic genotypes (particularly, null genotype for GSTM1 and the PON1 192R allele) appear to have an increased risk of genotoxic DNA damage. Environ. Mol. Mutagen. 56:437-445, 2015. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

The effect of the impactor diameter and temperature on low velocity impact behavior of CFRP laminates

NASA Astrophysics Data System (ADS)

Evci, C.; Uyandıran, I.

2017-02-01

Impact damage is one of the major concerns that should be taken into account with the new aircraft and spacecraft structures which employ ever-growing use of composite materials. Considering the thermal loads encountered at different altitudes, both low and high temperatures can affect the properties and impact behavior of composite materials. This study aims to investigate the effect of temperature and impactor diameter on the impact behavior and damage development in balanced and symmetrical CFRP laminates which were manufactured by employing vacuum bagging process with autoclave cure. Instrumented drop-weight impact testing system is used to perform the low velocity impact tests in a range of temperatures ranged from 60 down to -50 °C. Impact tests for each temperature level were conducted using three different hemispherical impactor diameters varying from 10 to 20 mm. Energy profile method is employed to determine the impact threshold energies for damage evolution. The level of impact damage is determined from the dent depth on the impacted face and delamination damage detected using ultrasonic C-Scan technique. Test results reveal that the threshold of penetration energy, main failure force and delamination area increase with impactor diameter at all temperature levels. No clear influence of temperature on the critical force thresholds could be derived. However, penetration threshold energy decreased as the temperature was lowered. Drop in the penetration threshold was more obvious with quite low temperatures. Delamination damage area increased while the temperature decreased from +60 °C to -50 °C.

Space Radiation Effects on Human Cells: Modeling DNA Breakage, DNA Damage Foci Distribution, Chromosomal Aberrations and Tissue Effects

NASA Technical Reports Server (NTRS)

Ponomarev, A. L.; Huff, J. L.; Cucinotta, F. A.

2011-01-01

Future long-tem space travel will face challenges from radiation concerns as the space environment poses health risk to humans in space from radiations with high biological efficiency and adverse post-flight long-term effects. Solar particles events may dramatically affect the crew performance, while Galactic Cosmic Rays will induce a chronic exposure to high-linear-energy-transfer (LET) particles. These types of radiation, not present on the ground level, can increase the probability of a fatal cancer later in astronaut life. No feasible shielding is possible from radiation in space, especially for the heavy ion component, as suggested solutions will require a dramatic increase in the mass of the mission. Our research group focuses on fundamental research and strategic analysis leading to better shielding design and to better understanding of the biological mechanisms of radiation damage. We present our recent effort to model DNA damage and tissue damage using computational models based on the physics of heavy ion radiation, DNA structure and DNA damage and repair in human cells. Our particular area of expertise include the clustered DNA damage from high-LET radiation, the visualization of DSBs (DNA double strand breaks) via DNA damage foci, image analysis and the statistics of the foci for different experimental situations, chromosomal aberration formation through DSB misrepair, the kinetics of DSB repair leading to a model-derived spectrum of chromosomal aberrations, and, finally, the simulation of human tissue and the pattern of apoptotic cell damage. This compendium of theoretical and experimental data sheds light on the complex nature of radiation interacting with human DNA, cells and tissues, which can lead to mutagenesis and carcinogenesis later in human life after the space mission.

Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats

PubMed Central

Walter, Patrick B.; Knutson, Mitchell D.; Paler-Martinez, Andres; Lee, Sonia; Xu, Yu; Viteri, Fernando E.; Ames, Bruce N.

2002-01-01

Approximately two billion people, mainly women and children, are iron deficient. Two studies examined the effects of iron deficiency and supplementation on rats. In study 1, mitochondrial functional parameters and mitochondrial DNA (mtDNA) damage were assayed in iron-deficient (≤5 μg/day) and iron-normal (800 μg/day) rats and in both groups after daily high-iron supplementation (8,000 μg/day) for 34 days. This dose is equivalent to the daily dose commonly given to iron-deficient humans. Iron-deficient rats had lower liver mitochondrial respiratory control ratios and increased levels of oxidants in polymorphonuclear-leukocytes, as assayed by dichlorofluorescein (P < 0.05). Rhodamine 123 fluorescence of polymorphonuclear-leukocytes also increased (P < 0.05). Lowered respiratory control ratios were found in daily high-iron-supplemented rats regardless of the previous iron status (P < 0.05). mtDNA damage was observed in both iron-deficient rats and rats receiving daily high-iron supplementation, compared with iron-normal rats (P < 0.05). Study 2 compared iron-deficient rats given high doses of iron (8,000 μg) either daily or every third day and found that rats given iron supplements every third day had less mtDNA damage on the second and third day after the last dose compared to daily high iron doses. Both inadequate and excessive iron (10 × nutritional need) cause significant mitochondrial malfunction. Although excess iron has been known to cause oxidative damage, the observation of oxidant-induced damage to mitochondria from iron deficiency has been unrecognized previously. Untreated iron deficiency, as well as excessive-iron supplementation, are deleterious and emphasize the importance of maintaining optimal iron intake. PMID:11854522

Use of atomic force microscopy for characterizing damage evolution during fatigue

NASA Astrophysics Data System (ADS)

Cretegny, Laurent

2000-10-01

A study of the development of surface fatigue damage in PH 13-8 Mo stainless steel and copper by atomic force microscopy (AFM) was performed. AFM observations allow highly automated, quantitative characterization of surface deformation with a resolution of 5 nm or better, which is ideal for understanding fatigue damage evolution. A secondary objective was to establish a correlation between fatigue life exhausted and impedance spectroscopy. Strain controlled fatigue tests were conducted both in high and low cycle fatigue regimes, and interruptions of the fatigue tests allowed characterizing the evolution of the surface upset at various life-fractions. In the low strain amplitude tests on stainless steel (Deltaepsilonpl/2 = 0.0026%), surface damage occurred in the shape of narrow streaks at the interface between martensite laths where reverted austenite was present. The streaks eventually coalesced to form crack nuclei. In high strain amplitude tests (Deltaepsilon pl/2 = 0.049%), fatigue surface damage was essentially dominated by the formation of extrusions. In copper, both low (Deltaepsilonpl/2 = 0.061%) and high (Deltaepsilonpl/2 = 0.134%) strain amplitude tests showed the formation of slip bands (mainly extrusions) across entire grains. Protrusions were present only in copper specimens tested at the high strain amplitude. Crack nucleation in the low strain amplitude tests occurred in both materials at the interface between a region that sustained a high level of deformation and one with little evidence of surface upset. This commonality between these two materials that are otherwise very dissimilar in nature suggests a universal scheme for location of fatigue crack nucleation sites during HCF. A procedure was developed in this study to quantitatively characterize the amount of irreversible surface strain. The proposed formalism is applicable to any material, independently of the type of surface damage, and leads to a criterion for crack nucleation based on physical evidence of surface damage. A correlation between fatigue damage and impedance spectroscopy measurements was shown in copper, in particular during the primary cyclic hardening stage. The measurements were however less sensitive to the development of surface upset that occurred beyond that stage.

Bamboo salt attenuates CCl4-induced hepatic damage in Sprague-Dawley rats

PubMed Central

Zhao, Xin; Song, Jia-Le; Kil, Jeung-Ha

2013-01-01

Bamboo salt, a Korean folk medicine, is prepared with solar salt (sea salt) and baked several times at high temperatures in a bamboo case. In this study, we compared the preventive effects of bamboo salt and purified and solar salts on hepatic damage induced by carbon tetrachloride in Sprague-Dawley rats. Compared with purified and solar salts, bamboo salts prevented hepatic damage in rats, as evidenced by significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase (P < 0.05). Bamboo salt (baked 9×) triggered the greatest reduction in these enzyme levels. In addition, it also reduced the levels of the proinflammatory cytokines interleukin (IL)-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. Histopathological sections of liver tissue demonstrated the protective effect of bamboo salt, whereas sections from animals treated with the other salt groups showed a greater degree of necrosis. We also performed reverse transcription-polymerase chain reaction and western blot analyses of the inflammation-related genes iNOS, COX-2, TNF-α, and IL-1β in rat liver tissues. Bamboo salt induced a significant decrease (~80%) in mRNA and protein expression levels of COX-2, iNOS, TNF-α, and IL-1β, compared with the other salts. Thus, we found that baked bamboo salt preparations could prevent CCl4-induced hepatic damage in vivo. PMID:23964314

The impact of cortisol in steatotic and non-steatotic liver surgery.

PubMed

Cornide-Petronio, María Eugenia; Bujaldon, Esther; Mendes-Braz, Mariana; Avalos de León, Cindy G; Jiménez-Castro, Mónica B; Álvarez-Mercado, Ana I; Gracia-Sancho, Jordi; Rodés, Juan; Peralta, Carmen

2017-10-01

The intent of this study was to examine the effects of regulating cortisol levels on damage and regeneration in livers with and without steatosis subjected to partial hepatectomy under ischaemia-reperfusion. Ultimately, we found that lean animals undergoing liver resection displayed no changes in cortisol, whereas cortisol levels in plasma, liver and adipose tissue were elevated in obese animals undergoing such surgery. Such elevations were attributed to enzymatic upregulation, ensuring cortisol production, and downregulation of enzymes controlling cortisol clearance. In the absence of steatosis, exogenous cortisol administration boosted circulating cortisol, while inducing clearance of hepatic cortisol, thus maintaining low cortisol levels and preventing related hepatocellular harm. In the presence of steatosis, cortisol administration was marked by a substantial rise in intrahepatic availability, thereby exacerbating tissue damage and regenerative failure. The injurious effects of cortisol were linked to high hepatic acethylcholine levels. Upon administering an α7 nicotinic acethylcholine receptor antagonist, no changes in terms of tissue damage or regenerative lapse were apparent in steatotic livers. However, exposure to an M3 muscarinic acetylcholine receptor antagonist protected livers against damage, enhancing parenchymal regeneration and survival rate. These outcomes for the first time provide new mechanistic insight into surgically altered steatotic livers, underscoring the compelling therapeutic potential of cortisol-acetylcholine-M3 muscarinic receptors. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Physiological and biochemical responses of Prorocentrum minimum to high light stress

NASA Astrophysics Data System (ADS)

Park, So Yun; Choi, Eun Seok; Hwang, Jinik; Kim, Donggiun; Ryu, Tae Kwon; Lee, Taek-Kyun

2009-12-01

Prorocentrum minimum is a common bloomforming photosynthetic dinoflagellate found along the southern coast of Korea. To investigate the adaptive responses of P. minimum to high light stress, we measured growth rate, and generation of reactive oxidative species (ROS), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in cultures exposed to normal (NL) and high light levels (HL). The results showed that HL (800 μmol m-2 s-1) inhibited growth of P. minimum, with maximal inhibition after 7-9 days. HL also increased the amount of ROS and MDA, suggesting that HL stress leads to oxidative damage and lipid peroxidation in this species. Under HL, we first detected superoxide on day 4 and H2O2 on day 5. We also detected SOD activity on day 5 and CAT activity on day 6. The level of lipid peroxidation, an indicator of cell death, was high on day 8. Addition of diphenyleneiodonium (DPI), an NAD(P)H inhibitor, decreased the levels of superoxide generation and lipid peroxidation. Our results indicate that the production of ROS which results from HL stress in P. minimum also induces antioxidative enzymes that counteract oxidative damage and allow P. minimum to survive.

Sperm DNA damage has a negative association with live-birth rates after IVF.

PubMed

Simon, L; Proutski, I; Stevenson, M; Jennings, D; McManus, J; Lutton, D; Lewis, S E M

2013-01-01

Sperm DNA damage has a negative impact on pregnancy rates following assisted reproduction treatment (ART). The aim of the present study was to examine the relationship between sperm DNA fragmentation and live-birth rates after IVF and intracytoplasmic sperm injection (ICSI). The alkaline Comet assay was employed to measure sperm DNA fragmentation in native semen and in spermatozoa following density-gradient centrifugation in semen samples from 203 couples undergoing IVF and 136 couples undergoing ICSI. Men were divided into groups according to sperm DNA damage. Following IVF, couples with <25% sperm DNA fragmentation had a live-birth rate of 33%; in contrast, couples with >50% sperm DNA fragmentation had a much lower live-birth rate of 13%. Following ICSI, no significant differences in sperm DNA damage were found between any groups of patients. Sperm DNA damage was also associated with low live-birth rates following IVF in both men and couples with idiopathic infertility: 39% of couples and 41% of men with idiopathic infertility have high sperm DNA damage. Sperm DNA damage assessed by the Comet assay has a close inverse relationship with live-birth rates after IVF. Sperm DNA damage has a negative impact on assisted reproduction treatment outcome, in particular, on pregnancy rates. The aim of the present study was to examine the relationship between sperm DNA fragmentation and live-birth rates after IVF and intracytoplasmic sperm injection (ICSI). The alkaline Comet assay was employed to measure sperm DNA fragmentation in native semen and in spermatozoa following density-gradient centrifugation in semen samples from 203 couples undergoing IVF and 136 couples undergoing ICSI. Men were divided into groups according to sperm DNA damage and treatment outcome. Following IVF, couples with <25% sperm DNA fragmentation had a live birth rate of 33%. In contrast, couples with >50% sperm DNA fragmentation had a much lower live-birth rate of 13% following IVF. Following ICSI, there were no significant differences in levels of sperm DNA damage between any groups of patients. Sperm DNA damage was also associated with the very low live-birth rates following IVF in both men and couples with idiopathic infertility: 39% of couples and 41% of men have high level of sperm DNA damage. Sperm DNA damage assessed by the Comet assay has a close inverse relationship with live-birth rates after IVF. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Effect of kefir and low-dose aspirin on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet.

PubMed

Kanbak, Güngör; Uzuner, Kubilay; Kuşat Ol, Kevser; Oğlakçı, Ayşegül; Kartkaya, Kazım; Şentürk, Hakan

2014-01-01

Abstract We aim to study the effect of low-dose aspirin and kefir on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet. Forty adult male Sprague-Dawley rats were divided into five groups: control, high-salt (HS) (8.0% NaCl), HS+aspirin (10 mg/kg), HS+kefir (10.0%w/v), HS+aspirin +kefir. We measured sistolic blood pressure (SBP), mean arterial pressure (MAP), diastolic pressure, pulse pressure in the rats. Cathepsin B, L, DNA fragmentation and caspase-3 activities were determined from rat kidney tissues and rats clearance of creatinine calculated. Although HS diet increased significantly SBP, MAP, diastolic pressure, pulse pressure parameters compared the control values. They were not as high as accepted hypertension levels. When compared to HS groups, kefir groups significantly decrease Cathepsin B and DNA fragmentation levels. Caspase levels were elevated slightly in other groups according to control group. While, we also found that creatinine clearance was higher in HS+kefir and HS+low-dose aspirin than HS group. Thus, using low-dose aspirin had been approximately decreased of renal function damage. Kefir decreased renal function damage playing as Angiotensin-converting enzyme inhibitor. But, low-dose aspirin together with kefir worsened rat renal function damage. Cathepsin B might play role both apoptosis and prorenin-processing enzyme. But not caspase pathway may be involved in the present HS diet induced apoptosis. In conclusion, kefir and low-dose aspirin used independently protect renal function and renal damage induced by HS diet in rats.

Dual current readout for precision plating

NASA Technical Reports Server (NTRS)

Iceland, W. F.

1970-01-01

Bistable amplifier prevents damage in the low range circuitry of a dual scale ammeter. It senses the current and switches automatically to the high range circuitry as the current rises above a preset level.

Coagulopathy in patients with acute pulmonary embolism: a pilot study of whole blood coagulation and markers of endothelial damage.

PubMed

Lehnert, Per; Johansson, Pär I; Ostrowski, Sisse R; Møller, Christian H; Bang, Lia E; Olsen, Peter Skov; Carlsen, Jørn

2017-02-01

Whole blood coagulation and markers of endothelial damage were studied in patients with acute pulmonary embolism (PE), and evaluated in relation to PE severity. Twenty-five patients were enrolled prospectively each having viscoelastical analysis of whole blood done using thrombelastography (TEG) and Multiplate aggregometry. Fourteen of these patients were investigated for endothelial damage by ELISA measurements of Syndecan-1 (endothelial glycocalyx degradation), soluble endothelial Selectin (endothelial cell activation), soluble Thrombomodulin (endothelial cell injury) and Histone Complexed DNA fragments (endothelial cytotoxic histones). The mean values of TEG and Multiplate parameters were all within the reference levels, but a significant difference between patients with high and intermediate risk PE was observed for Ly30 (lytic activity) 1.5% [0-10] vs. 0.2% [0-2.2] p = .04, and ADP (platelet reactivity) 92 U [20-145] vs. 59 U [20-111] p = .03. A similar difference was indicated for functional fibrinogen 21 mm [17-29] vs. 18 mm [3-23] p = .05. Analysis of endothelial markers identified a significant difference in circulating levels between high and intermediate risk PE patients for Syndecan-1 118.6 ng/mL [76-133] vs. 36.3 ng/mL [11.8-102.9] p = .008. In conclusion, patients with acute PE had normal whole blood coagulation, but high risk PE patients had signs of increased activity of the haemostatic system and significantly increased level of endothelial glycocalyx degradation.

Whales Use Distinct Strategies to Counteract Solar Ultraviolet Radiation

PubMed Central

Martinez-Levasseur, Laura M.; Birch-Machin, Mark A.; Bowman, Amy; Gendron, Diane; Weatherhead, Elizabeth; Knell, Robert J.; Acevedo-Whitehouse, Karina

2013-01-01

A current threat to the marine ecosystem is the high level of solar ultraviolet radiation (UV). Large whales have recently been shown to suffer sun-induced skin damage from continuous UV exposure. Genotoxic consequences of such exposure remain unknown for these long-lived marine species, as does their capacity to counteract UV-induced insults. We show that UV exposure induces mitochondrial DNA damage in the skin of seasonally sympatric fin, sperm, and blue whales and that this damage accumulates with age. However, counteractive molecular mechanisms are markedly different between species. For example, sperm whales, a species that remains for long periods at the sea surface, activate genotoxic stress pathways in response to UV exposure whereas the paler blue whale relies on increased pigmentation as the season progresses. Our study also shows that whales can modulate their responses to fluctuating levels of UV, and that different evolutionary constraints may have shaped their response strategies. PMID:23989080

Transport properties of damaged materials. Cementitious barriers partnership

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

Langton, C.

2014-11-01

The objective of the Cementitious Barriers Partnership (CBP) project is to develop tools to improve understanding and prediction of the long-term structural, hydraulic, and chemical performance of cementitious barriers used in low-level waste storage applications. One key concern for the long-term durability of concrete is the degradation of the cementitious matrix, which occurs as a result of aggressive chemical species entering the material or leaching out in the environment, depending on the exposure conditions. The objective of the experimental study described in this report is to provide experimental data relating damage in cementitious materials to changes in transport properties, whichmore » can eventually be used to support predictive model development. In order to get results within a reasonable timeframe and to induce as much as possible uniform damage level in materials, concrete samples were exposed to freezing and thawing (F/T) cycles. The methodology consisted in exposing samples to F/T cycles and monitoring damage level with ultrasonic pulse velocity measurements. Upon reaching pre-selected damage levels, samples were tested to evaluate changes in transport properties. Material selection for the study was motivated by the need to get results rapidly, in order to assess the relevance of the methodology. Consequently, samples already available at SIMCO from past studies were used. They consisted in three different concrete mixtures cured for five years in wet conditions. The mixtures had water-to-cement ratios of 0.5, 0.65 and 0.75 and were prepared with ASTM Type I cement only. The results showed that porosity is not a good indicator for damage caused by the formation of microcracks. Some materials exhibited little variations in porosity even for high damage levels. On the other hand, significant variations in tortuosity were measured in all materials. This implies that damage caused by internal pressure does not necessarily create additional pore space in the microstructure, but likely creates new thin pathways between existing pore space for species to travel. These results have a significant impact on modeling efforts. Models relating porosity to tortuosity and permeability are unlikely to provide the correct basis for predicting long-term durability of concrete sustaining internal pressures and microcrack formation. Other avenues like the modeling of internal crystallization pressure need to be explored.« less

Integrated health management and control of complex dynamical systems

NASA Astrophysics Data System (ADS)

Tolani, Devendra K.

2005-11-01

A comprehensive control and health management strategy for human-engineered complex dynamical systems is formulated for achieving high performance and reliability over a wide range of operation. Results from diverse research areas such as Probabilistic Robust Control (PRC), Damage Mitigating/Life Extending Control (DMC), Discrete Event Supervisory (DES) Control, Symbolic Time Series Analysis (STSA) and Health and Usage Monitoring System (HUMS) have been employed to achieve this goal. Continuous-domain control modules at the lower level are synthesized by PRC and DMC theories, whereas the upper-level supervision is based on DES control theory. In the PRC approach, by allowing different levels of risk under different flight conditions, the control system can achieve the desired trade off between stability robustness and nominal performance. In the DMC approach, component damage is incorporated in the control law to reduce the damage rate for enhanced structural durability. The DES controller monitors the system performance and, based on the mission requirements (e.g., performance metrics and level of damage mitigation), switches among various lower-level controllers. The core idea is to design a framework where the DES controller at the upper-level, mimics human intelligence and makes appropriate decisions to satisfy mission requirements, enhance system performance and structural durability. Recently developed tools in STSA have been used for anomaly detection and failure prognosis. The DMC deals with the usage monitoring or operational control part of health management, where as the issue of health monitoring is addressed by the anomaly detection tools. The proposed decision and control architecture has been validated on two test-beds, simulating the operations of rotorcraft dynamics and aircraft propulsion.

Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease

PubMed Central

Hasham, Muneer G.; Baxan, Nicoleta; Stuckey, Daniel J.; Branca, Jane; Perkins, Bryant; Dent, Oliver; Duffy, Ted; Hameed, Tolani S.; Stella, Sarah E.; Bellahcene, Mohammed; Schneider, Michael D.; Harding, Sian E.; Rosenthal, Nadia

2017-01-01

ABSTRACT Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8) agonist Resiquimod. We observe a cardiac phenotype reminiscent of autoimmune-mediated dilated cardiomyopathy, and identify auto-antibodies as major contributors to cardiac tissue damage. Resiquimod-induced heart disease is a highly relevant mouse model for mechanistic and therapeutic studies aiming to protect the heart during autoimmunity. PMID:28250051

Report on the Study of Radiation Damage in Calcium Fluoride and Magnesium Fluoride Crystals for use in Excimer Laser Applications

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

None, None

1999-10-04

A study was performed to investigate the effects of radiation damage in calcium fluoride and magnesium fluoride crystals caused by gamma rays and UV photons from excimer lasers. The purpose was to study and correlate the damage caused by these two different mechanisms in various types of material used for fabricating optical elements in high power excimer lasers and lens systems of lithography tools. These optical systems are easily damaged by the laser itself, and it is necessary to use only the most radiation resistant materials for certain key elements. It was found that a clear correlation exists between the,more » radiation induced damage caused by high energy gamma rays and that produced by UV photons from the excimer laser. This correlation allows a simple procedure to be developed to select the most radiation resistant material at the ingot level, which would be later used to fabricate various components of the optical system. This avoids incurring the additional cost of fabricating actual optical elements with material that would later be damaged under prolonged use. The result of this screening procedure can result in a considerable savings in the overall cost of the lens and laser system.« less

Corrupting the DNA damage response: a critical role for Rad52 in tumor cell survival.

PubMed

Lieberman, Rachel; You, Ming

2017-07-15

The DNA damage response enables cells to survive, maintain genome integrity, and to safeguard the transmission of high-fidelity genetic information. Upon sensing DNA damage, cells respond by activating this multi-faceted DNA damage response leading to restoration of the cell, senescence, programmed cell death, or genomic instability if the cell survives without proper repair. However, unlike normal cells, cancer cells maintain a marked level of genomic instability. Because of this enhanced propensity to accumulate DNA damage, tumor cells rely on homologous recombination repair as a means of protection from the lethal effect of both spontaneous and therapy-induced double-strand breaks (DSBs) in DNA. Thus, modulation of DNA repair pathways have important consequences for genomic instability within tumor cell biology and viability maintenance under high genotoxic stress. Efforts are underway to manipulate specific components of the DNA damage response in order to selectively induce tumor cell death by augmenting genomic instability past a viable threshold. New evidence suggests that RAD52, a component of the homologous recombination pathway, is important for the maintenance of tumor genome integrity. This review highlights recent reports indicating that reducing homologous recombination through inhibition of RAD52 may represent an important focus for cancer therapy and the specific efforts that are already demonstrating potential.

Radiation damages during synchrotron X-ray micro-analyses of Prussian blue and zinc white historic paintings: detection, mitigation and integration

NASA Astrophysics Data System (ADS)

Gervais, Claire; Thoury, Mathieu; Réguer, Solenn; Gueriau, Pierre; Mass, Jennifer

2015-11-01

High-flux synchrotron techniques allow microspectroscopic analyses of artworks that were not feasible even a few years ago, allowing for a more detailed characterization of their constituent materials and a better understanding of their chemistry. However, interaction between high-flux photons and matter at the sub-microscale can generate damages which are not visually detectable. We show here different methodologies allowing to evidence the damages induced by microscopic X-ray absorption near-edge structure spectroscopy analysis (μXANES) at the Fe and Zn K-edges of a painting dating from the turn of the twentieth century containing Prussian blue and zinc white. No significant degradation of the pigments was noticed, in agreement with the excellent condition of the painting. However, synchrotron radiation damages occurred at several levels, from chemical changes of the binder, modification of crystal defects in zinc oxide, to Prussian blue photoreduction. They could be identified by using both the μXANES signal during analysis and with photoluminescence imaging in the deep ultraviolet and visible ranges after analysis. We show that recording accurately damaged areas is a key step to prevent misinterpretation of results during future re-examination of the sample. We conclude by proposing good practices that could help in integrating radiation damage avoidance into the analytical pathway.

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

RSRM top hat cover simulator lightning test, volume 1

NASA Technical Reports Server (NTRS)

1990-01-01

The test sequence was to measure electric and magnetic fields induced inside a redesigned solid rocket motor case when a simulated lightning discharge strikes an exposed top hat cover simulator. The test sequence was conducted between 21 June and 17 July 1990. Thirty-six high rate-of-rise Marx generator discharges and eight high current bank discharges were injected onto three different test article configurations. Attach points included three locations on the top hat cover simulator and two locations on the mounting bolts. Top hat cover simulator and mounting bolt damage and grain cover damage was observed. Overall electric field levels were well below 30 kilowatts/meter. Electric field levels ranged from 184.7 to 345.9 volts/meter and magnetic field levels were calculated from 6.921 to 39.73 amperes/meter. It is recommended that the redesigned solid rocket motor top hat cover be used in Configuration 1 or Configuration 2 as an interim lightning protection device until a lightweight cover can be designed.

Floods of April-June 1952 in Utah and Nevada

USGS Publications Warehouse

Wells, J.V.B.

1957-01-01

The floods of April-June 1952 in the Great Basin and in the Green River basin in Utah came as the result of the heaviest snow cover recorded, a long period of near-record subnormal temperature during March and early April, and an abrupt change to above-normal temperature that induced rapid melting.Rainfall played an insignificant part. Low- and intermediate-elevation snow melted, bringing many streams to record-high level. Large diurnal fluctuations of discharge were evident on smaller streams. The temperature remained high until mid-May. As high-elevation snow became primed for runoff, the temperature dropped enough to refreeze and alter the structure of snow cover, thus reducing the effectiveness of the subsequent melting temperature. Had there been no respite from melting temperatures much greater peak discharges would have occurred, with damage greatly exceeding that experienced. Streams remained at high levels for several weeks.Record peaks were reached on Strawberry River, lower Weber River, Ogden River, Spanish Fork, lower Provo River, and Jordan River in Utah; Humboldt River and its tributaries draining the north area of the basin in Nevada; and the central Bear River in Idaho and Wyoming. Record volumes for the water year were measured on many streams in the northcentral part of Utah, the northeastern part of Nevada, and the central part of the Bear River basin in Idaho and Wyoming. Damage in the Great Basin reached \\$10 million and in the Green River basin, more than$300,000. Two lives were lost on Ogden River. The greatest urban damage, in Salt Lake City, totaled \\$1.9 million; the greatest single damage, to Denver and Rio Grande Western Railroad, was \\$510,000.

Iris Damage Is Associated With Elevated Cytokine Levels in Aqueous Humor.

PubMed

Aketa, Naohiko; Yamaguchi, Takefumi; Suzuki, Terumasa; Higa, Kazunari; Yagi-Yaguchi, Yukari; Satake, Yoshiyuki; Tsubota, Kazuo; Shimazaki, Jun

2017-05-01

To evaluate the association between iris damage and cytokine levels in the aqueous humor (AqH). A total of 201 AqH samples from 201 consecutive patients (mean age 73.7 ± 10.6) were collected at the beginning of corneal transplantation or cataract surgery. Iris damage of each case was assessed from preoperative slit-lamp findings based on its severity. The subjects were classified into three groups: eyes without iris damage (126 eyes), eyes with mild iris damage (51 eyes), and eyes with severe iris damage (24 eyes). The levels of cytokines (IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17a, interferon gamma-induced protein [IP]-10, monocyte chemotactic protein [MCP]-1, IFN-α, IFN-γ, macrophage inflammatory protein [MIP]-1α, MIP-1β, P-selectin, E-selectin, soluble intercellular adhesion molecule [sICAM]-1, TNF-α, and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in AqH were measured by multiplex beads immunoassay. The levels of aqueous protein, IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17A, MCP-1, TNF-α, E-selectin, P-selectin, and sICAM-1 in eyes with mild and severe iris damage were higher than in those without iris damage (P < 0.033). Multivariate analyses of clinical factors revealed that iris damage was associated with the history of complicated glaucoma, and the number of previous intraocular surgeries. The levels of AqH IL-6, IL-8, IL-13, MIP-1α, TNF-α, and sICAM-1 were significantly elevated in eyes with mild and severe iris damage in phakic eyes, and the levels of AqH IL-8 and sICAM-1 were significantly elevated in eyes with severe iris damage in pseudophakic eyes, compared with the eyes without iris damage (P < 0.045). Iris damage was associated with the elevation in the levels of aqueous protein and cytokines.

Assessing forest damage in high-elevation coniferous forests in Vermont and New Hampshire using Thematic Mapper data

NASA Technical Reports Server (NTRS)

Vogelmann, James E.; Rock, Barrett N.

1988-01-01

This study evaluates the potential of measuring/mapping forest damage in spruce-fir forests in the Green Mountains of Vermont and White Mountains of New Hampshire using Landsat Thematic Mapper (TM) data. The TM 1.65/0.83-micron (TM5/4) and 2.22/0.83-micron (TM7/4) band ratios were found to correlate well with ground-based measurements of forest damage (a measure of percentage foliar loss) at 11 spruce-fir stands located on Camels Hump, a mountain in northern Vermont. Images using 0.56 and 1.65-micron bands with 1.65/0.83-micron band ratios indicated locations of heavy conifer forest damage. Both 1.65/0.83 and 2.22/0.83-micron band ratios were used to quantify levels of conifer forest damage among individual mountains throughout many of the Green and White Mountains. Damage was found to be consistently higher for the Green than the White Mountains.

Damage detection of engine bladed-disks using multivariate statistical analysis

NASA Astrophysics Data System (ADS)

Fang, X.; Tang, J.

2006-03-01

The timely detection of damage in aero-engine bladed-disks is an extremely important and challenging research topic. Bladed-disks have high modal density and, particularly, their vibration responses are subject to significant uncertainties due to manufacturing tolerance (blade-to-blade difference or mistuning), operating condition change and sensor noise. In this study, we present a new methodology for the on-line damage detection of engine bladed-disks using their vibratory responses during spin-up or spin-down operations which can be measured by blade-tip-timing sensing technique. We apply a principle component analysis (PCA)-based approach for data compression, feature extraction, and denoising. The non-model based damage detection is achieved by analyzing the change between response features of the healthy structure and of the damaged one. We facilitate such comparison by incorporating the Hotelling's statistic T2 analysis, which yields damage declaration with a given confidence level. The effectiveness of the method is demonstrated by case studies.

Structural and Mechanical Repair of Diffuse Damage in Cortical Bone in vivo

PubMed Central

Seref-Ferlengez, Zeynep; Basta-Pljakic, Jelena; Kennedy, Oran D.; Philemon, Claudy J.; Schaffler, Mitchell B.

2014-01-01

Physiological wear and tear causes bone microdamage at several hierarchical levels, and these have different biological consequences. Bone remodeling is widely held to be the mechanism by which bone microdamage is repaired. However, recent studies showed that unlike typical linear microcracks, small crack damage, the clusters of submicron-sized matrix cracks also known as diffuse damage (Dif.Dx), does not activate remodeling. Thus, the fate of diffuse damage in vivo is not known. To examine this, we induced selectively Dif.Dx in rat ulnae in vivo by using end-load ulnar bending creep model. Changes in damage content were assessed by histomorphometry and mechanical testing immediately after loading (i.e., acute loaded) or at 14 days after damage induction (i.e., survival ulnae). Dif.Dx area was markedly reduced over the 14-day survival period after loading (p<0.02). We did not observe any intracortical resorption and there was no increase in cortical bone area in survival ulnae. The reduction in whole bone stiffness in acute loaded ulnae was restored to baseline levels in survival ulnae (p>0.6). Microindentation studies showed that Dif.Dx caused a highly localized reduction in elastic modulus in diffuse damage regions of the ulnar cortex. Moduli in these previously damaged bone areas were restored to control values by 14 days after loading. Our current findings indicate that small crack damage in bone can be repaired without bone remodeling, and suggest that alternative repair mechanisms exist in bone to deal with submicron-sized matrix cracks. Those mechanisms are currently unknown and further investigations are needed to elucidate the mechanisms by which this direct repair occurs. PMID:25042459

Meta-analysis of attitudes toward damage-causing mammalian wildlife.

PubMed

Kansky, Ruth; Kidd, Martin; Knight, Andrew T

2014-08-01

Many populations of threatened mammals persist outside formally protected areas, and their survival depends on the willingness of communities to coexist with them. An understanding of the attitudes, and specifically the tolerance, of individuals and communities and the factors that determine these is therefore fundamental to designing strategies to alleviate human-wildlife conflict. We conducted a meta-analysis to identify factors that affected attitudes toward 4 groups of terrestrial mammals. Elephants (65%) elicited the most positive attitudes, followed by primates (55%), ungulates (53%), and carnivores (44%). Urban residents presented the most positive attitudes (80%), followed by commercial farmers (51%) and communal farmers (26%). A tolerance to damage index showed that human tolerance of ungulates and primates was proportional to the probability of experiencing damage while elephants elicited tolerance levels higher than anticipated and carnivores elicited tolerance levels lower than anticipated. Contrary to conventional wisdom, experiencing damage was not always the dominant factor determining attitudes. Communal farmers had a lower probability of being positive toward carnivores irrespective of probability of experiencing damage, while commercial farmers and urban residents were more likely to be positive toward carnivores irrespective of damage. Urban residents were more likely to be positive toward ungulates, elephants, and primates when probability of damage was low, but not when it was high. Commercial and communal farmers had a higher probability of being positive toward ungulates, primates, and elephants irrespective of probability of experiencing damage. Taxonomic bias may therefore be important. Identifying the distinct factors explaining these attitudes and the specific contexts in which they operate, inclusive of the species causing damage, will be essential for prioritizing conservation investments. © 2014 The Authors. Conservation Biology published by Wiley Periodicals, Inc., on behalf of the Society for Conservation Biology.

Oxidative damage and antioxidant defense in thymus of malnourished lactating rats.

PubMed

Gavia-García, Graciela; González-Martínez, Haydeé; Miliar-García, Ángel; Bonilla-González, Edmundo; Rosas-Trejo, María de Los Ángeles; Königsberg, Mina; Nájera-Medina, Oralia; Luna-López, Armando; González-Torres, María Cristina

2015-01-01

Malnutrition has been associated with oxidative damage by altered antioxidant protection mechanisms. Specifically, the aim of this study was to evaluate oxidative damage (DNA and lipid) and antioxidant status (superoxide dismutase [SOD], glutathione peroxidase [GPx], and catalase [CAT] mRNA, and protein expression) in thymus from malnourished rat pups. Malnutrition was induced during the lactation period by the food competition method. Oxidative DNA damage was determined quantifying 8-oxo-7, 8-dihydro-2'-deoxyguanosine adduct by high-performance liquid chromatography. Lipid peroxidation was assessed by the formation of thiobarbituric acid-reactive substances. Levels of gene and protein expression of SOD, GPx, and CAT were evaluated by real-time polymerase chain reaction and Western blot, respectively. Antioxidant enzyme activities were measured spectrophotometrically. Oxidative DNA damage and lipid peroxidation significantly increased in second-degree (MN-2) and third-degree malnourished (MN-3) rats compared with well-nourished rats. Higher amounts of oxidative damage, lower mRNA expression, and lower relative concentrations of protein, as well as decreased antioxidant activity of SOD, GPx, and CAT were associated with the MN-2 and MN-3 groups. The results of this study demonstrated that higher body-weight deficits were related to alterations in antioxidant protection, which contribute to increased levels of damage in the thymus. To our knowledge, this study demonstrated for the first time that early in life, malnutrition leads to increased DNA and lipid oxidative damage, attributable to damaged antioxidant mechanisms including transcriptional and enzymatic activity alterations. These findings may contribute to the elucidation of the causes of previously reported thymus dysfunction, and might explain partially why children and adults who have overcome child undernourishment experience immunologic deficiencies. Copyright © 2015 Elsevier Inc. All rights reserved.

DETECTION OF BACTERIAL CYTOTOXIC ACTIVITIES FROM WATER-DAMAGED CEILING TILE MATERIAL FOLLOWING INCUBATION ON BLOOD AGAR

EPA Science Inventory

Samples of ceiling tiles with high levels of bacteria exhibited cytotoxic activities on a HEP-2 tissue culture assay. Ceiling tiles containing low levels of bacterial colonization did not show cytotoxic activities on the HEP-2 tissue culture assay. Using a spread plate procedure ...

The application of compressive sampling in rapid ultrasonic computerized tomography (UCT) technique of steel tube slab (STS).

PubMed

Jiang, Baofeng; Jia, Pengjiao; Zhao, Wen; Wang, Wentao

2018-01-01

This paper explores a new method for rapid structural damage inspection of steel tube slab (STS) structures along randomly measured paths based on a combination of compressive sampling (CS) and ultrasonic computerized tomography (UCT). In the measurement stage, using fewer randomly selected paths rather than the whole measurement net is proposed to detect the underlying damage of a concrete-filled steel tube. In the imaging stage, the ℓ1-minimization algorithm is employed to recover the information of the microstructures based on the measurement data related to the internal situation of the STS structure. A numerical concrete tube model, with the various level of damage, was studied to demonstrate the performance of the rapid UCT technique. Real-world concrete-filled steel tubes in the Shenyang Metro stations were detected using the proposed UCT technique in a CS framework. Both the numerical and experimental results show the rapid UCT technique has the capability of damage detection in an STS structure with a high level of accuracy and with fewer required measurements, which is more convenient and efficient than the traditional UCT technique.

Study of the Genes and Mechanism Involved in the Radioadaptive Response

NASA Technical Reports Server (NTRS)

Dasgupta, Pushan R.

2009-01-01

The radioadaptive response is a phenomenon where exposure to a prior low dose of radiation reduces the level of damage induced by a subsequent high radiation dose. The molecular mechanism behind this is still not well understood. Learning more about the radioadaptive response is critical for long duration spaceflight since astronauts are exposed to low levels of cosmic radiation. The micronucleus assay was used to measure the level of damage caused by radiation. Although cells which were not washed with phosphate buffered saline (PBS) after a low priming dose of 5cGy did not show adaptation to the challenge dose, washing the cells with PBS and giving the cells fresh media after the low dose did allow radioadaptation to occur. This is consistent with the results of a previous publication by another research group. In the present study, genes involved in DNA damage signaling and the oxidative stress response were studied using RT PCR techniques in order to look at changes in expression level after the low dose with or without washing. Our preliminary results indicate that upregulation of oxidative stress response genes ANGPTL7, NCF2, TTN, and SRXN1 may be involved in the radioadaptive response. The low dose of radiation alone was found to activate the oxidative stress response genes GPR156 and MTL5, whereas, washing the cells alone caused relatively robust upregulation of the oxidative stress response genes DUSP1 and PTGS2. Washing after the priming dose showed some changes in the expression level of several DNA damage signaling genes. In addition, we studied whether washing the cells after the priming dose has an effect on the level of nitric oxide in both the media and cells, since nitric oxide levels are known to increase in the media of the cells after a high dose of radiation only if the cells were already exposed to a low priming dose. Based on this preliminary study, we propose that washing the cells after priming exposure actually eliminates some factor secreted by the cells that inhibits radioadaptation leading to the upregulation of some genes which initiates the response.

Indicators of replicative damage in equine tendon fibroblast monolayers

PubMed Central

2013-01-01

Background Superficial digital flexor tendon (SDFT) injuries of horses usually follow cumulative matrix microdamage; it is not known why the reparative abilities of tendon fibroblasts are overwhelmed or subverted. Relevant in vitro studies of this process require fibroblasts not already responding to stresses caused by the cell culture protocols. We investigated indicators of replicative damage in SDFT fibroblast monolayers, effects of this on their reparative ability, and measures that can be taken to reduce it. Results We found significant evidence of replicative stress, initially observing consistently large numbers of binucleate (BN) cells. A more variable but prominent feature was the presence of numerous gammaH2AX (γH2AX) puncta in nuclei, this being a histone protein that is phosphorylated in response to DNA double-stranded breaks (DSBs). Enrichment for injury detection and cell cycle arrest factors (p53 (ser15) and p21) occurred most frequently in BN cells; however, their numbers did not correlate with DNA damage levels and it is likely that the two processes have different causative mechanisms. Such remarkable levels of injury and binucleation are usually associated with irradiation, or treatment with cytoskeletal-disrupting agents. Both DSBs and BN cells were greatest in subconfluent (replicating) monolayers. The DNA-damaged cells co-expressed the replication markers TPX2/repp86 and centromere protein F. Once damaged in the early stages of culture establishment, fibroblasts continued to express DNA breaks with each replicative cycle. However, significant levels of cell death were not measured, suggesting that DNA repair was occurring. Comet assays showed that DNA repair was delayed in proportion to levels of genotoxic stress. Conclusions Researchers using tendon fibroblast monolayers should assess their “health” using γH2AX labelling. Continued use of early passage cultures expressing initially high levels of γH2AX puncta should be avoided for mechanistic studies and ex-vivo therapeutic applications, as this will not be resolved with further replicative cycling. Low density cell culture should be avoided as it enriches for both DNA damage and mitotic defects (polyploidy). As monolayers differing only slightly in baseline DNA damage levels showed markedly variable responses to a further injury, studies of effects of various stressors on tendon cells must be very carefully controlled. PMID:24025445

Roles of PCNA ubiquitination and TLS polymerases κ and η in the bypass of methyl methanesulfonate-induced DNA damage

PubMed Central

Wit, Niek; Buoninfante, Olimpia Alessandra; van den Berk, Paul C.M.; Jansen, Jacob G.; Hogenbirk, Marc A.; de Wind, Niels; Jacobs, Heinz

2015-01-01

Translesion synthesis (TLS) provides a highly conserved mechanism that enables DNA synthesis on a damaged template. TLS is performed by specialized DNA polymerases of which polymerase (Pol) κ is important for the cellular response to DNA damage induced by benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), ultraviolet (UV) light and the alkylating agent methyl methanesulfonate (MMS). As TLS polymerases are intrinsically error-prone, tight regulation of their activity is required. One level of control is provided by ubiquitination of the homotrimeric DNA clamp PCNA at lysine residue 164 (PCNA-Ub). We here show that Polκ can function independently of PCNA modification and that Polη can function as a backup during TLS of MMS-induced lesions. Compared to cell lines deficient for PCNA modification (PcnaK164R) or Polκ, double mutant cell lines display hypersensitivity to MMS but not to BPDE or UV-C. Double mutant cells also displayed delayed post-replicative TLS, accumulate higher levels of replication stress and delayed S-phase progression. Furthermore, we show that Polη and Polκ are redundant in the DNA damage bypass of MMS-induced DNA damage. Taken together, we provide evidence for PCNA-Ub-independent activation of Polκ and establish Polη as an important backup polymerase in the absence of Polκ in response to MMS-induced DNA damage. PMID:25505145

Evaluation of DNA damage and mutagenicity induced by lead in tobacco plants.

