A probabilistic fatigue analysis of multiple site damage

NASA Technical Reports Server (NTRS)

Rohrbaugh, S. M.; Ruff, D.; Hillberry, B. M.; Mccabe, G.; Grandt, A. F., Jr.

1994-01-01

The variability in initial crack size and fatigue crack growth is incorporated in a probabilistic model that is used to predict the fatigue lives for unstiffened aluminum alloy panels containing multiple site damage (MSD). The uncertainty of the damage in the MSD panel is represented by a distribution of fatigue crack lengths that are analytically derived from equivalent initial flaw sizes. The variability in fatigue crack growth rate is characterized by stochastic descriptions of crack growth parameters for a modified Paris crack growth law. A Monte-Carlo simulation explicitly describes the MSD panel by randomly selecting values from the stochastic variables and then grows the MSD cracks with a deterministic fatigue model until the panel fails. Different simulations investigate the influences of the fatigue variability on the distributions of remaining fatigue lives. Six cases that consider fixed and variable conditions of initial crack size and fatigue crack growth rate are examined. The crack size distribution exhibited a dominant effect on the remaining fatigue life distribution, and the variable crack growth rate exhibited a lesser effect on the distribution. In addition, the probabilistic model predicted that only a small percentage of the life remains after a lead crack develops in the MSD panel.

Optimal strategies for the surveillance and control of forest pathogens: A case study with oak wilt

Treesearch

Tetsuya Horie; Robert G. Haight; Frances R. Homans; Robert C. Venette

2013-01-01

Cost-effective strategies are needed to find and remove diseased trees in forests damaged by pathogens. We develop a model of cost-minimizing surveillance and control of forest pathogens across multiple sites where there is uncertainty about the extent of the infestation in each site and when the goal is to minimize the expected number of new infections. We allow for a...

Characterization of the interactions of PARP-1 with UV-damaged DNA in vivo and in vitro

PubMed Central

Purohit, Nupur K.; Robu, Mihaela; Shah, Rashmi G.; Geacintov, Nicholas E.; Shah, Girish M.

2016-01-01

The existing methodologies for studying robust responses of poly (ADP-ribose) polymerase-1 (PARP-1) to DNA damage with strand breaks are often not suitable for examining its subtle responses to altered DNA without strand breaks, such as UV-damaged DNA. Here we describe two novel assays with which we characterized the interaction of PARP-1 with UV-damaged DNA in vivo and in vitro. Using an in situ fractionation technique to selectively remove free PARP-1 while retaining the DNA-bound PARP-1, we demonstrate a direct recruitment of the endogenous or exogenous PARP-1 to the UV-lesion site in vivo after local irradiation. In addition, using the model oligonucleotides with single UV lesion surrounded by multiple restriction enzyme sites, we demonstrate in vitro that DDB2 and PARP-1 can simultaneously bind to UV-damaged DNA and that PARP-1 casts a bilateral asymmetric footprint from −12 to +9 nucleotides on either side of the UV-lesion. These techniques will permit characterization of different roles of PARP-1 in the repair of UV-damaged DNA and also allow the study of normal housekeeping roles of PARP-1 with undamaged DNA. PMID:26753915

Capturing Snapshots of APE1 Processing DNA Damage

PubMed Central

Freudenthal, Bret D.; Beard, William A.; Cuneo, Matthew J.; Dyrkheeva, Nadezhda S.; Wilson, Samuel H.

2015-01-01

DNA apurinic-apyrimidinic (AP) sites are prevalent non-coding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive due in part to limited structural information. We report multiple high-resolution human APE1:DNA structures that divulge novel features of the APE1 reaction, including the metal binding site, nucleophile, and arginine clamps that mediate product release. We also report APE1:DNA structures with a T:G mismatch 5′ to the AP-site, representing a clustered lesion occurring in methylated CpG dinucleotides. These reveal that APE1 molds the T:G mismatch into a unique Watson-Crick like geometry that distorts the active site reducing incision. These snapshots provide mechanistic clarity for APE1, while affording a rational framework to manipulate biological responses to DNA damage. PMID:26458045

Capturing snapshots of APE1 processing DNA damage

DOE PAGES

Freudenthal, Bret D.; Beard, William A.; Cuneo, Matthew J.; ...

2015-10-12

DNA apurinic-apyrimidinic (AP) sites are prevalent noncoding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA-repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive, owing in part to limited structural information. Here we report multiple high-resolution human APE1-DNA structures that divulge new features of the APE1 reaction, including the metal-binding site, the nucleophile and the arginine clamps that mediate product release. We also report APE1-DNA structures with a T-G mismatch 5' to the AP site, representing a clustered lesion occurring in methylatedmore » CpG dinucleotides. Moreover, these structures reveal that APE1 molds the T-G mismatch into a unique Watson-Crick-like geometry that distorts the active site, thus reducing incision. Finally, these snapshots provide mechanistic clarity for APE1 while affording a rational framework to manipulate biological responses to DNA damage.« less

Development of Alternating Current Potential Drop (ACPD) Procedures for Crack Detection in Aluminum Aircraft Panels.

DOT National Transportation Integrated Search

1993-12-01

The Alternating Current Potential Drop (ACPD) method is investigated as a means of making measurements in laboratory experiments on the initiation and growth of multiple site damage (MSD) cracks in a common aluminum alloy used for aircraft constructi...

Modelling multi-hazard hurricane damages on an urbanized coast with a Bayesian Network approach

USGS Publications Warehouse

van Verseveld, H.C.W.; Van Dongeren, A. R.; Plant, Nathaniel G.; Jäger, W.S.; den Heijer, C.

2015-01-01

Hurricane flood impacts to residential buildings in coastal zones are caused by a number of hazards, such as inundation, overflow currents, erosion, and wave attack. However, traditional hurricane damage models typically make use of stage-damage functions, where the stage is related to flooding depth only. Moreover, these models are deterministic and do not consider the large amount of uncertainty associated with both the processes themselves and with the predictions. This uncertainty becomes increasingly important when multiple hazards (flooding, wave attack, erosion, etc.) are considered simultaneously. This paper focusses on establishing relationships between observed damage and multiple hazard indicators in order to make better probabilistic predictions. The concept consists of (1) determining Local Hazard Indicators (LHIs) from a hindcasted storm with use of a nearshore morphodynamic model, XBeach, and (2) coupling these LHIs and building characteristics to the observed damages. We chose a Bayesian Network approach in order to make this coupling and used the LHIs ‘Inundation depth’, ‘Flow velocity’, ‘Wave attack’, and ‘Scour depth’ to represent flooding, current, wave impacts, and erosion related hazards.The coupled hazard model was tested against four thousand damage observations from a case site at the Rockaway Peninsula, NY, that was impacted by Hurricane Sandy in late October, 2012. The model was able to accurately distinguish ‘Minor damage’ from all other outcomes 95% of the time and could distinguish areas that were affected by the storm, but not severely damaged, 68% of the time. For the most heavily damaged buildings (‘Major Damage’ and ‘Destroyed’), projections of the expected damage underestimated the observed damage. The model demonstrated that including multiple hazards doubled the prediction skill, with Log-Likelihood Ratio test (a measure of improved accuracy and reduction in uncertainty) scores between 0.02 and 0.17 when only one hazard is considered and a score of 0.37 when multiple hazards are considered simultaneously. The LHIs with the most predictive skill were ‘Inundation depth’ and ‘Wave attack’. The Bayesian Network approach has several advantages over the market-standard stage-damage functions: the predictive capacity of multiple indicators can be combined; probabilistic predictions can be obtained, which include uncertainty; and quantitative as well as descriptive information can be used simultaneously.

Enhanced protective role in materials with gradient structural orientations: Lessons from Nature.

PubMed

Liu, Zengqian; Zhu, Yankun; Jiao, Da; Weng, Zhaoyong; Zhang, Zhefeng; Ritchie, Robert O

2016-10-15

Living organisms are adept at resisting contact deformation and damage by assembling protective surfaces with spatially varied mechanical properties, i.e., by creating functionally graded materials. Such gradients, together with multiple length-scale hierarchical structures, represent the two prime characteristics of many biological materials to be translated into engineering design. Here, we examine one design motif from a variety of biological tissues and materials where site-specific mechanical properties are generated for enhanced protection by adopting gradients in structural orientation over multiple length-scales, without manipulation of composition or microstructural dimension. Quantitative correlations are established between the structural orientations and local mechanical properties, such as stiffness, strength and fracture resistance; based on such gradients, the underlying mechanisms for the enhanced protective role of these materials are clarified. Theoretical analysis is presented and corroborated through numerical simulations of the indentation behavior of composites with distinct orientations. The design strategy of such bioinspired gradients is outlined in terms of the geometry of constituents. This study may offer a feasible approach towards generating functionally graded mechanical properties in synthetic materials for improved contact damage resistance. Living organisms are adept at resisting contact damage by assembling protective surfaces with spatially varied mechanical properties, i.e., by creating functionally-graded materials. Such gradients, together with multiple length-scale hierarchical structures, represent the prime characteristics of many biological materials. Here, we examine one design motif from a variety of biological tissues where site-specific mechanical properties are generated for enhanced protection by adopting gradients in structural orientation at multiple length-scales, without changes in composition or microstructural dimension. The design strategy of such bioinspired gradients is outlined in terms of the geometry of constituents. This study may offer a feasible approach towards generating functionally-graded mechanical properties in synthetic materials for improved damage resistance. Published by Elsevier Ltd.

Fracture and Fatigue Strength Evaluation of Multiple Site Damaged Aircraft Fuselages - Curved Panel Testing and Analysis.

DOT National Transportation Integrated Search

1994-01-01

As the fleet of commercial passenger aircraft is utilized beyond their design lives, flaws have developed at the rivet holes of fuselage lap joints on some aircraft, which can grow and link up into cracks of significant length. Understanding, predict...

Global and Regional Brain Non-Gaussian Diffusion Changes in Newly Diagnosed Patients with Obstructive Sleep Apnea.

PubMed

Tummala, Sudhakar; Palomares, Jose; Kang, Daniel W; Park, Bumhee; Woo, Mary A; Harper, Ronald M; Kumar, Rajesh

2016-01-01

Obstructive sleep apnea (OSA) patients show brain structural injury and functional deficits in autonomic, affective, and cognitive regulatory sites, as revealed by mean diffusivity (MD) and other imaging procedures. The time course and nature of gray and white matter injury can be revealed in more detail with mean kurtosis (MK) procedures, which can differentiate acute from chronic injury, and better show extent of damage over MD procedures. Our objective was to examine global and regional MK changes in newly diagnosed OSA, relative to control subjects. Two diffusion kurtosis image series were collected from 22 recently-diagnosed, treatment-naïve OSA and 26 control subjects using a 3.0-Tesla MRI scanner. MK maps were generated, normalized to a common space, smoothed, and compared voxel-by-voxel between groups using analysis of covariance (covariates; age, sex). No age or sex differences appeared, but body mass index, sleep, neuropsychologic, and cognitive scores significantly differed between groups. MK values were significantly increased globally in OSA over controls, and in multiple localized sites, including the basal forebrain, extending to the hypothalamus, hippocampus, thalamus, insular cortices, basal ganglia, limbic regions, cerebellar areas, parietal cortices, ventral temporal lobe, ventrolateral medulla, and midline pons. Multiple sites, including the insular cortices, ventrolateral medulla, and midline pons showed more injury over previously identified damage with MD procedures, with damage often lateralized. Global mean kurtosis values are significantly increased in obstructive sleep apnea (OSA), suggesting acute tissue injury, and these changes are principally localized in critical sites mediating deficient functions in the condition. The mechanisms for injury likely include altered perfusion and hypoxemia-induced processes, leading to acute tissue changes in recently diagnosed OSA. © 2016 Associated Professional Sleep Societies, LLC.

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

NASA Technical Reports Server (NTRS)

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

1994-01-01

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

Three-Dimensional Geometric Nonlinear Contact Stress Analysis of Riveted Joints

NASA Technical Reports Server (NTRS)

Shivakumar, Kunigal N.; Ramanujapuram, Vivek

1998-01-01

The problems associated with fatigue were brought into the forefront of research by the explosive decompression and structural failure of the Aloha Airlines Flight 243 in 1988. The structural failure of this airplane has been attributed to debonding and multiple cracking along the longitudinal lap splice riveted joint in the fuselage. This crash created what may be termed as a minor "Structural Integrity Revolution" in the commercial transport industry. Major steps have been taken by the manufacturers, operators and authorities to improve the structural airworthiness of the aging fleet of airplanes. Notwithstanding, this considerable effort there are still outstanding issues and concerns related to the formulation of Widespread Fatigue Damage which is believed to have been a contributing factor in the probable cause of the Aloha accident. The lesson from this accident was that Multiple-Site Damage (MSD) in "aging" aircraft can lead to extensive aircraft damage. A strong candidate in which MSD is highly probable to occur is the riveted lap joint.

Retrieving atmospheric transmissivity for biologically active daily dose, in various european sites

NASA Astrophysics Data System (ADS)

de La Casinière, A.; Touré, M. L.; Lenoble, J.; Cabot, T.

2003-04-01

In the frame of the European Project EDUCE, global UV irradiance spectra recorded all along the year in several European sites are stored in a common database located in Finland. From the spectra set of some of these stations, are calculated atmospheric transmissivities for daily doses of four biologically active UV radiation, namely: UV-B, erythema, DNA damage, and plant damage. A transmissivity is defined as the ratio of the ground level value of the daily dose of interest to its corresponding extra-atmospheric value. Multiple linear correlation of the various transmissivities with three predictors (daily sunshine fraction, cosine of the daily minimum SZA, and daily total ozone column) assumed to be independent variables, are done for year 2000. The coefficients obtained from year 2000 correlation in a given site are expected to retrieve, from the local predictors, the daily dose for year 2001 in the same site, the average error being lesser than 10% for monthly mean values, and lesser than 5% for three-monthly mean values, depending on the daily dose type. Comparison of yearly mean daily doses retrieved in a given site from coefficients obtained in other sites is also presented.

Numerical Simulation of Strong Ground Motion at Mexico City:A Hybrid Approach for Efficient Evaluation of Site Amplification and Path Effects for Different Types of Earthquakes

NASA Astrophysics Data System (ADS)

Cruz, H.; Furumura, T.; Chavez-Garcia, F. J.

2002-12-01

The estimation of scenarios of the strong ground motions caused by future great earthquakes is an important problem in strong motion seismology. This was pointed out by the great 1985 Michoacan earthquake, which caused a great damage in Mexico City, 300 km away from the epicenter. Since the seismic wavefield is characterized by the source, path and site effects, the pattern of strong motion damage from different types of earthquakes should differ significantly. In this study, the scenarios for intermediate-depth normal-faulting, shallow-interplate thrust faulting, and crustal earthquakes have been estimated using a hybrid simulation technique. The character of the seismic wavefield propagating from the source to Mexico City for each earthquake was first calculated using the pseudospectral method for 2D SH waves. The site amplifications in the shallow structure of Mexico City are then calculated using the multiple SH wave reverberation theory. The scenarios of maximum ground motion for both inslab and interplate earthquakes obtained by the simulation show a good agreement with the observations. This indicates the effectiveness of the hybrid simulation approach to investigate the strong motion damage for future earthquakes.

SUMOylation of ATRIP potentiates DNA damage signaling by boosting multiple protein interactions in the ATR pathway

PubMed Central

Wu, Ching-Shyi; Ouyang, Jian; Mori, Eiichiro; Nguyen, Hai Dang; Maréchal, Alexandre; Hallet, Alexander; Chen, David J.; Zou, Lee

2014-01-01

The ATR (ATM [ataxia telangiectasia-mutated]- and Rad3-related) checkpoint is a crucial DNA damage signaling pathway. While the ATR pathway is known to transmit DNA damage signals through the ATR–Chk1 kinase cascade, whether post-translational modifications other than phosphorylation are important for this pathway remains largely unknown. Here, we show that protein SUMOylation plays a key role in the ATR pathway. ATRIP, the regulatory partner of ATR, is modified by SUMO2/3 at K234 and K289. An ATRIP mutant lacking the SUMOylation sites fails to localize to DNA damage and support ATR activation efficiently. Surprisingly, the ATRIP SUMOylation mutant is compromised in the interaction with a protein group, rather than a single protein, in the ATR pathway. Multiple ATRIP-interacting proteins, including ATR, RPA70, TopBP1, and the MRE11–RAD50–NBS1 complex, exhibit reduced binding to the ATRIP SUMOylation mutant in cells and display affinity for SUMO2 chains in vitro, suggesting that they bind not only ATRIP but also SUMO. Fusion of a SUMO2 chain to the ATRIP SUMOylation mutant enhances its interaction with the protein group and partially suppresses its localization and functional defects, revealing that ATRIP SUMOylation promotes ATR activation by providing a unique type of protein glue that boosts multiple protein interactions along the ATR pathway. PMID:24990965

76 FR 59590 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-27

... web lap and tear strap splices of the aft pressure bulkhead at STA 1582 due to fatigue. We are... radial web lap and tear strap splices of the aft pressure bulkhead at station (STA) 1582 due to fatigue... prompted by reports of multiple site damage cracks in the radial web lap and tear strap splices of the aft...

76 FR 22311 - Airworthiness Directives; Lockheed Martin Corporation/Lockheed Martin Aeronautics Company Model...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-21

... a report of fatigue cracking of the wing upper and lower rainbow fittings during durability testing... are susceptible to multiple site fatigue damage. We are issuing this AD to detect and correct such fatigue cracks, which could grow large and lead to the failure of the fitting and a catastrophic failure...

75 FR 13695 - Airworthiness Directives; Lockheed Martin Corporation/Lockheed Martin Aeronautics Company Model...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-23

... proposed AD results from a report of fatigue cracking of the wing upper and lower rainbow fittings during... fittings are susceptible to multiple site fatigue damage. We are proposing this AD to detect and correct such fatigue cracks, which could grow large and lead to the failure of the fitting and a catastrophic...

Multiple factors affect pest and pathogen damage on 31 Populus clones in South Carolina

Treesearch

David R. Coyle; Mark D. Coleman; Jaclin A. Durant; Lee A. Newman

2006-01-01

Populus species and hybrids have many practical applications, but there is a paucity of data regarding selections that perform well in the southeastern US. We compared pest susceptibility of 31 Populus clones over 3 years in South Carolina, USA. Cuttings were planted in spring 2001 on two study sites. Clones planted in the...

Health Effects of Exposure to Water-Damaged New Orleans Homes Six Months After Hurricanes Katrina and Rita

PubMed Central

Cummings, Kristin J.; Cox-Ganser, Jean; Riggs, Margaret A.; Edwards, Nicole; Hobbs, Gerald R.; Kreiss, Kathleen

2008-01-01

Objectives. We investigated the relation between respiratory symptoms and exposure to water-damaged homes and the effect of respirator use in posthurricane New Orleans, Louisiana. Methods. We randomly selected 600 residential sites and then interviewed 1 adult per site. We created an exposure variable, calculated upper respiratory symptom (URS) and lower respiratory symptom (LRS) scores, and defined exacerbation categories by the effect on symptoms of being inside water-damaged homes. We used multiple linear regression to model symptom scores (for all participants) and polytomous logistic regression to model exacerbation of symptoms when inside (for those participating in clean-up). Results. Of 553 participants (response rate=92%), 372 (68%) had participated in clean-up; 233 (63%) of these used a respirator. Respiratory symptom scores increased linearly with exposure (P<.05 for trend). Disposable-respirator use was associated with lower odds of exacerbation of moderate or severe symptoms inside water-damaged homes for URS (odds ratio (OR)=.51; 95% confidence interval (CI)=0.24, 1.09) and LRS (OR=0.33; 95% CI=0.13, 0.83). Conclusions. Respiratory symptoms were positively associated with exposure to water-damaged homes, including exposure limited to being inside without participating in clean-up. Respirator use had a protective effect and should be considered when inside water-damaged homes regardless of activities undertaken. PMID:18381997

Boring crustaceans damage polystyrene floats under docks polluting marine waters with microplastic.

PubMed

Davidson, Timothy M

2012-09-01

Boring isopods damage expanded polystyrene floats under docks and, in the process, expel copious numbers of microplastic particles. This paper describes the impacts of boring isopods in aquaculture facilities and docks, quantifies and discusses the implications of these microplastics, and tests if an alternate foam type prevents boring. Floats from aquaculture facilities and docks were heavily damaged by thousands of isopods and their burrows. Multiple sites in Asia, Australia, Panama, and the USA exhibited evidence of isopod damage. One isopod creates thousands of microplastic particles when excavating a burrow; colonies can expel millions of particles. Microplastics similar in size to these particles may facilitate the spread of non-native species or be ingested by organisms causing physical or toxicological harm. Extruded polystyrene inhibited boring, suggesting this foam may prevent damage in the field. These results reveal boring isopods cause widespread damage to docks and are a novel source of microplastic pollution. Copyright © 2012 Elsevier Ltd. All rights reserved.

How distributed processing produces false negatives in voxel-based lesion-deficit analyses.

PubMed

Gajardo-Vidal, Andrea; Lorca-Puls, Diego L; Crinion, Jennifer T; White, Jitrachote; Seghier, Mohamed L; Leff, Alex P; Hope, Thomas M H; Ludersdorfer, Philipp; Green, David W; Bowman, Howard; Price, Cathy J

2018-07-01

In this study, we hypothesized that if the same deficit can be caused by damage to one or another part of a distributed neural system, then voxel-based analyses might miss critical lesion sites because preservation of each site will not be consistently associated with preserved function. The first part of our investigation used voxel-based multiple regression analyses of data from 359 right-handed stroke survivors to identify brain regions where lesion load is associated with picture naming abilities after factoring out variance related to object recognition, semantics and speech articulation so as to focus on deficits arising at the word retrieval level. A highly significant lesion-deficit relationship was identified in left temporal and frontal/premotor regions. Post-hoc analyses showed that damage to either of these sites caused the deficit of interest in less than half the affected patients (76/162 = 47%). After excluding all patients with damage to one or both of the identified regions, our second analysis revealed a new region, in the anterior part of the left putamen, which had not been previously detected because many patients had the deficit of interest after temporal or frontal damage that preserved the left putamen. The results illustrate how (i) false negative results arise when the same deficit can be caused by different lesion sites; (ii) some of the missed effects can be unveiled by adopting an iterative approach that systematically excludes patients with lesions to the areas identified in previous analyses, (iii) statistically significant voxel-based lesion-deficit mappings can be driven by a subset of patients; (iv) focal lesions to the identified regions are needed to determine whether the deficit of interest is the consequence of focal damage or much more extensive damage that includes the identified region; and, finally, (v) univariate voxel-based lesion-deficit mappings cannot, in isolation, be used to predict outcome in other patients. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

On multi-site damage identification using single-site training data

NASA Astrophysics Data System (ADS)

Barthorpe, R. J.; Manson, G.; Worden, K.

2017-11-01

This paper proposes a methodology for developing multi-site damage location systems for engineering structures that can be trained using single-site damaged state data only. The methodology involves training a sequence of binary classifiers based upon single-site damage data and combining the developed classifiers into a robust multi-class damage locator. In this way, the multi-site damage identification problem may be decomposed into a sequence of binary decisions. In this paper Support Vector Classifiers are adopted as the means of making these binary decisions. The proposed methodology represents an advancement on the state of the art in the field of multi-site damage identification which require either: (1) full damaged state data from single- and multi-site damage cases or (2) the development of a physics-based model to make multi-site model predictions. The potential benefit of the proposed methodology is that a significantly reduced number of recorded damage states may be required in order to train a multi-site damage locator without recourse to physics-based model predictions. In this paper it is first demonstrated that Support Vector Classification represents an appropriate approach to the multi-site damage location problem, with methods for combining binary classifiers discussed. Next, the proposed methodology is demonstrated and evaluated through application to a real engineering structure - a Piper Tomahawk trainer aircraft wing - with its performance compared to classifiers trained using the full damaged-state dataset.

Diphenylpyrazoles as Replication Protein A inhibitors

DOE PAGES

Waterson, Alex G.; Kennedy, J. Phillip; Patrone, James D.; ...

2014-11-11

Replication Protein A is the primary eukaryotic ssDNA binding protein that has a central role in initiating the cellular response to DNA damage. RPA recruits multiple proteins to sites of DNA damage via the N-terminal domain of the 70 kDa subunit (RPA70N). Here we describe the optimization of a diphenylpyrazole carboxylic acid series of inhibitors of these RPA–protein interactions. Lastly, we evaluated substituents on the aromatic rings as well as the type and geometry of the linkers used to combine fragments, ultimately leading to submicromolar inhibitors of RPA70N protein–protein interactions.

Computational predictive methods for fracture and fatigue

NASA Technical Reports Server (NTRS)

Cordes, J.; Chang, A. T.; Nelson, N.; Kim, Y.

1994-01-01

The damage-tolerant design philosophy as used by aircraft industries enables aircraft components and aircraft structures to operate safely with minor damage, small cracks, and flaws. Maintenance and inspection procedures insure that damages developed during service remain below design values. When damage is found, repairs or design modifications are implemented and flight is resumed. Design and redesign guidelines, such as military specifications MIL-A-83444, have successfully reduced the incidence of damage and cracks. However, fatigue cracks continue to appear in aircraft well before the design life has expired. The F16 airplane, for instance, developed small cracks in the engine mount, wing support, bulk heads, the fuselage upper skin, the fuel shelf joints, and along the upper wings. Some cracks were found after 600 hours of the 8000 hour design service life and design modifications were required. Tests on the F16 plane showed that the design loading conditions were close to the predicted loading conditions. Improvements to analytic methods for predicting fatigue crack growth adjacent to holes, when multiple damage sites are present, and in corrosive environments would result in more cost-effective designs, fewer repairs, and fewer redesigns. The overall objective of the research described in this paper is to develop, verify, and extend the computational efficiency of analysis procedures necessary for damage tolerant design. This paper describes an elastic/plastic fracture method and an associated fatigue analysis method for damage tolerant design. Both methods are unique in that material parameters such as fracture toughness, R-curve data, and fatigue constants are not required. The methods are implemented with a general-purpose finite element package. Several proof-of-concept examples are given. With further development, the methods could be extended for analysis of multi-site damage, creep-fatigue, and corrosion fatigue problems.

Computational predictive methods for fracture and fatigue

NASA Astrophysics Data System (ADS)

Cordes, J.; Chang, A. T.; Nelson, N.; Kim, Y.

1994-09-01

The damage-tolerant design philosophy as used by aircraft industries enables aircraft components and aircraft structures to operate safely with minor damage, small cracks, and flaws. Maintenance and inspection procedures insure that damages developed during service remain below design values. When damage is found, repairs or design modifications are implemented and flight is resumed. Design and redesign guidelines, such as military specifications MIL-A-83444, have successfully reduced the incidence of damage and cracks. However, fatigue cracks continue to appear in aircraft well before the design life has expired. The F16 airplane, for instance, developed small cracks in the engine mount, wing support, bulk heads, the fuselage upper skin, the fuel shelf joints, and along the upper wings. Some cracks were found after 600 hours of the 8000 hour design service life and design modifications were required. Tests on the F16 plane showed that the design loading conditions were close to the predicted loading conditions. Improvements to analytic methods for predicting fatigue crack growth adjacent to holes, when multiple damage sites are present, and in corrosive environments would result in more cost-effective designs, fewer repairs, and fewer redesigns. The overall objective of the research described in this paper is to develop, verify, and extend the computational efficiency of analysis procedures necessary for damage tolerant design. This paper describes an elastic/plastic fracture method and an associated fatigue analysis method for damage tolerant design. Both methods are unique in that material parameters such as fracture toughness, R-curve data, and fatigue constants are not required. The methods are implemented with a general-purpose finite element package. Several proof-of-concept examples are given. With further development, the methods could be extended for analysis of multi-site damage, creep-fatigue, and corrosion fatigue problems.

Method for producing damage resistant optics

DOEpatents

Hackel, Lloyd A.; Burnham, Alan K.; Penetrante, Bernardino M.; Brusasco, Raymond M.; Wegner, Paul J.; Hrubesh, Lawrence W.; Kozlowski, Mark R.; Feit, Michael D.

2003-01-01

The present invention provides a system that mitigates the growth of surface damage in an optic. Damage to the optic is minimally initiated. In an embodiment of the invention, damage sites in the optic are initiated, located, and then treated to stop the growth of the damage sites. The step of initiating damage sites in the optic includes a scan of the optic using a laser to initiate defects. The exact positions of the initiated sites are identified. A mitigation process is performed that locally or globally removes the cause of subsequent growth of the damaged sites.

Probability of Detection Study on Impact Damage to Honeycomb Composite Structure using Thermographic Inspection

NASA Technical Reports Server (NTRS)

Hodge, Andrew J.; Walker, James L., II

2008-01-01

A probability of detection study was performed for the detection of impact damage using flash heating infrared thermography on a full scale honeycomb composite structure. The honeycomb structure was an intertank structure from a previous NASA technology demonstration program. The intertank was fabricated from IM7/8552 carbon fiber/epoxy facesheets and aluminum honeycomb core. The intertank was impacted in multiple locations with a range of impact energies utilizing a spherical indenter. In a single blind study, the intertank was inspected with thermography before and after impact damage was incurred. Following thermographic inspection several impact sites were sectioned from the intertank and cross-sectioned for microscopic comparisons of NDE detection and actual damage incurred. The study concluded that thermographic inspection was a good method of detecting delamination damage incurred by impact. The 90/95 confidence level on the probability of detection was close to the impact energy that delaminations were first observed through cross-sectional analysis.

Widespread fatigue damage monitoring: Issues and concerns

NASA Technical Reports Server (NTRS)

Swift, T.

1994-01-01

This paper is intended to illustrate the considerable effect that small in-service undetectable multi-site-damage (MSD) can have on the residual strength capability of aging aircraft structures. In general, very few people in the industry believe that tiny cracks of undetectable size are a problem because they know that many aircraft have been able to survive much larger damage. In fact they have been certified for this large damage capability. However, this is not the issue. The real issue is the effect the tiny cracks, at multiple sites, have on the large damage capability which the industry has become accustomed to expect and which the aircraft have been certified to sustain. The concern is that this message does not appear to be fully understood by many people outside the fracture community. The prime purpose of this paper, therefore, has been to convey this message by describing in simple terms the net section yielding phenomenon in ductile materials which causes loss in lead crack residual strength in the presence of MSD. The explanation continues with a number of examples on complex stiffened structures, using the results of previous finite element analyses, which illustrate that the effect of MSD is extremely sensitive to structural configuration. It is hoped that those members of the aviation community who believe that tiny cracks are not a problem will read this paper very carefully.

Measurement of DNA damage in rat urinary bladder transitional cells: improved selective harvest of transitional cells and detailed Comet assay protocols.

PubMed

Wang, Amy; Robertson, John L; Holladay, Steven D; Tennant, Alan H; Lengi, Andrea J; Ahmed, S Ansar; Huckle, William R; Kligerman, Andrew D

2007-12-01

Urinary bladder transitional epithelium is the main site of bladder cancer, and the use of transitional cells to study carcinogenesis/genotoxicity is recommended over the use of whole bladders. Because the transitional epithelium is only a small fraction of the whole bladder, the alkaline single cell gel electrophoresis assay (Comet assay), which requires only a small number of cells per sample, is especially suitable for measuring DNA damage in transitional cells. However, existed procedures of cell collection did not yield transitional cells with a high purity, and pooling of samples was needed for Comet assay. The goal of this study was to develop an optimized protocol to evaluate DNA damage in the urinary bladder transitional epithelium. This was achieved by an enzymatic stripping method (trypsin-EDTA incubation plus gentle scraping) to selectively harvest transitional cells from rat bladders, and the use of the alkaline Comet assay to detect DNA strand breaks, alkaline labile sites, and DNA-protein crosslinks. Step by step procedures are reported here. Cells collected from a single rat bladder were sufficient for multiple Comet assays. With this new protocol, increases in DNA damage were detected in transitional cells after in vitro exposure to the positive control agents, hydrogen peroxide or formaldehyde. Repair of the induced DNA damage occurred within 4h. This indicated the capacity for DNA repair was maintained in the harvested cells. The new protocol provides a simple and inexpensive method to detect various types of DNA damage and to measure DNA damage repair in urinary bladder transitional cells.

Rapid analytical methods for on-site triage for traumatic brain injury.

PubMed

North, Stella H; Shriver-Lake, Lisa C; Taitt, Chris R; Ligler, Frances S

2012-01-01

Traumatic brain injury (TBI) results from an event that causes rapid acceleration and deceleration of the brain or penetration of the skull with an object. Responses to stimuli and questions, loss of consciousness, and altered behavior are symptoms currently used to justify brain imaging for diagnosis and therapeutic guidance. Tests based on such symptoms are susceptible to false-positive and false-negative results due to stress, fatigue, and medications. Biochemical markers of neuronal damage and the physiological response to that damage are being identified. Biosensors capable of rapid measurement of such markers in the circulation offer a solution for on-site triage, as long as three criteria are met: (a) Recognition reagents can be identified that are sufficiently sensitive and specific, (b) the biosensor can provide quantitative assessment of multiple markers rapidly and simultaneously, and (c) both the sensor and reagents are designed for use outside the laboratory.

Rapid Analytical Methods for On-Site Triage for Traumatic Brain Injury

NASA Astrophysics Data System (ADS)

North, Stella H.; Shriver-Lake, Lisa C.; Taitt, Chris R.; Ligler, Frances S.

2012-07-01

Traumatic brain injury (TBI) results from an event that causes rapid acceleration and deceleration of the brain or penetration of the skull with an object. Responses to stimuli and questions, loss of consciousness, and altered behavior are symptoms currently used to justify brain imaging for diagnosis and therapeutic guidance. Tests based on such symptoms are susceptible to false-positive and false-negative results due to stress, fatigue, and medications. Biochemical markers of neuronal damage and the physiological response to that damage are being identified. Biosensors capable of rapid measurement of such markers in the circulation offer a solution for on-site triage, as long as three criteria are met: (a) Recognition reagents can be identified that are sufficiently sensitive and specific, (b) the biosensor can provide quantitative assessment of multiple markers rapidly and simultaneously, and (c) both the sensor and reagents are designed for use outside the laboratory.

Two familial ALS proteins function in prevention/repair of transcription-associated DNA damage.

PubMed

Hill, Sarah J; Mordes, Daniel A; Cameron, Lisa A; Neuberg, Donna S; Landini, Serena; Eggan, Kevin; Livingston, David M

2016-11-29

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron dysfunction disease that leads to paralysis and death. There is currently no established molecular pathogenesis pathway. Multiple proteins involved in RNA processing are linked to ALS, including FUS and TDP43, and we propose a disease mechanism in which loss of function of at least one of these proteins leads to an accumulation of transcription-associated DNA damage contributing to motor neuron cell death and progressive neurological symptoms. In support of this hypothesis, we find that FUS or TDP43 depletion leads to increased sensitivity to a transcription-arresting agent due to increased DNA damage. Thus, these proteins normally contribute to the prevention or repair of transcription-associated DNA damage. In addition, both FUS and TDP43 colocalize with active RNA polymerase II at sites of DNA damage along with the DNA damage repair protein, BRCA1, and FUS and TDP43 participate in the prevention or repair of R loop-associated DNA damage, a manifestation of aberrant transcription and/or RNA processing. Gaining a better understanding of the role(s) that FUS and TDP43 play in transcription-associated DNA damage could shed light on the mechanisms underlying ALS pathogenesis.

Two familial ALS proteins function in prevention/repair of transcription-associated DNA damage

PubMed Central

Hill, Sarah J.; Mordes, Daniel A.; Cameron, Lisa A.; Neuberg, Donna S.; Landini, Serena; Eggan, Kevin; Livingston, David M.

2016-01-01

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron dysfunction disease that leads to paralysis and death. There is currently no established molecular pathogenesis pathway. Multiple proteins involved in RNA processing are linked to ALS, including FUS and TDP43, and we propose a disease mechanism in which loss of function of at least one of these proteins leads to an accumulation of transcription-associated DNA damage contributing to motor neuron cell death and progressive neurological symptoms. In support of this hypothesis, we find that FUS or TDP43 depletion leads to increased sensitivity to a transcription-arresting agent due to increased DNA damage. Thus, these proteins normally contribute to the prevention or repair of transcription-associated DNA damage. In addition, both FUS and TDP43 colocalize with active RNA polymerase II at sites of DNA damage along with the DNA damage repair protein, BRCA1, and FUS and TDP43 participate in the prevention or repair of R loop-associated DNA damage, a manifestation of aberrant transcription and/or RNA processing. Gaining a better understanding of the role(s) that FUS and TDP43 play in transcription-associated DNA damage could shed light on the mechanisms underlying ALS pathogenesis. PMID:27849576

System and method for laser-based, non-evaporative repair of damage sites in the surfaces of fused silica optics

DOEpatents

Adams, John J.; Bolourchi, Masoud; Bude, Jeffrey D.; Guss, Gabriel M.; Jarboe, Jeffery A.; Matthews, Manyalibo J.; Nostrand, Michael C; Wegner, Paul J.

2016-09-06

A method for repairing a damage site on a surface of an optical material is disclosed. The method may involve focusing an Infrared (IR) laser beam having a predetermined wavelength, with a predetermined beam power, to a predetermined full width ("F/W") 1/e.sup.2 diameter spot on the damage site. The focused IR laser beam is maintained on the damage site for a predetermined exposure period corresponding to a predetermined acceptable level of downstream intensification. The focused IR laser beam heats the damage site to a predetermined peak temperature, which melts and reflows material at the damage site of the optical material to create a mitigated site.

Comparison of glare in YAG-damaged intraocular lenses: injection-molded versus lathe-cut.

PubMed

Bath, P E; Dang, Y; Martin, W H

1986-11-01

A comparative analysis of YAG laser intraocular lens (IOL) damage was undertaken on injection-molded and lathe-cut IOLs. Damage sites were evaluated with polarized light. A consistent positive polarization was observed in the damage sites of lathe-cut IOLs. A consistent negative polarization was observed in the damage sites of injection-molded IOLs. The presence of positive polarization in IOL damage sites may be correlated with increased potential for glare. Results and clinical implications are discussed.

Genomic profiling of multiple sequentially acquired tumor metastatic sites from an “exceptional responder” lung adenocarcinoma patient reveals extensive genomic heterogeneity and novel somatic variants driving treatment response

PubMed Central

Biswas, Romi; Gao, Shaojian; Cultraro, Constance M.; Maity, Tapan K.; Venugopalan, Abhilash; Abdullaev, Zied; Shaytan, Alexey K.; Carter, Corey A.; Thomas, Anish; Rajan, Arun; Song, Young; Pitts, Stephanie; Chen, Kevin; Bass, Sara; Boland, Joseph; Hanada, Ken-Ichi; Chen, Jinqiu; Meltzer, Paul S.; Panchenko, Anna R.; Yang, James C.; Pack, Svetlana; Giaccone, Giuseppe; Schrump, David S.; Khan, Javed; Guha, Udayan

2016-01-01

We used next-generation sequencing to identify somatic alterations in multiple metastatic sites from an “exceptional responder” lung adenocarcinoma patient during his 7-yr course of ERBB2-directed therapies. The degree of heterogeneity was unprecedented, with ∼1% similarity between somatic alterations of the lung and lymph nodes. One novel translocation, PLAG1-ACTA2, present in both sites, up-regulated ACTA2 expression. ERBB2, the predominant driver oncogene, was amplified in both sites, more pronounced in the lung, and harbored an L869R mutation in the lymph node. Functional studies showed increased proliferation, migration, metastasis, and resistance to ERBB2-directed therapy because of L869R mutation and increased migration because of ACTA2 overexpression. Within the lung, a nonfunctional CDK12, due to a novel G879V mutation, correlated with down-regulation of DNA damage response genes, causing genomic instability, and sensitivity to chemotherapy. We propose a model whereby a subclone metastasized early from the primary site and evolved independently in lymph nodes. PMID:27900369

Multiple roles of the cell cycle inhibitor p21(CDKN1A) in the DNA damage response.

PubMed

Cazzalini, Ornella; Scovassi, A Ivana; Savio, Monica; Stivala, Lucia A; Prosperi, Ennio

2010-01-01

Among cell cycle regulatory proteins that are activated following DNA damage, the cyclin-dependent kinase inhibitor p21(CDKN1A) plays essential roles in the DNA damage response, by inducing cell cycle arrest, direct inhibition of DNA replication, as well as by regulating fundamental processes, like apoptosis and transcription. These functions are performed through the ability of p21 to interact with a number of proteins involved in these processes. Despite an initial controversy, during the last years several lines of evidence have also indicated that p21 may be directly involved in DNA repair. In particular, the participation of p21 in nucleotide excision repair (NER), base excision repair (BER), and DNA translesion synthesis (TLS), has been suggested to occur thanks to its interaction with proliferating cell nuclear antigen (PCNA), a crucial protein involved in several aspects of DNA metabolism, and cell-cycle regulation. In this review, the multiple roles of p21 in the DNA damage response, including regulation of cell cycle, apoptosis and gene transcription, are discussed together with the most recent findings supporting the direct participation of p21 protein in DNA repair processes. In particular, spatio-temporal dynamics of p21 recruitment to sites of DNA damage will be considered together with several lines of evidence indicating a regulatory role for p21. In addition, the relevance of post-translational regulation in the fate (e.g. degradation) of p21 protein after cell exposure to DNA damaging agents will be analyzed. Both sets of evidence will be discussed in terms of the overall DNA damage response. 2010 Elsevier B.V. All rights reserved.

DNA damage talks to inflammation.

PubMed

Cohen, Idan

2017-02-01

Interleukin-1 alpha (IL-1α) and beta (IL-1β) are pleiotropic cytokines affecting multiple cells and regulating many immune and inflammatory responses. The recent finding that nuclear IL-1α is recruited to sites of DNA damage, and its ability to actively sense and report genotoxic stress to the surrounding tissue, dramatically alters the way we view IL-1 biology. This discovery add a new face to the classical "danger theory" and show that danger signaling is not strictly limited to passive release or dying cells. Most importantly, as now physiological stresses are linked to the release or secretion of IL-1α, chronic danger signaling and the alarmin inhibition should be considered as a new therapeutic approach for many diseases that are characterized by ongoing DNA damage, stress signaling and inflammation. Copyright © 2016. Published by Elsevier Ltd.

Landscape-scale spatial patterns of winter injury to red spruce foliage in a year of heavy region-wide injury

Treesearch

Brynne E. Lazarus; Paul G. Schaberg; Gary J. Hawley; Donald H. DeHayes

2006-01-01

Red spruce (Picea rubens Sarg.) winter injury is caused by freezing damage that results in the abscission of the most recent foliar age-class. Injury was widespread and severe in the northeastern United States in 2003 and was assessed at multiple elevations at 23 sites in Vermont and adjacent states. This paper presents a spatial analysis of these...

Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: preliminary comparative PET studies with [11C]vinpocetine and [11C]PK11195 in patients.

PubMed

Vas, Adám; Shchukin, Yevgeni; Karrenbauer, Virginija D; Cselényi, Zsolt; Kostulas, Kosta; Hillert, Jan; Savic, Ivanka; Takano, Akihiro; Halldin, Christer; Gulyás, Balázs

2008-01-15

With the purpose of demonstrating the use of positron emission tomography (PET) and radiolabelled glia markers to indicate regional cerebral damage, we measured with PET in four young multiplex sclerosis (MS) patients in two consecutive measurements the global and regional brain uptake as well as regional distribution and binding potential (BP) of [(11)C]vinpocetine and [(11)C]PK11195. Both ligands showed increased uptake and BP in the regions of local brain damage. However, regional BP values for [(11)C]vinpocetine were markedly higher than those for [(11)C]PK11195. This feature of the former radioligand may be related to its high brain uptake and marked affinity to the peripheral benzodiazepine receptor binding sites (PBBS), characteristic for glia cells. As local brain traumas entail reactive glia accumulation in and around the site of the damage, the present findings may indicate that [(11)C]vinpocetine marks the place or boundaries of local brain damage by binding to the PBBS present in glia cells, which, in turn, accumulate in the region of the damage. The present findings (i) confirm earlier observations with [(11)C]PK11195 as a potential glia marker in PET studies and (ii) support the working hypothesis that [(11)C]vinpocetine is a potentially useful PET marker of regional and global brain damage resulting in glia accumulation locally or globally in the human brain. The comparative analysis of the two ligands indicate that [(11)C]vinpocetine shows a number of characteristics favourable in comparison with [(11)C]PK11195.

Recruitment of TRF2 to laser-induced DNA damage sites.

PubMed

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

2012-09-01

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

Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach.

PubMed

Stampanoni Bassi, Mario; Gilio, Luana; Buttari, Fabio; Maffei, Pierpaolo; Marfia, Girolama A; Restivo, Domenico A; Centonze, Diego; Iezzi, Ennio

2017-01-01

Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the "clinico-radiological paradox." The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

Increased methylation of repetitive elements and DNA repair genes is associated with higher DNA oxidation in children in an urbanized, industrial environment.

PubMed

Alvarado-Cruz, Isabel; Sánchez-Guerra, Marco; Hernández-Cadena, Leticia; De Vizcaya-Ruiz, Andrea; Mugica, Violeta; Pelallo-Martínez, Nadia Azenet; Solís-Heredia, María de Jesús; Byun, Hyang-Min; Baccarelli, Andrea; Quintanilla-Vega, Betzabet

2017-01-01

DNA methylation in DNA repair genes participates in the DNA damage regulation. Particulate matter (PM), which has metals and polycyclic aromatic hydrocarbons (PAHs) adsorbed, among others has been linked to adverse health outcomes and may modify DNA methylation. To evaluate PM exposure impact on repetitive elements and gene-specific DNA methylation and DNA damage, we conducted a cross-sectional study in 150 schoolchildren (7-10 years old) from an urbanized, industrial area of the metropolitan area of Mexico City (MAMC), which frequently exhibits PM concentrations above safety standards. Methylation (5mC) of long interspersed nuclear element-1 (LINE1) and DNA repair gene (OGG1, APEX, and PARP1) was assessed by pyrosequencing in peripheral mononuclear cells, DNA damage by comet assay and DNA oxidation by 8-OHdG content. PAH and metal contents in PM 10 (≤10μm aerodynamic diameter) were determined by HPLC-MS and ICP-AES, respectively. Multiple regression analysis between DNA methylation, DNA damage, and PM 10 exposure showed that PM 10 was significantly associated with oxidative DNA damage; a 1% increase in 5mC at all CpG sites in PARP1 promoter was associated with a 35% increase in 8-OHdG, while a 1% increase at 1, 2, and 3 CpG sites resulted in 38, 9, and 56% increments, respectively. An increase of 10pg/m 3 in benzo[b]fluoranthene content of PM 10 was associated with a 6% increase in LINE1 methylation. Acenaphthene, indene [1,2,3-cd] pyrene, and pyrene concentrations correlated with higher dinucleotide methylation in OGG1, APEX and PARP1 genes, respectively. Vanadium concentration correlated with increased methylation at selected APEX and PARP1 CpG sites. DNA repair gene methylation was significantly correlated with DNA damage and with specific PM 10 -associated PAHs and Vanadium. Data suggest that exposure to PM and its components are associated with differences in DNA methylation of repair genes in children, which may contribute to DNA damage. Copyright © 2016 Elsevier B.V. All rights reserved.