PubMed

Gichner, Tomás; Znidar, Irena; Száková, Jirina

2008-04-30

Tobacco (Nicotiana tabacum L. var. xanthi) seedlings were treated with aqueous solutions of lead nitrate (Pb2+) at concentrations ranging from 0.4 mM to 2.4 mM for 24 h and from 25 microM to 200 microM for 7 days. The DNA damage measured by the comet assay was high in the root nuclei, but in the leaf nuclei a slight but significant increase in DNA damage could be demonstrated only after a 7-day treatment with 200 microM Pb2+. In tobacco plants growing for 6 weeks in soil polluted with Pb2+ severe toxic effects, expressed by the decrease in leaf area, and a slight but significant increase in DNA damage were observed. The tobacco plants with increased levels of DNA damage were severely injured and showed stunted growth, distorted leaves and brown root tips. The frequency of somatic mutations in tobacco plants growing in the Pb2+-polluted soil did not significantly increase. Analytical studies by inductively coupled plasma optical emission spectrometry demonstrate that after a 24-h treatment of tobacco with 2.4 mM Pb2+, the accumulation of the heavy metal is 40-fold higher in the roots than in the above-ground biomass. Low Pb2+ accumulation in the above-ground parts may explain the lower levels or the absence of Pb2+-induced DNA damage in leaves.

miR-520 promotes DNA-damage-induced trophoblast cell apoptosis by targeting PARP1 in recurrent spontaneous abortion (RSA).

PubMed

Dong, Xiujuan; Yang, Long; Wang, Hui

2017-04-01

The establishment and maintenance of successful pregnancy mainly depends on trophoblast cells. Their dysfunction has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy. However, the underlying mechanisms of trophoblasts dysfunction remain unclear. DNA-damage-induced cell apoptosis has been reported to play a vital role in cell death. In this study, we identified a novel microRNA (miR-520) in RSA progression via regulating trophoblast cell apoptosis. Microarray analysis showed that miR-520 was highly expressed in villus of RSA patients. By using flow cytometry analysis, we observed miR-520 expression was correlated with human trophoblast cell apoptosis in vitro, along with decreased poly (ADP-ribose) polymerase-1 (PARP1) expression. With the analysis of clinic samples, we observed that miR-520 level was negatively correlated with PARP1 level in RSA villus. In addition, overexpression of PARP1 restored the miR-520-induced trophoblast cell apoptosis in vitro. The status of chromosome in trophoblast implied that miR-520-promoted DNA-damage-induced cell apoptosis to regulate RSA progression. These results indicated that the level of miR-520 might associate with RSA by prompting trophoblast cell apoptosis via PARP1 dependent DNA-damage pathway.

The effect of estrogen on muscle damage biomarkers following prolonged aerobic exercise in eumenorrheic women.

PubMed

Williams, T; Walz, E; Lane, A R; Pebole, M; Hackney, A C

2015-09-01

This study assessed the influence of estrogen (E2) on muscle damage biomarkers [skeletal muscle - creatine kinase (CK); cardiac muscle - CK-MB] responses to prolonged aerobic exercise. Eumenorrheic women (n=10) who were physically active completed two 60-minute treadmill running sessions at ∼60-65% maximal intensity during low E2 (midfollicular menstrual phase) and high E2 (midluteal menstrual phase) hormonal conditions. Blood samples were collected prior to exercise (following supine rest), immediately post-, 30 min post-, and 24 hours post-exercise to determine changes in muscle biomarkers. Resting blood samples confirmed appropriate E2 hormonal levels Total CK concentrations increased following exercise and at 24 hours post-exercise were higher in the midfollicular low E2 phase (p<0.001). However, CK-MB concentrations were unaffected by E2 level or exercise (p=0.442) resulting in the ratio of CK-MB to total CK being consistently low in subject responses (i.e., indicative of skeletal muscle damage). Elevated E2 levels reduce the CK responses of skeletal muscle, but had no effect on CK-MB responses following prolonged aerobic exercise. These findings support earlier work showing elevated E2 is protective of skeletal muscle from exercise-induced damage associated with prolonged aerobic exercise.

The effect of estrogen on muscle damage biomarkers following prolonged aerobic exercise in eumenorrheic women

PubMed Central

Walz, E; Lane, AR; Pebole, M; Hackney, AC

2015-01-01

This study assessed the influence of estrogen (E2) on muscle damage biomarkers [skeletal muscle - creatine kinase (CK); cardiac muscle - CK-MB] responses to prolonged aerobic exercise. Eumenorrheic women (n=10) who were physically active completed two 60-minute treadmill running sessions at ∼60-65% maximal intensity during low E2 (midfollicular menstrual phase) and high E2 (midluteal menstrual phase) hormonal conditions. Blood samples were collected prior to exercise (following supine rest), immediately post-, 30 min post-, and 24 hours post-exercise to determine changes in muscle biomarkers. Resting blood samples confirmed appropriate E2 hormonal levels Total CK concentrations increased following exercise and at 24 hours post-exercise were higher in the midfollicular low E2 phase (p<0.001). However, CK-MB concentrations were unaffected by E2 level or exercise (p=0.442) resulting in the ratio of CK-MB to total CK being consistently low in subject responses (i.e., indicative of skeletal muscle damage). Elevated E2 levels reduce the CK responses of skeletal muscle, but had no effect on CK-MB responses following prolonged aerobic exercise. These findings support earlier work showing elevated E2 is protective of skeletal muscle from exercise-induced damage associated with prolonged aerobic exercise. PMID:26424921

Cell Damage, Antioxidant Status, and Cortisol Levels Related to Nutrition in Ski Mountaineering During a Two-Day Race

PubMed Central

Diaz, Elena; Ruiz, Fatima; Hoyos, Itziar; Zubero, Jaime; Gravina, Leyre; Gil, Javier; Irazusta, Jon; Gil, Susana Maria

2010-01-01

The aim of this study was to measure the effect of nutrition on cell damage, antioxidant enzymes, and cortisol during a two-day ski mountaineering competition. Twenty-one male skiers participated in the study. Creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase (AP), cortisol and C-reactive protein (CRP), glutathione peroxidase (GPx) and reductase activities (GR) and C-reactive protein (CRP) levels, total antioxidant status, and cortisol levels were measured in serum the day before and immediately after the race. Their diet was also analysed during the competition. Enzymes and cortisol levels significantly increased after the competition. CK and LDH and cortisol levels were negatively correlated to total energy, protein, and fat intake. Intake of vitamin A, B1, B2, B6 and niacin was negatively correlated to LDH and AP. A negative correlation was also found between CK activity and Na, Fe, and Zn intake. Cortisol levels were negatively correlated to the intake of vitamins C, B1 and B2, and niacin. A positive correlation was found between serum GPx and intake of energy, carbohydrates, proteins, A and B vitamins, and folic acid. Skiers with the lowest nutrient intake during the competition were the ones who showed greater cell damage and lower antioxidant enzyme activity and cortisol levels, which may impair performance and also cause injuries and accidents. Particularly, skiers should have high intakes of total energy, macronutrients, vitamins A and B, Na, Zn, and Fe in order to decrease the deleterious effect of strenuous exercise. Key points A two-day ski mountaineering race produced muscle cell damage and oxidative stress and an increase in cortisol levels. There was a marked insufficient intake of carbohydrates which has been shown to affect performance Those skiers with lowest nutrient intake showed greater cell damage, lower antioxidant activity and higher cortisol levels. Nutrition should be carefully monitored and assessed in order to minimize the mentioned blood changes to avoid fatigue, injuries and also accidents in this type of sport; particularly when skiers must carry their own food. PMID:24149705

Adaptive Finite Element Methods for Continuum Damage Modeling

NASA Technical Reports Server (NTRS)

Min, J. B.; Tworzydlo, W. W.; Xiques, K. E.

1995-01-01

The paper presents an application of adaptive finite element methods to the modeling of low-cycle continuum damage and life prediction of high-temperature components. The major objective is to provide automated and accurate modeling of damaged zones through adaptive mesh refinement and adaptive time-stepping methods. The damage modeling methodology is implemented in an usual way by embedding damage evolution in the transient nonlinear solution of elasto-viscoplastic deformation problems. This nonlinear boundary-value problem is discretized by adaptive finite element methods. The automated h-adaptive mesh refinements are driven by error indicators, based on selected principal variables in the problem (stresses, non-elastic strains, damage, etc.). In the time domain, adaptive time-stepping is used, combined with a predictor-corrector time marching algorithm. The time selection is controlled by required time accuracy. In order to take into account strong temperature dependency of material parameters, the nonlinear structural solution a coupled with thermal analyses (one-way coupling). Several test examples illustrate the importance and benefits of adaptive mesh refinements in accurate prediction of damage levels and failure time.

Laser damage of HR, AR-coatings, monolayers and bare surfaces at 1064 nm

NASA Technical Reports Server (NTRS)

Garnov, S. V.; Klimentov, S. M.; Said, A. A.; Soileau, M. J.

1993-01-01

Laser induced damage thresholds and morphologies were investigated in a variety of uncoated and coated surfaces, including monolayers and multi-layers of different chemical compositions. Both antireflective (AR) and highly reflective (HR) were tested. Testing was done at 1064 nm with 25 picosecond and 8 nanosecond YAG/Nd laser single pulses. Spot diameter in the experiments varied from 0.09 to 0.22 mm. The laser damage measurement procedure consisted of 1-on-1 (single laser pulse in the selected site) and N-on-1 experiments including repeated irradiation by pulses of the same fluence and subsequently raised from pulse to pulse fluence until damage occurred. The highest picosecond damage thresholds of commercially available coatings averaged 12 - 14 J/sq cm, 50 percent less than thresholds obtained in bare fused silica. Some coatings and bare surfaces revealed a palpable preconditioning effect (an increase in threshold of 1.2 to 1.8 times). Picosecond and nanosecond data were compared to draw conclusions about pulse width dependence. An attempt was made to classify damage morphologies according to the type of coating, class of irradiating, and damage level.

Object-based classification of earthquake damage from high-resolution optical imagery using machine learning

NASA Astrophysics Data System (ADS)

Bialas, James; Oommen, Thomas; Rebbapragada, Umaa; Levin, Eugene

2016-07-01

Object-based approaches in the segmentation and classification of remotely sensed images yield more promising results compared to pixel-based approaches. However, the development of an object-based approach presents challenges in terms of algorithm selection and parameter tuning. Subjective methods are often used, but yield less than optimal results. Objective methods are warranted, especially for rapid deployment in time-sensitive applications, such as earthquake damage assessment. Herein, we used a systematic approach in evaluating object-based image segmentation and machine learning algorithms for the classification of earthquake damage in remotely sensed imagery. We tested a variety of algorithms and parameters on post-event aerial imagery for the 2011 earthquake in Christchurch, New Zealand. Results were compared against manually selected test cases representing different classes. In doing so, we can evaluate the effectiveness of the segmentation and classification of different classes and compare different levels of multistep image segmentations. Our classifier is compared against recent pixel-based and object-based classification studies for postevent imagery of earthquake damage. Our results show an improvement against both pixel-based and object-based methods for classifying earthquake damage in high resolution, post-event imagery.

Evaluating the potential genotoxicity of phthalates esters (PAEs) in perfumes using in vitro assays.

PubMed

Al-Saleh, Iman; Al-Rajudi, Tahreer; Al-Qudaihi, Ghofran; Manogaran, Pulicat

2017-10-01

We previously reported high levels of phthalate esters (PAEs) added as solvents or fixatives in 47 brands of perfumes. Diethyl phthalate was the most abundant compound (0.232-23,649 ppm), and 83.3% of the perfumes had levels >1 ppm, the threshold limit cited by a Greenpeace investigation. All samples had dimethyl phthalate levels higher than its threshold limit of 0.1 ppm, and 88, 38, and 7% of the perfumes had benzyl butyl phthalate, di(2-ethylhexyl) phthalate, and dibutyl phthalate levels, respectively, above their threshold limits. The role of PAEs as endocrine disruptors has been well documented, but their effect on genotoxic behavior has received little attention. We used in vitro single-cell gel electrophoresis (comet) and micronucleus (MN) assays with human lymphoblastoid TK6 cells to evaluate the genotoxic potency of 42 of the same perfumes and to determine its association with PAEs. All perfumes induced more DNA damage than a negative control (NEG), ≥ 90% of the samples caused more damage than cells treated with the vehicles possibly used in perfume's preparations such as methanol (ME) and ethanol (ET), and 11.6% of the perfumes caused more DNA damage than a positive control (hydrogen peroxide). Chromosome breakage expressed as MN frequency was higher in cells treated with 71.4, 64.3, 57.1, and 4.8% of the perfumes than in NEG, cells treated with ME or ET, and another positive control (x-rays), respectively. The genotoxic responses in the comet and MN assays were not correlated. The comet assay indicated that the damage in TK6 cells treated with five PAEs at concentrations of 0.05 and 0.2 ppm either individually or as a mixture did not differ significantly from the damage in cells treated with the perfumes. Unlike the comet assay, the sensitivity of the MN assay to PAEs was weak at both low and high concentrations, and MN frequencies were generally low. This study demonstrates for the first time the possible contribution of PAEs in perfumes to DNA damage and suggests that their use as solvents or fixatives should be regulated. Other ingredients with mutagenic/genotoxic properties, however, may also have contributed to the DNA damage. Future studies should focus on applying a series of assays that use different cellular models with various endpoints to identify the spectrum of genotoxic mechanisms involved.

Nonylphenol exposure is associated with oxidative and nitrative stress in pregnant women.

PubMed

Wang, Pei-Wei; Chen, Mei-Lien; Huang, Li-Wei; Yang, Winnie; Wu, Kuen-Yuh; Huang, Yu-Fang

2015-01-01

Animal studies have shown that exposure to nonylphenol (NP) increases oxidative/nitrative stress, but whether it does so in humans is unknown. This study examines prenatal exposure to NP and its effects on oxidatively/nitratively damaged DNA, lipid peroxidation, and the activities of antioxidants. A total of 146 urine and blood specimens were collected during gestational weeks 27-38 and hospital admission for delivery, respectively. Urinary NP was analyzed by high-performance liquid chromatography (HPLC). Urinary biomarkers of oxidatively/nitratively damaged DNA and lipid peroxidation, including 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-nitroguanine (8-NO(2)Gua), 8-iso-prostaglandin F(2α) (8-isoPF(2α)) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), were simultaneously analyzed using isotope-dilution liquid-chromatography/electron spray ionization tandem mass spectrometry. The activities of maternal plasma superoxide dismutase and glutathione peroxidase were analyzed by enzyme-linked immunosorbent assay. Urinary NP level was significantly associated with 8-oxodG and 8-NO(2)Gua levels in late pregnancy, suggesting that NP may enhance oxidatively and nitratively damaged DNA. The adjusted odds ratios for high 8-oxodG level exhibited a significantly dose-response relationship with NP levels, stratified into four quartiles. 8-oxodG appears to be a more sensitive and effective biomarker of NP exposure than 8-NO(2)Gua. These relationships suggest NP may play a role in the pregnancy complications.

[Effects of flavonoids from Pyrrosiae folium on pathological changes and inflammatory response of diabetic nephropathy].

PubMed

Liu, Xu-Lin; Liu, Wen-Ping; Wang, Li-Li; Feng, Liang

2018-06-01

Diabetic nephropathy (DN) is closely related to immune-mediated inflammatory damage. Pyrrosiae folium is used commonly for the urinary system diseases with a good efficacy, which contains abundant flavonoids (SWHT). This study was performed to investigate the therapeutic effect of SWHT on DN and its effect on inflammatory response. In this study, the main active components of SWHT were identified by high performance liquid chromatography (HPLC). The results showed that SWHT mainly contained mangiferin and isomucoside. Rat model of diabetic nephropathy (DN) was established by feeding high glucose & high fat diet and injecting streptozocin (STZ). Then the rats were randomly divided into control group, DN model group, positive control group, and SWHT groups (50, 100, 200 mg·kg⁻¹, ig). The levels of AGEs and RAGE in serum were measured by ELISA after 12 weeks of drug administration. The serum creatinine, blood urea nitrogen and total protein levels were detected by using test kit. HE staining and transmission electron microscopy were applied to observe the pathological changes and structure of renal tissue. Western blot and ELISA were used to detect the protein expression and content levels of interleukin 6 (IL-6), tumor necrosis factor (TNF-α) and IL-1β in renal tissue. Results showed that SWHT significantly decreased serum AGEs and RAGE levels in DN rats; decreased serum creatinine, blood urea nitrogen and total urinary protein levels, improved renal pathological damages and reduced basement membrane thickening in DN rats. In addition, SWHT down-regulated the protein expression levels of inflammatory mediators IL-6, TNF-α and IL-1β. The research studies indicated that SWHT component had a potential anti-diabetic nephropathy activity, and its improvement effect on pathological damages may be related to reducing inflammation. This provides the basis for the scientific and rational application of P. folium, and also provides active components for further development of Chinese medicine for diabetic nephropathy. Copyright© by the Chinese Pharmaceutical Association.

Oxidative stress, DNA damage, and inflammation induced by ambient air and wood smoke particulate matter in human A549 and THP-1 cell lines.

PubMed

Danielsen, Pernille Høgh; Møller, Peter; Jensen, Keld Alstrup; Sharma, Anoop Kumar; Wallin, Håkan; Bossi, Rossana; Autrup, Herman; Mølhave, Lars; Ravanat, Jean-Luc; Briedé, Jacob Jan; de Kok, Theo Martinus; Loft, Steffen

2011-02-18

Combustion of biomass and wood for residential heating and/or cooking contributes substantially to both ambient air and indoor levels of particulate matter (PM). Toxicological characterization of ambient air PM, especially related to traffic, is well advanced, whereas the toxicology of wood smoke PM (WSPM) is poorly assessed. We assessed a wide spectrum of toxicity end points in human A549 lung epithelial and THP-1 monocytic cell lines comparing WSPM from high or low oxygen combustion and ambient PM collected in a village with many operating wood stoves and from a rural background area. In both cell types, all extensively characterized PM samples (1.25-100 μg/mL) induced dose-dependent formation of reactive oxygen species and DNA damage in terms of strand breaks and formamidopyrimidine DNA glycosylase sites assessed by the comet assay with WSPM being most potent. The WSPM contained more polycyclic aromatic hydrocarbons (PAH), less soluble metals, and expectedly also had a smaller particle size than PM collected from ambient air. All four types of PM combined increased the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine dose-dependently in A549 cells, whereas there was no change in the levels of etheno-adducts or bulky DNA adducts. Furthermore, mRNA expression of the proinflammatory genes monocyte chemoattractant protein-1, interleukin-8, and tumor necrosis factor-α as well as the oxidative stress gene heme oxygenase-1 was upregulated in the THP-1 cells especially by WSPM and ambient PM sampled from the wood stove area. Expression of oxoguanine glycosylase 1, lymphocyte function-associated antigen-1, and interleukin-6 did not change. We conclude that WSPM has small particle size, high level of PAH, low level of water-soluble metals, and produces high levels of free radicals, DNA damage as well as inflammatory and oxidative stress response gene expression in cultured human cells.

Role of platinum DNA damage-induced transcriptional inhibition in chemotherapy-induced neuronal atrophy and peripheral neurotoxicity.

PubMed

Yan, Fang; Liu, Johnson J; Ip, Virginia; Jamieson, Stephen M F; McKeage, Mark J

2015-12-01

Platinum-based anticancer drugs cause peripheral neurotoxicity by damaging sensory neurons within the dorsal root ganglia (DRG), but the mechanisms are incompletely understood. The roles of platinum DNA binding, transcription inhibition and altered cell size were investigated in primary cultures of rat DRG cells. Click chemistry quantitative fluorescence imaging of RNA-incorporated 5-ethynyluridine showed high, but wide ranging, global levels of transcription in individual neurons that correlated with their cell body size. Treatment with platinum drugs reduced neuronal transcription and cell body size to an extent that corresponded to the amount of preceding platinum DNA binding, but without any loss of neuronal cells. The effects of platinum drugs on neuronal transcription and cell body size were inhibited by blocking platinum DNA binding with sodium thiosulfate, and mimicked by treatment with a model transcriptional inhibitor, actinomycin D. In vivo oxaliplatin treatment depleted the total RNA content of DRG tissue concurrently with altering DRG neuronal size. These findings point to a mechanism of chemotherapy-induced peripheral neurotoxicity, whereby platinum DNA damage induces global transcriptional arrest leading in turn to neuronal atrophy. DRG neurons may be particularly vulnerable to this mechanism of toxicity because of their requirements for high basal levels of global transcriptional activity. Findings point to a new stepwise mechanism of chemotherapy-induced peripheral neurotoxicity, whereby platinum DNA damage induces global transcriptional arrest leading in turn to neuronal atrophy. Dorsal root ganglion neurons may be particularly vulnerable to this neurotoxicity because of their high global transcriptional outputs, demonstrated in this study by click chemistry quantitative fluorescence imaging. © 2015 International Society for Neurochemistry.

Increasing extreme water level flood risk as a result of future sea-level rise: A case study on a coastal city in China

NASA Astrophysics Data System (ADS)

Feng, A.; Wu, S.

2016-12-01

Extreme water levels, caused by the joint occurrence of storm surges and high tides, always lead to super floods along coastlines. In the context of climate change, this study explored the impact of future sea-level rise on the flood risk of extreme water levels. Using Rongcheng City in Shandong Province, China as a case study, flooded area, expected direct damage losses, and affected population and GDP were assessed for 2050 and 2100 under three greenhouse gas concentration Representative Concentration Pathways (RCP) scenarios, 2.6, 4.5, and 8.5. Results indicate that, as a result of sea-level rise induced by climate change, the flooded areas of Rongcheng City would increase by 3.23% to 10.64% in 2050 and by as much as 4.98% to 19.87% in 2100, compared with current recurrence periods. Residential land and farmland are at greatest risk of flooding in terms of exposure and losses than other land-use types, and under a high degree RCP 8.5 scenario, expected damage losses would be between 59.84 billion and 86.45 billion in 2050. Results show that the increase in total direct damage losses would reach an average of 60% in 2100 as a result of a 0.82 m sea-level rise. Similarly, affected population and GDP would increase by between 4.95% and 13.87% and between 3.66% and 10.95% in 2050, and by as much as 7.69% to 29.01% and 5.30% to 20.50% in 2100. This study shows that sea-level rise significantly shortens recurrence periods of extreme water levels, makes extreme flood events more frequent, and exacerbates the risk of future flooding. Our results suggest that, if there is no adaptation, sea-level rise will greatly increase the risk of flooding and severely impact human habitability along coastlines.

Uncertainty in urban flood damage assessment due to urban drainage modelling and depth-damage curve estimation.

PubMed

Freni, G; La Loggia, G; Notaro, V

2010-01-01

Due to the increased occurrence of flooding events in urban areas, many procedures for flood damage quantification have been defined in recent decades. The lack of large databases in most cases is overcome by combining the output of urban drainage models and damage curves linking flooding to expected damage. The application of advanced hydraulic models as diagnostic, design and decision-making support tools has become a standard practice in hydraulic research and application. Flooding damage functions are usually evaluated by a priori estimation of potential damage (based on the value of exposed goods) or by interpolating real damage data (recorded during historical flooding events). Hydraulic models have undergone continuous advancements, pushed forward by increasing computer capacity. The details of the flooding propagation process on the surface and the details of the interconnections between underground and surface drainage systems have been studied extensively in recent years, resulting in progressively more reliable models. The same level of was advancement has not been reached with regard to damage curves, for which improvements are highly connected to data availability; this remains the main bottleneck in the expected flooding damage estimation. Such functions are usually affected by significant uncertainty intrinsically related to the collected data and to the simplified structure of the adopted functional relationships. The present paper aimed to evaluate this uncertainty by comparing the intrinsic uncertainty connected to the construction of the damage-depth function to the hydraulic model uncertainty. In this way, the paper sought to evaluate the role of hydraulic model detail level in the wider context of flood damage estimation. This paper demonstrated that the use of detailed hydraulic models might not be justified because of the higher computational cost and the significant uncertainty in damage estimation curves. This uncertainty occurs mainly because a large part of the total uncertainty is dependent on depth-damage curves. Improving the estimation of these curves may provide better results in term of uncertainty reduction than the adoption of detailed hydraulic models.

Mold exposure and health effects following hurricanes Katrina and Rita.

PubMed

Barbeau, Deborah N; Grimsley, L Faye; White, LuAnn E; El-Dahr, Jane M; Lichtveld, Maureen

2010-01-01

The extensive flooding in the aftermath of Hurricanes Katrina and Rita created conditions ideal for indoor mold growth, raising concerns about the possible adverse health effects associated with indoor mold exposure. Studies evaluating the levels of indoor and outdoor molds in the months following the hurricanes found high levels of mold growth. Homes with greater flood damage, especially those with >3 feet of indoor flooding, demonstrated higher levels of mold growth compared with homes with little or no flooding. Water intrusion due to roof damage was also associated with mold growth. However, no increase in the occurrence of adverse health outcomes has been observed in published reports to date. This article considers reasons why studies of mold exposure after the hurricane do not show a greater health impact.

True Memory, False Memory, and Subjective Recollection Deficits after Focal Parietal Lobe Lesions

PubMed Central

Drowos, David B.; Berryhill, Marian; André, Jessica M.; Olson, Ingrid R.

2010-01-01

Objective There is mounting evidence that the posterior parietal cortex (PPC) plays an important role in episodic memory. We previously found that patients with PPC damage exhibit retrieval-related episodic memory deficits. Our objective was to assess whether parietal lobe damage affects episodic memory on a different task: the Deese-Roediger-McDermott (DRM) false-memory paradigm. Method Two patients with bilateral PPC damage and matched controls were tested. In Experiment 1, the task was to remember words; in Experiment 2 the task was to remember pictures of common objects. Prior studies have shown that normal participants have high levels of false memory to words, low levels to pictures. Results The patients exhibited significantly lower levels of false memory to words. The patients' false memories were accompanied by reduced levels of recollection, as tested by a Remember/Know procedure. It is unlikely that a failure of gist processing accounts for these results, as patients accurately remembered thematic elements of short vignettes, but failed to remember details. These results support the view that portions of the PPC play a critical role in objective and subjective aspects of recollection. PMID:20604621

Cellular characterization of compression-induceddamage in live biological samples

NASA Astrophysics Data System (ADS)

Bo, Chiara; Balzer, Jens; Hahnel, Mark; Rankin, Sara M.; Brown, Katherine A.; Proud, William

2012-03-01

Understanding the damage that high intensity compression waves induce in human tissues is critical for developing improved therapies for patients suffering from blast injuries. Experimentally based models of blast injury using live biological samples are needed. In this study we have developed a system to directly assess the effects of dynamic loading conditions on live cells. Here, we describe a confinement chamber designed to subject live cell cultures in a liquid environment to high intensity compression waves using a split Hopkinson pressure bar system. Signals from the strain gauges mounted on the bars and the chamber allow the measurement of parameters such as pressure and duration of the stimulus. The chamber itself also allows recovery of cells subjected to compression for assessment of cellular damage. In these studies we present evidence of increased levels of damage and loss of cellular integrity in cultured mouse mesenchymal stem cells subjected to a high-intensity compression wave with a peak pressure of 7.6 ± 0.8 MPa.

High power beta electron device - Beyond betavoltaics

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

Ayers, William M.; Gentile, Charles A.

Developing watt level power sources with beta emitting radioisotopes has been limited by the inability to utilize high energy (> 100 KeV) beta emitters at high radioisotope loadings without damaging the energy conversion materials. A new type of beta electron power source is described that removes those restrictions. This approach contains the radioisotope in a beta transparent titanium tube and confines beta electrons emitted through the tube wall to spiral trajectories around the tube with an axial magnetic field. The confined beta electrons dissipate energy though multiple interactions with surrounding excimer precursor gas atoms to efficiently generate photons. Photovoltaic cellsmore » convert the photons to electrical power. Since the beta electrons dissipate energy in the excimer precursor gas, the device can be loaded with more than 10 13 Bq of radioisotope to generate 100 milliwatt to watt levels of electrical power without damaging the device materials or degrading its performance. Furthermore, the power source can use a variety of beta radioisotopes and scales by stacking the devices.« less

High power beta electron device - Beyond betavoltaics

DOE PAGES

Ayers, William M.; Gentile, Charles A.

2017-11-10

Developing watt level power sources with beta emitting radioisotopes has been limited by the inability to utilize high energy (> 100 KeV) beta emitters at high radioisotope loadings without damaging the energy conversion materials. A new type of beta electron power source is described that removes those restrictions. This approach contains the radioisotope in a beta transparent titanium tube and confines beta electrons emitted through the tube wall to spiral trajectories around the tube with an axial magnetic field. The confined beta electrons dissipate energy though multiple interactions with surrounding excimer precursor gas atoms to efficiently generate photons. Photovoltaic cellsmore » convert the photons to electrical power. Since the beta electrons dissipate energy in the excimer precursor gas, the device can be loaded with more than 10 13 Bq of radioisotope to generate 100 milliwatt to watt levels of electrical power without damaging the device materials or degrading its performance. Furthermore, the power source can use a variety of beta radioisotopes and scales by stacking the devices.« less

High power beta electron device - Beyond betavoltaics.

PubMed

Ayers, William M; Gentile, Charles A

2018-01-01

Developing watt level power sources with beta emitting radioisotopes has been limited by the inability to utilize high energy (> 100KeV) beta emitters at high radioisotope loadings without damaging the energy conversion materials. A new type of beta electron power source is described that removes those restrictions. The approach contains the radioisotope in a beta transparent titanium tube and confines beta electrons emitted through the tube wall to spiral trajectories around the tube with an axial magnetic field. The confined beta electrons dissipate energy though multiple interactions with surrounding excimer precursor gas atoms to efficiently generate photons. Photovoltaic cells convert the photons to electrical power. Since the beta electrons dissipate energy in the excimer precursor gas, the device can be loaded with more than 10 13 Bq of radioisotope to generate 100 milliwatt to watt levels of electrical power without damaging the device materials or degrading its performance. The power source can use a variety of beta radioisotopes and scales by stacking the devices. Copyright © 2017. Published by Elsevier Ltd.

Increased serum alkaline phosphatase levels correlate with high disease activity and low bone mineral density in patients with axial spondyloarthritis.

PubMed

Kang, Kwi Young; Hong, Yeon Sik; Park, Sung-Hwan; Ju, Ji Hyeon

2015-10-01

Recent studies report an association between serum alkaline phosphatase (ALP) levels and inflammation. The present study examined the relationship between ALP and disease activity, bone mineral density (BMD), and radiological damage in axial spondyloarthritis (SpA). A total of 115 patients who fulfilled the ASAS axial SpA criteria were enrolled. Serum ALP, bone-specific ALP (BALP), serum cross-linked telopeptide of type-I collagen (sCTX), and inflammatory markers were measured. Clinical parameters, BMD, grade of sacroiliitis, and the modified Stoke AS Spinal Score (mSASSS) were also assessed. The Ankylosing Spondylitis Disease Activity Score (ASDAS) was also calculated. The associations between serum ALP, disease activity score, BMD, and radiologic damage were evaluated. The mean serum ALP level was 77 ± 26 U/l. Serum ALP levels increased in 14 patients (13%). Serum ALP levels increased along with ASDAS-CRP after adjusting for age and sex (p = 0.004), and were significantly correlated with ASDAS-ESR and ASDAS-CRP (p = 0.001 and p < 0.001, respectively), negatively correlated with BMD in the lumbar spine and femoral neck (p = 0.003 and 0.046, respectively), and positively correlated with sacroiliitis grade and the mSASSS (p < 0.001 and p < 0.002, respectively). BALP and sCTX were not associated with disease activity or BMD. Multivariate analysis showed that serum ALP was independently associated with ASDAS-CRP (p = 0.010). Increased serum ALP levels were associated with high disease activity, low BMD, and higher structural damage scores in SpA patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Baseline serum level of matrix metalloproteinase-3 as a biomarker of progressive joint damage in rheumatoid arthritis patients.

PubMed

Galil, Sahar Mahfouz Abdel; El-Shafey, Abeer Mohamed; Hagrass, Hoda A; Fawzy, Faten; Sammak, Ahmed El

2016-04-01

Matrix metalloproteinase-3 (MMP-3) plays a pivotal role in the destruction of bone and degradation of cartilage components in rheumatoid arthritis (RA). We aimed in this study to analyze the relation between baseline levels of MMP-3 and the progression of joint damage in RA. Eighty-one untreated RA patients with joint symptoms for <1 year were evaluated at baseline and after 12 months as regards erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) and plain X-ray of both hands and wrists. Baseline levels of MMP-3 were measured by enzyme-linked immunosorbent assay and magnetic resonance imaging (MRI) of hands/wrists was performed. Disease Activity Score (DAS28) and Health Assessment Questionnaire (HAQ) were performed at baseline evaluation and after 12 months. The baseline MMP-3 levels were significantly higher in the high-progression group compared with the low-progression one (95.75 ± 42.84 vs. 50.45 ± 12.83, P < 0.001). There was a positive correlation between baseline levels of MMP-3 and MRI erosion score and other baseline clinical parameters, except for HAQ and the van der Heijde modification of the Sharp scoring system (SvdH) scores, while after 12 months, there were high positive correlations between MMP-3 and SvdH score, as well as all parameters except for ESR. Serum baseline levels of MMP-3 are strong prognostic markers of disease activity, and act well as an early predictor of progressive joint damage in recent-onset RA disease. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Oral administration of vitamin C prevents alveolar bone resorption induced by high dietary cholesterol in rats.

PubMed

Sanbe, Toshihiro; Tomofuji, Takaaki; Ekuni, Daisuke; Azuma, Tetsuji; Tamaki, Naofumi; Yamamoto, Tatsuo

2007-11-01

A high-cholesterol diet stimulates alveolar bone resorption, which may be induced via tissue oxidative damage. Vitamin C reduces tissue oxidative damage by neutralizing free radicals and scavenging hydroxyl radicals, and its antioxidant effect may offer the clinical benefit of preventing alveolar bone resorption in cases of hyperlipidemia. We examined whether vitamin C could suppress alveolar bone resorption in rats fed a high-cholesterol diet. In this 12-week study, rats were divided into four groups: a control group (fed a regular diet) and three experimental groups (fed a high-cholesterol diet supplemented with 0, 1, or 2 g/l vitamin C). Vitamin C was provided by adding it to the drinking water. The bone mineral density of the alveolar bone was analyzed by microcomputerized tomography. As an index of tissue oxidative damage, the 8-hydroxydeoxyguanosine level in the periodontal tissue was determined using a competitive enzyme-linked immunosorbent assay. Hyperlipidemia, induced by a high-cholesterol diet, decreased rat alveolar bone density and increased the number of tartrate-resistant acid phosphatase-positive osteoclasts. The expression of 8-hydroxydeoxyguanosine was upregulated in the periodontal tissues. Intake of vitamin C reduced the effect of a high-cholesterol diet on alveolar bone density and osteoclast differentiation and decreased periodontal 8-hydroxydeoxyguanosine expression. In the rat model, vitamin C suppressed alveolar bone resorption, induced by high dietary cholesterol, by decreasing the oxidative damage of periodontal tissue.

On 1064 nm and 350 nm laser damage thresholds of high index oxide films deposited from organic solutions and sols

NASA Astrophysics Data System (ADS)

Thomas, I.; Wilder, J.; Gonzales, R.; George, D.

1987-06-01

High index oxide coatings TiO2, Ta2O5, ZrO2 and HfO2 have been prepared from organic solutions of metal organic precursors or from colloidal oxide suspensions. Room temperature processing gives porous coatings of comparatively low index (1.8 to 1.9). Heat treatments can, in some cases, increase the index. Laser damage threshold levels at 1064 nm with a single 1 ns pulse are in the range 6 to 10 J/sq cm. Lower figures are obtained at 350 nm with a 25 ns pulse under multishot (25 Hz) conditions.

Damage localization by statistical evaluation of signal-processed mode shapes

NASA Astrophysics Data System (ADS)

Ulriksen, M. D.; Damkilde, L.

2015-07-01

Due to their inherent, ability to provide structural information on a local level, mode shapes and t.lieir derivatives are utilized extensively for structural damage identification. Typically, more or less advanced mathematical methods are implemented to identify damage-induced discontinuities in the spatial mode shape signals, hereby potentially facilitating damage detection and/or localization. However, by being based on distinguishing damage-induced discontinuities from other signal irregularities, an intrinsic deficiency in these methods is the high sensitivity towards measurement, noise. The present, article introduces a damage localization method which, compared to the conventional mode shape-based methods, has greatly enhanced robustness towards measurement, noise. The method is based on signal processing of spatial mode shapes by means of continuous wavelet, transformation (CWT) and subsequent, application of a generalized discrete Teager-Kaiser energy operator (GDTKEO) to identify damage-induced mode shape discontinuities. In order to evaluate whether the identified discontinuities are in fact, damage-induced, outlier analysis of principal components of the signal-processed mode shapes is conducted on the basis of T2-statistics. The proposed method is demonstrated in the context, of analytical work with a free-vibrating Euler-Bernoulli beam under noisy conditions.

Occupational exposure to antineoplastic agents induces a high level of chromosome damage. Lack of an effect of GST polymorphisms

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

Testa, Antonella; Giachelia, Manuela; Palma, Selena

The aim of our study was to investigate whether occupational exposure to antineoplastic drugs (AND) resulted in genetic damage, possibly indicative of adverse health effects in the long term. We performed a chromosomal aberrations (CA) analysis in peripheral blood lymphocytes (PBL) of a group of 76 trained nurses occupationally exposed to AND. Furthermore, we analysed whether genetic polymorphisms in four metabolic genes of the glutathione S-transferase (GST) family involved in antineoplastic drugs detoxification (GSTM1, GSTT1, GSTP1, GSTA1) had any effect on the yield of chromosomal aberrations in nurses exposed to antineoplastic agents. The exposed group showed a very significant increasemore » of genetic damage (p < 0.0001) potentially indicative of an increased risk of cancer. Unexpectedly, besides the elevated level of chromatid-type aberrations usually related to exposure to chemical agents, we found also severe chromosome damages such as chromosome deletions and dicentric chromosomes, usually related to radiation exposure. No significant association was detected between all GSTs genotypes and chromosome damage. In conclusion, our data show how the occupational exposure to AND is associated to a potential cancer risk, suggesting that current prevention methods do not completely eliminate opportunities for exposure and supporting the need to improve the actual safety practices.« less

Chronic inflammation-associated genomic instability paves the way for human esophageal carcinogenesis.

PubMed

Lin, Runhua; Zhang, Chong; Zheng, Jiaxuan; Tian, Dongping; Lei, Zhijin; Chen, Donglin; Xu, Zexin; Su, Min

2016-04-26

Chronic inflammation is associated with increased risk of cancer development, whereas the link between chronic inflammation and esophageal carcinogenesis is still obscure heretofore. This study aimed to investigate the relationship between chronic inflammation and DNA damage, as well as the possible role of DNA damage in esophageal carcinogenic process. Endoscopic esophageal biopsies from 109 individuals from Chaoshan littoral, a high-risk region for esophageal squamous cell carcinoma (ESCC), were examined to evaluate the association between chronic inflammation and histological severity, while additional 204 esophageal non-tumor samples from patients with ESCC were collected. Immunohistochemistry was performed to detect the oxidative DNA damage and DNA double-strand breaks (DSBs). Significantly positive correlation was observed between degree of chronic inflammation and esophageal precursor lesions (rs = 0.37, P < 0.01). Immunohistochemical analysis showed that oxidative DNA damage level was positively correlated with the degree of chronic inflammation (rs = 0.21, P < 0.05). Moreover, the level of oxidative DNA damage positively correlated with histological severity (rs = 0.49, P < 0.01). We found that the extent of DSBs was progressively increased with inflammation degree (P < 0.01) and the progression of precancerous lesions (P < 0.001). Collectively, these findings provide evidence linking chronic inflammation-associated genomic instability with esophageal carcinogenesis and suggest possibilities for early detection and intervention of esophageal carcinogenesis.

Comparing the clastogenic potential of atrazine with caffeine using Chinese hamster ovary (CHO) cells.

PubMed

Rayburn, A L; Bouma, J; Northcott, C A

2001-04-08

The agronomically important herbicide atrazine has been reported to cause damage to animal chromosomes at levels of atrazine found contaminating drinking water supplies. While documenting potential chromosome damage is important it is equally important to compare the damage with the potential consequences of compounds readily found in our food and water supply. In this study atrazine and caffeine, a ubiquitous food additive, were compared at equal levels and at real exposure levels for their ability to damage animals chromosomes in cell culture. Nuclei and chromosomes from treated and control cells were analyzed by flow cytometry. At extremely low levels, atrazine was found to be a more potent clastogen. Caffeine had no effect on the chromosomes at the lower levels. Both chemicals were genotoxic at the potential exposure levels with caffeine being more disruptive than atrazine. Atrazine appears to be a more potent damaging agent than caffeine at similar levels of exposure; however, the levels of caffeine one is exposed to during everyday life appears to be more damaging on the endpoints analyzed in this study than the levels of atrazine found contaminating water supplies. The advantages and limitations of whole cell clasotgenicity are also presented in light of these results.

Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice

PubMed Central

Salgueiro, Andréia Caroline Fernandes; da Silva, Marianne Pires; Mendez, Andreas Sebastian Loureiro; Zemolin, Ana Paula Pegoraro; Posser, Thaís; Puntel, Robson Luiz; Puntel, Gustavo Orione

2016-01-01

This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF) tea on oxidative stress and liver damage in streptozotocin (STZ)-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1) BF chemical composition; (2) glucose levels; (3) liver/body weight ratio and liver transaminases; (4) reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation in liver; (5) superoxide dismutase (SOD) and catalase (CAT) activities in liver; (6) δ-aminolevulinate dehydratase (δ-ALA-D) and nonprotein thiols (NPSH) in liver; (7) Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential. PMID:26839634

Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice.

PubMed

Salgueiro, Andréia Caroline Fernandes; Folmer, Vanderlei; da Silva, Marianne Pires; Mendez, Andreas Sebastian Loureiro; Zemolin, Ana Paula Pegoraro; Posser, Thaís; Franco, Jeferson Luis; Puntel, Robson Luiz; Puntel, Gustavo Orione

2016-01-01

This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF) tea on oxidative stress and liver damage in streptozotocin (STZ)-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1) BF chemical composition; (2) glucose levels; (3) liver/body weight ratio and liver transaminases; (4) reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation in liver; (5) superoxide dismutase (SOD) and catalase (CAT) activities in liver; (6) δ-aminolevulinate dehydratase (δ-ALA-D) and nonprotein thiols (NPSH) in liver; (7) Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential.

Cr(VI) induces DNA damage, cell cycle arrest and polyploidization: a flow cytometric and comet assay study in Pisum sativum.

PubMed

Rodriguez, Eleazar; Azevedo, Raquel; Fernandes, Pedro; Santos, Conceição

2011-07-18

Chromium(VI) is recognized as the most toxic valency of Cr, but its genotoxicity and cytostaticity in plants is still poorly studied. In order to analyze Cr(VI) cyto- and gentotoxicity, Pisum sativum L. plants were grown in soil and watered with solutions with different concentrations of Cr up to 2000 mg/L. After 28 days of exposure, leaves showed no significant variations in either cell cycle dynamics or ploidy level. As for DNA damage, flow cytometric (FCM) histograms showed significant differences in full peak coefficient of variation (FPCV) values, suggesting clastogenicity. This is paralleled by the Comet assay results, showing an increase in DNA damage for 1000 and 2000 mg/L. In roots, exposure to 2000 mg/L resulted in cell cycle arrest at the G(2)/M checkpoint. It was also verified that under the same conditions 40% of the individuals analyzed suffered polyploidization having both 2C and 4C levels. DNA damage analysis by the Comet assay and FCM revealed dose-dependent increases in DNA damage and FPCV. Through this, we have unequivocally demonstrated for the first time in plants that Cr exposure can result in DNA damage, cell cycle arrest, and polyploidization. Moreover, we critically compare the validity of the Comet assay and FCM in evaluating cytogenetic toxicity tests in plants and demonstrate that the data provided by both techniques complement each other and present high correlation levels. In conclusion, the data presented provides new insight on Cr effects in plants in general and supports the use of the parameters tested in this study as reliable endpoints for this metal toxicity in plants. © 2011 American Chemical Society

Characterizing the spatial distribution of brown marmorated stink bug, Halyomorpha halys Stål (Hemiptera: Pentatomidae), populations in peach orchards

PubMed Central

Hahn, Noel G.

2017-01-01

Geospatial analyses were used to investigate the spatial distribution of populations of Halyomorpha halys, an important invasive agricultural pest in mid-Atlantic peach orchards. This spatial analysis will improve efficiency by allowing growers and farm managers to predict insect arrangement and target management strategies. Data on the presence of H. halys were collected from five peach orchards at four farms in New Jersey from 2012–2014 located in different land-use contexts. A point pattern analysis, using Ripley’s K function, was used to describe clustering of H. halys. In addition, the clustering of damage indicative of H. halys feeding was described. With low populations early in the growing season, H. halys did not exhibit signs of clustering in the orchards at most distances. At sites with low populations throughout the season, clustering was not apparent. However, later in the season, high infestation levels led to more evident clustering of H. halys. Damage, although present throughout the entire orchard, was found at low levels. When looking at trees with greater than 10% fruit damage, damage was shown to cluster in orchards. The Moran’s I statistic showed that spatial autocorrelation of H. halys was present within the orchards on the August sample dates, in relation to both populations density and levels of damage. Kriging the abundance of H. halys and the severity of damage to peaches revealed that the estimations of these are generally found in the same region of the orchards. This information on the clustering of H. halys populations will be useful to help predict presence of insects for use in management or scouting programs. PMID:28362797

Rhabdomyolysis after sleeve gastrectomy: increase in muscle enzymes does not predict fatal outcome.

PubMed

Foresteri, Pietro; Pietro, Forestieri; Formato, Antonio; Antonio, Formato; Pilone, Vincenzo; Vincenzo, Pilone; Romano, Antonietta; Antonietta, Romano; Monda, Antonietta; Angela, Monda; Tramontano, Salvatore; Salvatore, Tramontano

2008-03-01

Rhabdomyolysis (RML) is a clinical and biochemical syndrome caused by destruction of skeletal muscles and constitutes a complication of bariatric surgery, with an incidence near to 22%. It is accompanied by increase in serum of intracellular enzymes. Laboratory data as predictive of prognosis have been evaluated by some authors. We report a case of RML after a sleeve gastrectomy, with good prognosis despite a very extensive muscle damage and very high seric and urinary peaks of intracellular enzymes. We describe a 34-years-old super-obese male (body mass index, 54.3 kg/m2) who underwent to laparoscopic sleeve gastrectomy. After 24 h, patient complained of pain in gluteal region, oliguria, and high levels of creatine phosphokinase that reached to 58,395 IU/l. Acute renal failure related to RML was diagnosed. Dialysis was not necessary. Ambulatorial control of renal function after dimission did not reveal a permanent damage. RML is a biochemical syndrome recently associated with bariatric surgery. Early diagnosis is ever necessary. Laboratory data represent markers for diagnosis and prognostic indicator of renal failure. There is no clear relation between seric levels of intracellular enzymes and irreversible renal damage and RML-related mortality.

Protection of cadmium chloride induced DNA damage by Lamiaceae plants

PubMed Central

Thirugnanasampandan, Ramaraj; Jayakumar, Rajarajeswaran

2011-01-01

Objective To analyze the total phenolic content, DNA protecting and radical scavenging activity of ethanolic leaf extracts of three Lamiaceae plants, i.e. Anisomelos malabarica (A. malabarica), Leucas aspera (L. aspera) and Ocimum basilicum (O. basilicum). Methods The total polyphenols and flavonoids were analyzed in the ethanolic leaf extracts of the lamiaceae plants. To determine the DNA protecting activity, various concentrations of the plant extracts were prepared and treated on cultured HepG2 human lung cancer cells. The pretreated cells were exposed to H2O2 to induce DNA damage through oxidative stress. Comet assay was done and the tail length of individual comets was measured. Nitric oxide and superoxide anion scavenging activities of lamiaceae plants were analyzed. Results Among the three plant extracts, the highest amount of total phenolic content was found in O. basilicum (189.33 mg/g), whereas A. malabarica showed high levels of flavonoids (10.66 mg/g). O. basilicum also showed high levels of DNA protecting (85%) and radical scavenging activity. Conclusions The results of this study shows that bioactive phenols present in lamiaceae plants may prevent carcinogenesis through scavenging free radicals and inhibiting DNA damage. PMID:23569799

Spirulina improves antioxidant status by reducing oxidative stress in rabbits fed a high-cholesterol diet.

PubMed

Kim, Mi Yeon; Cheong, Sun Hee; Lee, Jeung Hee; Kim, Min Ji; Sok, Dai-Eun; Kim, Mee Ree

2010-04-01

The beneficial effect of Spirulina (Spirulina platensis) on tissue lipid peroxidation and oxidative DNA damage was tested in the hypercholesterolemic New Zealand White rabbit model. After hypercholesterolemia was induced by feeding a high cholesterol (0.5%) diet (HCD) for 4 weeks, then HCD supplemented with 1% or 5% Spirulina (SP1 or SP5, respectively) was provided for an additional 8 weeks. Spirulina supplementation significantly reduced the increased lipid peroxidation level in HCD-fed rabbits, and levels recovered to control values. Oxidative stress biomarkers such as glutathione, glutathione peroxidase, glutathione reductase, and glutathione S-transferase were significantly improved in the liver and red blood cells of rabbits fed SP1. Furthermore, SP5 induced antioxidant enzyme activity by 3.1-fold for glutathione, 2.5-fold for glutathione peroxidase, 2.7-fold for glutathione reductase, and 2.3-fold for glutathione S-transferase in liver, compared to the HCD group. DNA damage in lymphocytes was significantly reduced in both the SP1 and SP5 groups, based on the comet assay. Findings from the present study suggest that dietary supplementation with Spirulina may be useful to protect the cells from lipid peroxidation and oxidative DNA damage.

Climate mitigation: sustainable preferences and cumulative carbon

NASA Astrophysics Data System (ADS)

Buckle, Simon

2010-05-01

We develop a stylized AK growth model with both climate damages to ecosystem goods and services and sustainable preferences that allow trade-offs between present discounted utility and long-run climate damages. The simplicity of the model permits analytical solutions. Concern for the long-term provides a strong driver for mitigation action. One plausible specification of sustainable preferences leads to the result that, for a range of initial parameter values, an optimizing agent would choose a level of cumulative carbon dioxide (CO2) emissions independent of initial production capital endowment and CO2 levels. There is no technological change so, for economies with sufficiently high initial capital and CO2 endowments, optimal mitigation will lead to disinvestment. For lower values of initial capital and/or CO2 levels, positive investment can be optimal, but still within the same overall level of cumulative emissions. One striking aspect of the model is the complexity of possible outcomes, in addition to these optimal solutions. We also identify a resource constrained region and several regions where climate damages exceed resources available for consumption. Other specifications of sustainable preferences are discussed, as is the case of a hard constraint on long-run damages. Scientists are currently highlighting the potential importance of the cumulative carbon emissions concept as a robust yet flexible target for climate policymakers. This paper shows that it also has an ethical interpretation: it embodies an implicit trade off in global welfare between present discounted welfare and long-term climate damages. We hope that further development of the ideas presented here might contribute to the research and policy debate on the critical areas of intra- and intergenerational welfare.

Glaucomatous Optic Neuropathy Associated with Nocturnal Dip in Blood Pressure: Findings from the Maracaibo Aging Study.

PubMed

Melgarejo, Jesús D; Lee, Joseph H; Petitto, Michele; Yépez, Juan B; Murati, Felipe A; Jin, Zhezhen; Chávez, Carlos A; Pirela, Rosa V; Calmón, Gustavo E; Lee, Winston; Johnson, Matthew P; Mena, Luis J; Al-Aswad, Lama A; Terwilliger, Joseph D; Allikmets, Rando; Maestre, Gladys E; De Moraes, C Gustavo

2018-06-01

To determine which nocturnal blood pressure (BP) parameters (low levels or extreme dipper status) are associated with an increased risk of glaucomatous damage in Hispanics. Observational cross-sectional study. A subset (n = 93) of the participants from the Maracaibo Aging Study (MAS) who met the study eligibility criteria were included. These participants, who were at least 40 years of age, had measurements for optical tomography coherence, visual field (VF) tests, 24-hour BP, office BP, and intraocular pressure <22 mmHg. Univariate and multivariate logistic regression analyses under the generalized estimating equations (GEE) framework were used to examine the relationships between glaucomatous damage and BP parameters, with particular attention to decreases in nocturnal BP. Glaucomatous optic neuropathy (GON) based on the presence of optic nerve damage and VF defects. The mean age was 61.9 years, and 87.1% were women. Of 185 eyes evaluated, 19 (26.5%) had signs of GON. Individuals with GON had significantly lower 24-hour and nighttime diastolic BP levels than those without. However, results of the multivariate GEE models indicated that the glaucomatous damage was not related to the average systolic or diastolic BP levels measured over 24 hours, daytime, or nighttime. In contrast, extreme decreases in nighttime systolic and diastolic BP (>20% compared with daytime BP) were significant risk factors for glaucomatous damage (odds ratio, 19.78 and 5.55, respectively). In this population, the link between nocturnal BP and GON is determined by extreme dipping effects rather than low nocturnal BP levels alone. Further studies considering extreme decreases in nocturnal BP in individuals at high risk of glaucoma are warranted. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Removal of the blue component of light significantly decreases retinal damage after high intensity exposure.

PubMed

Vicente-Tejedor, Javier; Marchena, Miguel; Ramírez, Laura; García-Ayuso, Diego; Gómez-Vicente, Violeta; Sánchez-Ramos, Celia; de la Villa, Pedro; Germain, Francisco

2018-01-01

Light causes damage to the retina (phototoxicity) and decreases photoreceptor responses to light. The most harmful component of visible light is the blue wavelength (400-500 nm). Different filters have been tested, but so far all of them allow passing a lot of this wavelength (70%). The aim of this work has been to prove that a filter that removes 94% of the blue component may protect the function and morphology of the retina significantly. Three experimental groups were designed. The first group was unexposed to light, the second one was exposed and the third one was exposed and protected by a blue-blocking filter. Light damage was induced in young albino mice (p30) by exposing them to white light of high intensity (5,000 lux) continuously for 7 days. Short wavelength light filters were used for light protection. The blue component was removed (94%) from the light source by our filter. Electroretinographical recordings were performed before and after light damage. Changes in retinal structure were studied using immunohistochemistry, and TUNEL labeling. Also, cells in the outer nuclear layer were counted and compared among the three different groups. Functional visual responses were significantly more conserved in protected animals (with the blue-blocking filter) than in unprotected animals. Also, retinal structure was better kept and photoreceptor survival was greater in protected animals, these differences were significant in central areas of the retina. Still, functional and morphological responses were significantly lower in protected than in unexposed groups. In conclusion, this blue-blocking filter decreases significantly photoreceptor damage after exposure to high intensity light. Actually, our eyes are exposed for a very long time to high levels of blue light (screens, artificial light LED, neons…). The potential damage caused by blue light can be palliated.

Perceived Service Need After Hurricane Sandy in a Representative Sample of Survivors: The Roles of Community-Level Damage and Individual-Level Stressors.

PubMed

Sampson, Laura; Lowe, Sarah R; Gruebner, Oliver; Cohen, Gregory H; Galea, Sandro

2016-06-01

We aimed to explore how individually experienced disaster-related stressors and collectively experienced community-level damage influenced perceived need for mental health services in the aftermath of Hurricane Sandy. In a cross-sectional study we analyzed 418 adults who lived in the most affected areas of New York City at the time of the storm. Participants indicated whether they perceived a need for mental health services since the storm and reported on their exposure to disaster-related stressors (eg, displacement, property damage). We located participants in communities (n=293 census tracts) and gathered community-level demographic data through the US Census and data on the number of damaged buildings in each community from the Federal Emergency Management Agency Modeling Task Force. A total of 7.9% of participants reported mental health service need since the hurricane. Through multilevel binomial logistic regression analysis, we found a cross-level interaction (P=0.04) between individual-level exposure to disaster-related stressors and community-level building damage. Individual-level stressors were significantly predictive of individual service needs in communities with building damage (adjusted odds ratio: 2.56; 95% confidence interval: 1.58-4.16) and not in communities without damage. Individuals who experienced individual stressors and who lived in more damaged communities were more likely to report need for services than were other persons after Hurricane Sandy. (Disaster Med Public Health Preparedness. 2016;10:428-435).

Protection against oxidative DNA damage and stress in human prostate by glutathione S-transferase P1

PubMed Central

Kanwal, Rajnee; Pandey, Mitali; Bhaskaran, Natarajan; MacLennan, Gregory T; Fu, Pingfu; Ponsky, Lee E; Gupta, Sanjay

2014-01-01

The pi-class glutathione S-transferase (GSTP1) actively protect cells from carcinogens and electrophilic compounds. Loss of GSTP1 expression via promoter hypermethylation is the most common epigenetic alteration observed in human prostate cancer. Silencing of GSTP1 can increase generation of reactive oxygen species (ROS) and DNA damage in cells. In this study we investigated whether loss of GSTP1 contributes to increased DNA damage that may predispose men to a higher risk of prostate cancer. We found significantly elevated (103%; P<0.0001) levels of 8-oxo-2′-deoxogunosine (8-OHdG), an oxidative DNA damage marker, in adenocarcinomas, compared to benign counterparts, which positively correlated (r=0.2) with loss of GSTP1 activity (34%; P<0.0001). Silencing of GSTP1 using siRNA approach in normal human prostate epithelial RWPE1 cells caused increased intracellular production of ROS and higher susceptibility of cells to H2O2-mediated oxidative stress. Additionally, human prostate carcinoma LNCaP cells, which contain a silenced GSTP1 gene, were genetically modified to constitutively express high levels of GSTP1. Induction of GSTP1 activity lowered endogenous ROS levels in LNCaP-pLPCX-GSTP1 cells, and when exposed to H2O2, these cells exhibited significantly reduced production of ROS and 8-OHdG levels, compared to vector control LNCaP-pLPCX cells. Furthermore, exposure of LNCaP cells to green tea polyphenols caused re-expression of GSTP1, which protected the cells from H2O2-mediated DNA damage through decreased ROS production compared to non-exposed cells. These results suggest that loss of GSTP1 expression in human prostate cells, a process that increases their susceptibility to oxidative stress-induced DNA damage, may be an important target for primary prevention of prostate cancer. PMID:22833520

Ozone concentrations and damage for realistic future European climate and air quality scenarios

NASA Astrophysics Data System (ADS)

Hendriks, Carlijn; Forsell, Nicklas; Kiesewetter, Gregor; Schaap, Martijn; Schöpp, Wolfgang

2016-11-01

Ground level ozone poses a significant threat to human health from air pollution in the European Union. While anthropogenic emissions of precursor substances (NOx, NMVOC, CH4) are regulated by EU air quality legislation and will decrease further in the future, the emissions of biogenic NMVOC (mainly isoprene) may increase significantly in the coming decades if short-rotation coppice plantations are expanded strongly to meet the increased biofuel demand resulting from the EU decarbonisation targets. This study investigates the competing effects of anticipated trends in land use change, anthropogenic ozone precursor emissions and climate change on European ground level ozone concentrations and related health and environmental impacts until 2050. The work is based on a consistent set of energy consumption scenarios that underlie current EU climate and air quality policy proposals: a current legislation case, and an ambitious decarbonisation case. The Greenhouse Gas-Air Pollution Interactions and Synergies (GAINS) integrated assessment model was used to calculate air pollutant emissions for these scenarios, while land use change because of bioenergy demand was calculated by the Global Biosphere Model (GLOBIOM). These datasets were fed into the chemistry transport model LOTOS-EUROS to calculate the impact on ground level ozone concentrations. Health damage because of high ground level ozone concentrations is projected to decline significantly towards 2030 and 2050 under current climate conditions for both energy scenarios. Damage to plants is also expected to decrease but to a smaller extent. The projected change in anthropogenic ozone precursor emissions is found to have a larger impact on ozone damage than land use change. The increasing effect of a warming climate (+2-5 °C across Europe in summer) on ozone concentrations and associated health damage, however, might be higher than the reduction achieved by cutting back European ozone precursor emissions. Global action to reduce air pollutant emissions is needed to make sure that ozone damage in Europe decreases towards the middle of this century.

Prediabetes:MedlinePlus Health Topic

MedlinePlus

... levels that are higher than normal but not high enough to be called diabetes . Glucose comes from the foods you eat. Too much glucose in your blood can damage your body over time. If you have prediabetes, you are ...

Environmental Barrier Coating Fracture, Fatigue and High-Heat-Flux Durability Modeling and Stochastic Progressive Damage Simulation

NASA Technical Reports Server (NTRS)

Zhu, Dongming; Nemeth, Noel N.

2017-01-01

Advanced environmental barrier coatings will play an increasingly important role in future gas turbine engines because of their ability to protect emerging light-weight SiC/SiC ceramic matrix composite (CMC) engine components, further raising engine operating temperatures and performance. Because the environmental barrier coating systems are critical to the performance, reliability and durability of these hot-section ceramic engine components, a prime-reliant coating system along with established life design methodology are required for the hot-section ceramic component insertion into engine service. In this paper, we have first summarized some observations of high temperature, high-heat-flux environmental degradation and failure mechanisms of environmental barrier coating systems in laboratory simulated engine environment tests. In particular, the coating surface cracking morphologies and associated subsequent delamination mechanisms under the engine level high-heat-flux, combustion steam, and mechanical creep and fatigue loading conditions will be discussed. The EBC compostion and archtechture improvements based on advanced high heat flux environmental testing, and the modeling advances based on the integrated Finite Element Analysis Micromechanics Analysis Code/Ceramics Analysis and Reliability Evaluation of Structures (FEAMAC/CARES) program will also be highlighted. The stochastic progressive damage simulation successfully predicts mud flat damage pattern in EBCs on coated 3-D specimens, and a 2-D model of through-the-thickness cross-section. A 2-parameter Weibull distribution was assumed in characterizing the coating layer stochastic strength response and the formation of damage was therefore modeled. The damage initiation and coalescence into progressively smaller mudflat crack cells was demonstrated. A coating life prediction framework may be realized by examining the surface crack initiation and delamination propagation in conjunction with environmental degradation under high-heat-flux and environment load test conditions.

Finite element thermal analysis of multispectral coatings for the ABL

NASA Astrophysics Data System (ADS)

Shah, Rashmi S.; Bettis, Jerry R.; Stewart, Alan F.; Bonsall, Lynn; Copland, James; Hughes, William; Echeverry, Juan C.

1999-04-01

The thermal response of a coated optical surface is an important consideration in the design of any high average power system. Finite element temperature distribution were calculated for both coating witness samples and calorimetry wafers and were compared to actual measured data under tightly controlled conditions. Coatings for ABL were deposited on various substrates including fused silica, ULE, Zerodur, and silicon. The witness samples were irradiate data high power levels at 1.315micrometers to evaluate laser damage thresholds and study absorption levels. Excellent agreement was obtained between temperature predictions and measured thermal response curves. When measured absorption values were not available, the code was used to predict coating absorption based on the measured temperature rise on the back surface. Using the finite element model, the damaging temperature rise can be predicted for a coating with known absorption based on run time, flux, and substrate material.

Stress regulation and incision in borderline personality disorder--a pilot study modeling cutting behavior.

PubMed

Reitz, Sarah; Krause-Utz, Annegret; Pogatzki-Zahn, Esther M; Ebner-Priemer, Ulrich; Bohus, Martin; Schmahl, Christian

2012-08-01

Emotion dysregulation in Borderline Personality Disorder (BPD) is characterized by high baseline negative intensity, high reactivity, and slow return to baseline. Patients with BPD often engage in self-injurious behavior because it leads to immediate relief of stress levels. We aimed to assess stress regulation as well as the influence of tissue damage on subjective (aversive tension) and objective (heart rate) stress correlates in BPD. In 14 unmedicated patients with BPD and 18 healthy controls, a stress induction was followed by an incision into the forearm conducted by an investigator. For aversive tension, we found elevated baseline levels as well as slower return to baseline in BPD. In controls, incision resulted in a short-term increase of aversive tension, whereas tension and heart rate decreased in the BPD group. Our preliminary results support the hypothesis that tissue damage may play a role in disturbed stress regulation in BPD.

Blast Performance of Commercially Available Demining Footwear: A Summary of Experimental Trials on Surrogate Legs

DTIC Science & Technology

2008-10-01

Equipment Department of the Dutch Ministry of Defence tasked TNO Defence, Security and Safety to perform AP mine shoe tests to study the protection level...would not provide more insight. Therefore only two tests at 75 g were performed . The test results are summarized in Table 2. The high speed video...be able to better place foot into shoe . But still damage of gelatine prior to test. Pretest x-ray performed to show damage prior to test. The

Evaluation of spatial and temporal patterns of insect damage and aflatoxin level in the pre-harvest corn fields to improve management tactics.

PubMed

Ni, Xinzhi; Wilson, Jeffrey P; Toews, Michael D; Buntin, G David; Lee, R Dewey; Li, Xin; Lei, Zhongren; He, Kanglai; Xu, Wenwei; Li, Xianchun; Huffaker, Alisa; Schmelz, Eric A

2014-10-01

Spatial and temporal patterns of insect damage in relation to aflatoxin contamination in a corn field with plants of uniform genetic background are not well understood. After previous examination of spatial patterns of insect damage and aflatoxin in pre-harvest corn fields, we further examined both spatial and temporal patterns of cob- and kernel-feeding insect damage, and aflatoxin level with two samplings at pre-harvest in 2008 and 2009. The feeding damage by each of the ear/kernel-feeding insects (i.e., corn earworm/fall armyworm damage on the silk/cob, and discoloration of corn kernels by stink bugs) and maize weevil population were assessed at each grid point with five ears. Sampling data showed a field edge effect in both insect damage and aflatoxin contamination in both years. Maize weevils tended toward an aggregated distribution more frequently than either corn earworm or stink bug damage in both years. The frequency of detecting aggregated distribution for aflatoxin level was less than any of the insect damage assessments. Stink bug damage and maize weevil number were more closely associated with aflatoxin level than was corn earworm damage. In addition, the indices of spatial-temporal association (χ) demonstrated that the number of maize weevils was associated between the first (4 weeks pre-harvest) and second (1 week pre-harvest) samplings in both years on all fields. In contrast, corn earworm damage between the first and second samplings from the field on the Belflower Farm, and aflatoxin level and corn earworm damage from the field on the Lang Farm were dissociated in 2009. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

Treating chronic arsenic toxicity with high selenium lentil diets

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

Sah, Shweta; Vandenberg, Albert; Smits, Judit, E-mail: judit.smits@ucalgary.ca

2013-10-01

Arsenic (As) toxicity causes serious health problems in humans, especially in the Indo-Gangetic plains and mountainous areas of China. Selenium (Se), an essential micronutrient is a potential mitigator of As toxicity due to its antioxidant and antagonistic properties. Selenium is seriously deficient in soils world-wide but is present at high, yet non-toxic levels in the great plains of North America. We evaluate the potential of dietary Se in counteracting chronic As toxicity in rats through serum biochemistry, blood glutathione levels, immunotoxicity (antibody response), liver peroxidative stress, thyroid response and As levels in tissues and excreta. To achieve this, we comparemore » diets based on high-Se Saskatchewan (SK) lentils versus low-Se lentils from United States. Rats drank control (0 ppm As) or As (40 ppm As) water while consuming SK lentils (0.3 ppm Se) or northwestern USA lentils (< 0.01 ppm Se) diets for 14 weeks. Rats on high Se diets had higher glutathione levels regardless of As exposure, recovered antibody responses in As-exposed group, higher fecal and urinary As excretion and lower renal As residues. Selenium deficiency caused greater hepatic peroxidative damage in the As exposed animals. Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were not different. After 14 weeks of As exposure, health indicators in rats improved in response to the high Se lentil diets. Our results indicate that high Se lentils have a potential to mitigate As toxicity in laboratory mammals, which we hope will translate into benefits for As exposed humans. - Highlights: • We reduce chronic arsenic toxicity in rats with a whole food solution. • High selenium lentils decrease liver damage and increase blood glutathione levels. • High selenium lentil diets increase urinary and fecal arsenic excretion. • High selenium lentil diets decrease arsenic levels in kidney, the storage organ. • High selenium lentil diets reverse arsenic suppression of the B cell response.« less

Rapid Disaster Damage Estimation

NASA Astrophysics Data System (ADS)

Vu, T. T.

2012-07-01

The experiences from recent disaster events showed that detailed information derived from high-resolution satellite images could accommodate the requirements from damage analysts and disaster management practitioners. Richer information contained in such high-resolution images, however, increases the complexity of image analysis. As a result, few image analysis solutions can be practically used under time pressure in the context of post-disaster and emergency responses. To fill the gap in employment of remote sensing in disaster response, this research develops a rapid high-resolution satellite mapping solution built upon a dual-scale contextual framework to support damage estimation after a catastrophe. The target objects are building (or building blocks) and their condition. On the coarse processing level, statistical region merging deployed to group pixels into a number of coarse clusters. Based on majority rule of vegetation index, water and shadow index, it is possible to eliminate the irrelevant clusters. The remaining clusters likely consist of building structures and others. On the fine processing level details, within each considering clusters, smaller objects are formed using morphological analysis. Numerous indicators including spectral, textural and shape indices are computed to be used in a rule-based object classification. Computation time of raster-based analysis highly depends on the image size or number of processed pixels in order words. Breaking into 2 level processing helps to reduce the processed number of pixels and the redundancy of processing irrelevant information. In addition, it allows a data- and tasks- based parallel implementation. The performance is demonstrated with QuickBird images captured a disaster-affected area of Phanga, Thailand by the 2004 Indian Ocean tsunami are used for demonstration of the performance. The developed solution will be implemented in different platforms as well as a web processing service for operational uses.

Aldosterone and Mineralocorticoid Receptors-Physiology and Pathophysiology.

PubMed

Funder, John W

2017-05-11

Aldosterone is a uniquely terrestrial hormone, first appearing in lungfish, which have both gills and lungs. Mineralocorticoid receptors (MRs), on the other hand, evolved much earlier, and are found in cartilaginous and bony fish, presumptive ligand cortisol. MRs have equivalent high affinity for aldosterone, progesterone, and cortisol; in epithelia, despite much higher cortisol circulating levels, aldosterone selectively activates MRs by co-expression of the enzyme 11β-hydroxysteroid dehydrogenase, Type 11. In tissues in which the enzyme is not expressed, MRs are overwhelmingly occupied but not activated by cortisol, which normally thus acts as an MR antagonist; in tissue damage, however, cortisol mimics aldosterone and acts as an MR agonist. The risk profile for primary aldosteronism (PA) is much higher than that in age-, sex-, and blood pressure-matched essential hypertensives. High levels of aldosterone per se are not the problem: in chronic sodium deficiency, as seen in the monsoon season in the highlands of New Guinea, plasma aldosterone levels are extraordinarily high, but cause neither hypertension nor cardiovascular damage. Such damage occurs when aldosterone levels are out of the normal feedback control, and are inappropriately elevated for the salt status of the individual (or experimental animal). The question thus remains of how excess salt can synergize with elevated aldosterone levels to produce deleterious cardiovascular effects. One possible mechanism is through the agency of the elusive ouabain-like factors (OLFs). Such factors are secreted from the adrenal in response to ACTH (adrenalocortical tropic hormone), to angiotensin via AT2R, and-the polar opposite of aldosterone-to sodium loading. They act on blood vessels to cause vasoconstriction and thus elevate blood pressure to dump excess sodium through pressure natriuresis. Their levels are chronically elevated in PA in response to the continually elevated sodium status, and they thus act to constrict coronary and systemic arteries. In the context of the elevated blood volume and total body sodium in a PA patient, this raises blood pressure and acts as the proximate cause of cardiovascular damage. If this is the case, it would appear to offer new insights into therapy for PA. One would be the use of digibindin, or its more recent successors as antagonists of OLFs acting on Na/K ATPase at the vessel wall. A second would be to routinely combine a low dose MR antagonist, an ENaC inhibitor, and sodium restriction as first-line therapy for bilateral aldosterone overproduction. Finally, for unilateral cases post-surgery, there is good reason to include low-dose MRs in drug therapy if required, given the ability of cortisol in damaged blood vessels to mimic aldosterone vasoconstrictor action.

Survey of Codes Employing Nuclear Damage Assessment

DTIC Science & Technology

1977-10-01

surveyed codes were com- DO 73Mu 1473 ETN OF 1NOVSSSOLETE UNCLASSIFIED 1 SECURITY CLASSIFICATION OF THIS f AGE (Wh*11 Date Efntered)S<>-~C. I UNCLASSIFIED...level and above) TALLEY/TOTEM not nuclear TARTARUS too highly aggregated (battalion level and above) UNICORN highly aggregated force allocation code...vulnerability data can bq input by the user as he receives them, and there is the abil ’ity to replay any situation using hindsight. The age of target

Self-Directed Student Research through Analysis of Microarray Datasets: A Computer-Based Functional Genomics Practical Class for Masters-Level Students

ERIC Educational Resources Information Center

Grenville-Briggs, Laura J.; Stansfield, Ian

2011-01-01

This report describes a linked series of Masters-level computer practical workshops. They comprise an advanced functional genomics investigation, based upon analysis of a microarray dataset probing yeast DNA damage responses. The workshops require the students to analyse highly complex transcriptomics datasets, and were designed to stimulate…

Tolerance to hypometabolism and arousal induced by hibernation in the apple snail Pomacea canaliculata (Caenogastropoda, Ampullariidae).

PubMed

Giraud-Billoud, Maximiliano; Castro-Vazquez, Alfredo; Campoy-Diaz, Alejandra D; Giuffrida, Pablo M; Vega, Israel A

2017-12-19

Pomacea canaliculata may serve as a model organism for comparative studies of oxidative damage and antioxidant defenses in active, hibernating and arousing snails. Oxidative damage (as TBARS), free radical scavenging capacity (as ABTS + oxidation), uric acid (UA) and glutathione (GSH) concentrations, activities of superoxide dismutase (SOD) and catalase (CAT), and the protein expression levels of heat shock proteins (Hsp70, Hsc70, Hsp90) were studied in digestive gland, kidney and foot. Tissue TBARS of hibernating snails (45days) was higher than active snails. Hibernation produced an increase of ABTS + in digestive gland, probably because of the sustained antioxidant defenses (UA and/or GSH and SOD levels). Kidney protection during the activity-hibernation cycle seemed provided by increased UA concentrations. TBARS in the foot remained high 30min after arousal with no changes in ABTS + , but this tissue increased ABTS + oxidation at 24h to expenses increased UA and decreased GSH levels, and with no changes in SOD and CAT activities. The level of Hsp70 in kidney showed no changes throughout the activity-hibernation cycle but it increased in the foot after hibernation. The tissue levels of Hsp90 in snails hibernating were higher than active snails and returned to baseline 24h after arousal. Results showed that chronic cooling produces a significant oxidative damage in three studied tissues and that these tissue damages are overcome quickly (between 30min to 24h) with fluctuations in different antioxidant defenses (UA, GSH, CAT) and heat shock proteins (Hsp70 and Hsp90). Copyright © 2017 Elsevier Inc. All rights reserved.

The development of a high sensitivity neutron displacement damage sensor

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

Tonigan, Andrew M.; Parma, Edward J.; Martin, William J.

Here, the capability to characterize the neutron energy spectrum and fluence received by a test object is crucial to under-standing the damage effects observed in electronic components. For nuclear research reactors and high energy density physics fa-cilities this can pose exceptional challenges, especially with low level neutron fluences. An ASTM test method for characterizing neutron environments utilizes the 2N2222A transistor as a 1-MeV equivalent neutron fluence sensor and is applicable for environ-ments with 1 x 10 12 - 1 x 10 14 1-MeV(Si)-Eqv.-n/cm 2. In this work we seek to extend the range of this test method to lower fluencemore » environments utilizing the 2N1486 transistor. Here, the 2N1486 is shown to be an effective neutron displacement damage sensor as low as 1 x 10 10 1-MeV(Si)-Eqv.-n/cm 2.« less

The development of a high sensitivity neutron displacement damage sensor

DOE PAGES

Tonigan, Andrew M.; Parma, Edward J.; Martin, William J.

2016-11-23

Here, the capability to characterize the neutron energy spectrum and fluence received by a test object is crucial to under-standing the damage effects observed in electronic components. For nuclear research reactors and high energy density physics fa-cilities this can pose exceptional challenges, especially with low level neutron fluences. An ASTM test method for characterizing neutron environments utilizes the 2N2222A transistor as a 1-MeV equivalent neutron fluence sensor and is applicable for environ-ments with 1 x 10 12 - 1 x 10 14 1-MeV(Si)-Eqv.-n/cm 2. In this work we seek to extend the range of this test method to lower fluencemore » environments utilizing the 2N1486 transistor. Here, the 2N1486 is shown to be an effective neutron displacement damage sensor as low as 1 x 10 10 1-MeV(Si)-Eqv.-n/cm 2.« less

Effects of Peach Cultivar on Enzymatic Browning Following Cell Damage from High-Pressure Processing.

PubMed

Techakanon, Chukwan; Gradziel, Thomas M; Barrett, Diane M

2016-10-12

Peach cultivars contribute to unique product characteristics and may affect the degree of browning after high-pressure processing (HPP). Nine peach cultivars were subjected to HPP at 0, 100, and 400 MPa for 10 min. Proton nuclear magnetic resonance ( 1 H NMR) relaxometry, light microscopy, color, polyphenol oxidase (PPO) activity, and total phenols were evaluated. The development of enzymatic browning during refrigerated storage occurred because of damage during HPP that triggered loss of cell integrity, allowing substrates to interact with enzymes. Increasing pressure levels resulted in greater damage, as determined by shifts in transverse relaxation time (T 2 ) and by light micrographs. Discoloration was triggered by membrane decompartmentalization but limited by PPO activity, which was found to correlate to cultivar harvest time (early, mid, and late season). Outcomes from the microstructure, 1 H NMR ,and PPO activity evaluation were an effective means of determining membrane decompartmentalization and allowed for prediction of browning scenarios.

Plasmatic endothelin-1 levels in hyperthyroid patients before and after antithyroid therapy.

PubMed

Cesareo, R; Tarabuso, A; Di Benedetto, M; Lacerna, F; Reda, G

2000-03-01

The Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide produced by endothelial cells in many vascular diseases probably as a response to vessel damage. In hyperthyroidism as in other endocrinological diseases elevated ET-1 plasma levels have been found. The effect of antithyroid therapy on ET-1 plasmatic levels was evaluated by measuring ET-1 plasma levels before and 2 and 6 months after treatment with methimazole in 14 patients affected by hyperthyroidism. The hyperthyroid patients had significantly higher ET-1 levels than the controls (18.85 +/- 5.7 vs 10.9 +/- 2.1 pg/ml), while after treatment no difference was found. The ET-1 plasma levels of hyperthyroid patients correlated closely with the raised thyroid metabolic activity independently of its cause. It is possible that the increased ET-1 levels in hyperthyroid patients are the expression of blood vessel damage caused by high thyroid hormone levels. Moreover the results of this study could suggest that, in future, ET-1 plasmatic levels might be considered as a functional thyroid index in hyperthyroid diseases.

MDMA and heightened cortisol: a neurohormonal perspective on the pregnancy outcomes of mothers used 'Ecstasy' during pregnancy.

PubMed

Parrott, Andrew C; Moore, Derek G; Turner, John J D; Goodwin, Julia; Min, Meeyoung O; Singer, Lynn T

2014-01-01

The illicit recreational drug 3,4-methylenedioxymethamphetamine (MDMA) or Ecstasy has strong neurohormonal effects. When taken by recreational users at dance clubs and raves, it can generate an 800% increase in the stress hormone cortisol, whereas drug-free users show chronically raised levels of cortisol. The aim here is to critically debate this neurohormonal influence for the children of pregnant MDMA-using mothers. High levels of cortisol are known to be damaging for neuropsychobiological well-being in adult humans. MDMA can damage foetal development in laboratory animals, and the prospective Drugs and Infancy Study was established to monitor the effects of MDMA taken recreationally by pregnant women. The Drugs and Infancy Study revealed that young mothers, who took MDMA during the first trimester of pregnancy, gave birth to babies with significant gross psychomotor retardation. These mothers would have experienced high levels of cortisol due to Ecstasy/MDMA use, and since cortisol can cross the placenta, this is likely to have also occurred in the foetus. In terms of causation, the developmental problems may reflect a combination of neurotransmitter and neurohormonal effects on the hypothalamic-pituitary-adrenal axis, with serotonergic activity being influenced by the high levels of cortisol. Copyright © 2014 John Wiley & Sons, Ltd.

Predicting the location of missing outer hair cells using the electrical signal recorded at the round window

PubMed Central

Chertoff, Mark E.; Earl, Brian R.; Diaz, Francisco J.; Sorensen, Janna L.; Thomas, Megan L. A.; Kamerer, Aryn M.; Peppi, Marcello

2014-01-01

The electrical signal recorded at the round window was used to estimate the location of missing outer hair cells. The cochlear response was recorded to a low frequency tone embedded in high-pass filtered noise conditions. Cochlear damage was created by either overexposure to frequency-specific tones or laser light. In animals with continuous damage along the partition, the amplitude of the cochlear response increased as the high-pass cutoff frequency increased, eventually reaching a plateau. The cochlear distance at the onset of the plateau correlated with the anatomical onset of outer hair cell loss. A mathematical model replicated the physiologic data but was limited to cases with continuous hair cell loss in the middle and basal turns. The neural contribution to the cochlear response was determined by recording the response before and after application of Ouabain. Application of Ouabain eliminated or reduced auditory neural activity from approximately two turns of the cochlea. The amplitude of the cochlear response was reduced for moderate signal levels with a limited effect at higher levels, indicating that the cochlear response was dominated by outer hair cell currents at high signal levels and neural potentials at low to moderate signal levels. PMID:25190395

Peripheral blood lymphocytes: a model for monitoring physiological adaptation to high altitude.

PubMed

Mariggiò, Maria A; Falone, Stefano; Morabito, Caterina; Guarnieri, Simone; Mirabilio, Alessandro; Pilla, Raffaele; Bucciarelli, Tonino; Verratti, Vittore; Amicarelli, Fernanda

2010-01-01

Depending on the absolute altitude and the duration of exposure, a high altitude environment induces various cellular effects that are strictly related to changes in oxidative balance. In this study, we used in vitro isolated peripheral blood lymphocytes as biosensors to test the effect of hypobaric hypoxia on seven climbers by measuring the functional activity of these cells. Our data revealed that a 21-day exposure to high altitude (5000 m) (1) increased intracellular Ca(2+) concentration, (2) caused a significant decrease in mitochondrial membrane potential, and (3) despite possible transient increases in intracellular levels of reactive oxygen species, did not significantly change the antioxidant and/or oxidative damage-related status in lymphocytes and serum, assessed by measuring Trolox-equivalent antioxidant capacity, glutathione peroxidase activity, vitamin levels, and oxidatively modified proteins and lipids. Overall, these results suggest that high altitude might cause an impairment in adaptive antioxidant responses. This, in turn, could increase the risk of oxidative-stress-induced cellular damage. In addition, this study corroborates the use of peripheral blood lymphocytes as an easily handled model for monitoring adaptive response to environmental challenge.

The α-lipoic acid improves high-fat diet-induced cerebral damage through inhibition of oxidative stress and inflammatory reaction.

PubMed

Liu, Yang; Zhang, Qinghua; Wang, Li; Wang, Hui; Sun, Tao; Xia, Hechun; Yang, Yi; Zhang, Li

2017-12-01

This study is to clarify the protective role of α-lipoic acid in high-fat diet-induced cerebral damage mice. The mice were divided into 5 groups: normal control group, high-fat diet (HFD) group, low-dose α-lipoic acid group for prevention, high-dose α-lipoic acid group for prevention, and high-dose α-lipoic acid group for treatment. The groups' weights and blood glucose changes were monitored. We used HE staining to observe morphological changes in the cerebral cortex. The expression levels of the oxidative stress proteins SOD2, catalase, and the inflammatory pathway proteins p-JNK, p-ERK were measured by western blot and immunochemistry. Compared with the control group, the quantity of cortical neurons in the HFD group was decreased, and the samples exhibited retrogression. However, the lipoic acid significantly protected and promoted the cortical neurons survival. Moreover, compared with the HFD group, the expression levels of SOD2 and catalase in the three α-lipoic acid obtained groups were significantly increased. However, the expression levels of the inflammatory pathway proteins p-JNK and p-ERK were significantly decreased. These results indicate that theα-lipoic acid greatly protects the cortical neurons, and inhibited the oxidative stress and inflammatory reactions in the high-fat diet mice. Copyright © 2017 Elsevier B.V. All rights reserved.

Post-Disaster Damage Assessment Through Coherent Change Detection on SAR Imagery

NASA Astrophysics Data System (ADS)

Guida, L.; Boccardo, P.; Donevski, I.; Lo Schiavo, L.; Molinari, M. E.; Monti-Guarnieri, A.; Oxoli, D.; Brovelli, M. A.

2018-04-01

Damage assessment is a fundamental step to support emergency response and recovery activities in a post-earthquake scenario. In recent years, UAVs and satellite optical imagery was applied to assess major structural damages before technicians could reach the areas affected by the earthquake. However, bad weather conditions may harm the quality of these optical assessments, thus limiting the practical applicability of these techniques. In this paper, the application of Synthetic Aperture Radar (SAR) imagery is investigated and a novel approach to SAR-based damage assessment is presented. Coherent Change Detection (CCD) algorithms on multiple interferometrically pre-processed SAR images of the area affected by the seismic event are exploited to automatically detect potential damages to buildings and other physical structures. As a case study, the 2016 Central Italy earthquake involving the cities of Amatrice and Accumoli was selected. The main contribution of the research outlined above is the integration of a complex process, requiring the coordination of a variety of methods and tools, into a unitary framework, which allows end-to-end application of the approach from SAR data pre-processing to result visualization in a Geographic Information System (GIS). A prototype of this pipeline was implemented, and the outcomes of this methodology were validated through an extended comparison with traditional damage assessment maps, created through photo-interpretation of high resolution aerial imagery. The results indicate that the proposed methodology is able to perform damage detection with a good level of accuracy, as most of the detected points of change are concentrated around highly damaged buildings.

AtPDCD5 Plays a Role in Programmed Cell Death after UV-B Exposure in Arabidopsis1[OPEN

PubMed Central

Falcone Ferreyra, María Lorena; D’Andrea, Lucio; AbdElgawad, Hamada

2016-01-01

DNA damage responses have evolved to sense and react to DNA damage; the induction of DNA repair mechanisms can lead to genomic restoration or, if the damaged DNA cannot be adequately repaired, to the execution of a cell death program. In this work, we investigated the role of an Arabidopsis (Arabidopsis thaliana) protein, AtPDCD5, which is highly similar to the human PDCD5 protein; it is induced by ultraviolet (UV)-B radiation and participates in programmed cell death in the UV-B DNA damage response. Transgenic plants expressing AtPDCD5 fused to GREEN FLUORESCENT PROTEIN indicate that AtPDCD5 is localized both in the nucleus and the cytosol. By use of pdcd5 mutants, we here demonstrate that these plants have an altered antioxidant metabolism and accumulate higher levels of DNA damage after UV-B exposure, similar to levels in ham1ham2 RNA interference transgenic lines with decreased expression of acetyltransferases from the MYST family. By coimmunoprecipitation and pull-down assays, we provide evidence that AtPDCD5 interacts with HAM proteins, suggesting that both proteins participate in the same pathway of DNA damage responses. Plants overexpressing AtPDCD5 show less DNA damage but more cell death in root tips upon UV-B exposure. Finally, we here show that AtPDCD5 also participates in age-induced programmed cell death. Together, the data presented here demonstrate that AtPDCD5 plays an important role during DNA damage responses induced by UV-B radiation in Arabidopsis and also participates in programmed cell death programs. PMID:26884483

NLRP3 Inflammasome Mediates Aldosterone-Induced Vascular Damage.

PubMed

Bruder-Nascimento, Thiago; Ferreira, Nathanne S; Zanotto, Camila Z; Ramalho, Fernanda; Pequeno, Isabela O; Olivon, Vania C; Neves, Karla B; Alves-Lopes, Rheure; Campos, Eduardo; Silva, Carlos Alberto A; Fazan, Rubens; Carlos, Daniela; Mestriner, Fabiola L; Prado, Douglas; Pereira, Felipe V; Braga, Tarcio; Luiz, Joao Paulo M; Cau, Stefany B; Elias, Paula C; Moreira, Ayrton C; Câmara, Niels O; Zamboni, Dario S; Alves-Filho, Jose Carlos; Tostes, Rita C

2016-12-06

Inflammation is a key feature of aldosterone-induced vascular damage and dysfunction, but molecular mechanisms by which aldosterone triggers inflammation remain unclear. The NLRP3 inflammasome is a pivotal immune sensor that recognizes endogenous danger signals triggering sterile inflammation. We analyzed vascular function and inflammatory profile of wild-type (WT), NLRP3 knockout (NLRP3 -/- ), caspase-1 knockout (Casp-1 -/- ), and interleukin-1 receptor knockout (IL-1R -/- ) mice treated with vehicle or aldosterone (600 µg·kg -1 ·d -1 for 14 days through osmotic mini-pump) while receiving 1% saline to drink. Here, we show that NLRP3 inflammasome plays a central role in aldosterone-induced vascular dysfunction. Long-term infusion of aldosterone in mice resulted in elevation of plasma interleukin-1β levels and vascular abnormalities. Mice lacking the IL-1R or the inflammasome components NLRP3 and caspase-1 were protected from aldosterone-induced vascular damage. In vitro, aldosterone stimulated NLRP3-dependent interleukin-1β secretion by bone marrow-derived macrophages by activating nuclear factor-κB signaling and reactive oxygen species generation. Moreover, chimeric mice reconstituted with NLRP3-deficient hematopoietic cells showed that NLRP3 in immune cells mediates aldosterone-induced vascular damage. In addition, aldosterone increased the expression of NLRP3, active caspase-1, and mature interleukin-1β in human peripheral blood mononuclear cells. Hypertensive patients with hyperaldosteronism or normal levels of aldosterone exhibited increased activity of NLRP3 inflammasome, suggesting that the effect of hyperaldosteronism on the inflammasome may be mediated through high blood pressure. Together, these data demonstrate that NLRP3 inflammasome, through activation of IL-1R, is critically involved in the deleterious vascular effects of aldosterone, placing NLRP3 as a potential target for therapeutic interventions in conditions with high aldosterone levels. © 2016 American Heart Association, Inc.