On-Chip Sorting of Long Semiconducting Carbon Nanotubes for Multiple Transistors along an Identical Array.

PubMed

Otsuka, Keigo; Inoue, Taiki; Maeda, Etsuo; Kometani, Reo; Chiashi, Shohei; Maruyama, Shigeo

2017-11-28

Ballistic transport and sub-10 nm channel lengths have been achieved in transistors containing one single-walled carbon nanotube (SWNT). To fill the gap between single-tube transistors and high-performance logic circuits for the replacement of silicon, large-area, high-density, and purely semiconducting (s-) SWNT arrays are highly desired. Here we demonstrate the fabrication of multiple transistors along a purely semiconducting SWNT array via an on-chip purification method. Water- and polymer-assisted burning from site-controlled nanogaps is developed for the reliable full-length removal of metallic SWNTs with the damage to s-SWNTs minimized even in high-density arrays. All the transistors with various channel lengths show large on-state current and excellent switching behavior in the off-state. Since our method potentially provides pure s-SWNT arrays over a large area with negligible damage, numerous transistors with arbitrary dimensions could be fabricated using a conventional semiconductor process, leading to SWNT-based logic, high-speed communication, and other next-generation electronic devices.

Clinical evaluation of expanded mesh connective tissue graft in the treatment for multiple adjacent gingival recessions in the esthetic zone

PubMed Central

Shanmugam, M.; Shivakumar, B.; Meenapriya, B.; Anitha, V.; Ashwath, B.

2015-01-01

Background: Multiple approaches have been used to replace lost, damaged or diseased gingival tissues. The connective tissue graft (CTG) procedure is the golden standard method for root coverage. Although multiple sites often need grafting, the palatal mucosa supplies only a limited area of grafting material. To overcome this limitation, expanded mesh graft provides a method whereby a graft can be stretched to cover a large area. The aim of this study was to evaluate the effectiveness and the predictability of expanded mesh CTG (e-MCTG) in the treatment of adjacent multiple gingival recessions. Materials and Methods: Sixteen patients aged 20–50 years contributed to 55 sites, each site falling into at least three adjacent Miller's Class 1 or Class 2 gingival recession. The CTG obtained from the palatal mucosa was expanded to cover the recipient bed, which was 1.5 times larger than the graft. Clinical measurements were recorded at baseline and 3 months, 12 months postoperatively. Results: A mean coverage of 1.96 mm ± 0.66 mm and 2.22 mm ± 0.68 mm was obtained at the end of 3rd and 12th month, respectively. Twelve months after surgery a statistically significant increase in CAL (2.2 mm ± 0.68 mm, P < 0.001) and increasing WKT (1.75 ± 0.78, P < 0.001) were obtained. In 80% of the treated sites, 100% root coverage was achieved (mean 93.5%). Conclusions: The results of this study demonstrated that multiple adjacent recessions were treated by using e-MCTG technique can be applied and highly predictable root coverage can be achieved. PMID:26321829

Combining remote sensing and on-site monitoring methods to investigate footpath erosion within a popular recreational heathland environment.

PubMed

Rodway-Dyer, Sue; Ellis, Nicola

2018-06-01

Footpaths are a prominent consequence of natural area tourism and reflect damage caused to valuable, sensitive habitats by people pressure. Degradation impacts on vegetation, wildlife, on and off-site soil movement and loss, creation of additional informal off-path footpaths (desire lines), and visual destruction of landscapes. Impacts need to be measured and monitored on a large temporal and spatial scale to aid in land management to maintain access and preserve natural environments. This study combined remote sensing (Light Detection and Ranging [LiDAR] and aerial photography) with on-site measurement of footpaths within a sensitive heathland habitat (Land's End, Cornwall, UK). Soil loss, slope angle change, vegetation damage and a hydrology model were combined to comprehensively study the site. Results showed 0.09 m mean soil loss over five years, footpath widening, increasing grass cover into heathland, and water channelling on the footpaths exacerbating erosion. The environments surrounding the footpaths were affected with visitors walking off path, requiring further management and monitoring. Multiple remote sensing techniques were highly successful in comprehensively assessing the area, particularly the hydrology model, demonstrating the potential of providing a valuable objective and quantitative monitoring and management tool. Copyright © 2018 Elsevier Ltd. All rights reserved.

Higher certainty of the laser-induced damage threshold test with a redistributing data treatment

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

Jensen, Lars; Mrohs, Marius; Gyamfi, Mark

2015-10-15

As a consequence of its statistical nature, the measurement of the laser-induced damage threshold holds always risks to over- or underestimate the real threshold value. As one of the established measurement procedures, the results of S-on-1 (and 1-on-1) tests outlined in the corresponding ISO standard 21 254 depend on the amount of data points and their distribution over the fluence scale. With the limited space on a test sample as well as the requirements on test site separation and beam sizes, the amount of data from one test is restricted. This paper reports on a way to treat damage testmore » data in order to reduce the statistical error and therefore measurement uncertainty. Three simple assumptions allow for the assignment of one data point to multiple data bins and therefore virtually increase the available data base.« less

New Experiments and a Model-Driven Approach for Interpreting Middle Stone Age Lithic Point Function Using the Edge Damage Distribution Method.

PubMed

Schoville, Benjamin J; Brown, Kyle S; Harris, Jacob A; Wilkins, Jayne

2016-01-01

The Middle Stone Age (MSA) is associated with early evidence for symbolic material culture and complex technological innovations. However, one of the most visible aspects of MSA technologies are unretouched triangular stone points that appear in the archaeological record as early as 500,000 years ago in Africa and persist throughout the MSA. How these tools were being used and discarded across a changing Pleistocene landscape can provide insight into how MSA populations prioritized technological and foraging decisions. Creating inferential links between experimental and archaeological tool use helps to establish prehistoric tool function, but is complicated by the overlaying of post-depositional damage onto behaviorally worn tools. Taphonomic damage patterning can provide insight into site formation history, but may preclude behavioral interpretations of tool function. Here, multiple experimental processes that form edge damage on unretouched lithic points from taphonomic and behavioral processes are presented. These provide experimental distributions of wear on tool edges from known processes that are then quantitatively compared to the archaeological patterning of stone point edge damage from three MSA lithic assemblages-Kathu Pan 1, Pinnacle Point Cave 13B, and Die Kelders Cave 1. By using a model-fitting approach, the results presented here provide evidence for variable MSA behavioral strategies of stone point utilization on the landscape consistent with armature tips at KP1, and cutting tools at PP13B and DK1, as well as damage contributions from post-depositional sources across assemblages. This study provides a method with which landscape-scale questions of early modern human tool-use and site-use can be addressed.

New Experiments and a Model-Driven Approach for Interpreting Middle Stone Age Lithic Point Function Using the Edge Damage Distribution Method

PubMed Central

Schoville, Benjamin J.; Brown, Kyle S.; Harris, Jacob A.; Wilkins, Jayne

2016-01-01

The Middle Stone Age (MSA) is associated with early evidence for symbolic material culture and complex technological innovations. However, one of the most visible aspects of MSA technologies are unretouched triangular stone points that appear in the archaeological record as early as 500,000 years ago in Africa and persist throughout the MSA. How these tools were being used and discarded across a changing Pleistocene landscape can provide insight into how MSA populations prioritized technological and foraging decisions. Creating inferential links between experimental and archaeological tool use helps to establish prehistoric tool function, but is complicated by the overlaying of post-depositional damage onto behaviorally worn tools. Taphonomic damage patterning can provide insight into site formation history, but may preclude behavioral interpretations of tool function. Here, multiple experimental processes that form edge damage on unretouched lithic points from taphonomic and behavioral processes are presented. These provide experimental distributions of wear on tool edges from known processes that are then quantitatively compared to the archaeological patterning of stone point edge damage from three MSA lithic assemblages—Kathu Pan 1, Pinnacle Point Cave 13B, and Die Kelders Cave 1. By using a model-fitting approach, the results presented here provide evidence for variable MSA behavioral strategies of stone point utilization on the landscape consistent with armature tips at KP1, and cutting tools at PP13B and DK1, as well as damage contributions from post-depositional sources across assemblages. This study provides a method with which landscape-scale questions of early modern human tool-use and site-use can be addressed. PMID:27736886

Mismatch repair proteins recruited to ultraviolet light-damaged sites lead to degradation of licensing factor Cdt1 in the G1 phase.

PubMed

Tanaka, Miyuki; Takahara, Michiyo; Nukina, Kohei; Hayashi, Akiyo; Sakai, Wataru; Sugasawa, Kaoru; Shiomi, Yasushi; Nishitani, Hideo

2017-04-03

Cdt1 is rapidly degraded by CRL4 Cdt2 E3 ubiquitin ligase after UV (UV) irradiation. Previous reports revealed that the nucleotide excision repair (NER) pathway is responsible for the rapid Cdt1-proteolysis. Here, we show that mismatch repair (MMR) proteins are also involved in the degradation of Cdt1 after UV irradiation in the G1 phase. First, compared with the rapid (within ∼15 min) degradation of Cdt1 in normal fibroblasts, Cdt1 remained stable for ∼30 min in NER-deficient XP-A cells, but was degraded within ∼60 min. The delayed degradation was also dependent on PCNA and CRL4 Cdt2 . The MMR proteins Msh2 and Msh6 were recruited to the UV-damaged sites of XP-A cells in the G1 phase. Depletion of these factors with small interfering RNAs prevented Cdt1 degradation in XP-A cells. Similar to the findings in XP-A cells, depletion of XPA delayed Cdt1 degradation in normal fibroblasts and U2OS cells, and co-depletion of Msh6 further prevented Cdt1 degradation. Furthermore, depletion of Msh6 alone delayed Cdt1 degradation in both cell types. When Cdt1 degradation was attenuated by high Cdt1 expression, repair synthesis at the damaged sites was inhibited. Our findings demonstrate that UV irradiation induces multiple repair pathways that activate CRL4 Cdt2 to degrade its target proteins in the G1 phase of the cell cycle, leading to efficient repair of DNA damage.

Probability of growth of small damage sites on the exit surface of fused silica optics.

PubMed

Negres, Raluca A; Abdulla, Ghaleb M; Cross, David A; Liao, Zhi M; Carr, Christopher W

2012-06-04

Growth of laser damage on fused silica optical components depends on several key parameters including laser fluence, wavelength, pulse duration, and site size. Here we investigate the growth behavior of small damage sites on the exit surface of SiO₂ optics under exposure to tightly controlled laser pulses. Results demonstrate that the onset of damage growth is not governed by a threshold, but is probabilistic in nature and depends both on the current size of a damage site and the laser fluence to which it is exposed. We also develop models for use in growth prediction. In addition, we show that laser exposure history also influences the behavior of individual sites.

Pathomorphism of spiral tibial fractures in computed tomography imaging.

PubMed

Guzik, Grzegorz

2011-01-01

Spiral fractures of the tibia are virtually homogeneous with regard to their pathomorphism. The differences that are seen concern the level of fracture of the fibula, and, to a lesser extent, the level of fracture of the tibia, the length of fracture cleft, and limb shortening following the trauma. While conventional radiographs provide sufficient information about the pathomorphism of fractures, computed tomography can be useful in demonstrating the spatial arrangement of bone fragments and topography of soft tissues surrounding the fracture site. Multiple cross-sectional computed tomography views of spiral fractures of the tibia show the details of the alignment of bone chips at the fracture site, axis of the tibial fracture cleft, and topography of soft tissues that are not visible on standard radiographs. A model of a spiral tibial fracture reveals periosteal stretching with increasing spiral and longitudinal displacement. The cleft in tibial fractures has a spiral shape and its line is invariable. Every spiral fracture of both crural bones results in extensive damage to the periosteum and may damage bellies of the long flexor muscle of toes, flexor hallucis longus as well as the posterior tibial muscle. Computed tomography images of spiral fractures of the tibia show details of damage that are otherwise invisible on standard radiographs. Moreover, CT images provide useful information about the spatial location of the bone chips as well as possible threats to soft tissues that surround the fracture site. Every spiral fracture of the tibia is associated with disruption of the periosteum. 1. Computed tomography images of spiral fractures of the tibia show details of damage otherwise invisible on standard radiographs, 2. The sharp end of the distal tibial chip can damage the tibialis posterior muscle, long flexor muscles of the toes and the flexor hallucis longus, 3. Every spiral fracture of the tibia is associated with disruption of the periosteum.

The Meninges: New Therapeutic Targets For Multiple Sclerosis

PubMed Central

Russi, Abigail E.; Brown, Melissa A.

2014-01-01

The CNS is largely comprised of non-regenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an “immune specialized” status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data has established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood barrier integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting of the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the blood brain barrier. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments. PMID:25241937

A ruggedness evaluation of procedures for damage threshold testing optical materials

NASA Technical Reports Server (NTRS)

Hooker, Matthew W.; Thomas, Milfred E.; Wise, Stephanie A.; Tappan, Nina D.

1995-01-01

A ruggedness evaluation of approaches to damage threshold testing was performed to determine the influence of three procedural variables on damage threshold data. The differences between the number of test sites evaluated at an applied fluence level (1 site versus 10 sites), the number of laser pulses at each test site (1 pulse versus 200 pulses), and the beam diameter (0.35 mm versus 0.70 mm) were all found to significantly influence the damage threshold data over a 99-percent confidence interval.

Reactive Oxygen Species (ROS)-Activated ATM-Dependent Phosphorylation of Cytoplasmic Substrates Identified by Large-Scale Phosphoproteomics Screen*

PubMed Central

Kozlov, Sergei V.; Waardenberg, Ashley J.; Engholm-Keller, Kasper; Arthur, Jonathan W.; Graham, Mark E.; Lavin, Martin

2016-01-01

Ataxia-telangiectasia, mutated (ATM) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signaling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle checkpoints, initiating DNA repair, and regulating gene expression. ATM kinase can be activated by a variety of stimuli, including oxidative stress. Here, we confirmed activation of cytoplasmic ATM by autophosphorylation at multiple sites. Then we employed a global quantitative phosphoproteomics approach to identify cytoplasmic proteins altered in their phosphorylation state in control and ataxia-telangiectasia (A-T) cells in response to oxidative damage. We demonstrated that ATM was activated by oxidative damage in the cytoplasm as well as in the nucleus and identified a total of 9,833 phosphorylation sites, including 6,686 high-confidence sites mapping to 2,536 unique proteins. A total of 62 differentially phosphorylated peptides were identified; of these, 43 were phosphorylated in control but not in A-T cells, and 19 varied in their level of phosphorylation. Motif enrichment analysis of phosphopeptides revealed that consensus ATM serine glutamine sites were overrepresented. When considering phosphorylation events, only observed in control cells (not observed in A-T cells), with predicted ATM sites phosphoSerine/phosphoThreonine glutamine, we narrowed this list to 11 candidate ATM-dependent cytoplasmic proteins. Two of these 11 were previously described as ATM substrates (HMGA1 and UIMCI/RAP80), another five were identified in a whole cell extract phosphoproteomic screens, and the remaining four proteins had not been identified previously in DNA damage response screens. We validated the phosphorylation of three of these proteins (oxidative stress responsive 1 (OSR1), HDGF, and ccdc82) as ATM dependent after H2O2 exposure, and another protein (S100A11) demonstrated ATM-dependence for translocation from the cytoplasm to the nucleus. These data provide new insights into the activation of ATM by oxidative stress through identification of novel substrates for ATM in the cytoplasm. PMID:26699800

Rapid Multi-Damage Identification for Health Monitoring of Laminated Composites Using Piezoelectric Wafer Sensor Arrays

PubMed Central

Si, Liang; Wang, Qian

2016-01-01

Through the use of the wave reflection from any damage in a structure, a Hilbert spectral analysis-based rapid multi-damage identification (HSA-RMDI) technique with piezoelectric wafer sensor arrays (PWSA) is developed to monitor and identify the presence, location and severity of damage in carbon fiber composite structures. The capability of the rapid multi-damage identification technique to extract and estimate hidden significant information from the collected data and to provide a high-resolution energy-time spectrum can be employed to successfully interpret the Lamb waves interactions with single/multiple damage. Nevertheless, to accomplish the precise positioning and effective quantification of multiple damage in a composite structure, two functional metrics from the RMDI technique are proposed and used in damage identification, which are the energy density metric and the energy time-phase shift metric. In the designed damage experimental tests, invisible damage to the naked eyes, especially delaminations, were detected in the leftward propagating waves as well as in the selected sensor responses, where the time-phase shift spectra could locate the multiple damage whereas the energy density spectra were used to quantify the multiple damage. The increasing damage was shown to follow a linear trend calculated by the RMDI technique. All damage cases considered showed completely the developed RMDI technique potential as an effective online damage inspection and assessment tool. PMID:27153070

Femtosecond near-infrared laser microirradiation reveals a crucial role for PARP signaling on factor assemblies at DNA damage sites

PubMed Central

Saquilabon Cruz, Gladys Mae; Kong, Xiangduo; Silva, Bárbara Alcaraz; Khatibzadeh, Nima; Thai, Ryan; Berns, Michael W.; Yokomori, Kyoko

2016-01-01

Laser microirradiation is a powerful tool for real-time single-cell analysis of the DNA damage response (DDR). It is often found, however, that factor recruitment or modification profiles vary depending on the laser system employed. This is likely due to an incomplete understanding of how laser conditions/dosages affect the amounts and types of damage and the DDR. We compared different irradiation conditions using a femtosecond near-infrared laser and found distinct damage site recruitment thresholds for 53BP1 and TRF2 correlating with the dose-dependent increase of strand breaks and damage complexity. Low input-power microirradiation that induces relatively simple strand breaks led to robust recruitment of 53BP1 but not TRF2. In contrast, increased strand breaks with complex damage including crosslinking and base damage generated by high input-power microirradiation resulted in TRF2 recruitment to damage sites with no 53BP1 clustering. We found that poly(ADP-ribose) polymerase (PARP) activation distinguishes between the two damage states and that PARP activation is essential for rapid TRF2 recruitment while suppressing 53BP1 accumulation at damage sites. Thus, our results reveal that careful titration of laser irradiation conditions allows induction of varying amounts and complexities of DNA damage that are gauged by differential PARP activation regulating protein assembly at the damage site. PMID:26424850

Subcatchment deltas and upland features influence multiscale aquatic ecosystem recovery in damaged landscapes.

PubMed

Kielstra, Brian W; Arnott, Shelley E; Gunn, John M

2017-12-01

Assessing biological recovery in damaged aquatic environments requires the consideration of multiple spatial and temporal scales. Past research has focused on assessing lake recovery from atmospheric or catchment disturbance at regional or catchment levels. Studies have also rarely considered the influences of adjacent terrestrial characteristics on within-lake habitats, such as subcatchment delta confluences. We used Hyalella azteca, a ubiquitous freshwater amphipod, as a sensitive indicator to assess the importance of local subcatchment scale factors in the context of multiscale lake recovery within the metal mining region of Sudbury, Canada following a period of major reductions in atmospheric pollution. At the regional scale, data from repeated surveys of 40 lakes showed higher probabilities of H. azteca occurrence with higher lake water conductivity, alkalinity, and pH and lower metal concentrations. The importance of metals decreased through time and the importance of higher conductivity, alkalinity, and pH increased. At the subcatchment scale, a subset of six lakes sampled across a colonization gradient revealed higher H. azteca abundances at subcatchment delta sites than non-delta sites in early colonization stages, and that abundance at delta sites was correlated with both within-lake habitat and terrestrial subcatchment characteristics. For example, wetland cover reduced the strength of positive associations between H. azteca abundance and macrophyte density. A single lake from this subset also revealed higher abundances at delta sites associated with higher concentrations of terrestrial organic matter and larger subcatchments. Our results demonstrate that factors affecting recovery can change with the scale of study, and that managing terrestrial-aquatic linkages is important for facilitating recovery processes within damaged lake ecosystems. © 2017 by the Ecological Society of America.

Simplified computational methods for elastic and elastic-plastic fracture problems

NASA Technical Reports Server (NTRS)

Atluri, Satya N.

1992-01-01

An overview is given of some of the recent (1984-1991) developments in computational/analytical methods in the mechanics of fractures. Topics covered include analytical solutions for elliptical or circular cracks embedded in isotropic or transversely isotropic solids, with crack faces being subjected to arbitrary tractions; finite element or boundary element alternating methods for two or three dimensional crack problems; a 'direct stiffness' method for stiffened panels with flexible fasteners and with multiple cracks; multiple site damage near a row of fastener holes; an analysis of cracks with bonded repair patches; methods for the generation of weight functions for two and three dimensional crack problems; and domain-integral methods for elastic-plastic or inelastic crack mechanics.

Repair of Clustered Damage and DNA Polymerase Iota.

PubMed

Belousova, E A; Lavrik, O I

2015-08-01

Multiple DNA lesions occurring within one or two turns of the DNA helix known as clustered damage are a source of double-stranded DNA breaks, which represent a serious threat to the cells. Repair of clustered lesions is accomplished in several steps. If a clustered lesion contains oxidized bases, an individual DNA lesion is repaired by the base excision repair (BER) mechanism involving a specialized DNA polymerase after excising DNA damage. Here, we investigated DNA synthesis catalyzed by DNA polymerase iota using damaged DNA templates. Two types of DNA substrates were used as model DNAs: partial DNA duplexes containing breaks of different length, and DNA duplexes containing 5-formyluracil (5-foU) and uracil as a precursor of apurinic/apyrimidinic sites (AP) in opposite DNA strands. For the first time, we showed that DNA polymerase iota is able to catalyze DNA synthesis using partial DNA duplexes having breaks of different length as substrates. In addition, we found that DNA polymerase iota could catalyze DNA synthesis during repair of clustered damage via the BER system by using both undamaged and 5-foU-containing templates. We found that hPCNA (human proliferating cell nuclear antigen) increased efficacy of DNA synthesis catalyzed by DNA polymerase iota.

Scalable process for mitigation of laser-damaged potassium dihydrogen phosphate crystal optic surfaces with removal of damaged antireflective coating

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

Elhadj, S.; Steele, W. A.; VanBlarcom, D. S.

Here, we investigate an approach for the recycling of laser-damaged large-aperture deuterated potassium dihydrogen phosphate (DKDP) crystals used for optical switching (KDP) and for frequency conversion (DKDP) in megajoule-class high-power laser systems. The approach consists of micromachining the surface laser damage sites (mitigation), combined with multiple soaks and ultrasonication steps in a coating solvent to remove, synergistically, both the highly adherent machining debris and the laser-damage-affected antireflection coating. We then identify features of the laser-damage-affected coating, such as the “solvent-persistent” coating and the “burned-in” coating, that are difficult to remove by conventional approaches without damaging the surface. We also providemore » a solution to the erosion problem identified in this work when colloidal coatings are processed during ultrasonication. Finally, we provide a proof of principle of the approach by testing the full process that includes laser damage mitigation of DKDP test parts, coat stripping, reapplication of a new antireflective coat, and a laser damage test demonstrating performance up to at least 12 J/cm 2 at UV wavelengths, which is well above current requirements. Our approach ultimately provides a potential path to a scalable recycling loop for the management of optics in large, high-power laser systems that can reduce cost and extend lifetime of highly valuable and difficult to grow large DKDP crystals.« less

Scalable process for mitigation of laser-damaged potassium dihydrogen phosphate crystal optic surfaces with removal of damaged antireflective coating

DOE PAGES

Elhadj, S.; Steele, W. A.; VanBlarcom, D. S.; ...

2017-03-07

Here, we investigate an approach for the recycling of laser-damaged large-aperture deuterated potassium dihydrogen phosphate (DKDP) crystals used for optical switching (KDP) and for frequency conversion (DKDP) in megajoule-class high-power laser systems. The approach consists of micromachining the surface laser damage sites (mitigation), combined with multiple soaks and ultrasonication steps in a coating solvent to remove, synergistically, both the highly adherent machining debris and the laser-damage-affected antireflection coating. We then identify features of the laser-damage-affected coating, such as the “solvent-persistent” coating and the “burned-in” coating, that are difficult to remove by conventional approaches without damaging the surface. We also providemore » a solution to the erosion problem identified in this work when colloidal coatings are processed during ultrasonication. Finally, we provide a proof of principle of the approach by testing the full process that includes laser damage mitigation of DKDP test parts, coat stripping, reapplication of a new antireflective coat, and a laser damage test demonstrating performance up to at least 12 J/cm 2 at UV wavelengths, which is well above current requirements. Our approach ultimately provides a potential path to a scalable recycling loop for the management of optics in large, high-power laser systems that can reduce cost and extend lifetime of highly valuable and difficult to grow large DKDP crystals.« less

Genotoxic and oxidative effects induced on A549 cells by extract of PM10 collected in an electric steel plant.

PubMed

Cavallo, Delia; Ursini, Cinzia L; Maiello, Raffaele; Apostoli, Pietro; Catalani, Simona; Ciervo, Aureliano; Iavicoli, Sergio

2008-01-01

The present study was aimed at assessing the carcinogenic risk of occupational exposure to PM10 in electric steel plants. PM10 was collected on cellulose filter respectively outside (site 1) and inside (site 2) the furnace area, was measured, extracted and its metal content was analysed by ICP-MS. Cells were exposed for 30 min, 2 and 4 hours to extract of filter from each site diluted at 0.004, 0.008 and 0.02%. The direct/oxidative DNA damage caused by PM10 was evaluated on A549 cells by Fpg-modified comet assay, analysing Tail moment (TM) and comet percentage. Air samples contained 1.08 mg/m3 of PM10 in site 1 and 5.54 mg/m3in site 2 and different amounts of metals with higher levels of Zn, Al, Ni, Pb, Cd, Cr, Ba in site 2 and of Fe, Mn, Sb in site 1. In cells exposed for 2h to PM10 from both sites, an oxidative DNA damage was found concentrations of 0.008% and 0.02%. For site 2, a direct DNA damage at 0.02% was also found. After 4h a direct/oxidative DNA damage was detected at 0.02% for site 2 and an oxidative DNA damage for site 1. The results indicate a moderate DNA damage induction by used diluitions of PM10 extracts with higher extent for more polluted site 2. These findings show the suitability of this experimental model to evaluate early DNA damage induced by complex mixtures containing metals on target organ, suggesting its use to study biological effects of occupational exposure to such substances.

Delayed repair of radiation induced clustered DNA damage: Friend or foe?

PubMed Central

Eccles, Laura J.; O’Neill, Peter; Lomax, Martine E.

2011-01-01

A signature of ionizing radiation exposure is the induction of DNA clustered damaged sites, defined as two or more lesions within one to two helical turns of DNA by passage of a single radiation track. Clustered damage is made up of double strand breaks (DSB) with associated base lesions or abasic (AP) sites, and non-DSB clusters comprised of base lesions, AP sites and single strand breaks. This review will concentrate on the experimental findings of the processing of non-DSB clustered damaged sites. It has been shown that non-DSB clustered damaged sites compromise the base excision repair pathway leading to the lifetime extension of the lesions within the cluster, compared to isolated lesions, thus the likelihood that the lesions persist to replication and induce mutation is increased. In addition certain non-DSB clustered damaged sites are processed within the cell to form additional DSB. The use of E. coli to demonstrate that clustering of DNA lesions is the major cause of the detrimental consequences of ionizing radiation is also discussed. The delayed repair of non-DSB clustered damaged sites in humans can be seen as a “friend”, leading to cell killing in tumour cells or as a “foe”, resulting in the formation of mutations and genetic instability in normal tissue. PMID:21130102

Variability in wood-frame building damage using broad-band synthetic ground motions: a comparative numerical study with recorded motions

USGS Publications Warehouse

Pei, Shiling; van de Lindt, John W.; Hartzell, Stephen; Luco, Nicolas

2014-01-01

Earthquake damage to light-frame wood buildings is a major concern for North America because of the volume of this construction type. In order to estimate wood building damage using synthetic ground motions, we need to verify the ability of synthetically generated ground motions to simulate realistic damage for this structure type. Through a calibrated damage potential indicator, four different synthetic ground motion models are compared with the historically recorded ground motions at corresponding sites. We conclude that damage for sites farther from the fault (>20 km) is under-predicted on average and damage at closer sites is sometimes over-predicted.

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

PubMed Central

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

2015-01-01

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

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

Freudenthal, Bret D.; Beard, William A.; Cuneo, Matthew J.

DNA apurinic-apyrimidinic (AP) sites are prevalent noncoding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA-repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive, owing in part to limited structural information. Here we report multiple high-resolution human APE1-DNA structures that divulge new features of the APE1 reaction, including the metal-binding site, the nucleophile and the arginine clamps that mediate product release. We also report APE1-DNA structures with a T-G mismatch 5' to the AP site, representing a clustered lesion occurring in methylatedmore » CpG dinucleotides. Moreover, these structures reveal that APE1 molds the T-G mismatch into a unique Watson-Crick-like geometry that distorts the active site, thus reducing incision. Finally, these snapshots provide mechanistic clarity for APE1 while affording a rational framework to manipulate biological responses to DNA damage.« less

Iatrogenic deep musculocutaneous radiation injury following percutaneous coronary intervention.

PubMed

Monaco, JoAn L; Bowen, Kanika; Tadros, Peter N; Witt, Peter D

2003-08-01

Radiation-induced skin injury has been reported for multiple fluoroscopic procedures. Previous studies have indicated that prolonged fluoroscopic exposure during even a single percutaneous coronary intervention (PCI) may lead to cutaneous radiation injury. We document a novel case of deep muscle damage requiring wide local debridement and muscle flap reconstruction in a 59-year-old man with a large radiation-induced wound to the lower thoracic region following 1 prolonged PCI procedure. The deep muscular iatrogenic injury described in this report may be the source of significant morbidity. Recommendations to reduce radiation-induced damage include careful examination of the skin site before each procedure, minimized fluoroscopy time, utilization of pulse fluoroscopy, employment of radiation filters, and collimator s and rotation of the location of the image intensifier.

Thoracic Unilateral Spinal Cord Injury After Spinal Anaesthesia for Total Hip Replacement: Fate or Mistake?

PubMed Central

Fabio, Costa; Romualdo, Del Buono; Eugenio, Agrò Felice; Vittoradolfo, Tambone; Massimiliano, Vitali Andrea; Giovanna, Ricci

2017-01-01

Spinal anaesthesia is the most preffered anesthesia technique for total hip replacement, and its complications range from low entity (insignificant) to life threatening. The incidence of neurologic complications after neuraxial anaesthesia is not perfectly clear, although there are several described cases of spinal cord ischaemia. We present a case of unilateral T8–T11 spinal cord ischaemia following L2–L3 spinal anaesthesia for total hip replacement. Magnetic resonance imaging showed a hyperintense T8–T11 signal alteration on the leftside of paramedian spinal cord. A temporal epidemiologic linkage between the damage and the surgery seems to be present. The injury occurred without anatomical proximity between the injury site and the spinal needle entry site. This may be due to multiple contributing factors, each of them is probably not enough to determine the damage by itself; however, acting simultaneously, they could have been responsible for the complication. The result was unpredictable and unavoidable and was caused by unforeseeable circumstances and not by inadequate medical practice. PMID:28439446

Proliferating Cell Nuclear Antigen-dependent Rapid Recruitment of Cdt1 and CRL4Cdt2 at DNA-damaged Sites after UV Irradiation in HeLa Cells*

PubMed Central

Ishii, Takashi; Shiomi, Yasushi; Takami, Toshihiro; Murakami, Yusuke; Ohnishi, Naho; Nishitani, Hideo

2010-01-01

The licensing factor Cdt1 is degraded by CRL4Cdt2 ubiquitin ligase dependent on proliferating cell nuclear antigen (PCNA) during S phase and when DNA damage is induced in G1 phase. Association of both Cdt2 and PCNA with chromatin was observed in S phase and after UV irradiation. Here we used a micropore UV irradiation assay to examine Cdt2 accumulation at cyclobutane pyrimidine dimer-containing DNA-damaged sites in the process of Cdt1 degradation in HeLa cells. Cdt2, present in the nucleus throughout the cell cycle, accumulated rapidly at damaged DNA sites during G1 phase. The recruitment of Cdt2 is dependent on prior PCNA chromatin binding because Cdt2 association was prevented when PCNA was silenced. Cdt1 was also recruited to damaged sites soon after UV irradiation through its PIP-box. As Cdt1 was degraded, the Cdt2 signal at damaged sites was reduced, but PCNA, cyclobutane pyrimidine dimer, and XPA (xeroderma pigmentosum, complementation group A) signals remained at the same levels. These findings suggest that Cdt1 degradation following UV irradiation occurs rapidly at damaged sites due to PCNA chromatin loading and the recruitment of Cdt1 and CRL4Cdt2, before DNA damage repair is completed. PMID:20929861

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.

The meninges: new therapeutic targets for multiple sclerosis.

PubMed

Russi, Abigail E; Brown, Melissa A

2015-02-01

The central nervous system (CNS) largely comprises nonregenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell-mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an "immune-specialized" status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data have established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood-brain barrier (BBB) integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the BBB. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

Single-digit arithmetic processing—anatomical evidence from statistical voxel-based lesion analysis

PubMed Central

Mihulowicz, Urszula; Willmes, Klaus; Karnath, Hans-Otto; Klein, Elise

2014-01-01

Different specific mechanisms have been suggested for solving single-digit arithmetic operations. However, the neural correlates underlying basic arithmetic (multiplication, addition, subtraction) are still under debate. In the present study, we systematically assessed single-digit arithmetic in a group of acute stroke patients (n = 45) with circumscribed left- or right-hemispheric brain lesions. Lesion sites significantly related to impaired performance were found only in the left-hemisphere damaged (LHD) group. Deficits in multiplication and addition were related to subcortical/white matter brain regions differing from those for subtraction tasks, corroborating the notion of distinct processing pathways for different arithmetic tasks. Additionally, our results further point to the importance of investigating fiber pathways in numerical cognition. PMID:24847238

Transcription and DNA Damage: Holding Hands or Crossing Swords?

PubMed

D'Alessandro, Giuseppina; d'Adda di Fagagna, Fabrizio

2017-10-27

Transcription has classically been considered a potential threat to genome integrity. Collision between transcription and DNA replication machinery, and retention of DNA:RNA hybrids, may result in genome instability. On the other hand, it has been proposed that active genes repair faster and preferentially via homologous recombination. Moreover, while canonical transcription is inhibited in the proximity of DNA double-strand breaks, a growing body of evidence supports active non-canonical transcription at DNA damage sites. Small non-coding RNAs accumulate at DNA double-strand break sites in mammals and other organisms, and are involved in DNA damage signaling and repair. Furthermore, RNA binding proteins are recruited to DNA damage sites and participate in the DNA damage response. Here, we discuss the impact of transcription on genome stability, the role of RNA binding proteins at DNA damage sites, and the function of small non-coding RNAs generated upon damage in the signaling and repair of DNA lesions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clusters of DNA damage induced by ionizing radiation: formation of short DNA fragments. II. Experimental detection

NASA Technical Reports Server (NTRS)

Rydberg, B.; Chatterjee, A. (Principal Investigator)

1996-01-01

The basic 30-nm chromatin fiber in the mammalian cell consists of an unknown (possibly helical) arrangement of nucleosomes, with about 1.2 kb of DNA per 10-nm length of fiber. Track-structure considerations suggest that interactions of single delta rays or high-LET particles with the chromatin fiber might result in the formation of multiple lesions spread over a few kilobases of DNA (see the accompanying paper: W.R. Holley and A. Chatterjee, Radiat. Res. 145, 188-199, 1996). In particular, multiple DNA double-strand breaks and single-strand breaks may form. To test this experimentally, primary human fibroblasts were labeled with [3H]thymidine and exposed at 0 degrees C to X rays or accelerated nitrogen or iron ions in the LET range of 97-440 keV/microns. DNA was isolated inside agarose plugs and subjected to agarose gel electrophoresis under conditions that allowed good separation of 0.1-2 kb size DNA. The bulk of DNA remained in the well or migrated only a small distance into the gel. It was found that DNA fragments in the expected size range were formed linearly with dose with an efficiency that increased with LET. A comparison of the yield of such fragments with the yield of total DNA double-strand breaks suggests that for the high-LET ions a substantial proportion (20-90%) of DNA double-strand breaks are accompanied within 0.1-2 kb by at least one additional DNA double-strand break. It is shown that these results are in good agreement with theoretical calculations based on treating the 30-nm chromatin fiber as the target for ionizing particles. Theoretical considerations also predict that the clusters will contain numerous single-strand breaks and base damages. It is proposed that such clusters be designated "regionally multiply damaged sites." Postirradiation incubation at 37 degrees C resulted in a decline in the number of short DNA fragments, suggesting a repair activity. The biological significance of regionally multiply damaged sites is presently unknown.

Double-strand break repair-adox: Restoration of suppressed double-strand break repair during mitosis induces genomic instability

PubMed Central

Terasawa, Masahiro; Shinohara, Akira; Shinohara, Miki

2014-01-01

Double-strand breaks (DSBs) are one of the severest types of DNA damage. Unrepaired DSBs easily induce cell death and chromosome aberrations. To maintain genomic stability, cells have checkpoint and DSB repair systems to respond to DNA damage throughout most of the cell cycle. The failure of this process often results in apoptosis or genomic instability, such as aneuploidy, deletion, or translocation. Therefore, DSB repair is essential for maintenance of genomic stability. During mitosis, however, cells seem to suppress the DNA damage response and proceed to the next G1 phase, even if there are unrepaired DSBs. The biological significance of this suppression is not known. In this review, we summarize recent studies of mitotic DSB repair and discuss the mechanisms of suppression of DSB repair during mitosis. DSB repair, which maintains genomic integrity in other phases of the cell cycle, is rather toxic to cells during mitosis, often resulting in chromosome missegregation and aberration. Cells have multiple safeguards to prevent genomic instability during mitosis: inhibition of 53BP1 or BRCA1 localization to DSB sites, which is important to promote non-homologous end joining or homologous recombination, respectively, and also modulation of the non-homologous end joining core complex to inhibit DSB repair. We discuss how DSBs during mitosis are toxic and the multiple safeguard systems that suppress genomic instability. PMID:25287622

mBAND Analysis of Early and Late Damages in the Chromosome of Human Lymphocytes after Exposures to Gamma Rays and Fe Ions

NASA Technical Reports Server (NTRS)

Sunagawa, Mayumi; Zhang, Ye; Yeshitla, Samrawit; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

2013-01-01

Stable type chromosome aberrations that survive multiple generations of cell division include translocation and inversions. An efficient method to detect an inversion is multi-color banding fluorescent in situ hybridization (mBAND) which allows identification of both inter- and intrachromosome aberrations simultaneously. Post irradiation, chromosome aberrations may also arise after multiple cell divisions as a result of genomic instability. To investigate the stable or late-arising chromosome aberrations induced after radiation exposure, we exposed human lymphocytes to gamma rays and Fe ions ex vivo, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis and at several time intervals during the culture period post irradiation. With gamma irradiation, about half of the damages observed at first mitosis remained after 7 day- and 14 day- culture, suggesting the transmissibility of damages to the surviving progeny. At the doses that produced similar frequencies of gamma-induced chromosome aberrations as observed at first mitosis, a significantly lower yield of aberrations remained at the same population doublings after Fe ion exposure. At these equitoxic doses, more complex type aberrations were observed for Fe ions, indicating that Fe ion-induced initial chromosome damages are more severe and may lead to cell death. Detailed analysis of breaks participating in total chromosome exchanges within the first cell cycle post irradiation revealed a common hotspot located in the 3p21 region, which is a known fragile site corresponding to the band 6 in the mBand analysis. The breakpoint distribution in chromosomes collected at 7 days, but not at 14 days, post irradiation appeared similar to the distribution in cells collected within the first cell cycle post irradiation. The breakpoint distribution for human lymphocytes after radiation exposure was different from the previously published distribution for human mammary epithelial cells, indicating that interphase chromatin folding structures play a role in the distribution of radiation-induced breaks.

Acutely damaged axons are remyelinated in multiple sclerosis and experimental models of demyelination.

PubMed

Schultz, Verena; van der Meer, Franziska; Wrzos, Claudia; Scheidt, Uta; Bahn, Erik; Stadelmann, Christine; Brück, Wolfgang; Junker, Andreas

2017-08-01

Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de- and remyelination, we employed cuprizone- and focal lysolecithin-induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage. We observed damaged axons with signs of remyelination after cuprizone diet cessation and lysolecithin injection. Similar observations were made in early multiple sclerosis lesions. To assess the correlation of remyelination and axonal damage in multiple sclerosis lesions, we took advantage of a cohort of patients with early and late stage remyelinated lesions and assessed the number of APP- and SMI32- positive damaged axons and the density of SMI31-positive and silver impregnated preserved axons. Early de- and remyelinating lesions did not differ with respect to axonal density and axonal damage, but we observed a lower axonal density in late stage demyelinated multiple sclerosis lesions than in remyelinated multiple sclerosis lesions. Our findings suggest that remyelination may not only be protective over a long period of time, but may play an important role in the immediate axonal recuperation after a demyelinating insult. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

Evaluation of impairment of DNA in marine gastropod, Morula granulata as a biomarker of marine pollution.

PubMed

Sarkar, A; Bhagat, Jacky; Sarker, Subhodeep

2014-08-01

The impairment of DNA in marine gastropod Morula granulata was evaluated in terms of the loss of DNA integrity in the species as a measure of the impact of genotoxic contaminants prevalent in the marine environment along the coast of Goa, India. The extent of DNA damage occurred in the marine gastropods collected from different sampling sites such as Arambol, Anjuna, Sinquerim, Dona Paula, Bogmalo, Hollant, Velsao, Betul and Palolem along the coast of Goa was measured following the technique of partial alkaline unwinding as well as comet assays. The highest DNA integrity was observed at Arambol (F, 0.75), identified as the reference site, whereas the lowest DNA integrity at Hollant (F, 0.33) situated between the two most contaminated sites at Bogmalo and Velsao. The impact of genotoxic contaminants on marine gastropods was pronounced by their low DNA integrity at Sinquerim (F, 0.40) followed by Betul (F, 0.47), Velsao (F, 0.51), Anjuna (F, 0.54), Bogmalo (F, 0.55), Dona Paula (F, 0.67) and Palolem (F, 0.70). The extent of DNA damage occurred in M. granulata due to ecotoxicological impact of the prevailing marine pollutants along the coast of Goa was further substantiated by comet assay and expressed in terms of %head-DNA, %tail DNA, tail length and Olive tail moment. The single cell gel electrophoresis of M. granulata clearly showed relatively higher olive tail moment in the marine gastropod from the contaminated sites, Anjuna, Hollant, Velsao and Betul. The variation in the mean %head DNA at different sampling sites clearly indicated that the extent of DNA damage in marine gastropod increases with the increase in the levels of contamination at different sampling sites along the coast. The stepwise multiple regression analysis of the water quality parameters showed significant correlation between the variation in DNA integrity and PAH in combination with NO3, salinity and PO4 (R¯(2), 0.90). The measurement of DNA integrity in M. granulata thus provides an early warning signal of contamination of the coastal ecosystem of Goa by genotoxic contaminants. Copyright © 2014 Elsevier Inc. All rights reserved.

Precision Laser Annealing of Focal Plane Arrays

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

Bender, Daniel A.; DeRose, Christopher; Starbuck, Andrew Lea

2015-09-01

We present results from laser annealing experiments in Si using a passively Q-switched Nd:YAG microlaser. Exposure with laser at fluence values above the damage threshold of commercially available photodiodes results in electrical damage (as measured by an increase in photodiode dark current). We show that increasing the laser fluence to values in excess of the damage threshold can result in annealing of a damage site and a reduction in detector dark current by as much as 100x in some cases. A still further increase in fluence results in irreparable damage. Thus we demonstrate the presence of a laser annealing windowmore » over which performance of damaged detectors can be at least partially reconstituted. Moreover dark current reduction is observed over the entire operating range of the diode indicating that device performance has been improved for all values of reverse bias voltage. Additionally, we will present results of laser annealing in Si waveguides. By exposing a small (<10 um) length of a Si waveguide to an annealing laser pulse, the longitudinal phase of light acquired in propagating through the waveguide can be modified with high precision, <15 milliradian per laser pulse. Phase tuning by 180 degrees is exhibited with multiple exposures to one arm of a Mach-Zehnder interferometer at fluence values below the morphological damage threshold of an etched Si waveguide. No reduction in optical transmission at 1550 nm was found after 220 annealing laser shots. Modeling results for laser annealing in Si are also presented.« less

On-Line Multi-Damage Scanning Spatial-Wavenumber Filter Based Imaging Method for Aircraft Composite Structure.

PubMed

Ren, Yuanqiang; Qiu, Lei; Yuan, Shenfang; Bao, Qiao

2017-05-11

Structural health monitoring (SHM) of aircraft composite structure is helpful to increase reliability and reduce maintenance costs. Due to the great effectiveness in distinguishing particular guided wave modes and identifying the propagation direction, the spatial-wavenumber filter technique has emerged as an interesting SHM topic. In this paper, a new scanning spatial-wavenumber filter (SSWF) based imaging method for multiple damages is proposed to conduct on-line monitoring of aircraft composite structures. Firstly, an on-line multi-damage SSWF is established, including the fundamental principle of SSWF for multiple damages based on a linear piezoelectric (PZT) sensor array, and a corresponding wavenumber-time imaging mechanism by using the multi-damage scattering signal. Secondly, through combining the on-line multi-damage SSWF and a PZT 2D cross-shaped array, an image-mapping method is proposed to conduct wavenumber synthesis and convert the two wavenumber-time images obtained by the PZT 2D cross-shaped array to an angle-distance image, from which the multiple damages can be directly recognized and located. In the experimental validation, both simulated multi-damage and real multi-damage introduced by repeated impacts are performed on a composite plate structure. The maximum localization error is less than 2 cm, which shows good performance of the multi-damage imaging method. Compared with the existing spatial-wavenumber filter based damage evaluation methods, the proposed method requires no more than the multi-damage scattering signal and can be performed without depending on any wavenumber modeling or measuring. Besides, this method locates multiple damages by imaging instead of the geometric method, which helps to improve the signal-to-noise ratio. Thus, it can be easily applied to on-line multi-damage monitoring of aircraft composite structures.