Building damage concentrated in Longtoushan town during the 2014 Ms. 6.5 Ludian earthquake, Yunnan, China: examination of cause and implications based on ground motion and vulnerability analyses

NASA Astrophysics Data System (ADS)

Wang, Xin; Kurahashi, Susumu; Wu, Hao; Si, Hongjun; Ma, Qiang; Dang, Ji; Tao, Dongwang; Feng, Jiwei; Irikura, Kojiro

2017-09-01

Though the 2014 Ludian Earthquake had only a moderate magnitude (Ms 6.5), high-level ground motions of almost 1 g occurred at Longtoushan Town (seismic station 53LLT), which located near the intersection of a conjugate-shaped seismogenic fault. The building damages on the pluvial fan and the river terrace at Longtoushan was clearly different. In order to examine the generation of the large acceleration at 53LLT, the focal mechanisms and the rupture processes of the conjugate-shaped seismogenic fault were determined. We found that there were two continuous impulsive waves in the records of 53LLT that were generated from two different faults, the Baogunao fault and the Xiaohe fault, respectively. Site effects on the pluvial fan and the river terrace at Longtoushan Town and their relations to different building damages were examined. We found that the predominant period at the pluvial fan was about 0.25 s, close to the fundamental natural period of multi-story confined masonry buildings. Ground motions on the pluvial fan and the river terrace were simulated through convolving synthesized bedrock motions with the transfer functions, which were analyzed using the one-dimensional underground velocity structures identified from H/V spectral ratios of ambient noise. Building collapse ratios (CRs) are estimated based on the vulnerability function of the 2008 Wenchuan Earthquake and are compared with the observed values. We found that the observed building CRs on the pluvial fan are much higher than the estimated values. High-level ground shaking that is far beyond the design level was a reason for serious building damage.

Sub-Frequency Interval Approach in Electromechanical Impedance Technique for Concrete Structure Health Monitoring

PubMed Central

Yang, Yaowen; Divsholi, Bahador Sabet

2010-01-01

The electromechanical (EM) impedance technique using piezoelectric lead zirconate titanate (PZT) transducers for structural health monitoring (SHM) has attracted considerable attention in various engineering fields. In the conventional EM impedance technique, the EM admittance of a PZT transducer is used as a damage indicator. Statistical analysis methods such as root mean square deviation (RMSD) have been employed to associate the damage level with the changes in the EM admittance signatures, but it is difficult to determine the location of damage using such methods. This paper proposes a new approach by dividing the large frequency (30–400 kHz) range into sub-frequency intervals and calculating their respective RMSD values. The RMSD of the sub-frequency intervals (RMSD-S) will be used to study the severity and location of damage. An experiment is carried out on a real size concrete structure subjected to artificial damage. It is observed that damage close to the PZT changes the high frequency range RMSD-S significantly, while the damage far away from the PZT changes the RMSD-S in the low frequency range significantly. The relationship between the frequency range and the PZT sensing region is also presented. Finally, a damage identification scheme is proposed to estimate the location and severity of damage in concrete structures. PMID:22163548

Atomic layer deposition for fabrication of HfO2/Al2O3 thin films with high laser-induced damage thresholds.

PubMed

Wei, Yaowei; Pan, Feng; Zhang, Qinghua; Ma, Ping

2015-01-01

Previous research on the laser damage resistance of thin films deposited by atomic layer deposition (ALD) is rare. In this work, the ALD process for thin film generation was investigated using different process parameters such as various precursor types and pulse duration. The laser-induced damage threshold (LIDT) was measured as a key property for thin films used as laser system components. Reasons for film damaged were also investigated. The LIDTs for thin films deposited by improved process parameters reached a higher level than previously measured. Specifically, the LIDT of the Al2O3 thin film reached 40 J/cm(2). The LIDT of the HfO2/Al2O3 anti-reflector film reached 18 J/cm(2), the highest value reported for ALD single and anti-reflect films. In addition, it was shown that the LIDT could be improved by further altering the process parameters. All results show that ALD is an effective film deposition technique for fabrication of thin film components for high-power laser systems.

Structural damages observed in state buildings after Simav/Turkey earthquake occurred on 19 May 2011

NASA Astrophysics Data System (ADS)

Tama, Y. S.

2012-08-01

Different levels of damages occurred in state buildings, especially in educational facilities, during the Simav earthquake (ML=5.7) on 19 May 2011. A site survey was carried out in the area after the earthquake, where six state buildings were examined in detail. The results of the survey showed that main reasons for the formation of damages in these buildings are the use of low strength concrete, insufficient reinforcement, inappropriate detailing, and low-quality workmanship. The investigated buildings were also evaluated by P25-rapid assessment method. The method demonstrates that two of the buildings in question are in "high risk band"; the other two fall into "detailed evaluation band", and the rest are in the "low risk band". This figure also matches with the damages observed in the site survey.

Sea Level Rise Impacts On Infrastructure Vulnerability

NASA Astrophysics Data System (ADS)

Pasqualini, D.; Mccown, A. W.; Backhaus, S.; Urban, N. M.

2015-12-01

Increase of global sea level is one of the potential consequences of climate change and represents a threat for the U.S.A coastal regions, which are highly populated and home of critical infrastructures. The potential danger caused by sea level rise may escalate if sea level rise is coupled with an increase in frequency and intensity of storms that may strike these regions. These coupled threats present a clear risk to population and critical infrastructure and are concerns for Federal, State, and particularly local response and recovery planners. Understanding the effect of sea level rise on the risk to critical infrastructure is crucial for long planning and for mitigating potential damages. In this work we quantify how infrastructure vulnerability to a range of storms changes due to an increase of sea level. Our study focuses on the Norfolk area of the U.S.A. We assess the direct damage of drinking water and wastewater facilities and the power sector caused by a distribution of synthetic hurricanes. In addition, our analysis estimates indirect consequences of these damages on population and economic activities accounting also for interdependencies across infrastructures. While projections unanimously indicate an increase in the rate of sea level rise, the scientific community does not agree on the size of this rate. Our risk assessment accounts for this uncertainty simulating a distribution of sea level rise for a specific climate scenario. Using our impact assessment results and assuming an increase of future hurricanes frequencies and intensities, we also estimate the expected benefits for critical infrastructure.

Effect of Hibiscus sabdariffa extract on high fat diet-induced obesity and liver damage in hamsters.

PubMed

Huang, To-Wei; Chang, Chia-Ling; Kao, Erl-Shyh; Lin, Jenq-Horng

2015-01-01

Obesity is a chronic metabolic disorder associated with an increase in adipogenesis and often accompanied with fatty liver disease. In this study, we investigated the anti-obesity effects of Hibiscus sabdariffa water extract (HSE) in vivo. Eight-weeks-old male mice were divided into six groups (n=8 per group) and were fed either normal feed, a high fat diet (HFD), HFD supplemented with different concentrations of HSE, or HFD supplemented with anthocyanin. After 10 weeks of feeding, all the blood and livers were collected for further analysis. Mesocricetus auratus hamster fed with a high-fat diet developed symptoms of obesity, as determined from their body weight change and from their plasma lipid levels. Meanwhile, HSE treatment reduced fat accumulation in the livers of hamsters fed with HFD in a concentration-dependent manner. Administration of HSE reduced the levels of liver cholesterol and triglycerides, which were elevated by HFD. Analysis of the effect of HSE on paraoxonase 1, an antioxidant liver enzyme, revealed that HSE potentially regulates lipid peroxides and protects organs from oxidation-associated damage. The markers of liver damage such as serum alanine aminotransferase and aspartate aminotransferase levels that were elevated by HFD were also reduced on HSE treatment. The effects of HSE were as effective as treatment with anthocyanin; therefore the anthocyanins present in the HSE may play a crucial role in the protection established against HFD-induced obesity. In conclusion HSE administration constitutes an effective and viable treatment strategy against the development and consequences of obesity.

Effect of Hibiscus sabdariffa extract on high fat diet–induced obesity and liver damage in hamsters

PubMed Central

Huang, To-Wei; Chang, Chia-Ling; Kao, Erl-Shyh; Lin, Jenq-Horng

2015-01-01

Background Obesity is a chronic metabolic disorder associated with an increase in adipogenesis and often accompanied with fatty liver disease. Objective In this study, we investigated the anti-obesity effects of Hibiscus sabdariffa water extract (HSE) in vivo. Method Eight-weeks-old male mice were divided into six groups (n=8 per group) and were fed either normal feed, a high fat diet (HFD), HFD supplemented with different concentrations of HSE, or HFD supplemented with anthocyanin. After 10 weeks of feeding, all the blood and livers were collected for further analysis. Results Mesocricetus auratus hamster fed with a high-fat diet developed symptoms of obesity, as determined from their body weight change and from their plasma lipid levels. Meanwhile, HSE treatment reduced fat accumulation in the livers of hamsters fed with HFD in a concentration-dependent manner. Administration of HSE reduced the levels of liver cholesterol and triglycerides, which were elevated by HFD. Analysis of the effect of HSE on paraoxonase 1, an antioxidant liver enzyme, revealed that HSE potentially regulates lipid peroxides and protects organs from oxidation-associated damage. The markers of liver damage such as serum alanine aminotransferase and aspartate aminotransferase levels that were elevated by HFD were also reduced on HSE treatment. The effects of HSE were as effective as treatment with anthocyanin; therefore the anthocyanins present in the HSE may play a crucial role in the protection established against HFD-induced obesity. Conclusions In conclusion HSE administration constitutes an effective and viable treatment strategy against the development and consequences of obesity. PMID:26475512

He diffusion in zircon: Observations from (U-Th)/He age suites and 4He diffusion experiments and implications for radiation damage and anisotropic effects

NASA Astrophysics Data System (ADS)

Guenthner, W. R.; Reiners, P. W.

2009-12-01

Despite widespread use of zircon (U-Th)/He thermochronometry in many geologic applications, our understanding of the kinetics of He diffusion in this system is rudimentary. Previous studies have shown that both radiation damage and crystallographic anisotropy may strongly influence diffusion kinetics and ages. We present observations of zircon He ages from multiple single-grain analyses from both detrital and bedrock suites from a wide variety of locations, showing relationships consistent with effects arising from the interaction of radiation damage and anisotropy. Individual zircons in each suite have experienced the same post-depositional or exhumational t-T history but grains appear to have experienced differential He loss that is correlated with effective uranium (eU) content, a proxy for the relative extent of radiation damage within each suite. Several suites of zircons heated to partial resetting upon burial or that have experienced slow cooling show positive correlations between age and eU. Examples of partially reset detrital samples include Cretaceous Sevier foreland basin sandstones buried to ~6-8 km depth, with ages ranging from 88-309 Ma across an eU range of 215-1453 ppm, and Apennines and Olympics greywackes heated to >~120 °C, showing similar trends. Some slowly-cooled bedrock samples also show positive age-eU correlations, suggesting increasing closure temperature with higher extents of radiation damage. Conversely, zircons from cratonal bedrock samples with high levels of radiation damage—measured as accumulated alpha dosage (in this case >~10^18 α/g)—generally show negative age-eU correlations. We interpret these contrasting age-eU relationships as a manifestation of the interaction of radiation damage and anisotropic diffusion: at low damage, He diffusivity is relatively high and preferentially through c-axis-parallel channels. As suggested by Farley (2007), however, with increasing damage, channels are progressively blocked and He diffusivity decreases. Eventually, a crystal reaches a threshold level (>~10^18 α/g ) wherein radiation damage is so extensive that damage zones become interconnected and He diffusivity increases once again. In order to evaluate these assertions, we conducted a series of step-heating experiments on several pairs of zircon slabs. Individual slabs were crystallographically oriented either orthogonal or parallel to the c-axis and each pair possessed varying degrees of radiation damage. Results from these experiments provide new closure temperature estimates, explain age-eU correlations within a data set, and allow us to construct diffusion models that more accurately describe the t-T history of a given sample.

High-fat enteral nutrition reduces intestinal mucosal barrier damage after peritoneal air exposure.

PubMed

Tan, Shan-Jun; Yu, Chao; Yu, Zhen; Lin, Zhi-Liang; Wu, Guo-Hao; Yu, Wen-Kui; Li, Jie-Shou; Li, Ning

2016-05-01

Peritoneal air exposure is needed in open abdominal surgery, but long-time exposure could induce intestinal mucosal barrier dysfunction followed by many postoperative complications. High-fat enteral nutrition can ameliorate intestinal injury and improve intestinal function in many gastrointestinal diseases. In the present study, we investigated the effect of high-fat enteral nutrition on intestinal mucosal barrier after peritoneal air exposure and the underlying mechanism. Male adult rats were administrated saline, low-fat or high-fat enteral nutrition via gavage before and after peritoneal air exposure for 3 h. Rats undergoing anesthesia without laparotomy received saline as control. Twenty four hours after surgery, samples were collected to assess intestinal mucosal barrier changes in serum D-lactate levels, intestinal permeability, intestinal tight junction protein ZO-1 and occludin levels, and intestinal histopathology. The levels of malondialdehyde and the activity of superoxide dismutase in the ileum tissue were also measured to assess the status of intestinal oxidative stress. High-fat enteral nutrition significantly decreased the serum D-lactate level and increased the intestinal tight junction protein ZO-1 level when compared to the group treated with low-fat enteral nutrition (P < 0.05). Meanwhile, histopathologic findings showed that the intestinal mucosal injury assessed by the Chiu's score and the intestinal epithelial tight junction were also improved much more in the high-fat enteral nutrition-treated group (P < 0.05). In addition, the intestinal malondialdehyde level was lower, and the intestinal superoxide dismutase activity was higher in the high-fat enteral nutrition-treated group than that in the low-fat enteral nutrition-treated group (P < 0.05). These results suggest that high-fat enteral nutrition could reduce intestinal mucosal barrier damage after peritoneal air exposure, and the underlying mechanism may be associated with its antioxidative action. Perioperative administration of high-fat enteral nutrition may be a promising intervention to preserve intestinal mucosal barrier function in open abdominal surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of the systemic antiinflammatory effects of levosimendan in an experimental blunt thoracic trauma model.

PubMed

Ateş, Gökay; Yaman, Ferda; Bakar, Bülent; Kısa, Üçler; Atasoy, Pınar; Büyükkoçak, Ünase

2017-09-01

Blunt thoracic injury often leads to pulmonary contusion and the development of acute respiratory distress syndrome, which carries a high risk of morbidity and mortality, originating from the local and systemic inflammatory states. This study aimed to investigate the local and systemic antiinflammatory effects of levosimendan in rat models of blunt chest trauma. A total of 32 Wistar albino rats were randomly assigned to one of the following four groups: control, sham, low-dose levosimendan (LDL) (5 µg/kg loading dose for 10 min and 0.05 µg/kg/min intravenous infusion), and high-dose levosimendan (HDL) (10 µg/kg loading dose for 10 min and 0.1 µg/kg/min intravenous infusion). Blunt chest trauma was induced, and after 6 h, the contused pulmonary tissues were histopathologically and immunohistopathologically evaluated, serum TNF-α, IL-1ß, IL-6, and NO levels were biochemically evaluated. The mean arterial pressure was low throughout the experiment in the LDL and HDL groups, with no statistically difference between the groups. Levosimendan reduced the alveolar congestion and hemorrhage, which developed after inducing trauma. Neutrophil infiltration to the damaged pulmonary tissue was also reduced in both the LDL and HDL groups. In rats in which pulmonary contusion (PC) was observed, increased activation of nuclear factor kappa B was observed in the pulmonary tissue, and levosimendan did not reduce this activation. Both high and low doses of levosimendan reduced serum IL-1ß levels, and high doses of levosimendan reduced IL-6 and NO levels. TNF-α levels were not reduced. In conclusion, the results showed that in a rat model of PC, the experimental agent levosimendan could reduce neutrophil cell infiltration to damaged pulmonary tissues and the systemic expressions of some cytokines (IL-1ß, IL-6, and NO), thereby partially reducing and/or correcting pulmonary damage. Systemic inflammatory response that occurs after trauma could also be reduced.

The systemic iron-regulatory proteins hepcidin and ferroportin are reduced in the brain in Alzheimer’s disease

PubMed Central

2013-01-01

Background The pathological features of the common neurodegenerative conditions, Alzheimer’s disease (AD), Parkinson’s disease and multiple sclerosis are all known to be associated with iron dysregulation in regions of the brain where the specific pathology is most highly expressed. Iron accumulates in cortical plaques and neurofibrillary tangles in AD where it participates in redox cycling and causes oxidative damage to neurons. To understand these abnormalities in the distribution of iron the expression of proteins that maintain systemic iron balance was investigated in human AD brains and in the APP-transgenic (APP-tg) mouse. Results Protein levels of hepcidin, the iron-homeostatic peptide, and ferroportin, the iron exporter, were significantly reduced in hippocampal lysates from AD brains. By histochemistry, hepcidin and ferroportin were widely distributed in the normal human brain and co-localised in neurons and astrocytes suggesting a role in regulating iron release. In AD brains, hepcidin expression was reduced and restricted to the neuropil, blood vessels and damaged neurons. In the APP-tg mouse immunoreactivity for ferritin light-chain, the iron storage isoform, was initially distributed throughout the brain and as the disease progressed accumulated in the core of amyloid plaques. In human and mouse tissues, extensive AD pathology with amyloid plaques and severe vascular damage with loss of pericytes and endothelial disruption was seen. In AD brains, hepcidin and ferroportin were associated with haem-positive granular deposits in the region of damaged blood vessels. Conclusion Our results suggest that the reduction in ferroportin levels are likely associated with cerebral ischaemia, inflammation, the loss of neurons due to the well-characterised protein misfolding, senile plaque formation and possibly the ageing process itself. The reasons for the reduction in hepcidin levels are less clear but future investigation could examine circulating levels of the peptide in AD and a possible reduction in the passage of hepcidin across damaged vascular endothelium. Imbalance in the levels and distribution of ferritin light-chain further indicate a failure to utilize and release iron by damaged and degenerating neurons. PMID:24252754

Protective effects of various ratios of DHA/EPA supplementation on high-fat diet-induced liver damage in mice.

PubMed

Shang, Tingting; Liu, Liang; Zhou, Jia; Zhang, Mingzhen; Hu, Qinling; Fang, Min; Wu, Yongning; Yao, Ping; Gong, Zhiyong

2017-03-29

A sedentary lifestyle and poor diet are risk factors for the progression of non-alcoholic fatty liver disease. However, the pathogenesis of hepatic lipid accumulation is not completely understood. Therefore, the present study explored the effects of dietary supplementation of various ratios of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on a high-fat diet-induced lipid metabolism disorder and the concurrent liver damage. Using high-fat diet-fed C57BL/6 J mice as the animal model, diets of various ratios of DHA/EPA (2:1, 1:1, and 1:2) with an n-6/n-3 ratio of 4:1 were prepared using fish and algae oils enriched in DHA and/or EPA and sunflower seed oils to a small extent instead of the high-fat diet. Significantly decreased hepatic lipid deposition, body weight, serum lipid profile, inflammatory reactions, lipid peroxidation, and expression of adipogenesis-related proteins and inflammatory factors were observed for mice that were on a diet supplemented with DHA/EPA compared to those in the high-fat control group. The DHA/EPA 1:2 group showed lower serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol levels, lower SREBP-1C, FAS, and ACC-1 relative mRNA expression, and higher Fra1 mRNA expression, with higher relative mRNA expression of enzymes such as AMPK, PPARα, and HSL observed in the DHA/EPA 1:1 group. Lower liver TC and TG levels and higher superoxide dismutase levels were found in the DHA/EPA 2:1 group. Nonetheless, no other notable effects were observed on the biomarkers mentioned above in the groups treated with DHA/EPA compared with the DHA group. The results showed that supplementation with a lower DHA/EPA ratio seems to be more effective at alleviating high-fat diet-induced liver damage in mice, and a DHA/EPA ratio of 1:2 mitigated inflammatory risk factors. These effects of n-3 polyunsaturated fatty acids (PUFA) on lipid metabolism may be linked to the upregulation of Fra1 and attenuated activity of c-Jun and c-Fos, thus ultimately reducing the severity of the lipid metabolism disorder and liver damage to some extent.

Higher dermal exposure of cashiers to BPA and its association with DNA oxidative damage.

PubMed

Lv, Yanshan; Lu, Shaoyou; Dai, Yanyan; Rui, Caiyan; Wang, Yongjun; Zhou, Yuanxiu; Li, Yanru; Pang, Qihua; Fan, Ruifang

2017-01-01

Bisphenol A (BPA) is a widely used chemical in the production of many polycarbonate plastics, epoxy resin linings for food and beverage containers and thermal papers. Oral intakes from the contaminated diets were considered as the predominant source of BPA exposure for humans. However, due to the high levels of BPA on thermal receipts and their wide applications in our daily life, the amount of BPA be transferred to the skin after holding thermal paper should not be underestimated, particularly for cashiers. To investigate the contribution of BPA exposure levels via the dermal contact route and the relationship between BPA exposure level and oxidative DNA damage, six male volunteers were recruited and required to simulate the cashiers' work and handle the thermal receipts during the study period. Triclosan (TCS, an antimicrobial compound used widely in personal health and skin care products) was applied as a reference compound. Their urinary BPA, TCS and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations were determined by high performance liquid chromatography/ tandem spectrometer (LC/MS/MS). The results showed that after handling the thermal receipts, the urinary BPA concentrations of volunteers increased 3 times of those before the experimental period. But TCS levels in urine kept stable. There existed a correlation between BPA exposure and 8-OHdG (R 2 =0.237, p<0.001), but not between TCS and 8-OHdG concentrations (R 2 =0.026, p<0.777), indicating that more BPA exposure could lead to higher oxidative DNA damage. That the increases in 8-OHdG levels in urine being almost consistent with those of BPA suggested that handling thermal receipts resulted in the increasing BPA intakes and BPA exposure was correlated with DNA oxidative damage. After 48h of the end of handling thermal receipts, the urinary BPA levels did not descend to the levels before experiment, suggesting that the excretion of BPA via dermal contact was over 48h. BPA exposure through dermal contact route contributed 51.9% to 84% to urinary BPA levels with the GM ratio of 70.9% for cashiers, indicating that it might be seriously underestimated for cashiers according to the previous studies. More attentions should be paid on the exposure of BPA via dermal penetration for cashiers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multi Resolution In-Situ Testing and Multiscale Simulation for Creep Fatigue Damage Analysis of Alloy 617

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

Liu, Yongming; Oskay, Caglar

This report outlines the research activities that were carried out for the integrated experimental and simulation investigation of creep-fatigue damage mechanism and life prediction of Nickel-based alloy, Inconel 617 at high temperatures (950° and 850°). First, a novel experimental design using a hybrid control technique is proposed. The newly developed experimental technique can generate different combinations of creep and fatigue damage by changing the experimental design parameters. Next, detailed imaging analysis and statistical data analysis are performed to quantify the failure mechanisms of the creep fatigue of alloy 617 at high temperatures. It is observed that the creep damage ismore » directly associated with the internal voids at the grain boundaries and the fatigue damage is directly related to the surface cracking. It is also observed that the classical time fraction approach does not has a good correlation with the experimental observed damage features. An effective time fraction parameter is seen to have an excellent correlation with the material microstructural damage. Thus, a new empirical damage interaction diagram is proposed based on the experimental observations. Following this, a macro level viscoplastic model coupled with damage is developed to simulate the stress/strain response under creep fatigue loadings. A damage rate function based on the hysteresis energy and creep energy is proposed to capture the softening behavior of the material and a good correlation with life prediction and material hysteresis behavior is observed. The simulation work is extended to include the microstructural heterogeneity. A crystal plasticity finite element model considering isothermal and large deformation conditions at the microstructural scale has been developed for fatigue, creep-fatigue as well as creep deformation and rupture at high temperature. The model considers collective dislocation glide and climb of the grains and progressive damage accumulation of the grain boundaries. The glide model incorporates a slip resistance evolution model that characterizes the solute-drag creep effects and can capture well the stress-strain and stress time response of fatigue and creep-fatigue tests at various strain ranges and hold times. In order to accurately capture the creep strains that accumulate particularly at relatively low stress levels, a dislocation climb model has been incorporated into the crystal plasticity modeling framework. The dislocation climb model parameters are calibrated and verified through experimental creep tests performed at 950°. In addition, a cohesive zone model has been fully implemented in the context of the crystal plasticity finite element model to capture the intergranular creep damage. The parameters of the cohesive zone model have been calibrated using available experimental data. The numerical simulations illustrate the capability of the proposed model in capturing damage initiation and growth under creep loads as compared to the experimental observations. The microscale analysis sheds light on the crack initiation sites and propagation patterns within the microstructure. The model is also utilized to investigate the hybrid-controlled creep-fatigue tests and has been found to capture reasonably well the stress-strain response with different hold times and hold stress magnitudes.« less

Preclinical manifestations of organ damage associated with the metabolic syndrome and its factors in outpatient children.

PubMed

Di Bonito, Procolo; Moio, Nicola; Scilla, Carolina; Cavuto, Luigi; Sibilio, Girolamo; Forziato, Claudia; Sanguigno, Eduardo; Saitta, Francesco; Iardino, Maria Rosaria; Capaldo, Brunella

2010-12-01

To evaluate whether the pediatric metabolic syndrome (MetS) or its factors are useful to detect subclinical abnormalities of cardiac, liver, and glomerular damage in an outpatient population. The population study included 799 children (age 10 ± 3 years, mean ± SD), 24% of whom were normalweight, 25% overweight, and 51% obese. Alanine-aminotransferase (ALT) levels, estimated glomerular filtration rate (eGFR) and HOMA-IR were analyzed in all children. Microalbuminuria (MA) and left ventricular (LV) geometry and function were evaluated in 501 and 247 children, respectively. MetS was defined using Cook's criteria. MetS was diagnosed in 131 children (16%). Children with MetS+ and MetS- were similar for age, gender and Tanner stage distribution. Children with MetS+ showed higher ALT levels (31 ± 19 vs 21 ± 11 IU/L, p<0.0001), LV mass (39 ± 10 vs 34 ± 10 g/h(2.7), p<0.001) and relative wall thickness (0.37 ± 0.06 vs 0.35 ± 0.05, p<0.01) than MetS-. The two groups were similar for MA and eGFR. At multiple logistic regression analysis, children MetS+ showed a higher risk (OR, 95% Cl) adjusted for confounding factors, of high ALT levels (1.71, 1.12-2.59, p=0.012) and concentric LV hypertrophy (2.17, 1.01-4.66, p=0.047) than children MetS-. The risk of preclinical liver and cardiac damage associated with the MetS phenotype was not higher than predicted by its single components. Children with MetS show a 2-fold greater risk of having high ALT levels and concentric LV hypertrophy. However, the risk of subclinical manifestations of liver and cardiac damage can be predicted equally well by the single components of the syndrome. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Tubular overexpression of Gremlin in transgenic mice aggravates renal damage in diabetic nephropathy.

PubMed

Marchant, Vanessa; Droguett, Alejandra; Valderrama, Graciela; Burgos, M Eugenia; Carpio, Daniel; Kerr, Bredford; Ruiz-Ortega, Marta; Egido, Jesús; Mezzano, Sergio

2015-09-15

Diabetic nephropathy (DN) is currently a leading cause of end-stage renal failure worldwide. Gremlin was identified as a gene differentially expressed in mesangial cells exposed to high glucose and in experimental diabetic kidneys. We have described that Gremlin is highly expressed in biopsies from patients with diabetic nephropathy, predominantly in areas of tubulointerstitial fibrosis. In streptozotocin (STZ)-induced experimental diabetes, Gremlin deletion using Grem1 heterozygous knockout mice or by gene silencing, ameliorates renal damage. To study the in vivo role of Gremlin in renal damage, we developed a diabetic model induced by STZ in transgenic (TG) mice expressing human Gremlin in proximal tubular epithelial cells. The albuminuria/creatinuria ratio, determined at week 20 after treatment, was significantly increased in diabetic mice but with no significant differences between transgenic (TG/STZ) and wild-type mice (WT/STZ). To assess the level of renal damage, kidney tissue was analyzed by light microscopy (periodic acid-Schiff and Masson staining), electron microscopy, and quantitative PCR. TG/STZ mice had significantly greater thickening of the glomerular basement membrane, increased mesangial matrix, and podocytopenia vs. WT/STZ. At the tubulointerstitial level, TG/STZ showed increased cell infiltration and mild interstitial fibrosis. In addition, we observed a decreased expression of podocin and overexpression of monocyte chemoattractant protein-1 and fibrotic-related markers, including transforming growth factor-β1, Col1a1, and α-smooth muscle actin. Together, these results show that TG mice overexpressing Gremlin in renal tubules develop greater glomerular and tubulointerstitial injury in response to diabetic-mediated damage and support the involvement of Gremlin in diabetic nephropathy. Copyright © 2015 the American Physiological Society.

Probabilistic estimation of numbers and costs of future landslides in the San Francisco Bay region

USGS Publications Warehouse

Crovelli, R.A.; Coe, J.A.

2009-01-01

We used historical records of damaging landslides triggered by rainstorms and a newly developed Probabilistic Landslide Assessment Cost Estimation System (PLACES) to estimate the numbers and direct costs of future landslides in the 10-county San Francisco Bay region. Historical records of damaging landslides in the region are incomplete. Therefore, our estimates of numbers and costs of future landslides are minimal estimates. The estimated mean annual number of future damaging landslides for the entire 10-county region is about 65. Santa Cruz County has the highest estimated mean annual number of damaging future landslides (about 18), whereas Napa, San Francisco, and Solano Counties have the lowest estimated mean numbers of damaging landslides (about 1 each). The estimated mean annual cost of future landslides in the entire region is about US $14.80 million (year 2000 $). The estimated mean annual cost is highest for San Mateo County ($3.24 million) and lowest for Solano County ($0.18 million). The annual per capita cost for the entire region will be about $2.10. Santa Cruz County will have the highest annual per capita cost at $8.45, whereas San Francisco County will have the lowest per capita cost at $0.31. Normalising costs by dividing by the percentage of land area with slopes equal to or greater than 17% indicates that San Francisco County will have the highest cost per square km ($7,101), whereas Santa Clara County will have the lowest cost per square km ($229). These results indicate that the San Francisco Bay region has one of the highest levels of landslide risk in the United States. Compared with landslide cost estimates from the rest of the world, the risk level in the Bay region seems high, but not exceptionally high.

Modulation of DNA repair capacity and mRNA expression levels of XRCC1, hOGG1 and XPC genes in styrene-exposed workers.

PubMed

Hanova, Monika; Stetina, Rudolf; Vodickova, Ludmila; Vaclavikova, Radka; Hlavac, Pavel; Smerhovsky, Zdenek; Naccarati, Alessio; Polakova, Veronika; Soucek, Pavel; Kuricova, Miroslava; Manini, Paola; Kumar, Rajiv; Hemminki, Kari; Vodicka, Pavel

2010-11-01

Decreased levels of single-strand breaks in DNA (SSBs), reflecting DNA damage, have previously been observed with increased styrene exposure in contrast to a dose-dependent increase in the base-excision repair capacity. To clarify further the above aspects, we have investigated the associations between SSBs, micronuclei, DNA repair capacity and mRNA expression in XRCC1, hOGG1 and XPC genes on 71 styrene-exposed and 51 control individuals. Styrene concentrations at workplace and in blood characterized occupational exposure. The workers were divided into low (below 50 mg/m³) and high (above 50 mg/m³)) styrene exposure groups. DNA damage and DNA repair capacity were analyzed in peripheral blood lymphocytes by Comet assay. The mRNA expression levels were determined by qPCR. A significant negative correlation was observed between SSBs and styrene concentration at workplace (R=-0.38, p=0.001); SSBs were also significantly higher in men (p=0.001). The capacity to repair irradiation-induced DNA damage was the highest in the low exposure group (1.34±1.00 SSB/10⁹ Da), followed by high exposure group (0.72±0.81 SSB/10⁹ Da) and controls (0.65±0.82 SSB/10⁹ Da). The mRNA expression levels of XRCC1, hOGG1 and XPC negatively correlated with styrene concentrations in blood and at workplace (p<0.001) and positively with SSBs (p<0.001). Micronuclei were not affected by styrene exposure, but were higher in older persons and in women (p<0.001). In this study, we did not confirm previous findings on an increased DNA repair response to styrene-induced genotoxicity. However, negative correlations of SSBs and mRNA expression levels of XRCC1, hOGG1 and XPC with styrene exposure warrant further highly-targeted study. Copyright © 2010 Elsevier Inc. All rights reserved.

Tornado Damage Assessment: Reconstructing the Wind Through Debris Tracking and Treefall Pattern Analysis

NASA Astrophysics Data System (ADS)

Godfrey, C. M.; Peterson, C. J.; Lombardo, F.

2017-12-01

Efforts to enhance the resilience of communities to tornadoes requires an understanding of the interconnected nature of debris and damage propagation in both the built and natural environment. A first step toward characterizing the interconnectedness of these elements within a given community involves detailed post-event surveys of tornado damage. Such damage surveys immediately followed the 22 January 2017 EF3 tornadoes in the southern Georgia towns of Nashville and Albany. After assigning EF-scale ratings to impacted structures, the authors geotagged hundreds of pieces of debris scattered around selected residential structures and outbuildings in each neighborhood and paired each piece of debris with its source structure. Detailed information on trees in the vicinity of the structures supplements the debris data, including the species, dimensions, location, fall direction, and level of damage. High-resolution satellite imagery helps to identify the location and fall direction of hundreds of additional forest trees. These debris and treefall patterns allow an estimation of the near-surface wind field using a Rankine vortex model coupled with both a tree stability model and an infrastructure fragility model that simulates debris flight. Comparisons between the modeled damage and the actual treefall and debris field show remarkable similarities for a selected set of vortex parameters, indicating the viability of this approach for estimating enhanced Fujita scale levels, determining the near-surface wind field of a tornado during its passage through a neighborhood, and identifying how debris may contribute to the overall risk from tornadoes.

Roles of PCNA ubiquitination and TLS polymerases κ and η in the bypass of methyl methanesulfonate-induced DNA damage.

PubMed

Wit, Niek; Buoninfante, Olimpia Alessandra; van den Berk, Paul C M; Jansen, Jacob G; Hogenbirk, Marc A; de Wind, Niels; Jacobs, Heinz

2015-01-01

Translesion synthesis (TLS) provides a highly conserved mechanism that enables DNA synthesis on a damaged template. TLS is performed by specialized DNA polymerases of which polymerase (Pol) κ is important for the cellular response to DNA damage induced by benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), ultraviolet (UV) light and the alkylating agent methyl methanesulfonate (MMS). As TLS polymerases are intrinsically error-prone, tight regulation of their activity is required. One level of control is provided by ubiquitination of the homotrimeric DNA clamp PCNA at lysine residue 164 (PCNA-Ub). We here show that Polκ can function independently of PCNA modification and that Polη can function as a backup during TLS of MMS-induced lesions. Compared to cell lines deficient for PCNA modification (Pcna(K164R)) or Polκ, double mutant cell lines display hypersensitivity to MMS but not to BPDE or UV-C. Double mutant cells also displayed delayed post-replicative TLS, accumulate higher levels of replication stress and delayed S-phase progression. Furthermore, we show that Polη and Polκ are redundant in the DNA damage bypass of MMS-induced DNA damage. Taken together, we provide evidence for PCNA-Ub-independent activation of Polκ and establish Polη as an important backup polymerase in the absence of Polκ in response to MMS-induced DNA damage. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via mitochondrial ROS production.

PubMed

El-Amine, Rawan; Germini, Diego; Zakharova, Vlada V; Tsfasman, Tatyana; Sheval, Eugene V; Louzada, Ruy A N; Dupuy, Corinne; Bilhou-Nabera, Chrystèle; Hamade, Aline; Najjar, Fadia; Oksenhendler, Eric; Lipinski, Marс; Chernyak, Boris V; Vassetzky, Yegor S

2018-05-01

Human immunodeficiency virus (HIV) infection is associated with B-cell malignancies in patients though HIV-1 is not able to infect B-cells. The rate of B-cell lymphomas in HIV-infected individuals remains high even under the combined antiretroviral therapy (cART) that reconstitutes the immune function. Thus, the contribution of HIV-1 to B-cell oncogenesis remains enigmatic. HIV-1 induces oxidative stress and DNA damage in infected cells via multiple mechanisms, including viral Tat protein. We have detected elevated levels of reactive oxygen species (ROS) and DNA damage in B-cells of HIV-infected individuals. As Tat is present in blood of infected individuals and is able to transduce cells, we hypothesized that it could induce oxidative DNA damage in B-cells promoting genetic instability and malignant transformation. Indeed, incubation of B-cells isolated from healthy donors with purified Tat protein led to oxidative stress, a decrease in the glutathione (GSH) levels, DNA damage and appearance of chromosomal aberrations. The effects of Tat relied on its transcriptional activity and were mediated by NF-κB activation. Tat stimulated oxidative stress in B-cells mostly via mitochondrial ROS production which depended on the reverse electron flow in Complex I of respiratory chain. We propose that Tat-induced oxidative stress, DNA damage and chromosomal aberrations are novel oncogenic factors favoring B-cell lymphomas in HIV-1 infected individuals. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

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.

Biomarkers of oxidative stress and inflammation after wood smoke exposure in a reconstructed Viking Age house.

PubMed

Jensen, Annie; Karottki, Dorina Gabriela; Christensen, Jannie Marie; Bønløkke, Jakob Hjort; Sigsgaard, Torben; Glasius, Marianne; Loft, Steffen; Møller, Peter

2014-10-01

Exposure to particles from combustion of wood is associated with respiratory symptoms, whereas there is limited knowledge about systemic effects. We investigated effects on systemic inflammation, oxidative stress and DNA damage in humans who lived in a reconstructed Viking Age house, with indoor combustion of wood for heating and cooking. The subjects were exposed to high indoor concentrations of PM2.5 (700-3,600 µg/m(3)), CO (10.7-15.3 ppm) and NO2 (140-154 µg/m(3)) during a 1-week stay. Nevertheless, there were unaltered levels of genotoxicity, determined as DNA strand breaks and formamidopyrimidine DNA glycosylase and oxoguanine DNA glycosylase 1 sensitive sites in peripheral blood mononuclear cells. There were also unaltered expression levels of OGG1, HMOX1, CCL2, IL8, and TNF levels in leukocytes. In serum, there were unaltered levels of C-reactive protein, IL6, IL8, TNF, lactate dehydrogenase, cholesterol, triglycerides, and high-density lipoproteins. The wood smoke exposure was associated with decreased serum levels of sICAM-1, and a tendency to decreased sVCAM-1 levels. There was a minor increase in the levels of circulating monocytes expressing CD31, whereas there were unaltered expression levels of CD11b, CD49d, and CD62L on monocytes after the stay in the house. In conclusion, even a high inhalation exposure to wood smoke was associated with limited systemic effects on markers of oxidative stress, DNA damage, inflammation, and monocyte activation. © 2014 Wiley Periodicals, Inc.

Prevention of renal damage caused by Shiga toxin type 2: Action of Miglustat on human endothelial and epithelial cells.

PubMed

Girard, Magalí C; Sacerdoti, Flavia; Rivera, Fulton P; Repetto, Horacio A; Ibarra, Cristina; Amaral, María M

2015-10-01

Typical hemolytic uremic syndrome (HUS) is responsible for acute and chronic renal failure in children younger than 5 years old in Argentina. Renal damages have been associated with Shiga toxin type 1 and/or 2 (Stx1, Stx2) produced by Escherichia coli O157:H7, although strains expressing Stx2 are highly prevalent in Argentina. Human glomerular endothelial cells (HGEC) and proximal tubule epithelial cells are very Stx-sensitive since they express high levels of Stx receptor (Gb3). Nowadays, there is no available therapy to protect patients from acute toxin-mediated cellular injury. New strategies have been developed based on the Gb3 biosynthesis inhibition through blocking the enzyme glucosylceramide (GL1) synthase. We assayed the action of a GL1 inhibitor (Miglustat: MG), on the prevention of the renal damage induced by Stx2. HGEC primary cultures and HK-2 cell line were pre-treated with MG and then incubated with Stx2. HK- 2 and HGEC express Gb3 and MG was able to decrease the levels of this receptor. As a consequence, both types of cells were protected from Stx2 cytotoxicity and morphology damage. MG was able to avoid Stx2 effects in human renal cells and could be a feasible strategy to protect kidney tissues from the cytotoxic effects of Stx2 in vivo. Copyright © 2015 Elsevier Ltd. All rights reserved.

Porcine skin damage thresholds for pulsed nanosecond-scale laser exposure at 1064-nm

NASA Astrophysics Data System (ADS)

DeLisi, Michael P.; Peterson, Amanda M.; Noojin, Gary D.; Shingledecker, Aurora D.; Tijerina, Amanda J.; Boretsky, Adam R.; Schmidt, Morgan S.; Kumru, Semih S.; Thomas, Robert J.

2018-02-01

Pulsed high-energy lasers operating in the near-infrared (NIR) band are increasingly being used in medical, industrial, and military applications, but there are little available experimental data to characterize their hazardous effects on skin tissue. The current American National Standard for the Safe Use of Lasers (ANSI Z136.1-2014) defines the maximum permissible exposure (MPE) on the skin as either a single-pulse or total exposure time limit. This study determined the minimum visible lesion (MVL) damage thresholds in Yucatan miniature pig skin for the single-pulse case and several multiple-pulse cases over a wide range of pulse repetition frequencies (PRFs) (10, 125, 2,000, and 10,000 Hz) utilizing nanosecond-scale pulses (10 or 60 ns). The thresholds are expressed in terms of the median effective dose (ED50) based on varying individual pulse energy with other laser parameters held constant. The results confirm a decrease in MVL threshold as PRF increases for exposures with a constant number of pulses, while also noting a PRF-dependent change in the threshold as a function of the number of pulses. Furthermore, this study highlights a change in damage mechanism to the skin from melanin-mediated photomechanical events at high irradiance levels and few numbers of pulses to bulk tissue photothermal additivity at lower irradiance levels and greater numbers of pulses. The observed trends exceeded the existing exposure limits by an average factor of 9.1 in the photothermally-damaged cases and 3.6 in the photomechanicallydamaged cases.

Season and light affect constitutive defenses of understory shrub species against folivorous insects

NASA Astrophysics Data System (ADS)

Karolewski, Piotr; Giertych, Marian J.; Żmuda, Michał; Jagodziński, Andrzej M.; Oleksyn, Jacek

2013-11-01

Understory shrubs contribute to overall species diversity, providing habitat and forage for animals, influence soil chemistry and forest microclimate. However, very little is known about the chemical defense of various shrub species against folivorous insects. Using six shrub species, we tested how seasonal changes and light conditions affect their constitutive defense to insect damage. We monitored leaf perforation, concentrations of total phenols, condensed tannins, nitrogen (N), and total nonstructural carbohydrates (TNC). Leaf damage caused by insects was low in Sambucus nigra, Cornus sanguinea, and Frangula alnus, intermediate in Corylus avellana and Prunus serotina, and high in Prunus padus. Leaves of all the species, when growing in high light conditions, had high concentrations of defense metabolites. Except for C. avellana, leaves of the other shrub species growing in full sun were less injured than those in shade. This may be due to higher concentrations of defense metabolites and lower concentrations of nitrogen. Similar patterns of the effects of light on metabolites studied and N were observed for leaves with varying location within the crown of individual shrubs (from the top of the south direction to the bottom of the north), as for leaves from shrubs growing in full sun and shrubs in the shade of canopy trees. A probable cause of the greater damage of more sunlit leaves of C. avellana was the fact that they were herbivorized mostly by Altica brevicollis, a specialist insect that prefers plant tissues with a high TNC level and is not very sensitive to a high level of phenolic compounds.

Metabolic muscle damage and oxidative stress markers in an America's Cup yachting crew.