On-Line Multi-Damage Scanning Spatial-Wavenumber Filter Based Imaging Method for Aircraft Composite Structure

PubMed Central

Ren, Yuanqiang; Qiu, Lei; Yuan, Shenfang; Bao, Qiao

2017-01-01

Structural health monitoring (SHM) of aircraft composite structure is helpful to increase reliability and reduce maintenance costs. Due to the great effectiveness in distinguishing particular guided wave modes and identifying the propagation direction, the spatial-wavenumber filter technique has emerged as an interesting SHM topic. In this paper, a new scanning spatial-wavenumber filter (SSWF) based imaging method for multiple damages is proposed to conduct on-line monitoring of aircraft composite structures. Firstly, an on-line multi-damage SSWF is established, including the fundamental principle of SSWF for multiple damages based on a linear piezoelectric (PZT) sensor array, and a corresponding wavenumber-time imaging mechanism by using the multi-damage scattering signal. Secondly, through combining the on-line multi-damage SSWF and a PZT 2D cross-shaped array, an image-mapping method is proposed to conduct wavenumber synthesis and convert the two wavenumber-time images obtained by the PZT 2D cross-shaped array to an angle-distance image, from which the multiple damages can be directly recognized and located. In the experimental validation, both simulated multi-damage and real multi-damage introduced by repeated impacts are performed on a composite plate structure. The maximum localization error is less than 2 cm, which shows good performance of the multi-damage imaging method. Compared with the existing spatial-wavenumber filter based damage evaluation methods, the proposed method requires no more than the multi-damage scattering signal and can be performed without depending on any wavenumber modeling or measuring. Besides, this method locates multiple damages by imaging instead of the geometric method, which helps to improve the signal-to-noise ratio. Thus, it can be easily applied to on-line multi-damage monitoring of aircraft composite structures. PMID:28772879

Ten problems and solutions when predicting individual outcome from lesion site after stroke.

PubMed

Price, Cathy J; Hope, Thomas M; Seghier, Mohamed L

2017-01-15

In this paper, we consider solutions to ten of the challenges faced when trying to predict an individual's functional outcome after stroke on the basis of lesion site. A primary goal is to find lesion-outcome associations that are consistently observed in large populations of stroke patients because consistent associations maximise confidence in future individualised predictions. To understand and control multiple sources of inter-patient variability, we need to systematically investigate each contributing factor and how each factor depends on other factors. This requires very large cohorts of patients, who differ from one another in typical and measurable ways, including lesion site, lesion size, functional outcome and time post stroke (weeks to decades). These multivariate investigations are complex, particularly when the contributions of different variables interact with one another. Machine learning algorithms can help to identify the most influential variables and indicate dependencies between different factors. Multivariate lesion analyses are needed to understand how the effect of damage to one brain region depends on damage or preservation in other brain regions. Such data-led investigations can reveal predictive relationships between lesion site and outcome. However, to understand and improve the predictions we need explanatory models of the neural networks and degenerate pathways that support functions of interest. This will entail integrating the results of lesion analyses with those from functional imaging (fMRI, MEG), transcranial magnetic stimulation (TMS) and diffusor tensor imaging (DTI) studies of healthy participants and patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Ten problems and solutions when predicting individual outcome from lesion site after stroke

PubMed Central

Price, Cathy J.; Hope, Thomas M.; Seghier, Mohamed L.

2016-01-01

In this paper, we consider solutions to ten of the challenges faced when trying to predict an individual’s functional outcome after stroke on the basis of lesion site. A primary goal is to find lesion-outcome associations that are consistently observed in large populations of stroke patients because consistent associations maximise confidence in future individualised predictions. To understand and control multiple sources of inter-patient variability, we need to systematically investigate each contributing factor and how each factor depends on other factors. This requires very large cohorts of patients, who differ from one another in typical and measurable ways, including lesion site, lesion size, functional outcome and time post stroke (weeks to decades). These multivariate investigations are complex, particularly when the contributions of different variables interact with one another. Machine learning algorithms can help to identify the most influential variables and indicate dependencies between different factors. Multivariate lesion analyses are needed to understand how the effect of damage to one brain region depends on damage or preservation in other brain regions. Such data-led investigations can reveal predictive relationships between lesion site and outcome. However, to understand and improve predictions we need explanatory models of the neural networks and degenerate pathways that support functions of interest. This will entail integrating the results of lesion analyses with those from functional imaging (fMRI, MEG), transcranial magnetic stimulation (TMS) and diffusor tensor imaging (DTI) studies of healthy participants and patients. PMID:27502048

Fracture Strength of Fused Silica From Photonic Signatures Around Collision Sites

NASA Technical Reports Server (NTRS)

Yost, William T.; Cramer, K Elliott

2015-01-01

Impact sites in glass affect its fracture strength. An analytical model that predicts fracture strength from grey-field polariscope (GFP) readings (photoelastic retardations) has been developed and reported in the literature. The model is suggestive that stress fields, resulting from impact damage, destablizes sites within the glass, which lead to pathways that cause strength degradation. Using data collected from fused silica specimens fabricated from outer window panes that were designed for the space shuttle, the model was tested against four categories of inflicted damage. The damage sites were cored from the window carcasses, examined with the GFP and broken using the ASTM Standard C1499-09 to measure the fracture strength. A correlation is made between the fracture strength and the photoelastic retardation measured at the damage site in each specimen. A least-squares fit is calculated. The results are compared with the predictions from the model. A plausible single-sided NDE damage site inspection method (a version of which is planned for glass inspection in the Orion Project) that relates photoelastic retardation in glass components to its fracture strength is presented.

DNA damage during the G0/G1 phase triggers RNA-templated, Cockayne syndrome B-dependent homologous recombination.

PubMed

Wei, Leizhen; Nakajima, Satoshi; Böhm, Stefanie; Bernstein, Kara A; Shen, Zhiyuan; Tsang, Michael; Levine, Arthur S; Lan, Li

2015-07-07

Damage repair mechanisms at transcriptionally active sites during the G0/G1 phase are largely unknown. To elucidate these mechanisms, we introduced genome site-specific oxidative DNA damage and determined the role of transcription in repair factor assembly. We find that KU and NBS1 are recruited to damage sites independent of transcription. However, assembly of RPA1, RAD51C, RAD51, and RAD52 at such sites is strictly governed by active transcription and requires both wild-type Cockayne syndrome protein B (CSB) function and the presence of RNA in the G0/G1 phase. We show that the ATPase activity of CSB is indispensable for loading and binding of the recombination factors. CSB counters radiation-induced DNA damage in both cells and zebrafish models. Taken together, our results have uncovered a novel, RNA-based recombination mechanism by which CSB protects genome stability from strand breaks at transcriptionally active sites and may provide insight into the clinical manifestations of Cockayne syndrome.

Structure of the human gene encoding the protein repair L-isoaspartyl (D-aspartyl) O-methyltransferase.

PubMed

DeVry, C G; Tsai, W; Clarke, S

1996-11-15

The protein L-isoaspartyl/D-aspartyl O-methyltransferase (EC 2.1.1.77) catalyzes the first step in the repair of proteins damaged in the aging process by isomerization or racemization reactions at aspartyl and asparaginyl residues. A single gene has been localized to human chromosome 6 and multiple transcripts arising through alternative splicing have been identified. Restriction enzyme mapping, subcloning, and DNA sequence analysis of three overlapping clones from a human genomic library in bacteriophage P1 indicate that the gene spans approximately 60 kb and is composed of 8 exons interrupted by 7 introns. Analysis of intron/exon splice junctions reveals that all of the donor and acceptor splice sites are in agreement with the mammalian consensus splicing sequence. Determination of transcription initiation sites by primer extension analysis of poly(A)+ mRNA from human brain identifies multiple start sites, with a major site 159 nucleotides upstream from the ATG start codon. Sequence analysis of the 5'-untranslated region demonstrates several potential cis-acting DNA elements including SP1, ETF, AP1, AP2, ARE, XRE, CREB, MED-1, and half-palindromic ERE motifs. The promoter of this methyltransferase gene lacks an identifiable TATA box but is characterized by a CpG island which begins approximately 723 nucleotides upstream of the major transcriptional start site and extends through exon 1 and into the first intron. These features are characteristic of housekeeping genes and are consistent with the wide tissue distribution observed for this methyltransferase activity.

DNA damage induced by the direct effect of radiation

NASA Astrophysics Data System (ADS)

Yokoya, A.; Shikazono, N.; Fujii, K.; Urushibara, A.; Akamatsu, K.; Watanabe, R.

2008-10-01

We have studied the nature of DNA damage induced by the direct effect of radiation. The yields of single- (SSB) and double-strand breaks (DSB), base lesions and clustered damage were measured using the agarose gel electrophoresis method after exposing to various kinds of radiations to a simple model DNA molecule, fully hydrated closed-circular plasmid DNA (pUC18). The yield of SSB does not show significant dependence on linear energy transfer (LET) values. On the other hand, the yields of base lesions revealed by enzymatic probes, endonuclease III (Nth) and formamidopyrimidine DNA glycosylase (Fpg), which excise base lesions and leave a nick at the damage site, strongly depend on LET values. Soft X-ray photon (150 kVp) irradiation gives a maximum yield of the base lesions detected by the enzymatic probes as SSB and clustered damage, which is composed of one base lesion and proximate other base lesions or SSBs. The clustered damage is visualized as an enzymatically induced DSB. The yields of the enzymatically additional damages strikingly decrease with increasing levels of LET. These results suggest that in higher LET regions, the repair enzymes used as probes are compromised because of the dense damage clustering. The studies using simple plasmid DNA as a irradiation sample, however, have a technical difficulty to detect multiple SSBs in a plasmid DNA. To detect the additional SSBs induced in opposite strand of the first SSB, we have also developed a novel technique of DNA-denaturation assay. This allows us to detect multiply induced SSBs in both strand of DNA, but not induced DSB.

EROD activity, chromosomal damage, and oxidative stress in response to contaminants exposure in tree swallow (Tachycineta bicolor) nestlings from Great Lakes Areas of Concern

USGS Publications Warehouse

Custer, Thomas W.; Custer, Christine M.; Dummer, Paul; Bigorgne, Emilie; Oziolor, Elias; Karouna-Renier, Natalie K.; Schultz, Sandra; Erickson, Richard A.; Aagaard, Kevin; Matson, Cole W.

2017-01-01

Tree swallow, Tachycineta bicolor, nestlings were collected from 60 sites in the Great Lakes, which included multiple sites within 27 Areas of Concern (AOCs) and six sites not listed as AOCs from 2010 to 2014. Nestlings, approximately 12 days-of-age, were evaluated for ethoxyresorufin-O-dealkylase (EROD) activity, chromosomal damage, and six measures of oxidative stress. Data on each of these biomarkers were divided into four equal numbered groups from the highest to lowest values and the groups were compared to contaminant concentrations using multivariate analysis. Contaminant concentrations, from the same nestlings, included polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), perfluorinated compounds (PFCs), and 17 elements. Alkylated polycyclic aromatic hydrocarbons (aPAHs) and parent PAHs (pPAHs) were measured in pooled nestling dietary samples. Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and pesticides were measured in sibling eggs. Concentrations of aPAHs, pPAHs, chlordane, dieldrin, heptachlor, and PCBs, in that order, were the major contributors to the significant differences between the lowest and highest EROD activities; PFCs, PBDEs, the remaining pesticides, and all elements were of secondary importance. The four categories of chromosomal damage did not separate out well based on the contaminants measured. Concentrations of aPAHs, pPAHs, heptachlor, PCBs, chlordane, and dieldrin were the major contributors to the significant differences between the lowest and highest activities of two oxidative stress measures, total sulfhydryl (TSH) activity and protein bound sulfhydryl (PBSH) activity. The four categories of thiobarbituric acid reacting substances (TBARS), oxidized glutathione (GSSG), reduced glutathione (GSH), and the ratio of GSSG/GSH did not separate well based on the contaminants measured.

EROD activity, chromosomal damage, and oxidative stress in response to contaminants exposure in tree swallow (Tachycineta bicolor) nestlings from Great Lakes Areas of Concern.

PubMed

Custer, Thomas W; Custer, Christine M; Dummer, Paul M; Bigorgne, Emilie; Oziolor, Elias M; Karouna-Renier, Natalie; Schultz, Sandra; Erickson, Richard A; Aagaard, Kevin; Matson, Cole W

2017-12-01

Tree swallow, Tachycineta bicolor, nestlings were collected from 60 sites in the Great Lakes, which included multiple sites within 27 Areas of Concern (AOCs) and six sites not listed as AOCs from 2010 to 2014. Nestlings, approximately 12 days-of-age, were evaluated for ethoxyresorufin-O-dealkylase (EROD) activity, chromosomal damage, and six measures of oxidative stress. Data on each of these biomarkers were divided into four equal numbered groups from the highest to lowest values and the groups were compared to contaminant concentrations using multivariate analysis. Contaminant concentrations, from the same nestlings, included polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), perfluorinated compounds (PFCs), and 17 elements. Alkylated polycyclic aromatic hydrocarbons (aPAHs) and parent PAHs (pPAHs) were measured in pooled nestling dietary samples. Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and pesticides were measured in sibling eggs. Concentrations of aPAHs, pPAHs, chlordane, dieldrin, heptachlor, and PCBs, in that order, were the major contributors to the significant differences between the lowest and highest EROD activities; PFCs, PBDEs, the remaining pesticides, and all elements were of secondary importance. The four categories of chromosomal damage did not separate out well based on the contaminants measured. Concentrations of aPAHs, pPAHs, heptachlor, PCBs, chlordane, and dieldrin were the major contributors to the significant differences between the lowest and highest activities of two oxidative stress measures, total sulfhydryl (TSH) activity and protein bound sulfhydryl (PBSH) activity. The four categories of thiobarbituric acid reacting substances (TBARS), oxidized glutathione (GSSG), reduced glutathione (GSH), and the ratio of GSSG/GSH did not separate well based on the contaminants measured.

Aging as an Epigenetic Phenomenon

PubMed Central

Ashapkin, Vasily V.; Kutueva, Lyudmila I.; Vanyushin, Boris F.

2017-01-01

Introduction: Hypermethylation of genes associated with promoter CpG islands, and hypomethylation of CpG poor genes, repeat sequences, transposable elements and intergenic genome sections occur during aging in mammals. Methylation levels of certain CpG sites display strict correlation to age and could be used as “epigenetic clock” to predict biological age. Multi-substrate deacetylases SIRT1 and SIRT6 affect aging via locus-specific modulations of chromatin structure and activity of multiple regulatory proteins involved in aging. Random errors in DNA methylation and other epigenetic marks during aging increase the transcriptional noise, and thus lead to enhanced phenotypic variation between cells of the same tissue. Such variation could cause progressive organ dysfunction observed in aged individuals. Multiple experimental data show that induction of NF-κB regulated gene sets occurs in various tissues of aged mammals. Upregulation of multiple miRNAs occurs at mid age leading to downregulation of enzymes and regulatory proteins involved in basic cellular functions, such as DNA repair, oxidative phosphorylation, intermediate metabolism, and others. Conclusion: Strong evidence shows that all epigenetic systems contribute to the lifespan control in various organisms. Similar to other cell systems, epigenome is prone to gradual degradation due to the genome damage, stressful agents, and other aging factors. But unlike mutations and other kinds of the genome damage, age-related epigenetic changes could be fully or partially reversed to a “young” state. PMID:29081695

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.

Multifocal Neuropathy: Expanding the Scope of Double Crush Syndrome.

PubMed

Cohen, Brian H; Gaspar, Michael P; Daniels, Alan H; Akelman, Edward; Kane, Patrick M

2016-12-01

Double crush syndrome (DCS), as it is classically defined, is a clinical condition composed of neurological dysfunction due to compressive pathology at multiple sites along a single peripheral nerve. The traditional definition of DCS is narrow in scope because many systemic pathologic processes, such as diabetes mellitus, drug-induced neuropathy, vascular disease and autoimmune neuronal damage, can have deleterious effects on nerve function. Multifocal neuropathy is a more appropriate term describing the multiple etiologies (including compressive lesions) that may synergistically contribute to nerve dysfunction and clinical symptoms. This paper examines the history of DCS and multifocal neuropathy, including the epidemiology and pathophysiology in addition to principles of evaluation and management. Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

3-ω damage threshold evaluation of final optics components using Beamlet Mule and off-line testing

NASA Astrophysics Data System (ADS)

Kozlowski, Mark R.; Maricle, Stephen M.; Mouser, Ron P.; Schwartz, Sheldon; Wegner, Paul J.; Weiland, Timothy L.

1999-07-01

A statistics-based model is being develop to predict the laser-damage-limited lifetime of UV optical components on the NIF laser. In order to provide data for the mode, laser damage experiments were performed on the Beamlet laser system at LLNL. An early protoype NIF focus lens was exposed to twenty 351 nm pulses at an average fluence of 5 J/cm2, 3ns. Using a high resolution optic inspection inspection system a total of 353 damage sites was detected within the 1160 cm2 beam aperture. Through inspections of the lens before, after and, in some cases, during the campaign, pulse to pulse damage growth rates were measured for damage initiating both on the surface and at bulk inclusions. Growth rates as high as 79 micrometers /pulse were observed for damage initiating at pre-existing scratches in the surface. For most damage sites on the optic, both on the surface and at bulk inclusions. Growth rates as high as 79 micrometers /pulse were observed for damage initiating at per- existing scratches in the surface. For most damage sites on the optic, both surface and bulk, the damage growth rate was approximately 10(Mu) m/pulse.

Extracting the distribution of laser damage precursors on fused silica surfaces for 351 nm, 3 ns laser pulses at high fluences (20-150 J/cm2).

PubMed

Laurence, Ted A; Bude, Jeff D; Ly, Sonny; Shen, Nan; Feit, Michael D

2012-05-07

Surface laser damage limits the lifetime of optics for systems guiding high fluence pulses, particularly damage in silica optics used for inertial confinement fusion-class lasers (nanosecond-scale high energy pulses at 355 nm/3.5 eV). The density of damage precursors at low fluence has been measured using large beams (1-3 cm); higher fluences cannot be measured easily since the high density of resulting damage initiation sites results in clustering. We developed automated experiments and analysis that allow us to damage test thousands of sites with small beams (10-30 µm), and automatically image the test sites to determine if laser damage occurred. We developed an analysis method that provides a rigorous connection between these small beam damage test results of damage probability versus laser pulse energy and the large beam damage results of damage precursor densities versus fluence. We find that for uncoated and coated fused silica samples, the distribution of precursors nearly flattens at very high fluences, up to 150 J/cm2, providing important constraints on the physical distribution and nature of these precursors.

The FHA domain determines Drosophila Chk2/Mnk localization to key mitotic structures and is essential for early embryonic DNA damage responses.

PubMed

Takada, Saeko; Collins, Eric R; Kurahashi, Kayo

2015-05-15

DNA damage responses, including mitotic centrosome inactivation, cell-cycle delay in mitosis, and nuclear dropping from embryo cortex, maintain genome integrity in syncytial Drosophila embryos. A conserved signaling kinase, Chk2, known as Mnk/Loki, is essential for the responses. Here we demonstrate that functional EGFP-Mnk expressed from a transgene localizes to the nucleus, centrosomes, interkinetochore/centromere region, midbody, and pseudocleavage furrows without DNA damage and in addition forms numerous foci/aggregates on mitotic chromosomes upon DNA damage. We expressed EGFP-tagged Mnk deletion or point mutation variants and investigated domain functions of Mnk in vivo. A triple mutation in the phosphopeptide-binding site of the forkhead-associated (FHA) domain disrupted normal Mnk localization except to the nucleus. The mutation also disrupted Mnk foci formation on chromosomes upon DNA damage. FHA mutations and deletion of the SQ/TQ-cluster domain (SCD) abolished Mnk transphosphorylations and autophosphorylations, indicative of kinase activation after DNA damage. A potent NLS was found at the C-terminus, which is required for normal Mnk function. We propose that the FHA domain in Mnk plays essential dual functions in mediating embryonic DNA damage responses by means of its phosphopeptide-binding ability: activating Mnk in the nucleus upon DNA damage and recruiting Mnk to multiple subcellular structures independently of DNA damage. © 2015 Takada et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Cerebellar Degeneration

MedlinePlus

... cause inflammation in the brain, including the cerebellum multiple sclerosis, in which damage to the insulating membrane (myelin) ... cause inflammation in the brain, including the cerebellum multiple sclerosis, in which damage to the insulating membrane (myelin) ...

A Loblolly Pine Management Guide: Managing Site Damage from Logging

Treesearch

W.H. McKee; G.E. Hatchell; A.E. Tiarks

1985-01-01

Serious damage to forest sites during logging can be avoided through careful planning of logging, preparation of the site for logging, and close supervision of the work.Losses in productivity caused by compaction can be largely restored by cultivation and fertilization.

Oral streptococci utilize a Siglec-like domain of serine-rich repeat adhesins to preferentially target platelet sialoglycans in human blood.

PubMed

Deng, Lingquan; Bensing, Barbara A; Thamadilok, Supaporn; Yu, Hai; Lau, Kam; Chen, Xi; Ruhl, Stefan; Sullam, Paul M; Varki, Ajit

2014-12-01

Damaged cardiac valves attract blood-borne bacteria, and infective endocarditis is often caused by viridans group streptococci. While such bacteria use multiple adhesins to maintain their normal oral commensal state, recognition of platelet sialoglycans provides an intermediary for binding to damaged valvular endocardium. We use a customized sialoglycan microarray to explore the varied binding properties of phylogenetically related serine-rich repeat adhesins, the GspB, Hsa, and SrpA homologs from Streptococcus gordonii and Streptococcus sanguinis species, which belong to a highly conserved family of glycoproteins that contribute to virulence for a broad range of Gram-positive pathogens. Binding profiles of recombinant soluble homologs containing novel sialic acid-recognizing Siglec-like domains correlate well with binding of corresponding whole bacteria to arrays. These bacteria show multiple modes of glycan, protein, or divalent cation-dependent binding to synthetic glycoconjugates and isolated glycoproteins in vitro. However, endogenous asialoglycan-recognizing clearance receptors are known to ensure that only fully sialylated glycans dominate in the endovascular system, wherein we find these particular streptococci become primarily dependent on their Siglec-like adhesins for glycan-mediated recognition events. Remarkably, despite an excess of alternate sialoglycan ligands in cellular and soluble blood components, these adhesins selectively target intact bacteria to sialylated ligands on platelets, within human whole blood. These preferred interactions are inhibited by corresponding recombinant soluble adhesins, which also preferentially recognize platelets. Our data indicate that circulating platelets may act as inadvertent Trojan horse carriers of oral streptococci to the site of damaged endocardium, and provide an explanation why it is that among innumerable microbes that gain occasional access to the bloodstream, certain viridans group streptococci have a selective advantage in colonizing damaged cardiac valves and cause infective endocarditis.

Liquefaction-induced lateral spreading in Oceano, California, during the 2003 San Simeon Earthquake

USGS Publications Warehouse

Holzer, Thomas L.; Noce, Thomas E.; Bennett, Michael J.; Di Alessandro, Carola; Boatwright, John; Tinsley, John C.; Sell, Russell W.; Rosenberg, Lewis I.

2004-01-01

The December 22, 2003, San Simeon, California, (M6.5) earthquake caused damage to houses, road surfaces, and underground utilities in Oceano, California. The community of Oceano is approximately 50 miles (80 km) from the earthquake epicenter. Damage at this distance from a M6.5 earthquake is unusual. To understand the causes of this damage, the U.S. Geological Survey conducted extensive subsurface exploration and monitoring of aftershocks in the months after the earthquake. The investigation included 37 seismic cone penetration tests, 5 soil borings, and aftershock monitoring from January 28 to March 7, 2004. The USGS investigation identified two earthquake hazards in Oceano that explain the San Simeon earthquake damage?site amplification and liquefaction. Site amplification is a phenomenon observed in many earthquakes where the strength of the shaking increases abnormally in areas where the seismic-wave velocity of shallow geologic layers is low. As a result, earthquake shaking is felt more strongly than in surrounding areas without similar geologic conditions. Site amplification in Oceano is indicated by the physical properties of the geologic layers beneath Oceano and was confirmed by monitoring aftershocks. Liquefaction, which is also commonly observed during earthquakes, is a phenomenon where saturated sands lose their strength during an earthquake and become fluid-like and mobile. As a result, the ground may undergo large permanent displacements that can damage underground utilities and well-built surface structures. The type of displacement of major concern associated with liquefaction is lateral spreading because it involves displacement of large blocks of ground down gentle slopes or towards stream channels. The USGS investigation indicates that the shallow geologic units beneath Oceano are very susceptible to liquefaction. They include young sand dunes and clean sandy artificial fill that was used to bury and convert marshes into developable lots. Most of the 2003 damage was caused by lateral spreading in two separate areas, one near Norswing Drive and the other near Juanita Avenue. The areas coincided with areas with the highest liquefaction potential found in Oceano. Areas with site amplification conditions similar to those in Oceano are particularly vulnerable to earthquakes. Site amplification may cause shaking from distant earthquakes, which normally would not cause damage, to increase locally to damaging levels. The vulnerability in Oceano is compounded by the widespread distribution of highly liquefiable soils that will reliquefy when ground shaking is amplified as it was during the San Simeon earthquake. The experience in Oceano can be expected to repeat because the region has many active faults capable of generating large earthquakes. In addition, liquefaction and lateral spreading will be more extensive for moderate-size earthquakes that are closer to Oceano than was the 2003 San Simeon earthquake. Site amplification and liquefaction can be mitigated. Shaking is typically mitigated in California by adopting and enforcing up-to-date building codes. Although not a guarantee of safety, application of these codes ensures that the best practice is used in construction. Building codes, however, do not always require the upgrading of older structures to new code requirements. Consequently, many older structures may not be as resistant to earthquake shaking as new ones. For older structures, retrofitting is required to bring them up to code. Seismic provisions in codes also generally do not apply to nonstructural elements such as drywall, heating systems, and shelving. Frequently, nonstructural damage dominates the earthquake loss. Mitigation of potential liquefaction in Oceano presently is voluntary for existing buildings, but required by San Luis Obispo County for new construction. Multiple mitigation procedures are available to individual property owners. These procedures typically involve either

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.

Phenothiazinium based photosensitisers--photodynamic agents with a multiplicity of cellular targets and clinical applications.

PubMed

Harris, F; Chatfield, L K; Phoenix, D A

2005-08-01

PhBPs show selectivity for tumour and microbial cells, which appears to be based on electrostatic interactions between the positive charge generally carried by these molecules and the negative charge found on the outer surface of these target cells. In some cases, a site of action for photoactivated PhBPs is the outer membrane/envelope of the target cell. Such action can involve the modification of membrane lipid and/or lipopolysaccharide, and the inactivation of essential proteins and enzymes, with these effects usually leading to cell lysis and death. However, more often, PhBPs are internalised by target cells, promoted by a variety of factors, including low pH and enzymatic reduction, and upon photoactivation, internalised, PhBPs are able to inflict damage on a number of intracellular targets. In tumour cells, PhBPs can photodamage DNA and the membranes of organelles, thereby inducing necrosis and/or apoptosis. In bacterial cells, whilst DNA is generally a primary target of PhBPs, these compounds can exhibit multiple sites of action within a given cell and show different sites of action between different bacterial species. This variable targeting makes PhBPs attractive propositions as alternatives to conventional antibiotics in that the emergence of bacterial strains with acquired resistance to these compounds appears to be highly unlikely.

Hypochlorite-induced damage to DNA, RNA, and polynucleotides: formation of chloramines and nitrogen-centered radicals.

PubMed

Hawkins, Clare L; Davies, Michael J

2002-01-01

Stimulated monocytes and neutrophils generate hypochlorite (HOCl) via the release of the enzyme myeloperoxidase and hydrogen peroxide. HOCl is a key bactericidal agent, but can also damage host tissue. As there is a strong link between chronic inflammation and some cancers, we have investigated HOCl damage to DNA, RNA, and polynucleotides. Reaction of HOCl with these materials is shown to yield multiple semistable chloramines (RNHCl/RR'NCl), which are the major initial products, and account for 50-95% of the added HOCl. These chloramines decay by thermal and metal-ion catalyzed processes, to give nucleoside-derived, nitrogen-centered, radicals. The latter have been characterized by EPR spin trapping. The propensity for radical formation with polynucleotides is cytidine > adenosine = guanosine > uridine = thymidine. The rates of decay, and yield of radicals formed, are dependent on the nature of the nucleobase on which they are formed, with chloramines formed from ring heterocyclic amine groups being less stable than those formed on exocyclic amines (RNH2 groups). Evidence is presented for chlorine transfer from the former, kinetically favored, sites to the more thermodynamically favored exocyclic amines. EPR experiments have also provided evidence for the rapid addition of pyrimidine-derived nitrogen-centered radicals to other nucleobases to give dimers and the oxidation of DNA by radicals derived from preformed nucleoside chloramines. Direct reaction of HOCl with plasmid DNA gives rise to single- and double-strand breaks via chloramine-mediated reactions. Preformed nucleoside chloramines also induce plasmid cleavage, though this only occurs to a significant extent with unstable thymidine- and uridine-derived chloramines, where radical formation is rapid. Overall the data rationalize the preferential formation of chlorinated 2'-deoxycytidine and 2'-deoxyadenosine in DNA and suggest that DNA damage induced by HOCl, and preformed chloramines, occurs at sequence-specific sites.

Double-strand break repair-adox: Restoration of suppressed double-strand break repair during mitosis induces genomic instability.

PubMed

Terasawa, Masahiro; Shinohara, Akira; Shinohara, Miki

2014-12-01

Double-strand breaks (DSBs) are one of the severest types of DNA damage. Unrepaired DSBs easily induce cell death and chromosome aberrations. To maintain genomic stability, cells have checkpoint and DSB repair systems to respond to DNA damage throughout most of the cell cycle. The failure of this process often results in apoptosis or genomic instability, such as aneuploidy, deletion, or translocation. Therefore, DSB repair is essential for maintenance of genomic stability. During mitosis, however, cells seem to suppress the DNA damage response and proceed to the next G1 phase, even if there are unrepaired DSBs. The biological significance of this suppression is not known. In this review, we summarize recent studies of mitotic DSB repair and discuss the mechanisms of suppression of DSB repair during mitosis. DSB repair, which maintains genomic integrity in other phases of the cell cycle, is rather toxic to cells during mitosis, often resulting in chromosome missegregation and aberration. Cells have multiple safeguards to prevent genomic instability during mitosis: inhibition of 53BP1 or BRCA1 localization to DSB sites, which is important to promote non-homologous end joining or homologous recombination, respectively, and also modulation of the non-homologous end joining core complex to inhibit DSB repair. We discuss how DSBs during mitosis are toxic and the multiple safeguard systems that suppress genomic instability. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Affective brain areas and sleep disordered breathing

PubMed Central

Harper, Ronald M.; Kumar, Rajesh; Macey, Paul M.; Woo, Mary A.; Ogren, Jennifer A.

2014-01-01

The neural damage accompanying the hypoxia, reduced perfusion, and other consequences of sleep-disordered breathing found in obstructive sleep apnea, heart failure (HF), and congenital central hypoventilation syndrome (CCHS), appears in areas that serve multiple functions, including emotional drives to breathe, and involve systems that serve affective, cardiovascular, and breathing roles. The damage, assessed with structural magnetic resonance imaging (MRI) procedures, shows tissue loss or water content and diffusion changes indicative of injury, and impaired axonal integrity between structures; damage is preferentially unilateral. Functional MRI responses in affected areas also are time- or amplitude- distorted to ventilatory or autonomic challenges. Among the structures injured are the insular, cingulate, and ventral medial prefrontal cortices, as well as cerebellar deep nuclei and cortex, anterior hypothalamus, raphé, ventrolateral medulla, basal ganglia and, in CCHS, the locus coeruleus. Raphé and locus coeruleus injury may modify serotonergic and adrenergic modulation of upper airway and arousal characteristics. Since both axons and gray matter show injury, the consequences to function, especially to autonomic, cognitive, and mood regulation, are major. Several affected rostral sites, including the insular and cingulate cortices and hippocampus, mediate aspects of dyspnea, especially in CCHS, while others, including the anterior cingulate and thalamus, participate in initiation of inspiration after central breathing pauses, and the medullary injury can impair baroreflex and breathing control. The ancillary injury associated with sleep-disordered breathing to central structures can elicit multiple other distortions in cardiovascular, cognitive, and emotional functions in addition to effects on breathing regulation. PMID:24746053

Wind damage effects of Hurricane Andrew on mangrove communities along the southwest coast of Florida, USA

USGS Publications Warehouse

Doyle, T.W.; Smith, T. J.; Robblee, M.B.

1995-01-01

On August 24, 1992, Hurricane Andrew downed and defoliated an extensive swath of mangrove trees across the lower Florida peninsula. Permanent field sites were established to assess the extent of forest damage and to monitor the rate and process of forest recovery. Canopy trees suffered the highest mortality particularly for sites within and immediately north of the storm's eyewall. The type and extent of site damage, windthrow, branch loss, and defoliation generally decreased exponentially with increasing distance from the storm track. Forest damage was greater for sites in the storm's right quadrant than in the left quadrant tor the same given distance from the storm center. Stand exposure, both horizontally and vertically, increased the susceptibility and probability of forest damage and accounted for much of the local variability. Slight species differences were found. Laguncularia racemosa exceeded Avicennia germinans and Rhizophora mangle in damage tendency under similar wind conditions. Azimuths of downed trees were strongly correlated with maximum wind speed and vector based on a hurricane simulation of the storm. Lateral branch loss and leaf defoliation on sites without windthrow damage indicated a degree of crown thinning and light penetration equivalent to treefall gaps under normally intact forest conditions. Mangrove species and forests are susceptible to catastrophic disturbance by hurricanes; the impacts of which are significant to changes in forest structure and function.

Characterization of micron-sized, optical coating defects by photothermal deflection microscopy

NASA Astrophysics Data System (ADS)

Abate, J. A.; Schmid, A. W.; Guardalben, M. G.; Smith, D. J.; Jacobs, S. D.

1984-04-01

Information about the localized absorbing defects in optical thin films is required for a better understanding of laser induced damage. Photothermal deflection microscopy offers a nondestructive optical diagnostic which yields spatially resolved absorption data on simple and multiple layer AR and HR dielectric coatings. The computer controlled apparatus used to generate absorption maps of dielectric thin films and an experiment in which a partial correlation between localized absorption sites and damage caused by nanosecond laser irradiation at 351 nm is established are described. An absolute calibration of absorption for our measurement technique is presented here. Micron sized absorbtive defects of Cu were introduced into our coatings to provide a means of calibration. Also presented here are some preliminary data on the modification of the absorption signatures measured by photothermal deflection as a function of the location of the defect within the coating layers.

Simulation of spread and control of lesions in brain.

PubMed

Thamattoor Raman, Krishna Mohan

2012-01-01

A simulation model for the spread and control of lesions in the brain is constructed using a planar network (graph) representation for the central nervous system (CNS). The model is inspired by the lesion structures observed in the case of multiple sclerosis (MS), a chronic disease of the CNS. The initial lesion site is at the center of a unit square and spreads outwards based on the success rate in damaging edges (axons) of the network. The damaged edges send out alarm signals which, at appropriate intensity levels, generate programmed cell death. Depending on the extent and timing of the programmed cell death, the lesion may get controlled or aggravated akin to the control of wild fires by burning of peripheral vegetation. The parameter phase space of the model shows smooth transition from uncontrolled situation to controlled situation. The simulations show that the model is capable of generating a wide variety of lesion growth and arrest scenarios.

Pleurotus eryngii Ameliorates Lipopolysaccharide-Induced Lung Inflammation in Mice

PubMed Central

Andoh, Tsugunobu; Ouchi, Kenji; Inatomi, Satoshi

2014-01-01

Pleurotus eryngii (P. eryngii) is consumed as a fresh cultivated mushroom worldwide and demonstrated to have multiple beneficial effects. We investigated the anti-inflammatory effect of P. eryngii in mice with acute lung injury (ALI). Intranasal instillation of lipopolysaccharide (LPS) (10 μg/site/mouse) induced marked lung inflammation (increase in the number of inflammatory cells, protein leakage, and production of nitric oxide in bronchoalveolar lavage fluid) as well as histopathological damage in the lung, 6 h after treatment. Mice administered heat-treated P. eryngii (0.3–1 g/kg, p.o. (HTPE)) 1 h before LPS challenge showed decreased pulmonary inflammation and ameliorated histopathological damage. These results suggest that HTPE has anti-inflammatory effects against ALI. Thus, P. eryngii itself may also have anti-inflammatory effects and could be a beneficial food for the prevention of ALI induced by bacterial infection. PMID:24799939

Pleurotus eryngii Ameliorates Lipopolysaccharide-Induced Lung Inflammation in Mice.

PubMed

Kawai, Junya; Andoh, Tsugunobu; Ouchi, Kenji; Inatomi, Satoshi

2014-01-01

Pleurotus eryngii (P. eryngii) is consumed as a fresh cultivated mushroom worldwide and demonstrated to have multiple beneficial effects. We investigated the anti-inflammatory effect of P. eryngii in mice with acute lung injury (ALI). Intranasal instillation of lipopolysaccharide (LPS) (10  μ g/site/mouse) induced marked lung inflammation (increase in the number of inflammatory cells, protein leakage, and production of nitric oxide in bronchoalveolar lavage fluid) as well as histopathological damage in the lung, 6 h after treatment. Mice administered heat-treated P. eryngii (0.3-1 g/kg, p.o. (HTPE)) 1 h before LPS challenge showed decreased pulmonary inflammation and ameliorated histopathological damage. These results suggest that HTPE has anti-inflammatory effects against ALI. Thus, P. eryngii itself may also have anti-inflammatory effects and could be a beneficial food for the prevention of ALI induced by bacterial infection.

DNA damage during the G0/G1 phase triggers RNA-templated, Cockayne syndrome B-dependent homologous recombination

PubMed Central

Wei, Leizhen; Nakajima, Satoshi; Böhm, Stefanie; Bernstein, Kara A.; Shen, Zhiyuan; Tsang, Michael; Levine, Arthur S.; Lan, Li

2015-01-01

Damage repair mechanisms at transcriptionally active sites during the G0/G1 phase are largely unknown. To elucidate these mechanisms, we introduced genome site-specific oxidative DNA damage and determined the role of transcription in repair factor assembly. We find that KU and NBS1 are recruited to damage sites independent of transcription. However, assembly of RPA1, RAD51C, RAD51, and RAD52 at such sites is strictly governed by active transcription and requires both wild-type Cockayne syndrome protein B (CSB) function and the presence of RNA in the G0/G1 phase. We show that the ATPase activity of CSB is indispensable for loading and binding of the recombination factors. CSB counters radiation-induced DNA damage in both cells and zebrafish models. Taken together, our results have uncovered a novel, RNA-based recombination mechanism by which CSB protects genome stability from strand breaks at transcriptionally active sites and may provide insight into the clinical manifestations of Cockayne syndrome. PMID:26100862

Determination on Damage Mechanism of the Planet Gear of Heavy Vehicle Final Drive

NASA Astrophysics Data System (ADS)

Ramdan, RD; Setiawan, R.; Sasmita, F.; Suratman, R.; Taufiqulloh

2018-02-01

The works focus on the investigation of damage mechanism of fractured in the form of spalling of the planet gears from the final drive assembly of 160-ton heavy vehicles. The objective of this work is to clearly understand the mechanism of damage. The work is the first stage of the on-going research on the remaining life estimation of such gears. The understanding of the damage mechanism is critical in order to provide accurate estimate of the gear’s remaining life with observed initial damage. The analysis was performed based on the metallurgy laboratory works, including visual observation, macro-micro fractography by optical stereo and optical microscope and micro-vickers hardness test. From visual observation it was observed pitting that form lining defect at common position, which is at gear flank position. From spalling sample it was observed ratchet mark at the boundary between macro pitting and the edge of fractured parts. Further observation on the cross-section of the samples by optical microscope confirm that initial micro pitting occur without spalling of the case hardened surface. Spalling occur when pitting achieve certain critical size, and occur at multiple initiation site of crack propagation. From the present research it was concluded that pitting was resulted due to repeated contact fatigue. In addition, development of micro to macro pitting as well as spalling occur at certain direction towards the top of the gear teeth.

DNA damage and repair after high LET radiation

NASA Astrophysics Data System (ADS)

O'Neill, Peter; Cucinotta, Francis; Anderson, Jennifer

Predictions from biophysical models of interactions of radiation tracks with cellular DNA indicate that clustered DNA damage sites, defined as two or more lesions formed within one or two helical turns of the DNA by passage of a single radiation track, are formed in mammalian cells. These complex DNA damage sites are regarded as a signature of ionizing radiation exposure particularly as the likelihood of clustered damage sites arising endogenously is low. For instance, it was predicted from biophysical modelling that 30-40% of low LET-induced double strand breaks (DSB), a form of clustered damage, are complex with the yield increasing to >90% for high LET radiation, consistent with the reduced reparability of DSB with increasing ionization density of the radiation. The question arises whether the increased biological effects such as mutagenesis, carcinogenesis and lethality is in part related to DNA damage complexity and/or spatial distribution of the damage sites, which may lead to small DNA fragments. With particle radiation it is also important to consider not only delta-rays which may cause clustered damaged sites and may be highly mutagenic but the non-random spatial distribution of DSB which may lead to deletions. In this overview I will concentrate on the molecular aspects of the variation of the complexity of DNA damage on radiation quality and the challenges this complexity presents the DNA damage repair pathways. I will draw on data from micro-irradiations which indicate that the repair of DSBs by non-homologous end joining is highly regulated with pathway choice and kinetics of repair dependent on the chemical complexity of the DSB. In summary the aim is to emphasis the link between the spatial distribution of energy deposition events related to the track, the molecular products formed and the consequence of damage complexity contributing to biological effects and to present some of the outstanding molecular challenges with particle radiation.

Experimental and simulated ultrasonic characterization of complex damage in fused silica.

PubMed

Martin, L Peter; Chambers, David H; Thomas, Graham H

2002-02-01

The growth of a laser-induced, surface damage site in a fused silica window was monitored by the ultrasonic pulse-echo technique. The laser damage was grown using 12-ns pulses of 1.053-microm wavelength light at a fluence of approximately 27 J/cm2. The ultrasonic data were acquired after each pulse of the laser beam for 19 pulses. In addition, optical images of the surface and subsurface damage shape were recorded after each pulse of the laser. The ultrasonic signal amplitude exhibited variations with the damage size, which were attributed to the subsurface morphology of the damage site. A mechanism for the observed ultrasonic data based on the interaction of the ultrasound with cracks radiating from the damage site was tested using two-dimensional numerical simulations. The simulated results exhibit qualitatively similar characteristics to the experimental data and demonstrate the usefulness of numerical simulation as an aid for ultrasonic signal interpretation. The observed sensitivity to subsurface morphology makes the ultrasonic methodology a promising tool for monitoring laser damage in large aperture laser optics used in fusion energy research.

[New challenge of tissue repair and regenerative medicine: to achieve a perfect repair and regeneration of multiple tissues in wound sites].

PubMed

Fu, X B

2016-01-01

Great achievements in the study of tissue repair and regeneration have been made, and many of these successes have been shown to be beneficial to the patients in recent years. However, perfect tissue repair and regeneration of damaged tissues and organs remain to be great challenges in the management of trauma and diseases. Based on the progress in developmental biology in animals and advances in stem cell biology, it is possible to attain the aim of perfect repair and regeneration by means of somatic cell reprogramming and different inducing techniques.

Local x-ray structure analysis of optically manipulated biological micro-objects

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

Cojoc, Dan; Ferrari, Enrico; Santucci, Silvia C.

2010-12-13

X-ray diffraction using micro- and nanofocused beams is well suited for nanostructure analysis at different sites of a biological micro-object. To conduct in vitro studies without mechanical contact, we developed object manipulation by optical tweezers in a microfluidic cell. Here we report x-ray microdiffraction analysis of a micro-object optically trapped in three dimensions. We revealed the nanostructure of a single starch granule at different points and investigated local radiation damage induced by repeated x-ray exposures at the same position, demonstrating high stability and full control of the granule orientation by multiple optical traps.

Put a RING on it: regulation and inhibition of RNF8 and RNF168 RING finger E3 ligases at DNA damage sites

PubMed Central

Bartocci, Cristina; Denchi, Eros Lazzerini

2013-01-01

RING (Really Interesting New Gene) domain-containing E3 ubiquitin ligases comprise a large family of enzymes that in combination with an E2 ubiquitin-conjugating enzyme, modify target proteins by attaching ubiquitin moieties. A number of RING E3s play an essential role in the cellular response to DNA damage highlighting a crucial contribution for ubiquitin-mediated signaling to the genome surveillance pathway. Among the RING E3s, RNF8 and RNF168 play a critical role in the response to double stranded breaks, one of the most deleterious types of DNA damage. These proteins act as positive regulators of the signaling cascade that initiates at DNA lesions. Inactivation of these enzymes is sufficient to severely impair the ability of cells to respond to DNA damage. Given their central role in the pathway, several layers of regulation act at this nodal signaling point. Here we will summarize current knowledge on the roles of RNF8 and RNF168 in maintaining genome integrity with particular emphasis on recent insights into the multiple layers of regulation that act on these enzymes to fine-tune the cellular response to DNA lesions. PMID:23847653

Does enemy damage vary across the range of exotic plant species? Evidence from two coastal dune plant species in eastern Australia.

PubMed

Tabassum, Samiya; Leishman, Michelle R

2018-02-01

Release from natural enemies is often cited as a key factor for understanding the success of invasive plant species in novel environments. However, with time invasive species will accumulate native enemies in their invaded range, with factors such as spread distance from the site of introduction, climate and leaf-level traits potentially affecting enemy acquisition rates. However, the influence of such factors is difficult to assess without examining enemy attack across the entire species' range. We tested the significance of factors associated with range expansion (distance from source population and maximum population density), climatic variables (annual temperature and rainfall) and leaf-level traits [specific leaf area (SLA) and foliar nitrogen concentration] in explaining variation in enemy damage across multiple populations of two coastal invasive plants (Gladiolus gueinzii Kunze and Hydrocotyle bonariensis Lam.) along their entire introduced distribution in eastern Australia. We found that for H. bonariensis, amount of foliar damage increased with distance from source population. In contrast, for G. gueinzii, probability and amount of foliar damage decreased with decreasing temperature and increasing rainfall, respectively. Our results show that patterns of enemy attack across species' ranges are complex and cannot be generalised between species or even range edges.

Neuronal growth cones respond to laser-induced axonal damage

PubMed Central

Wu, Tao; Mohanty, Samarendra; Gomez-Godinez, Veronica; Shi, Linda Z.; Liaw, Lih-Huei; Miotke, Jill; Meyer, Ronald L.; Berns, Michael W.

2012-01-01

Although it is well known that damage to neurons results in release of substances that inhibit axonal growth, release of chemical signals from damaged axons that attract axon growth cones has not been observed. In this study, a 532 nm 12 ns laser was focused to a diffraction-limited spot to produce site-specific damage to single goldfish axons in vitro. The axons underwent a localized decrease in thickness (‘thinning’) within seconds. Analysis by fluorescence and transmission electron microscopy indicated that there was no gross rupture of the cell membrane. Mitochondrial transport along the axonal cytoskeleton immediately stopped at the damage site, but recovered over several minutes. Within seconds of damage nearby growth cones extended filopodia towards the injury and were often observed to contact the damaged site. Turning of the growth cone towards the injured axon also was observed. Repair of the laser-induced damage was evidenced by recovery of the axon thickness as well as restoration of mitochondrial movement. We describe a new process of growth cone response to damaged axons. This has been possible through the interface of optics (laser subcellular surgery), fluorescence and electron microscopy, and a goldfish retinal ganglion cell culture model. PMID:21831892

RNF8- and Ube2S-Dependent Ubiquitin Lysine 11-Linkage Modification in Response to DNA Damage.

PubMed

Paul, Atanu; Wang, Bin

2017-05-18

Ubiquitin modification of proteins plays pivotal roles in the cellular response to DNA damage. Given the complexity of ubiquitin conjugation due to the formation of poly-conjugates of different linkages, functional roles of linkage-specific ubiquitin modification at DNA damage sites are largely unclear. We identify that Lys11-linkage ubiquitin modification occurs at DNA damage sites in an ATM-dependent manner, and ubiquitin-modifying enzymes, including Ube2S E2-conjugating enzyme and RNF8 E3 ligase, are responsible for the assembly of Lys11-linkage conjugates on damaged chromatin, including histone H2A/H2AX. We show that RNF8- and Ube2S-dependent Lys11-linkage ubiquitin conjugation plays an important role in regulating DNA damage-induced transcriptional silencing, distinct from the role of Lys63-linkage ubiquitin in the recruitment of DNA damage repair proteins 53BP1 and BRCA1. Thus, our study highlights the importance of linkage-specific ubiquitination at DNA damage sites, and it reveals that Lys11-linkage ubiquitin modification plays a crucial role in the DNA damage response. Copyright © 2017 Elsevier Inc. All rights reserved.

Neighboring base damage induced by permanganate oxidation of 8-oxoguanine in DNA.

PubMed Central

Koizume, S; Inoue, H; Kamiya, H; Ohtsuka, E

1998-01-01

We found that single-stranded DNA oligomers containing a 7, 8-dihydro-8-oxoguanine (8-oxo-G) residue have high reactivity toward KMnO4; the oxidation of 8-oxo-G induces damage to the neighboring nucleotide residues. This paper describes the novel reaction in detail, including experiments that demonstrate the mechanism involved in the induction of DNA damage. The results using DNAs of various base compositions indicated that damaged G, T and C (but not A) sites caused strand scissions after hot piperidine treatment and that the damage around the 8-oxo-G occurred at G sites in both single and double strands with high frequency. The latter substrates were less sensitive to damage. Further, kinetic studies of the KMnO4reaction of single-stranded oligomers suggested that thereactivity of the DNA bases at the site 5'-adjacent to the 8-oxo-G was in the order G >A >T, C. This preference correlates with the electron donating abilities of the bases. In addition, we found that the DNA damage at the G site, which was connected with the 8-oxo-G by a long abasic chain, was inhibited in the above order by the addition of dG, dA or dC. On the other hand, the damage reactions proceeded even after the addition of scavengers for active oxygen species. This study suggests the involvement of a redox process in the unique DNA damage initiated by the oxidation of the 8-oxo-G. PMID:9671825

Anisotropic constitutive model incorporating multiple damage mechanisms for multiscale simulation of dental enamel.

PubMed

Ma, Songyun; Scheider, Ingo; Bargmann, Swantje

2016-09-01

An anisotropic constitutive model is proposed in the framework of finite deformation to capture several damage mechanisms occurring in the microstructure of dental enamel, a hierarchical bio-composite. It provides the basis for a homogenization approach for an efficient multiscale (in this case: multiple hierarchy levels) investigation of the deformation and damage behavior. The influence of tension-compression asymmetry and fiber-matrix interaction on the nonlinear deformation behavior of dental enamel is studied by 3D micromechanical simulations under different loading conditions and fiber lengths. The complex deformation behavior and the characteristics and interaction of three damage mechanisms in the damage process of enamel are well captured. The proposed constitutive model incorporating anisotropic damage is applied to the first hierarchical level of dental enamel and validated by experimental results. The effect of the fiber orientation on the damage behavior and compressive strength is studied by comparing micro-pillar experiments of dental enamel at the first hierarchical level in multiple directions of fiber orientation. A very good agreement between computational and experimental results is found for the damage evolution process of dental enamel. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

PTMscape: an open source tool to predict generic post-translational modifications and map modification crosstalk in protein domains and biological processes.

PubMed

Li, Ginny X H; Vogel, Christine; Choi, Hyungwon

2018-06-07

While tandem mass spectrometry can detect post-translational modifications (PTM) at the proteome scale, reported PTM sites are often incomplete and include false positives. Computational approaches can complement these datasets by additional predictions, but most available tools use prediction models pre-trained for single PTM type by the developers and it remains a difficult task to perform large-scale batch prediction for multiple PTMs with flexible user control, including the choice of training data. We developed an R package called PTMscape which predicts PTM sites across the proteome based on a unified and comprehensive set of descriptors of the physico-chemical microenvironment of modified sites, with additional downstream analysis modules to test enrichment of individual or pairs of PTMs in protein domains. PTMscape is flexible in the ability to process any major modifications, such as phosphorylation and ubiquitination, while achieving the sensitivity and specificity comparable to single-PTM methods and outperforming other multi-PTM tools. Applying this framework, we expanded proteome-wide coverage of five major PTMs affecting different residues by prediction, especially for lysine and arginine modifications. Using a combination of experimentally acquired sites (PSP) and newly predicted sites, we discovered that the crosstalk among multiple PTMs occur more frequently than by random chance in key protein domains such as histone, protein kinase, and RNA recognition motifs, spanning various biological processes such as RNA processing, DNA damage response, signal transduction, and regulation of cell cycle. These results provide a proteome-scale analysis of crosstalk among major PTMs and can be easily extended to other types of PTM.

Ohio River main stem study - The role of geographic information systems and remote sensing in flood damage assessments

NASA Technical Reports Server (NTRS)

Edwardo, H. A.; Moulis, F. R.; Merry, C. J.; Mckim, H. L.; Kerber, A. G.; Miller, M. A.

1985-01-01

The Pittsburgh District, Corps of Engineers, has conducted feasibility analyses of various procedures for performing flood damage assessments along the main stem of the Ohio River. Procedures using traditional, although highly automated, techniques and those based on geographic information systems have been evaluated at a test site, the City of New Martinsville, Wetzel County, WV. The flood damage assessments of the test site developed from an automated, conventional structure-by-structure appraisal served as the ground truth data set. A geographic information system was developed for the test site which includes data on hydraulic reach, ground and reference flood elevations, and land use/cover. Damage assessments were made using land use mapping developed from an exhaustive field inspection of each tax parcel. This ground truth condition was considered to provide the best comparison of flood damages to the conventional approach. Also, four land use/cover data sets were developed from Thematic Mapper Simulator (TMS) and Landsat-4 Thematic Mapper (TM) data. One of these was also used to develop a damage assessment of the test site. This paper presents the comparative absolute and relative accuracies of land use/cover mapping and flood damage assessments, and the recommended role of geographic information systems aided by remote sensing for conducting flood damage assessments and updates along the main stem of the Ohio River.

Ecological carrying capacity assessment of diving site: A case study of Mabul Island, Malaysia.

PubMed

Zhang, Li-Ye; Chung, Shan-Shan; Qiu, Jian-Wen

2016-12-01

Despite considered a non-consumptive use of the marine environment, diving-related activities can cause damages to coral reefs. It is imminent to assess the maximum numbers of divers that can be accommodated by a diving site before it is subject to irreversible deterioration. This study aimed to assess the ecological carrying capacity of a diving site in Mabul Island, Malaysia. Photo-quadrat line transect method was used in the benthic survey. The ecological carrying capacity was assessed based on the relationship between the number of divers and the proportion of diver damaged hard corals in Mabul Island. The results indicated that the proportion of diver damaged hard corals occurred exponentially with increasing use. The ecological carrying capacity of Mabul Island is 15,600-16,800 divers per diving site per year at current levels of diver education and training with a quarterly threshold of 3900-4200 per site. Our calculation shows that management intervention (e.g. limiting diving) is justified at 8-14% of hard coral damage. In addition, the use of coral reef dominated diving sites should be managed according to their sensitivity to diver damage and the depth of the reefs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alternative conceptions of memory consolidation and the role of the hippocampus at the systems level in rodents.

PubMed

Sutherland, R J; Lehmann, H

2011-06-01

We discuss very recent experiments with rodents addressing the idea that long-term memories initially depending on the hippocampus, over a prolonged period, become independent of it. No unambiguous recent evidence exists to substantiate that this occurs. Most experiments find that recent and remote memories are equally affected by hippocampus damage. Nearly all experiments that report spared remote memories suffer from two problems: retrieval could be based upon substantial regions of spared hippocampus and recent memory is tested at intervals that are of the same order of magnitude as cellular consolidation. Accordingly, we point the way beyond systems consolidation theories, both the Standard Model of Consolidation and the Multiple Trace Theory, and propose a simpler multiple storage site hypothesis. On this view, with event reiterations, different memory representations are independently established in multiple networks. Many detailed memories always depend on the hippocampus; the others may be established and maintained independently. Copyright © 2011 Elsevier Ltd. All rights reserved.

Damage Detection Sensor System for Aerospace and Multiple Applications

NASA Technical Reports Server (NTRS)

Williams, Martha; Lewis, Mark; Gibson, Tracy L.; Lane, John; Medelius, Pedro

2017-01-01

NASA has identified structural health monitoring and damage detection and verification as critical needs in multiple technology roadmaps. The sensor systems can be customized for detecting location, damage size, and depth, with velocity options and can be designed for particular environments for monitoring of impact or physical damage to a structure. The damage detection system has been successfully demonstrated in a harsh environment and remote integration tested over 1000 miles apart. Multiple applications includes: Spacecraft and Aircraft; Inflatable, Deployable and Expandable Structures; Space Debris Monitoring; Space Habitats; Military Shelters; Solar Arrays, Smart Garments and Wearables, Extravehicular activity (EVA) suits; Critical Hardware Enclosures; Embedded Composite Structures; and Flexible Hybrid Printed Electronics and Systems. For better implementation and infusion into more flexible architectures, important and improved designs in advancing embedded software and GUI interface, and increasing flexibility, modularity, and configurable capabilities of the system are currently being carried out.

Speciation and distribution of copper in a mining soil using multiple synchrotron-based bulk and microscopic techniques.

PubMed

Yang, Jianjun; Liu, Jin; Dynes, James J; Peak, Derek; Regier, Tom; Wang, Jian; Zhu, Shenhai; Shi, Jiyan; Tse, John S

2014-02-01

Molecular-level understanding of soil Cu speciation and distribution assists in management of Cu contamination in mining sites. In this study, one soil sample, collected from a mining site contaminated since 1950s, was characterized complementarily by multiple synchrotron-based bulk and spatially resolved techniques for the speciation and distribution of Cu as well as other related elements (Fe, Ca, Mn, K, Al, and Si). Bulk X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectroscopy revealed that soil Cu was predominantly associated with Fe oxides instead of soil organic matter. This agreed with the closest association of Cu to Fe by microscopic X-ray fluorescence (U-XRF) and scanning transmission X-ray microscopy (STXM) nanoanalysis, along with the non-occurrence of photoreduction of soil Cu(II) by quick Cu L3,2-edge XANES spectroscopy (Q-XANES) which often occurs when Cu organic complexes are present. Furthermore, bulk-EXAFS and STXM-coupled Fe L3,2-edge nano-XANES analysis revealed soil Cu adsorbed primarily to Fe(III) oxides by inner-sphere complexation. Additionally, Cu K-edge μ-XANES, L3,2-edge bulk-XANES, and successive Q-XANES results identified the presence of Cu2S rather than radiation-damage artifacts dominant in certain microsites of the mining soil. This study demonstrates the great benefits in use of multiple combined synchrotron-based techniques for comprehensive understanding of Cu speciation in heterogeneous soil matrix, which facilitates our prediction of Cu reactivity and environmental fate in the mining site.

Historical Cavern Floor Rise for All SPR Sites

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

Moriarty, Dylan Michael

2016-09-01

The Strategic Petroleum Reserve (SPR) contains the largest supply is the largest stockpile of government-owned emergency crude oil in the world. The oil is stored in multiple salt caverns spread over four sites in Louisiana and Texas. Cavern infrastructure near the bottom of the cavern can be damaged from vertical floor movement. This report presents a comprehensive history of floor movements in each cavern. Most of the cavern floor rise rates ranged from 0.5-3.5 ft/yr, however, there were several caverns with much higher rise rates. BH103, BM106, and BH105 had the three highest rise rates. Information from this report willmore » be used to better predict future vertical floor movements and optimally place cavern infrastructure. The reasons for floor rise are not entirely understood and should be investigated.« less

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

PubMed

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

2013-04-08

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

PROTEOMIC IDENTIFICATION OF CARBONYLATED PROTEINS AND THEIR OXIDATION SITES

PubMed Central

Madian, Ashraf G.; Regnier, Fred E.

2011-01-01

Excessive oxidative stress leaves a protein carbonylation fingerprint in biological systems. Carbonylation is an irreversible post translational modification (PTM) that often leads to the loss of protein function and can be a component of multiple diseases. Protein carbonyl groups can be generated directly (by amino acids oxidation and the a-amidation pathway) or indirectly by forming adducts with lipid peroxidation products or glycation and advanced glycation end-products. Studies of oxidative stress are complicated by the low concentration of oxidation products and wide array of routes by which proteins are carbonylated. The development of new selection and enrichment techniques coupled with advances in mass spectrometry are allowing identification of hundreds of new carbonylated protein products from a broad range of proteins located at many sites in biological systems. The focus of this review is on the use of proteomics tools and methods to identify oxidized proteins along with specific sites of oxidative damage and the consequences of protein oxidation. PMID:20521848

Black bear damage to northwestern conifers in California: a review

Treesearch

Kenneth O. Fulgham; Dennis Hosack

2017-01-01

A total of 789 black bear damaged trees were investigate over a multi-year period on 14 different study sites chosen on lands of four participating timber companies. The sites ranged from 30 to 50 years of age. Four different conifer species were found to have black bear damage: coastal redwood (Sequoia sempervirens (D. Don) Endl.), Douglas-fir (...

SITE AMPLIFICATION OF EARTHQUAKE GROUND MOTION.

USGS Publications Warehouse

Hays, Walter W.

1986-01-01

When analyzing the patterns of damage in an earthquake, physical parameters of the total earthquake-site-structure system are correlated with the damage. Soil-structure interaction, the cause of damage in many earthquakes, involves the frequency-dependent response of both the soil-rock column and the structure. The response of the soil-rock column (called site amplification) is controversial because soil has strain-dependent properties that affect the way the soil column filters the input body and surface seismic waves, modifying the amplitude and phase spectra and the duration of the surface ground motion.

Analysis of LexA binding sites and transcriptomics in response to genotoxic stress in Leptospira interrogans.

PubMed

Schons-Fonseca, Luciane; da Silva, Josefa B; Milanez, Juliana S; Domingos, Renan H; Smith, Janet L; Nakaya, Helder I; Grossman, Alan D; Ho, Paulo L; da Costa, Renata M A

2016-02-18

We determined the effects of DNA damage caused by ultraviolet radiation on gene expression in Leptospira interrogans using DNA microarrays. These data were integrated with DNA binding in vivo of LexA1, a regulator of the DNA damage response, assessed by chromatin immunoprecipitation and massively parallel DNA sequencing (ChIP-seq). In response to DNA damage, Leptospira induced expression of genes involved in DNA metabolism, in mobile genetic elements and defective prophages. The DNA repair genes involved in removal of photo-damage (e.g. nucleotide excision repair uvrABC, recombinases recBCD and resolvases ruvABC) were not induced. Genes involved in various metabolic pathways were down regulated, including genes involved in cell growth, RNA metabolism and the tricarboxylic acid cycle. From ChIP-seq data, we observed 24 LexA1 binding sites located throughout chromosome 1 and one binding site in chromosome 2. Expression of many, but not all, genes near those sites was increased following DNA damage. Binding sites were found as far as 550 bp upstream from the start codon, or 1 kb into the coding sequence. Our findings indicate that there is a shift in gene expression following DNA damage that represses genes involved in cell growth and virulence, and induces genes involved in mutagenesis and recombination. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Shelters of leaf-tying herbivores decompose faster than leaves damaged by free-living insects: Implications for nutrient turnover in polluted habitats.

PubMed

Kozlov, Mikhail V; Zverev, Vitali; Zvereva, Elena L

2016-10-15

Leaf-eating insects can influence decomposition processes by modifying quality of leaf litter, and this impact can be especially pronounced in habitats where leaf-eating insects reach high densities, for example in heavily polluted areas. We hypothesized that the decomposition rate is faster for shelters of leaf-tying larvae than for leaves damaged by free-living insects, in particular due to the accumulation of larval frass within shelters. We exposed litter bags containing samples of three different compositions (shelters built by moth larvae, leaves damaged by free-living insects and intact leaves of mountain birch, Betula pubescens ssp. czerepanovii) for one year at two heavily polluted sites near the nickel-copper smelter at Monchegorsk in north-western Russia and at two unpolluted sites. The decomposition rate of leaves damaged by free-living insects was 91% of that of undamaged leaves, whereas the mass loss of leaves composing shelters did not differ of that of undamaged leaves. These differences between leaves damaged by different guilds of herbivorous insects were uniform across the study sites, although the decomposition rate in polluted sites was reduced to 77% of that in unpolluted sites. Addition of larval frass to undamaged leaves had no effect on the subsequent decomposition rate. Therefore we suggest that damaged leaves tied by shelter-building larvae decompose faster than untied damaged leaves due to a looser physical structure of the litter, which creates favourable conditions for detritivores and soil decomposers. Thus, while leaf damage by insects per se reduces litter quality and its decomposition rate, structuring of litter by leaf-tying insects counterbalances these negative effects. We conclude that leaf-tying larvae, in contrast to free-living defoliators, do not impose negative effects on nutrient turnover rate even at their high densities, which are frequently observed in heavily polluted sites. Copyright © 2016 Elsevier B.V. All rights reserved.

Damage detection of structures identified with deterministic-stochastic models using seismic data.

PubMed

Huang, Ming-Chih; Wang, Yen-Po; Chang, Ming-Lian

2014-01-01

A deterministic-stochastic subspace identification method is adopted and experimentally verified in this study to identify the equivalent single-input-multiple-output system parameters of the discrete-time state equation. The method of damage locating vector (DLV) is then considered for damage detection. A series of shaking table tests using a five-storey steel frame has been conducted. Both single and multiple damage conditions at various locations have been considered. In the system identification analysis, either full or partial observation conditions have been taken into account. It has been shown that the damaged stories can be identified from global responses of the structure to earthquakes if sufficiently observed. In addition to detecting damage(s) with respect to the intact structure, identification of new or extended damages of the as-damaged counterpart has also been studied. This study gives further insights into the scheme in terms of effectiveness, robustness, and limitation for damage localization of frame systems.

Detection of damaged DNA bases by DNA glycosylase enzymes.

PubMed

Friedman, Joshua I; Stivers, James T

2010-06-22

A fundamental and shared process in all forms of life is the use of DNA glycosylase enzymes to excise rare damaged bases from genomic DNA. Without such enzymes, the highly ordered primary sequences of genes would rapidly deteriorate. Recent structural and biophysical studies are beginning to reveal a fascinating multistep mechanism for damaged base detection that begins with short-range sliding of the glycosylase along the DNA chain in a distinct conformation we call the search complex (SC). Sliding is frequently punctuated by the formation of a transient "interrogation" complex (IC) where the enzyme extrahelically inspects both normal and damaged bases in an exosite pocket that is distant from the active site. When normal bases are presented in the exosite, the IC rapidly collapses back to the SC, while a damaged base will efficiently partition forward into the active site to form the catalytically competent excision complex (EC). Here we review the unique problems associated with enzymatic detection of rare damaged DNA bases in the genome and emphasize how each complex must have specific dynamic properties that are tuned to optimize the rate and efficiency of damage site location.

Acoustic emission monitoring of low velocity impact damage in graphite/epoxy laminates during tensile loading

NASA Technical Reports Server (NTRS)

Parker, Bradford H.

1992-01-01

An acoustic emission (AE) system was set up in a linear location data acquisition mode to monitor the tensile loading of eight-ply quasi-isotropic graphite/epoxy specimens containing low velocity impact damage. The impact damage was induced using an instrumented drop weight tower. During impact, specimens were supported by either an aluminum plate or a membrane configuration. Cross-sectional examinations revealed that the aluminum plate configuration resulted in primarily matrix cracking and back surface fiber failure. The membrane support resulted in only matrix cracking and delamination damage. Penetrant enhanced radiography and immersion ultrasonics were used in order to assess the amount of impact damage in each tensile specimen. During tensile loading, AE reliably detected and located the damage sites which included fiber failure. All specimens with areas of fiber breakage ultimately failed at the impact site. AE did not reliably locate damage which consisted of only delaminations and matrix cracking. Specimens with this type of damage did not ultimately fail at the impact site. In summary, AE demonstrated the ability to increase the reliability of structural proof tests; however, the successful use of this technique requires extensive baseline testing.

Recombinant human hyaluronidase PH20 (rHuPH20) facilitates subcutaneous infusions of large volumes of immunoglobulin in a swine model.

PubMed

Kang, David W; Jadin, Laurence; Nekoroski, Tara; Drake, Fred H; Zepeda, Monica L

2012-08-01

Many patients with primary immunodeficiency disease (PIDD) require lifelong immunoglobulin (Ig) replacement therapy. Home-based subcutaneous (SC) infusion provides advantages to patients with PIDD compared to hospital-based intravenous infusion. One limitation of current practice with SCIg infusion is the need for small-volume infusions at multiple injection sites on a frequent basis. A method was developed for large-volume SC infusion that uses preinfusion of recombinant human hyaluronidase (rHuPH20) to facilitate fluid dispersion. Miniature swine was used as a preclinical model to assess the effects of rHuPH20-facilitated infusions, of a single monthly dose, on fluid dispersion, infusion-related pressure, swelling, induration, and tissue damage. Preinfusion of vehicle (control) or rHuPH20 (75 U/g Ig) was performed simultaneously on contralateral abdominal sites on each animal, followed by infusion of 300 mL 10 % Ig (30 g) at each site. Compared to control infusions, rHuPH20 significantly reduced infusion pressure and induration (p < 0.05) and accelerated postinfusion Ig dispersion. Histological evaluation of infusion site tissue showed moderate to severe swelling for the control. Swelling after rHuPH20-facilitated infusion was mild on day 1 and had completely resolved shortly thereafter. Laser Doppler imaging of control infusion sites revealed local cutaneous hypoperfusion during Ig infusion, which was reduced almost 7-fold (p < 0.05) with the use of rHuPH20. These results demonstrate that rHuPH20-facilitated Ig infusion is associated with improved dispersion of Ig, resulting in reduced tissue pressure, induration, and reduced risk of tissue damage from mechanical trauma or local ischemia, thus enabling SC administration of large volumes of Ig at a single site.

The sequence specificity of UV-induced DNA damage in a systematically altered DNA sequence.

PubMed

Khoe, Clairine V; Chung, Long H; Murray, Vincent

2018-06-01

The sequence specificity of UV-induced DNA damage was investigated in a specifically designed DNA plasmid using two procedures: end-labelling and linear amplification. Absorption of UV photons by DNA leads to dimerisation of pyrimidine bases and produces two major photoproducts, cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs). A previous study had determined that two hexanucleotide sequences, 5'-GCTC*AC and 5'-TATT*AA, were high intensity UV-induced DNA damage sites. The UV clone plasmid was constructed by systematically altering each nucleotide of these two hexanucleotide sequences. One of the main goals of this study was to determine the influence of single nucleotide alterations on the intensity of UV-induced DNA damage. The sequence 5'-GCTC*AC was designed to examine the sequence specificity of 6-4PPs and the highest intensity 6-4PP damage sites were found at 5'-GTTC*CC nucleotides. The sequence 5'-TATT*AA was devised to investigate the sequence specificity of CPDs and the highest intensity CPD damage sites were found at 5'-TTTT*CG nucleotides. It was proposed that the tetranucleotide DNA sequence, 5'-YTC*Y (where Y is T or C), was the consensus sequence for the highest intensity UV-induced 6-4PP adduct sites; while it was 5'-YTT*C for the highest intensity UV-induced CPD damage sites. These consensus tetranucleotides are composed entirely of consecutive pyrimidines and must have a DNA conformation that is highly productive for the absorption of UV photons. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Metyrapone prevents acute glucose hypermetabolism and short-term brain damage induced by intrahippocampal administration of 4-aminopyridine in rats.

PubMed

García-García, Luis; Fernández de la Rosa, Rubén; Delgado, Mercedes; Silván, Ágata; Bascuñana, Pablo; Bankstahl, Jens P; Gomez, Francisca; Pozo, Miguel A

2018-02-01

Intracerebral administration of the potassium channel blocker 4-aminopyridine (4-AP) triggers neuronal depolarization and intense acute seizure activity followed by neuronal damage. We have recently shown that, in the lithium-pilocarpine rat model of status epilepticus (SE), a single administration of metyrapone, an inhibitor of the 11β-hydroxylase enzyme, had protective properties of preventive nature against signs of brain damage and neuroinflammation. Herein, our aim was to investigate to which extent, pretreatment with metyrapone (150 mg/kg, i.p.) was also able to prevent eventual changes in the acute brain metabolism and short-term neuronal damage induced by intrahippocampal injection of 4-AP (7 μg/5 μl). To this end, regional brain metabolism was assessed by 2-deoxy-2-[ 18 F]fluoro-d-glucose ([ 18 F]FDG) positron emission tomography (PET) during the ictal period. Three days later, markers of neuronal death and hippocampal integrity and apoptosis (Nissl staining, NeuN and active caspase-3 immunohistochemistry), neurodegeneration (Fluoro-Jade C labeling), astrogliosis (glial fibrillary acidic protein (GFAP) immunohistochemistry) and microglia-mediated neuroinflammation (in vitro [ 18 F]GE180 autoradiography) were evaluated. 4-AP administration acutely triggered marked brain hypermetabolism within and around the site of injection as well as short-term signs of brain damage and inflammation. Most important, metyrapone pretreatment was able to reduce ictal hypermetabolism as well as all the markers of brain damage except microglia-mediated neuroinflammation. Overall, our study corroborates the neuroprotective effects of metyrapone against multiple signs of brain damage caused by seizures triggered by 4-AP. Ultimately, our data add up to the consistent protective effect of metyrapone pretreatment reported in other models of neurological disorders of different etiology. Copyright © 2017 Elsevier Ltd. All rights reserved.

The environmental implications of intensified land use in developing countries

PubMed Central

Tinker, P. B.

1997-01-01

The major agricultural intensifications in the developed world over the last half century have produced a range of important environmental problems. These include pollution, damage to wildlife and landscape and other issues, both on- and off-site. These are largely being controlled by scientific investigation and Government regulation. As developing countries increase agricultural production over the next 30 years, this may also cause even more serious environmental damage.
The paper distinguishes between production-related on-site damage, and off-site and more extensive effects. Both may involve soil and water effects, such as soil erosion, salinization, siltation, eutrophication and loss of water quality. The use of more agrochemicals can damage water quality, health, wildlife and biodiversity. Loss of habitat from the extension of farming is particularly damaging to biodiversity. A developing off-site problem is the production of greenhouse gases by farming systems, including the conversion of forests to farmland. In the future the introduction of genetically engineered species of plants, animals or microbes will need secure control.
Work, probably on a catchment basis, is necessary to understand and control these problems. The three main requirements are much better environmental information from the developing world; the selection of environmental indicators to be monitored; and the support of local farmers in protecting the environment. There are encouraging indications of farmer concern and action over obvious on-site damage, but this may not extend to extensive off-site issues. The main danger is that developing food scarcity would cause the environmental issues to be ignored in a race for production.

Single and multiple in-season measurements as indicators of at-harvest cotton boll damage caused by verde plant bug (Hemiptera: Miridae).

PubMed

Brewer, Michael J; Armstrong, J Scott; Parker, Roy D

2013-06-01

The ability to monitor verde plant bug, Creontiades signatus Distant (Hemiptera: Miridae), and the progression of cotton, Gossypium hirsutum L., boll responses to feeding and associated cotton boll rot provided opportunity to assess if single in-season measurements had value in evaluating at-harvest damage to bolls and if multiple in-season measurements enhanced their combined use. One in-season verde plant bug density measurement, three in-season plant injury measurements, and two at-harvest damage measurements were taken in 15 cotton fields in South Texas, 2010. Linear regression selected two measurements as potentially useful indicators of at-harvest damage: verde plant bug density (adjusted r2 = 0.68; P = 0.0004) and internal boll injury of the carpel wall (adjusted r2 = 0.72; P = 0.004). Considering use of multiple measurements, a stepwise multiple regression of the four in-season measurements selected a univariate model (verde plant bug density) using a 0.15 selection criterion (adjusted r2 = 0.74; P = 0.0002) and a bivariate model (verde plant bug density-internal boll injury) using a 0.25 selection criterion (adjusted r2 = 0.76; P = 0.0007) as indicators of at-harvest damage. In a validation using cultivar and water regime treatments experiencing low verde plant bug pressure in 2011 and 2012, the bivariate model performed better than models using verde plant bug density or internal boll injury separately. Overall, verde plant bug damaging cotton bolls exemplified the benefits of using multiple in-season measurements in pest monitoring programs, under the challenging situation when at-harvest damage results from a sequence of plant responses initiated by in-season insect feeding.

Temperature changes across porcelain during multiple exposure CO2 lasing

NASA Astrophysics Data System (ADS)

Barron, Joseph R.; Zakariasen, Kenneth L.; Peacocke, Larry

1990-06-01

Research indicates that laser energy may provide a useful method for glazing and fusing porcelain for intraoral prosthetic purposes. However, it is not known whether such lasing will result in the production of heat levels that may be damaging to adjacent vital tissues such as the dental pulp and periodontal tissues. This research is designed to measure the magnitude of temperature rise across porcelain observed during multiple exposure C02 lasing. Fifteen porcelain examples of 1000 jim (5), 1500 pm (5) and 2000 tm (5) x each received five C02 laser exposures on the same exposure site at 1.0 sec. intervals at 8.0 watts (0.2 sec. per exposure with a 1 mm focal spot). A YSI 144201 thermilinear precision thermistor was placed on the porcelain surface opposite each laser exposure site. Temperature rise above ambient was recorded by an HP3421A data acquisition unit and HP9816 technical microcomputer. Recording continued for sufficient time to allow temperatures to return to ambient. The mean temperature elevations ranged from a low of 2.97 0C (2000 pm) to a high of 7.77 °C (1000 μm). ANOVA and Duncan's Multiple Range Test indicated significant differences in temperature rise by porcelain thickness. It would appear from the results of this research that temperature elevations adjacent to lased porcelain may be sufficiently controllable that safe intraoral porcelain lasing will be possible.

Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia.

PubMed

Tang, Jinsong; Fan, Yu; Li, Hong; Xiang, Qun; Zhang, Deng-Feng; Li, Zongchang; He, Ying; Liao, Yanhui; Wang, Ya; He, Fan; Zhang, Fengyu; Shugart, Yin Yao; Liu, Chunyu; Tang, Yanqing; Chan, Raymond C K; Wang, Chuan-Yue; Yao, Yong-Gang; Chen, Xiaogang

2017-06-20

Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive. We implemented whole-genome sequencing (WGS) analysis of 8 families with monozygotic (MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations (DNMs) or inherited variants with susceptibility to schizophrenia. Eight non-synonymous DNMs (including one splicing site) were identified and shared by twins, which were either located in previously reported schizophrenia risk genes (p.V24689I mutation in TTN, p.S2506T mutation in GCN1L1, IVS3+1G > T in DOCK1) or had a benign to damaging effect according to in silico prediction analysis. By searching the inherited rare damaging or loss-of-function (LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes, we were able to distill genetic alterations in several schizophrenia risk genes, including GAD1, PLXNA2, RELN and FEZ1. Four inherited copy number variations (CNVs; including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families, respectively. Most of families carried both missense DNMs and inherited risk variants, which might suggest that DNMs, inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility. Our results support that schizophrenia is caused by a combination of multiple genetic factors, with each DNM/variant showing a relatively small effect size. Copyright © 2017 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. All rights reserved.

Soluble thrombomodulin levels in plasma of multiple sclerosis patients and their implication.

PubMed

Festoff, Barry W; Li, Chaoyang; Woodhams, Barry; Lynch, Sharon

2012-12-15

Thrombomodulin (TM) on the cell-surface of cerebrovascular endothelial cells (CECs) is released into blood upon CEC damage. TM promotes activation of protein C (APC), an anticoagulant, anti-inflammatory, neuroprotective molecule that protects CECs and impedes inflammatory cell migration across the blood-brain barrier (BBB). Multiple sclerosis (MS) is associated with CEC damage and BBB dysfunction. We evaluated soluble TM (sTM) levels as a biomarker of BBB integrity and whether glatiramer acetate (GA) influenced sTM levels in MS patients. sTM levels quantified by 2-site ELISA from sera of healthy controls and systemic lupus erythematosus (SLE) patients (CEC-damage positive control) were compared with levels from patients with relapsing-remitting (RRMS) or secondary-progressive MS (SPMS), stratified as: RRMS/GA/no relapse, RRMS/GA/in relapse, RRMS no GA/no relapse, RRMS/no GA/in relapse; and SPMS/no GA. Additionally, soluble endothelial protein C receptor (sEPCR) levels were assessed in the non-stratified MS group, SLE patients, and controls. sTM levels were highest in RRMS patients taking GA with or without relapse, followed in decreasing order by SLE, RRMS/no GA/in relapse, SPMS, RRMS/no GA/no relapse, healthy controls. sEPCR levels were highest in MS patients, then SLE, then controls. sTM may be a useful biomarker of BBB integrity in RRMS patients. Further evaluation of sEPCR is needed. The finding that the highest sTM levels were in RRMS patients taking GA is interesting and warrants further investigation. Published by Elsevier B.V.

Detection of multiple damages employing best achievable eigenvectors under Bayesian inference

NASA Astrophysics Data System (ADS)

Prajapat, Kanta; Ray-Chaudhuri, Samit

2018-05-01

A novel approach is presented in this work to localize simultaneously multiple damaged elements in a structure along with the estimation of damage severity for each of the damaged elements. For detection of damaged elements, a best achievable eigenvector based formulation has been derived. To deal with noisy data, Bayesian inference is employed in the formulation wherein the likelihood of the Bayesian algorithm is formed on the basis of errors between the best achievable eigenvectors and the measured modes. In this approach, the most probable damage locations are evaluated under Bayesian inference by generating combinations of various possible damaged elements. Once damage locations are identified, damage severities are estimated using a Bayesian inference Markov chain Monte Carlo simulation. The efficiency of the proposed approach has been demonstrated by carrying out a numerical study involving a 12-story shear building. It has been found from this study that damage scenarios involving as low as 10% loss of stiffness in multiple elements are accurately determined (localized and severities quantified) even when 2% noise contaminated modal data are utilized. Further, this study introduces a term parameter impact (evaluated based on sensitivity of modal parameters towards structural parameters) to decide the suitability of selecting a particular mode, if some idea about the damaged elements are available. It has been demonstrated here that the accuracy and efficiency of the Bayesian quantification algorithm increases if damage localization is carried out a-priori. An experimental study involving a laboratory scale shear building and different stiffness modification scenarios shows that the proposed approach is efficient enough to localize the stories with stiffness modification.

Iceberg Scour and Shell Damage in the Antarctic Bivalve Laternula elliptica

PubMed Central

Harper, Elizabeth M.; Clark, Melody S.; Hoffman, Joseph I.; Philipp, Eva E. R.; Peck, Lloyd S.; Morley, Simon A.

2012-01-01

We document differences in shell damage and shell thickness in a bivalve mollusc (Laternula elliptica) from seven sites around Antarctica with differing exposures to ice movement. These range from 60% of the sea bed impacted by ice per year (Hangar Cove, Antarctic Peninsula) to those protected by virtually permanent sea ice cover (McMurdo Sound). Patterns of shell damage consistent with blunt force trauma were observed in populations where ice scour frequently occurs; damage repair frequencies and the thickness of shells correlated positively with the frequency of iceberg scour at the different sites with the highest repair rates and thicker shells at Hangar Cove (74.2% of animals damaged) compared to the other less impacted sites (less than 10% at McMurdo Sound). Genetic analysis of population structure using Amplified Fragment Length Polymorphisms (AFLPs) revealed no genetic differences between the two sites showing the greatest difference in shell morphology and repair rates. Taken together, our results suggest that L. elliptica exhibits considerable phenotypic plasticity in response to geographic variation in physical disturbance. PMID:23029484

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

Zhang, Yanwen; Jin, Ke; Xue, Haizhou

We report that historically, alloy development with better radiation performance has been focused on traditional alloys with one or two principal element(s) and minor alloying elements, where enhanced radiation resistance depends on microstructural or nanoscale features to mitigate displacement damage. In sharp contrast to traditional alloys, recent advances of single-phase concentrated solid solution alloys (SP-CSAs) have opened up new frontiers in materials research. In these alloys, a random arrangement of multiple elemental species on a crystalline lattice results in disordered local chemical environments and unique site-to-site lattice distortions. Based on closely integrated computational and experimental studies using a novel setmore » of SP-CSAs in a face-centered cubic structure, we have explicitly demonstrated that increasing chemical disorder can lead to a substantial reduction in electron mean free paths, as well as electrical and thermal conductivity, which results in slower heat dissipation in SP-CSAs. The chemical disorder also has a significant impact on defect evolution under ion irradiation. Considerable improvement in radiation resistance is observed with increasing chemical disorder at electronic and atomic levels. Finally, the insights into defect dynamics may provide a basis for understanding elemental effects on evolution of radiation damage in irradiated materials and may inspire new design principles of radiation-tolerant structural alloys for advanced energy systems.« less

Sleep loss and acute drug abuse can induce DNA damage in multiple organs of mice.

PubMed

Alvarenga, T A; Ribeiro, D A; Araujo, P; Hirotsu, C; Mazaro-Costa, R; Costa, J L; Battisti, M C; Tufik, S; Andersen, M L

2011-09-01

The purpose of the present study was to characterize the genetic damage induced by paradoxical sleep deprivation (PSD) in combination with cocaine or ecstasy (3,4-methylenedioxymethamphetamine; MDMA) in multiple organs of male mice using the single cell gel (comet) assay. C57BL/6J mice were submitted to PSD by the platform technique for 72 hours, followed by drug administration and evaluation of DNA damage in peripheral blood, liver and brain tissues. Cocaine was able to induce genetic damage in the blood, brain and liver cells of sleep-deprived mice at the majority of the doses evaluated. Ecstasy also induced increased DNA migration in peripheral blood cells for all concentrations tested. Analysis of damaged cells by the tail moment data suggests that ecstasy is a genotoxic chemical at the highest concentrations tested, inducing damage in liver or brain cells after sleep deprivation in mice. Taken together, our results suggest that cocaine and ecstasy/MDMA act as potent genotoxins in multiple organs of mice when associated with sleep loss.

The distribution of DNA damage is defined by region-specific susceptibility to DNA damage formation rather than repair differences.

PubMed

Strand, Janne M; Scheffler, Katja; Bjørås, Magnar; Eide, Lars

2014-06-01

The cellular genomes are continuously damaged by reactive oxygen species (ROS) from aerobic processes. The impact of DNA damage depends on the specific site as well as the cellular state. The steady-state level of DNA damage is the net result of continuous formation and subsequent repair, but it is unknown to what extent heterogeneous damage distribution is caused by variations in formation or repair of DNA damage. Here, we used a restriction enzyme/qPCR based method to analyze DNA damage in promoter and coding regions of four nuclear genes: the two house-keeping genes Gadph and Tbp, and the Ndufa9 and Ndufs2 genes encoding mitochondrial complex I subunits, as well as mt-Rnr1 encoded by mitochondrial DNA (mtDNA). The distribution of steady-state levels of damage varied in a site-specific manner. Oxidative stress induced damage in nDNA to a similar extent in promoter and coding regions, and more so in mtDNA. The subsequent removal of damage from nDNA was efficient and comparable with recovery times depending on the initial damage load, while repair of mtDNA was delayed with subsequently slower repair rate. The repair was furthermore found to be independent of transcription or the transcription-coupled repair factor CSB, but dependent on cellular ATP. Our results demonstrate that the capacity to repair DNA is sufficient to remove exogenously induced damage. Thus, we conclude that the heterogeneous steady-state level of DNA damage in promoters and coding regions is caused by site-specific DNA damage/modifications that take place under normal metabolism. Copyright © 2014 Elsevier B.V. All rights reserved.

Categorizing natural disaster damage assessment using satellite-based geospatial techniques

USGS Publications Warehouse

Myint, S.W.; Yuan, M.; Cerveny, R.S.; Giri, C.

2008-01-01

Remote sensing of a natural disaster's damage offers an exciting backup and/or alternative to traditional means of on-site damage assessment. Although necessary for complete assessment of damage areas, ground-based damage surveys conducted in the aftermath of natural hazard passage can sometimes be potentially complicated due to on-site difficulties (e.g., interaction with various authorities and emergency services) and hazards (e.g., downed power lines, gas lines, etc.), the need for rapid mobilization (particularly for remote locations), and the increasing cost of rapid physical transportation of manpower and equipment. Satellite image analysis, because of its global ubiquity, its ability for repeated independent analysis, and, as we demonstrate here, its ability to verify on-site damage assessment provides an interesting new perspective and investigative aide to researchers. Using one of the strongest tornado events in US history, the 3 May 1999 Oklahoma City Tornado, as a case example, we digitized the tornado damage path and co-registered the damage path using pre- and post-Landsat Thematic Mapper image data to perform a damage assessment. We employed several geospatial approaches, specifically the Getis index, Geary's C, and two lacunarity approaches to categorize damage characteristics according to the original Fujita tornado damage scale (F-scale). Our results indicate strong relationships between spatial indices computed within a local window and tornado F-scale damage categories identified through the ground survey. Consequently, linear regression models, even incorporating just a single band, appear effective in identifying F-scale damage categories using satellite imagery. This study demonstrates that satellite-based geospatial techniques can effectively add spatial perspectives to natural disaster damages, and in particular for this case study, tornado damages.

Categorizing natural disaster damage assessment using satellite-based geospatial techniques

NASA Astrophysics Data System (ADS)

Myint, S. W.; Yuan, M.; Cerveny, R. S.; Giri, C.

2008-07-01

Remote sensing of a natural disaster's damage offers an exciting backup and/or alternative to traditional means of on-site damage assessment. Although necessary for complete assessment of damage areas, ground-based damage surveys conducted in the aftermath of natural hazard passage can sometimes be potentially complicated due to on-site difficulties (e.g., interaction with various authorities and emergency services) and hazards (e.g., downed power lines, gas lines, etc.), the need for rapid mobilization (particularly for remote locations), and the increasing cost of rapid physical transportation of manpower and equipment. Satellite image analysis, because of its global ubiquity, its ability for repeated independent analysis, and, as we demonstrate here, its ability to verify on-site damage assessment provides an interesting new perspective and investigative aide to researchers. Using one of the strongest tornado events in US history, the 3 May 1999 Oklahoma City Tornado, as a case example, we digitized the tornado damage path and co-registered the damage path using pre- and post-Landsat Thematic Mapper image data to perform a damage assessment. We employed several geospatial approaches, specifically the Getis index, Geary's C, and two lacunarity approaches to categorize damage characteristics according to the original Fujita tornado damage scale (F-scale). Our results indicate strong relationships between spatial indices computed within a local window and tornado F-scale damage categories identified through the ground survey. Consequently, linear regression models, even incorporating just a single band, appear effective in identifying F-scale damage categories using satellite imagery. This study demonstrates that satellite-based geospatial techniques can effectively add spatial perspectives to natural disaster damages, and in particular for this case study, tornado damages.

Relationship of acute axonal damage, Wallerian degeneration, and clinical disability in multiple sclerosis.

PubMed

Singh, Shailender; Dallenga, Tobias; Winkler, Anne; Roemer, Shanu; Maruschak, Brigitte; Siebert, Heike; Brück, Wolfgang; Stadelmann, Christine

2017-03-17

Axonal damage and loss substantially contribute to the incremental accumulation of clinical disability in progressive multiple sclerosis. Here, we assessed the amount of Wallerian degeneration in brain tissue of multiple sclerosis patients in relation to demyelinating lesion activity and asked whether a transient blockade of Wallerian degeneration decreases axonal loss and clinical disability in a mouse model of inflammatory demyelination. Wallerian degeneration and acute axonal damage were determined immunohistochemically in the periplaque white matter of multiple sclerosis patients with early actively demyelinating lesions, chronic active lesions, and inactive lesions. Furthermore, we studied the effects of Wallerian degeneration blockage on clinical severity, inflammatory pathology, acute axonal damage, and long-term axonal loss in experimental autoimmune encephalomyelitis using Wallerian degeneration slow (Wld S ) mutant mice. The highest numbers of axons undergoing Wallerian degeneration were found in the perilesional white matter of multiple sclerosis patients early in the disease course and with actively demyelinating lesions. Furthermore, Wallerian degeneration was more abundant in patients harboring chronic active as compared to chronic inactive lesions. No co-localization of neuropeptide Y-Y1 receptor, a bona fide immunohistochemical marker of Wallerian degeneration, with amyloid precursor protein, frequently used as an indicator of acute axonal transport disturbance, was observed in human and mouse tissue, indicating distinct axon-degenerative processes. Experimentally, a delay of Wallerian degeneration, as observed in Wld S mice, did not result in a reduction of clinical disability or acute axonal damage in experimental autoimmune encephalomyelitis, further supporting that acute axonal damage as reflected by axonal transport disturbances does not share common molecular mechanisms with Wallerian degeneration. Furthermore, delaying Wallerian degeneration did not result in a net rescue of axons in late lesion stages of experimental autoimmune encephalomyelitis. Our data indicate that in multiple sclerosis, ongoing demyelination in focal lesions is associated with axonal degeneration in the perilesional white matter, supporting a role for focal pathology in diffuse white matter damage. Also, our results suggest that interfering with Wallerian degeneration in inflammatory demyelination does not suffice to prevent acute axonal damage and finally axonal loss.