PubMed

Barrios, Carlos; Hadala, Michal; Almansa, Inmaculada; Bosch-Morell, Francisco; Palanca, José M; Romero, Francisco J

2011-07-01

Activities of enzymes involved in muscle damage [creatine kinase (CK) and aspartate aminotransferase (AST)] and levels of malondialdehyde (MDA) as a marker of oxidative stress were monitored in the plasma of 27 members of an America's Cup yachting crew. The preventive benefits of allopurinol on muscle damage were also tested. In racing period A, the crew was divided into two groups according to their tasks on board. Blood samples from all 27 sailors were obtained before the start of a 5-day fleet race, after the last race, and after the ten match races. In period B, crew members were divided at random into two groups. One group (13 participants) received 300 mg/day of allopurinol 3 h before racing. The other ten members received placebo. Blood samples were collected just before and after the second round of the Louis Vuitton Cup. All participants showed increased CK and AST activities after the racing period A. The increase in CK activity was highest in sailors involved in strenuous physical work. At the end of period A, plasma MDA levels were higher in all participants as compared with non-participant athletes. In period B, a significant decrease in CK activity, but not in AST, appeared among participants receiving allopurinol. Plasma MDA decreased in sailors treated with allopurinol, but this reduction did not reach statistical significance. America's Cup is a sailing sport with high physical demands, as shown by the increase in muscle-damage markers. Treatment with allopurinol appeared to decrease the levels of muscle damage markers.

Damage-Tolerance Characteristics of Composite Fuselage Sandwich Structures with Thick Facesheets

NASA Technical Reports Server (NTRS)

McGowan, David M.; Ambur, Damodar R.

1997-01-01

Damage tolerance characteristics and results from experimental and analytical studies of a composite fuselage keel sandwich structure subjected to low-speed impact damage and discrete-source damage are presented. The test specimens are constructed from graphite-epoxy skins borided to a honeycomb core, and they are representative of a highly loaded fuselage keel structure. Results of compression-after-impact (CAI) and notch-length sensitivity studies of 5-in.-wide by 10-in.long specimens are presented. A correlation between low-speed-impact dent depth, the associated damage area, and residual strength for different impact-energy levels is described; and a comparison of the strength for undamaged and damaged specimens with different notch-length-to-specimen-width ratios is presented. Surface strains in the facesheets of the undamaged specimens as well as surface strains that illustrate the load redistribution around the notch sites in the notched specimens are presented and compared with results from finite element analyses. Reductions in strength of as much as 53.1 percent for the impacted specimens and 64.7 percent for the notched specimens are observed.

Extrafloral nectary phenotypic plasticity is damage- and resource-dependent in Vicia faba

PubMed Central

Mondor, Edward B; Tremblay, Michelle N; Messing, Russell H

2006-01-01

Phenotypic plasticity enables many damaged plants to increase nectar secretion rates from extrafloral nectaries (EFNs), or in the case of broad bean, Vicia faba L., to produce additional EFNs, to attract natural enemies of herbivores. While plants benefit greatly from these defensive mutualisms, the costs of producing EFNs are largely unknown. We hypothesized that if EFN production is costly, then damaged plants with high resource levels would be able to produce more EFNs than plants that are resource-limited. Here, we show that this indirect inducible defence does follow this general pattern. Vicia faba enriched with 6 or 12 g of 14 : 14 : 14 NPK fertilizer increased EFN numbers after leaf damage by 46 and 60%, respectively, compared with nutrient-poor plants. Thus, EFN production is both damage- and resource-dependent. Analogous to direct defences, production of EFNs may limit the overall loss of leaf tissue when risk of herbivory increases. PMID:17148294

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.

The application of compressive sampling in rapid ultrasonic computerized tomography (UCT) technique of steel tube slab (STS)

PubMed Central

Jiang, Baofeng; Jia, Pengjiao; Zhao, Wen; Wang, Wentao

2018-01-01

This paper explores a new method for rapid structural damage inspection of steel tube slab (STS) structures along randomly measured paths based on a combination of compressive sampling (CS) and ultrasonic computerized tomography (UCT). In the measurement stage, using fewer randomly selected paths rather than the whole measurement net is proposed to detect the underlying damage of a concrete-filled steel tube. In the imaging stage, the ℓ1-minimization algorithm is employed to recover the information of the microstructures based on the measurement data related to the internal situation of the STS structure. A numerical concrete tube model, with the various level of damage, was studied to demonstrate the performance of the rapid UCT technique. Real-world concrete-filled steel tubes in the Shenyang Metro stations were detected using the proposed UCT technique in a CS framework. Both the numerical and experimental results show the rapid UCT technique has the capability of damage detection in an STS structure with a high level of accuracy and with fewer required measurements, which is more convenient and efficient than the traditional UCT technique. PMID:29293593

Influence of heavy metal stress on antioxidant status and DNA damage in Urtica dioica.

PubMed

Gjorgieva, Darinka; Kadifkova Panovska, Tatjana; Ruskovska, Tatjana; Bačeva, Katerina; Stafilov, Trajče

2013-01-01

Heavy metals have the potential to interact and induce several stress responses in the plants; thus, effects of heavy metal stress on DNA damages and total antioxidants level in Urtica dioica leaves and stems were investigated. The samples are sampled from areas with different metal exposition. Metal content was analyzed by Inductively Coupled Plasma-Atomic Emission Spectrometer (ICP-AES), for total antioxidants level assessment the Ferric-Reducing Antioxidant Power (FRAP) assay was used, and genomic DNA isolation from frozen plant samples was performed to obtain DNA fingerprints of investigated plant. It was found that heavy metal contents in stems generally changed synchronously with those in leaves of the plant, and extraneous metals led to imbalance of mineral nutrient elements. DNA damages were investigated by Random Amplified Polymorphic DNA (RAPD) technique, and the results demonstrated that the samples exposed to metals yielded a large number of new fragments (total 12) in comparison with the control sample. This study showed that DNA stability is highly affected by metal pollution which was identified by RAPD markers. Results suggested that heavy metal stress influences antioxidant status and also induces DNA damages in U. dioica which may help to understand the mechanisms of metals genotoxicity.

Bimodal regulation of p21waf1 protein as function of DNA damage levels

PubMed Central

Buscemi, G; Ricci, C; Zannini, L; Fontanella, E; Plevani, P; Delia, D

2014-01-01

Human p21Waf1 protein is well known for being transcriptionally induced by p53 and activating the cell cycle checkpoint arrest in response to DNA breaks. Here we report that p21Waf1 protein undergoes a bimodal regulation, being upregulated in response to low doses of DNA damage but rapidly and transiently degraded in response to high doses of DNA lesions. Responsible for this degradation is the checkpoint kinase Chk1, which phosphorylates p21Waf1 on T145 and S146 residues and induces its proteasome-dependent proteolysis. The initial p21Waf1 degradation is then counteracted by the ATM-Chk2 pathway, which promotes the p53-dependent accumulation of p21Waf1 at any dose of damage. We also found that p21Waf1 ablation favors the activation of an apoptotic program to eliminate otherwise irreparable cells. These findings support a model in which in human cells a balance between ATM-Chk2-p53 and the ATR-Chk1 pathways modulates p21Waf1 protein levels in relation to cytostatic and cytotoxic doses of DNA damage. PMID:25486478

DNA damage as a biomarker for assessing the effects of suspended solids on the orange-spotted grouper, Epinephelus coioides.

PubMed

Tse, C Y; Chan, K M; Wong, C K

2010-06-01

In Hong Kong, suspended solids (SS) introduced by dredging and mud disposal activities are a major cause of mass mortality in cage-cultured marine fish. We have used DNA damage in liver cells, as determined by the comet assay, to assess the impact of SS on the orange-spotted grouper Epinephelus coioides. Seabed sediments were collected from a heavily polluted site in Victoria Harbor and two less polluted sites in Port Shelter and Mirs Bay. Sediments from Victoria Harbor contained higher levels of copper (Cu) and polycyclic aromatic hydrocarbons (PAHs) than those from the other sites. In a 10-day experiment, SS from all three sites induced significant increase in comet tail length, but not in percentage (%) tail DNA. In a 20-day experiment, fish exposed to polluted SS from Victoria Harbor exhibited a significant increase in comet tail length after 5 days and % tail DNA after 10 days. After a 10-day recovery period, however, DNA damage was reduced as tail length and % tail DNA returned to control levels. These results suggest that DNA damage measured by the comet assay is a highly sensitive biomarker for assessing the genotoxic effects of SS to marine fish.

Acute oral dose of sodium nitrite induces redox imbalance, DNA damage, metabolic and histological changes in rat intestine.

PubMed

Ansari, Fariheen Aisha; Ali, Shaikh Nisar; Arif, Hussain; Khan, Aijaz Ahmed; Mahmood, Riaz

2017-01-01

Industrialization and unchecked use of nitrate/nitrite salts for various purposes has increased human exposure to high levels of sodium nitrite (NaNO2) which can act as a pro-oxidant and pro-carcinogen. Oral exposure makes the gastrointestinal tract particularly susceptible to nitrite toxicity. In this work, the effect of administration of a single acute oral dose of NaNO2 on rat intestine was studied. Animals were randomly divided into four groups and given single doses of 20, 40, 60 and 75 mg NaNO2/kg body weight. Untreated animals served as the control group. An NaNO2 dose-dependent decline in the activities of brush border membrane enzymes, increase in lipid peroxidation, protein oxidation, hydrogen peroxide levels and decreased thiol content was observed in all treated groups. The activities of various metabolic and antioxidant defense enzymes were also altered. NaNO2 induced a dose-dependent increase in DNA damage and DNA-protein crosslinking. Histopathological studies showed marked morphological damage in intestinal cells. The intestinal damage might be due to nitrite-induced oxidative stress, direct action of nitrite anion or chemical modification by reaction intermediates.

Advanced glycation end-products: modifiable environmental factors profoundly mediate insulin resistance

PubMed Central

Ottum, Mona S.; Mistry, Anahita M.

2015-01-01

Advanced glycation end-products are toxic by-products of metabolism and are also acquired from high-temperature processed foods. They promote oxidative damage to proteins, lipids and nucleotides. Aging and chronic diseases are strongly associated with markers for oxidative stress, especially advanced glycation end-products, and resistance to peripheral insulin-mediated glucose uptake. Modifiable environmental factors including high levels of refined and simple carbohydrate diets, hypercaloric diets and sedentary lifestyles drive endogenous formation of advanced glycation end-products via accumulation of highly reactive glycolysis intermediates and activation of the polyol/aldose reductase pathway producing high intracellular fructose. High advanced glycation end-products overwhelm innate defenses of enzymes and receptor-mediated endocytosis and promote cell damage via the pro-inflammatory and pro-oxidant receptor for advanced glycation end-products. Oxidative stress disturbs cell signal transduction, especially insulin-mediated metabolic responses. Here we review emerging evidence that restriction of dietary advanced glycation end-products significantly reduces total systemic load and insulin resistance in animals and humans in diabetes, polycystic ovary syndrome, healthy populations and dementia. Of clinical importance, this insulin sensitizing effect is independent of physical activity, caloric intake and adiposity level. PMID:26236094

Reproductive Benefit of Oxidative Damage: An Oxidative Stress “Malevolence”?

PubMed Central

Poljsak, B.; Milisav, I.; Lampe, T.; Ostan, I.

2011-01-01

High levels of reactive oxygen species (ROS) compared to antioxidant defenses are considered to play a major role in diverse chronic age-related diseases and aging. Here we present an attempt to synthesize information about proximate oxidative processes in aging (relevant to free radical or oxidative damage hypotheses of aging) with an evolutionary scenario (credited here to Dawkins hypotheses) involving tradeoffs between the costs and benefits of oxidative stress to reproducing organisms. Oxidative stress may be considered a biological imperfection; therefore, the Dawkins' theory of imperfect adaptation of beings to environment was applied to the role of oxidative stress in processes like famine and infectious diseases and their consequences at the molecular level such as mutations and cell signaling. Arguments are presented that oxidative damage is not necessarily an evolutionary mistake but may be beneficial for reproduction; this may prevail over its harmfulness to health and longevity in evolution. Thus, Dawkins' principle of biological “malevolence” may be an additional biological paradigm for explaining the consequences of oxidative stress. PMID:21969876

Effects of zinc and cholesterol/choleate on serum lipoproteins and the liver in rats

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

Cho, C.H.; Chen, S.M.; Ogle, C.W.

1989-01-01

The effects of short-term treatment with orally-administered zinc sulfate and/or a mixture of cholesterol/choleate on serum lipoprotein and hepatic enzyme levels were studied. Administration of graded doses of zinc sulfate for 5 days, dose-dependently increased serum and hepatic zinc levels but depressed the serum high-density lipoprotein-cholesterol (HDL-C) concentration and liver cytochrome P-450 activity. However, it did not affect hepatic concentrations of malondialdehyde and free {beta}-glucuronidase. Cholesterol/choleate treatment for 5 days markedly damaged the liver, as reflected by elevations of hepatic concentrations of malondialdehyde (both in the mitochondrial and microsomal fractions) and of free {beta}-glucuronidase; total cholesterol and low-density lipoprotein-cholesterol inmore » the blood were increased, whereas HDL-C was decreased significantly. Concomitant administration of zinc sulfate with cholesterol/choleate further lowered HDL-C levels, but reversed the high hepatic concentrations of both malondialdehyde and free {beta}-glucuronidase. The present study indicates that both zinc ions and cholesterol can decrease circulatory HDL-C levels and that zinc protects against cholesterol-induced hepatic damage by reducing lysosomal enzyme release and preventing lipid peroxidation in the liver.« less

Force Criterion Prediction of Damage for Carbon/Epoxy Composite Panels Impacted by High Velocity Ice

NASA Astrophysics Data System (ADS)

Rhymer, Jennifer D.

The use of advanced fiber-reinforced polymer matrix composites in load-bearing aircraft structures is increasing, as evident by the various composites-intensive transport aircraft presently under development. A major impact source of concern for these structures is hail ice, which affects design and skin-sizing (skin thickness determination) at various locations of the aircraft. Impacts onto composite structures often cause internal damage that is not visually detectable due to the high strength and resiliency of the composite material (unlike impacts onto metallic structures). This internal damage and its effect on the performance of the structure are of great concern to the aircraft industry. The prediction of damage in composite structures due to SHI impact has been accomplished via experimental work, explicit dynamic nonlinear finite element analysis (FEA) and the definition of design oriented relationships. Experiments established the critical threshold and corresponding analysis provided contact force results not readily measurable in high velocity SHI impact experiments. The design oriented relationships summarize the FEA results and experimental database into contact force estimation curves that can be easily applied for damage prediction. Failure thresholds were established for the experimental conditions (panel thickness ranging from 1.56 to 4.66 mm and ice diameters from 38.1 to 61.0 mm). Additionally, the observations made by high-speed video during the impact event, and ultrasonic C-scan post-impact, showed how the ice failed during impact and the overall shape and location of the panel damage. Through analysis, the critical force, the force level where damage occurs above but not below, of a SHI impact onto the panel was found to be dependent only on the target structure. However, the peak force generated during impact was dependent on both the projectile and target. Design-oriented curves were generated allowing the prediction of the allowable velocity for given SHI diameter impact onto a known panel in order to estimated damage. Finally, a scaling relationship was established to predict the peak force developed onto composite panels impacted by SHI. This is useful in reducing the amount of experimental investigations, or computationally expensive simulation work, that would otherwise need to be performed to obtain these results.

Radiation damage and sensitization effects on thermoluminescence of LiF:Mg,Ti (TLD-700)

NASA Astrophysics Data System (ADS)

Farag, M. A.; Sadek, A. M.; Shousha, Hany. A.; El-Hagg, A. A.; Atta, M. R.; Kitis, G.

2017-09-01

The radiation damage effects and enhancement the thermoluminescence (TL) efficiency of LiF:Mg,Ti (TLD-700)dosimeters via sensitization method were discussed. Attempts to eliminate the effects of damage and sensitization were made using different types of annealing processes. The results showed that after irradiating the dosimeters with dose > 250 Gy of 60Co gamma source, damage effects were observed. The sensitivity of the total area under the curve was decreased by a factor of ∼0.5 after irradiation at a pre-test dose of 2 kGy. However, the effects of radiation damage on each glow-peak are different. The glow-peak 2 was the only peak that was not affected by the high-dose irradiation. It has been shown that the degree of the radiation damage effect is related to the maximum dose-response function, f(D)max of the glow-peak. In general, significant radiation damage effects were observed for the glow-peaks of high f(D)max . Post-irradiation anneal at 280 °C for 30 min causes dramatic effects on the shape of the glow-curve and as well as on the sensitivity of the dosimeters. An increasing by a factor of ∼35 in the sensitivity of the total area under the curve was observed at a pre-test dose of 2 kGy. Improving the sensitivity of peak 7 by a factor of∼22 was the dominant factor in increasing the sensitivity of the dosimeters. On the other hand, an increasing by factors of ∼2.5 and ∼4 was found for peaks 2 and 5 respectively. On the other hand, a decreasing by a factor ∼0.5 was observed for peaks 3 and 4. At pre-test dose levels >250 Gy, a very strange and high intensity tail was observed in the high-temperature region of the glow-curves. The readout anneal was not enough to remove this tail. While, the furnace anneal could eliminate the sensitization effects but not the radiation damage effects on the sensitivity of the dosimeters.

The receptor for advanced glycation end-products (RAGE) is only present in mammals, and belongs to a family of cell adhesion molecules (CAMs).

PubMed

Sessa, Luca; Gatti, Elena; Zeni, Filippo; Antonelli, Antonella; Catucci, Alessandro; Koch, Michael; Pompilio, Giulio; Fritz, Günter; Raucci, Angela; Bianchi, Marco E

2014-01-01

The human receptor for advanced glycation endproducts (RAGE) is a multiligand cell surface protein belonging to the immunoglobulin superfamily, and is involved in inflammatory and immune responses. Most importantly, RAGE is considered a receptor for HMGB1 and several S100 proteins, which are Damage-Associated Molecular Pattern molecules (DAMPs) released during tissue damage. In this study we show that the Ager gene coding for RAGE first appeared in mammals, and is closely related to other genes coding for cell adhesion molecules (CAMs) such as ALCAM, BCAM and MCAM that appeared earlier during metazoan evolution. RAGE is expressed at very low levels in most cells, but when expressed at high levels, it mediates cell adhesion to extracellular matrix components and to other cells through homophilic interactions. Our results suggest that RAGE evolved from a family of CAMs, and might still act as an adhesion molecule, in particular in the lung where it is highly expressed or under pathological conditions characterized by an increase of its protein levels.

Proton irradiation effects on advanced digital and microwave III-V components

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

Hash, G.L.; Schwank, J.R.; Shaneyfelt, M.R.

1994-09-01

A wide range of advanced III-V components suitable for use in high-speed satellite communication systems were evaluated for displacement damage and single-event effects in high-energy, high-fluence proton environments. Transistors and integrated circuits (both digital and MMIC) were irradiated with protons at energies from 41 to 197 MeV and at fluences from 10{sup 10} to 2 {times} 10{sup 14} protons/cm{sup 2}. Large soft-error rates were measured for digital GaAs MESFET (3 {times} 10{sup {minus}5} errors/bit-day) and heterojunction bipolar circuits (10{sup {minus}5} errors/bit-day). No transient signals were detected from MMIC circuits. The largest degradation in transistor response caused by displacement damage wasmore » observed for 1.0-{mu}m depletion- and enhancement-mode MESFET transistors. Shorter gate length MESFET transistors and HEMT transistors exhibited less displacement-induced damage. These results show that memory-intensive GaAs digital circuits may result in significant system degradation due to single-event upset in natural and man-made space environments. However, displacement damage effects should not be a limiting factor for fluence levels up to 10{sup 14} protons/cm{sup 2} [equivalent to total doses in excess of 10 Mrad(GaAs)].« less

Proton irradiation effects on advanced digital and microwave III-V components

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

Hash, G.L.; Schwank, J.R.; Shaneyfelt, M.R.

1994-12-01

A wide range of advanced III-V components suitable for use in high-speed satellite communication systems were evaluated for displacement damage and single-event effects in high-energy, high-fluence proton environments. Transistors and integrated circuits (both digital and MMIC) were irradiated with protons at energies from 41 to 197 MeV and at fluences from 10[sup 10] to 2 [times] 10[sup 14] protons/cm[sup 2]. Large soft-error rates were measured for digital GaAs MESFET (3 [times] 10[sup [minus]5] errors/bit-day) and heterojunction bipolar circuits (10[sup [minus]5] errors/bit-day). No transient signals were detected from MMIC circuits. The largest degradation in transistor response caused by displacement damage wasmore » observed for 1.0-[mu]m depletion- and enhancement-mode MESFET transistors. Shorter gate length MESFET transistors and HEMT transistors exhibited less displacement-induced damage. These results show that memory-intensive GaAs digital circuits may result in significant system degradation due to single-event upset in natural and man-made space environments. However, displacement damage effects should not be a limiting factor for fluence levels up to 10[sup 14] protons/cm[sup 2] [equivalent to total doses in excess of 10 Mrad (GaAs)].« less

Genotoxicity studies of organically grown broccoli (Brassica oleracea var. italica) and its interactions with urethane, methyl methanesulfonate and 4-nitroquinoline-1-oxide genotoxicity in the wing spot test of Drosophila melanogaster.

PubMed

Heres-Pulido, María Eugenia; Dueñas-García, Irma; Castañeda-Partida, Laura; Santos-Cruz, Luis Felipe; Vega-Contreras, Viridiana; Rebollar-Vega, Rosa; Gómez-Luna, Juan Carlos; Durán-Díaz, Angel

2010-01-01

Broccoli (Brassica oleracea var. italica) has been defined as a cancer preventive food. Nevertheless, broccoli contains potentially genotoxic compounds as well. We performed the wing spot test of Drosophila melanogaster in treatments with organically grown broccoli (OGB) and co-treatments with the promutagen urethane (URE), the direct alkylating agent methyl methanesulfonate (MMS) and the carcinogen 4-nitroquinoline-1-oxide (4-NQO) in the standard (ST) and high bioactivation (HB) crosses with inducible and high levels of cytochrome P450s (CYPs), respectively. Larvae of both crosses were chronically fed with OGB or fresh market broccoli (FMB) as a non-organically grown control, added with solvents or mutagens solutions. In both crosses, the OGB added with Tween-ethanol yielded the expected reduction in the genotoxicity spontaneous rate. OGB co-treatments did not affect the URE effect, MMS showed synergy and 4-NQO damage was modulated in both crosses. In contrast, FMB controls produced damage increase; co-treatments modulated URE genotoxicity, diminished MMS damage, and did not change the 4-NQO damage. The high dietary consumption of both types of broccoli and its protective effects in D. melanogaster are discussed. Copyright 2009 Elsevier Ltd. All rights reserved.

Chromosome damage evolution after low and high LET irradiation

NASA Astrophysics Data System (ADS)

Andreev, Sergey; Eidelman, Yuri

Ionizing radiation induces DNA and chromatin lesions which are converted to chromosome lesions detected in the first post-irradiation mitosis by classic cytogenetic techniques as chromosomal aberrations (CAs). These techniques allow to monitor also delayed aberrations observed after many cell generations post-irradiation - the manifestation of chromosomal instability phenotype (CIN). The problem discussed is how to predict time evolution from initial to delayed DNA/chromosome damage. To address this question, in the present work a mechanistic model of CIN is elaborated which integrates pathways of (*) DNA damage induction and its conversion to chromosome lesions (aberrations), (**) lesion transmission and generation through cell cycles. Delayed aberrations in subsequent cycles are formed in the model owing to two pathways, DNA damage generation de novo as well as CA transmission from previous cycles. DNA damage generation rate is assumed to consist of bystander and non-bystander components. Bystander signals impact all cells roughly equally, whereas non-bystander DSB generation rate differs for the descendants of unirradiated and irradiated cells. Monte Carlo simulation of processes underlying CIN allows to predict the time evolution of initial radiation-induced damage - kinetics curve for delayed unstable aberrations (dicentrics) together with dose response and RBE as a function of time after high vs low LET irradiation. The experimental data for radiation-induced CIN in TK6 lymphoblastoid cells and human lymphocytes irradiated with low (gamma) and high (Fe, C) LET radiation are analyzed on the basis of the proposed model. One of the conclusions is that without bystander signaling, just taking into account the initial DNA damage and non-bystander DSB generation, it is impossible to describe the available experimental data for high-LET-induced CIN. The exact contribution of bystander effects for high vs low LET remains unknown, but the relative contribution may be assessed at large times after initial acute irradiation. RBE for delayed aberrations depends on LET, time and cell line, which probably reflects a genetic background for bystander component. The proposed modeling approach creates a basis for integration of complex network of bystander/inflammatory signaling in systems-level platform for quantification of radiation induced CIN.

Empirical Models for Quantification of Machining Damage in Composite Materials

NASA Astrophysics Data System (ADS)

Machado, Carla Maria Moreira

The tremendous growth which occurs at a global level of demand and use of composite materials brings with the need to develop new manufacturing tools and methodologies. One of the major uses of such materials, in particular plastics reinforced with carbon fibres, is their application in structural components for the aircraft industry with low weight and high stiffness. These components are produced in near-final form but the so-called secondary processes such as machining are often unavoidable. In this type of industry, drilling is the most frequent operation due to the need to obtain holes for riveting and fastening bolt assembly of structures. However, the problems arising from drilling, particularly the damage caused during the operation, may lead to rejection of components because it is an origin of lack of resistance. The delamination is the most important damage, as it causes a decrease of the mechanical properties of the components of an assembly and, irrefutably, a reduction of its reliability in use. It can also raise problems with regard to the tolerances of the assemblies. Moreover, the high speed machining is increasingly recognized to be a manufacturing technology that promotes productivity by reducing production times. However, the investigation whose focus is in high speed drilling is quite limited, and few studies on this subject have been found in the literature review. Thus, this thesis aims to investigate the effects of process variables in high speed drilling on the damage produced. The empirical models that relate the delamination damage, the thrust force and the torque with the process parameters were established using Response Surface Methodology. The process parameters considered as input factors were the spindle speed, the feed per tooth, the tool diameter and the workpiece thickness. A new method for fixing the workpiece was developed and tested. The results proved to be very promising since in the same cutting conditions and with this new methodology, it was observed a significant reduction of the delamination damage. Finally, it has been found that is possible to use high speed drilling, using conventional twist drills, to produce holes with good quality, minimizing the damage.

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

Chronic Oxidative Damage together with Genome Repair Deficiency in the Neurons is a Double Whammy for Neurodegeneration: Is Damage Response Signaling a Potential Therapeutic Target?

PubMed Central

Wang, Haibo; Dharmalingam, Prakash; Vasquez, Velmarini; Mitra, Joy; Boldogh, Istvan; Rao, K. S.; Kent, Thomas A.; Mitra, Sankar; Hegde, Muralidhar L.

2016-01-01

A foremost challenge for the neurons, which are among the most oxygenated cells, is the genome damage caused by chronic exposure to endogenous reactive oxygen species (ROS), formed as cellular respiratory byproducts. Strong metabolic activity associated with high transcriptional levels in these long lived post-mitotic cells render them vulnerable to oxidative genome damage, including DNA strand breaks and mutagenic base lesions. There is growing evidence for the accumulation of unrepaired DNA lesions in the central nervous system (CNS) during accelerated ageing and progressive neurodegeneration. Several germ line mutations in DNA repair or DNA damage response (DDR) signaling genes are uniquely manifested in the phenotype of neuronal dysfunction and are etiologically linked to many neurodegenerative disorders. Studies in our lab and elsewhere revealed that pro-oxidant metals, ROS and misfolded amyloidogenic proteins not only contribute to genome damage in CNS, but also impede their repair/DDR signaling leading to persistent damage accumulation, a common feature in sporadic neurodegeneration. Here, we have reviewed recent advances in our understanding of the etiological implications of DNA damage vs. repair imbalance, abnormal DDR signaling in triggering neurodegeneration and potential of DDR as a target for the amelioration of neurodegenerative diseases. PMID:27663141

Enhancing the efficacy of AREDS antioxidants in light-induced retinal degeneration

PubMed Central

Wong, Paul; Markey, M.; Rapp, C. M.; Darrow, R. M.; Ziesel, A.

2017-01-01

Purpose Light-induced photoreceptor cell degeneration and disease progression in age-related macular degeneration (AMD) involve oxidative stress and visual cell loss, which can be prevented, or slowed, by antioxidants. Our goal was to test the protective efficacy of a traditional Age-related Eye Disease Study antioxidant formulation (AREDS) and AREDS combined with non-traditional antioxidants in a preclinical animal model of photooxidative retinal damage. Methods Male Sprague-Dawley rats were reared in a low-intensity (20 lux) or high-intensity (200 lux) cyclic light environment for 6 weeks. Some animals received a daily dietary supplement consisting of a small cracker infused with an AREDS antioxidant mineral mixture, AREDS antioxidants minus zinc, or zinc oxide alone. Other rats received AREDS combined with a detergent extract of the common herb rosemary, AREDS plus carnosic acid, zinc oxide plus rosemary, or rosemary alone. Antioxidant efficacy was determined by measuring retinal DNA levels 2 weeks after 6 h of intense exposure to white light (9,000 lux). Western blotting was used to determine visual cell opsin and arrestin levels following intense light treatment. Rhodopsin regeneration was determined after 1 h of exposure to light. Gene array analysis was used to determine changes in the expression of retinal genes resulting from light rearing environment or from antioxidant supplementation. Results Chronic high-intensity cyclic light rearing resulted in lower levels of rod and cone opsins, retinal S-antigen (S-ag), and medium wavelength cone arrestin (mCAR) than found for rats maintained in low cyclic light. However, as determined by retinal DNA, and by residual opsin and arrestin levels, 2 weeks after acute photooxidative damage, visual cell loss was greater in rats reared in low cyclic light. Retinal damage decreased with AREDS plus rosemary, or with zinc oxide plus rosemary whereas AREDS alone and zinc oxide alone (at their daily recommended levels) were both ineffective. One week of supplemental AREDS plus carnosic acid resulted in higher levels of rod and cone cell proteins, and higher levels of retinal DNA than for AREDS alone. Rhodopsin regeneration was unaffected by the rosemary treatment. Retinal gene array analysis showed reduced expression of medium- wavelength opsin 1 and arrestin C in the high-light reared rats versus the low-light rats. The transition of rats from low cyclic light to a high cyclic light environment resulted in the differential expression of 280 gene markers, enriched for genes related to inflammation, apoptosis, cytokine, innate immune response, and receptors. Rosemary, zinc oxide plus rosemary, and AREDS plus rosemary suppressed 131, 241, and 266 of these genes (respectively) in high-light versus low-light animals and induced a small subset of changes in gene expression that were independent of light rearing conditions. Conclusions Long-term environmental light intensity is a major determinant of retinal gene and protein expression, and of visual cell survival following acute photooxidative insult. Rats preconditioned by high-light rearing exhibit lower levels of cone opsin mRNA and protein, and lower mCAR protein, than low-light reared animals, but greater retention of retinal DNA and proteins following photooxidative damage. Rosemary enhanced the protective efficacy of AREDS and led to the greatest effect on the retinal genome in animals reared in high environmental light. Chronic administration of rosemary antioxidants may be a useful adjunct to the therapeutic benefit of AREDS in slowing disease progression in AMD. PMID:29062223

High hepatotoxic dose of paracetamol produces generalized convulsions and brain damage in rats. A counteraction with the stable gastric pentadecapeptide BPC 157 (PL 14736).

PubMed

Ilic, S; Drmic, D; Zarkovic, K; Kolenc, D; Coric, M; Brcic, L; Klicek, R; Radic, B; Sever, M; Djuzel, V; Ivica, M; Boban Blagaic, A; Zoricic, Z; Anic, T; Zoricic, I; Djidic, S; Romic, Z; Seiwerth, S; Sikiric, P

2010-04-01

We focused on stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, an anti-ulcer peptide efficient in inflammatory bowel disease trials (PL 14736), no toxicity reported) because of its hepatoprotective effects. We investigate a particular aspect of the sudden onset of encephalopathy with extreme paracetamol overdose (5 g/kg intraperitoneally) so far not reported: rapidly induced progressive hepatic encephalopathy with generalized convulsions in rats. BPC 157 therapy (10 microg, 10 ng, 10 pg/kg, intraperitoneally or intragastrically) was effective (microg-ng range) against paracetamol toxicity, given in early (BPC 157 immediately after paracetamol, prophylactically) or advanced stage (BPC 157 at 3 hours after paracetamol, therapeutically). At 25 min post-paracetamol increased ALT, AST and ammonium serum values precede liver lesion while in several brain areas, significant damage became apparent, accompanied by generalized convulsions. Through the next 5 hour seizure period and thereafter, the brain damage, liver damage enzyme values and hyperammonemia increased, particularly throughout the 3-24 h post-paracetamol period. BPC 157 demonstrated clinical (no convulsions (prophylactic application) or convulsions rapidly disappeared (therapeutic effect within 25 min)), microscopical (markedly less liver and brain lesions) and biochemical (enzyme and ammonium serum levels decreased) counteraction. Both, the prophylactic and therapeutic benefits (intraperitoneally and intragastrically) clearly imply BPC 157 (microg-ng range) as a highly effective paracetamol antidote even against highly advanced damaging processes induced by an extreme paracetamol over-dose.

Predictability of state-level flood damage in the conterminous United States: the role of hazard, exposure and vulnerability

DOE PAGES

Zhou, Qianqian; Leng, Guoyong; Feng, Leyang

2017-07-13

Understanding historical changes in flood damage and the underlying mechanisms is critical for predicting future changes for better adaptations. In this study, a detailed assessment of flood damage for 1950–1999 is conducted at the state level in the conterminous United States (CONUS). Geospatial datasets on possible influencing factors are then developed by synthesizing natural hazards, population, wealth, cropland and urban area to explore the relations with flood damage. A considerable increase in flood damage in CONUS is recorded for the study period which is well correlated with hazards. Comparably, runoff indexed hazards simulated by the Variable Infiltration Capacity (VIC) modelmore » can explain a larger portion of flood damage variations than precipitation in 84% of the states. Cropland is identified as an important factor contributing to increased flood damage in central US while urbanland exhibits positive and negative relations with total flood damage and damage per unit wealth in 20 and 16 states, respectively. Altogether, flood damage in 34 out of 48 investigated states can be predicted at the 90% confidence level. In extreme cases, ~76% of flood damage variations can be explained in some states, highlighting the potential of future flood damage prediction based on climate change and socioeconomic scenarios.« less

Predictability of state-level flood damage in the conterminous United States: the role of hazard, exposure and vulnerability

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

Zhou, Qianqian; Leng, Guoyong; Feng, Leyang

Understanding historical changes in flood damage and the underlying mechanisms is critical for predicting future changes for better adaptations. In this study, a detailed assessment of flood damage for 1950–1999 is conducted at the state level in the conterminous United States (CONUS). Geospatial datasets on possible influencing factors are then developed by synthesizing natural hazards, population, wealth, cropland and urban area to explore the relations with flood damage. A considerable increase in flood damage in CONUS is recorded for the study period which is well correlated with hazards. Comparably, runoff indexed hazards simulated by the Variable Infiltration Capacity (VIC) modelmore » can explain a larger portion of flood damage variations than precipitation in 84% of the states. Cropland is identified as an important factor contributing to increased flood damage in central US while urbanland exhibits positive and negative relations with total flood damage and damage per unit wealth in 20 and 16 states, respectively. Altogether, flood damage in 34 out of 48 investigated states can be predicted at the 90% confidence level. In extreme cases, ~76% of flood damage variations can be explained in some states, highlighting the potential of future flood damage prediction based on climate change and socioeconomic scenarios.« less

Applying 3D Full Waveform Inversion in resolving fracture damage zones around a modelled geological disposal facility in granite

NASA Astrophysics Data System (ADS)

Bentham, H. L. M.; Morgan, J. V.; Angus, D. A.

2016-12-01

The UK has a large volume of high level and intermediate level radioactive waste and government policy is to dispose of this waste in a Geological Disposal Facility (GDF). This will be a highly-engineered facility capable of isolating radioactive waste within multiple protective barriers, deep underground, to ensure that no harmful quantities of radioactivity ever reach the surface environment. Although no specific GDF site in the UK has been chosen, granite is one of the candidate host rocks due to its strength, in engineering terms, and because of its low permeability in consideration of groundwater movement. We design time-lapse seismic surveys to characterise geological models of naturally fractured granite with GDF-related tunnel damage zones at a potential disposal depth of 1000 m (the UK GDF might be shallower). Additionally, we use effective medium models to calculate the velocity change when the fracture density is increased in the damage zones, and find a reduction of 60 m/s in P-wave velocity when the fracture density is doubled. Next, we simulate seismic surveys and apply 3D Full Waveform Inversion (FWI) to see how well we can recover the low-velocity damage zones. Furthermore we evaluate the effectiveness of using a survey design consisting of surface and tunnel receivers (a combined array) to resolve the target. After applying FWI we find the velocity anomaly within the damage zone can be resolved to within 2 m/s (3%) and the shape of the damage zone is resolved to 12.5 m (within a single grid cell). Using the combined array we are able to resolve the anomaly strength and shape more completely. When we add further complexity to the model by including tunnel infrastructure, we conclude the combined array is essential in recovering the tunnel damage zone. Our findings show that it is beneficial to use 3D FWI and novel survey designs for characterising subtle variations as may be present in granite, information that could assist in the GDF site selection process and also with GDF design.

A comparative survey of the impacts of extreme rainfall in two international case studies

NASA Astrophysics Data System (ADS)

Spekkers, Matthieu; Rözer, Viktor; Thieken, Annegret; ten Veldhuis, Marie-Claire; Kreibich, Heidi

2017-08-01

Flooding is assessed as the most important natural hazard in Europe, causing thousands of deaths, affecting millions of people and accounting for large economic losses in the past decade. Little is known about the damage processes associated with extreme rainfall in cities, due to a lack of accurate, comparable and consistent damage data. The objective of this study is to investigate the impacts of extreme rainfall on residential buildings and how affected households coped with these impacts in terms of precautionary and emergency actions. Analyses are based on a unique dataset of damage characteristics and a wide range of potential damage explaining variables at the household level, collected through computer-aided telephone interviews (CATI) and an online survey. Exploratory data analyses based on a total of 859 completed questionnaires in the cities of Münster (Germany) and Amsterdam (the Netherlands) revealed that the uptake of emergency measures is related to characteristics of the hazardous event. In case of high water levels, more efforts are made to reduce damage, while emergency response that aims to prevent damage is less likely to be effective. The difference in magnitude of the events in Münster and Amsterdam, in terms of rainfall intensity and water depth, is probably also the most important cause for the differences between the cities in terms of the suffered financial losses. Factors that significantly contributed to damage in at least one of the case studies are water contamination, the presence of a basement in the building and people's awareness of the upcoming event. Moreover, this study confirms conclusions by previous studies that people's experience with damaging events positively correlates with precautionary behaviour. For improving future damage data acquisition, we recommend the inclusion of cell phones in a CATI survey to avoid biased sampling towards certain age groups.

Chronic inflammation-associated genomic instability paves the way for human esophageal carcinogenesis

PubMed Central

Tian, Dongping; Lei, Zhijin; Chen, Donglin; Xu, Zexin; Su, Min

2016-01-01

Chronic inflammation is associated with increased risk of cancer development, whereas the link between chronic inflammation and esophageal carcinogenesis is still obscure heretofore. This study aimed to investigate the relationship between chronic inflammation and DNA damage, as well as the possible role of DNA damage in esophageal carcinogenic process. Endoscopic esophageal biopsies from 109 individuals from Chaoshan littoral, a high-risk region for esophageal squamous cell carcinoma (ESCC), were examined to evaluate the association between chronic inflammation and histological severity, while additional 204 esophageal non-tumor samples from patients with ESCC were collected. Immunohistochemistry was performed to detect the oxidative DNA damage and DNA double-strand breaks (DSBs). Significantly positive correlation was observed between degree of chronic inflammation and esophageal precursor lesions (rs = 0.37, P < 0.01). Immunohistochemical analysis showed that oxidative DNA damage level was positively correlated with the degree of chronic inflammation (rs = 0.21, P < 0.05). Moreover, the level of oxidative DNA damage positively correlated with histological severity (rs = 0.49, P < 0.01). We found that the extent of DSBs was progressively increased with inflammation degree (P < 0.01) and the progression of precancerous lesions (P < 0.001). Collectively, these findings provide evidence linking chronic inflammation-associated genomic instability with esophageal carcinogenesis and suggest possibilities for early detection and intervention of esophageal carcinogenesis. PMID:27028857

Distribution of melanosomes across the retinal pigment epithelium of a hooded rat: implications for light damage

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

Howell, W.L.; Rapp, L.M.; Williams, T.P.

1982-02-01

Distribution of melanosomes across the retinal pigment epithelium of hooded rats (Long-Evans) is studied at the light microscopic and electron microscopic levels. This distribution is shown to be nonuniform: more melanosomes exist in the periphery than elsewhere and, importantly, there are very few melanosomes in a restricted area of the central portion of the superior hemisphere compared with the corresponding part of the inferior hemisphere. The region with fewest melanosomes is precisely the one that is highly susceptible to light damage. Because this region is the same in both pigmented and albino eyes, the paucity of melanin in this regionmore » is not the cause of its great sensitivity to light damage. Nor does light cause the nonuniform distribution of melanin. A possible explanation, involving a proposed vestigial tapetum, is given in order to explain the correlation of melanosome counts and sensitivity to light damage.« less

Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

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

Feinendegen, L.E.; Bond, V.P.; Sondhaus, C.A.

This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in themore » low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.« less

Herbivores and pathogens on Alnus viridis subsp. fruticosa in interior Alaska: effects of leaf, tree, and neighbour characteristics on damage levels

Treesearch

Christa P.H. Mulder; Bitty A. Roy; Sabine Gusewell

2008-01-01

Parasite damage strongly affects dynamics of boreal forests. Damage levels may be affected by climate change, either directly or indirectly through changes in properties of host trees. We examined how herbivore and pathogen damage in Alnus viridis subsp. fruticosa (Rupr.) Nym. depend on leaf morphology and chemistry, tree size...

Genotypic variability and relationships between mite infestation levels, mite damage, grooming intensity, and removal of Varroa destructor mites in selected strains of worker honey bees (Apis mellifera L.).

PubMed

Guzman-Novoa, Ernesto; Emsen, Berna; Unger, Peter; Espinosa-Montaño, Laura G; Petukhova, Tatiana

2012-07-01

The objective of this study was to demonstrate genotypic variability and analyze the relationships between the infestation levels of the parasitic mite Varroa destructor in honey bee (Apis mellifera) colonies, the rate of damage of fallen mites, and the intensity with which bees of different genotypes groom themselves to remove mites from their bodies. Sets of paired genotypes that are presumably susceptible and resistant to the varroa mite were compared at the colony level for number of mites falling on sticky papers and for proportion of damaged mites. They were also compared at the individual level for intensity of grooming and mite removal success. Bees from the "resistant" colonies had lower mite population rates (up to 15 fold) and higher percentages of damaged mites (up to 9 fold) than bees from the "susceptible" genotypes. At the individual level, bees from the "resistant" genotypes performed significantly more instances of intense grooming (up to 4 fold), and a significantly higher number of mites were dislodged from the bees' bodies by intense grooming than by light grooming (up to 7 fold) in all genotypes. The odds of mite removal were high and significant for all "resistant" genotypes when compared with the "susceptible" genotypes. The results of this study strongly suggest that grooming behavior and the intensity with which bees perform it, is an important component in the resistance of some honey bee genotypes to the growth of varroa mite populations. The implications of these results are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

Roles of oxidative stress in synchrotron radiation X-ray-induced testicular damage of rodents

PubMed Central

Ma, Yingxin; Nie, Hui; Sheng, Caibin; Chen, Heyu; Wang, Ban; Liu, Tengyuan; Shao, Jiaxiang; He, Xin; Zhang, Tingting; Zheng, Chaobo; Xia, Weiliang; Ying, Weihai

2012-01-01

Synchrotron radiation (SR) X-ray has characteristic properties such as coherence and high photon flux, which has excellent potential for its applications in medical imaging and cancer treatment. However, there is little information regarding the mechanisms underlying the damaging effects of SR X-ray on biological tissues. Oxidative stress plays an important role in the tissue damage induced by conventional X-ray, while the role of oxidative stress in the tissue injury induced by SR X-ray remains unknown. In this study we used the male gonads of rats as a model to study the roles of oxidative stress in SR X-ray-induced tissue damage. Exposures of the testes to SR X-ray at various radiation doses did not significantly increase the lipid peroxidation of the tissues, assessed at one day after the irradiation. No significant decreases in the levels of GSH or total antioxidation capacity were found in the SR X-ray-irradiated testes. However, the SR X-ray at 40 Gy induced a marked increase in phosphorylated H2AX – a marker of double-strand DNA damage, which was significantly decreased by the antioxidant N-acetyl cysteine (NAC). NAC also attenuated the SR X-ray-induced decreases in the cell layer number of seminiferous tubules. Collectively, our observations have provided the first characterization of SR X-ray-induced oxidative damage of biological tissues: SR X-ray at high doses can induce DNA damage and certain tissue damage during the acute phase of the irradiation, at least partially by generating oxidative stress. However, SR X-ray of various radiation doses did not increase lipid peroxidation. PMID:22837810

Effect of administration of high-protein diet in rats submitted to resistance training.