Site response, shallow shear-wave velocity, and damage in Los Gatos, California, from the 1989 Loma Prieta earthquake

USGS Publications Warehouse

Hartzell, S.; Carver, D.; Williams, R.A.

2001-01-01

Aftershock records of the 1989 Loma Prieta earthquake are used to calculate site response in the frequency band of 0.5-10 Hz at 24 locations in Los Gatos, California, on the edge of the Santa Clara Valley. Two different methods are used: spectral ratios relative to a reference site on rock and a source/site spectral inversion method. These two methods complement each other and give consistent results. Site amplification factors are compared with surficial geology, thickness of alluvium, shallow shear-wave velocity measurements, and ground deformation and structural damage resulting from the Loma Prieta earthquake. Higher values of site amplification are seen on Quaternary alluvium compared with older Miocene and Cretaceous units of Monterey and Franciscan Formation. However, other more detailed correlations with surficial geology are not evident. A complex pattern of alluvial sediment thickness, caused by crosscutting thrust faults, is interpreted as contributing to the variability in site response and the presence of spectral resonance peaks between 2 and 7 Hz at some sites. Within the range of our field measurements, there is a correlation between lower average shear-wave velocity of the top 30 m and 50% higher values of site amplification. An area of residential homes thrown from their foundations correlates with high site response. This damage may also have been aggravated by local ground deformation. Severe damage to commercial buildings in the business district, however, is attributed to poor masonry construction.

In vivo photothermal treatment with real-time monitoring by optical fiber-needle array.

PubMed

Yang, Taeseok Daniel; Park, Kwanjun; Kim, Hyung-Jin; Im, Nu-Ri; Kim, Byoungjae; Kim, TaeHoon; Seo, Sohyun; Lee, Jae-Seung; Kim, Beop-Min; Choi, Youngwoon; Baek, Seung-Kuk

2017-07-01

Photothermal treatment (PTT) using gold nanoshells (gold-NSs) is accepted as a method for treating cancer. However, owing to restrictions in therapeutic depth and skin damage caused by excessive light exposure, its application has been limited to lesions close to the epidermis. Here, we demonstrate an in vivo PTT method that uses gold-NSs with a flexible optical fiber-needle array (OFNA), which is an array of multiple needles in which multimode optical fibers are inserted, one in each, for light delivery. The light for PTT was directly administrated to subcutaneous tissues through the OFNA, causing negligible thermal damage to the skin. Enhancement of light energy delivery assisted by the OFNA in a target area was confirmed by investigation using artificial tissues. The ability of OFNA to treat cancer without causing cutaneous thermal damage was also verified by hematoxylin and eosin (H&E) staining and optical coherence tomography in cancer models in mice. In addition, the OFNA allowed for observation of the target site through an imaging fiber bundle. By imaging the activation of the injected gold-NSs, we were able to obtain information on the PTT process in real-time.

Analysis Concerning the Inspection Threshold for Multi-Site Damage.

DOT National Transportation Integrated Search

1993-12-01

Periodic inspections, at a prescribed interval, for Multi-Site Damage (MS) in longitudinal fuselage lap-joints start when the aircraft has accumulated a certain number of flights, the inspection threshold. The work reported here was an attempt to obt...

33 CFR 136.109 - Removal costs and multiple items of damages.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Removal costs and multiple items of damages. 136.109 Section 136.109 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL...

33 CFR 136.109 - Removal costs and multiple items of damages.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Removal costs and multiple items of damages. 136.109 Section 136.109 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL...

33 CFR 136.109 - Removal costs and multiple items of damages.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Removal costs and multiple items of damages. 136.109 Section 136.109 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL...

33 CFR 136.109 - Removal costs and multiple items of damages.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Removal costs and multiple items of damages. 136.109 Section 136.109 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL...

33 CFR 136.109 - Removal costs and multiple items of damages.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Removal costs and multiple items of damages. 136.109 Section 136.109 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL...

Satellite imagery-based monitoring of archaeological site damage in the Syrian civil war

PubMed Central

Laugier, Elise Jakoby

2017-01-01

Since the start of the Syrian civil war in 2011, the rich archaeological heritage of Syria and northern Iraq has faced severe threats, including looting, combat-related damage, and intentional demolition of monuments. However, the inaccessibility of the conflict zone to archaeologists or cultural heritage specialists has made it difficult to produce accurate damage assessments, impeding efforts to develop mitigation strategies and policies. This paper presents results of a project, undertaken in collaboration with the American Schools of Oriental Research (ASOR) and the US Department of State, to monitor damage to archaeological sites in Syria, northern Iraq, and southern Turkey using recent, high-resolution satellite imagery. Leveraging a large database of archaeological and heritage sites throughout the region, as well as access to continually updated satellite imagery from DigitalGlobe, this project has developed a flexible and efficient methodology to log observations of damage in a manner that facilitates spatial and temporal queries. With nearly 5000 sites carefully evaluated, analysis reveals unexpected patterns in the timing, severity, and location of damage, helping us to better understand the evolving cultural heritage crisis in Syria and Iraq. Results also offer a model for future remote sensing-based archaeological and heritage monitoring efforts in the Middle East and beyond. PMID:29190783

Satellite imagery-based monitoring of archaeological site damage in the Syrian civil war.

PubMed

Casana, Jesse; Laugier, Elise Jakoby

2017-01-01

Since the start of the Syrian civil war in 2011, the rich archaeological heritage of Syria and northern Iraq has faced severe threats, including looting, combat-related damage, and intentional demolition of monuments. However, the inaccessibility of the conflict zone to archaeologists or cultural heritage specialists has made it difficult to produce accurate damage assessments, impeding efforts to develop mitigation strategies and policies. This paper presents results of a project, undertaken in collaboration with the American Schools of Oriental Research (ASOR) and the US Department of State, to monitor damage to archaeological sites in Syria, northern Iraq, and southern Turkey using recent, high-resolution satellite imagery. Leveraging a large database of archaeological and heritage sites throughout the region, as well as access to continually updated satellite imagery from DigitalGlobe, this project has developed a flexible and efficient methodology to log observations of damage in a manner that facilitates spatial and temporal queries. With nearly 5000 sites carefully evaluated, analysis reveals unexpected patterns in the timing, severity, and location of damage, helping us to better understand the evolving cultural heritage crisis in Syria and Iraq. Results also offer a model for future remote sensing-based archaeological and heritage monitoring efforts in the Middle East and beyond.

Tissue damage drives co-localization of NF-κB, Smad3, and Nrf2 to direct Rev-erb sensitive wound repair in mouse macrophages

PubMed Central

Eichenfield, Dawn Z; Troutman, Ty Dale; Link, Verena M; Lam, Michael T; Cho, Han; Gosselin, David; Spann, Nathanael J; Lesch, Hanna P; Tao, Jenhan; Muto, Jun; Gallo, Richard L; Evans, Ronald M; Glass, Christopher K

2016-01-01

Although macrophages can be polarized to distinct phenotypes in vitro with individual ligands, in vivo they encounter multiple signals that control their varied functions in homeostasis, immunity, and disease. Here, we identify roles of Rev-erb nuclear receptors in regulating responses of mouse macrophages to complex tissue damage signals and wound repair. Rather than reinforcing a specific program of macrophage polarization, Rev-erbs repress subsets of genes that are activated by TLR ligands, IL4, TGFβ, and damage-associated molecular patterns (DAMPS). Unexpectedly, a complex damage signal promotes co-localization of NF-κB, Smad3, and Nrf2 at Rev-erb-sensitive enhancers and drives expression of genes characteristic of multiple polarization states in the same cells. Rev-erb-sensitive enhancers thereby integrate multiple damage-activated signaling pathways to promote a wound repair phenotype. DOI: http://dx.doi.org/10.7554/eLife.13024.001 PMID:27462873

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

PubMed

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

2009-12-01

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

Impact damage resistance of carbon/epoxy composite tubes for the DC-XA liquid hydrogen feedline

NASA Technical Reports Server (NTRS)

Nettles, A. T.

1995-01-01

Low-velocity impacts were inflicted upon two elbow sections of carbon/epoxy feedline that are to be a part of the Delta Clipper-XA flight vehicle. A soap-based liquid leak detector solution was used to inspect the impact sites for leaks of pressurized gas that was pumped into the tube. Visual surface damage was noted and recorded for each impact site. After impact testing of each of the two sections of tubes was completed, the damage zones were disected from the tube and cross sectioned through the impact site. These specimens were polished after potting them in epoxy and were examined for microcracking using a fluorescent dye penetrant technique. The results showed that nonvisible damage could cause microcracking, thereby resulting in leaks through the tube wall.

Spectroscopic investigation on assisted sonocatalytic damage of bovine serum albumin (BSA) by metronidazole (MTZ) under ultrasonic irradiation combined with nano-sized ZnO

NASA Astrophysics Data System (ADS)

Gao, Jingqun; Liu, Bin; Wang, Jun; Jin, Xudong; Jiang, Renzheng; Liu, Lijun; Wang, Baoxin; Xu, Yongnan

2010-11-01

The previous work proved that the bovine serum albumin (BSA) could be damaged under the combined action of ultrasonic irradiation and ZnO. In this work, the assisted sonocatalytic damage of BSA using metronidazole (MTZ) as a sensitizer was further investigated by means of UV-vis and fluorescence spectra. The results indicated that the adding of MTZ could obviously promote the sonocatalytic damage of BSA under ultrasonic irradiation in the presence of nano-sized ZnO powder. Furthermore, it was found that the damage degree of BSA was aggravated by some influencing factors except ionic kind and strength. In addition, the damage site of BSA was also studied with synchronous fluorescence technology. It was found that the damage site was mainly at tryptophan (Trp) residue.

Detection of Damaged DNA Bases by DNA Glycosylase Enzymes†

PubMed Central

Friedman, Joshua I.; Stivers, James T.

2010-01-01

A fundamental and shared process in all forms of life is the use of DNA glycosylase enzymes to excise rare damaged bases from genomic DNA. Without such enzymes, the highly-ordered primary sequences of genes would rapidly deteriorate. Recent structural and biophysical studies are beginning to reveal a fascinating multistep mechanism for damaged base detection that begins with short-range sliding of the glycosylase along the DNA chain in a distinct conformation we refer to as the search complex (SC). Sliding is frequently punctuated by the formation of a transient “interrogation” complex (IC) where the enzyme extrahelically inspects both normal and damaged bases in an exosite pocket that is distant from the active site. When normal bases are presented in the exosite, the IC rapidly collapses back to the SC, while a damaged base will efficiently partition forward into the active site to form the catalytically competent excision complex (EC). Here we review the unique problems associated with enzymatic detection of rare damaged DNA bases in the genome, and emphasize how each complex must have specific dynamic properties that are tuned to optimize the rate and efficiency of damage site location. PMID:20469926

Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework

PubMed Central

Kong, Eric F.; Tsui, Christina; Nguyen, M. Hong; Clancy, Cornelius J.; Fidel, Paul L.; Noverr, Mairi

2016-01-01

Historically, the nature and extent of host damage by a microbe were considered highly dependent on virulence attributes of the microbe. However, it has become clear that disease is a complex outcome which can arise because of pathogen-mediated damage, host-mediated damage, or both, with active participation from the host microbiota. This awareness led to the formulation of the damage response framework (DRF), a revolutionary concept that defined microbial virulence as a function of host immunity. The DRF outlines six classifications of host damage outcomes based on the microbe and the strength of the immune response. In this review, we revisit this concept from the perspective of Candida albicans, a microbial pathogen uniquely adapted to its human host. This fungus commonly colonizes various anatomical sites without causing notable damage. However, depending on environmental conditions, a diverse array of diseases may occur, ranging from mucosal to invasive systemic infections resulting in microbe-mediated and/or host-mediated damage. Remarkably, C. albicans infections can fit into all six DRF classifications, depending on the anatomical site and associated host immune response. Here, we highlight some of these diverse and site-specific diseases and how they fit the DRF classifications, and we describe the animal models available to uncover pathogenic mechanisms and related host immune responses. PMID:27430274

Spatiotemporal recruitment of human DNA polymerase delta to sites of UV damage

PubMed Central

Chea, Jennifer; Zhang, Sufang; Zhao, Hong; Zhang, Zhongtao; Lee, Ernest Y.C.; Darzynkiewicz, Zbigniew; Lee, Marietta Y.W.T.

2012-01-01

Human DNA polymerase δ (Pol δ) is involved in various DNA damage responses in addition to its central role in DNA replication. The Pol δ4 holoenzyme consists of four subunits, p125, p50, p68 and p12. It has been established that the p12 subunit is rapidly degraded in response to DNA damage by UV leading to the in vivo conversion of Pol δ4 to Pol δ3, a trimeric form lacking the p12 subunit. We provide the first analysis of the time-dependent recruitment of the individual Pol δ subunits to sites of DNA damage produced by UV irradiation through 5 μm polycarbonate filters by immunofluorescence microscopy and laser scanning cytometry (LSC). Quantitative analysis demonstrates that the recruitments of the three large subunits was near complete by 2 h and did not change significantly up to 4 h after UV exposure. However, the recruitment of p12 was incomplete even at 4 h, with about 70% of the Pol δ lacking the p12 subunit. ChIP analysis of Pol δ after global UV irradiation further demonstrates that only p125, p50 and p68 were present. Thus, Pol δ3 is the predominant form of Pol δ at sites of UV damage as a result of p12 degradation. Using LSC, we have further confirmed that Pol δ was recruited to CPD damage sites in all phases of the cell cycle. Collectively, our results show that Pol δ at the DNA damage site is the Pol δ trimer lacking p12 regardless of the cell cycle phase. PMID:22801543

Retinotomy using an erbium:YAG laser on human autopsy eyes

NASA Astrophysics Data System (ADS)

Ellsworth, Lansing G.; Kramer, Theresa R.; Noecker, Robert J.; Snyder, Robert W.; Yarborough, J. Michael

1994-06-01

Mid-IR lasers that operate near the absorption peak of water have a short penetration depth in ocular tissues. Ablation of tissue can be accomplished with minimal coagulative damage to underlying structures. We used an erbium:YAG laser equipped with a contact probe to create retinotomy sites in the human retina of eye bank eyes. An erbium:YAG laser (2.94 micrometers ) equipped with an infrared transmitting glass fiber and a sapphire tip (400 micrometers ) was used to directly ablate the surface of the retina. We administered both single and multiple pulses to the macula and peripheral retina using energy levels from 4 to 16 mJ per pulse. The retinas were then examined histopathologically to evaluate the extent of ablation and coagulative damage. Single pulses at low energy levels were noted to cause ablative damage to the nerve fiber layer and ganglion cell layer without a notable coagulative effect. The mean ablation depth at lower energy levels was less than the mean ablation depth at higher energy levels. Extensive laser application produced disruption of the retinal pigment epithelium, choroid and sclera. the erbium:YAG laser equipped with a contact probe is an effective means of creating retinotomies in human autopsy eyes. When used in the single pulse mode at lower energy levels, the erbium:YAG laser appears capable of removing superficial retinal layers without damaging deeper structures.

"What--me worry?" "Why so serious?": a personal view on the Fukushima nuclear reactor accidents.

PubMed

Gallucci, Raymond

2012-09-01

Infrequently, it seems that a significant accident precursor or, worse, an actual accident, involving a commercial nuclear power reactor occurs to remind us of the need to reexamine the safety of this important electrical power technology from a risk perspective. Twenty-five years since the major core damage accident at Chernobyl in the Ukraine, the Fukushima reactor complex in Japan experienced multiple core damages as a result of an earthquake-induced tsunami beyond either the earthquake or tsunami design basis for the site. Although the tsunami itself killed tens of thousands of people and left the area devastated and virtually uninhabitable, much concern still arose from the potential radioactive releases from the damaged reactors, even though there was little population left in the area to be affected. As a lifelong probabilistic safety analyst in nuclear engineering, even I must admit to a recurrence of the doubt regarding nuclear power safety after Fukushima that I had experienced after Three Mile Island and Chernobyl. This article is my attempt to "recover" my personal perspective on acceptable risk by examining both the domestic and worldwide history of commercial nuclear power plant accidents and attempting to quantify the risk in terms of the frequency of core damage that one might glean from a review of operational history. © 2012 Society for Risk Analysis.

Examination of Relationship Between Photonic Signatures and Fracture Strength of Fused Silica Used in Orbiter Windows

NASA Technical Reports Server (NTRS)

Yost, William T.; Cramer, K. Elliott; Estes, Linda R.; Salem, Jonathan A.; Lankford, James, Jr.; Lesniak, Jon

2011-01-01

A commercially available grey-field polariscope (GFP) instrument for photoelastic examination is used to assess impact damage inflicted upon the outermost pane of the orbiter windows. Four categories of damage: hyper-velocity impacts that occur during space-flight (HVI); hypervelocity impacts artificially made at the Hypervelocity Impact Technology Facility (HIT-F); impacts made by larger objects falling onto the pane surface to simulate dropped items on the window during service/storage of vehicle (Bruises); and light scratches from dull objects designed to mimic those that might occur by dragging a dull object across the glass surface (Chatter Checks) are examined. The damage sites are cored from fused silica window carcasses, examined with the GFP and other methodologies, and broken using the ASTM Standard C1499-09 to measure the fracture strength. A correlation is made between the fracture strength and damage-site measurements including geometrical measurements and GFP measurements of photoelastic retardation (stress patterns) surrounding the damage sites. An analytical damage model to predict fracture strength from photoelastic retardation measurements is presented and compared with experimental results.

Structure of transcribed chromatin is a sensor of DNA damage

PubMed Central

Pestov, Nikolay A.; Gerasimova, Nadezhda S.; Kulaeva, Olga I.; Studitsky, Vasily M.

2015-01-01

Early detection and repair of damaged DNA is essential for cell functioning and survival. Although multiple cellular systems are involved in the repair of single-strand DNA breaks (SSBs), it remains unknown how SSBs present in the nontemplate strand (NT-SSBs) of DNA organized in chromatin are detected. The effect of NT-SSBs on transcription through chromatin by RNA polymerase II was studied. NT-SSBs localized in the promoter-proximal region of nucleosomal DNA and hidden in the nucleosome structure can induce a nearly quantitative arrest of RNA polymerase downstream of the break, whereas more promoter-distal SSBs moderately facilitate transcription. The location of the arrest sites on nucleosomal DNA suggests that formation of small intranucleosomal DNA loops causes the arrest. This mechanism likely involves relief of unconstrained DNA supercoiling accumulated during transcription through chromatin by NT-SSBs. These data suggest the existence of a novel chromatin-specific mechanism that allows the detection of NT-SSBs by the transcribing enzyme. PMID:26601207

TAM receptors regulate multiple features of microglial physiology.

PubMed

Fourgeaud, Lawrence; Través, Paqui G; Tufail, Yusuf; Leal-Bailey, Humberto; Lew, Erin D; Burrola, Patrick G; Callaway, Perri; Zagórska, Anna; Rothlin, Carla V; Nimmerjahn, Axel; Lemke, Greg

2016-04-14

Microglia are damage sensors for the central nervous system (CNS), and the phagocytes responsible for routine non-inflammatory clearance of dead brain cells. Here we show that the TAM receptor tyrosine kinases Mer and Axl regulate these microglial functions. We find that adult mice deficient in microglial Mer and Axl exhibit a marked accumulation of apoptotic cells specifically in neurogenic regions of the CNS, and that microglial phagocytosis of the apoptotic cells generated during adult neurogenesis is normally driven by both TAM receptor ligands Gas6 and protein S. Using live two-photon imaging, we demonstrate that the microglial response to brain damage is also TAM-regulated, as TAM-deficient microglia display reduced process motility and delayed convergence to sites of injury. Finally, we show that microglial expression of Axl is prominently upregulated in the inflammatory environment that develops in a mouse model of Parkinson's disease. Together, these results establish TAM receptors as both controllers of microglial physiology and potential targets for therapeutic intervention in CNS disease.

Advances in Fatigue and Fracture Mechanics Analyses for Aircraft Structures

NASA Technical Reports Server (NTRS)

Newman, J. C., Jr.

1999-01-01

This paper reviews some of the advances that have been made in stress analyses of cracked aircraft components, in the understanding of the fatigue and fatigue-crack growth process, and in the prediction of residual strength of complex aircraft structures with widespread fatigue damage. Finite-element analyses of cracked structures are now used to determine accurate stress-intensity factors for cracks at structural details. Observations of small-crack behavior at open and rivet-loaded holes and the development of small-crack theory has lead to the prediction of stress-life behavior for components with stress concentrations under aircraft spectrum loading. Fatigue-crack growth under simulated aircraft spectra can now be predicted with the crack-closure concept. Residual strength of cracked panels with severe out-of-plane deformations (buckling) in the presence of stiffeners and multiple-site damage can be predicted with advanced elastic-plastic finite-element analyses and the critical crack-tip-opening angle (CTOA) fracture criterion. These advances are helping to assure continued safety of aircraft structures.

Advances in Fatigue and Fracture Mechanics Analyses for Metallic Aircraft Structures

NASA Technical Reports Server (NTRS)

Newman, J. C., Jr.

2000-01-01

This paper reviews some of the advances that have been made in stress analyses of cracked aircraft components, in the understanding of the fatigue and fatigue-crack growth process, and in the prediction of residual strength of complex aircraft structures with widespread fatigue damage. Finite-element analyses of cracked metallic structures are now used to determine accurate stress-intensity factors for cracks at structural details. Observations of small-crack behavior at open and rivet-loaded holes and the development of small-crack theory has lead to the prediction of stress-life behavior for components with stress concentrations under aircraft spectrum loading. Fatigue-crack growth under simulated aircraft spectra can now be predicted with the crack-closure concept. Residual strength of cracked panels with severe out-of-plane deformations (buckling) in the presence of stiffeners and multiple-site damage can be predicted with advanced elastic-plastic finite-element analyses and the critical crack-tip-opening angle (CTOA) fracture criterion. These advances are helping to assure continued safety of aircraft structures.

Monitoring impacts of Tamarix leaf beetles (Diorhabda elongata) on the leaf phenology and water use of Tamarix spp. using ground and remote sensing methods

NASA Astrophysics Data System (ADS)

Nagler, P. L.; Brown, T.; Hultine, K. R.; van Riper, C.; Bean, D. A.; Murray, R.; Pearlstein, S.; Glenn, E. P.

2010-12-01

Tamarix leaf beetles (Diorhabda elongata) have been released in several locations on western U.S. rivers to control the introduced shrub, Tamarix ramosissima and related species. As they are expanding widely throughout the region, information is needed on their impact on Tamarix leaf phenology and water use over multiple cycles of annual defoliation. We used networked digital cameras (phenocams) and ground surveys to monitor the defoliation process from 2008-2010 at multiple sites on the Dolores River, and MODIS satellite imagery from 2000 to 2009 to monitor leaf phenology and evapotranspiration (ET) at beetle release sites on the Dolores, Lower Colorado, Carson, Walker and Bighorn Rivers. Enhanced Vegetation Index (EVI) values for selected MODIS pixels were used to estimate green foliage density before and after beetle releases at each site. EVI values were transformed into estimates of ET using an empirical algorithm relating ET to EVI and potential ET (ETo) at each site. Phenocam and ground observations show that beetle damage is temporary, and plants regenerate new leaves following an eight week defoliation period in summer. The original biocontrol model predicted that Tamarix mortality would reach 75-85% over several years of defoliation due to progressive weakening of the shrubs each year, but over the early stages of leaf beetle-Tamarix interactions studied here (3-8 years), our preliminary findings show actual reductions in EVI and ET of only 13-15% across sites due to the relatively brief period of defoliation and because not all plants at a site were defoliated. Also, baseline ET rates varied across sites but averaged only 329 mm yr-1 (23% of ETo), constraining the possibilities for water salvage through biocontrol of Tamarix. The spatial and temperol resolution of MODIS imagery were too coarse to capture the details of the defoliation process, and high-resolution imagery or expanded phenocam networks are needed for future monitoring programs.

RING finger and WD repeat domain 3 (RFWD3) associates with replication protein A (RPA) and facilitates RPA-mediated DNA damage response.

PubMed

Liu, Shangfeng; Chu, Jessica; Yucer, Nur; Leng, Mei; Wang, Shih-Ya; Chen, Benjamin P C; Hittelman, Walter N; Wang, Yi

2011-06-24

DNA damage response is crucial for maintaining genomic integrity and preventing cancer by coordinating the activation of checkpoints and the repair of damaged DNA. Central to DNA damage response are the two checkpoint kinases ATM and ATR that phosphorylate a wide range of substrates. RING finger and WD repeat domain 3 (RFWD3) was initially identified as a substrate of ATM/ATR from a proteomic screen. Subsequent studies showed that RFWD3 is an E3 ubiquitin ligase that ubiquitinates p53 in vitro and positively regulates p53 levels in response to DNA damage. We report here that RFWD3 associates with replication protein A (RPA), a single-stranded DNA-binding protein that plays essential roles in DNA replication, recombination, and repair. Binding of RPA to single-stranded DNA (ssDNA), which is generated by DNA damage and repair, is essential for the recruitment of DNA repair factors to damaged sites and the activation of checkpoint signaling. We show that RFWD3 is physically associated with RPA and rapidly localizes to sites of DNA damage in a RPA-dependent manner. In vitro experiments suggest that the C terminus of RFWD3, which encompass the coiled-coil domain and the WD40 domain, is necessary for binding to RPA. Furthermore, DNA damage-induced phosphorylation of RPA and RFWD3 is dependent upon each other. Consequently, loss of RFWD3 results in the persistent foci of DNA damage marker γH2AX and the repair protein Rad51 in damaged cells. These findings suggest that RFWD3 is recruited to sites of DNA damage and facilitates RPA-mediated DNA damage signaling and repair.

Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation

NASA Technical Reports Server (NTRS)

Sutherland, B. M.; Bennett, P. V.; Sidorkina, O.; Laval, J.; Lowenstein, D. I. (Principal Investigator)

2000-01-01

Clustered DNA damages-two or more closely spaced damages (strand breaks, abasic sites, or oxidized bases) on opposing strands-are suspects as critical lesions producing lethal and mutagenic effects of ionizing radiation. However, as a result of the lack of methods for measuring damage clusters induced by ionizing radiation in genomic DNA, neither the frequencies of their production by physiological doses of radiation, nor their repairability, nor their biological effects are known. On the basis of methods that we developed for quantitating damages in large DNAs, we have devised and validated a way of measuring ionizing radiation-induced clustered lesions in genomic DNA, including DNA from human cells. DNA is treated with an endonuclease that induces a single-strand cleavage at an oxidized base or abasic site. If there are two closely spaced damages on opposing strands, such cleavage will reduce the size of the DNA on a nondenaturing gel. We show that ionizing radiation does induce clustered DNA damages containing abasic sites, oxidized purines, or oxidized pyrimidines. Further, the frequency of each of these cluster classes is comparable to that of frank double-strand breaks; among all complex damages induced by ionizing radiation, double-strand breaks are only about 20%, with other clustered damage constituting some 80%. We also show that even low doses (0.1-1 Gy) of high linear energy transfer ionizing radiation induce clustered damages in human cells.

Surface damage of thin AlN films with increased oxygen content by nanosecond and femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Gruzdev, Vitaly; Salakhutdinov, Ildar; Chen, J. K.; Danylyuk, Yuriy; McCullen, Erik; Auner, Gregory

2009-10-01

AlN films deposited on sapphire substrates were damaged by single UV nanosecond (at 248 nm) and IR femtosecond (at 775 nm) laser pulses in air at normal pressure. The films had high (27-35 atomic %) concentration of oxygen introduced into thin surface layer (5-10 nm thickness). We measured damage threshold and studied morphology of the damage sites with atomic force and Nomarski optical microscopes with the objective to determine a correlation between damage processes and oxygen content. The damage produced by nanosecond pulses was accompanied by significant thermal effects with evident signatures of melting, chemical modification of the film surface, and specific redistribution of micro-defect rings around the damage spots. The nanosecond-damage threshold exhibited pronounced increase with increase of the oxygen content. In contrast to that, the femtosecond pulses produced damage without any signs of thermal, thermo-mechanical or chemical effects. No correlation between femtosecond-damage threshold and oxygen content as well as presence of defects within the laser-damage spot was found. We discuss the influence of the oxygen contamination on film properties and related mechanisms responsible for the specific damage effects and morphology of the damage sites observed in the experiments.

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.

Multiple pulse nanosecond laser induced damage threshold on hybrid mirrors

NASA Astrophysics Data System (ADS)

Vanda, Jan; Muresan, Mihai-George; Bilek, Vojtech; Sebek, Matej; Hanus, Martin; Lucianetti, Antonio; Rostohar, Danijela; Mocek, Tomas; Škoda, Václav

2017-11-01

So-called hybrid mirrors, consisting of broadband metallic surface coated with dielectric reflector designed for specific wavelength, becoming more important with progressing development of broadband mid-IR sources realized using parametric down conversion system. Multiple pulse nanosecond laser induced damage on such mirrors was tested by method s-on-1, where s stands for various numbers of pulses. We show difference in damage threshold between common protected silver mirrors and hybrid silver mirrors prepared by PVD technique and their variants prepared by IAD. Keywords: LIDT,

Tube cutter tool and method of use for coupon removal

DOEpatents

Nachbar, H.D.; Etten, M.P. Jr.; Kurowski, P.A.

1997-05-06

A tube cutter tool is insertable into a tube for cutting a coupon from a damaged site on the exterior of the tube. Prior to using the tool, the damaged site is first located from the interior of the tube using a multi-coil pancake eddy current test probe. The damaged site is then marked. A fiber optic probe is used to monitor the subsequent cutting procedure which is performed using a hole saw mounted on the tube cutter tool. Prior to completion of the cutting procedure, a drill in the center of the hole saw is drilled into the coupon to hold it in place. 4 figs.

Tube cutter tool and method of use for coupon removal

DOEpatents

Nachbar, Henry D.; Etten, Jr., Marvin P.; Kurowski, Paul A.

1997-01-01

A tube cutter tool is insertable into a tube for cutting a coupon from a damaged site on the exterior of the tube. Prior to using the tool, the damaged site is first located from the interior of the tube using a multi-coil pancake eddy current test probe. The damaged site is then marked. A fiber optic probe is used to monitor the subsequent cutting procedure which is performed using a hole saw mounted on the tube cutter tool. Prior to completion of the cutting procedure, a drill in the center of the hole saw is drilled into the coupon to hold it in place.

Reduction of skin damage from transcutaneous oxygen electrodes using a spray on dressing.

PubMed Central

Evans, N J; Rutter, N

1986-01-01

A spray on, copolymer acrylic dressing (Op-Site) was used to limit the skin damage caused by a transcutaneous oxygen electrode and its adhesive ring. Two identical electrodes were applied to the abdominal skin of 10 preterm infants, one on untreated skin, the other after application of Op-Site. It was found that Op-Site prevented the epidermal damage (as measured by transepidermal water loss) that occurs when the adhesive ring is removed from untreated skin. It did not interfere with transcutaneous oxygen measurements; absolute values and response times were unchanged. Op-Site is therefore useful in preventing the skin trauma that occurs when transcutaneous oxygen monitoring is being performed in preterm infants below 30 weeks' gestation in the first week of life. Care must be taken, however, to prevent a build up of Op-Site--it should be applied as a single layer, allowed to dry, and removed after use. PMID:3767417

Reduction of skin damage from transcutaneous oxygen electrodes using a spray on dressing.

PubMed

Evans, N J; Rutter, N

1986-09-01

A spray on, copolymer acrylic dressing (Op-Site) was used to limit the skin damage caused by a transcutaneous oxygen electrode and its adhesive ring. Two identical electrodes were applied to the abdominal skin of 10 preterm infants, one on untreated skin, the other after application of Op-Site. It was found that Op-Site prevented the epidermal damage (as measured by transepidermal water loss) that occurs when the adhesive ring is removed from untreated skin. It did not interfere with transcutaneous oxygen measurements; absolute values and response times were unchanged. Op-Site is therefore useful in preventing the skin trauma that occurs when transcutaneous oxygen monitoring is being performed in preterm infants below 30 weeks' gestation in the first week of life. Care must be taken, however, to prevent a build up of Op-Site--it should be applied as a single layer, allowed to dry, and removed after use.

Xeroderma Pigmentosum Group A Suppresses Mutagenesis Caused by Clustered Oxidative DNA Adducts in the Human Genome.

PubMed

Sassa, Akira; Kamoshita, Nagisa; Kanemaru, Yuki; Honma, Masamitsu; Yasui, Manabu

2015-01-01

Clustered DNA damage is defined as multiple sites of DNA damage within one or two helical turns of the duplex DNA. This complex damage is often formed by exposure of the genome to ionizing radiation and is difficult to repair. The mutagenic potential and repair mechanisms of clustered DNA damage in human cells remain to be elucidated. In this study, we investigated the involvement of nucleotide excision repair (NER) in clustered oxidative DNA adducts. To identify the in vivo protective roles of NER, we established a human cell line lacking the NER gene xeroderma pigmentosum group A (XPA). XPA knockout (KO) cells were generated from TSCER122 cells derived from the human lymphoblastoid TK6 cell line. To analyze the mutagenic events in DNA adducts in vivo, we previously employed a system of tracing DNA adducts in the targeted mutagenesis (TATAM), in which DNA adducts were site-specifically introduced into intron 4 of thymidine kinase genes. Using the TATAM system, one or two tandem 7,8-dihydro-8-oxoguanine (8-oxoG) adducts were introduced into the genomes of TSCER122 or XPA KO cells. In XPA KO cells, the proportion of mutants induced by a single 8-oxoG (7.6%) was comparable with that in TSCER122 cells (8.1%). In contrast, the lack of XPA significantly enhanced the mutant proportion of tandem 8-oxoG in the transcribed strand (12%) compared with that in TSCER122 cells (7.4%) but not in the non-transcribed strand (12% and 11% in XPA KO and TSCER122 cells, respectively). By sequencing the tandem 8-oxoG-integrated loci in the transcribed strand, we found that the proportion of tandem mutations was markedly increased in XPA KO cells. These results indicate that NER is involved in repairing clustered DNA adducts in the transcribed strand in vivo.

Xeroderma Pigmentosum Group A Suppresses Mutagenesis Caused by Clustered Oxidative DNA Adducts in the Human Genome

PubMed Central

Sassa, Akira; Kamoshita, Nagisa; Kanemaru, Yuki; Honma, Masamitsu; Yasui, Manabu

2015-01-01

Clustered DNA damage is defined as multiple sites of DNA damage within one or two helical turns of the duplex DNA. This complex damage is often formed by exposure of the genome to ionizing radiation and is difficult to repair. The mutagenic potential and repair mechanisms of clustered DNA damage in human cells remain to be elucidated. In this study, we investigated the involvement of nucleotide excision repair (NER) in clustered oxidative DNA adducts. To identify the in vivo protective roles of NER, we established a human cell line lacking the NER gene xeroderma pigmentosum group A (XPA). XPA knockout (KO) cells were generated from TSCER122 cells derived from the human lymphoblastoid TK6 cell line. To analyze the mutagenic events in DNA adducts in vivo, we previously employed a system of tracing DNA adducts in the targeted mutagenesis (TATAM), in which DNA adducts were site-specifically introduced into intron 4 of thymidine kinase genes. Using the TATAM system, one or two tandem 7,8-dihydro-8-oxoguanine (8-oxoG) adducts were introduced into the genomes of TSCER122 or XPA KO cells. In XPA KO cells, the proportion of mutants induced by a single 8-oxoG (7.6%) was comparable with that in TSCER122 cells (8.1%). In contrast, the lack of XPA significantly enhanced the mutant proportion of tandem 8-oxoG in the transcribed strand (12%) compared with that in TSCER122 cells (7.4%) but not in the non-transcribed strand (12% and 11% in XPA KO and TSCER122 cells, respectively). By sequencing the tandem 8-oxoG-integrated loci in the transcribed strand, we found that the proportion of tandem mutations was markedly increased in XPA KO cells. These results indicate that NER is involved in repairing clustered DNA adducts in the transcribed strand in vivo. PMID:26559182

Quantifying clustered DNA damage induction and repair by gel electrophoresis, electronic imaging and number average length analysis

NASA Technical Reports Server (NTRS)

Sutherland, Betsy M.; Georgakilas, Alexandros G.; Bennett, Paula V.; Laval, Jacques; Sutherland, John C.; Gewirtz, A. M. (Principal Investigator)

2003-01-01

Assessing DNA damage induction, repair and consequences of such damages requires measurement of specific DNA lesions by methods that are independent of biological responses to such lesions. Lesions affecting one DNA strand (altered bases, abasic sites, single strand breaks (SSB)) as well as damages affecting both strands (clustered damages, double strand breaks) can be quantified by direct measurement of DNA using gel electrophoresis, gel imaging and number average length analysis. Damage frequencies as low as a few sites per gigabase pair (10(9)bp) can be quantified by this approach in about 50ng of non-radioactive DNA, and single molecule methods may allow such measurements in DNA from single cells. This review presents the theoretical basis, biochemical requirements and practical aspects of this approach, and shows examples of their applications in identification and quantitation of complex clustered damages.

Transverse Diffusivity of Cerebral Parenchyma Predicts Visual Tracking Performance in Relapsing-Remitting Multiple Sclerosis

ERIC Educational Resources Information Center

Warlop, Nele P.; Achten, Eric; Fieremans, Els; Debruyne, Jan; Vingerhoets, Guy

2009-01-01

This study investigated the relation between cerebral damage related to multiple sclerosis (MS) and cognitive decline as determined by two classical mental tracking tests. Cerebral damage in 15 relapsing-remitting MS patients was measured by diffusion tensor imaging (DTI). Fractional anisotropy, longitudinal and transverse diffusivity were defined…

A comparison of campfire impacts and policies in seven protected areas

USGS Publications Warehouse

Reid, S.E.; Marion, J.L.

2005-01-01

Using resource-monitoring data from seven protected areas, the effectiveness of three campfire policies-campfire ban, designated campfires, and unregulated campfires-were assessed based on the number of fire sites and the amount of tree damage. Results indicate that unregulated campfire policies permitted substantial numbers of fire sites and tree damage in campsites, although fire bans did not eliminate or even substantially decrease these problems. A designated campfire policy was effective in decreasing number of fire sites, but little difference was found among policies regarding tree damage. Given the importance of campfires to visitor experiences, campfire prohibitions could be viewed as unnecessarily restrictive based on their limited success in preventing resource damage. Conclusions encourage protected-area managers to consider designated campfire policies and prohibitions on axes, hatchets, and saws to better meet resource protection and visitor experience mandates.

Cryptic biodiversity effects: importance of functional redundancy revealed through addition of food web complexity.

PubMed

Philpott, Stacy M; Pardee, Gabriella L; Gonthier, David J

2012-05-01

Interactions between predators and the degree of functional redundancy among multiple predator species may determine whether herbivores experience increased or decreased predation risk. Specialist parasites can modify predator behavior, yet rarely have cascading effects on multiple predator species and prey been evaluated. We examined influences of specialist phorid parasites (Pseudacteon spp.) on three predatory ant species and herbivores in a coffee agroecosystem. Specifically, we examined whether changes in ant richness affected fruit damage by the coffee berry borer (Hypothenemus hampei) and whether phorids altered multi-predator effects. Each ant species reduced borer damage, and without phorids, increasing predator richness did not further decrease borer damage. However, with phorids, activity of one ant species was reduced, indicating that the presence of multiple ant species was necessary to limit borer damage. In addition, phorid presence revealed synergistic effects of multiple ant species, not observed without the presence of this parasite. Thus, a trait-mediated cascade resulting from a parasite-induced predator behavioral change revealed the importance of functional redundancy, predator diversity, and food web complexity for control of this important pest.

PARP-1 dependent recruitment of the amyotrophic lateral sclerosis-associated protein FUS/TLS to sites of oxidative DNA damage

PubMed Central

Rulten, Stuart L.; Rotheray, Amy; Green, Ryan L.; Grundy, Gabrielle J.; Moore, Duncan A. Q.; Gómez-Herreros, Fernando; Hafezparast, Majid; Caldecott, Keith W

2014-01-01

Amyotrophic lateral sclerosis (ALS) is associated with progressive degeneration of motor neurons. Several of the genes associated with this disease encode proteins involved in RNA processing, including fused-in-sarcoma/translocated-in-sarcoma (FUS/TLS). FUS is a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family of proteins that bind thousands of pre-mRNAs and can regulate their splicing. Here, we have examined the possibility that FUS is also a component of the cellular response to DNA damage. We show that both GFP-tagged and endogenous FUS re-localize to sites of oxidative DNA damage induced by UVA laser, and that FUS recruitment is greatly reduced or ablated by an inhibitor of poly (ADP-ribose) polymerase activity. Consistent with this, we show that recombinant FUS binds directly to poly (ADP-ribose) in vitro, and that both GFP-tagged and endogenous FUS fail to accumulate at sites of UVA laser induced damage in cells lacking poly (ADP-ribose) polymerase-1. Finally, we show that GFP-FUSR521G, harbouring a mutation that is associated with ALS, exhibits reduced ability to accumulate at sites of UVA laser-induced DNA damage. Together, these data suggest that FUS is a component of the cellular response to DNA damage, and that defects in this response may contribute to ALS. PMID:24049082

A Peptide Targeting Inflammatory CNS Lesions in the EAE Rat Model of Multiple Sclerosis.

PubMed

Boiziau, Claudine; Nikolski, Macha; Mordelet, Elodie; Aussudre, Justine; Vargas-Sanchez, Karina; Petry, Klaus G

2018-06-01

Multiple sclerosis is characterized by inflammatory lesions dispersed throughout the central nervous system (CNS) leading to severe neurological handicap. Demyelination, axonal damage, and blood brain barrier alterations are hallmarks of this pathology, whose precise processes are not fully understood. In the experimental autoimmune encephalomyelitis (EAE) rat model that mimics many features of human multiple sclerosis, the phage display strategy was applied to select peptide ligands targeting inflammatory sites in CNS. Due to the large diversity of sequences after phage display selection, a bioinformatics procedure called "PepTeam" designed to identify peptides mimicking naturally occurring proteins was used, with the goal to predict peptides that were not background noise. We identified a circular peptide CLSTASNSC called "Ph48" as an efficient binder of inflammatory regions of EAE CNS sections including small inflammatory lesions of both white and gray matter. Tested on human brain endothelial cells hCMEC/D3, Ph48 was able to bind efficiently when these cells were activated with IL1β to mimic inflammatory conditions. The peptide is therefore a candidate for further analyses of the molecular alterations in inflammatory lesions.

Physical Association of Saccharomyces cerevisiae Polo-like Kinase Cdc5 with Chromosomal Cohesin Facilitates DNA Damage Response.

PubMed

Pakchuen, Sujiraporn; Ishibashi, Mai; Takakusagi, Emi; Shirahige, Katsuhiko; Sutani, Takashi

2016-08-12

At the onset of anaphase, a protease called separase breaks the link between sister chromatids by cleaving the cohesin subunit Scc1. This irreversible step in the cell cycle is promoted by degradation of the separase inhibitor, securin, and polo-like kinase (Plk) 1-dependent phosphorylation of the Scc1 subunit. Plk could recognize substrates through interaction between its phosphopeptide interaction domain, the polo-box domain, and a phosphorylated priming site in the substrate, which has been generated by a priming kinase beforehand. However, the physiological relevance of this targeting mechanism remains to be addressed for many of the Plk1 substrates. Here, we show that budding yeast Plk1, Cdc5, is pre-deposited onto cohesin engaged in cohesion on chromosome arms in G2/M phase cells. The Cdc5-cohesin association is mediated by direct interaction between the polo-box domain of Cdc5 and Scc1 phosphorylated at multiple sites in its middle region. Alanine substitutions of the possible priming phosphorylation sites (scc1-15A) impair Cdc5 association with chromosomal cohesin, but they make only a moderate impact on mitotic cell growth even in securin-deleted cells (pds1Δ), where Scc1 phosphorylation by Cdc5 is indispensable. The same scc1-15A pds1Δ double mutant, however, exhibits marked sensitivity to the DNA-damaging agent phleomycin, suggesting that the priming phosphorylation of Scc1 poses an additional layer of regulation that enables yeast cells to adapt to genotoxic environments. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Accumulation of p21 proteins at DNA damage sites independent of p53 and core NHEJ factors following irradiation

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

Koike, Manabu, E-mail: m_koike@nirs.go.jp; Yutoku, Yasutomo; Graduate School of Science, Chiba University, Chiba 263-8522

2011-08-19

Highlights: {yields} p21 accumulated rapidly at laser-irradiated sites via its C-terminal region. {yields} p21 colocalized with the DSB marker {gamma}-H2AX and the DSB sensor Ku80. {yields} Accumulation of p21 is dependent on PCNA, but not p53 and the NHEJ core factors. {yields} Accumulation activity of p21 was conserved among human and animal cells. {yields} p21 is a useful tool as a detection marker of DNA damaged sites. -- Abstract: The cyclin-dependent kinase (CDK) inhibitor p21 plays key roles in p53-dependent DNA-damage responses, i.e., cell cycle checkpoints, senescence, or apoptosis. p21 might also play a role in DNA repair. p21 focimore » arise at heavy-ion-irradiated DNA-double-strand break (DSB) sites, which are mainly repaired by nonhomologous DNA-end-joining (NHEJ). However, no mechanisms of p21 accumulation at double-strand break (DSB) sites have been clarified in detail. Recent works indicate that Ku70 and Ku80 are essential for the accumulation of other NHEJ core factors, e.g., DNA-PKcs, XRCC4 and XLF, and other DNA damage response factors, e.g., BRCA1. Here, we show that p21 foci arise at laser-irradiated sites in cells from various tissues from various species. The accumulation of EGFP-p21 was detected in not only normal cells, but also transformed or cancer cells. Our results also showed that EGFP-p21 accumulated rapidly at irradiated sites, and colocalized with the DSB marker {gamma}-H2AX and with the DSB sensor protein Ku80. On the other hand, the accumulation occurred in Ku70-, Ku80-, or DNA-PKcs-deficient cell lines and in human papillomavirus 18-positive cells, whereas the p21 mutant without the PCNA-binding region (EGFP-p21(1-146)) failed to accumulate at the irradiated sites. These findings suggest that the accumulation of p21, but not functional p53 and the NHEJ core factors, is dependent on PCNA. These findings also suggest that the accumulation activity of p21 at DNA damaged sites is conserved among human and animal cells, and p21 is a useful tool as a detection marker of DNA damaged sites.« less

Development of Micro and Nanostructured Materials for Interfacial Self-Healing

ERIC Educational Resources Information Center

Blaiszik, Benjamin James

2009-01-01

Damage in polymeric coatings, adhesives, microelectronic components, and composites spans many length scales. For small scale damage, autonomic self-healing can repair multiple damage modes without manual intervention. In autonomic self-healing materials, a healing response is triggered by damage to the material. Size scale considerations, such as…

Disaster damage detection through synergistic use of deep learning and 3D point cloud features derived from very high resolution oblique aerial images, and multiple-kernel-learning

NASA Astrophysics Data System (ADS)

Vetrivel, Anand; Gerke, Markus; Kerle, Norman; Nex, Francesco; Vosselman, George

2018-06-01

Oblique aerial images offer views of both building roofs and façades, and thus have been recognized as a potential source to detect severe building damages caused by destructive disaster events such as earthquakes. Therefore, they represent an important source of information for first responders or other stakeholders involved in the post-disaster response process. Several automated methods based on supervised learning have already been demonstrated for damage detection using oblique airborne images. However, they often do not generalize well when data from new unseen sites need to be processed, hampering their practical use. Reasons for this limitation include image and scene characteristics, though the most prominent one relates to the image features being used for training the classifier. Recently features based on deep learning approaches, such as convolutional neural networks (CNNs), have been shown to be more effective than conventional hand-crafted features, and have become the state-of-the-art in many domains, including remote sensing. Moreover, often oblique images are captured with high block overlap, facilitating the generation of dense 3D point clouds - an ideal source to derive geometric characteristics. We hypothesized that the use of CNN features, either independently or in combination with 3D point cloud features, would yield improved performance in damage detection. To this end we used CNN and 3D features, both independently and in combination, using images from manned and unmanned aerial platforms over several geographic locations that vary significantly in terms of image and scene characteristics. A multiple-kernel-learning framework, an effective way for integrating features from different modalities, was used for combining the two sets of features for classification. The results are encouraging: while CNN features produced an average classification accuracy of about 91%, the integration of 3D point cloud features led to an additional improvement of about 3% (i.e. an average classification accuracy of 94%). The significance of 3D point cloud features becomes more evident in the model transferability scenario (i.e., training and testing samples from different sites that vary slightly in the aforementioned characteristics), where the integration of CNN and 3D point cloud features significantly improved the model transferability accuracy up to a maximum of 7% compared with the accuracy achieved by CNN features alone. Overall, an average accuracy of 85% was achieved for the model transferability scenario across all experiments. Our main conclusion is that such an approach qualifies for practical use.

Site effects in Avcilar, West of Istanbul, Turkey, from strong- and weak-motion data

USGS Publications Warehouse

Ozel, O.; Cranswick, E.; Meremonte, M.; Erdik, M.; Safak, E.

2002-01-01

Approximately 1000 people were killed in the collapse of buildings in Istanbul, Turkey, during the 17 August 1999 I??zmit earthquake, whose epicenter was roughly 90 km east of the city. Most of the fatalities and damage occurred in the suburb of Avcilar that is 20 km further west of the epicenter than the city proper. To investigate this pattern of damage, the U.S. Geological Survey, in cooperation with the Kandilli Observatory and Earthquake Research Institute (KOERI), deployed portable digital seismographs at seven free-field sites in western Istanbul, to record aftershocks during the period from 24 August to 2 September. The primary objective of this deployment was to study the site effects by comparing the aftershock ground motions recorded at sites inside and outside the damaged area, and to correlate site effects with the distribution of the damaged buildings. In addition to using weak-motion data, mainshock and aftershock acceleration records from the KOERI permanent strong-motion array were also used in estimating the site effects. Site effects were estimated using S waves from both types of records. For the weak-motion data set, 22 events were selected according to the criteria of signal-to-noise ratio (S/N ratio) and the number of stations recording the same event. The magnitudes of these events ranged from 3.0 to 5.2. The acceleration data set consisted of 12 events with magnitudes ranging from 4.3 to 5.8 and included two mainshock events. Results show that the amplifying frequency band is, in general, less than 4 Hz, and the physical properties of the geologic materials are capable of amplifying the motions by a factor of 5-10. In this frequency band, there is a good agreement among the spectral ratios obtained from the two mainshocks and their aftershocks. The damage pattern for the 17 August I??zmit earthquake is determined by several factors. However, our study suggests that the site effects in Avcilar played an important role in contributing to the damage.

Damage Evaluation Based on a Wave Energy Flow Map Using Multiple PZT Sensors

PubMed Central

Liu, Yaolu; Hu, Ning; Xu, Hong; Yuan, Weifeng; Yan, Cheng; Li, Yuan; Goda, Riu; Alamusi; Qiu, Jinhao; Ning, Huiming; Wu, Liangke

2014-01-01

A new wave energy flow (WEF) map concept was proposed in this work. Based on it, an improved technique incorporating the laser scanning method and Betti's reciprocal theorem was developed to evaluate the shape and size of damage as well as to realize visualization of wave propagation. In this technique, a simple signal processing algorithm was proposed to construct the WEF map when waves propagate through an inspection region, and multiple lead zirconate titanate (PZT) sensors were employed to improve inspection reliability. Various damages in aluminum and carbon fiber reinforced plastic laminated plates were experimentally and numerically evaluated to validate this technique. The results show that it can effectively evaluate the shape and size of damage from wave field variations around the damage in the WEF map. PMID:24463430

Building vulnerability to hydro-geomorphic hazards: Estimating damage probability from qualitative vulnerability assessment using logistic regression

NASA Astrophysics Data System (ADS)

Ettinger, Susanne; Mounaud, Loïc; Magill, Christina; Yao-Lafourcade, Anne-Françoise; Thouret, Jean-Claude; Manville, Vern; Negulescu, Caterina; Zuccaro, Giulio; De Gregorio, Daniela; Nardone, Stefano; Uchuchoque, Juan Alexis Luque; Arguedas, Anita; Macedo, Luisa; Manrique Llerena, Nélida

2016-10-01

The focus of this study is an analysis of building vulnerability through investigating impacts from the 8 February 2013 flash flood event along the Avenida Venezuela channel in the city of Arequipa, Peru. On this day, 124.5 mm of rain fell within 3 h (monthly mean: 29.3 mm) triggering a flash flood that inundated at least 0.4 km2 of urban settlements along the channel, affecting more than 280 buildings, 23 of a total of 53 bridges (pedestrian, vehicle and railway), and leading to the partial collapse of sections of the main road, paralyzing central parts of the city for more than one week. This study assesses the aspects of building design and site specific environmental characteristics that render a building vulnerable by considering the example of a flash flood event in February 2013. A statistical methodology is developed that enables estimation of damage probability for buildings. The applied method uses observed inundation height as a hazard proxy in areas where more detailed hydrodynamic modeling data is not available. Building design and site-specific environmental conditions determine the physical vulnerability. The mathematical approach considers both physical vulnerability and hazard related parameters and helps to reduce uncertainty in the determination of descriptive parameters, parameter interdependency and respective contributions to damage. This study aims to (1) enable the estimation of damage probability for a certain hazard intensity, and (2) obtain data to visualize variations in damage susceptibility for buildings in flood prone areas. Data collection is based on a post-flood event field survey and the analysis of high (sub-metric) spatial resolution images (Pléiades 2012, 2013). An inventory of 30 city blocks was collated in a GIS database in order to estimate the physical vulnerability of buildings. As many as 1103 buildings were surveyed along the affected drainage and 898 buildings were included in the statistical analysis. Univariate and bivariate analyses were applied to better characterize each vulnerability parameter. Multiple corresponding analyses revealed strong relationships between the "Distance to channel or bridges", "Structural building type", "Building footprint" and the observed damage. Logistic regression enabled quantification of the contribution of each explanatory parameter to potential damage, and determination of the significant parameters that express the damage susceptibility of a building. The model was applied 200 times on different calibration and validation data sets in order to examine performance. Results show that 90% of these tests have a success rate of more than 67%. Probabilities (at building scale) of experiencing different damage levels during a future event similar to the 8 February 2013 flash flood are the major outcomes of this study.

DNA damage as a biomarker of genotoxic contamination in Mytilus galloprovincialis from the south coast of Portugal.

PubMed

Almeida, Catarina; Pereira, Catarina; Gomes, Tânia; Bebianno, Maria João; Cravo, Alexandra

2011-09-01

DNA damage was evaluated in the haemolymph of Mytilus galloprovincialis from nine sites along the south coast of Portugal using the comet assay. DNA damage was low, in the same range of sites considered to suffer low impact from genotoxic contaminants. Even so, differences between sites, seasons and genders were found. Highest values were in mussels from the main estuaries and the fishery harbour, reflecting higher genotoxin levels, whereas the lowest values can be used as a baseline for future work. Non-contaminant related factors (e.g. temperature and oxygen) were also shown to influence DNA damage. Between seasons, highest values were in summer related not only to the increase of tourism in this region (∼10-fold), but also to temperature. Between genders, males were found to be more sensitive. The condition index was also generally higher in summer. Lipid peroxidation, another damage biomarker, was measured in gills to assess if there is any association between the responses of both biomarkers and if they are similarly affected by the same environmental conditions. LPO like DNA damage was higher in summer. This work confirms that DNA damage is a sensitive biomarker to discriminate genotoxic contamination, even in areas considered to suffer low impact from genotoxins.

Data fusion of multi-scale representations for structural damage detection

NASA Astrophysics Data System (ADS)

Guo, Tian; Xu, Zili

2018-01-01

Despite extensive researches into structural health monitoring (SHM) in the past decades, there are few methods that can detect multiple slight damage in noisy environments. Here, we introduce a new hybrid method that utilizes multi-scale space theory and data fusion approach for multiple damage detection in beams and plates. A cascade filtering approach provides multi-scale space for noisy mode shapes and filters the fluctuations caused by measurement noise. In multi-scale space, a series of amplification and data fusion algorithms are utilized to search the damage features across all possible scales. We verify the effectiveness of the method by numerical simulation using damaged beams and plates with various types of boundary conditions. Monte Carlo simulations are conducted to illustrate the effectiveness and noise immunity of the proposed method. The applicability is further validated via laboratory cases studies focusing on different damage scenarios. Both results demonstrate that the proposed method has a superior noise tolerant ability, as well as damage sensitivity, without knowing material properties or boundary conditions.

Morphometric analysis of small arteries in the human retina using adaptive optics imaging: relationship with blood pressure and focal vascular changes

PubMed Central

Koch, Edouard; Rosenbaum, David; Brolly, Aurélie; Sahel, José-Alain; Chaumet-Riffaud, Philippe; Girerd, Xavier; Rossant, Florence; Paques, Michel

2014-01-01

Objectives: The wall-to-lumen ratio (WLR) of retinal arteries is a recognized surrogate of end-organ damage due to aging and/or arterial hypertension. However, parietal morphometry remains difficult to assess in vivo. Recently, it was shown that adaptive optics retinal imaging can resolve parietal structures of retinal arterioles in humans in vivo. Here, using adaptive optics retinal imaging, we investigated the variations of parietal thickness of small retinal arteries with blood pressure and focal vascular damage. Methods: Adaptive optics imaging of the superotemporal retinal artery was done in 49 treatment-naive individuals [mean age (±SD) 44.9 years (±14); mean systolic pressure 132 mmHg (±22)]. Semi-automated segmentation allowed extracting parietal thickness and lumen diameter. In a distinct cohort, adaptive optics images of arteriovenous nicking (AVN; n = 12) and focal arteriolar narrowing (FAN; n = 10) were also analyzed qualitatively and quantitatively. Results: In the cohort of treatment-naive individuals, by multiple regression taking into account age, body mass index, mean, systolic, diastolic and pulse blood pressure, the WLR was found positively correlated to mean blood pressure and age which in combination accounted for 43% of the variability of WLR. In the cohort of patients with focal vascular damage, neither FANs or AVNs showed evidence of parietal growth; instead, at sites of FANs, decreased outer diameter suggestive of vasoconstriction was consistently found, while at sites of AVNs venous narrowing could be seen in the absence of arteriovenous contact. Conclusion: High resolution imaging of retinal vessels by adaptive optics allows quantitative microvascular phenotyping, which may contribute to a better understanding and management of hypertensive retinopathy. PMID:24406779

An experimental test of the EICA hypothesis in multiple ranges: invasive populations outperform those from the native range independent of insect herbivore suppression

PubMed Central

DeWalt, Saara J.; Zou, Jianwen; Rogers, William E.

2017-01-01

Abstract The success of invasive plants may reflect environmental differences in their native and introduced ranges including both abiotic and biotic conditions, such as release from aboveground herbivory. However, in response to these novel conditions, plants from invasive populations may have higher growth rates and lower defence levels compared with those in the native range. This may contribute to their success in the introduced range but perhaps not in the native range. Here, we grew 1000 Triadica sebifera plants from 14 native and introduced populations in seven common gardens with unmanaged background vegetation for three growing seasons in three geographic venues that varied in T. sebifera status and insect herbivore communities: Texas—T. sebifera is invasive, low levels of generalist herbivory; Hawaii—T. sebifera introduced but not invasive, high levels of generalist herbivory from exotic herbivores; China—native range, both generalist and specialist herbivores. We suppressed aboveground insects with insecticide on half the plants. Aboveground damage in the first growing season was lowest in Texas and insecticide sprays reduced damage in China. At the end of the first growing season, plants were tallest on an average in China and shortest in Hawaii. However, height in later years and mass were the highest on average in Texas and the lowest in Hawaii. However, there was large variation in damage and plant performance among gardens within venues. Our results suggest that more rapid aboveground growth rates contribute to T. sebifera’s success in both the invasive and native ranges independent of aboveground herbivory. However, strong variation among sites indicates that T. sebifera plants from invasive populations only have a strong advantage in a subset of sites in Texas. PMID:28039113

An experimental test of the EICA Hypothesis in multiple ranges: invasive populations outperform those from the native range independent of insect herbivore suppression.

PubMed

Siemann, Evan; DeWalt, Saara J; Zou, Jianwen; Rogers, William E

2016-12-30

The success of invasive plants may reflect environmental differences in their native and introduced ranges including both abiotic and biotic conditions, such as release from aboveground herbivory. However, in response to these novel conditions, plants from invasive populations may have higher growth rates and lower defense levels compared to those in the native range. This may contribute to their success in the introduced range but perhaps not in the native range. Here, we grew 1000 Triadica sebifera plants from 14 native and introduced populations in seven common gardens with unmanaged background vegetation for three growing seasons in three geographic venues that varied in T. sebifera status and insect herbivore communities: Texas -T. sebifera is invasive, low levels of generalist herbivory; Hawaii - T. sebifera introduced but not invasive, high levels of generalist herbivory from exotic herbivores; China - native range, both generalist and specialist herbivores. We suppressed aboveground insects with insecticide on half the plants. Aboveground damage in the first growing season was lowest in Texas and insecticide sprays reduced damage in China. At the end of the first growing season, plants were tallest on average in China and shortest in Hawaii. However, height in later years and mass were highest on average in Texas and lowest in Hawaii. However, there was large variation in damage and plant performance among gardens within venues. Our results suggest that more rapid aboveground growth rates contribute to T. sebifera's success in both the invasive and native ranges independent of aboveground herbivory. However, strong variation among sites indicates that T. sebifera plants from invasive populations only have a strong advantage in a subset of sites in Texas. Published by Oxford University Press on behalf of the Annals of Botany Company.

Taperin (c9orf75), a mutated gene in nonsyndromic deafness, encodes a vertebrate specific, nuclear localized protein phosphatase one alpha (PP1α) docking protein

PubMed Central

Ferrar, Tony; Chamousset, Delphine; De Wever, Veerle; Nimick, Mhairi; Andersen, Jens; Trinkle-Mulcahy, Laura; Moorhead, Greg B. G.

2012-01-01

Summary The promiscuous activity of protein phosphatase one (PP1) is controlled in the cell by associated proteins termed regulatory or targeting subunits. Using biochemical and proteomic approaches we demonstrate that the autosomal recessive nonsyndromic hearing loss gene, taperin (C9orf75), encodes a protein that preferentially docks the alpha isoform of PP1. Taperin associates with PP1 through a classic ‘RVxF’ motif and suppresses the general phosphatase activity of the enzyme. The steady-state localization of taperin is predominantly nuclear, however we demonstrate here that the protein can shuttle between the nucleus and cytoplasm and that it is found complexed to PP1 in both of these cellular compartments. Although originally identified as a hearing loss gene, Western blot analyses with taperin-specific antibodies revealed that the protein is widely expressed across mammalian tissues as multiple splice variants. Taperin is a recent proteome addition appearing during the vertebrate lineage with the PP1 binding site embedded within the most conserved region of the protein. Taperin also shares an ancestral relationship with the cytosolic actin binding protein phostensin, another PP1 interacting partner. Quantitative Stable Isotope Labeling by Amino acids in Culture (SILAC)-based mass spectrometry was employed to uncover additional taperin binding partners, and revealed an interaction with the DNA damage response proteins Ku70, Ku80, PARP and topoisomerases I and IIα. Consistent with this, we demonstrate the active recruitment of taperin to sites of DNA damage. This makes taperin a new addition to the family of PP1 targeting subunits involved in the DNA damage repair pathway. PMID:23213405

Morphometric analysis of small arteries in the human retina using adaptive optics imaging: relationship with blood pressure and focal vascular changes.

PubMed

Koch, Edouard; Rosenbaum, David; Brolly, Aurélie; Sahel, José-Alain; Chaumet-Riffaud, Philippe; Girerd, Xavier; Rossant, Florence; Paques, Michel

2014-04-01

The wall-to-lumen ratio (WLR) of retinal arteries is a recognized surrogate of end-organ damage due to aging and/or arterial hypertension. However, parietal morphometry remains difficult to assess in vivo. Recently, it was shown that adaptive optics retinal imaging can resolve parietal structures of retinal arterioles in humans in vivo. Here, using adaptive optics retinal imaging, we investigated the variations of parietal thickness of small retinal arteries with blood pressure and focal vascular damage. Adaptive optics imaging of the superotemporal retinal artery was done in 49 treatment-naive individuals [mean age (±SD) 44.9 years (±14); mean systolic pressure 132  mmHg (±22)]. Semi-automated segmentation allowed extracting parietal thickness and lumen diameter. In a distinct cohort, adaptive optics images of arteriovenous nicking (AVN; n = 12) and focal arteriolar narrowing (FAN; n = 10) were also analyzed qualitatively and quantitatively. In the cohort of treatment-naive individuals, by multiple regression taking into account age, body mass index, mean, systolic, diastolic and pulse blood pressure, the WLR was found positively correlated to mean blood pressure and age which in combination accounted for 43% of the variability of WLR. In the cohort of patients with focal vascular damage, neither FANs or AVNs showed evidence of parietal growth; instead, at sites of FANs, decreased outer diameter suggestive of vasoconstriction was consistently found, while at sites of AVNs venous narrowing could be seen in the absence of arteriovenous contact. High resolution imaging of retinal vessels by adaptive optics allows quantitative microvascular phenotyping, which may contribute to a better understanding and management of hypertensive retinopathy.

Integration of genotoxicity and population genetic analyses in kangaroo rats (Dipodomys merriami) exposed to radionuclide contamination at the Nevada Test Site, USA

USGS Publications Warehouse

Theodorakis, Christopher W.; Bickham, John W.; Lamb, Trip; Medica, Philip A.; Lyne, T. Barrett

2001-01-01

We examined effects of radionuclide exposure at two atomic blast sites on kangaroo rats (Dipodomys merriami) at the Nevada Test Site, Nevada, USA, using genotoxicity and population genetic analyses. We assessed chromosome damage by micronucleus and flow cytometric assays and genetic variation by randomly amplified polymorphic DNA (RAPD) and mitochondrial DNA (mtDNA) analyses. The RAPD analysis showed no population structure, but mtDNA exhibited differentiation among and within populations. Genotoxicity effects were not observed when all individuals were analyzed. However, individuals with mtDNA haplotypes unique to the contaminated sites had greater chromosomal damage than contaminated-site individuals with haplotypes shared with reference sites. When interpopulation comparisons used individuals with unique haplotypes, one contaminated site had greater levels of chromosome damage than one or both of the reference sites. We hypothesize that shared-haplotype individuals are potential migrants and that unique-haplotype individuals are potential long-term residents. A parsimony approach was used to estimate the minimum number of migration events necessary to explain the haplotype distributions on a phylogenetic tree. The observed predominance of migration events into the contaminated sites supported our migration hypothesis. We conclude the atomic blast sites are ecological sinks and that immigration masks the genotoxic effects of radiation on the resident populations.

Site location and optical properties of Eu implanted sapphire

NASA Astrophysics Data System (ADS)

Marques, C.; Wemans, A.; Maneira, M. J. P.; Kozanecki, A.; da Silva, R. C.; Alves, E.

2005-10-01

Synthetic colourless transparent (0 0 0 1) sapphire crystals were implanted at room temperature with 100 keV europium ions to fluences up to 1 × 1016 cm-2. Surface damage is observed at low fluences, as seen by Rutherford backscattering spectrometry under channelling conditions. Optical absorption measurements revealed a variety of structures, most probably related to F-type defects characteristic of implantation damage. Thermal treatments in air or in vacuum up to 1000 °C do not produce noticeable changes both in the matrix or the europium profiles. However, the complete recovery of the implantation damage and some redistribution of the europium ions is achieved after annealing at 1300 °C in air. Detailed lattice site location studies performed for various axial directions allowed to assess the damage recovery and the incorporation of the Eu ions into well defined crystallographic sites, possibly in an oxide phase also inferred from optical absorption measurements.

DNA damage and external lesions in brown bullheads (Ameiurus nebulosus) from contaminated habitats

USGS Publications Warehouse

Yang, X.; Meier, J.; Chang, L.; Rowan, M.; Baumann, P.C.

2006-01-01

The Comet assay was used to compare levels of DNA damage in brown bullheads (Ameiurus nebulosus) collected from three known contaminated locations, the Cuyahoga River (OH, USA), Ashtabula River (OH, USA; both tributaries to Lake Erie, USA), and Ashumet Pond (Cape Cod, MA, USA), with brown bullheads collected from three paired reference sites, Old Woman Creek (OH, USA), Conneaut River (OH, USA; both tributaries to Lake Erie), and Great Herring Pond (mainland MA, USA), respectively. Blood was sampled from each fish, and the Comet assay was conducted on erythrocytes. The assay results demonstrate that fish from the three contaminated sites each suffered higher DNA damage compared with fish from their respective reference sites. The results also show that the genetic damage was associated with the occurrence of external lesions and deformities in fish. The Comet assay is sufficiently sensitive to detect exposure of natural fish populations to environmental levels of genotoxic contaminants. ?? 2006 SETAC.

A comparative MRI study of cartilage damage in gout versus rheumatoid arthritis.

PubMed

Popovich, Ivor; Lee, Arier C L; Doyle, Anthony; McHaffie, Alexandra; Clarke, Andrew; Reeves, Quentin; Dalbeth, Nicola; McQueen, Fiona M

2015-08-01

Magnetic resonance imaging (MRI) is useful for detecting joint inflammation and damage in the inflammatory arthropathies. This study aimed to investigate MRI cartilage damage and its associations with joint inflammation in patients with gout compared with a group with rheumatoid arthritis (RA). Forty patients with gout and 38 with seropositive RA underwent 3T-MRI of the wrist with assessment of cartilage damage at six carpal sites, using established scoring systems. Synovitis and bone oedema (BME) were graded according to Rheumatoid Arthritis MRI Scoring System criteria. Cartilage damage was compared between the groups adjusting for synovitis and disease duration using logistic regression analysis. Compared with RA, there were fewer sites of cartilage damage and lower total damage scores in the gout group (P = 0.02 and 0.003), adjusting for their longer disease duration and lesser degree of synovitis. Cartilage damage was strongly associated with synovitis in both conditions (R = 0.59, P < 0.0001 and R = 0.52, P = 0.0045 respectively) and highly correlated with BME in RA (R = 0.69, P < 0.0001) but not in gout (R = 0.095, P = 0.56). Cartilage damage is less severe in gout than in RA, with fewer sites affected and lower overall scores. It is associated with synovitis in both diseases, likely indicating an effect of pro-inflammatory cytokine production on cartilage integrity. However, the strong association between cartilage damage and BME observed in RA was not identified in gout. This emphasizes differences in the underlying pathophysiology of joint damage in these two conditions. © 2015 The Royal Australian and New Zealand College of Radiologists.

VAM populations in relation to grass invasion associated with forest decline.

PubMed

Vosatka, M; Cudlin, P; Mejstrik, V

1991-01-01

Spruce stands in Northern Bohemia forests, damaged to various degrees by industrial pollution, have shown establishment of grass cover following tree defoliation. Populations of vesicular-arbuscular mycorrhizal (VAM) fungi were studied under this grass cover in four permanent plots with spruce under different levels of pollution stress. Soil and root samples were collected in April and June within each plot as follows: (1) sites without grass, (2) sites with initial stages of grass invasion, and (3) sites with fully developed grass cover. In all plots, the highest number of propagules were recovered from samples taken from sites having full grass cover. Mycorrhizal infection of grass was highest in the plot with the severest pollution damage and lowest in the least damaged plot. The development of grass cover and VAM infection of grass increased with tree defoliation caused by air pollution.

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

PubMed

Kobayashi, S; Ueda, K; Komano, T

1990-01-01

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

Influence of chemical disorder on energy dissipation and defect evolution in advanced alloys

DOE PAGES

Zhang, Yanwen; Jin, Ke; Xue, Haizhou; ...

2016-08-01

We report that historically, alloy development with better radiation performance has been focused on traditional alloys with one or two principal element(s) and minor alloying elements, where enhanced radiation resistance depends on microstructural or nanoscale features to mitigate displacement damage. In sharp contrast to traditional alloys, recent advances of single-phase concentrated solid solution alloys (SP-CSAs) have opened up new frontiers in materials research. In these alloys, a random arrangement of multiple elemental species on a crystalline lattice results in disordered local chemical environments and unique site-to-site lattice distortions. Based on closely integrated computational and experimental studies using a novel setmore » of SP-CSAs in a face-centered cubic structure, we have explicitly demonstrated that increasing chemical disorder can lead to a substantial reduction in electron mean free paths, as well as electrical and thermal conductivity, which results in slower heat dissipation in SP-CSAs. The chemical disorder also has a significant impact on defect evolution under ion irradiation. Considerable improvement in radiation resistance is observed with increasing chemical disorder at electronic and atomic levels. Finally, the insights into defect dynamics may provide a basis for understanding elemental effects on evolution of radiation damage in irradiated materials and may inspire new design principles of radiation-tolerant structural alloys for advanced energy systems.« less

Single-Input and Multiple-Output Surface Acoustic Wave Sensing for Damage Quantification in Piezoelectric Sensors.

PubMed

Pamwani, Lavish; Habib, Anowarul; Melandsø, Frank; Ahluwalia, Balpreet Singh; Shelke, Amit

2018-06-22

The main aim of the paper is damage detection at the microscale in the anisotropic piezoelectric sensors using surface acoustic waves (SAWs). A novel technique based on the single input and multiple output of Rayleigh waves is proposed to detect the microscale cracks/flaws in the sensor. A convex-shaped interdigital transducer is fabricated for excitation of divergent SAWs in the sensor. An angularly shaped interdigital transducer (IDT) is fabricated at 0 degrees and ±20 degrees for sensing the convex shape evolution of SAWs. A precalibrated damage was introduced in the piezoelectric sensor material using a micro-indenter in the direction perpendicular to the pointing direction of the SAW. Damage detection algorithms based on empirical mode decomposition (EMD) and principal component analysis (PCA) are implemented to quantify the evolution of damage in piezoelectric sensor material. The evolution of the damage was quantified using a proposed condition indicator (CI) based on normalized Euclidean norm of the change in principal angles, corresponding to pristine and damaged states. The CI indicator provides a robust and accurate metric for detection and quantification of damage.

Endangerment of cultural heritage sites by strong rain

NASA Astrophysics Data System (ADS)

Krauß, Thomas; Fischer, Peter

2017-09-01

Due to climate change extreme weather conditions become more and more frequent in the last years. Especially in Germany nearly every year a large flood event happens. Most of these events are caused by strong rain. There are at most two causes for these floodings: The first is locally strong rain in the area of damage, the second happens at damage sites located near confluxes and strong rain in the upper stream areas of the joining rivers. The amount of damage is often strongly correlated with unreasonable designation of new construction in such endangered regions. Our presented study is based on an earlier project together with a German insurance company. In this project we analyzed correlations of geographical settings with the insurance data of flood damages over ten years. The result of this study was a strong relation of the terrain with the amount and the probability of damages. Further investigations allow us to derive a system for estimating potential endangerment due to strong rain just from suitable digital terrain models (DTMs). In the presented study we apply this method to different types of cultural heritage (CH) sites in Germany and other parts of the world to detect which type of CH sites were build with potential endangerment of strong rain events in mind and which ones are prone to such events.

23 CFR 668.211 - Notification, damage assessment, and finding.

Code of Federal Regulations, 2010 CFR

2010-04-01

... disaster or catastrophic failure, each applicant will notify the DFDE of its tentative intent to apply for... destruction. (e) Detailed site inspections. (1) If an Affirmative Finding is made, the applicant shall cooperate with the DFDE to make a detailed inspection of each damage site. (2) If it appears certain an...

Protective effect of extract of Crataegus pinnatifida pollen on DNA damage response to oxidative stress.

PubMed

Cheng, Ni; Wang, Yuan; Gao, Hui; Yuan, Jialing; Feng, Fan; Cao, Wei; Zheng, Jianbin

2013-09-01

The protective effect of extract of Crataegus pinnatifida (Rosaceae) pollen (ECPP) on the DNA damage response to oxidative stress was investigated and assessed with an alkaline single-cell gel electrophoresis (SCGE) assay and pBR322 plasmid DNA breaks in site-specific and non-site-specific systems. Total phenolic content, total flavonoid content, individual phenolic compounds, antioxidant activities (1,1-diphenyl-2-picrylhydrazyl (DPPH), radical scavenging activity, FRAP, and chelating activity) were also determined. The results showed that ECPP possessed a strong ability to protect DNA from being damaged by hydroxyl radicals in both the site-specific system and the non-site-specific system. It also exhibited a cytoprotection effect in mouse lymphocytes against H₂O₂-induced DNA damage. These protective effects may be related to its high total phenolic content (17.65±0.97 mg GAE/g), total flavonoid content (8.04±0.97 mg rutin/g), strong free radical scavenging activity and considerable ferrous ion chelating ability (14.48±0.21 mg Na₂EDTA/g). Copyright © 2013 Elsevier Ltd. All rights reserved.

Localised hydrodynamics influence vulnerability of coral communities to environmental disturbances

NASA Astrophysics Data System (ADS)

Shedrawi, George; Falter, James L.; Friedman, Kim J.; Lowe, Ryan J.; Pratchett, Morgan S.; Simpson, Christopher J.; Speed, Conrad W.; Wilson, Shaun K.; Zhang, Zhenlin

2017-09-01

The movement of water can have a significant influence on the vulnerability of hermatypic corals to environmental disturbances such as cyclone damage, heat stress and anoxia. Here, we explore the relationship between small reef-scale water circulation patterns and measured differences in the abundance, composition and vulnerability of coral assemblages over decades. Changes in coral cover and community structure within Bill's Bay (Ningaloo Reef, Western Australia) over a 22-yr period, during which multiple disturbance events (including mass bleaching, anoxia, and tropical cyclones) have impacted the area, were compared with spatial variation in water residence times (WRT). We found that reef sites associated with longer water residence times (WRT >15 h) experienced higher rates of coral mortality during acute environmental disturbances compared to reef sites with shorter WRT. Shifts in coral community composition from acroporid to faviid-dominated assemblages were also more prominent at sites with long WRT compared to reef sites with shorter WRT, although shifts in community composition were also observed at sites close to shore. Interestingly, these same long-WRT sites also tended to have the fastest recovery rates so that coral cover was returned to original levels of approximately 20% over two decades. This study provides empirical evidence that spatial patterns in water circulation and flushing can influence the resilience of coral communities, thus identifying areas sensitive to emerging threats associated with global climate change.

Cdt2-mediated XPG degradation promotes gap-filling DNA synthesis in nucleotide excision repair

PubMed Central

Han, Chunhua; Wani, Gulzar; Zhao, Ran; Qian, Jiang; Sharma, Nidhi; He, Jinshan; Zhu, Qianzheng; Wang, Qi-En; Wani, Altaf A

2015-01-01

Xeroderma pigmentosum group G (XPG) protein is a structure-specific repair endonuclease, which cleaves DNA strands on the 3′ side of the DNA damage during nucleotide excision repair (NER). XPG also plays a crucial role in initiating DNA repair synthesis through recruitment of PCNA to the repair sites. However, the fate of XPG protein subsequent to the excision of DNA damage has remained unresolved. Here, we show that XPG, following its action on bulky lesions resulting from exposures to UV irradiation and cisplatin, is subjected to proteasome-mediated proteolytic degradation. Productive NER processing is required for XPG degradation as both UV and cisplatin treatment-induced XPG degradation is compromised in NER-deficient XP-A, XP-B, XP-C, and XP-F cells. In addition, the NER-related XPG degradation requires Cdt2, a component of an E3 ubiquitin ligase, CRL4Cdt2. Micropore local UV irradiation and in situ Proximity Ligation assays demonstrated that Cdt2 is recruited to the UV-damage sites and interacts with XPG in the presence of PCNA. Importantly, Cdt2-mediated XPG degradation is crucial to the subsequent recruitment of DNA polymerase δ and DNA repair synthesis. Collectively, our data support the idea of PCNA recruitment to damage sites which occurs in conjunction with XPG, recognition of the PCNA-bound XPG by CRL4Cdt2 for specific ubiquitylation and finally the protein degradation. In essence, XPG elimination from DNA damage sites clears the chromatin space needed for the subsequent recruitment of DNA polymerase δ to the damage site and completion of gap-filling DNA synthesis during the final stage of NER. PMID:25483071

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.

Nucleolar-nucleoplasmic shuttling of TARG1 and its control by DNA damage-induced poly-ADP-ribosylation and by nucleolar transcription.

PubMed

Bütepage, Mareike; Preisinger, Christian; von Kriegsheim, Alexander; Scheufen, Anja; Lausberg, Eva; Li, Jinyu; Kappes, Ferdinand; Feederle, Regina; Ernst, Sabrina; Eckei, Laura; Krieg, Sarah; Müller-Newen, Gerhard; Rossetti, Giulia; Feijs, Karla L H; Verheugd, Patricia; Lüscher, Bernhard

2018-04-30

Macrodomains are conserved protein folds associated with ADP-ribose binding and turnover. ADP-ribosylation is a posttranslational modification catalyzed primarily by ARTD (aka PARP) enzymes in cells. ARTDs transfer either single or multiple ADP-ribose units to substrates, resulting in mono- or poly-ADP-ribosylation. TARG1/C6orf130 is a macrodomain protein that hydrolyzes mono-ADP-ribosylation and interacts with poly-ADP-ribose chains. Interactome analyses revealed that TARG1 binds strongly to ribosomes and proteins associated with rRNA processing and ribosomal assembly factors. TARG1 localized to transcriptionally active nucleoli, which occurred independently of ADP-ribose binding. TARG1 shuttled continuously between nucleoli and nucleoplasm. In response to DNA damage, which activates ARTD1/2 (PARP1/2) and promotes synthesis of poly-ADP-ribose chains, TARG1 re-localized to the nucleoplasm. This was dependent on the ability of TARG1 to bind to poly-ADP-ribose. These findings are consistent with the observed ability of TARG1 to competitively interact with RNA and PAR chains. We propose a nucleolar role of TARG1 in ribosome assembly or quality control that is stalled when TARG1 is re-located to sites of DNA damage.

AP1000{sup R} nuclear power plant safety overview for spent fuel cooling

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

Gorgemans, J.; Mulhollem, L.; Glavin, J.

2012-07-01

The AP1000{sup R} plant is an 1100-MWe class pressurized water reactor with passive safety features and extensive plant simplifications that enhance construction, operation, maintenance, safety and costs. The AP1000 design uses passive features to mitigate design basis accidents. The passive safety systems are designed to function without safety-grade support systems such as AC power, component cooling water, service water or HVAC. Furthermore, these passive features 'fail safe' during a non-LOCA event such that DC power and instrumentation are not required. The AP1000 also has simple, active, defense-in-depth systems to support normal plant operations. These active systems provide the first levelmore » of defense against more probable events and they provide investment protection, reduce the demands on the passive features and support the probabilistic risk assessment. The AP1000 passive safety approach allows the plant to achieve and maintain safe shutdown in case of an accident for 72 hours without operator action, meeting the expectations provided in the U.S. Utility Requirement Document and the European Utility Requirements for passive plants. Limited operator actions are required to maintain safe conditions in the spent fuel pool via passive means. In line with the AP1000 approach to safety described above, the AP1000 plant design features multiple, diverse lines of defense to ensure spent fuel cooling can be maintained for design-basis events and beyond design-basis accidents. During normal and abnormal conditions, defense-in-depth and other systems provide highly reliable spent fuel pool cooling. They rely on off-site AC power or the on-site standby diesel generators. For unlikely design basis events with an extended loss of AC power (i.e., station blackout) or loss of heat sink or both, spent fuel cooling can still be provided indefinitely: - Passive systems, requiring minimal or no operator actions, are sufficient for at least 72 hours under all possible pool heat load conditions. - After 3 days, several different means are provided to continue spent fuel cooling using installed plant equipment as well as off-site equipment with built-in connections. Even for beyond design basis accidents with postulated pool damage and multiple failures in the passive safety-related systems and in the defense-in-depth active systems, the AP1000 multiple spent fuel pool spray and fill systems provide additional lines of defense to prevent spent fuel damage. (authors)« less

DNA damage and lipid peroxidation vs. protection responses in the gill of Dicentrarchus labrax L. from a contaminated coastal lagoon (Ria de Aveiro, Portugal).

PubMed

Ahmad, I; Maria, V L; Oliveira, M; Serafim, A; Bebianno, M J; Pacheco, M; Santos, M A

2008-11-15

The present research work aimed to investigate the damage vs. protection responses in gill of European sea bass (Dicentrarchus labrax) captured at a polluted coastal lagoon, Ria de Aveiro (Portugal), as a tool to evaluate the human impacts on environmental health. Damage was assessed as DNA strand breakage and lipid peroxidation (LPO) whereas protection was evaluated by measuring catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione S-transferase (GST), total glutathione (GSHt), thiols and metallothioneins (MT). Fish were caught at five locations: Gafanha (GAF), Rio Novo do Príncipe (RIO), Laranjo (LAR) and Vagos (VAG) presenting each a different recognized source of contamination, and Torreira (TOR), assumed as reference site. Among the surveyed sites, gill damage was observed only at GAF, as measured by DNA integrity loss and LPO increase. An overall induction in enzymatic antioxidant protection was perceptible in fish from GAF and VAG, expressed as higher GPX, GR and GST activities. In addition, LAR fish showed elevated GST and CAT activities. Thiols content was higher in all study sites irrespective to the pollution spectrum, whereas GSHt increase was only observed at GAF and VAG. The highest MT level was detected in fish from VAG and the lowest level from RIO suggesting a low contamination degree on this particular site. Globally, the results expressed site-specific response patterns, signalling two critical areas - GAF and VAG. Additionally, a joint analysis (damage vs. protection) allowed the following ordering of surveyed sites according to the contamination degree and risk to fish health; GAF>VAG>LAR>RIO>TOR. D. labrax gill responses demonstrated their efficacy as early warning signals of the contaminants presence. Moreover, the adopted approach, considering simultaneously protection responses and damaging effects, also revealed its usefulness on the pollution extent assessment.

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.

Direct Binding to Replication Protein A (RPA)-coated Single-stranded DNA Allows Recruitment of the ATR Activator TopBP1 to Sites of DNA Damage*

PubMed Central

Acevedo, Julyana; Yan, Shan; Michael, W. Matthew

2016-01-01

A critical event for the ability of cells to tolerate DNA damage and replication stress is activation of the ATR kinase. ATR activation is dependent on the BRCT (BRCA1 C terminus) repeat-containing protein TopBP1. Previous work has shown that recruitment of TopBP1 to sites of DNA damage and stalled replication forks is necessary for downstream events in ATR activation; however, the mechanism for this recruitment was not known. Here, we use protein binding assays and functional studies in Xenopus egg extracts to show that TopBP1 makes a direct interaction, via its BRCT2 domain, with RPA-coated single-stranded DNA. We identify a point mutant that abrogates this interaction and show that this mutant fails to accumulate at sites of DNA damage and that the mutant cannot activate ATR. These data thus supply a mechanism for how the critical ATR activator, TopBP1, senses DNA damage and stalled replication forks to initiate assembly of checkpoint signaling complexes. PMID:27129245

Comparing the ISO-recommended and the cumulative data-reduction algorithms in S-on-1 laser damage test by a reverse approach method

NASA Astrophysics Data System (ADS)

Zorila, Alexandru; Stratan, Aurel; Nemes, George

2018-01-01

We compare the ISO-recommended (the standard) data-reduction algorithm used to determine the surface laser-induced damage threshold of optical materials by the S-on-1 test with two newly suggested algorithms, both named "cumulative" algorithms/methods, a regular one and a limit-case one, intended to perform in some respects better than the standard one. To avoid additional errors due to real experiments, a simulated test is performed, named the reverse approach. This approach simulates the real damage experiments, by generating artificial test-data of damaged and non-damaged sites, based on an assumed, known damage threshold fluence of the target and on a given probability distribution function to induce the damage. In this work, a database of 12 sets of test-data containing both damaged and non-damaged sites was generated by using four different reverse techniques and by assuming three specific damage probability distribution functions. The same value for the threshold fluence was assumed, and a Gaussian fluence distribution on each irradiated site was considered, as usual for the S-on-1 test. Each of the test-data was independently processed by the standard and by the two cumulative data-reduction algorithms, the resulting fitted probability distributions were compared with the initially assumed probability distribution functions, and the quantities used to compare these algorithms were determined. These quantities characterize the accuracy and the precision in determining the damage threshold and the goodness of fit of the damage probability curves. The results indicate that the accuracy in determining the absolute damage threshold is best for the ISO-recommended method, the precision is best for the limit-case of the cumulative method, and the goodness of fit estimator (adjusted R-squared) is almost the same for all three algorithms.

Spectroscopic Axonal Damage of the Right Locus Coeruleus Relates to Selective Attention Impairment in Early Stage Relapsing-Remitting Multiple Sclerosis

ERIC Educational Resources Information Center

Gadea, Marien; Martinez-Bisbal, M. Carmen; Marti-Bonmati, Luis; Espert, Raul; Casanova, Bonaventura; Coret, Francisco; Celda, Bernardo

2004-01-01

Lower levels of N-acetylaspartate (NAA), a marker of axonal damage, have been found in the normal-appearing white matter (NAWM) of relapsing-remitting multiple sclerosis (RRMS) patients with low physical disability. However, its relation to the clinical status of these patients remains unclear. We explored the association between NAA levels…

Climatology of salt transitions and implications for stone weathering.

PubMed

Grossi, C M; Brimblecombe, P; Menéndez, B; Benavente, D; Harris, I; Déqué, M

2011-06-01

This work introduces the notion of salt climatology. It shows how climate affects salt thermodynamic and the potential to relate long-term salt damage to climate types. It mainly focuses on specific sites in Western Europe, which include some cities in France and Peninsular Spain. Salt damage was parameterised using the number of dissolution-crystallisation events for unhydrated (sodium chloride) and hydrated (sodium sulphate) systems. These phase transitions have been calculated using daily temperature and relative humidity from observation meteorological data and Climate Change models' output (HadCM3 and ARPEGE). Comparing the number of transitions with meteorological seasonal data allowed us to develop techniques to estimate the frequency of salt transitions based on the local climatology. Results show that it is possible to associate the Köppen-Geiger climate types with potential salt weathering. Temperate fully humid climates seem to offer the highest potential for salt damage and possible higher number of transitions in summer. Climates with dry summers tend to show a lesser frequency of transitions in summer. The analysis of temperature, precipitation and relative output from Climate Change models suggests changes in the Köppen-Geiger climate types and changes in the patterns of salt damage. For instance, West Europe areas with a fully humid climate may change to a more Mediterranean like or dry climates, and consequently the seasonality of different salt transitions. The accuracy and reliability of the projections might be improved by simultaneously running multiple climate models (ensembles). Copyright © 2011 Elsevier B.V. All rights reserved.

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.

Comprehensive, Quantitative Risk Assessment of CO{sub 2} Geologic Sequestration

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

Lepinski, James

2013-09-30

A Quantitative Failure Modes and Effects Analysis (QFMEA) was developed to conduct comprehensive, quantitative risk assessments on CO{sub 2} capture, transportation, and sequestration or use in deep saline aquifers, enhanced oil recovery operations, or enhanced coal bed methane operations. The model identifies and characterizes potential risks; identifies the likely failure modes, causes, effects and methods of detection; lists possible risk prevention and risk mitigation steps; estimates potential damage recovery costs, mitigation costs and costs savings resulting from mitigation; and ranks (prioritizes) risks according to the probability of failure, the severity of failure, the difficulty of early failure detection and themore » potential for fatalities. The QFMEA model generates the necessary information needed for effective project risk management. Diverse project information can be integrated into a concise, common format that allows comprehensive, quantitative analysis, by a cross-functional team of experts, to determine: What can possibly go wrong? How much will damage recovery cost? How can it be prevented or mitigated? What is the cost savings or benefit of prevention or mitigation? Which risks should be given highest priority for resolution? The QFMEA model can be tailored to specific projects and is applicable to new projects as well as mature projects. The model can be revised and updated as new information comes available. It accepts input from multiple sources, such as literature searches, site characterization, field data, computer simulations, analogues, process influence diagrams, probability density functions, financial analysis models, cost factors, and heuristic best practices manuals, and converts the information into a standardized format in an Excel spreadsheet. Process influence diagrams, geologic models, financial models, cost factors and an insurance schedule were developed to support the QFMEA model. Comprehensive, quantitative risk assessments were conducted on three (3) sites using the QFMEA model: (1) SACROC Northern Platform CO{sub 2}-EOR Site in the Permian Basin, Scurry County, TX, (2) Pump Canyon CO{sub 2}-ECBM Site in the San Juan Basin, San Juan County, NM, and (3) Farnsworth Unit CO{sub 2}-EOR Site in the Anadarko Basin, Ochiltree County, TX. The sites were sufficiently different from each other to test the robustness of the QFMEA model.« less

In vivo assessment of cytological changes by means of reflectance confocal microscopy - demonstration of the effect of topical vitamin E on skin irritation caused by sodium lauryl sulfate.