PubMed

da Rosa Lima, Thiago; Ávila, Eudes Thiago Pereira; Fraga, Géssica Alves; de Souza Sena, Mariana; de Souza Dias, Arlyson Batista; de Almeida, Paula Caroline; Dos Santos Trombeta, Joice Cristina; Junior, Roberto Carlos Vieira; Damazo, Amílcar Sabino; Navalta, James Wilfred; Prestes, Jonato; Voltarelli, Fabrício Azevedo

2018-04-01

Although there is limited evidence regarding the pathophysiological effects of a high-protein diet (HD), it is believed that this type of diet could overload the body and cause damage to the organs directly involved with protein metabolism and excretion. The aim of this study was to verify the effects of HD on biochemical and morphological parameters of rats that completed a resistance training protocol (RT; aquatic jump) for 8 weeks. Thirty-two adult male Wistar rats were divided into four groups (n = 8 for each group): sedentary normal protein diet (SN-14%), sedentary high-protein diet (SH-35%), trained normal protein diet (TN-14%), and trained high-protein diet (TH-35%). Biochemical, tissue, and morphological measurements were made. Kidney (1.91 ± 0.34) and liver weights (12.88 ± 1.42) were higher in the SH. Soleus muscle weight was higher in the SH (0.22 ± 0.03) when compared to all groups. Blood glucose (123.2 ± 1.8), triglycerides (128.5 ± 44.0), and HDL cholesterol levels (65.7 ± 20.9) were also higher in the SH compared with the other experimental groups. Exercise reduced urea levels in the trained groups TN and TH (31.0 ± 4.1 and 36.8 ± 6.6), respectively. Creatinine levels were lower in TH and SH groups (0.68 ± 0.12; 0.54 ± 0.19), respectively. HD negatively altered renal morphology in SH, but when associated with RT, the apparent damage was partially reversed. In addition, the aquatic jump protocol reversed the damage to the gastrocnemius muscle caused by the HD. A high-protein diet promoted negative metabolic and morphological changes, while RT was effective in reversing these deleterious effects.

Track structure model for damage to mammalian cell cultures during solar proton events

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Wilson, J. W.; Townsend, L. W.; Shinn, J. L.; Katz, R.

1992-01-01

Solar proton events (SPEs) occur infrequently and unpredictably, thus representing a potential hazard to interplanetary space missions. Biological damage from SPEs will be produced principally through secondary electron production in tissue, including important contributions due to delta rays from nuclear reaction products. We review methods for estimating the biological effectiveness of SPEs using a high energy proton model and the parametric cellular track model. Results of the model are presented for several of the historically largest flares using typical levels and body shielding.

Seismic response of reinforced concrete frames at different damage levels

NASA Astrophysics Data System (ADS)

Morales-González, Merangeli; Vidot-Vega, Aidcer L.

2017-03-01

Performance-based seismic engineering is focused on the definition of limit states to represent different levels of damage, which can be described by material strains, drifts, displacements or even changes in dissipating properties and stiffness of the structure. This study presents a research plan to evaluate the behavior of reinforced concrete (RC) moment resistant frames at different performance levels established by the ASCE 41-06 seismic rehabilitation code. Sixteen RC plane moment frames with different span-to-depth ratios and three 3D RC frames were analyzed to evaluate their seismic behavior at different damage levels established by the ASCE 41-06. For each span-to-depth ratio, four different beam longitudinal reinforcement steel ratios were used that varied from 0.85 to 2.5% for the 2D frames. Nonlinear time history analyses of the frames were performed using scaled ground motions. The impact of different span-to-depth and reinforcement ratios on the damage levels was evaluated. Material strains, rotations and seismic hysteretic energy changes at different damage levels were studied.

The evaluation of oxidative DNA damage in children with brain damage using 8-hydroxydeoxyguanosine levels.

PubMed

Fukuda, Miho; Yamauchi, Hiroshi; Yamamoto, Hitoshi; Aminaka, Masahito; Murakami, Hiroshi; Kamiyama, Noriko; Miyamoto, Yusaku; Koitabashi, Yasushi

2008-02-01

Urinary and cerebrospinal fluid (CSF) levels of 8-hydroxydeoxyguanosine (8-OHdG) were examined to estimate the relevance of oxidative stress in children with brain damage. Urinary 8-OHdG levels were measured in 51 children with various forms of central nervous system (CNS) disorders (status epilepticus [SE], hypoxic-ischemic encephalopathy [HIE], CNS infections and chronic epilepsy) and these levels were compared with those in 51 healthy children. CSF 8-OHdG levels were measured in 25 children with brain damage and in 19 control subjects. In addition, urinary and CSF levels of 8-OHdG were compared between the children with brain damage and healthy children. Finally, the relationship between urinary and CSF levels of 8-OHdG was determined in 12 children that provided both urinary and CSF samples. Our results showed that urinary 8-OHdG levels in children with HIE and CNS infections were higher than those of controls (Steel test; p < 0.05 and p < 0.05, respectively) and that CSF 8-OHdG levels were higher in children with SE, HIE, and CNS infections than in control subjects (Steel test; p < 0.01, 0.05 and 0.05, respectively). In addition, a positive correlation between the levels of urinary and CSF 8-OHdG was noted in the 12 children that provided both CSF and urinary samples (Spearman's rank correlation; rho = 0.82, p < 0.01). Further, we observed changes in the urinary 8-OHdG in a patient with HHV-6 encephalopathy, and found that the changes correlated well with the patient's clinical condition. These results suggest that oxidative stress is strongly related to acute brain damage in children, and that 8-OHdG is a useful marker of brain damage. Therefore, repeated measurements of urinary 8-OHdG may be helpful in estimating the extent of brain damage.

Comparative evaluation of environmental contamination and DNA damage induced by electronic-waste in Nigeria and China.

PubMed

Alabi, Okunola A; Bakare, Adekunle A; Xu, Xijin; Li, Bin; Zhang, Yuling; Huo, Xia

2012-04-15

In the last decade, China and Nigeria have been prime destinations for the world's e-waste disposal leading to serious environmental contamination. We carried out a comparative study of the level of contamination using soils and plants from e-waste dumping and processing sites in both countries. Levels of polyaromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) were analyzed using gas chromatography/spectrophotometry and heavy metals using atomic absorption spectrophotometry. DNA damage was assayed in human peripheral blood lymphocytes using an alkaline comet assay. Soils and plants were highly contaminated with toxic PAHs, PCBs, PBDEs, and heavy metals in both countries. Soil samples from China and plant samples from Nigeria were more contaminated. There was a positive correlation between the concentrations of organics and heavy metals in plant samples and the surrounding soils. In human lymphocytes, all tested samples induced significant (p<0.05) concentration-dependent increases in DNA damage compared with the negative control. These findings suggest that e-waste components/constituents can accumulate, in soil and surrounding vegetation, to toxic and genotoxic levels that could induce adverse health effects in exposed individuals. Copyright © 2012 Elsevier B.V. All rights reserved.

Default operational intervention levels (OILs) for severe nuclear power plant or spent fuel pool emergencies.

PubMed

McKenna, T; Kutkov, V; Vilar Welter, P; Dodd, B; Buglova, E

2013-05-01

Experience and studies show that for an emergency at a nuclear power plant involving severe core damage or damage to the fuel in spent fuel pools, the following actions may need to be taken in order to prevent severe deterministic health effects and reduce stochastic health effects: (1) precautionary protective actions and other response actions for those near the facility (i.e., within the zones identified by the International Atomic Energy Agency) taken immediately upon detection of facility conditions indicating possible severe damage to the fuel in the core or in the spent fuel pool; and (2) protective actions and other response actions taken based on environmental monitoring and sampling results following a release. This paper addresses the second item by providing default operational intervention levels [OILs, which are similar to the U.S. derived response levels (DRLs)] for promptly assessing radioactive material deposition, as well as skin, food, milk and drinking water contamination, following a major release of fission products from the core or spent fuel pool of a light water reactor (LWR) or a high power channel reactor (RBMK), based on the International Atomic Energy Agency's guidance.

Human Lung Cancer Risks from Radon – Part II – Influence from Combined Adaptive Response and Bystander Effects – A Microdose Analysis

PubMed Central

Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

2010-01-01

In the prior Part I, the potential influence of the low level alpha radiation induced bystander effect (BE) on human lung cancer risks was examined. Recent analysis of adaptive response (AR) research results with a Microdose Model has shown that single low LET radiation induced charged particles traversals through the cell nucleus activates AR. We have here conducted an analysis based on what is presently known about adaptive response and the bystander effect (BE) and what new research is needed that can assist in the further evaluation human cancer risks from radon. We find that, at the UNSCEAR (2000) worldwide average human exposures from natural background and man-made radiations, the human lung receives about a 25% adaptive response protection against the radon alpha bystander damage. At the UNSCEAR (2000) minimum range of background exposure levels, the lung receives minimal AR protection but at higher background levels, in the high UNSCEAR (2000) range, the lung receives essentially 100% protection from both the radon alpha damage and also the endogenic, spontaneously occurring, potentially carcinogenic, lung cellular damage. PMID:22461760

High prolactin levels are independently associated with damage accrual in systemic lupus erythematosus patients.

PubMed

Ugarte-Gil, M F; Gamboa-Cárdenas, R V; Zevallos, F; Medina, M; Cucho-Venegas, J M; Perich-Campos, R A; Alfaro-Lozano, J L; Rodriguez-Bellido, Z; Alarcón, G S; Pastor-Asurza, C A

2014-09-01

to determine whether prolactin levels are independently associated with disease damage in systemic lupus erythematosus (SLE) patients. these cross-sectional analyses were conducted in SLE patient members of the Almenara Lupus Cohort who were seen between January 2012 and June 2013. Disease damage was ascertained with the System Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI). Prolactin was measured in ng/ml. The association between prolactin levels and the SDI (total and its domains) was evaluated using Spearman's correlation. Subsequently, adjusted Poisson regression models were performed to evaluate these associations. 160 patients were included. 147 (91.9%) were female; their median age at diagnosis was 33.4 (interquartile range (IQR): 26.0-44.3) years; their disease duration was 5.5 (IQR: 2.6-9.7) years. The median prolactin value was 16.8 (IQR: 11.8-24.5) ng/ml. After adjusting for confounders in the Poisson regression model the estimated rate ratios (RR) and 95% confidence interval (CI) for each 10 ng/ml increment of prolactin were 1.13 (95% CI 1.60-1.20, p<0.001) for the total SDI score, 1.15 (1.03-1.28, p=0.003) for the renal domain and 1.41 (1.11-1.79, p=0.003) for the cardiac/peripheral vascular domains. there was a positive association between prolactin levels and the SDI (overall and its renal and cardiac/peripheral vascular domains), independently of other well-known risk factors. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Identification of multiple ear-colonizing insect and disease resistance in CIMMYT maize inbred lines with varying levels of silk maysin.

PubMed

Ni, Xinzhi; Krakowsky, Matthew D; Buntin, G David; Rector, Brian G; Guo, Baozhu; Snook, Maurice E

2008-08-01

Ninety four corn inbred lines selected from International Center for the Improvement of Maize and Wheat (CIMMYT) in Mexico were evaluated for levels of silk maysin in 2001 and 2002. Damage by major ear-feeding insects [i.e., corn earworm, Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae); maize weevil, Sitophilus zeamais (Motschulsky) (Coleoptera: Curculionidae); brown stink bug, Euschistus servus (Say); southern green stink bugs, Nezara viridula (L.) (Heteroptera: Pentatomidae)], and common smut [Ustilago maydis DC (Corda)] infection on these inbred lines were evaluated in 2005 and 2006 under subtropical conditions at Tifton, GA. Ten inbred lines possessing good agronomic traits were also resistant to the corn earworm. The correlation between ear-feeding insect damage or smut infection and three phenotypic traits (silk maysin level, husk extension, and husk tightness of corn ears) was also examined. Corn earworm and stink bug damage was negatively correlated to husk extension, but not to either silk maysin levels or husk tightness. In combination with the best agronomic trait ratings that show the least corn earworm and stink bug damage, lowest smut infection rate, and good insect-resistant phenotypic traits (i.e., high maysin and good husk coverage and husk tightness), 10 best inbred lines (CML90, CML92, CML94, CML99, CML104, CML108, CML114, CML128, CML137, and CML373) were identified from the 94 lines examined. These selected inbred lines will be used for further examination of their resistance mechanisms and development of new corn germplasm that confers multiple ear-colonizing pest resistance.

Effect of low velocity impact damage on the natural frequency of composite plates

NASA Astrophysics Data System (ADS)

Chok, E. Y. L.; Majid, D. L. A. A.; Harmin, M. Y.

2017-12-01

Biodegradable natural fibers have been suggested to replace the hazardous synthetic fibers in many aerospace applications. However, this notion has been limited due to their low mechanical properties, which leads to the idea of hybridizing the two materials. Many aircraft components such as radome, aft body and wing are highly susceptible to low velocity impact damage while in-service. The damages degrade the structural integrity of the components and change their dynamic characteristics. In worst case scenario, the changes can lead to resonance, which is an excessive vibration. This research is conducted to study the dynamic characteristic changes of low velocity impact damaged hybrid composites that is designed for aircraft radome applications. Three materials, which are glass fiber, kenaf fiber and kenaf/glass fiber hybrid composites, have been impacted with 3J, 6J and 9J of energy. Cantilevered and also vertically clamped boundary conditions are used and the natural frequencies are extracted for each of the specimens. The obtained results show that natural frequency decreases with increasing impact level. Cantilevered condition is found to induce lower modes due to the gravitational pull. To eliminate mass and geometrical effects, normalized modes are computed. Among the three materials considered, glass fiber composites have displayed the highest normalized frequency that reflects on its higher stiffness compared to the other two materials. As the damage level is increased, glass fiber composites have shown the highest frequency reduction to a maximum of 35% while kenaf composites have the least frequency reduction in the range of 1 - 18%. Thus, kenaf fiber is taken to be helpful in stalling the damage progression and reducing the effect of damage. This has been proven when the percentage frequency decrement shown by kenaf/glass fiber composite lies between glass fiber and kenaf fiber composites.

The intensity dependence of lesion position shift during focused ultrasound surgery.

PubMed

Meaney, P M; Cahill, M D; ter Haar, G R

2000-03-01

Knowledge of the spatial distribution of intensity loss from an ultrasonic beam is critical for predicting lesion formation in focused ultrasound (US) surgery (FUS). To date, most models have used linear propagation models to predict intensity profiles required to compute the temporally varying temperature distributions used to compute thermal dose contours. These are used to predict the extent of thermal damage. However, these simulations fail to describe adequately the abnormal lesion formation behaviour observed during ex vivo experiments in cases for which the transducer drive levels are varied over a wide range. In such experiments, the extent of thermal damage has been observed to move significantly closer to the transducer with increased transducer drive levels than would be predicted using linear-propagation models. The first set of simulations described herein use the KZK (Khokhlov-Zabolotskaya-Kuznetsov) nonlinear propagation model with the parabolic approximation for highly focused US waves to demonstrate that both the peak intensity and the lesion positions do, indeed, move closer to the transducer. This illustrates that, for accurate modelling of heating during FUS, nonlinear effects should be considered. Additionally, a first order approximation has been employed that attempts to account for the abnormal heat deposition distributions that accompany high transducer drive level FUS exposures where cavitation and boiling may be present. The results of these simulations are presented. It is suggested that this type of approach may be a useful tool in understanding thermal damage mechanisms.

The evolution of senescence through decelerating selection for system reliability.

PubMed

Laird, R A; Sherratt, T N

2009-05-01

Senescence is a universal phenomenon in organisms, characterized by increasing mortality and decreasing fecundity with advancing chronological age. Most proximate agents of senescence, such as reactive oxygen species and UV radiation, are thought to operate by causing a gradual build-up of bodily damage. Yet most current evolutionary theories of senescence emphasize the deleterious effects of functioning genes in late life, leaving a gap between proximate and ultimate explanations. Here, we present an evolutionary model of senescence based on reliability theory, in which beneficial genes or gene products gradually get damaged and thereby fail, rather than actively cause harm. Specifically, the model allows organisms to evolve multiple redundant copies of a gene product (or gene) that performs a vital function, assuming that organisms can avoid condition-dependent death so long as at least one copy remains undamaged. We show that organisms with low levels of extrinsic mortality, and high levels of genetic damage, tend to evolve high levels of redundancy, and that mutation-selection balance results in a stable population distribution of the number of redundant elements. In contrast to previous evolutionary models of senescence, the mortality curves that emerge from such populations match empirical senescence patterns in three key respects: they exhibit: (1) an initially low, but rapidly increasing mortality rate at young ages, (2) a plateau in mortality at advanced ages and (3) 'mortality compensation', whereby the height of the mortality plateau is independent of the environmental conditions under which different populations evolved.

Evaluating the Human Damage of Tsunami at Each Time Frame in Aggregate Units Based on GPS data

NASA Astrophysics Data System (ADS)

Ogawa, Y.; Akiyama, Y.; Kanasugi, H.; Shibasaki, R.; Kaneda, H.

2016-06-01

Assessments of the human damage caused by the tsunami are required in order to consider disaster prevention at such a regional level. Hence, there is an increasing need for the assessments of human damage caused by earthquakes. However, damage assessments in japan currently usually rely on static population distribution data, such as statistical night time population data obtained from national census surveys. Therefore, human damage estimation that take into consideration time frames have not been assessed yet. With these backgrounds, the objectives of this study are: to develop a method for estimating the population distribution of the for each time frame, based on location positioning data observed with mass GPS loggers of mobile phones, to use a evacuation and casualties models for evaluating human damage due to the tsunami, and evaluate each time frame by using the data developed in the first objective, and 3) to discuss the factors which cause the differences in human damage for each time frame. By visualizing the results, we clarified the differences in damage depending on time frame, day and area. As this study enables us to assess damage for any time frame in and high resolution, it will be useful to consider provision for various situations when an earthquake may hit, such as during commuting hours or working hours and week day or holiday.

Stability Study on Steel Structural Columns with Initial Blast Damage under High Temperatures

NASA Astrophysics Data System (ADS)

Baoxin, Qi; Yan, Shi; Li, Peng

2018-03-01

Blast may bring light-weight steel columns with initial damages, resulting in lowering its critical fire-resistance temperature whose reduced amplitude is relevant to the form and degree of the damages. Finite element analysis software ANSYS was used in the paper to analyze the issue of the fire-resistance temperature of the column with the blast damages, and the coupling method for heat and structure was applied during the simulation. The emphasis was laid on parametric factors of axial compression ratio, the form and the degree of the initial damages, as well as the confined condition at the ends of the columns. The numerical results showed that the fire-resistance temperature will lower as increasing of the axial compression ratio, the form and the degree of the initial damages and it will be also affected by the restraint conditions at the ends of the columns. The critical stress formula with initial bending damage under elevated temperature was set up under flexural small deformation condition, then the stability coefficient was determined and the method for evaluating the limit temperature of the column was put forward. The theoretical result was also compared with that of the finite element method (FEM). The results both showed that the stability capacity for the damaged columns was dramatically reduced as increasing the temperature and the initial damage level.

Cellular defense against singlet oxygen-induced oxidative damage by cytosolic NADP+-dependent isocitrate dehydrogenase.

PubMed

Kim, Sun Yee; Park, Jeen-Woo

2003-03-01

Singlet oxygen (1O2) is a highly reactive form of molecular oxygen that may harm living systems by oxidizing critical cellular macromolecules. Recently, we have shown that NADP+-dependent isocitrate dehydrogenase is involved in the supply of NADPH needed for GSH production against cellular oxidative damage. In this study, we investigated the role of cytosolic form of NADP+-dependent isocitrate dehydrogenase (IDPc) against singlet oxygen-induced cytotoxicity by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 2.3-fold higher and 39% lower, respectively, than that in the parental cells carrying the vector alone. Upon exposure to singlet oxygen generated from photoactivated dye, the cells with low levels of IDPc became more sensitive to cell killing. Lipid peroxidation, protein oxidation, oxidative DNA damage and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly over-expressed IDPc exhibited enhanced resistance against singlet oxygen, compared to the control cells. The data indicate that IDPc plays an important role in cellular defense against singlet oxygen-induced oxidative injury.

DNA damage in blood cells exposed to low-level lasers.

PubMed

Sergio, Luiz Philippe da Silva; Silva, Ana Paula Almeida da; Amorim, Philipi Freitas; Campos, Vera Maria Araújo; Magalhães, Luis Alexandre Gonçalves; de Paoli, Flavia; de Souza da Fonseca, Adenilson

2015-04-01

In regenerative medicine, there are increasing applications of low-level lasers in therapeutic protocols for treatment of diseases in soft and in bone tissues. However, there are doubts about effects on DNA, and an adequate dosimetry could improve the safety of clinical applications of these lasers. This work aimed to evaluate DNA damage in peripheral blood cells of Wistar rats induced by low-level red and infrared lasers at different fluences, powers, and emission modes according to therapeutic protocols. Peripheral blood samples were exposed to lasers and DNA damage was accessed by comet assay. In other experiments, DNA damage was accessed in blood cells by modified comet assay using formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III enzymes. Data show that exposure to low-level red and infrared lasers induce DNA damage depending on fluence, power and emission mode, which are targeted by Fpg and endonuclease III. Oxidative DNA damage should be considered for therapeutic efficacy and patient safety in clinical applications based on low-level red and infrared lasers. © 2015 Wiley Periodicals, Inc.

DNA Damage Levels Determine Cyclobutyl Pyrimidine Dimer Repair Mechanisms in Alfalfa Seedlings.

PubMed Central

Quaite, F. E.; Takayanagi, S.; Ruffini, J.; Sutherland, J. C.; Sutherland, B. M.

1994-01-01

Ultraviolet radiation in sunlight damages DNA in plants, but little is understood about the types, lesion capacity, and coordination of repair pathways. We challenged intact alfalfa seedlings with UV doses that induced different initial levels of cyclobutyl pyrimidine dimers and measured repair by excision and photoreactivation. By using alkaline gel electrophoresis of nonradioactive DNAs treated with a cyclobutyl pyrimidine dimer-specific UV endonuclease, we quantitated ethidium-stained DNA by electronic imaging and calculated lesion frequencies from the number average molecular lengths. At low initial dimer frequencies (less than ~30 dimers per million bases), the seedlings used only photoreactivation to repair dimers; excision repair was not significant. At higher damage levels, both excision and photorepair contributed significantly. This strategy would allow plants with low damage levels to use error-free repair requiring only an external light energy source, whereas seedlings subjected to higher damage frequencies could call on additional repair processes requiring cellular energy. Characterization of repair in plants thus requires an investigation of a range of conditions, including the level of initial damage. PMID:12244228

[Critical level of radiation damage of root apical meristem and mechanisms for its recovery in Pisum sativum L].

PubMed

Kravets, E A; Mikheev, A N; Ovsiannikova, L G; Grodzinskiĭ, D M

2011-01-01

The dose dependencies of growth and cytogenetical values have been built to determine the critical level of root apical meristem damage induced by cute irradiation in the range from 2 to 20 Gr. We have analyzed the frequencies of aberrant anaphases and the aberration distribution per cell, on the one hand, and the growth of biomass, the survival and regeneration of the root meristem, on the other hand. The critical level of damage to the stem apical meristem and root of seedlings was defined as 44-48% of aberrant anaphase. Exceeding of this level leads to the launch of suicidal program through induction of multiaberrant damages and interphase cell death. It appears that competition of clones of non-aberrant cells, the cells bearing 1 and 2 damages and multiaberrant cells plays the primary role in the mechanisms of recovery. The regeneration provides full or partial restoration of the main root apical meristem. However these local processes are insufficient to restore morphogenesis and survival of seedlings in excess of the critical level damage.

Optimal CO2 mitigation under damage risk valuation

NASA Astrophysics Data System (ADS)

Crost, Benjamin; Traeger, Christian P.

2014-07-01

The current generation has to set mitigation policy under uncertainty about the economic consequences of climate change. This uncertainty governs both the level of damages for a given level of warming, and the steepness of the increase in damage per warming degree. Our model of climate and the economy is a stochastic version of a model employed in assessing the US Social Cost of Carbon (DICE). We compute the optimal carbon taxes and CO2 abatement levels that maximize welfare from economic consumption over time under different risk states. In accordance with recent developments in finance, we separate preferences about time and risk to improve the model's calibration of welfare to observed market interest. We show that introducing the modern asset pricing framework doubles optimal abatement and carbon taxation. Uncertainty over the level of damages at a given temperature increase can result in a slight increase of optimal emissions as compared to using expected damages. In contrast, uncertainty governing the steepness of the damage increase in temperature results in a substantially higher level of optimal mitigation.

A robust signal processing method for quantitative high-cycle fatigue crack monitoring using soft elastomeric capacitor sensors

NASA Astrophysics Data System (ADS)

Kong, Xiangxiong; Li, Jian; Collins, William; Bennett, Caroline; Laflamme, Simon; Jo, Hongki

2017-04-01

A large-area electronics (LAE) strain sensor, termed soft elastomeric capacitor (SEC), has shown great promise in fatigue crack monitoring. The SEC is able to monitor strain changes over a mesoscale structural surface and endure large deformations without being damaged under cracking. Previous tests verified that the SEC is able to detect, localize, and monitor fatigue crack activities under low-cycle fatigue loading. In this paper, to examine the SEC's capability of monitoring high-cycle fatigue cracks, a compact specimen is tested under cyclic tension, designed to ensure realistic crack opening sizes representative of those in real steel bridges. To overcome the difficulty of low signal amplitude and relatively high noise level under high-cycle fatigue loading, a robust signal processing method is proposed to convert the measured capacitance time history from the SEC sensor to power spectral densities (PSD) in the frequency domain, such that signal's peak-to-peak amplitude can be extracted at the dominant loading frequency. A crack damage indicator is proposed as the ratio between the square root of the amplitude of PSD and load range. Results show that the crack damage indicator offers consistent indication of crack growth.

Numerical Simulation of Hydraulic Fracturing in Low-/High-Permeability, Quasi-Brittle and Heterogeneous Rocks

NASA Astrophysics Data System (ADS)

Pakzad, R.; Wang, S. Y.; Sloan, S. W.

2018-04-01

In this study, an elastic-brittle-damage constitutive model was incorporated into the coupled fluid/solid analysis of ABAQUS to iteratively calculate the equilibrium effective stress of Biot's theory of consolidation. The Young's modulus, strength and permeability parameter of the material were randomly assigned to the representative volume elements of finite element models following the Weibull distribution function. The hydraulic conductivity of elements was associated with their hydrostatic effective stress and damage level. The steady-state permeability test results for sandstone specimens under different triaxial loading conditions were reproduced by employing the same set of material parameters in coupled transient flow/stress analyses of plane-strain models, thereby indicating the reliability of the numerical model. The influence of heterogeneity on the failure response and the absolute permeability was investigated, and the post-peak permeability was found to decrease with the heterogeneity level in the coupled analysis with transient flow. The proposed model was applied to the plane-strain simulation of the fluid pressurization of a cavity within a large-scale block under different conditions. Regardless of the heterogeneity level, the hydraulically driven fractures propagated perpendicular to the minimum principal far-field stress direction for high-permeability models under anisotropic far-field stress conditions. Scattered damage elements appeared in the models with higher degrees of heterogeneity. The partially saturated areas around propagating fractures were simulated by relating the saturation degree to the negative pore pressure in low-permeability blocks under high pressure. By replicating previously reported trends in the fracture initiation and breakdown pressure for different pressurization rates and hydraulic conductivities, the results showed that the proposed model for hydraulic fracture problems is reliable for a wide range of pressurization rates and permeability conditions.

Benefits of jasmonate-dependent defenses against vertebrate herbivores in nature.

PubMed

Machado, Ricardo Ar; McClure, Mark; Hervé, Maxime R; Baldwin, Ian T; Erb, Matthias

2016-06-29

Endogenous jasmonates are important regulators of plant defenses. If and how they enable plants to maintain their reproductive output when facing community-level herbivory under natural conditions, however, remains unknown. We demonstrate that jasmonate-deficient Nicotiana attenuata plants suffer more damage by arthropod and vertebrate herbivores than jasmonate-producing plants in nature. However, only damage by vertebrate herbivores translates into a significant reduction in flower production. Vertebrate stem peeling has the strongest negative impact on plant flower production. Stems are defended by jasmonate-dependent nicotine, and the native cottontail rabbit Sylvilagus nuttallii avoids jasmonate-producing N. attenuata shoots because of their high levels of nicotine. Thus, endogenous jasmonates enable plants to resist different types of herbivores in nature, and jasmonate-dependent defenses are important for plants to maintain their reproductive potential when facing vertebrate herbivory. Ecological and evolutionary models on plant defense signaling should aim at integrating arthropod and vertebrate herbivory at the community level.

Higher levels of oxidative DNA damage in cervical cells are correlated with the grade of dysplasia and HPV infection.

PubMed

Visalli, Giuseppa; Riso, Romana; Facciolà, Alessio; Mondello, Placido; Caruso, Carmela; Picerno, Isa; Di Pietro, Angela; Spataro, Pasquale; Bertuccio, Maria Paola

2016-02-01

The Human papillomavirus is responsible for the most common sexually transmitted infection and is also known to be an oncogenic virus that is associated with cervical, anogenital, and head-neck cancers. The present study aims to assess whether oxidative DNA damage is correlated with the grade of HPV-related lesions. Moreover, we evaluated clinical data and unhealthy lifestyles to verify their possible influence on the genesis of oxidative DNA damage in cervical cells. We quantified the amount of 8-Oxo-2'-deoxyguanosine in DNA as a biomarker of oxidative damage in women with and without HPV infection. We also correlated oxidative damage with different stages of cervical lesions and available clinical data (e.g., HPV genotypes). To identify HPV infections, in which proteins with a transforming potential are produced, we performed a qualitative detection of HPV E6/E7 mRNA. Our results showed greater oxidative damage in HPV-related dysplastic cervical lesions compared to samples with normal cytology, especially in women with high-grade squamous intraepithelial lesions. The latter showed a closed link with high-risk HPV genotypes. Reactive oxygen species can induce DNA double-strand breaks in both the host DNA and in the circular viral episome; this could facilitate the integration of the virus, promoting HPV carcinogenesis. Therefore, in HPV-infected women, it could be useful to reduce additional resources of reactive oxygen/nitrogen species (RONS) with a healthy lifestyle. © 2015 Wiley Periodicals, Inc.

Urea transporter UT-B deletion induces DNA damage and apoptosis in mouse bladder urothelium.

PubMed

Dong, Zixun; Ran, Jianhua; Zhou, Hong; Chen, Jihui; Lei, Tianluo; Wang, Weiling; Sun, Yi; Lin, Guiting; Bankir, Lise; Yang, Baoxue

2013-01-01

Previous studies found that urea transporter UT-B is abundantly expressed in bladder urothelium. However, the dynamic role of UT-B in bladder urothelial cells remains unclear. The objective of this study is to evaluate the physiological roles of UT-B in bladder urothelium using UT-B knockout mouse model and T24 cell line. Urea and NO measurement, mRNA expression micro-array analysis, light and transmission electron microscopy, apoptosis assays, DNA damage and repair determination, and intracellular signaling examination were performed in UT-B null bladders vs wild-type bladders and in vitro T24 epithelial cells. UT-B was highly expressed in mouse bladder urothelium. The genes, Dcaf11, MCM2-4, Uch-L1, Bnip3 and 45 S pre rRNA, related to DNA damage and apoptosis were significantly regulated in UT-B null urothelium. DNA damage and apoptosis highly occurred in UT-B null urothelium. Urea and NO levels were significantly higher in UT-B null urothelium than that in wild-type, which may affect L-arginine metabolism and the intracellular signals related to DNA damage and apoptosis. These findings were consistent with the in vitro study in T24 cells that, after urea loading, exhibited cell cycle delay and apoptosis. UT-B may play an important role in protecting bladder urothelium by balancing intracellular urea concentration. Disruption of UT-B function induces DNA damage and apoptosis in bladder, which can result in bladder disorders.

Urea Transporter UT-B Deletion Induces DNA Damage and Apoptosis in Mouse Bladder Urothelium

PubMed Central

Zhou, Hong; Chen, Jihui; Lei, Tianluo; Wang, Weiling; Sun, Yi; Lin, Guiting; Bankir, Lise; Yang, Baoxue

2013-01-01

Background Previous studies found that urea transporter UT-B is abundantly expressed in bladder urothelium. However, the dynamic role of UT-B in bladder urothelial cells remains unclear. The objective of this study is to evaluate the physiological roles of UT-B in bladder urothelium using UT-B knockout mouse model and T24 cell line. Methodology/Principal Findings Urea and NO measurement, mRNA expression micro-array analysis, light and transmission electron microscopy, apoptosis assays, DNA damage and repair determination, and intracellular signaling examination were performed in UT-B null bladders vs wild-type bladders and in vitro T24 epithelial cells. UT-B was highly expressed in mouse bladder urothelium. The genes, Dcaf11, MCM2-4, Uch-L1, Bnip3 and 45 S pre rRNA, related to DNA damage and apoptosis were significantly regulated in UT-B null urothelium. DNA damage and apoptosis highly occurred in UT-B null urothelium. Urea and NO levels were significantly higher in UT-B null urothelium than that in wild-type, which may affect L-arginine metabolism and the intracellular signals related to DNA damage and apoptosis. These findings were consistent with the in vitro study in T24 cells that, after urea loading, exhibited cell cycle delay and apoptosis. Conclusions/Significance UT-B may play an important role in protecting bladder urothelium by balancing intracellular urea concentration. Disruption of UT-B function induces DNA damage and apoptosis in bladder, which can result in bladder disorders. PMID:24204711

High fat diet feeding results in gender specific steatohepatitis and inflammasome activation.

PubMed

Ganz, Michal; Csak, Timea; Szabo, Gyongyi

2014-07-14

To develop an animal model that encompasses the different facets of non-alcoholic steatohepatitis (NASH), which has been a challenge. In this study, we used a high fat diet (HFD) feeding supplemented with fructose and sucrose in the water mimicking the high-fructose corn syrup that is abundant in the diet in the United States. We used C57Bl/6 wild-type mice for short and long-term feedings of 6 and 16 wk respectively, and evaluated the extent of liver damage, steatosis, and inflammasome activation. Our methods included histopathological analysis to assess liver damage and steatosis, which involved H and E and oil-red-o staining; biochemical studies to look at ALT and triglyceride levels; RNA analysis using quantitative polymerase chain reaction; and cytokine analysis, which included the enzyme-linked immunosorbent assay method to look at interleukin (IL)-1β and tumor necrosis factor-α (TNFα) levels. Furthermore, at each length of feeding we also looked at insulin resistance and glucose tolerance using insulin tolerance tests (ITT) and glucose tolerance tests. There was no insulin resistance, steatosis, or inflammasome activation at 6 wk. In contrast, at 16 wk we found significant insulin resistance demonstrated by impaired glucose and ITT in male, but not female mice. In males, elevated alanine aminotransferase and triglyceride levels, indicated liver damage and steatosis, respectively. Increased liver TNFα and monocyte chemoattractant protein-1 mRNA and protein, correlated with steatohepatitis. The inflammasome components, adaptor molecule, Aim2, and NOD-like receptor 4, increased at the mRNA level, and functional inflammasome activation was indicated by increased caspase-1 activity and IL-1β protein levels in male mice fed a long-term HFD. Male mice on HFD had increased α-smooth muscle actin and pro-collagen-1 mRNA indicating evolving fibrosis. In contrast, female mice displayed only elevated triglyceride levels, steatosis, and no fibrosis. Our data indicate gender differences in NASH. Male mice fed a long-term HFD display steatohepatitis and inflammasome activation, whereas female mice have steatosis without inflammation.

Investigation of Sideband Index Response to Prototype Gear Tooth Damage

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.

2013-01-01

The objective of this analysis was to evaluate the ability of gear condition indicators (CI) to detect contact fatigue damage on spiral bevel gear teeth. Tests were performed in the NASA Glenn Spiral Bevel Gear Fatigue Rig on eight prototype gear sets (pinion/gear). Damage was initiated and progressed on the gear and pinion teeth. Vibration data was measured during damage progression at varying torque values while varying damage modes to the gear teeth were observed and documented with inspection photos. Sideband indexes (SI) and root mean square (RMS) CIs were calculated from the time synchronous averaged vibration data. Results found that both CIs respond differently to varying torque levels, damage levels and damage modes

Cranes and Crops: Investigating Farmer Tolerances toward Crop Damage by Threatened Blue Cranes ( Anthropoides paradiseus) in the Western Cape, South Africa

NASA Astrophysics Data System (ADS)

van Velden, Julia L.; Smith, Tanya; Ryan, Peter G.

2016-12-01

The Western Cape population of Blue Cranes ( Anthropoides paradiseus) in South Africa is of great importance as the largest population throughout its range. However, Blue Cranes are strongly associated with agricultural lands in the Western Cape, and therefore may come into conflict with farmers who perceive them as damaging to crops. We investigated the viability of this population by exploring farmer attitudes toward crane damage in two regions of the Western Cape, the Swartland and Overberg, using semi-structured interviews. Perceptions of cranes differed widely between regions: farmers in the Swartland perceived crane flocks to be particularly damaging to the feed crop sweet lupin (65 % of farmers reported some level of damage by cranes), and 40 % of these farmers perceived cranes as more problematic than other common bird pests. Farmers in the Overberg did not perceive cranes as highly damaging, although there was concern about cranes eating feed at sheep troughs. Farmers who had experienced large flocks on their farms and farmers who ranked cranes as more problematic than other bird pests more often perceived cranes to be damaging to their livelihoods. Biographical variables and crop profiles could not be related to the perception of damage, indicating the complexity of this human-wildlife conflict. Farmers' need for management alternatives was related to the perceived severity of damage. These results highlight the need for location-specific management solutions to crop damage by cranes, and contribute to the management of this vulnerable species.

Gene 33/Mig6 inhibits hexavalent chromium-induced DNA damage and cell transformation in human lung epithelial cells

PubMed Central

Park, Soyoung; Li, Cen; Zhao, Hong; Darzynkiewicz, Zbigniew; Xu, Dazhong

2016-01-01

Hexavalent Chromium [Cr(VI)] compounds are human lung carcinogens and environmental/occupational hazards. The molecular mechanisms of Cr(VI) carcinogenesis appear to be complex and are poorly defined. In this study, we investigated the potential role of Gene 33 (ERRFI1, Mig6), a multifunctional adaptor protein, in Cr(VI)-mediated lung carcinogenesis. We show that the level of Gene 33 protein is suppressed by both acute and chronic Cr(VI) treatments in a dose- and time-dependent fashion in BEAS-2B lung epithelial cells. The inhibition also occurs in A549 lung bronchial carcinoma cells. Cr(VI) suppresses Gene 33 expression mainly through post-transcriptional mechanisms, although the mRNA level of gene 33 also tends to be lower upon Cr(VI) treatments. Cr(VI)-induced DNA damage appears primarily in the S phases of the cell cycle despite the high basal DNA damage signals at the G2M phase. Knockdown of Gene 33 with siRNA significantly elevates Cr(VI)-induced DNA damage in both BEAS-2B and A549 cells. Depletion of Gene 33 also promotes Cr(VI)-induced micronucleus (MN) formation and cell transformation in BEAS-2B cells. Our results reveal a novel function of Gene 33 in Cr(VI)-induced DNA damage and lung epithelial cell transformation. We propose that in addition to its role in the canonical EGFR signaling pathway and other signaling pathways, Gene 33 may also inhibit Cr(VI)-induced lung carcinogenesis by reducing DNA damage triggered by Cr(VI). PMID:26760771

Hypothermia modulates the DNA damage response to ionizing radiation in human peripheral blood lymphocytes.

PubMed

Lisowska, Halina; Cheng, Lei; Sollazzo, Alice; Lundholm, Lovisa; Wegierek-Ciuk, Aneta; Sommer, Sylwester; Lankoff, Anna; Wojcik, Andrzej

2018-06-01

Low temperature at exposure has been shown to act in a radioprotective manner at the level of cytogenetic damage. It was suggested to be due to an effective transformation of DNA damage to chromosomal damage at low temperature. The purpose of the study was to analyze the kinetics of aberration formation during the first hours after exposing human peripheral blood lymphocytes to ionizing radiation at 0.8 °C and 37 °C. To this end, we applied the technique of premature chromosome condensation. In addition, DNA damage response was analyzed by measuring the levels of phosphorylated DNA damage responsive proteins ATM, DNA-PK and p53 and mRNA levels of the radiation-responsive genes BBC3, FDXR, GADD45A, XPC, MDM2 and CDKN1A. A consistently lower frequency of chromosomal breaks was observed in cells exposed at 0.8 °C as compared to 37 °C already after 30 minutes postexposure. This effect was accompanied by elevated levels of phosphorylated ATM and DNA-PK proteins and a reduced immediate level of phosphorylated p53 and of the responsive genes. Low temperature at exposure appears to promote DNA repair leading to reduced transformation of DNA damage to chromosomal aberrations.

S100A8/A9, a potent serum and molecular imaging biomarker for synovial inflammation and joint destruction in seronegative experimental arthritis.

PubMed

Geven, Edwin J W; van den Bosch, Martijn H J; Di Ceglie, Irene; Ascone, Giuliana; Abdollahi-Roodsaz, Shahla; Sloetjes, Annet W; Hermann, Sven; Schäfers, Michael; van de Loo, Fons A J; van der Kraan, Peter M; Koenders, Marije I; Foell, Dirk; Roth, Johannes; Vogl, Thomas; van Lent, Peter L E M

2016-10-24

Seronegative joint diseases are characterized by a lack of well-defined biomarkers since autoantibodies are not elevated. Calprotectin (S100A8/A9) is a damage-associated molecular pattern (DAMP) which is released by activated phagocytes, and high levels are found in seronegative arthritides. In this study, we investigated the biomarker potential of systemic and local levels of these S100 proteins to assess joint inflammation and joint destruction in an experimental model for seronegative arthritis. Serum levels of S100A8/A9 and various cytokines were monitored during disease development in interleukin-1 receptor antagonist (IL-1Ra) -/- mice using ELISA and multiplex bead-based immunoassay, and were correlated to macroscopic and microscopic parameters for joint inflammation, bone erosion, and cartilage damage. Local expression of S100A8 and S100A9 and matrix metalloproteinase (MMP)-mediated cartilage damage in the ankle joints were investigated by immunohistochemistry. In addition, local S100A8 and activated MMPs were monitored in vivo by optical imaging using anti-S100A8-Cy7 and AF489-Cy5.5, a specific tracer for activated MMPs. Serum levels of S100A8/A9 were significantly increased in IL-1Ra -/- mice and correlated with macroscopic joint swelling and histological inflammation, while serum levels of pro-inflammatory cytokines did not correlate with joint swelling. In addition, early serum S100A8/A9 levels were prognostic for disease outcome at a later stage. The increased serum S100A8/A9 levels were reflected by an increased expression of S100A8 and S100A9 within the ankle joint, as visualized by molecular imaging. Next to inflammatory processes, serum S100A8/A9 also correlated with histological parameters for bone erosion and cartilage damage. In addition, arthritic IL-1Ra -/- mice with increased synovial S100A8 and S100A9 expression showed increased cartilage damage that coincided with MMP-mediated neoepitope expression and in vivo imaging of activated MMPs. Expression of S100A8 and S100A9 in IL-1Ra -/- mice strongly correlates with synovial inflammation, bone erosion, and cartilage damage, underlining the potential of S100A8/A9 as a systemic and local biomarker in seronegative arthritis not only for assessing inflammation but also for assessing severity of inflammatory joint destruction.

Dendrobium candidum Wall. ex Lindl. attenuates CCl4-induced hepatic damage in imprinting control region mice.