PubMed

Casari, Alice; Farnetani, Francesca; De Pace, Barbara; Losi, Amanda; Pittet, Jean-Christophe; Pellacani, Giovanni; Longo, Caterina

2017-03-01

Irritant contact dermatitis is caused by skin barrier damage. Vitamin E is an antioxidant that is commonly used in cosmetics to prevent photo-damage. To show the usefulness of reflectance confocal microscopy in the assessment of irritant skin damage caused by sodium lauryl sulfate (SLS) and of the protective action of vitamin E applied prior to skin irritation. Ten healthy volunteers were enrolled. Irritation was induced by the application of a patch test containing SLS 5% aq. for 24 h. Three sites were compared: one site on which a product with vitamin E was applied before SLS treatment, one site on which the same product was applied after SLS treatment, and one control site (SLS only). Each site was evaluated with reflectance confocal microscopy, providing in vivo tissue images at nearly histological resolution. We also performed a computerized analysis of the VivaStack® images. Reflectance confocal microscopy is able to identify signs of skin irritation and the preventive effect of vitamin E application. Reflectance confocal microscopy is useful in the objective assessment of irritative skin damage. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

High richness of insect herbivory from the early Miocene Hindon Maar crater, Otago, New Zealand

PubMed Central

Lee, Daphne E.; Wappler, Torsten

2017-01-01

Plants and insects are key components of terrestrial ecosystems and insect herbivory is the most important type of interaction in these ecosystems. This study presents the first analysis of associations between plants and insects for the early Miocene Hindon Maar fossil lagerstätte, Otago, New Zealand. A total of 584 fossil angiosperm leaves representing 24 morphotypes were examined to determine the presence or absence of insect damage types. Of these leaves, 73% show signs of insect damage; they comprise 821 occurrences of damage from 87 damage types representing all eight functional feeding groups. In comparison to other fossil localities, the Hindon leaves display a high abundance of insect damage and a high diversity of damage types. Leaves of Nothofagus(southern beech), the dominant angiosperm in the fossil assemblage, exhibit a similar leaf damage pattern to leaves from the nearby mid to late Miocene Dunedin Volcano Group sites but display a more diverse spectrum and much higher percentage of herbivory damage than a comparable dataset of leaves from Palaeocene and Eocene sites in the Antarctic Peninsula. PMID:28224051

Multiple binding sites for transcriptional repressors can produce regular bursting and enhance noise suppression

NASA Astrophysics Data System (ADS)

Lengyel, Iván M.; Morelli, Luis G.

2017-04-01

Cells may control fluctuations in protein levels by means of negative autoregulation, where transcription factors bind DNA sites to repress their own production. Theoretical studies have assumed a single binding site for the repressor, while in most species it is found that multiple binding sites are arranged in clusters. We study a stochastic description of negative autoregulation with multiple binding sites for the repressor. We find that increasing the number of binding sites induces regular bursting of gene products. By tuning the threshold for repression, we show that multiple binding sites can also suppress fluctuations. Our results highlight possible roles for the presence of multiple binding sites of negative autoregulators.

Expression of the Antioxidative Enzyme Peroxiredoxin 2 in Multiple Sclerosis Lesions in Relation to Inflammation

PubMed Central

Voigt, David; Scheidt, Uta; Derfuss, Tobias; Brück, Wolfgang; Junker, Andreas

2017-01-01

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by demyelination and axonal damage as well as neuronal degeneration. Since oxygen-derived free radicals are an important factor leading to tissue damage in inflammatory multiple sclerosis (MS) lesions, research on antioxidative systems is essential to identify endogenous factors which can possibly counteract oxidative damage. As an important scavenging enzyme family, peroxiredoxins (PRDXs) play a crucial role in preventing oxidative damage; however little is known about their expression and function in MS lesions. In the present study we examined the expression of PRDX2 in white matter lesions of MS patients with long-standing, chronic disease. PRDX2 expression was investigated by immunohistochemistry in the context of oxidative stress and inflammation (determined by microglia/macrophage and T cell infiltration) in ten MS autopsy cases as well as seven control autopsy cases. PRDX2 was found to be upregulated in white matter MS lesions mainly in astrocytes, and its expression level was positively correlated with the degree of inflammation and oxidative stress. Our data suggest that PRDX2 expression contributes to the resistance of astrocytes against oxidative damage. PMID:28375164

Tankyrase1-mediated poly(ADP-ribosyl)ation of TRF1 maintains cell survival after telomeric DNA damage

PubMed Central

Yang, Lu; Sun, Luxi; Teng, Yaqun; Chen, Hao; Gao, Ying; Levine, Arthur S.; Nakajima, Satoshi

2017-01-01

Abstract Oxidative DNA damage triggers telomere erosion and cellular senescence. However, how repair is initiated at telomeres is largely unknown. Here, we found unlike PARP1-mediated Poly-ADP-Ribosylation (PARylation) at genomic damage sites, PARylation at telomeres is mainly dependent on tankyrase1 (TNKS1). TNKS1 is recruited to damaged telomeres via its interaction with TRF1, which subsequently facilitates the PARylation of TRF1 after damage. TNKS inhibition abolishes the recruitment of the repair proteins XRCC1 and polymerase β at damaged telomeres, while the PARP1/2 inhibitor only has such an effect at non-telomeric damage sites. The ANK domain of TNKS1 is essential for the telomeric damage response and TRF1 interaction. Mutation of the tankyrase-binding motif (TBM) on TRF1 (13R/18G to AA) disrupts its interaction with TNKS1 concomitant recruitment of TNKS1 and repair proteins after damage. Either TNKS1 inhibition or TBM mutated TRF1 expression markedly sensitizes cells to telomere oxidative damage as well as XRCC1 inhibition. Together, our data reveal a novel role of TNKS1 in facilitating SSBR at damaged telomeres through PARylation of TRF1, thereby protecting genome stability and cell viability. PMID:28160604

Surface-based reconstruction and diffusion MRI in the assessment of gray and white matter damage in multiple sclerosis

NASA Astrophysics Data System (ADS)

Caffini, Matteo; Bergsland, Niels; LaganÃ, Marcella; Tavazzi, Eleonora; Tortorella, Paola; Rovaris, Marco; Baselli, Giuseppe

2014-03-01

Despite advances in the application of nonconventional MRI techniques in furthering the understanding of multiple sclerosis pathogenic mechanisms, there are still many unanswered questions, such as the relationship between gray and white matter damage. We applied a combination of advanced surface-based reconstruction and diffusion tensor imaging techniques to address this issue. We found significant relationships between white matter tract integrity indices and corresponding cortical structures. Our results suggest a direct link between damage in white and gray matter and contribute to the notion of gray matter loss relating to clinical disability.

Systemic Injection of Neural Stem/Progenitor Cells in Mice with Chronic EAE

PubMed Central

Donegà, Matteo; Giusto, Elena; Cossetti, Chiara; Schaeffer, Julia; Pluchino, Stefano

2014-01-01

Neural stem/precursor cells (NPCs) are a promising stem cell source for transplantation approaches aiming at brain repair or restoration in regenerative neurology. This directive has arisen from the extensive evidence that brain repair is achieved after focal or systemic NPC transplantation in several preclinical models of neurological diseases. These experimental data have identified the cell delivery route as one of the main hurdles of restorative stem cell therapies for brain diseases that requires urgent assessment. Intraparenchymal stem cell grafting represents a logical approach to those pathologies characterized by isolated and accessible brain lesions such as spinal cord injuries and Parkinson's disease. Unfortunately, this principle is poorly applicable to conditions characterized by a multifocal, inflammatory and disseminated (both in time and space) nature, including multiple sclerosis (MS). As such, brain targeting by systemic NPC delivery has become a low invasive and therapeutically efficacious protocol to deliver cells to the brain and spinal cord of rodents and nonhuman primates affected by experimental chronic inflammatory damage of the central nervous system (CNS). This alternative method of cell delivery relies on the NPC pathotropism, specifically their innate capacity to (i) sense the environment via functional cell adhesion molecules and inflammatory cytokine and chemokine receptors; (ii) cross the leaking anatomical barriers after intravenous (i.v.) or intracerebroventricular (i.c.v.) injection; (iii) accumulate at the level of multiple perivascular site(s) of inflammatory brain and spinal cord damage; and (i.v.) exert remarkable tissue trophic and immune regulatory effects onto different host target cells in vivo. Here we describe the methods that we have developed for the i.v. and i.c.v. delivery of syngeneic NPCs in mice with experimental autoimmune encephalomyelitis (EAE), as model of chronic CNS inflammatory demyelination, and envisage the systemic stem cell delivery as a valuable technique for the selective targeting of the inflamed brain in regenerative neurology. PMID:24798882

Localized epigenetic silencing of a damage-activated WNT enhancer limits regeneration in mature Drosophila imaginal discs

PubMed Central

Harris, Robin E; Setiawan, Linda; Saul, Josh; Hariharan, Iswar K

2016-01-01

Many organisms lose the capacity to regenerate damaged tissues as they mature. Damaged Drosophila imaginal discs regenerate efficiently early in the third larval instar (L3) but progressively lose this ability. This correlates with reduced damage-responsive expression of multiple genes, including the WNT genes wingless (wg) and Wnt6. We demonstrate that damage-responsive expression of both genes requires a bipartite enhancer whose activity declines during L3. Within this enhancer, a damage-responsive module stays active throughout L3, while an adjacent silencing element nucleates increasing levels of epigenetic silencing restricted to this enhancer. Cas9-mediated deletion of the silencing element alleviates WNT repression, but is, in itself, insufficient to promote regeneration. However, directing Myc expression to the blastema overcomes repression of multiple genes, including wg, and restores cellular responses necessary for regeneration. Localized epigenetic silencing of damage-responsive enhancers can therefore restrict regenerative capacity in maturing organisms without compromising gene functions regulated by developmental signals. DOI: http://dx.doi.org/10.7554/eLife.11588.001 PMID:26840050

Neuroanatomy and neuropathology associated with Korsakoff's syndrome.

PubMed

Kril, Jillian J; Harper, Clive G

2012-06-01

Although the neuropathology of Korsakoff's syndrome (KS) was first described well over a century ago and the characteristic brain pathology does not pose a diagnostic challenge to pathologists, there is still controversy over the neuroanatomical substrate of the distinctive memory impairment in these patients. Cohort studies of KS suggest a central role for the mammillary bodies and mediodorsal thalamus, and quantitative studies suggest additional damage to the anterior thalamus is required. Rare cases of KS caused by pathologies other than those of nutritional origin provide support for the role of the anterior thalamus and mammillary bodies. Taken together the evidence to date shows that damage to the thalamus and hypothalamus is required, in particular the anterior thalamic nucleus and the medial mammillary nucleus of the hypothalamus. As these nuclei form part of wider memory circuits, damage to the inter-connecting white matter tracts can also result in a similar deficit as direct damage to the nuclei. Although these nuclei and their connections appear to be the primary site of damage, input from other brain regions within the circuits, such as the frontal cortex and hippocampus, or more distant regions, including the cerebellum and amygdala, may have a modulatory role on memory function. Further studies to confirm the precise site(s) and extend of brain damage necessary for the memory impairment of KS are required.

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

Kozlowski, M.F.; Maricle, S.; Mouser, R.

A statistics-based model is being developed to predict the laser-damage-limited lifetime of UV optical components on the NIF laser. In order to provide data for the model, laser damage experiments were performed on the Beamlet laser system at LLNL. An early prototype NIF focus lens was exposed to twenty 35 1 nm pulses at an average fluence of 5 J/cm{sup 2}, 3ns. Using a high resolution optic inspection system a total of 353 damage sites was detected within the 1160 cm{sup 2} beam aperture. Through inspections of the lens before, after and, in some cases, during the campaign, pulse tomore » pulse damage growth rates were measured for damage initiating both on the surface and at bulk inclusions. Growth rates as high as 79 {micro}m/pulse (surface diameter) were observed for damage initiating at pre-existing scratches in the surface. For most damage sites on the optic, both surface and bulk, the damage growth rate was approximately l0{micro}m/pulse. The lens was also used in Beamlet for a subsequent 1053 {micro}m/526 {micro}m campaign. The 352 {micro}m-initiated damage continued to grow during that campaign although at generally lower growth rate.« less

Multiple Sclerosis

MedlinePlus

Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the ... attacks healthy cells in your body by mistake. Multiple sclerosis affects women more than men. It often begins ...

[Damage control in trauma patients with hemodynamic instability].

PubMed

Müller, Thorben; Doll, Dietrich; Kliebe, Frank; Ruchholtz, Steffen; Kühne, Christian

2010-10-01

The term "Damage-control" is borrowed from naval terminology. It means the initial control of a damaged ship. Because of the lethal triad in multiple injured patients the classical concept of definitive surgically therapy in the acute phase of the injury has a high rate of complications such as exsanguination, sepsis, heart failure and multiple organ failure. The core idea of the damage control concept was to minimize the additional trauma by surgical operations in these critical patients in the first phase. This means temporary control of a hemorrhage and measures for stopping abdominal contamination. After 24 - 48 hours in the intensive care unit and correction of physiological disturbances further interventions are performed for definitively treatment of the injuries. Summarized, the damage control strategy comprises an abbreviated operation, intensive care unit resuscitation, and a return to the operating room for the definitive operation after hemodynamic stabilisation of the patient. © Georg Thieme Verlag Stuttgart · New York.

Meningeal mast cells affect early T cell central nervous system infiltration and blood-brain barrier integrity through TNF: a role for neutrophil recruitment?

PubMed

Sayed, Blayne A; Christy, Alison L; Walker, Margaret E; Brown, Melissa A

2010-06-15

Mast cells contribute to the pathogenesis of experimental autoimmune encephalomyelitis, a rodent model of the human demyelinating disease multiple sclerosis. Yet their site and mode of action is unknown. In both diseases, myelin-specific T cells are initially activated in peripheral lymphoid organs. However, for disease to occur, these cells must enter the immunologically privileged CNS through a breach in the relatively impermeable blood-brain barrier. In this study, we demonstrate that a dense population of resident mast cells in the meninges, structures surrounding the brain and spinal cord, regulate basal CNS barrier function, facilitating initial T cell CNS entry. Through the expression of TNF, mast cells recruit an early wave of neutrophils to the CNS. We propose that neutrophils in turn promote the blood-brain barrier breach and together with T cells lead to further inflammatory cell influx and myelin damage. These findings provide specific targets for intervention in multiple sclerosis as well as other immune-mediated CNS diseases.

Damage detection of an in-service condensation pipeline joint

NASA Astrophysics Data System (ADS)

Briand, Julie; Rezaei, Davood; Taheri, Farid

2010-04-01

The early detection of damage in structural or mechanical systems is of vital importance. With early detection, the damage may be repaired before the integrity of the system is jeopardized, resulting in monetary losses, loss of life or limb, and environmental impacts. Among the various types of structural health monitoring techniques, vibration-based methods are of significant interest since the damage location does not need to be known beforehand, making it a more versatile approach. The non-destructive damage detection method used for the experiments herein is a novel vibration-based method which uses an index called the EMD Energy Damage Index, developed with the aim of providing improved qualitative results compared to those methods currently available. As part of an effort to establish the integrity and limitation of this novel damage detection method, field testing was completed on a mechanical pipe joint on a condensation line, located in the physical plant of Dalhousie University. Piezoceramic sensors, placed at various locations around the joint were used to monitor the free vibration of the pipe imposed through the use of an impulse hammer. Multiple damage progression scenarios were completed, each having a healthy state and multiple damage cases. Subsequently, the recorded signals from the healthy and damaged joint were processed through the EMD Energy Damage Index developed in-house in an effort to detect the inflicted damage. The proposed methodology successfully detected the inflicted damages. In this paper, the effects of impact location, sensor location, frequency bandwidth, intrinsic mode functions, and boundary conditions are discussed.

Development of impact design methods for ceramic gas turbine components

NASA Technical Reports Server (NTRS)

Song, J.; Cuccio, J.; Kington, H.

1990-01-01

Impact damage prediction methods are being developed to aid in the design of ceramic gas turbine engine components with improved impact resistance. Two impact damage modes were characterized: local, near the impact site, and structural, usually fast fracture away from the impact site. Local damage to Si3N4 impacted by Si3N4 spherical projectiles consists of ring and/or radial cracks around the impact point. In a mechanistic model being developed, impact damage is characterized as microcrack nucleation and propagation. The extent of damage is measured as volume fraction of microcracks. Model capability is demonstrated by simulating late impact tests. Structural failure is caused by tensile stress during impact exceeding material strength. The EPIC3 code was successfully used to predict blade structural failures in different size particle impacts on radial and axial blades.

Transduction of a Foreign Histocompatibility Gene into the Arterial Wall Induces Vasculitis

NASA Astrophysics Data System (ADS)

Nabel, Elizabeth G.; Plautz, Gregory; Nabel, Gary J.

1992-06-01

Autoimmune vasculitis represents a disease characterized by focal inflammation within arteries at multiple sites in the vasculature. Therapeutic interventions in this disease are empirical and often unsuccessful, and the mechanisms of immune injury are not well-defined. The direct transfer of recombinant genes and their expression in the arterial wall provides an opportunity to explore the pathogenesis and treatment of vascular disease. In this report, an animal model for vasculitis has been developed. Inflammation has been elicited by direct gene transfer of a foreign class I major histocompatibility complex gene, HLA-B7, to specific sites in porcine arteries. Transfer and expression of this recombinant gene was confirmed by a polymerase chain reaction and immunohistochemistry, and cytolytic T cells specific for HLA-B7 were detected. These findings demonstrate that expression of a recombinant gene in the vessel wall can induce a focal immune response and suggest that vessel damage induced by cell-mediated immune injury can initiate vasculitis.

The Neutrophil Btk Signalosome Regulates Integrin Activation during Sterile Inflammation

PubMed Central

Volmering, Stephanie; Block, Helena; Boras, Mark; Lowell, Clifford A.; Zarbock, Alexander

2016-01-01

SUMMARY Neutrophils are recruited from the blood to sites of sterile inflammation, where they are involved in wound healing but can also cause tissue damage. During sterile inflammation, necrotic cells release pro-inflammatory molecules including formylated peptides. However, the signaling pathway triggered by formylated peptides to integrin activation and leukocyte recruitment is unknown. By using spinning-disk confocal intravital microscopy, we examined the molecular mechanisms of leukocyte recruitment to sites of focal hepatic necrosis in vivo. We demonstrated that the Bruton’s tyrosine kinase (Btk) was required for multiple Mac-1 activation events involved in neutrophil recruitment and functions during sterile inflammation triggered by fMLF. The Src family kinase Hck, Wiskott-Aldrich-syndrome protein, and phospholipase Cγ2 were also involved in this pathway required for fMLF-triggered Mac-1 activation and neutrophil recruitment. Thus, we have identified a neutrophil Btk signalosome that is involved in a signaling pathway triggered by formylated peptides leading to the selective activation of Mac-1 and neutrophil recruitment during sterile inflammation. PMID:26777396

Genotoxicity of Styrene–Acrylonitrile Trimer in Brain, Liver, and Blood Cells of Weanling F344 Rats

PubMed Central

Hobbs, Cheryl A.; Chhabra, Rajendra S.; Recio, Leslie; Streicker, Michael; Witt, Kristine L.

2012-01-01

Styrene–acrylonitrile Trimer (SAN Trimer), a by-product in production of acrylonitrile styrene plastics, was identified at a Superfund site in Dover Township, NJ, where childhood cancer incidence rates were elevated for a period of several years. SAN Trimer was therefore tested by the National Toxicology Program in a 2-year perinatal carcinogenicity study in F344/N rats and a bacterial mutagenicity assay; both studies gave negative results. To further characterize its genotoxicity, SAN Trimer was subsequently evaluated in a combined micronucleus (MN)/Comet assay in juvenile male and female F344 rats. SAN Trimer (37.5, 75, 150, or 300 mg/kg/day) was administered by gavage once daily for 4 days. Micronucleated reticulocyte (MN-RET) frequencies in blood were determined by flow cytometry, and DNA damage in blood, liver, and brain cells was assessed using the Comet assay. Highly significant dose-related increases (P < 0.0001) in MN-RET were measured in both male and female rats administered SAN Trimer. The RET population was reduced in high dose male rats, suggesting chemical-related bone marrow toxicity. Results of the Comet assay showed significant, dose-related increases in DNA damage in brain cells of male (P < 0.0074) and female (P < 0.0001) rats; increased levels of DNA damage were also measured in liver cells and leukocytes of treated rats. Chemical-related cytotoxicity was not indicated in any of the tissues examined for DNA damage. The results of this subacute MN/Comet assay indicate induction of significant genetic damage in multiple tissues of weanling F344 male and female rats after oral exposure to SAN Trimer. PMID:22351108

Deficiencies in the Fanconi anemia DNA damage response pathway increase sensitivity to HPV-associated head and neck cancer.

PubMed

Park, Jung Wook; Pitot, Henry C; Strati, Katerina; Spardy, Nicole; Duensing, Stefan; Grompe, Markus; Lambert, Paul F

2010-12-01

Patients with the rare genetic disease, Fanconi anemia (FA), are highly susceptible to squamous cell carcinomas arising at multiple anatomic sites including the head and neck region. Human papillomaviruses (HPVs), particularly HPV16, are associated with ∼20% of head and neck squamous cell carcinomas (HNSCCs) in the general population. Some but not other investigators have reported that HNSCCs in FA patients are much more frequently positive for HPV. In addition, studies have demonstrated an interaction between the HPV16 E7 oncoprotein and the FA pathway, a DNA damage response pathway deficient in FA patients. On the basis of these studies, it was hypothesized that the FA pathway contributes to repair of DNA damage induced by HPV16 E7, providing one explanation for why FA patients are predisposed to HPV-associated HNSCCs. To determine the importance of the FA pathway in modulating the oncogenic abilities of E7, we crossed K14E7 transgenic (K14E7) and fancD2 knockout mice (FancD2(-/-)) to establish K14E7/FancD2(-/-) and K14E7/FancD2(+/+) mice and monitored their susceptibility to HNSCC when treated with a chemical carcinogen. K14E7/FancD2(-/-) mice had a significantly higher incidence of HNSCC compared with K14E7/FancD2(+/+) mice. This difference correlated with an increased proliferative index and the increase in expression of biomarkers that are used to assess levels of DNA damage. These animal studies support the hypotheses that FA patients have increased susceptibility to HPV-associated cancer and that the FA DNA damage response pathway normally attenuates the oncogenic potential of HPV16 E7.

High incidence of HPV-associated head and neck cancers in FA deficient mice is associated with E7's induction of DNA damage through its inactivation of pocket proteins.

PubMed

Park, Jung Wook; Shin, Myeong-Kyun; Pitot, Henry C; Lambert, Paul F

2013-01-01

Fanconi anemia (FA) patients are highly susceptible to solid tumors at multiple anatomical sites including head and neck region. A subset of head and neck cancers (HNCs) is associated with 'high-risk' HPVs, particularly HPV16. However, the correlation between HPV oncogenes and cancers in FA patients is still unclear. We previously learned that FA deficiency in mice predisposes HPV16 E7 transgenic mice to HNCs. To address HPV16 E6's oncogenic potential under FA deficiency in HNCs, we utilized HPV16 E6-transgenic mice (K14E6) and HPV16 E6/E7-bi-transgenic mice (K14E6E7) on genetic backgrounds sufficient or deficient for one of the fanc genes, fancD2 and monitored their susceptibility to HNCs. K14E6 mice failed to develop tumor. However, E6 and fancD2-deficiency accelerated E7-driven tumor development in K14E6E7 mice. The increased tumor incidence was more correlated with E7-driven DNA damage than proliferation. We also found that deficiency of pocket proteins, pRb, p107, and p130 that are well-established targets of E7, could recapitulate E7's induction of DNA damage. Our findings support the hypothesis that E7 induces HPV-associated HNCs by promoting DNA damage through the inactivation of pocket proteins, which explains why a deficiency in DNA damage repair would increase susceptibility to E7-driven cancer. Our results further demonstrate the unexpected finding that FA deficiency does not predispose E6 transgenic mice to HNCs, indicating a specificity in the synergy between FA deficiency and HPV oncogenes in causing HNCs.

Does variable-density thinning increase wind damage in conifer stands on the Olympic Peninsula?

Treesearch

S.D. Roberts; C.A. Harrington; K.R. Buermeyer

2007-01-01

Silvicultural treatments designed to enhance stand structural diversity may result in increased wind damage. The ability to avoid conditions that might lead to excessive wind damage would benefit forest managers. We analyzed wind damage following implementation of a variable-density thinning at four sites on the Olympic National Forest in northwest Washington. The...

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.

Archaeoseismology in Algeria: observed damages related to probable past earthquakes on archaeological remains on Roman sites (Tel Atlas of Algeria)

NASA Astrophysics Data System (ADS)

Roumane, Kahina; Ayadi, Abdelhakim

2017-04-01

The seismological catalogue for Algeria exhibits significant lack for the period before 1365. Some attempts led to retrieve ancient earthquakes evidenced by historical documents and achieves. Archaeoseismology allows a study of earthquakes that have affected archaeological sites, based on the analysis of damage observed on remains. We have focused on the Antiquity period that include Roman, Vandal and Byzantine period from B.C 146 to A.D. 533. This will contribute significantly to the understanding of seismic hazard of the Tell Atlas region known as an earthquake prone area. The Tell Atlas (Algeria) experienced during its history many disastrous earthquakes their impacts are graved on landscape and archaeological monuments. On Roman sites such, Lambaesis (Lambèse), Thamugadi (Timgad) Thibilis (Salaoua Announa) or Thevest (Tebessa), damage were observed on monuments and remains related to seismic events following strong shacking or other ground deformation (subsidence, landslide). Examples of observed damage and disorders on several Roman sites are presented as a contribution to Archaeoseismology in Algeria based on effects of earthquakes on ancient structures and monuments. Keywords : Archaeoseismology. Lambaesis. Drop columns. Aspecelium. Ancient earthquakes

Molecular insights into the recruitment of TFIIH to sites of DNA damage

PubMed Central

Oksenych, Valentyn; de Jesus, Bruno Bernardes; Zhovmer, Alexander; Egly, Jean-Marc; Coin, Frédéric

2009-01-01

XPB and XPD subunits of TFIIH are central genome caretakers involved in nucleotide excision repair (NER), although their respective role within this DNA repair pathway remains difficult to delineate. To obtain insight into the function of XPB and XPD, we studied cell lines expressing XPB or XPD ATPase-deficient complexes. We show the involvement of XPB, but not XPD, in the accumulation of TFIIH to sites of DNA damage. Recruitment of TFIIH occurs independently of the helicase activity of XPB, but requires two recently identified motifs, a R-E-D residue loop and a Thumb-like domain. Furthermore, we show that these motifs are specifically involved in the DNA-induced stimulation of the ATPase activity of XPB. Together, our data demonstrate that the recruitment of TFIIH to sites of damage is an active process, under the control of the ATPase motifs of XPB and suggest that this subunit functions as an ATP-driven hook to stabilize the binding of the TFIIH to damaged DNA. PMID:19713942

Comparison of the sand liquefaction estimated based on codes and practical earthquake damage phenomena

NASA Astrophysics Data System (ADS)

Fang, Yi; Huang, Yahong

2017-12-01

Conducting sand liquefaction estimated based on codes is the important content of the geotechnical design. However, the result, sometimes, fails to conform to the practical earthquake damages. Based on the damage of Tangshan earthquake and engineering geological conditions, three typical sites are chosen. Moreover, the sand liquefaction probability was evaluated on the three sites by using the method in the Code for Seismic Design of Buildings and the results were compared with the sand liquefaction phenomenon in the earthquake. The result shows that the difference between sand liquefaction estimated based on codes and the practical earthquake damage is mainly attributed to the following two aspects: The primary reasons include disparity between seismic fortification intensity and practical seismic oscillation, changes of groundwater level, thickness of overlying non-liquefied soil layer, local site effect and personal error. Meanwhile, although the judgment methods in the codes exhibit certain universality, they are another reason causing the above difference due to the limitation of basic data and the qualitative anomaly of the judgment formulas.

Advances in Structural Integrity Analysis Methods for Aging Metallic Airframe Structures with Local Damage

NASA Technical Reports Server (NTRS)

Starnes, James H., Jr.; Newman, James C., Jr.; Harris, Charles E.; Piascik, Robert S.; Young, Richard D.; Rose, Cheryl A.

2003-01-01

Analysis methodologies for predicting fatigue-crack growth from rivet holes in panels subjected to cyclic loads and for predicting the residual strength of aluminum fuselage structures with cracks and subjected to combined internal pressure and mechanical loads are described. The fatigue-crack growth analysis methodology is based on small-crack theory and a plasticity induced crack-closure model, and the effect of a corrosive environment on crack-growth rate is included. The residual strength analysis methodology is based on the critical crack-tip-opening-angle fracture criterion that characterizes the fracture behavior of a material of interest, and a geometric and material nonlinear finite element shell analysis code that performs the structural analysis of the fuselage structure of interest. The methodologies have been verified experimentally for structures ranging from laboratory coupons to full-scale structural components. Analytical and experimental results based on these methodologies are described and compared for laboratory coupons and flat panels, small-scale pressurized shells, and full-scale curved stiffened panels. The residual strength analysis methodology is sufficiently general to include the effects of multiple-site damage on structural behavior.

Residual Strength Pressure Tests and Nonlinear Analyses of Stringer- and Frame-Stiffened Aluminum Fuselage Panels with Longitudinal Cracks

NASA Technical Reports Server (NTRS)

Young, Richard D.; Rouse, Marshall; Ambur, Damodar R.; Starnes, James H., Jr.

1999-01-01

The results of residual strength pressure tests and nonlinear analyses of stringer- and frame-stiffened aluminum fuselage panels with longitudinal cracks are presented. Two types of damage are considered: a longitudinal crack located midway between stringers, and a longitudinal crack adjacent to a stringer and along a row of fasteners in a lap joint that has multiple-site damage (MSD). In both cases, the longitudinal crack is centered on a severed frame. The panels are subjected to internal pressure plus axial tension loads. The axial tension loads are equivalent to a bulkhead pressure load. Nonlinear elastic-plastic residual strength analyses of the fuselage panels are conducted using a finite element program and the crack-tip-opening-angle (CTOA) fracture criterion. Predicted crack growth and residual strength results from nonlinear analyses of the stiffened fuselage panels are compared with experimental measurements and observations. Both the test and analysis results indicate that the presence of MSD affects crack growth stability and reduces the residual strength of stiffened fuselage shells with long cracks.

Residual Strength Pressure Tests and Nonlinear Analyses of Stringer-and Frame-Stiffened Aluminum Fuselage Panels with Longitudinal Cracks

NASA Technical Reports Server (NTRS)

Young, Richard D.; Rouse, Marshall; Ambur, Damodar R.; Starnes, James H., Jr.

1998-01-01

The results of residual strength pressure tests and nonlinear analyses of stringer- and frame-stiffened aluminum fuselage panels with longitudinal cracks are presented. Two types of damage are considered: a longitudinal crack located midway between stringers, and a longitudinal crack adjacent to a stringer and along a row of fasteners in a lap joint that has multiple-site damage (MSD). In both cases, the longitudinal crack is centered on a severed frame. The panels are subjected to internal pressure plus axial tension loads. The axial tension loads are equivalent to a bulkhead pressure load. Nonlinear elastic-plastic residual strength analyses of the fuselage panels are conducted using a finite element program and the crack-tip-opening-angle (CTOA) fracture criterion. Predicted crack growth and residual strength results from nonlinear analyses of the stiffened fuselage panels are compared with experimental measurements and observations. Both the test and analysis results indicate that the presence of MSD affects crack growth stability and reduces the residual strength of stiffened fuselage shells with long cracks.

Recruitment of Fanconi Anemia and Breast Cancer Proteins to DNA Damage Sites is differentially Governed by Replication

PubMed Central

Shen, Xi; Do, Huong; Li, Yongjian; Chung, Woo-Hyun; Tomasz, Maria; de Winter, Johan P.; Xia, Bing; Elledge, Stephen J.; Wang, Weidong; Li, Lei

2009-01-01

Summary Fanconi anemia (FA) is characterized by cellular hypersensivity to DNA crosslinking agents, but how the Fanconi pathway protects cells from DNA crosslinks and whether FA proteins act directly on crosslinks remains unclear. We developed a chromatin-IP-based strategy termed eChIP and detected association of multiple FA proteins with DNA crosslinks in vivo. Inter-dependence analyses revealed that crosslink-specific enrichment of various FA proteins is controlled by distinct mechanisms. BRCA-related FA proteins (BRCA2, FANCJ/BACH1, and FANCN/PALB2), but not FA core and I/D2 complexes, require replication for their crosslink association. FANCD2, but not FANCJ and FANCN, requires the FA core complex for its recruitment. FA core complex requires nucleotide excision repair proteins XPA and XPC for its association. Consistent with the distinct recruitment mechanism, recombination-independent crosslink repair was inversely affected in cells deficient of FANC-core versus BRCA-related FA proteins. Thus, FA proteins participate in distinct DNA damage response mechanisms governed by DNA replication status. PMID:19748364

Effects of topographic position and geology on shaking damage to residential wood-framed structures during the 2003 San Simeon earthquake, western San Luis obispo county, California

USGS Publications Warehouse

McCrink, T.P.; Wills, C.J.; Real, C.R.; Manson, M.W.

2010-01-01

A statistical evaluation of shaking damage to wood-framed houses caused by the 2003 M6.5 San Simeon earthquake indicates that both the rate and severity of damage, independent of structure type, are significantly greater on hilltops compared to hill slopes when underlain by Cretaceous or Tertiary sedimentary rocks. This increase in damage is interpreted to be the result of topographic amplification. An increase in the damage rate is found for all structures built on Plio-Pleistocene rocks independent of topographic position, and this is interpreted to be the result of amplified shaking caused by geologic site response. Damage rate and severity to houses built on Tertiary rocks suggest that amplification due to both topographic position and geologic site response may be occurring in these rocks, but effects from other topographic parameters cannot be ruled out. For all geologic and topographic conditions, houses with raised foundations are more frequently damaged than those with slab foundations. However, the severity of damage to houses on raised foundations is only significantly greater for those on hill slopes underlain by Tertiary rocks. Structures with some damage-resistant characteristics experienced greater damage severity on hilltops, suggesting a spectral response to topographic amplification. ?? 2010, Earthquake Engineering Research Institute.

Biology and Mucosal Immunity to Myxozoans

PubMed Central

Gómez, Daniela; Bartholomew, Jerri; Sunyer, J. Oriol

2014-01-01

Myxozoans are among the most abundant parasites in nature. Their life cycles involve two hosts: an invertebrate, usually an annelid, and a vertebrate, usually a fish. They affect fish species in their natural habitats but also constitute a menace for fish aquaculture. Using different strategies they are able to parasitize and cause damage in multiple organs, including mucosal tissues, which they use also as portals of entry. In fish, the main mucosal sites include the intestine, skin and gills. Recently the finding of a specific mucosal immunoglobulin in teleost (IgT), analogous to mammalian IgA, and the capacity of fish to develop a specific mucosal immune response against different pathogens, has highlighted the importance of studying immune responses at mucosal sites. In this review, we describe the major biological characteristics of myxozoan parasites and present the data available regarding immune responses for species that infect mucosal sites. As models for mucosal immunity we review the responses to Enteromyxum spp. and Ceratomyxa shasta, both of which parasitize the intestine. The immune response at the skin and gills is also described, as these mucosal tissues are used by myxozoans as attaching surfaces and portal of entry, and some species also parasitize these sites. Finally, the development of immunoprophylactic strategies is discussed. PMID:23994774

Bioaccumulation of trace metals and total petroleum and genotoxicity responses in an edible fish population as indicators of marine pollution.

PubMed

D'Costa, Avelyno; Shyama, S K; Praveen Kumar, M K

2017-08-01

The present study reports the genetic damage and the concentrations of trace metals and total petroleum hydrocarbons prevailing in natural populations of an edible fish, Arius arius in different seasons along the coast of Goa, India as an indicator of the pollution status of coastal water. Fish were collected from a suspected polluted site and a reference site in the pre-monsoon, monsoon and post-monsoon seasons. Physico-chemical parameters as well as the concentrations of total petroleum hydrocarbons (TPH) and trace metals in the water and sediment as well as the tissues of fish collected from these sites were recorded. The genotoxicity status of the fish was assessed employing the micronucleus test and comet assay. A positive correlation (p<0.001) was observed between the tail DNA and micronuclei in all the fish collected. Multiple regression analysis revealed that tissue and environmental pollutant concentrations and genotoxicity were positively associated and higher in the tissues of the fish collected from the polluted site. Pollution indicators and genotoxicity tests, combined with other physiological or biochemical parameters represent an essential integrated approach for efficient monitoring of aquatic ecosystems in Goa. Copyright © 2017 Elsevier Inc. All rights reserved.

Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation

NASA Astrophysics Data System (ADS)

Viswanathan, Kavitha; Dhabhar, Firdaus S.

2005-04-01

Effective immunoprotection requires rapid recruitment of leukocytes into sites of surgery, wounding, infection, or vaccination. In contrast to immunosuppressive chronic stressors, short-term acute stressors have immunoenhancing effects. Here, we quantify leukocyte infiltration within a surgical sponge to elucidate the kinetics, magnitude, subpopulation, and chemoattractant specificity of an acute stress-induced increase in leukocyte trafficking to a site of immune activation. Mice acutely stressed before sponge implantation showed 200-300% higher neutrophil, macrophage, natural killer cell, and T cell infiltration than did nonstressed animals. We also quantified the effects of acute stress on lymphotactin- (LTN; a predominantly lymphocyte-specific chemokine), and TNF-- (a proinflammatory cytokine) stimulated leukocyte infiltration. An additional stress-induced increase in infiltration was observed for neutrophils, in response to TNF-, macrophages, in response to TNF- and LTN, and natural killer cells and T cells in response to LTN. These results show that acute stress initially increases trafficking of all major leukocyte subpopulations to a site of immune activation. Tissue damage-, antigen-, or pathogen-driven chemoattractants subsequently determine which subpopulations are recruited more vigorously. Such stress-induced increases in leukocyte trafficking may enhance immunoprotection during surgery, vaccination, or infection, but may also exacerbate immunopathology during inflammatory (cardiovascular disease or gingivitis) or autoimmune (psoriasis, arthritis, or multiple sclerosis) diseases. chemokine | psychophysiological stress | surgical sponge | wound healing | lymphotactin

Recognition of earthquake-related damage in archaeological sites: Examples from the Dead Sea fault zone

NASA Astrophysics Data System (ADS)

Marco, Shmuel

2008-06-01

Archaeological structures that exhibit seismogenic damage expand our knowledge of temporal and spatial distribution of earthquakes, afford independent examination of historical accounts, provide information on local earthquake intensities and enable the delineation of macroseismic zones. They also illustrate what might happen in future earthquakes. In order to recover this information, we should be able to distinguish earthquake damage from anthropogenic damage and from other natural processes of wear and tear. The present paper reviews several types of damage that can be attributed with high certainty to earthquakes and discusses associated caveats. In the rare cases, where faults intersect with archaeological sites, offset structures enable precise determination of sense and size of slip, and constrain its time. Among the characteristic off-fault damage types, I consider horizontal shifting of large building blocks, downward sliding of one or several blocks from masonry arches, collapse of heavy, stably-built walls, chipping of corners of building blocks, and aligned falling of walls and columns. Other damage features are less conclusive and require additional evidence, e.g., fractures that cut across several structures, leaning walls and columns, warps and bulges in walls. Circumstantial evidence for catastrophic earthquake-related destruction includes contemporaneous damage in many sites in the same area, absence of weapons or other anthropogenic damage, stratigraphic data on collapse of walls and ceilings onto floors and other living horizons and burial of valuable artifacts, as well as associated geological palaeoseismic phenomena such as liquefaction, land- and rock-slides, and fault ruptures. Additional support may be found in reliable historical accounts. Special care must be taken in order to avoid circular reasoning by maintaining the independence of data acquisition methods.

Analysis of multiple tank car releases in train accidents.

PubMed

Liu, Xiang; Liu, Chang; Hong, Yili

2017-10-01

There are annually over two million carloads of hazardous materials transported by rail in the United States. The American railroads use large blocks of tank cars to transport petroleum crude oil and other flammable liquids from production to consumption sites. Being different from roadway transport of hazardous materials, a train accident can potentially result in the derailment and release of multiple tank cars, which may result in significant consequences. The prior literature predominantly assumes that the occurrence of multiple tank car releases in a train accident is a series of independent Bernoulli processes, and thus uses the binomial distribution to estimate the total number of tank car releases given the number of tank cars derailing or damaged. This paper shows that the traditional binomial model can incorrectly estimate multiple tank car release probability by magnitudes in certain circumstances, thereby significantly affecting railroad safety and risk analysis. To bridge this knowledge gap, this paper proposes a novel, alternative Correlated Binomial (CB) model that accounts for the possible correlations of multiple tank car releases in the same train. We test three distinct correlation structures in the CB model, and find that they all outperform the conventional binomial model based on empirical tank car accident data. The analysis shows that considering tank car release correlations would result in a significantly improved fit of the empirical data than otherwise. Consequently, it is prudent to consider alternative modeling techniques when analyzing the probability of multiple tank car releases in railroad accidents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Question of bone marrow stromal fibroblast traffic

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

Maloney, M.A.; Lamela, R.A.; Patt, H.M.

Bone marrow stromal fibroblasts (CFU-F) normally do not exchange bone marrow sites in vivo. Restitution of the CFU-F after radiation damage is primarily recovery by the local fibroblasts from potentially lethal damage. Migration of stromal fibroblasts from shielded sites to an irradiated site makes a minimal contribution, if any, to CFU-F recovery. Determination of the relative contribution of donor stromal cells in bone marrow transplants by karyotyping the proliferating bone marrow stromal cells in vitro may not reflect the relative distribution of fibroblasts in the marrow. If there is residual damage to the host stromal fibroblasts from treatment before transplantation,more » these cells may not be able to proliferate in vitro. Therefore, an occasional transplanted fibroblast may contribute most of the metaphase figures scored for karyotype.« less

Identification of ATM Protein Kinase Phosphorylation Sites by Mass Spectrometry.

PubMed

Graham, Mark E; Lavin, Martin F; Kozlov, Sergei V

2017-01-01

ATM (ataxia-telangiectasia mutated) protein kinase is a key regulator of cellular responses to DNA damage and oxidative stress. DNA damage triggers complex cascade of signaling events leading to numerous posttranslational modification on multitude of proteins. Understanding the regulation of ATM kinase is therefore critical not only for understanding the human genetic disorder ataxia-telangiectasia and potential treatment strategies, but essential for deciphering physiological responses of cells to stress. These responses play an important role in carcinogenesis, neurodegeneration, and aging. We focus here on the identification of DNA damage inducible ATM phosphorylation sites to understand the importance of autophosphorylation in the mechanism of ATM kinase activation. We demonstrate the utility of using immunoprecipitated ATM in quantitative LC-MS/MS workflow with stable isotope dimethyl labeling of ATM peptides for identification of phosphorylation sites.

The Molecular Origin of the MMR-dependent Apoptosis Pathway from Dynamics Analysis of MutSα-DNA Complexes

PubMed Central

Negureanu, Lacramioara; Salsbury, Freddie R.

2012-01-01

The cellular response to DNA damage signaling by MMR proteins is incompletely understood. It is generally accepted that MMR-dependent apoptosis pathway in response to DNA damage detection is independent of MMR's DNA repair function. In this study we investigate correlated motions in response to the binding of mismatched and PCL DNA fragments by MutSα, as derived from 50 ns molecular dynamics simulations. The protein dynamics in response to the mismatched and damaged DNA recognition suggests that MutSα signals their recognition through independent pathways providing evidence for the molecular origin of the MMR-dependent apoptosis. MSH2 subunit is indicated to play a key role in signaling both mismatched and damaged DNA recognition; localized and collective motions within the protein allow identifying sites on the MSH2 surface possible involved in recruiting proteins responsible for downstream events. Unlike in the mismatch complex, predicted key communication sites specific for the damage recognition are on the list of known cancer causing mutations or deletions. This confirms MSH2's role in signaling DNA-damage induced apoptosis and suggests that defects in MMR alone is sufficient to trigger tumorigenesis, supporting the experimental evidence that MMR-damage response function could protect from the early occurrence of tumors. Identifying these particular communication sites may have implications for the treatment of cancers that are not defective for MMR, but are unable to function optimally for MMR-dependent responses following DNA damage such as the case of resistance to cisplatin. PMID:22712459

Genome-wide map of Apn1 binding sites under oxidative stress in Saccharomyces cerevisiae.

PubMed

Morris, Lydia P; Conley, Andrew B; Degtyareva, Natalya; Jordan, I King; Doetsch, Paul W

2017-11-01

The DNA is cells is continuously exposed to reactive oxygen species resulting in toxic and mutagenic DNA damage. Although the repair of oxidative DNA damage occurs primarily through the base excision repair (BER) pathway, the nucleotide excision repair (NER) pathway processes some of the same lesions. In addition, damage tolerance mechanisms, such as recombination and translesion synthesis, enable cells to tolerate oxidative DNA damage, especially when BER and NER capacities are exceeded. Thus, disruption of BER alone or disruption of BER and NER in Saccharomyces cerevisiae leads to increased mutations as well as large-scale genomic rearrangements. Previous studies demonstrated that a particular region of chromosome II is susceptible to chronic oxidative stress-induced chromosomal rearrangements, suggesting the existence of DNA damage and/or DNA repair hotspots. Here we investigated the relationship between oxidative damage and genomic instability utilizing chromatin immunoprecipitation combined with DNA microarray technology to profile DNA repair sites along yeast chromosomes under different oxidative stress conditions. We targeted the major yeast AP endonuclease Apn1 as a representative BER protein. Our results indicate that Apn1 target sequences are enriched for cytosine and guanine nucleotides. We predict that BER protects these sites in the genome because guanines and cytosines are thought to be especially susceptible to oxidative attack, thereby preventing large-scale genome destabilization from chronic accumulation of DNA damage. Information from our studies should provide insight into how regional deployment of oxidative DNA damage management systems along chromosomes protects against large-scale rearrangements. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Widespread Increases in Malondialdehyde Immunoreactivity in Dopamine-Rich and Dopamine-Poor Regions of Rat Brain Following Multiple, High Doses of Methamphetamine

PubMed Central

Horner, Kristen A.; Gilbert, Yamiece E.; Cline, Susan D.