PubMed

Li, Gui-Jie; Sun, Peng; Wang, Qiang; Qian, Yu; Zhu, Kai; Zhao, Xin

2014-09-01

The aim of the present study was to determine the preventive effect of the traditional Chinese medicine, Dendrobium candidum Wall ex Lindl. ( D. candidum ), on CCl 4 -induced hepatic damage in mice. The CCl 4 -induced hepatic damage mice were treated with D. candidum, and the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), triglyceride (TG) and total cholesterol (TC) were determined. In addition, serum cytokine levels of interleukin (IL)-6, IL-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were analyzed with kits, while liver tissues were analyzed using hematoxylin and eosin staining and reverse transcription polymerase chain reaction (RT-PCR). Furthermore, the contents of D. candidum were determined by nuclear magnetic resonance (NMR). D. candidum was demonstrated to successfully prevent hepatic damage in mice. The serum levels of AST, ALT and LDH were significantly decreased when the mice were treated with 200 and 400 mg/kg D. candidum, as compared with the control mice (P<0.05). The lowest enzymatic activities were exhibited in the 400 mg/kg D. candidum group, which produced similar results to the positive control drug, silymarin. In addition, in the 400 mg/kg D. candidum group, the highest levels of TG and TC were observed among the treated groups. D. candidum -treated groups also demonstrated reduced levels of the serum proinflammatory cytokines, IL-6, IL-12, TNF-α and IFN-γ. The sections of liver tissue examined during histopathology in the high concentration 400 mg/kg D. candidum group recovered well from CCl 4 damage; however, the sections in the 200 mg/kg D. candidum group revealed necrosis to a more serious degree. RT-PCR analysis was conducted on inflammation-associated genes, including nuclear factor (NF)-κB, IκB-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, in the livers of the mice. The 400 mg/kg D. candidum group demonstrated significantly decreased mRNA expression levels of NF-κB, iNOS and COX-2, but an increased expression level of IκB-α when compared with the CCl 4 -treated control group. Furthermore, using NMR, 11 compounds were identified in the D. candidum leaf, whose functional contents may aid the preventive effect observed in the current study. Therefore, D. candidum may potentially contribute to the prevention of CCl 4 -induced hepatic damage in vivo .

Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension

PubMed Central

Muñoz-Durango, Natalia; Fuentes, Cristóbal A.; Castillo, Andrés E.; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E.; Kalergis, Alexis M.

2016-01-01

Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage. PMID:27347925

Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension.

PubMed

Muñoz-Durango, Natalia; Fuentes, Cristóbal A; Castillo, Andrés E; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E; Kalergis, Alexis M

2016-06-23

Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage.

ICAM-1 and AMPK regulate cell detachment and apoptosis by N-methyl-N Prime -nitro-N-nitrosoguanidine, a widely spread environmental chemical, in human hormone-refractory prostate cancers

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

Chen, Yi-Cheng; Lu, Pin-Hsuan; Hsu, Jui-Ling

2011-12-15

Poly(ADP-ribose) polymerase-1 (PARP-1), a sensor of DNA damage, plays a crucial role in the regulation of DNA repair. PARP-1 hyperactivation causes DNA damage and cell death. The underlying mechanism is complicated and is through diverse pathways. The understanding of responsible signaling pathways may offer implications for effective therapies. After concentration-response determination of N-Methyl-N Prime -Nitro-N-Nitrosoguanidine (MNNG, a PARP-1 activating agent and an environmental mutagen) in human hormone-refractory prostate cancers, the data showed that concentrations below 5 {mu}M did not change cell survival but cause a time-dependent up-regulation of intracellular adhesion molecule-1 (ICAM-1) in mRNA, total protein and cell surface levels.more » Detection of phosphorylation and degradation of I{kappa}B-{alpha} and nuclear translocation of NF-{kappa}B showed that MNNG induced the activation of NF-{kappa}B that was responsible for the ICAM-1 up-regulation since PDTC (a NF-{kappa}B inhibitor) significantly abolished this effect. However, higher concentrations (e.g., 10 {mu}M) of MNNG induced a 61% detachment of the cells which were apoptosis associated with the activation of AMP-activated protein kinase (AMPK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Further identification showed that both AMPK and JNK other than p38 MAPK functionally contributed to cell death. The remaining 39% attached cells were survival associated with high ICAM-1 expression. In conclusion, the data suggest that NF-{kappa}B-dependent up-regulation of ICAM-1 plays a key role on cell attachment and survival; whereas, activation of AMPK and JNK participates in cytotoxic signaling pathways in detached cells caused by PARP-1 activation. Highlights: Black-Right-Pointing-Pointer Low level of DNA damage helps cell attachment and survival via ICAM-1 upregulation. Black-Right-Pointing-Pointer High level of DNA damage causes AMPK- and JNK-involved cell detachment and death. Black-Right-Pointing-Pointer The study provides an anticancer approach targeting PARP-1 and DNA damage response.« less

Introduction to the focus section on the 2015 Gorkha, Nepal, earthquake

USGS Publications Warehouse

Hough, Susan E.

2015-01-01

It has long been recognized that Nepal faces high earthquake hazard, with the most recent large (Mw>7.5) events in 1833 and 1934. When the 25 April 2015Mw 7.8 Gorkha earthquake struck, it appeared initially to be a realization of worst fears. In spite of its large magnitude and proximity to the densely populated Kathmandu valley, however, the level of damage was lower than anticipated, with most vernacular structures within the valley experiencing little or no structural damage. Outside the valley, catastrophic damage did occur in some villages, associated with the high vulnerability of stone masonry construction and, in many cases, landsliding. The unexpected observations from this expected earthquake provide an urgent impetus to understand the event itself and to better characterize hazard from future large Himalayan earthquakes. Toward this end, articles in this special focus section present and describe available data sets and initial results that better illuminate and interpret the earthquake and its effects.

Radical Acceleration

ERIC Educational Resources Information Center

Gross, Miraca U. M.; Van Vliet, Helen E.

2005-01-01

Research has found that teachers' objections to accelerating gifted students are mainly based on a fear that acceleration will lead to social or emotional damage. Ironically, it is the academic and emotional maturity which characterizes intellectually gifted students, coupled with their high levels of academic achievement, which makes them such…

Tool enables proper mating of accelerometer and cable connector

NASA Technical Reports Server (NTRS)

Steed, C. N.

1966-01-01

Tool supports accelerometer in axial alignment with an accelerometer cable connector and permits tightening of the accelerometer to the cable connector with a torque wrench. This is done without damaging the components or permitting them to work loose under sustained, high-level vibrations.

Advances in automated nut sorting

USDA-ARS?s Scientific Manuscript database

Nuts in general, and tree nuts in particular, are a high value crop in many countries. Products with defects, contamination, insects or fungal damage can cause serious losses to producers, so almost all products are subjected to some level of sorting to remove these undesirable products. This chap...

Genetic compensation of high dose radiation-induced damage in an anhydrobiotic insect

NASA Astrophysics Data System (ADS)

Gusev, Oleg; Nakahara, Yuichi; Sakashita, Tetsuya; Kikawada, Takahiro; Okuda, Takashi

Anhydrobiotic larvae of African chironomid Polypedilum vanderplanki are known to show an extremely high tolerance against a range of stresses. The tolerance against various extreme environments exhibited by that insect might be due to being almost completely desiccated replacing water with trehalose, a state where little or no chemical reactions occur. From 2005 dried larvae of this insect are being used in a number of space experiments, both inside and outside of ISS as a model organism for estimation the limits of higher organisms' resistance to space environment stresses and long-term storage of the alive anhydrobiotic organisms during continues spaceflight. We have shown previously that both hydrated and dried larvae of Polypedilum vanderplanki have very higher tolerance against both highand low-linear energy transfer (LET), surviving after 7000Gy irradiation. It was suggested that the larvae would have effective DNA-reparation system in addition to artificial protection provided by glass-stage without water. In the present study we conducted analysis of stress-related gene expression in the larvae after 70-2000 Gy irradiations. Both DNA damage level and activity of DNA-reparation, anti-apoptotic and protein-damage related genes were analyzed. Direct visualization of DNA damage in the larvae fat body cells using Comet Assay showed that fragmented by radiation DNA is re-arranged within 76-98 hours after exposure. We found that massive overexpression of hsp and anti-oxidant genes occur in larvae entering anhydrobiosis , and provides refolding of proteins after rehydration. In the irradiated larvae overexpression of DNA-reparation enzymes anti-apoptotic genes was confirmed, suggesting that survival after high-dose irradiation is a result of combination of highly effective blocking of entering the apoptosis after severe DNA damage and DNA reparation.

Enhanced blood pressure variability in a high cardiovascular risk group of African Americans: FIT4Life Study.

PubMed

Veerabhadrappa, Praveen; Diaz, Keith M; Feairheller, Deborah L; Sturgeon, Kathleen M; Williamson, Sheara; Crabbe, Deborah L; Kashem, Abul; Ahrensfield, Debra; Brown, Michael D

2010-01-01

High blood pressure (BP) levels in African Americans elicit vascular inflammation resulting in vascular remodeling. BP variability (BPV) correlates with target organ damage. We aimed to investigate the relationship between inflammatory markers and BPV in African Americans. Thirty-six African Americans underwent 24-hour ambulatory BP monitoring (ABPM). BPV was calculated using the average real variability index. Fasting blood samples were assayed for high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-alpha), and white blood cell (WBC) count. Significant associations between hs-CRP and 24-hour systolic variability (r=0.50; P=.012) and awake systolic variability (r=0.45; P=.02) were identified after adjusting for age, body mass index, and 24-hour mean BP. ABPM variables were compared between the hs-CRP tertile groups. In post-hoc analysis, there was a significant difference in 24-hour and awake periods for both systolic and diastolic variability among the groups. TNF-alpha and WBC count showed no associations with ABPM variables. hs-CRP was associated with systolic variability, and higher levels of hs-CRP were related with greater BPV. Higher inflammatory status influences wider fluctuations in systolic BP, which in turn could facilitate early progression to target organ damage independent of absolute BP levels in African Americans.

Understanding the relationships between self-esteem, experiential avoidance, and paranoia: structural equation modelling and experience sampling studies.

PubMed

Udachina, Alisa; Thewissen, Viviane; Myin-Germeys, Inez; Fitzpatrick, Sam; O'kane, Aisling; Bentall, Richard P

2009-09-01

Hypothesized relationships between experiential avoidance (EA), self-esteem, and paranoia were tested using structural equation modeling in a sample of student participants (N = 427). EA in everyday life was also investigated using the Experience Sampling Method in a subsample of students scoring high (N = 17) and low (N = 15) on paranoia. Results showed that paranoid students had lower self-esteem and reported higher levels of EA than nonparanoid participants. The interactive influence of EA and stress predicted negative self-esteem: EA was particularly damaging at high levels of stress. Greater EA and higher social stress independently predicted lower positive self-esteem. Low positive self-esteem predicted engagement in EA. A direct association between EA and paranoia was also found. These results suggest that similar mechanisms may underlie EA and thought suppression. Although people may employ EA to regulate self-esteem, this strategy is maladaptive as it damages self-esteem, incurs cognitive costs, and fosters paranoid thinking.

Stress assessment and spectral characterization of suspected acid deposition damage in red spruce (Picea Rubens) from Vermont

NASA Technical Reports Server (NTRS)

Rock, B. N.; Vogelmann, J. E.

1985-01-01

The effects of acid deposition on Picea rubens are studied. The Picea rubens located at Camels Hump Mt., Mt. Ascutney, and Ripton, VT were analyzed using stress level evaluations, in situ spectral data, pressure bomb analysis, and aircraft sensors. Spruce stress per circular plot and percent spruce mortality are calculated. The relation between stress levels and elevation and exposure and weather patterns is examined. It is observed that variations in the reflectance curves of the foliage and branches are related to cellular health, the type of cellular arrangement, and the degree of leaf tissue hydration; the leaf and twig specimens from high stress sites are more reflective in the red portion of the visible and less reflective in the NIR portion of the spectrum. The pressure bomb data reveal that the xylem water tension is higher in specimens from high stress sites. It is noted that remote sensing permits discrimination and mapping of suspected acid deposition damage.

The influence of Bauhinia forficata Link subsp. pruinosa tea on lipid peroxidation and non-protein SH groups in human erythrocytes exposed to high glucose concentrations.

PubMed

Salgueiro, Andréia C F; Leal, Carina Q; Bianchini, Matheus C; Prado, Ianeli O; Mendez, Andreas S L; Puntel, Robson L; Folmer, Vanderlei; Soares, Félix A; Avila, Daiana S; Puntel, Gustavo O

2013-06-21

Bauhinia forficata (BF) has been traditionally used as tea in folk medicine of Brazil for treatment of Diabetes mellitus (DM). To evaluate the effects of BF leaf tea on markers of oxidative damage and antioxidant levels in an experimental model of hyperglycemia in human erythrocytes in vitro. Human erythrocytes were incubated with high glucose concentrations or glucose and BF tea for 24h and 48h. After incubation lipid peroxidation and non-protein SH levels were analyzed. Moreover, quantification of polyphenols and flavonoids, iron chelating property, scavenging of DPPH, and prevention of lipid peroxidation in isolated lipids were also assessed. A significant amount of polyphenols and flavonoids was observed. The main components found by LC-MS analysis were quercetin-3-O-(2-rhamnosyl) rutinoside, kaempferol-3-O-(2-rhamnosyl) rutinoside, quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside. BF tea presents important antioxidant and chelating properties. Moreover, BF tea was effective to increase non-protein SH levels and reduce lipid peroxidation induced by high glucose concentrations in human erythrocytes. The antioxidant effects of BF tea could be related to the presence of different phenolic and flavonoids components. We believe that these components can be responsible to protect human erythrocytes exposed to high glucose concentrations against oxidative damage. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Modeling Space Radiation with Radiomimetic Agent Bleomycin

NASA Technical Reports Server (NTRS)

Lu, Tao

2017-01-01

Space radiation consists of proton and helium from solar particle events (SPE) and high energy heavy ions from galactic cosmic ray (GCR). This mixture of radiation with particles at different energy levels has different effects on biological systems. Currently, majority studies of radiation effects on human were based on single-source radiation due to the limitation of available method to model effects of space radiation on living organisms. While NASA Space Radiation Laboratory is working on advanced switches to make it possible to have a mixed field radiation with particles of different energies, the radiation source will be limited. Development of an easily available experimental model for studying effects of mixed field radiation could greatly speed up our progress in our understanding the molecular mechanisms of damage and responses from exposure to space radiation, and facilitate the discovery of protection and countermeasures against space radiation, which is critical for the mission to Mars. Bleomycin, a radiomimetic agent, has been widely used to study radiation induced DNA damage and cellular responses. Previously, bleomycin was often compared to low low Linear Energy Transfer (LET) gamma radiation without defined characteristics. Our recent work demonstrated that bleomycin could induce complex clustered DNA damage in human fibroblasts that is similar to DNA damage induced by high LET radiation. These type of DNA damage is difficult to repair and can be visualized by gamma-H2Ax staining weeks after the initial insult. The survival ratio between early and late plating of human fibroblasts after bleomycin treatment is between low LET and high LET radiation. Our results suggest that bleomycin induces DNA damage and other cellular stresses resembling those resulted from mixed field radiation with both low and high LET particles. We hypothesize that bleomycin could be used to mimic space radiation in biological systems. Potential advantages and limitations of using bleomycin to treat biological specimen as an easily available model to study effects of space radiation on biological systems and to develop countermeasures for space radiation associated risks will be discussed.

DNA damage checkpoint kinase ATM regulates germination and maintains genome stability in seeds

PubMed Central

Waterworth, Wanda M.; Footitt, Steven; Bray, Clifford M.; Finch-Savage, William E.; West, Christopher E.

2016-01-01

Genome integrity is crucial for cellular survival and the faithful transmission of genetic information. The eukaryotic cellular response to DNA damage is orchestrated by the DNA damage checkpoint kinases ATAXIA TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR). Here we identify important physiological roles for these sensor kinases in control of seed germination. We demonstrate that double-strand breaks (DSBs) are rate-limiting for germination. We identify that desiccation tolerant seeds exhibit a striking transcriptional DSB damage response during germination, indicative of high levels of genotoxic stress, which is induced following maturation drying and quiescence. Mutant atr and atm seeds are highly resistant to aging, establishing ATM and ATR as determinants of seed viability. In response to aging, ATM delays germination, whereas atm mutant seeds germinate with extensive chromosomal abnormalities. This identifies ATM as a major factor that controls germination in aged seeds, integrating progression through germination with surveillance of genome integrity. Mechanistically, ATM functions through control of DNA replication in imbibing seeds. ATM signaling is mediated by transcriptional control of the cell cycle inhibitor SIAMESE-RELATED 5, an essential factor required for the aging-induced delay to germination. In the soil seed bank, seeds exhibit increased transcript levels of ATM and ATR, with changes in dormancy and germination potential modulated by environmental signals, including temperature and soil moisture. Collectively, our findings reveal physiological functions for these sensor kinases in linking genome integrity to germination, thereby influencing seed quality, crucial for plant survival in the natural environment and sustainable crop production. PMID:27503884

XPF expression correlates with clinical outcome in squamous cell carcinoma of the head and neck

PubMed Central

Vaezi, Alec; Wang, XiaoZhe; Buch, Shama; Gooding, William; Wang, Lin; Seethala, Raja R.; Weaver, David T.; D’Andrea, Alan D.; Argiris, Athanassios; Romkes, Marjorie; Niedernhofer, Laura J.; Grandis, Jennifer R.

2011-01-01

Purpose Tumor-specific biomarkers that predict resistance to DNA damaging agents may improve therapeutic outcomes by guiding the selection of effective therapies and limiting morbidity related to ineffective approaches. XPF (ERCC4) is an essential component of several DNA repair pathways and XPF-deficient cells are exquisitely sensitive to DNA damaging agents. The purpose of this study was to determine whether XPF expression levels predict clinical response to DNA damaging agents in head and neck squamous cell carcinoma (HNSCC). Experimental Design Quantitative immunohistochemistry was used to measure XPF expression in tumors from a cohort of 80 patients with newly diagnosed HNSCC treated with radiation therapy with or without platinum-based chemotherapy; samples were collected prospectively. Genomic DNA isolated from blood samples was analyzed for nine single nucleotide polymorphisms in the XPF gene using a custom array. The primary endpoint was progression-free survival (PFS). Results XPF expression was higher in tumors from the oral cavity than from the other sites (p<0.01). High XPF expression correlated with early time to progression both by univariate (HR =1.87, p=0.03) and multivariate analysis (HR =1.83, p=0.05). The one year PFS for high expressers was 47% (95% CI = 31% – 62%) compared to 72% (95% CI = 55% – 83%) for low expressers. In addition, we identified four XPF single nucleotide polymorphisms (SNPs) that demonstrated marginal association with treatment failure. Conclusions Expression level of XPF in HNSCC tumors correlates with clinical response to DNA damaging agents. XPF has potential to guide next-generation personalized cancer therapy. PMID:21737503

DNA damage checkpoint kinase ATM regulates germination and maintains genome stability in seeds.

PubMed

Waterworth, Wanda M; Footitt, Steven; Bray, Clifford M; Finch-Savage, William E; West, Christopher E

2016-08-23

Genome integrity is crucial for cellular survival and the faithful transmission of genetic information. The eukaryotic cellular response to DNA damage is orchestrated by the DNA damage checkpoint kinases ATAXIA TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR). Here we identify important physiological roles for these sensor kinases in control of seed germination. We demonstrate that double-strand breaks (DSBs) are rate-limiting for germination. We identify that desiccation tolerant seeds exhibit a striking transcriptional DSB damage response during germination, indicative of high levels of genotoxic stress, which is induced following maturation drying and quiescence. Mutant atr and atm seeds are highly resistant to aging, establishing ATM and ATR as determinants of seed viability. In response to aging, ATM delays germination, whereas atm mutant seeds germinate with extensive chromosomal abnormalities. This identifies ATM as a major factor that controls germination in aged seeds, integrating progression through germination with surveillance of genome integrity. Mechanistically, ATM functions through control of DNA replication in imbibing seeds. ATM signaling is mediated by transcriptional control of the cell cycle inhibitor SIAMESE-RELATED 5, an essential factor required for the aging-induced delay to germination. In the soil seed bank, seeds exhibit increased transcript levels of ATM and ATR, with changes in dormancy and germination potential modulated by environmental signals, including temperature and soil moisture. Collectively, our findings reveal physiological functions for these sensor kinases in linking genome integrity to germination, thereby influencing seed quality, crucial for plant survival in the natural environment and sustainable crop production.

Insect detection and nitrogen management for irrigated potatoes using remote sensing from small unmanned aircraft systems

NASA Astrophysics Data System (ADS)

Hunt, E. Raymond; Rondon, Silvia I.; Hamm, Philip B.; Turner, Robert W.; Bruce, Alan E.; Brungardt, Josh J.

2016-05-01

Remote sensing with small unmanned aircraft systems (sUAS) has potential applications in agriculture because low flight altitudes allow image acquisition at very high spatial resolution. We set up experiments at the Oregon State University Hermiston Agricultural Research and Extension Center with different platforms and sensors to assess advantages and disadvantages of sUAS for precision farming. In 2013, we conducted an experiment with 4 levels of N fertilizer, and followed the changes in the normalized difference vegetation index (NDVI) over time. In late June, there were no differences in chlorophyll content or leaf area index (LAI) among the 3 higher application rates. Consistent with the field data, only plots with the lowest rate of applied N were distinguished by low NDVI. In early August, N deficiency was determined by NDVI, but it was too late to mitigate losses in potato yield and quality. Populations of the Colorado potato beetle (CPB) may rapidly increase, devouring the shoots, thus early detection and treatment could prevent yield losses. In 2014, we conducted an experiment with 4 levels of CPB infestation. Over one day, damage from CPB in some plots increased from 0 to 19%. A visual ranking of damage was not correlated with the total number of CPB or treatment. Plot-scale vegetation indices were not correlated with damage, although the damaged area determined by object-based feature extraction was highly correlated. Methods based on object-based image analysis of sUAS data have potential for early detection and reduced cost.

Acute coagulopathy of trauma: balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation.

PubMed

Johansson, P I; Ostrowski, S R

2010-12-01

Acute coagulopathy of trauma predicts a poor clinical outcome. Tissue trauma activates the sympathoadrenal system resulting in high circulating levels of catecholamines that influence hemostasis dose-dependently through immediate effects on the two major compartments of hemostasis, i.e., the circulating blood and the vascular endothelium. There appears to be a dose-dependency with regards to injury severity and the hemostatic response to trauma evaluated in whole blood by viscoelastic assays like thrombelastography (TEG), changing from normal to hypercoagulable, to hypocoagulable and finally hyperfibrinolytic in severely injured patients. Since high catecholamine levels may directly damage the endothelium and thereby promote systemic coagulation activation, we hypothesize that the progressive hypocoagulability and ultimate hyperfibrinolysis observed in whole blood with increasing injury severity, is an evolutionary developed response that counterbalances the injury and catecholamine induced endothelial activation and damage. Given this, the rise in circulating catecholamines in trauma patients may favor a switch from hyper- to hypocoagulability in the blood to keep the progressively more procoagulant microvasculature open. The hypothesis delineated in the present paper thus infers that the state of the fluid phase, including its cellular elements, is a consequence of the degree of the tissue injury and importantly, critically related to the degree of endothelial damage, with a progressively more procoagulant endothelium inducing a gradient of increasing anticoagulation towards the fluid phase. The implications of this hypothesis may include targeted treatment strategies according to the degree of sympathoadrenal response as evaluated by whole blood viscoelastical hemostatic assays in trauma patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

ERCC2/XPD Lys751Gln alter DNA repair efficiency of platinum-induced DNA damage through P53 pathway.

PubMed

Zhang, Guopei; Guan, Yangyang; Zhao, Yuejiao; van der Straaten, Tahar; Xiao, Sha; Xue, Ping; Zhu, Guolian; Liu, Qiufang; Cai, Yuan; Jin, Cuihong; Yang, Jinghua; Wu, Shengwen; Lu, Xiaobo

2017-02-01

Platinum-based treatment causes Pt-DNA adducts which lead to cell death. The platinum-induced DNA damage is recognized and repaired by the nucleotide excision repair (NER) system of which ERCC2/XPD is a critical enzyme. Single nucleotide polymorphisms in ERCC2/XPD have been found to be associated with platinum resistance. The aim of the present study was to investigate whether ERCC2/XPD Lys751Gln (rs13181) polymorphism is causally related to DNA repair capacity of platinum-induced DNA damage. First, cDNA clones expressing different genotypes of the polymorphism was transfected to an ERCC2/XPD defective CHO cell line (UV5). Second, all cells were treated with cisplatin. Cellular survival rate were investigated by MTT growth inhibition assay, DNA damage levels were investigated by comet assay and RAD51 staining. The distribution of cell cycle and the change of apoptosis rates were detected by a flow cytometric method (FCM). Finally, P53mRNA and phospho-P53 protein levels were further investigated in order to explore a possible explanation. As expected, there was a significantly increased in viability of UV5 ERCC2 (AA) as compared to UV5 ERCC2 (CC) after cisplatin treatment. The DNA damage level of UV5 ERCC2 (AA) was significant decreased compared to UV5 ERCC2 (CC) at 24 h of treatment. Mutation of ERCC2rs13181 AA to CC causes a prolonged S phase in cell cycle. UV5 ERCC2 (AA) alleviated the apoptosis compared to UV5 ERCC2 (CC) , meanwhile P53mRNA levels in UV ERCC2 (AA) was also lower when compared UV5 ERCC2 (CC) . It co-incides with a prolonged high expression of phospho-P53, which is relevant for cell cycle regulation, apoptosis, and the DNA damage response (DDR). We concluded that ERCC2/XPD rs13181 polymorphism is possibly related to the DNA repair capacity of platinum-induced DNA damage. This functional study provides some clues to clarify the relationship between cisplatin resistance and ERCC2/XPDrs13181 polymorphism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of lanthanum(III) on nitrogen metabolism of soybean seedlings under elevated UV-B radiation.

PubMed

Cao, Rui; Huang, Xiao-hua; Zhou, Qing; Cheng, Xiao-ying

2007-01-01

The hydroponic culture experiments of soybean bean seedlings were conducted to investigate the effect of lanthanum (La) on nitrogen metabolism under two different levels of elevated UV-B radiation (UV-B, 280-320 nm). The whole process of nitrogen metabolism involves uptake and transport of nitrate, nitrate assimilation, ammonium assimilation, amino acid biosynthesis, and protein synthesis. Compared with the control, UV-B radiation with the intensity of low level 0.15 W/m2 and high level 0.45 W/m2 significantly affected the whole nitrogen metabolism in soybean seedlings (p < 0.05). It restricted uptake and transport of NO3(-), inhibited activity of some key nitrogen-metabolism-related enzymes, such as: nitrate reductase (NR) to the nitrate reduction, glutamine systhetase (GS) and glutamine synthase (GOGAT) to the ammonia assimilation, while it increased the content of free amino acids and decreased that of soluble protein as well. The damage effect of high level of UV-B radiation on nitrogen metabolism was greater than that of low level. And UV-B radiation promoted the activity of the anti-adversity enzyme glutamate dehydrogenase (GDH), which reduced the toxicity of excess ammonia in plant. After pretreatment with the optimum concentration of La (20 mg/L), La could increase the activity of NR, GS, GOGAT, and GDH, and ammonia assimilation, but decrease nitrate and ammonia accumulation. In conclusion, La could relieve the damage effect of UV-B radiation on plant by regulating nitrogen metabolism process, and its alleviating effect under low level was better than that under the high one.

Damage Assessment of Composite Structures Using Digital Image Correlation

NASA Astrophysics Data System (ADS)

Caminero, M. A.; Lopez-Pedrosa, M.; Pinna, C.; Soutis, C.

2014-02-01

The steady increase of Carbon-Fiber Reinforced Polymer (CFRP) Structures in modern aircraft will reach a new dimension with the entry into service of the Boeing 787 and Airbus 350. Replacement of damaged parts will not be a preferable solution due to the high level of integration and the large size of the components involved. Consequently the need to develop repair techniques and processes for composite components is readily apparent. Bonded patch repair technologies provide an alternative to mechanically fastened repairs with significantly higher performance, especially for relatively thin skins. Carefully designed adhesively bonded patches can lead to cost effective and highly efficient repairs in comparison with conventional riveted patch repairs that cut fibers and introduce highly strained regions. In this work, the assessment of the damage process taking place in notched (open-hole) specimens under uniaxial tensile loading was studied. Two-dimensional (2D) and three-dimensional (3D) Digital Image Correlation (DIC) techniques were employed to obtain full-field surface strain measurements in carbon-fiber/epoxy T700/M21 composite plates with different stacking sequences in the presence of an open circular hole. Penetrant enhanced X-ray radiographs were taken to identify damage location and extent after loading around the hole. DIC strain fields were compared to finite element predictions. In addition, DIC techniques were used to characterise damage and performance of adhesively bonded patch repairs in composite panels under tensile loading. This part of work relates to strength/stiffness restoration of damaged composite aircraft that becomes more important as composites are used more extensively in the construction of modern jet airliners. The behaviour of bonded patches under loading was monitored using DIC full-field strain measurements. Location and extent of damage identified by X-ray radiography correlates well with DIC strain results giving confidence to the technique for structural health monitoring of bonded patches.

Normobaric Hyperoxia Reduces Blood Occludin Fragments in Rats and Patients With Acute Ischemic Stroke.

PubMed

Shi, Shuhai; Qi, Zhifeng; Ma, Qingfeng; Pan, Rong; Timmins, Graham S; Zhao, Yongmei; Shi, Wenjuan; Zhang, Yunzhou; Ji, Xunming; Liu, Ke Jian

2017-10-01

Damage of the blood-brain barrier (BBB) increases the incidence of neurovascular complications, especially for cerebral hemorrhage after tPA (tissue-type plasminogen activator) therapy. Currently, there is no effective method to evaluate the extent of BBB damage to guide tPA use. Herein, we investigated whether blood levels of tight junction proteins could serve as biomarker of BBB damages in acute ischemic stroke (AIS) in both rats and patients. We examined whether this biomarker could reflect the extent of BBB permeability during cerebral ischemia/reperfusion and the effects of normobaric hyperoxia (NBO) on BBB damage. Rats were exposed to NBO (100% O 2 ) or normoxia (21% O 2 ) during middle cerebral artery occlusion. BBB permeability was determined. Occludin and claudin-5 in blood and cerebromicrovessels were measured. Patients with AIS were assigned to oxygen therapy or room air for 4 hours, and blood occludin and claudin-5 were measured at different time points after stroke. Cerebral ischemia/reperfusion resulted in the degradation of occludin and claudin-5 in microvessels, leading to increased BBB permeability in rats. In blood samples, occludin increased with 4-hour ischemia and remained elevated during reperfusion, correlating well with its loss from ischemic cerebral microvessels. NBO treatment both prevented occludin degradation in microvessels and reduced occludin levels in blood, leading to improved neurological functions in rats. In patients with AIS receiving intravenous tPA thrombolysis, the blood occludin was already elevated when patients arrived at hospital (within 4.5 hours since symptoms appeared) and remained at a high level for 72 hours. NBO significantly lowered the level of blood occludin and improved neurological functions in patients with AIS. Blood occludin may be a clinically viable biomarker for evaluating BBB damage during ischemia/reperfusion. NBO therapy has the potential to reduce blood occludin, protect BBB, and improve outcome in AIS patients with intravenous tPA thrombolysis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02974283. © 2017 American Heart Association, Inc.

Telomere elongation protects heart and lung tissue cells from fatal damage in rats exposed to severe hypoxia.

PubMed

Wang, Yaping; Zhao, Zhen; Zhu, Zhiyong; Li, Pingying; Li, Xiaolin; Xue, Xiaohong; Duo, Jie; Ma, Yingcai

2018-02-17

The effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. This study aimed to investigate the change in telomere length of rat heart and lung tissue cells in response to acute exposure to severe hypoxia and its role in hypoxia-induced damage to heart and lung tissues. Forty male Wistar rats (6-week old) were randomized into control group (n = 10) and hypoxia group (n = 30). Rats in control group were kept at an altitude of 1500 m, while rats in hypoxia group were exposed to simulated hypoxia with an altitude of 5000 m in a low-pressure oxygen chamber for 1, 3, and 7 days (n = 10). The left ventricular and right middle lobe tissues of each rat were collected for measurement of telomere length and reactive oxygen species (ROS) content, and the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor1α (HIF-1α), and hypoxia-inducible factor1α (HIF-2α). Increased exposure to hypoxia damaged rat heart and lung tissue cells and increased ROS production and telomere length. The mRNA and protein levels of TERT and HIF-1α were significantly higher in rats exposed to hypoxia and increased with prolonged exposure; mRNA and protein levels of HIF-2α increased only in rats exposed to hypoxia for 7 days. TERT was positively correlated with telomere length and the levels of HIF-1α but not HIF-2α. Acute exposure to severe hypoxia causes damage to heart and lung tissues due to the production of ROS but promotes telomere length and adaptive response by upregulating TERT and HIF-1α, which protect heart and lung tissue cells from fatal damage.

Berberine attenuates oxidative stress and hepatocytes apoptosis via protecting mitochondria in blunt snout bream Megalobrama amblycephala fed high-fat diets.

PubMed

Lu, Kang-Le; Wang, Li-Na; Zhang, Ding-Dong; Liu, Wen-Bin; Xu, Wei-Na

2017-02-01

High-fat diets may have favorable effects on growth and cost, but high-fat diets often induce excessive fat deposition, resulting in liver damage. This study aimed to identify the hepatoprotective of a Chinese herb (berberine) for blunt snout bream (Megalobrama amblycephala). Fish were fed with a normal diet (LFD, 5 % fat), high-fat diet (HFD, 15 % fat) or berberine-supplemented diets (BSD, 15 % fat with berberine 50 or 100 mg/kg level) for 8 weeks. After the feeding, histology, oxidative status and mitochondrial function of liver were assessed. The results showed that HFD caused fat accumulation, oxidative stress and apoptosis in hepatocytes of fish. Hepatocytes in HFD group appeared to be hypertrophied, with larger liver cells diameter than these of LFD group. Berberine-supplemented diets could attenuate oxidative stress and hepatocytes apoptosis. HFD induced the decreasing mitochondrial complexes activities and bulk density and surface area density. Berberine improved function of mitochondrial respiratory chain via increasing the complex activities. Moreover, the histological results showed that berberine has the potential to repair mitochondrial ultrastructural damage and elevate the density in cells. In conclusion, our study demonstrated that berberine has attenuated liver damage induced by the high fat mainly via the protection for mitochondria.

Baseline frequency of chromosomal aberrations and sister chromatid exchanges in peripheral blood lymphocytes of healthy individuals living in Turin (North-Western Italy): assessment of the effects of age, sex and GSTs gene polymorphisms on the levels of genomic damage.

PubMed

Santovito, Alfredo; Cervella, Piero; Delpero, Massimiliano

2016-05-01

The increased exposure to environmental pollutants has led to the awareness of the necessity for constant monitoring of human populations, especially those living in urban areas. This study evaluated the background levels of genomic damage in a sample of healthy subjects living in the urban area of Turin (Italy). The association between DNA damage with age, sex and GSTs polymorphisms was assessed. One hundred and one individuals were randomly sampled. Sister Chromatid Exchanges (SCEs) and Chromosomal Aberrations (CAs) assays, as well as genotyping of GSTT1 and GSTM1 genes, were performed. Mean values of SCEs and CAs were 5.137 ± 0.166 and 0.018 ± 0.002, respectively. Results showed age and gender associated with higher frequencies of these two cytogenetic markers. The eldest subjects (51-65 years) showed significantly higher levels of genomic damage than younger individuals. GSTs polymorphisms did not appear to significantly influence the frequencies of either markers. The CAs background frequency observed in this study is one of the highest reported among European populations. Turin is one of the most polluted cities in Europe in terms of air fine PM10 and ozone and the clastogenic potential of these pollutants may explain the high frequencies of chromosomal rearrangements reported here.

S100A8/A9 as a biomarker for synovial inflammation and joint damage in patients with rheumatoid arthritis.

PubMed

Kang, Kwi Young; Woo, Jung-Won; Park, Sung-Hwan

2014-01-01

S100A8 and S100A9 are major leukocyte proteins, known as damage-associated molecular patterns, found at high concentrations in the synovial fluid of patients with rheumatoid arthritis (RA). A heterodimeric complex of S100A8/A9 is secreted by activated leukocytes and binds to Toll-like receptor 4, which mediates downstream signaling and promotes inflammation and autoimmunity. Serum and synovial fluid levels of S100A8/A9 are markedly higher in patients with RA than in patients with osteoarthritis or miscellaneous inflammatory arthritis. Serum levels of S100A8/A9 are significantly correlated with clinical and laboratory markers of inflammation, such as C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and the Disease Activity Score for 28 joints. Significant correlations have also been found between S100A8/A9 and radiographic and clinical assessments of joint damage, such as hand radiographs and the Rheumatoid Arthritis Articular Damage score. In addition, among known inflammatory markers, S100A8/A9 has the strongest correlation with total sum scores of ultrasonography assessment. Furthermore, baseline levels of S100A8/A9 are independently associated with progression of joint destruction in longitudinal studies and are responsive to change during conventional and biologic treatments. These findings suggest S100A8/A9 to be a valuable diagnostic and prognostic biomarker for RA.

Nuclear accumulation and activation of p53 in embryonic stem cells after DNA damage.

PubMed

Solozobova, Valeriya; Rolletschek, Alexandra; Blattner, Christine

2009-06-17

P53 is a key tumor suppressor protein. In response to DNA damage, p53 accumulates to high levels in differentiated cells and activates target genes that initiate cell cycle arrest and apoptosis. Since stem cells provide the proliferative cell pool within organisms, an efficient DNA damage response is crucial. In proliferating embryonic stem cells, p53 is localized predominantly in the cytoplasm. DNA damage-induced nuclear accumulation of p53 in embryonic stem cells activates transcription of the target genes mdm2, p21, puma and noxa. We observed bi-phasic kinetics for nuclear accumulation of p53 after ionizing radiation. During the first wave of nuclear accumulation, p53 levels were increased and the p53 target genes mdm2, p21 and puma were transcribed. Transcription of noxa correlated with the second wave of nuclear accumulation. Transcriptional activation of p53 target genes resulted in an increased amount of proteins with the exception of p21. While p21 transcripts were efficiently translated in 3T3 cells, we failed to see an increase in p21 protein levels after IR in embryonal stem cells. In embryonic stem cells where (anti-proliferative) p53 activity is not necessary, or even unfavorable, p53 is retained in the cytoplasm and prevented from activating its target genes. However, if its activity is beneficial or required, p53 is allowed to accumulate in the nucleus and activates its target genes, even in embryonic stem cells.

Probing the cellular damage in bacteria induced by GaN nanoparticles using confocal laser Raman spectroscopy

NASA Astrophysics Data System (ADS)

Sahoo, Prasana; Murthy, P. Sriyutha; Dhara, S.; Venugopalan, V. P.; Das, A.; Tyagi, A. K.

2013-08-01

Understanding the mechanism of nanoparticle (NP) induced toxicity in microbes is of potential importance to a variety of disciplines including disease diagnostics, biomedical implants, and environmental analysis. In this context, toxicity to bacterial cells and inhibition of biofilm formation by GaN NPs and their functional derivatives have been investigated against gram positive and gram negative bacterial species down to single cellular level. High levels of inhibition of biofilm formation (>80 %) was observed on treatments with GaN NPs at sub-micro molar concentrations. These results were substantiated with morphological features investigated with field emission scanning electron microscope, and the observed changes in vibrational modes of microbial cells using Raman spectroscopy. Raman spectra provided molecular interpretation of cell damage by registering signatures of molecular vibrations of individual living microbial cells and mapping the interplay of proteins at the cell membrane. As compared to the untreated cells, Raman spectra of NP-treated cells showed an increase in the intensities of characteristic protein bands, which confirmed membrane damage and subsequent release of cellular contents outside the cells. Raman spectral mapping at single cellular level can facilitate understanding of the mechanistic aspect of toxicity of GaN NPs. The effect may be correlated to passive diffusion causing mechanical damage to the membrane or ingress of Ga3+ (ionic radius 0.076 nm) which can potentially interfere with bacterial metabolism, as it resembles Fe2+ (ionic radius 0.077 nm), which is essential for energy metabolism.

Methodology of Historical Flood Evaluation from Korean Historical Documents during AD 1392 to 1910

NASA Astrophysics Data System (ADS)

Cho, H. B.; Kim, H.; Noh, S.; Jang, C.

2007-12-01

Study on extreme flood events has critical limitation of shortage of historical data because modern systematic data don't implement long time series. The historical documentary records hence can be one of the important sources to contribute additional information on extreme flood events which had occurred before the instrumental observations began. For the proper data mining, documentary records satisfying following four conditions are preferred. 1. Long enough time series, 2. Official archives covering over all Korean peninsular, 3. Abundant enough record number, and 4. Detailed damage description. The Annals of Choson Dynasty includes about 500 years and 511 number of flood records during Choson Dynasty in ancient Korea. According to the annals, there were highly dense flood damage records in the middle of 17th century and the largest human damage and residence damage occurred in 1739 and 1856 respectively. Another source is Jeungbo-Munheonbigo. Jeungbo-Munheonbigo is a taxonomic document categorized by the themes such as cultures, social systems, and climates as well as contains 79 number of flood damage records. An effective way to analyze those historical floods without water level data is to classify and categorize the flood damage records because all records are written in descriptive way. Consequently, 556 records are categorized into 10 items by flood damage types and each categorized record is classified into three grades by numerical level that is how much the record is expressed in numerical way. These grouping results are applied to decide reasonable period range to get detailed information from entire inspection period. In addition, Historical Flood Evaluation Index (HFEI) thereby can be derived from the processes in quantitative and statistical ways to evaluate the magnitude of each ancient flood. In this research, flood damage evaluation is mainly focused on the damage of human beings and residences. Also degree ranges based on cumulative probability are induced with two damage inventory. HFEI by conditional weighted factors is applied to every flood record and to analysis for flood distribution in annual series.

Characterization of γ-aminobutyric acid metabolism and oxidative damage in wheat (Triticum aestivum L.) seedlings under salt and osmotic stress.

PubMed

Al-Quraan, Nisreen A; Sartawe, Fatima Al-Batool; Qaryouti, Muien M

2013-07-15

The molecular response of plants to abiotic stresses has been considered a process mainly involved in the modulation of transcriptional activity of stress-related genes. Nevertheless, recent findings have suggested new layers of regulation and complexity. Upstream molecular mechanisms are involved in the plant response to abiotic stress. Plants gain resistance to abiotic stress by reprogramming metabolism and gene expression. GABA is proposed to be a signaling molecule involved in nitrogen metabolism, regulating the cytosolic pH, and protection against oxidative damage in response to various abiotic stresses. The aim of our study was to examine the role of the GABA shunt pathway-specific response in five wheat (Triticum aestivum L.) cultivars (Hurani 75, Sham I, Acsad 65, Um Qayes and Nodsieh) to salt and osmotic stress in terms of seed germination, seedling growth, oxidative damage (malondialdehyde (MDA) accumulation), and characterization of the glutamate decarboxylse gene (GAD) m-RNA level were determined using RT-PCR techniques. Our data showed a marked increase in GABA, MDA and GAD m-RNA levels under salt and osmotic stress in the five wheat cultivars. Um Qayes cultivar showed the highest germination percentage, GABA accumulation, and MDA level under salt and osmotic stresses. The marked increase in GAD gene expression explains the high accumulation of the GABA level under both stresses. Our results indicated that the GABA shunt is a key signaling and metabolic pathway that allows wheat to adapt to salt and osmotic stress. Based on our data, the Um Qayes wheat cultivar is the cultivar most recommended to be grown in soil with high salt and osmotic contents. Copyright © 2013 Elsevier GmbH. All rights reserved.

[Eyeball structure changes in high myopic patients and their significance for forensic assessment].

PubMed

Liu, Yi-Chang; Xia, Wen-Tao; Zhou, Xing-Tao; Liu, Rui-Jue; Bian, Shi-Zhong; Ying, Chong-Liang; Zhu, Guang-You

2008-10-01

There are irreversible eyeball structural changes in high myopic patients. These changes include axial length, corneal radius, anterior chamber depth, fundus degeneration, macula thickness, etc. There is a close relationship between the damage degree of visual function and these changes. The incidence of complications, such as vitreous opacity, posterior vitreous detachment, cataract, glaucoma, posterior staphyloma and retina detachment, is also highly related to the myopia diopter. More and more researches have indicated that the myopia diopter and the level of visual function are affected by multiple factors. It is promising to detect all of these changes by different kinds of methods, and to assess visual function through these changes. By clarifying these changes, it is also useful to distinguish traumatic damage from disease to provide evidence for forensic assessment of eye injuries.

Fabrication of spherical mitigation pit on KH2PO4 crystal by micro-milling and modeling of its induced light intensification.

PubMed

Cheng, Jian; Chen, Mingjun; Liao, Wei; Wang, Haijun; Xiao, Yong; Li, Mingquan

2013-07-15

Micro-machining is the most promising method for KH(2)PO(4) crystal to mitigate the surface damage growth in high power laser system. In this work, spherical mitigation pit is fabricated by micro-milling with an efficient machining procedure. The light intensification caused by rear surface features before and after mitigation is numerically modeled based on the finite-difference time-domain method. The results indicate that the occurrence of total internal reflections should be responsible for the largest light intensification inside the crystal. For spherical pits after mitigation, the light intensification can be greatly alleviated by preventing the occurrence of total internal reflections. The light intensification caused by spherical mitigation pit is strongly dependent on the width-depth ratio and it is suggested that the width-depth ratio of spherical mitigation pit must be devised to be larger than 5.0 to achieve the minimal light intensification for the mitigation of surface damage growth. Laser damage tests for KH(2)PO(4) crystal validate that the laser damage resistance of initially damaged surface can be retrieved to near the level of ideal surface by replacing initial damage site with predesigned mitigation pit.

Oxidative stress damages rRNA inside the ribosome and differentially affects the catalytic center

PubMed Central

Willi, Jessica; Küpfer, Pascal; Evéquoz, Damien; Fernandez, Guillermo; Polacek, Norbert

2018-01-01

Abstract Intracellular levels of reactive oxygen species (ROS) increase as a consequence of oxidative stress and represent a major source of damage to biomolecules. Due to its high cellular abundance RNA is more frequently the target for oxidative damage than DNA. Nevertheless the functional consequences of damage on stable RNA are poorly understood. Using a genome-wide approach, based on 8-oxo-guanosine immunoprecipitation, we present evidence that the most abundant non-coding RNA in a cell, the ribosomal RNA (rRNA), is target for oxidative nucleobase damage by ROS. Subjecting ribosomes to oxidative stress, we demonstrate that oxidized 23S rRNA inhibits the ribosome during protein biosynthesis. Placing single oxidized nucleobases at specific position within the ribosome's catalytic center by atomic mutagenesis resulted in markedly different functional outcomes. While some active site nucleobases tolerated oxidative damage well, oxidation at others had detrimental effects on protein synthesis by inhibiting different sub-steps of the ribosomal elongation cycle. Our data provide molecular insight into the biological consequences of RNA oxidation in one of the most central cellular enzymes and reveal mechanistic insight on the role of individual active site nucleobases during translation. PMID:29309687

Laser-induced damage threshold tests of ultrafast multilayer dielectric coatings in various environmental conditions relevant for operation of ELI beamlines laser systems

NASA Astrophysics Data System (ADS)

Ďurák, Michal; Velpula, Praveen Kumar; Kramer, Daniel; Cupal, Josef; Medřík, Tomáš; Hřebíček, Jan; Golasowski, Jiří; Peceli, Davorin; Kozlová, Michaela; Rus, Bedřich

2017-01-01

Increasing the laser-induced damage resistance of optical components is one of the major challenges in the development of Peta-watt (PW) class laser systems. The extreme light infrastructure (ELI) beamlines project will provide ultrafast laser systems with peak powers up to 10 PW available every minute and PW class beams at 10 Hz complemented by a 5-TW, 1-kHz beamline. Sustainable performance of PW class laser systems relies on the durability of the employed optical components. As part of an effort to evaluate the damage resistance of components utilized in ELI beamlines systems, damage thresholds of several optical multilayer dielectric coatings were measured with different laser parameters and in different environments. Three coatings were tested with 10 Hz and 1 kHz pulse repetition rates, and the effect of a cleaning treatment on their damage resistance was examined. To explore the damage threshold behavior at different vacuum levels, one coating was subject to tests at various residual gas pressures. No change of damage threshold in a high vacuum with respect to ambient pressure was recorded. The effect of the cleaning treatment was found to be inconsistent, suggesting that development of the optimal cleaning treatment for a given coating requires consideration of its specific properties.

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.

Nonlinear ultrasonic assessment of stress corrosion cracking damage in sensitized 304 stainless steel

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

Morlock, Florian, E-mail: fmorlock3@gatech.edu; Jacobs, Laurence J., E-mail: fmorlock3@gatech.edu; Kim, Jin-Yeon, E-mail: fmorlock3@gatech.edu

2015-03-31

This research uses nonlinear Rayleigh surface waves to characterize stress corrosion cracking (SCC) damage in welded 304 Stainless Steel (304 SS). 304 SS is widely used in reactor pressure vessels, where a corrosive environment in combination with applied stress due to high internal pressures can cause SCC. Welds and the nearby heat affected zones (HAZ) in the vessel material are especially sensitive to SCC damage. SCC damage results in microstructural changes such as dislocation formation and microcrack initiation that in the long term lead to reduced structural integrity and material failure. Therefore, the early detection of SCC is crucial tomore » ensure safe operation. It has been shown that the microstructural changes caused by SCC can generate higher harmonic waves when excited harmonically. This research considers different levels of SCC damage induced in samples of welded 304 SS by applying stress to a specimen held in a corrosive medium (Sodium Thiosulfate). A nonlinear Rayleigh surface wave is introduced in the material and the fundamental and the second harmonic waves are measured using wedge detection. The nonlinearity parameter that relates the fundamental and the second harmonic amplitudes, is computed to quantify the SCC damage in each sample. These results are used to demonstrate the feasibility of using nonlinear Rayleigh waves to characterize SCC damage.« less

Effect of high-intensity irradiation from dental photopolymerization on the isolated and superfused vertebrate retina.

PubMed

Rassaei, Mohammad; Thelen, Martin; Abumuaileq, Ramzi; Hescheler, Jürgen; Lüke, Matthias; Schneider, Toni

2013-03-01

Light or electromagnetic radiation may damage the neurosensory retina during irradiation of photopolymerizing resinous materials. Direct and indirect effects of irradiation emitted from polymerisation curing light may represent a severe risk factor for the eyes and the skin of the lamp operators, as well as for the patient's oral mucosa. Bovine superfused retinas were used to record their light-evoked electroretinogram (ERG) as ex vivo ERGs. Both the a- and the b-waves were used as indicators for retinal damage on the functional level. The isolated retinas were routinely superfused with a standard nutrient solution under normoglycemic conditions (5 mM D-glucose). The change in the a- and b-wave amplitude and implicit time, caused by low and high intensity irradiation, was calculated and followed over time. From the results, it can be deduced that the irradiation from LED high-power lamps affects severely the normal physiological function of the bovine retina. Irradiations of 1,200 lx irreversibly damaged the physiological response. In part, this may be reversible at lower intensities, but curing without using the appropriate filter will bleach the retinal rhodopsin to a large extent within 20 to 40 s of standard application times. Constant exposure to intense ambient irradiation affects phototransduction (a-wave) as well as transretinal signalling. The proper use of the UV- and blue-light filtering device is highly recommended, and may prevent acute and long lasting damage of the neurosensory retina.

Anti-type II collagen antibodies, anti-CCP, IgA RF and IgM RF are associated with joint damage, assessed eight years after onset of juvenile idiopathic arthritis (JIA)

PubMed Central

2014-01-01

Background Early appearance of antibodies specific for native human type II collagen (anti-CII) characterizes an early inflammatory and destructive phenotype in adults with rheumatoid arthritis (RA). The objective of this study was to investigate the occurrence of anti-CII, IgM RF, IgA RF and anti-CCP in serum samples obtained early after diagnosis, and to relate the occurrence of autoantibodies to outcome after eight years of disease in children with juvenile idiopathic arthritis (JIA). Methods The Nordic JIA database prospectively included JIA patients followed for eight years with data on remission and joint damage. From this database, serum samples collected from 192 patients, at a median of four months after disease onset, were analysed for IgG anti-CII, IgM RF, IgA RF and IgG anti-CCP. Joint damage was assessed based on Juvenile Arthritis Damage Index for Articular damage (JADI-A), a validated clinical instrument for joint damage. Results Elevated serum levels of anti-CII occurred in 3.1%, IgM RF in 3.6%, IgA RF in 3.1% and anti-CCP in 2.6% of the patients. Occurrence of RF and anti-CCP did to some extent overlap, but rarely with anti-CII. The polyarticular and oligoarticular extended categories were overrepresented in patients with two or more autoantibodies. Anti-CII occurred in younger children, usually without overlap with the other autoantibodies and was associated with high levels of C-reactive protein (CRP) early in the disease course. All four autoantibodies were significantly associated with joint damage, but not with active disease at the eight-year follow up. Conclusions Anti-CII, anti-CCP, IgA RF and IgM RF detected early in the disease course predicted joint damage when assessed after eight years of disease. The role of anti-CII in JIA should be further studied. PMID:24944545

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.

Infrared laser damage thresholds in corneal tissue phantoms using femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Boretsky, Adam R.; Clary, Joseph E.; Noojin, Gary D.; Rockwell, Benjamin A.

2018-02-01

Ultrafast lasers have become a fixture in many biomedical, industrial, telecommunications, and defense applications in recent years. These sources are capable of generating extremely high peak power that can cause laser-induced tissue breakdown through the formation of a plasma upon exposure. Despite the increasing prevalence of such lasers, current safety standards (ANSI Z136.1-2014) do not include maximum permissible exposure (MPE) values for the cornea with pulse durations less than one nanosecond. This study was designed to measure damage thresholds in corneal tissue phantoms in the near-infrared and mid-infrared to identify the wavelength dependence of laser damage thresholds from 1200-2500 nm. A high-energy regenerative amplifier and optical parametric amplifier outputting 100 femtosecond pulses with pulse energies up to 2 mJ were used to perform exposures and determine damage thresholds in transparent collagen gel tissue phantoms. Three-dimensional imaging, primarily optical coherence tomography, was used to evaluate tissue phantoms following exposure to determine ablation characteristics at the surface and within the bulk material. The determination of laser damage thresholds in the near-IR and mid-IR for ultrafast lasers will help to guide safety standards and establish the appropriate MPE levels for exposure sensitive ocular tissue such as the cornea. These data will help promote the safe use of ultrafast lasers for a wide range of applications.

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

Lee, Joon No; Dutta, Raghbendra Kumar; Kim, Seul-Gi

Highlights: •A fasting–refeeding high fat diet (HDF) model mimics irregular eating habit. •A fasting–refeeding HFD induces liver ballooning injury. •A fasting–refeeding HDF process elicits hepatic triglyceride accumulation. •Fenofibrate, PPARα ligand, prevents liver damage induced by refeeding HFD. -- Abstract: Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, is an anti-hyperlipidemic agent that has been widely used in the treatment of dyslipidemia. In this study, we examined the effect of fenofibrate on liver damage caused by refeeding a high-fat diet (HFD) in mice after 24 h fasting. Here, we showed that refeeding HFD after fasting causes liver damage in mice determinedmore » by liver morphology and liver cell death. A detailed analysis revealed that hepatic lipid droplet formation is enhanced and triglyceride levels in liver are increased by refeeding HFD after starvation for 24 h. Also, NF-κB is activated and consequently induces the expression of TNF-α, IL1-β, COX-2, and NOS2. However, treating with fenofibrate attenuates the liver damage and triglyceride accumulation caused by the fasting–refeeding HFD process. Fenofibrate reduces the expression of NF-κB target genes but induces genes for peroxisomal fatty acid oxidation, peroxisome biogenesis and mitochondrial fatty acid oxidation. These results strongly suggest that the treatment of fenofibrate ameliorates the liver damage induced by fasting–refeeding HFD, possibly through the activation of fatty acid oxidation.« less

The Random Telegraph Signal Behavior of Intermittently Stuck Bits in SDRAMs

NASA Astrophysics Data System (ADS)

Chugg, Andrew Michael; Burnell, Andrew J.; Duncan, Peter H.; Parker, Sarah; Ward, Jonathan J.

2009-12-01

This paper reports behavior analogous to the Random Telegraph Signal (RTS) seen in the leakage currents from radiation induced hot pixels in Charge Coupled Devices (CCDs), but in the context of stuck bits in Synchronous Dynamic Random Access Memories (SDRAMs). Our analysis suggests that pseudo-random sticking and unsticking of the SDRAM bits is due to thermally induced fluctuations in leakage current through displacement damage complexes in depletion regions that were created by high-energy neutron and proton interactions. It is shown that the number of observed stuck bits increases exponentially with temperature, due to the general increase in the leakage currents through the damage centers with temperature. Nevertheless, some stuck bits are seen to pseudo-randomly stick and unstick in the context of a continuously rising trend of temperature, thus demonstrating that their damage centers can exist in multiple widely spaced, discrete levels of leakage current, which is highly consistent with RTS. This implies that these intermittently stuck bits (ISBs) are a displacement damage phenomenon and are unrelated to microdose issues, which is confirmed by the observation that they also occur in unbiased irradiation. Finally, we note that observed variations in the periodicity of the sticking and unsticking behavior on several timescales is most readily explained by multiple leakage current pathways through displacement damage complexes spontaneously and independently opening and closing under the influence of thermal vibrations.

Effect of wheat stem sawfly damage on yield and quality of selected Canadian spring wheat.

PubMed

Beres, B L; Cárcamo, H A; Byers, J R

2007-02-01

The wheat stem sawfly, Cephus cinctus Norton (Hymenoptera: Cephidae), has reached outbreak status at most locations in the southern Canadian prairies. Solid-stemmed wheat, Triticum aestivum L., cultivars, which are less susceptible to damage, remain the primary management option. This article quantifies the effect of wheat stem sawfly damage on grain yield and quality at harvest and determines how cultivar selection affects harvest losses. Solid-stemmed cultivars were compared with hollow-stemmed cultivars and with blends of a 1:1 ratio of each. The hollow-stemmed cultivars with the exception of'McKenzie', which had intermediate levels of stem cutting, were all significantly more susceptible to stem cutting than solid-stemmed cultivars. Cultivar blends had lower damage but were still significantly higher than the solid-stemmed cultivars. The solid-stemmed 'AC Eatonia' and 'AC Abbey' had the lowest levels of stem cutting and ranked second and third overall for yield in 2001 and 2002. McKenzie ranked first, which reflects its yield potential in combination with its partial resistance to stem cutting. Lower cutting in AC Eatonia, AC Abbey, McKenzie, and the blend of AC Abbey/ McKenzie was significantly correlated with lower grain losses. Grain lost at harvest has major economic implications if sawfly pressure is moderate to high and susceptible cultivars predominate.

Vitamin C and E Supplementation Effects in Professional Soccer Players Under Regular Training

PubMed Central

Zoppi, Claudio C; Hohl, Rodrigo; Silva, Fernando C; Lazarim, Fernanda L; Neto, Joaquim MF Antunes; Stancanneli, Mirtes; Macedo, Denise V

2006-01-01

Exercise training is known to induce an increase in free radical production potentially leading to enhanced muscle injury. Vitamins C and E are well known antioxidants that may prevent muscle cell damage. The purpose of this study was to determine the effects of these supplemental antioxidant vitamins on markers of oxidative stress, muscle damage and performance of elite soccer players. Ten male young soccer players were divided into two groups. Supplementation group (n = 5) received vitamins C and E supplementation daily during the pre-competitive season (S group), while the placebo group (PL group, n = 5) received a pill containing maltodextrin. Both groups performed the same training load during the three-month pre-season training period. Erythrocyte antioxidant enzymes glutathione reductase, catalase and plasma carbonyl derivatives did not show any significant variation among the experimental groups. Similarly, fitness level markers did not differ among the experimental groups. However, S group demonstrated lower lipid peroxidation and muscle damage levels (p < 0.05) compared to PL group at the final phase of pre-competitive season. In conclusion, our data demonstrated that vitamin C and E supplementation in soccer players may reduce lipid peroxidation and muscle damage during high intensity efforts, but did not enhance performance. PMID:18500971

Biochemical changes to fibroblast cells subjected to ionizing radiation.

PubMed

Jones, Pamala; Benghuzzi, Hamed; Tucci, Michelle; Richards, Latoya; Harrison, George; Patel, Ramesh

2008-01-01

High energy X-rays are capable of interacting with biological membranes to cause both functional and structural modifications. The goal of the present study was to investigate the effects human fibroblast cells exposed multiple times to 10 Gy over time. Following exposures of 2, 3, or 4 times to 10 Gy/10min the cells were evaluated for cell number changes, membrane damage, and intracellular glutathione content after 24, 48 and 72 hours. Twenty-four hours following exposure the cell numbers were reduced and increased levels of cellular membrane damage was evident. This trend was observed for the duration of the study. Interestingly, there was not an exposure dependent increase in cell damage or cell loss with time. Intracellular antioxidant systems were activated as indicated by anincrease in total cellular glutathione content. Additional studies are needed to determine if the cellular reduction is caused by a direct effect of the X-rays targeting the DNA or an indirect effect of the X-ray targeting the cellular membrane, which then generates radicals that target cell cycle checkpoints or DNA damage. In conclusion, fibroblast cells can be used to determine early and late events of cellular function following exposure to harmful levels of radiation exposure and results of exposure can be seen within twenty four hours.

Influence of Heavy Metal Stress on Antioxidant Status and DNA Damage in Urtica dioica

PubMed Central

Kadifkova Panovska, Tatjana; Bačeva, Katerina; Stafilov, Trajče

2013-01-01

Heavy metals have the potential to interact and induce several stress responses in the plants; thus, effects of heavy metal stress on DNA damages and total antioxidants level in Urtica dioica leaves and stems were investigated. The samples are sampled from areas with different metal exposition. Metal content was analyzed by Inductively Coupled Plasma-Atomic Emission Spectrometer (ICP-AES), for total antioxidants level assessment the Ferric-Reducing Antioxidant Power (FRAP) assay was used, and genomic DNA isolation from frozen plant samples was performed to obtain DNA fingerprints of investigated plant. It was found that heavy metal contents in stems generally changed synchronously with those in leaves of the plant, and extraneous metals led to imbalance of mineral nutrient elements. DNA damages were investigated by Random Amplified Polymorphic DNA (RAPD) technique, and the results demonstrated that the samples exposed to metals yielded a large number of new fragments (total 12) in comparison with the control sample. This study showed that DNA stability is highly affected by metal pollution which was identified by RAPD markers. Results suggested that heavy metal stress influences antioxidant status and also induces DNA damages in U. dioica which may help to understand the mechanisms of metals genotoxicity. PMID:23862140

CSF inflammatory biomarkers responsive to treatment in progressive multiple sclerosis capture residual inflammation associated with axonal damage.

PubMed

Romme Christensen, Jeppe; Komori, Mika; von Essen, Marina Rode; Ratzer, Rikke; Börnsen, Lars; Bielekova, Bibi; Sellebjerg, Finn

2018-05-01

Development of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation. To validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers. CSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS. CSF concentrations of 20 inflammatory biomarkers and CSF biomarkers of axonal damage (neurofilament light chain (NFL)) and demyelination were analysed using electrochemiluminescent assay and enzyme-linked immunosorbent assay (ELISA). In all, 17 natalizumab- and 23 methylprednisolone-treated patients had paired CSF samples. CSF sCD27 displayed superior standardised response means and highly significant decreases during both natalizumab and methylprednisolone treatment; however, post-treatment levels remained above healthy donor reference levels. Correlation analyses of CSF inflammatory biomarkers and NFL before, during and after treatment demonstrated that CSF sCD27 consistently correlates with NFL. These findings validate CSF sCD27 as a responsive and sensitive biomarker of intrathecal inflammation in progressive MS, capturing residual inflammation after treatment. Importantly, CSF sCD27 correlates with NFL, consistent with residual inflammation after anti-inflammatory treatment being associated with axonal damage.

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

An association of cocoa consumption with improved physical fitness and decreased muscle damage and oxidative stress in athletes.

PubMed

González-Garrido, José A; García-Sánchez, José R; Garrido-Llanos, Silvia; Olivares-Corichi, Ivonne M

2017-04-01

Several studies have demonstrated the protective effects of cocoa consumption, due to its anti-inflammatory and antioxidant properties. Acute exercise induces oxidative stress and causes muscular damage during training. This study was designed to examine the effect of cocoa consumption on the markers of muscle damage, oxidative stress and physical fitness in professional soccer players. Fifteen players (15-18 years old) were included in the study. Biochemical parameters, markers of muscle damage and oxidative stress, and physical performance were evaluated before and after cocoa consumption. Biochemical parameters determined the healthy metabolic status of the study group; biomarkers of muscle and oxidative damage were measured in blood to establish muscle and redox status. However, high levels of biomarkers of muscle damage were detected. Interestingly, cocoa consumption decreased the muscle damage biomarkers of CK and LDH by 39.4% and 23.03%, respectively. The redox status was modified by a decrease in oxidative damage (carbonyl groups, 26.31%; thiol groups, 27.52%; MDA, 32.42%) and an increase in total antioxidant capacity (15.98%) and GSH-Px activity (26.37%). In addition, we observed an increase in physical performance by 4% in the Cooper Test. Our findings suggest that a short period of cocoa consumption could be useful in maintaining a good physical fitness, due to the favourable effects on muscle and redox status in athletes during exhaustive exercise.

Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells

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

Krüger, Katharina; Ziegler, Verena; Hartmann, Christina

The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model.more » The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury. - Highlights: • Lovastatin blocks ATM/ATR-regulated DDR of tubular cells following CisPt treatment. • Lovastatin attenuates CisPt-induced activation of protein kinase ATM in vitro. • Statin-mediated DDR inhibition is independent of initial DNA damage formation. • Statin-mediated blockage of CisPt-triggered DDR leads to cytoprotection. • Lovastatin attenuates CisPt-induced kidney DNA damage and apoptosis in vivo.« less

Quantification of impact damage in CMC thermal protection systems using thin-film piezoelectric sensors

NASA Astrophysics Data System (ADS)

Kuhr, Samuel J.; Blackshire, James L.

2007-04-01

Thermal protection systems (TPS) are frequently subjected to impacts from micrometeoroids and ground handling during refurbishment. The damage resulting from such impacts can greatly reduce the vehicle's overall ability to resist extreme temperatures. Therefore, it is essential to have a reliable method to detect and quantify the damage resulting from impacts. In this effort, the effectiveness of lightweight thin film piezoelectric sensors was evaluated for impact detection and quantification in CMC wrapped TPS. The sensors, which were adhered to the bottom of the TPS tile, were used to sense impact events occurring on the top of the tile, with the ultimate goal of quantifying the level of impact level and damage state based on the sensed signals. A reasonable correlation between impact load levels and sensed response were observed for load levels between 0.07-1.00 Joules. An increase in signal frequency content was also observed as impact levels were increased, with specific frequency bands occurring in the 2-16 kHz range. A preliminary nondestructive evaluation of the impact damage sites was also accomplished, where a reasonable correlation between the gross damage features (i.e. impact crater dimensions) and signal response was observed.

Predicted molecular signaling guiding photoreceptor cell migration following transplantation into damaged retina

NASA Astrophysics Data System (ADS)

Unachukwu, Uchenna John; Warren, Alice; Li, Ze; Mishra, Shawn; Zhou, Jing; Sauane, Moira; Lim, Hyungsik; Vazquez, Maribel; Redenti, Stephen

2016-03-01

To replace photoreceptors lost to disease or trauma and restore vision, laboratories around the world are investigating photoreceptor replacement strategies using subretinal transplantation of photoreceptor precursor cells (PPCs) and retinal progenitor cells (RPCs). Significant obstacles to advancement of photoreceptor cell-replacement include low migration rates of transplanted cells into host retina and an absence of data describing chemotactic signaling guiding migration of transplanted cells in the damaged retinal microenvironment. To elucidate chemotactic signaling guiding transplanted cell migration, bioinformatics modeling of PPC transplantation into light-damaged retina was performed. The bioinformatics modeling analyzed whole-genome expression data and matched PPC chemotactic cell-surface receptors to cognate ligands expressed in the light-damaged retinal microenvironment. A library of significantly predicted chemotactic ligand-receptor pairs, as well as downstream signaling networks was generated. PPC and RPC migration in microfluidic ligand gradients were analyzed using a highly predicted ligand-receptor pair, SDF-1α - CXCR4, and both PPCs and RPCs exhibited significant chemotaxis. This work present a systems level model and begins to elucidate molecular mechanisms involved in PPC and RPC migration within the damaged retinal microenvironment.

Measurement of the vacuum-ultraviolet absorption spectrum of low-k dielectrics using X-ray reflectivity

NASA Astrophysics Data System (ADS)

Choudhury, F. A.; Nguyen, H. M.; King, S. W.; Lee, C. H.; Lin, Y. H.; Fung, H. S.; Chen, C. C.; Li, W.; Benjamin, D.; Blatz, J. M.; Nishi, Y.; Shohet, J. L.

2018-02-01

During plasma processing, low-k dielectrics are exposed to high levels of vacuum ultraviolet (VUV) radiation that can cause severe damage to dielectric materials. The degree and nature of VUV-induced damage depend on the VUV photon energies and fluence. In this work, we examine the VUV-absorption spectrum of low-k organosilicate glass using specular X-ray reflectivity (XRR). Low-k SiCOH films were exposed to synchrotron VUV radiation with energies ranging from 7 to 21 eV, and the density vs. depth profile of the VUV-irradiated films was extracted from fitting the XRR experimental data. The results show that the depth of the VUV-induced damage layer is a function of the photon energy. Between 7 and 11 eV, the depth of the damaged layer decreases sharply from 110 nm to 60 nm and then gradually increases to 85 nm at 21 eV. The maximum VUV absorption in low-k films occurs between 11 and 15 eV. The depth of the damaged layer was found to increase with film porosity.

Satellite detection of vegetative damage and alteration caused by pollutants emitted by a zinc smelter

NASA Technical Reports Server (NTRS)

Mcmurtry, G. J.; Petersen, G. W. (Principal Investigator); Fritz, E. L.; Pennypacker, S. P.

1974-01-01

The author has identified the following significant results. Field observations and data collected by low flying aircraft were used to verify the accuracy of maps produced from the satellite data. Although areas of vegetation as small as six acres can accurately be detected, a white pine stand that was severely damaged by sulfur dioxide could not be differentiated from a healthy white pine stand because spectral differences were not large enough. When winter data were used to eliminate interference from herbaceous and deciduous vegetation, the damage was still undetectable. The analysis was able to produce a character map that accurately delineated areas of vegetative alteration due to high zinc levels accumulating in the soil. The map depicted a distinct gradient of less damage and alteration as the distance from the smelter increased. Although the satellite data will probably not be useful for detecting small acreages of damaged vegetation, it is concluded that the data may be very useful as an inventory tool to detect and delineate large vegetative areas possessing differing spectral signatures.

Continuous permeability measurements record healing inside the Wenchuan earthquake fault zone.

PubMed

Xue, Lian; Li, Hai-Bing; Brodsky, Emily E; Xu, Zhi-Qing; Kano, Yasuyuki; Wang, Huan; Mori, James J; Si, Jia-Liang; Pei, Jun-Ling; Zhang, Wei; Yang, Guang; Sun, Zhi-Ming; Huang, Yao

2013-06-28

Permeability controls fluid flow in fault zones and is a proxy for rock damage after an earthquake. We used the tidal response of water level in a deep borehole to track permeability for 18 months in the damage zone of the causative fault of the 2008 moment magnitude 7.9 Wenchuan earthquake. The unusually high measured hydraulic diffusivity of 2.4 × 10(-2) square meters per second implies a major role for water circulation in the fault zone. For most of the observation period, the permeability decreased rapidly as the fault healed. The trend was interrupted by abrupt permeability increases attributable to shaking from remote earthquakes. These direct measurements of the fault zone reveal a process of punctuated recovery as healing and damage interact in the aftermath of a major earthquake.

DNA damage induces down-regulation of Prp19 via impairing Prp19 stability in hepatocellular carcinoma cells.

PubMed

Yin, Jie; Zhang, Yi-An; Liu, Tao-Tao; Zhu, Ji-Min; Shen, Xi-Zhong

2014-01-01

Pre-mRNA processing factor 19 (Prp19) activates pre-mRNA spliceosome and also mediates DNA damage response. Prp19 overexpression in cells with functional p53 leads to decreased apoptosis and increases cell survival after DNA damage. Here we showed that in hepatocellular carcinoma (HCC) cells with inactive p53 or functional p53, Prp19 was down-regulated due to the impaired stability under chemotherapeutic drug treatment. Silencing Prp19 expression enhanced apoptosis of HCC cells with or without chemotherapeutic drug treatment. Furthermore high level of Prp19 may inhibit chemotherapeutic drugs induced apoptosis in hepatocellular carcinoma cells through modulating myeloid leukemia cell differentiation 1 expression. These results indicated that targeting Prp19 may potentiate pro-apoptotic effect of chemotherapeutic agents on HCC.

Impact damage in aircraft composite sandwich panels

NASA Astrophysics Data System (ADS)

Mordasky, Matthew D.

An experimental study was conducted to develop an improved understanding of the damage caused by runway debris and environmental threats on aircraft structures. The velocities of impacts for stationary aircraft and aircraft under landing and takeoff speeds was investigated. The impact damage by concrete, asphalt, aluminum, hail and rubber sphere projectiles was explored in detail. Additionally, a kinetic energy and momentum experimental study was performed to look at the nature of the impacts in more detail. A method for recording the contact force history of the impact by an instrumented projectile was developed and tested. The sandwich composite investigated was an IM7-8552 unidirectional prepreg adhered to a NOMEXRTM core with an FM300K film adhesive. Impact experiments were conducted with a gas gun built in-house specifically for delivering projectiles to a sandwich composite target in this specic velocity regime (10--140 m/s). The effect on the impact damage by the projectile was investigated by ultrasonic C-scan, high speed camera and scanning electron and optical microscopy. Ultrasonic C-scans revealed the full extent of damage caused by each projectile, while the high speed camera enabled precise projectile velocity measurements that were used for striking velocity, kinetic energy and momentum analyses. Scanning electron and optical images revealed specific features of the panel failure and manufacturing artifacts within the lamina and honeycomb core. The damage of the panels by different projectiles was found to have a similar damage area for equivalent energy levels, except for rubber which had a damage area that increased greatly with striking velocity. Further investigation was taken by kinetic energy and momentum based comparisons of 19 mm diameter stainless steel sphere projectiles in order to examine the dominating damage mechanisms. The sandwich targets were struck by acrylic, aluminum, alumina, stainless steel and tungsten carbide spheres of the same geometry (19mm diameter) and surface finish. A peak absorbed energy for perforation of 34.5J was identied regardless of the projectile density. The effect of composite panel manufacturing methods on the impact damage and energy absorption of the panel was also investigated. Specifically, damage related to pre-cured facesheets is compared to the co-cured facesheets used throughout the study.

Reinforced Carbon-Carbon Subcomponent Flat Plate Impact Testing for Space Shuttle Orbiter Return to Flight

NASA Technical Reports Server (NTRS)

Melis, Matthew E.; Brand, Jeremy H.; Pereira, J. Michael; Revilock, Duane M.

2007-01-01

Following the tragedy of the Space Shuttle Columbia on February 1, 2003, a major effort commenced to develop a better understanding of debris impacts and their effect on the Space Shuttle subsystems. An initiative to develop and validate physics-based computer models to predict damage from such impacts was a fundamental component of this effort. To develop the models it was necessary to physically characterize Reinforced Carbon-Carbon (RCC) and various debris materials which could potentially shed on ascent and impact the Orbiter RCC leading edges. The validated models enabled the launch system community to use the impact analysis software LS DYNA to predict damage by potential and actual impact events on the Orbiter leading edge and nose cap thermal protection systems. Validation of the material models was done through a three-level approach: fundamental tests to obtain independent static and dynamic material model properties of materials of interest, sub-component impact tests to provide highly controlled impact test data for the correlation and validation of the models, and full-scale impact tests to establish the final level of confidence for the analysis methodology. This paper discusses the second level subcomponent test program in detail and its application to the LS DYNA model validation process. The level two testing consisted of over one hundred impact tests in the NASA Glenn Research Center Ballistic Impact Lab on 6 by 6 in. and 6 by 12 in. flat plates of RCC and evaluated three types of debris projectiles: BX 265 External Tank foam, ice, and PDL 1034 External Tank foam. These impact tests helped determine the level of damage generated in the RCC flat plates by each projectile. The information obtained from this testing validated the LS DYNA damage prediction models and provided a certain level of confidence to begin performing analysis for full-size RCC test articles for returning NASA to flight with STS 114 and beyond.

Effects of the earthquake of March 27, 1964, on various communities: Chapter G in The Alaska earthquake, March 27, 1964: effects on communities

USGS Publications Warehouse

Plafker, George; Kachadoorian, Reuben; Eckel, Edwin B.; Mayo, Lawrence R.

1969-01-01

The 1964 earthquake caused wide-spread damage to inhabited places throughout more than 60,000 square miles of south-central Alaska. This report describes damage to all communities in the area except Anchorage, Whittier, Homer, Valdez, Seward, the communities of the Kodiak group of islands, and communities in the Copper River Basin; these were discussed in previous chapters of the Geological Survey's series of reports on the earthquake. At the communities discussed herein, damage resulted primarily from sea waves of diverse origins, displacements of the land relative to sea level, and seismic shaking. Waves took all of the 31 lives lost at those communities; physical damage was primarily from the waves and vertical displacements of the land relative to sea level. Destructive waves of local origin struck during or immediately after the earthquake throughout much of Prince William Sound, the southern Kenai Peninsula, and the shores of Kenai Lake. In Prince William Sound, waves demolished all but one home at the native village of Chenega, destroyed homesites at Point Nowell and Anderson Bay, and caused varying amounts of damage to waterfront facilities at Sawmill Bay, Latouche, Port Oceanic, Port Nellie Juan, Perry Island, and western Port Valdez. The local waves, which ran up as high as 70 feet above tide level at Chenega and more than 170 feet in several uninhabited parts of the Sound, took nearly all of the lives lost by drowning at these communities. Destructive local waves that devastated shores of Anderson Bay and adjacent parts of western Port Valdez probably were generated primarily by massive submarine slides of glacial and fluvioglacial deposits ; the origin of the waves that caused damage at most of the other communities and at extensive uninhabited segments of shoreline is not known. At these places the most probable generative mechanisms are: unidentified submarine slides of unconsolidated deposits, and (or) the horizontal tectonic displacements, of 20 to more than 60 feet, that occurred in the Prince William Sound region during the earthquake. A train of long-period seismic sea waves that began about 20 minutes after the start of the earthquake inundated shores along the Gulf of Alaska coast to a maximum height of 35 feet above tide level. At the communities described, they virtually destroyed two logging camps at Whidbey Bay and Puget Bay on the south coast of the Kenai Peninsula, caused moderate damage to boat harbors and docks at Seldovia and Cordova, floated away some beach cabins in the Cordova area, and drowned two people, one at Point Whitshed near Cordora and one at the Cape Saint Elias Light Station. The seismic sea waves were generated by regional tectonic uplift of the sea floor on the Continental Shelf. Vertical tectonic displacements of the land relative to sea level that accompanied the earthquake affected virtually all the coastal communities. Tectonic subsidence of 5 to 6 feet, augmented locally by surficial subsidence of unconsolidated deposits required either the relocation or raising of structures at Portage, Girdwood, and Hope on Turnagain Arm. Shoreline submergence resulting from about 3½ feet of tectonic subsidence at Seldovia necessitated raising all waterfront facilities and the airstrip above the level of high tides. On the other hand, tectonic uplift of the land in the Prince Williams Sound region required deepening of the small-boat harbors at Cordora and Tatitlek, dredging of the waterways in the Cordova area, and lengthening of some docks or piers at Cordova, the Cape Hinchinbrook Light Station, and in Sawmill Bay. Significant structural damage from direct seismic shaking was largely confined to fluid containers and a pier facility near Kenai. Indirect damage from fissuring and differential settling of foundation mterials in the vicinity of the Cordova airfield mused damage to a building, underground utilities, an airfield fill, and the highway. Minor amounts of direct and indirect damage from seismic vibrations were sustained by most of the communities situated on unconsolidated deposits as far east as Yakutat, north to Fairbanks, and west to King Salmon. Except for a few cracked or toppled chimney, all the damage from shaking was confined to areas of thick, unconsolidated deposits. Foundation damage was almost entirely restricted to water-saturated unconsolidated deposits which, when liquefied by seismic shaking, could spread laterally toward free faces and (or) settle differentially through compaction.

Serum brain-derived neurotrophic factor and interleukin-6 response to high-volume mechanically demanding exercise.

PubMed

Verbickas, Vaidas; Kamandulis, Sigitas; Snieckus, Audrius; Venckunas, Tomas; Baranauskiene, Neringa; Brazaitis, Marius; Satkunskiene, Danguole; Unikauskas, Alvydas; Skurvydas, Albertas

2018-01-01

The aim of this study was to follow circulating brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) levels in response to severe muscle-damaging exercise. Young healthy men (N = 10) performed a bout of mechanically demanding stretch-shortening cycle exercise consisting of 200 drop jumps. Voluntary and electrically induced knee extension torque, serum BDNF levels, and IL-6 levels were measured before and for up to 7 days after exercise. Muscle force decreased by up to 40% and did not recover by 24 hours after exercise. Serum BDNF was decreased 1 hour and 24 hours after exercise, whereas IL-6 increased immediately and 1 hour after but recovered to baseline by 24 hours after exercise. IL-6 and 100-Hz stimulation torque were correlated (r = -0.64, P < 0.05) 24 hours after exercise. In response to acute, severe muscle-damaging exercise, serum BDNF levels decrease, whereas IL-6 levels increase and are associated with peripheral fatigue. Muscle Nerve 57: E46-E51, 2018. © 2017 Wiley Periodicals, Inc.

Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels

PubMed Central

van Leeuwen, Elisabeth M; Sabo, Aniko; Bis, Joshua C; Huffman, Jennifer E; Manichaikul, Ani; Smith, Albert V; Feitosa, Mary F; Demissie, Serkalem; Joshi, Peter K; Duan, Qing; Marten, Jonathan; van Klinken, Jan B; Surakka, Ida; Nolte, Ilja M; Zhang, Weihua; Mbarek, Hamdi; Li-Gao, Ruifang; Trompet, Stella; Verweij, Niek; Evangelou, Evangelos; Lyytikäinen, Leo-Pekka; Tayo, Bamidele O; Deelen, Joris; van der Most, Peter J; van der Laan, Sander W; Arking, Dan E; Morrison, Alanna; Dehghan, Abbas; Franco, Oscar H; Hofman, Albert; Rivadeneira, Fernando; Sijbrands, Eric J; Uitterlinden, Andre G; Mychaleckyj, Josyf C; Campbell, Archie; Hocking, Lynne J; Padmanabhan, Sandosh; Brody, Jennifer A; Rice, Kenneth M; White, Charles C; Harris, Tamara; Isaacs, Aaron; Campbell, Harry; Lange, Leslie A; Rudan, Igor; Kolcic, Ivana; Navarro, Pau; Zemunik, Tatijana; Salomaa, Veikko; Kooner, Angad S; Kooner, Jaspal S; Lehne, Benjamin; Scott, William R; Tan, Sian-Tsung; de Geus, Eco J; Milaneschi, Yuri; Penninx, Brenda W J H; Willemsen, Gonneke; de Mutsert, Renée; Ford, Ian; Gansevoort, Ron T; Segura-Lepe, Marcelo P; Raitakari, Olli T; Viikari, Jorma S; Nikus, Kjell; Forrester, Terrence; McKenzie, Colin A; de Craen, Anton J M; de Ruijter, Hester M; Pasterkamp, Gerard; Snieder, Harold; Oldehinkel, Albertine J; Slagboom, P Eline; Cooper, Richard S; Kähönen, Mika; Lehtimäki, Terho; Elliott, Paul; van der Harst, Pim; Jukema, J Wouter; Mook-Kanamori, Dennis O; Boomsma, Dorret I; Chambers, John C; Swertz, Morris; Ripatti, Samuli; Willems van Dijk, Ko; Vitart, Veronique; Polasek, Ozren; Hayward, Caroline; Wilson, James G; Wilson, James F; Gudnason, Vilmundur; Rich, Stephen S; Psaty, Bruce M; Borecki, Ingrid B; Boerwinkle, Eric; Rotter, Jerome I; Cupples, L Adrienne; van Duijn, Cornelia M

2016-01-01

Background So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels. Methods We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ∼60 000 individuals in the discovery stage and ∼90 000 samples in the replication stage. Results Our study resulted in the identification of five new associations with circulating lipid levels at four loci. All four loci are within genes that can be linked biologically to lipid metabolism. One of the variants, rs116843064, is a damaging missense variant within the ANGPTL4 gene. Conclusions This study illustrates that GWAS with high-scale imputation may still help us unravel the biological mechanism behind circulating lipid levels. PMID:27036123

Embedded Ultrasonics for SHM of Space Applications

DTIC Science & Technology

2012-07-30

information on material properties and other forms of damage such as cracks, structural fatigue and/or impact events. This synergistic aspect of the embedded...larger the phase shift. However, high excitation levels could contribute to sensor fatigue and levels in a range 15 to 20 (110 to 130 volts) are...joints each featuring three bolts. Piezoelectric wafers ( PZT ) with UNF electrodes were bonded to the isogrid panels using 3M 2216 epoxy

DNA repair phenotype and dietary antioxidant supplementation.

PubMed

Guarnieri, Serena; Loft, Steffen; Riso, Patrizia; Porrini, Marisa; Risom, Lotte; Poulsen, Henrik E; Dragsted, Lars O; Møller, Peter

2008-05-01

Phytochemicals may protect cellular DNA by direct antioxidant effect or modulation of the DNA repair activity. We investigated the repair activity towards oxidised DNA in human mononuclear blood cells (MNBC) in two placebo-controlled antioxidant intervention studies as follows: (1) well-nourished subjects who ingested 600 g fruits and vegetables, or tablets containing the equivalent amount of vitamins and minerals, for 24 d; (2) poorly nourished male smokers who ingested 500 mg vitamin C/d as slow- or plain-release formulations together with 182 mg vitamin E/d for 4 weeks. The mean baseline levels of DNA repair incisions were 65.2 (95 % CI 60.4, 70.0) and 86.1 (95 % CI 76.2, 99.9) among the male smokers and well-nourished subjects, respectively. The male smokers also had high baseline levels of oxidised guanines in MNBC. After supplementation, only the male smokers supplemented with slow-release vitamin C tablets had increased DNA repair activity (27 (95 % CI 12, 41) % higher incision activity). These subjects also benefited from the supplementation by reduced levels of oxidised guanines in MNBC. In conclusion, nutritional status, DNA repair activity and DNA damage are linked, and beneficial effects of antioxidants might only be observed among poorly nourished subjects with high levels of oxidised DNA damage and low repair activity.

Anatomical manifestations of primary blast ocular trauma observed in a postmortem porcine model.

PubMed

Sherwood, Daniel; Sponsel, William E; Lund, Brian J; Gray, Walt; Watson, Richard; Groth, Sylvia L; Thoe, Kimberly; Glickman, Randolph D; Reilly, Matthew A

2014-02-24

We qualitatively describe the anatomic features of primary blast ocular injury observed using a postmortem porcine eye model. Porcine eyes were exposed to various levels of blast energy to determine the optimal conditions for future testing. We studied 53 enucleated porcine eyes: 13 controls and 40 exposed to a range of primary blast energy levels. Eyes were preassessed with B-scan and ultrasound biomicroscopy (UBM) ultrasonography, photographed, mounted in gelatin within acrylic orbits, and monitored with high-speed videography during blast-tube impulse exposure. Postimpact photography, ultrasonography, and histopathology were performed, and ocular damage was assessed. Evidence for primary blast injury was obtained. While some of the same damage was observed in the control eyes, the incidence and severity of this damage in exposed eyes increased with impulse and peak pressure, suggesting that primary blast exacerbated these injuries. Common findings included angle recession, internal scleral delamination, cyclodialysis, peripheral chorioretinal detachments, and radial peripapillary retinal detachments. No full-thickness openings of the eyewall were observed in any of the eyes tested. Scleral damage demonstrated the strongest associative tendency for increasing likelihood of injury with increased overpressure. These data provide evidence that primary blast alone (in the absence of particle impact) can produce clinically relevant ocular damage in a postmortem model. The blast parameters derived from this study are being used currently in an in vivo model. We also propose a new Cumulative Injury Score indicating the clinical relevance of observed injuries.

DisA and c-di-AMP act at the intersection between DNA-damage response and stress homeostasis in exponentially growing Bacillus subtilis cells.

PubMed

Gándara, Carolina; Alonso, Juan C

2015-03-01

Bacillus subtilis contains two vegetative diadenylate cyclases, DisA and CdaA, which produce cyclic di-AMP (c-di-AMP), and one phosphodiesterase, GdpP, that degrades it into a linear di-AMP. We report here that DisA and CdaA contribute to elicit repair of DNA damage generated by alkyl groups and H2O2, respectively, during vegetative growth. disA forms an operon with radA (also termed sms) that encodes a protein distantly related to RecA. Among different DNA damage agents tested, only methyl methane sulfonate (MMS) affected disA null strain viability, while radA showed sensitivity to all of them. A strain lacking both disA and radA was as sensitive to MMS as the most sensitive single parent (epistasis). Low c-di-AMP levels (e.g. by over-expressing GdpP) decreased the ability of cells to repair DNA damage caused by MMS and in less extent by H2O2, while high levels of c-di-AMP (absence of GdpP or expression of sporulation-specific diadenylate cyclase, CdaS) increased cell survival. Taken together, our results support the idea that c-di-AMP is a crucial signalling molecule involved in DNA repair with DisA and CdaA contributing to modulate different DNA damage responses during exponential growth. Copyright © 2015 Elsevier B.V. All rights reserved.