2011-01-01

Treatment with multiple high doses of methamphetamine (METH) can induce oxidative damage, including dopamine (DA)-mediated reactive oxygen species (ROS) formation, which may contribute to the neurotoxic damage of monoamine neurons and long-term depletion of DA in the caudate putamen (CPu) and substantia nigra pars compacta (SNpc). Malondialdehyde (MDA), a product of lipid peroxidation by ROS, is commonly used as a marker of oxidative damage and treatment with multiple high doses of METH increases MDA reactivity in the CPu of humans and experimental animals. Recent data indicate that MDA itself may contribute to the destruction of DA neurons, as MDA causes the accumulation of toxic intermediates of DA metabolism via its chemical modification of the enzymes necessary for the breakdown of DA. However, it has been shown that in human METH abusers there is also increased MDA reactivity in the frontal cortex, which receives relatively fewer DA afferents than the CPu. These data suggest that METH may induce neuronal damage regardless of the regional density of DA or origin of DA input. The goal of the current study was to examine the modification of proteins by MDA in the DA-rich nigrostriatal and mesoaccumbal systems, as well as the less DA-dense cortex and hippocampus following a neurotoxic regimen of METH treatment. Animals were treated with METH (10 mg/kg) every 2 h for 6 h, sacrificed 1 week later, and examined using immunocytochemistry for changes in MDA-adducted proteins. Multiple, high doses of METH significantly increased MDA immunoreactivity (MDA-ir) in the CPu, SNpc, cortex, and hippocampus. Multiple METH administration also increased MDA-ir in the ventral tegmental area and nucleus accumbens. Our data indicate that multiple METH treatment can induce persistent and widespread neuronal damage that may not necessarily be limited to the nigrostriatal DA system. PMID:21602916

Multiple Channel Bridges for Spinal Cord Injury: Cellular Characterization of Host Response

PubMed Central

Yang, Yang; Laporte, Laura De; Zelivyanskaya, Marina L.; Whittlesey, Kevin J.; Anderson, Aileen J.; Cummings, Brian J.

2009-01-01

Bridges for treatment of the injured spinal cord must stabilize the injury site to prevent secondary damage and create a permissive environment that promotes regeneration. The host response to the bridge is central to creating a permissive environment, as the cell types that respond to the injury have the potential to secrete both stimulatory and inhibitory factors. We investigated multiple channel bridges for spinal cord regeneration and correlated the bridge structure to cell infiltration and axonal elongation. Poly(lactide-co-glycolide) bridges were fabricated by a gas foaming/particulate leaching process. Channels within the bridge had diameters of 150 or 250 μm, and the main body of the bridge was highly porous with a controllable pore size. Upon implantation in a rat spinal cord hemisection site, cells infiltrated into the bridge pores and channels, with the pore size influencing the rate of infiltration. The pores had significant cell infiltration, including fibroblasts, macrophages, S-100β-positive cells, and endothelial cells. The channels of the bridge were completely infiltrated with cells, which had aligned axially, and consisted primarily of fibroblasts, S-100β-positive cells, and endothelial cells. Reactive astrocytes were observed primarily outside of the bridge, and staining for chondroitin sulfate proteoglycans was decreased in the region surrounding the bridge relative to studies without bridges. Neurofilament staining revealed a preferential growth of the neural fibers within the bridge channels relative to the pores. Multiple channel bridges capable of supporting cellular infiltration, creating a permissive environment, and directing the growth of neural fibers have potential for promoting and directing spinal cord regeneration. PMID:19382871

43 CFR 11.60 - Type B assessments-general.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 11.60 Public Lands: Interior Office of the Secretary of the Interior NATURAL RESOURCE DAMAGE... assessment is to provide alternative methodologies for conducting natural resource damage assessments in... specifically allocable to, site-specific efforts taken in the assessment of damages for a natural resource for...

43 CFR 11.60 - Type B assessments-general.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 11.60 Public Lands: Interior Office of the Secretary of the Interior NATURAL RESOURCE DAMAGE... assessment is to provide alternative methodologies for conducting natural resource damage assessments in... specifically allocable to, site-specific efforts taken in the assessment of damages for a natural resource for...

Spectroscopic analyses on sonocatalytic damage to bovine serum albumin (BSA) induced by ZnO/hydroxylapatite (ZnO/HA) composite under ultrasonic irradiation

NASA Astrophysics Data System (ADS)

Wang, Zhiqiu; Li, Ying; Wang, Jun; Zou, Mingming; Gao, Jingqun; Kong, Yumei; Li, Kai; Han, Guangxi

ZnO/hydroxylapatite (ZnO/HA) composite with HA molar content of 6.0% was prepared by the method of precipitation and heat-treated at 500 °C for 40 min and was characterized by powder X-ray diffraction (XRD). The sonocatalytic activities of ZnO/HA composite was carried out through the damage of bovine serum albumin (BSA) in aqueous solution. Furthermore, the effects of several factors on the damage of BSA molecules were evaluated by means of UV-vis and fluorescence spectra. Experimental results indicated that the damage degree of BSA aggravated with the increase of ultrasonic irradiation time, irradiation power and ZnO/HA addition amount, but weakened with the increase of solution acidity and ionic strength. In addition, the damage site to BSA was also studied by synchronous fluorescence technology and the damage site was mainly at tryptophan (Trp) residue. This paper provides a valuable reference for driving sonocatalytic method to treat tumor in clinic application.

Immunology and Oxidative Stress in Multiple Sclerosis: Clinical and Basic Approach

PubMed Central

Ortiz, Genaro G.; Pacheco-Moisés, Fermín P.; Bitzer-Quintero, Oscar K.; Ramírez-Anguiano, Ana C.; Flores-Alvarado, Luis J.; Ramírez-Ramírez, Viridiana; Macias-Islas, Miguel A.; Torres-Sánchez, Erandis D.

2013-01-01

Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle. PMID:24174971

Pathogenic implications of iron accumulation in multiple sclerosis

PubMed Central

Williams, Rachel; Buchheit, Cassandra L.; Berman, Nancy E. J.; LeVine, Steven M.

2011-01-01

Iron, an essential element used for a multitude of biochemical reactions, abnormally accumulates in the central nervous system of patients with multiple sclerosis (MS). The mechanisms of abnormal iron deposition in MS are not fully understood, nor do we know whether these deposits have adverse consequences, i.e., contribute to pathogenesis. With some exceptions, excess levels of iron are represented concomitantly in multiple deep gray matter structures often with bilateral representation, while in white matter pathological iron deposits are usually located at sites of inflammation that are associated with veins. These distinct spatial patterns suggest disparate mechanisms of iron accumulation between these regions. Iron has been postulated to promote disease activity in MS by various means: 1) iron can amplify the activated state of microglia resulting in the increased production of proinflammatory mediators; 2) excess intracellular iron deposits could promote mitochondria dysfunction; and 3) improperly managed iron could catalyze the production of damaging reactive oxygen species. The pathological consequences of abnormal iron deposits may be dependent on the affected brain region and/or accumulation process. Here we review putative mechanisms of enhanced iron uptake in MS and address the likely roles of iron in the pathogenesis of this disease. PMID:22004421

PRP19 Transforms into a Sensor of RPA-ssDNA after DNA Damage and Drives ATR Activation via a Ubiquitin-Mediated Circuitry

PubMed Central

Maréchal, Alexandre; Wu, Ching-Shyi; Yazinski, Stephanie A.; Nguyen, Hai Dang; Liu, Shizhou; Jiménez, Amanda E.; Jin, Jianping; Zou, Lee

2014-01-01

Summary PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). While the role for PRP19 in splicing is well characterized, its role in the DDR remains elusive. Through a proteomic screen for proteins that interact with RPA-coated single-stranded DNA (RPA-ssDNA), we identified PRP19 as a sensor of DNA damage. PRP19 binds RPA directly and localizes to DNA damage sites via RPA, promoting RPA ubiquitylation in a DNA damage-induced manner. PRP19 facilitates the accumulation of ATRIP, the regulatory partner of the ATR kinase, at DNA damage sites. Depletion of PRP19 compromised the phosphorylation of ATR substrates, the recovery of stalled replication forks, and the progression of replication forks on damaged DNA. Importantly, PRP19 mutants that cannot bind RPA or function as an E3 ligase failed to support the ATR response, revealing that PRP19 drives ATR activation by acting as an RPA-ssDNA-sensing ubiquitin ligase during the DDR. PMID:24332808

Testicular membrane lipid damage by complex mixture of leachate from municipal battery recycling site as indication of idiopathic male infertility in rat

PubMed Central

Oboh, Ganiyu; Akindahunsi, Akintunde A.

2013-01-01

Leachate from a municipal battery recycling site is a potent source of mixed-metal released into the environment. The present study investigated the degree at which mixed-metal exposure to the municipal auto-battery leachate (MABL) and to the Elewi Odo municipal auto-battery recycling site leachate (EOMABRL) affected the lipid membrane of the testes in in vitro experiment. The results showed elevated level of mixed-metals over the permissible levels in drinking water, as recommended by regulatory authorities. In the leachate samples, the levels of malondialdehyde (MDA), a biomarker of lipid damage, was significantly (p<0.05) increased in rat testes in a dose-dependent manner. MDA induced by the municipal auto-battery leachate (MABL) was significantly (p<0.05) higher than the leachate from Elewi Odo municipal auto-battery recycling site (EOMABRL). The testicular lipid membrane capacity was compromised following treatment with leachate from the municipal battery recycling site, implicating mixed-metal exposure as the causative agent of testicular damage and male infertility. PMID:24678257

Testicular membrane lipid damage by complex mixture of leachate from municipal battery recycling site as indication of idiopathic male infertility in rat.

PubMed

Akintunde, Jacob K; Oboh, Ganiyu; Akindahunsi, Akintunde A

2013-12-01

Leachate from a municipal battery recycling site is a potent source of mixed-metal released into the environment. The present study investigated the degree at which mixed-metal exposure to the municipal auto-battery leachate (MABL) and to the Elewi Odo municipal auto-battery recycling site leachate (EOMABRL) affected the lipid membrane of the testes in in vitro experiment. The results showed elevated level of mixed-metals over the permissible levels in drinking water, as recommended by regulatory authorities. In the leachate samples, the levels of malondialdehyde (MDA), a biomarker of lipid damage, was significantly (p<0.05) increased in rat testes in a dose-dependent manner. MDA induced by the municipal auto-battery leachate (MABL) was significantly (p<0.05) higher than the leachate from Elewi Odo municipal auto-battery recycling site (EOMABRL). The testicular lipid membrane capacity was compromised following treatment with leachate from the municipal battery recycling site, implicating mixed-metal exposure as the causative agent of testicular damage and male infertility.

A fracture criterion for widespread cracking in thin-sheet aluminum alloys

NASA Technical Reports Server (NTRS)

Newman, J. C., Jr.; Dawicke, D. S.; Sutton, M. A.; Bigelow, C. A.

1993-01-01

An elastic-plastic finite-element analysis was used with a critical crack-tip-opening angle (CTOA) fracture criterion to model stable crack growth in thin-sheet 2024-T3 aluminum alloy panels with single and multiple-site damage (MSD) cracks. Comparisons were made between critical angles determined from the analyses and those measured with photographic methods. Calculated load against crack extension and load against crack-tip displacement on single crack specimens agreed well with test data even for large-scale plastic deformations. The analyses were also able to predict the stable tearing behavior of large lead cracks in the presence of stably tearing MSD cracks. Small MSD cracks significantly reduced the residual strength for large lead cracks.

A core hSSB1–INTS complex participates in the DNA damage response

PubMed Central

Zhang, Feng; Ma, Teng; Yu, Xiaochun

2013-01-01

Summary Human single-stranded DNA-binding protein 1 (hSSB1) plays an important role in the DNA damage response and the maintenance of genomic stability. It has been shown that the core hSSB1 complex contains hSSB1, INTS3 and C9orf80. Using protein affinity purification, we have identified integrator complex subunit 6 (INTS6) as a major subunit of the core hSSB1 complex. INTS6 forms a stable complex with INTS3 and hSSB1 both in vitro and in vivo. In this complex, INTS6 directly interacts with INTS3. In response to the DNA damage response, along with INTS3 and hSSB1, INTS6 relocates to the DNA damage sites. Moreover, the hSSB1–INTS complex regulates the accumulation of RAD51 and BRCA1 at DNA damage sites and the correlated homologous recombination. PMID:23986477

Suicide Bombing Attacks

PubMed Central

Almogy, Gidon; Belzberg, Howard; Mintz, Yoaz; Pikarsky, Alon K.; Zamir, Gideon; Rivkind, Avraham I.

2004-01-01

Objective: To review the experience of a large-volume trauma center in managing and treating casualties of suicide bombing attacks. Summary Background Data: The threat of suicide bombing attacks has escalated worldwide. The ability of the suicide bomber to deliver a relatively large explosive load accompanied by heavy shrapnel to the proximity of his or her victims has caused devastating effects. Methods: The authors reviewed and analyzed the experience obtained in treating victims of suicide bombings at the level I trauma center of the Hadassah University Hospital in Jerusalem, Israel from 2000 to 2003. Results: Evacuation is usually rapid due to the urban setting of these attacks. Numerous casualties are brought into the emergency department over a short period. The setting in which the device is detonated has implications on the type of injuries sustained by survivors. The injuries sustained by victims of suicide bombing attacks in semi-confined spaces are characterized by the degree and extent of widespread tissue damage and include multiple penetrating wounds of varying severity and location, blast injury, and burns. Conclusions: The approach to victims of suicide bombings is based on the guidelines for trauma management. Attention is given to the moderately injured, as these patients may harbor immediate life-threatening injuries. The concept of damage control can be modified to include rapid packing of multiple soft-tissue entry sites. Optimal utilization of manpower and resources is achieved by recruiting all available personnel, adopting a predetermined plan, and a centrally coordinated approach. Suicide bombing attacks seriously challenge the most experienced medical facilities. PMID:15075644

Suicide bombing attacks: update and modifications to the protocol.

PubMed

Almogy, Gidon; Belzberg, Howard; Mintz, Yoaz; Pikarsky, Alon K; Zamir, Gideon; Rivkind, Avraham I

2004-03-01

To review the experience of a large-volume trauma center in managing and treating casualties of suicide bombing attacks. The threat of suicide bombing attacks has escalated worldwide. The ability of the suicide bomber to deliver a relatively large explosive load accompanied by heavy shrapnel to the proximity of his or her victims has caused devastating effects. The authors reviewed and analyzed the experience obtained in treating victims of suicide bombings at the level I trauma center of the Hadassah University Hospital in Jerusalem, Israel from 2000 to 2003. Evacuation is usually rapid due to the urban setting of these attacks. Numerous casualties are brought into the emergency department over a short period. The setting in which the device is detonated has implications on the type of injuries sustained by survivors. The injuries sustained by victims of suicide bombing attacks in semi-confined spaces are characterized by the degree and extent of widespread tissue damage and include multiple penetrating wounds of varying severity and location, blast injury, and burns. The approach to victims of suicide bombings is based on the guidelines for trauma management. Attention is given to the moderately injured, as these patients may harbor immediate life-threatening injuries. The concept of damage control can be modified to include rapid packing of multiple soft-tissue entry sites. Optimal utilization of manpower and resources is achieved by recruiting all available personnel, adopting a predetermined plan, and a centrally coordinated approach. Suicide bombing attacks seriously challenge the most experienced medical facilities.

Multiple Damage Progression Paths in Model-Based Prognostics

NASA Technical Reports Server (NTRS)

Daigle, Matthew; Goebel, Kai Frank

2011-01-01

Model-based prognostics approaches employ domain knowledge about a system, its components, and how they fail through the use of physics-based models. Component wear is driven by several different degradation phenomena, each resulting in their own damage progression path, overlapping to contribute to the overall degradation of the component. We develop a model-based prognostics methodology using particle filters, in which the problem of characterizing multiple damage progression paths is cast as a joint state-parameter estimation problem. The estimate is represented as a probability distribution, allowing the prediction of end of life and remaining useful life within a probabilistic framework that supports uncertainty management. We also develop a novel variance control mechanism that maintains an uncertainty bound around the hidden parameters to limit the amount of estimation uncertainty and, consequently, reduce prediction uncertainty. We construct a detailed physics-based model of a centrifugal pump, to which we apply our model-based prognostics algorithms. We illustrate the operation of the prognostic solution with a number of simulation-based experiments and demonstrate the performance of the chosen approach when multiple damage mechanisms are active

A global assessment of the societal impacts of glacier outburst floods

NASA Astrophysics Data System (ADS)

Carrivick, Jonathan L.; Tweed, Fiona S.

2016-09-01

Glacier outburst floods are sudden releases of large amounts of water from a glacier. They are a pervasive natural hazard worldwide. They have an association with climate primarily via glacier mass balance and their impacts on society partly depend on population pressure and land use. Given the ongoing changes in climate and land use and population distributions there is therefore an urgent need to discriminate the spatio-temporal patterning of glacier outburst floods and their impacts. This study presents data compiled from 20 countries and comprising 1348 glacier floods spanning 10 centuries. Societal impacts were assessed using a relative damage index based on recorded deaths, evacuations, and property and infrastructure destruction and disruption. These floods originated from 332 sites; 70% were from ice-dammed lakes and 36% had recorded societal impact. The number of floods recorded has apparently reduced since the mid-1990s in all major world regions. Two thirds of sites that have produced > 5 floods (n = 32) have floods occurring progressively earlier in the year. Glacier floods have directly caused at least: 7 deaths in Iceland, 393 deaths in the European Alps, 5745 deaths in South America and 6300 deaths in central Asia. Peru, Nepal and India have experienced fewer floods yet higher levels of damage. One in five sites in the European Alps has produced floods that have damaged farmland, destroyed homes and damaged bridges; 10% of sites in South America have produced glacier floods that have killed people and damaged infrastructure; 15% of sites in central Asia have produced floods that have inundated farmland, destroyed homes, damaged roads and damaged infrastructure. Overall, Bhutan and Nepal have the greatest national-level economic consequences of glacier flood impacts. We recommend that accurate, full and standardised monitoring, recording and reporting of glacier floods is essential if spatio-temporal patterns in glacier flood occurrence, magnitude and societal impact are to be better understood. We note that future modelling of the global impact of glacier floods cannot assume that the same trends will continue and will need to consider combining land-use change with probability distributions of geomorphological responses to climate change and to human activity.

Radiation damage-controlled localization of alteration haloes in albite: implications for alteration types and patterns vis-à-vis mineralization and element mobilization

NASA Astrophysics Data System (ADS)

Pal, D. C.; Chaudhuri, T.

2016-12-01

Uraninite, besides occurring in other modes, occurs as inclusions in albite in feldspathic schist in the Bagjata uranium deposits, Singhbhum shear zone, India. The feldspathic schist, considered the product of Na-metasomatism, witnessed multiple hydrothermal events, the signatures of which are preserved in the alteration halo in albite surrounding uraninite. Here we report radiation damage-controlled localization of alteration halo in albite and its various geological implications. Microscopic observation and SRIM/TRIM simulations reveal that the dimension of the alteration halo is dependent collectively on the zone of maximum cumulative α dose that albite was subjected to and by the extent of dissolution of uraninite during alteration. In well-preserved alteration haloes, from uraninite to the unaltered part of albite, the alteration minerals are systematically distributed in different zones; zone-1: K-feldspar; zone-2: chlorite; zone-3: LREE-phase/pyrite/U-Y-silicate. Based on textures of alteration minerals in the alteration microdomain, we propose a generalized Na+➔K+➔H+ alteration sequence, which is in agreement with the regional-scale alteration pattern. Integrating distribution of ore and alteration minerals in the alteration zone and their geochemistry, we further propose multiple events of U, REE, and sulfide mineralization/mobilization in the Bagjata deposit. The alteration process also involved interaction of the hydrothermal fluid with uraninite inclusions resulting in resorption of uraninite, redistribution of elements, including U and Pb, and resetting of isotopic clock. Thus, our study demonstrates that alteration halo is a miniature scale-model of the regional hydrothermal alteration types and patterns vis-à-vis mineralization/mobilization. This study further demonstrates that albite is vulnerable to radiation damage and damage-controlled fluid-assisted alteration, which may redistribute metals, including actinides, from radioactive minerals included in albite. This has important implications in geochronology. Such a study can also provide important clues to the chemical behavior of granite, in which albite is a common constituent, in a physico-chemical ambience analogous to a site of deep borehole disposal of radioactive waste.

A Survey of High Explosive-Induced Damage and Spall in Selected Metals Using Proton Radiography

NASA Astrophysics Data System (ADS)

Holtkamp, D. B.; Clark, D. A.; Ferm, E. N.; Gallegos, R. A.; Hammon, D.; Hemsing, W. F.; Hogan, G. E.; Holmes, V. H.; King, N. S. P.; Liljestrand, R.; Lopez, R. P.; Merrill, F. E.; Morris, C. L.; Morley, K. B.; Murray, M. M.; Pazuchanics, P. D.; Prestridge, K. P.; Quintana, J. P.; Saunders, A.; Schafer, T.; Shinas, M. A.; Stacy, H. L.

2004-07-01

Multiple spall and damage layers can be created in metal when the free surface reflects a Taylor wave generated by high explosives. These phenomena have been explored in different thicknesses of several metals (tantalum, copper, 6061 T6-aluminum, and tin) using high-energy proton radiography. Multiple images (up to 21) can be produced of the dynamic evolution of damaged material on the microsecond time scale with a <50 ns "shutter" time. Movies and multiframe still images of areal and (Abel inverted) volume densities are presented. An example of material that is likely melted on release (tin) is also presented.

Early performance of knobcone x monterey pine hybrids...on marginal timber sites

Treesearch

James R. Griffin; M. Thompson. Conkle

1967-01-01

Three plantations of knobcone X Monterey pine hybrids were established on marginal timber sites at elevations of 671 m.(2,200 ft.) to 991 m. (3,200 ft.) in northern California in 1964. After 3 years, the hybrids appear more promising than either parent species. Damage from snow and windthrow suggests high risk of storm damage to hybrids planted at higher elevations....

Accidents caused by hazardous trees on California forest recreation sites

Treesearch

Lee A. Paine

1966-01-01

From 1959 to early 1966, tree failures caused an average of more than two injuries or deaths per year on forest recreation sites in California. Annual property damage is estimated at $25,100. Conifers accounted for three of every four accidents reported; pines and true firs were involved in 6 of every 10 incidents involving property damage, and in 9 of every 10...

[Application of damage control concept in severe limbs fractures combining with multiple trauma].

PubMed

Bayin, Er-gu-le; Jin, Hong-bing; Li, Ming

2015-09-01

To discuss the application and clinical effect of damage control concept in the treatment of severe limbs fractures combining with multiple trauma. From July 2009 to July 2012, 30 patients with severe limbs fractures combining with multiple trauma were treated with the damage control concept, included 20 males and 10 females with an average age of (34.03 ± 12.81) years old ranging from 20 to 60 years old; the ISS averaged (35.00 ± 12.81) points (ranged from 26 to 54 points). And the control group also contained 30 patients with severe limbs fractures combining with multiple trauma treated by the traditional operation from June 2006 to June 2009, there were 23 males and 7 females with an average age of (34.23 ± 11.04) years old ranging from 18 to 65 years old. The ISS averaged (35.56 ± 11.04) points (ranged from 26 to 51 points). The age, gender, ISS, Gustilo classification, operation time, intraoperative blood loss, blood transfusion,postoperative complications and mortality rate were observed and compared. In the damage control concept group,there were 28 cases surviving and 2 cases (6.7%) death; 6 cases of postoperative complication included 2 cases of adult respiratory distress syndrome, 1 case of multiple organ failure, 1 case of disseminated intravascular coagulation and 2 cases of wound infection. In the control group, there were 22 cases surviving and 8 cases death(26.7%); 13 cases of postoperative complication included 4 cases of adult respiratory distress syndrome,2 cases of multiple organ failure, 2 cases of disseminated intravascular coagulation and 3 cases of wound infection. There were no statistically significant differences between two groups in age, gender, ISS, Gustilo classfication and complication (P > 0.05), however there were statistically significant differences in mortality rate, operation time, blodd loss, blodd transfusion between two groups (P < 0.05). Damage control concept is used to treat severe limbs fractures combining with multiple trauma which has the rapid and effective therapy, can improve survival rate and reduce complication.

Multivalent peptidic linker enables identification of preferred sites of conjugation for a potent thialanstatin antibody drug conjugate.

PubMed

Puthenveetil, Sujiet; He, Haiyin; Loganzo, Frank; Musto, Sylvia; Teske, Jesse; Green, Michael; Tan, Xingzhi; Hosselet, Christine; Lucas, Judy; Tumey, L Nathan; Sapra, Puja; Subramanyam, Chakrapani; O'Donnell, Christopher J; Graziani, Edmund I

2017-01-01

Antibody drug conjugates (ADCs) are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads beyond the mictotubule inhibitors and DNA damaging agents has led us to the recent discovery of an mRNA splicing inhibitor, thailanstatin, as a potent ADC payload. In our previous work, we observed that the potency of this payload was uniquely tied to the method of conjugation, with lysine conjugates showing much superior potency as compared to cysteine conjugates. However, the ADC field is rapidly shifting towards site-specific ADCs due to their advantages in manufacturability, characterization and safety. In this work we report the identification of a highly efficacious site-specific thailanstatin ADC. The site of conjugation played a critical role on both the in vitro and in vivo potency of these ADCs. During the course of this study, we developed a novel methodology of loading a single site with multiple payloads using an in situ generated multi-drug carrying peptidic linker that allowed us to rapidly screen for optimal conjugation sites. Using this methodology, we were able to identify a double-cysteine mutant ADC delivering four-loaded thailanstatin that was very efficacious in a gastric cancer xenograft model at 3mg/kg and was also shown to be efficacious against T-DM1 resistant and MDR1 overexpressing tumor cell lines.

Fukunaga-Koontz feature transformation for statistical structural damage detection and hierarchical neuro-fuzzy damage localisation

NASA Astrophysics Data System (ADS)

Hoell, Simon; Omenzetter, Piotr

2017-07-01

Considering jointly damage sensitive features (DSFs) of signals recorded by multiple sensors, applying advanced transformations to these DSFs and assessing systematically their contribution to damage detectability and localisation can significantly enhance the performance of structural health monitoring systems. This philosophy is explored here for partial autocorrelation coefficients (PACCs) of acceleration responses. They are interrogated with the help of the linear discriminant analysis based on the Fukunaga-Koontz transformation using datasets of the healthy and selected reference damage states. Then, a simple but efficient fast forward selection procedure is applied to rank the DSF components with respect to statistical distance measures specialised for either damage detection or localisation. For the damage detection task, the optimal feature subsets are identified based on the statistical hypothesis testing. For damage localisation, a hierarchical neuro-fuzzy tool is developed that uses the DSF ranking to establish its own optimal architecture. The proposed approaches are evaluated experimentally on data from non-destructively simulated damage in a laboratory scale wind turbine blade. The results support our claim of being able to enhance damage detectability and localisation performance by transforming and optimally selecting DSFs. It is demonstrated that the optimally selected PACCs from multiple sensors or their Fukunaga-Koontz transformed versions can not only improve the detectability of damage via statistical hypothesis testing but also increase the accuracy of damage localisation when used as inputs into a hierarchical neuro-fuzzy network. Furthermore, the computational effort of employing these advanced soft computing models for damage localisation can be significantly reduced by using transformed DSFs.

Nerve fiber layer (NFL) degeneration associated with acute q-switched laser exposure in the nonhuman primate

NASA Astrophysics Data System (ADS)

Zwick, Harry; Zuclich, Joseph A.; Stuck, Bruce E.; Gagliano, Donald A.; Lund, David J.; Glickman, Randolph D.

1995-01-01

We have evaluated acute laser retinal exposure in non-human primates using a Rodenstock scanning laser ophthalmoscope (SLO) equipped with spectral imaging laser sources at 488, 514, 633, and 780 nm. Confocal spectral imaging at each laser wavelength allowed evaluation of the image plane from deep within the retinal vascular layer to the more superficial nerve fiber layer in the presence and absence of the short wavelength absorption of the macular pigment. SLO angiography included both fluorescein and indocyanine green procedures to assess the extent of damage to the sensory retina, the retinal pigment epithelium (RPE), and the choroidal vasculature. All laser exposures in this experiment were from a Q-switched Neodymium laser source at an exposure level sufficient to produce vitreous hemorrhage. Confocal imaging of the nerve fiber layer revealed discrete optic nerve sector defects between the lesion site and the macula (retrograde degeneration) as well as between the lesion site and the optic disk (Wallerian degeneration). In multiple hemorrhagic exposures, lesions placed progressively distant from the macula or overlapping the macula formed bridging scars visible at deep retinal levels. Angiography revealed blood flow disturbance at the retina as well as at the choroidal vascular level. These data suggest that acute parafoveal laser retinal injury can involve both direct full thickness damage to the sensory and non-sensory retina and remote nerve fiber degeneration. Such injury has serious functional implications for both central and peripheral visual function.

Analysis of a Memory Device Failure

NASA Technical Reports Server (NTRS)

Nicolas, David P.; Devaney, John; Gores, Mark; Dicken, Howard

1998-01-01

The recent failure of a vintage memory device presented a unique challenge to failure analysts. Normally device layouts, fabrication parameters and other technical information were available to assist the analyst in the analysis. However, this device was out of production for many years and the manufacturer was no longer in business, so the information was not available. To further complicate this analysis, the package leads were all but removed making additional electrical testing difficult. Under these conditions, new and innovative methods were used to analyze the failure. The external visual exam, radiography, PIND, and leak testing were performed with nominal results. Since electrical testing was precluded by the short lead lengths, the device was delidded to expose the internal structures for microscopic examination. No failure mechanism was identified. The available electrical data suggested an ESD or low level EOS type mechanism which left no visible surface damage. Due to parallel electrical paths, electrical probing on the chip failed to locate the failure site. Two non-destructive Scanning Electron Microscopy techniques, CIVA (Charge Induced Voltage Alteration) and EBIC (Electron Beam Induced Current), and a liquid crystal decoration technique which detects localized heating were employed to aid in the analysis. CIVA and EBIC isolated two faults in the input circuitry, and the liquid crystal technique further localized two hot spots in regions on two input gates. Removal of the glassivation and metallization revealed multiple failure sites located in the gate oxide of two input transistors suggesting machine (testing) induced damage.

Synthesis and binding properties of new selective ligands for the nucleobase opposite the AP site.

PubMed

Abe, Yukiko; Nakagawa, Osamu; Yamaguchi, Rie; Sasaki, Shigeki

2012-06-01

DNA is continuously damaged by endogenous and exogenous factors such as oxidative stress or DNA alkylating agents. These damaged nucleobases are removed by DNA N-glycosylase and form apurinic/apyrimidinic sites (AP sites) as intermediates in the base excision repair (BER) pathway. AP sites are also representative DNA damages formed by spontaneous hydrolysis. The AP sites block DNA polymerase and a mismatch nucleobase is inserted opposite the AP sites by polymerization to cause acute toxicities and mutations. Thus, AP site specific compounds have attracted much attention for therapeutic and diagnostic purposes. In this study, we have developed nucleobase-polyamine conjugates as the AP site binding ligand by expecting that the nucleobase part would play a role in the specific recognition of the nucleobase opposite the AP site by the Watson-Crick base pair formation and that the polyamine part should contribute to the access of the ligand to the AP site by a non-specific interaction to the DNA phosphate backbone. The nucleobase conjugated with 3,3'-diaminodipropylamine (A-ligand, G-ligand, C-ligand, T-ligand and U-ligand) showed a specific stabilization of the duplex containing the AP site depending on the complementary combination with the nucleobase opposite the AP site; that is A-ligand to T, G-ligand to C, C-ligand to G, T- and U-ligand to A. The thermodynamic binding parameters clearly indicated that the specific stabilization is due to specific binding of the ligands to the complementary AP site. These results have suggested that the complementary base pairs of the Watson-Crick type are formed at the AP site. Copyright © 2012 Elsevier Ltd. All rights reserved.

Seasonal Liza aurata tissue-specific DNA integrity in a multi-contaminated coastal lagoon (Ria de Aveiro, Portugal).

PubMed

Oliveira, M; Maria, V L; Ahmad, I; Pacheco, M; Santos, M A

2010-10-01

In this study, the DNA integrity of golden grey mullet (Liza aurata) collected in differently contaminated sites of a coastal lagoon, Ria de Aveiro (Portugal), was assessed, over the period of 1 year, using the DNA alkaline unwinding assay, in four different tissues (gill, kidney, liver and blood) and compared to a reference site. The four tissues displayed different DNA integrity basal levels, clearly affected by seasonal factors. Gill and kidney were, respectively, the most and least sensitive tissues. All sites demonstrated the capacity to interfere with DNA integrity. The sites displaying the highest and lowest DNA damage capability were, respectively, Barra (subject to naval traffic) and Vagos (contaminated with polycyclic aromatic hydrocarbons). In terms of seasonal variability, autumn seems to be the more critical season (more DNA damage) unlike summer when no DNA damage was found in any tissue. Data recommend the continued monitoring of this aquatic system. Copyright © 2010 Elsevier Ltd. All rights reserved.

Characteristics of Fault Zones in Volcanic Rocks Near Yucca Flat, Nevada Test Site, Nevada

USGS Publications Warehouse

Sweetkind, Donald S.; Drake II, Ronald M.

2007-01-01

During 2005 and 2006, the USGS conducted geological studies of fault zones at surface outcrops at the Nevada Test Site. The objectives of these studies were to characterize fault geometry, identify the presence of fault splays, and understand the width and internal architecture of fault zones. Geologic investigations were conducted at surface exposures in upland areas adjacent to Yucca Flat, a basin in the northeastern part of the Nevada Test Site; these data serve as control points for the interpretation of the subsurface data collected at Yucca Flat by other USGS scientists. Fault zones in volcanic rocks near Yucca Flat differ in character and width as a result of differences in the degree of welding and alteration of the protolith, and amount of fault offset. Fault-related damage zones tend to scale with fault offset; damage zones associated with large-offset faults (>100 m) are many tens of meters wide, whereas damage zones associated with smaller-offset faults are generally a only a meter or two wide. Zeolitically-altered tuff develops moderate-sized damage zones whereas vitric nonwelded, bedded and airfall tuff have very minor damage zones, often consisting of the fault zone itself as a deformation band, with minor fault effect to the surrounding rock mass. These differences in fault geometry and fault zone architecture in surface analog sites can serve as a guide toward interpretation of high-resolution subsurface geophysical results from Yucca Flat.

Recent Advances in Composite Damage Mechanics

NASA Technical Reports Server (NTRS)

Reifsnider, Ken; Case, Scott; Iyengar, Nirmal

1996-01-01

The state of the art and recent developments in the field of composite material damage mechanics are reviewed, with emphasis on damage accumulation. The kinetics of damage accumulation are considered with emphasis on the general accumulation of discrete local damage events such as single or multiple fiber fractures or microcrack formation. The issues addressed include: how to define strength in the presence of widely distributed damage, and how to combine mechanical representations in order to predict the damage tolerance and life of engineering components. It is shown that a damage mechanics approach can be related to the thermodynamics of the damage accumulation processes in composite laminates subjected to mechanical loading and environmental conditions over long periods of time.

Protected areas mitigate diseases of reef-building corals by reducing damage from fishing.

PubMed

Lamb, Joleah B; Williamson, David H; Russ, Garry R; Willis, Bette L

2015-09-01

Parks and protected areas have been instrumental in reducing anthropogenic sources of damage in terrestrial and aquatic environments. Pathogen invasion often succeeds physical wounding and injury, yet links between the reduction of damage and the moderation of disease have not been assessed. Here, we examine the utility of no-take marine reserves as tools for mitigating diseases that affect reef-building corals. We found that sites located within reserves had fourfold reductions in coral disease prevalence compared to non-reserve sites (80466 corals surveyed). Of 31 explanatory variables assessed, coral damage and the abundance of derelict fishing line best explained differences in disease assemblages between reserves and non-reserves. Unexpectedly, we recorded significantly higher levels of disease, coral damage, and derelict fishing line in non-reserves with fishing gear restrictions than in those without gear restrictions. Fishers targeting stocks perceived to be less depleted, coupled with enhanced site access from immediately adjacent boat moorings, may explain these unexpected patterns. Significant correlations between the distance from mooring sites and prevalence values for a ciliate disease known to infest wounded tissue (r = -0.65), coral damage (r = -0.64), and the abundance of derelict fishing line (r = -0.85) corroborate this interpretation. This is the first study to link disease with recreational use intensity in a park, emphasizing the need to evaluate the placement of closures and their direct relationship to ecosystem health. Since corals are modular, ecological processes that govern reproductive and competitive fitness are frequently related to colony surface area therefore, even low levels of cumulative tissue loss from progressing diseases pose significant threats to reef coral persistence. Disease mitigation through reductions in physical injury in areas where human activities are concentrated is another mechanism by which protected areas may improve ecosystem resilience in a changing climate.

Ataxia telangiectasia mutated (ATM) interacts with p400 ATPase for an efficient DNA damage response.

PubMed

Smith, Rebecca J; Savoian, Matthew S; Weber, Lauren E; Park, Jeong Hyeon

2016-11-04

Ataxia telangiectasia mutated (ATM) and TRRAP proteins belong to the phosphatidylinositol 3-kinase-related kinase family and are involved in DNA damage repair and chromatin remodeling. ATM is a checkpoint kinase that is recruited to sites of DNA double-strand breaks where it phosphorylates a diverse range of proteins that are part of the chromatin and DNA repair machinery. As an integral subunit of the TRRAP-TIP60 complexes, p400 ATPase is a chromatin remodeler that is also targeted to DNA double-strand break sites. While it is understood that DNA binding transcriptional activators recruit p400 ATPase into a regulatory region of the promoter, how p400 recognises and moves to DNA double-strand break sites is far less clear. Here we investigate a possibility whether ATM serves as a shuttle to deliver p400 to break sites. Our data indicate that p400 co-immunoprecipitates with ATM independently of DNA damage state and that the N-terminal domain of p400 is vital for this interaction. Heterologous expression studies using Sf9 cells revealed that the ATM-p400 complex can be reconstituted without other mammalian bridging proteins. Overexpression of ATM-interacting p400 regions in U2OS cells induced dominant negative effects including the inhibition of both DNA damage repair and cell proliferation. Consistent with the dominant negative effect, the stable expression of an N-terminal p400 fragment showed a decrease in the association of p400 with ATM, but did not alter the association of p400 with TRRAP. Taken together, our findings suggest that a protein-protein interaction between ATM and p400 ATPase occurs independently of DNA damage and contributes to efficient DNA damage response and repair.

Posttranslational Regulation of Human DNA Polymerase ι.

PubMed

McIntyre, Justyna; McLenigan, Mary P; Frank, Ekaterina G; Dai, Xiaoxia; Yang, Wei; Wang, Yinsheng; Woodgate, Roger

2015-11-06

Human DNA polymerases (pols) η and ι are Y-family DNA polymerase paralogs that facilitate translesion synthesis past damaged DNA. Both polη and polι can be monoubiquitinated in vivo. Polη has been shown to be ubiquitinated at one primary site. When this site is unavailable, three nearby lysines may become ubiquitinated. In contrast, mass spectrometry analysis of monoubiquitinated polι revealed that it is ubiquitinated at over 27 unique sites. Many of these sites are localized in different functional domains of the protein, including the catalytic polymerase domain, the proliferating cell nuclear antigen-interacting region, the Rev1-interacting region, and its ubiquitin binding motifs UBM1 and UBM2. Polι monoubiquitination remains unchanged after cells are exposed to DNA-damaging agents such as UV light (generating UV photoproducts), ethyl methanesulfonate (generating alkylation damage), mitomycin C (generating interstrand cross-links), or potassium bromate (generating direct oxidative DNA damage). However, when exposed to naphthoquinones, such as menadione and plumbagin, which cause indirect oxidative damage through mitochondrial dysfunction, polι becomes transiently polyubiquitinated via Lys(11)- and Lys(48)-linked chains of ubiquitin and subsequently targeted for degradation. Polyubiquitination does not occur as a direct result of the perturbation of the redox cycle as no polyubiquitination was observed after treatment with rotenone or antimycin A, which both inhibit mitochondrial electron transport. Interestingly, polyubiquitination was observed after the inhibition of the lysine acetyltransferase KATB3/p300. We hypothesize that the formation of polyubiquitination chains attached to polι occurs via the interplay between lysine acetylation and ubiquitination of ubiquitin itself at Lys(11) and Lys(48) rather than oxidative damage per se. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Quantifying Damage at Multiple Loading Rates to Kevlar KM2 Fibers Due to Weaving and Finishing

DTIC Science & Technology

2013-06-01

ARL-TR-6465 June 2013 Approved for public release; distribution is unlimited. NOTICES...ARL-TR-6465 June 2013 Quantifying Damage at Multiple Loading Rates to Kevlar KM2 Fibers Due to Weaving and Finishing Brett D. Sanborn...OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) June 2013 2. REPORT TYPE Final 3. DATES

Inactivating UBE2M impacts the DNA damage response and genome integrity involving multiple cullin ligases.

PubMed

Cukras, Scott; Morffy, Nicholas; Ohn, Takbum; Kee, Younghoon

2014-01-01

Protein neddylation is involved in a wide variety of cellular processes. Here we show that the DNA damage response is perturbed in cells inactivated with an E2 Nedd8 conjugating enzyme UBE2M, measured by RAD51 foci formation kinetics and cell based DNA repair assays. UBE2M knockdown increases DNA breakages and cellular sensitivity to DNA damaging agents, further suggesting heightened genomic instability and defective DNA repair activity. Investigating the downstream Cullin targets of UBE2M revealed that silencing of Cullin 1, 2, and 4 ligases incurred significant DNA damage. In particular, UBE2M knockdown, or defective neddylation of Cullin 2, leads to a blockade in the G1 to S progression and is associated with delayed S-phase dependent DNA damage response. Cullin 4 inactivation leads to an aberrantly high DNA damage response that is associated with increased DNA breakages and sensitivity of cells to DNA damaging agents, suggesting a DNA repair defect is associated. siRNA interrogation of key Cullin substrates show that CDT1, p21, and Claspin are involved in elevated DNA damage in the UBE2M knockdown cells. Therefore, UBE2M is required to maintain genome integrity by activating multiple Cullin ligases throughout the cell cycle.

Plasma membrane repair and cellular damage control: the annexin survival kit.

PubMed

Draeger, Annette; Monastyrskaya, Katia; Babiychuk, Eduard B

2011-03-15

Plasmalemmal injury is a frequent event in the life of a cell. Physical disruption of the plasma membrane is common in cells that operate under conditions of mechanical stress. The permeability barrier can also be breached by chemical means: pathogens gain access to host cells by secreting pore-forming toxins and phospholipases, and the host's own immune system employs pore-forming proteins to eliminate both pathogens and the pathogen-invaded cells. In all cases, the influx of extracellular Ca(2+) is being sensed and interpreted as an "immediate danger" signal. Various Ca(2+)-dependent mechanisms are employed to enable plasma membrane repair. Extensively damaged regions of the plasma membrane can be patched with internal membranes delivered to the cell surface by exocytosis. Nucleated cells are capable of resealing their injured plasmalemma by endocytosis of the permeabilized site. Likewise, the shedding of membrane microparticles is thought to be involved in the physical elimination of pores. Membrane blebbing is a further damage-control mechanism, which is triggered after initial attempts at plasmalemmal resealing have failed. The members of the annexin protein family are ubiquitously expressed and function as intracellular Ca(2+) sensors. Most cells contain multiple annexins, which interact with distinct plasma membrane regions promoting membrane segregation, membrane fusion and--in combination with their individual Ca(2+)-sensitivity--allow spatially confined, graded responses to membrane injury. Copyright © 2011 Elsevier Inc. All rights reserved.

Development of small scale cell culture models for screening poloxamer 188 lot-to-lot variation.

PubMed

Peng, Haofan; Hall, Kaitlyn M; Clayton, Blake; Wiltberger, Kelly; Hu, Weiwei; Hughes, Erik; Kane, John; Ney, Rachel; Ryll, Thomas

2014-01-01

Shear protectants such as poloxamer 188 play a critical role in protecting cells during cell culture bioprocessing. Lot-to-lot variation of poloxamer 188 was experienced during a routine technology transfer across sites of similar scale and equipment. Cell culture medium containing a specific poloxamer 188 lot resulted in an unusual drop in cell growth, viability, and titer during manufacturing runs. After switching poloxamer lots, culture performance returned to the expected level. In order to control the quality of poloxamer 188 and thus maintain better consistency in manufacturing, multiple small scale screening models were developed. Initially, a 5L bioreactor model was established to evaluate cell damage by high sparge rates with different poloxamer 188 lots. Subsequently, a more robust, simple, and efficient baffled shake flask model was developed. The baffled shake flask model can be performed in a high throughput manner to investigate the cell damage in a bubbling environment. The main cause of the poor performance was the loss of protection, rather than toxicity. It was also suggested that suspicious lots can be identified using different cell line and media. The screening methods provide easy, yet remarkable models for understanding and controlling cell damage due to raw material lot variation as well as studying the interaction between poloxamer 188 and cells. © 2014 American Institute of Chemical Engineers.

Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy-relevant energies down to stopping

PubMed Central

Friedland, W.; Schmitt, E.; Kundrát, P.; Dingfelder, M.; Baiocco, G.; Barbieri, S.; Ottolenghi, A.

2017-01-01

Track structures and resulting DNA damage in human cells have been simulated for hydrogen, helium, carbon, nitrogen, oxygen and neon ions with 0.25–256 MeV/u energy. The needed ion interaction cross sections have been scaled from those of hydrogen; Barkas scaling formula has been refined, extending its applicability down to about 10 keV/u, and validated against established stopping power data. Linear energy transfer (LET) has been scored from energy deposits in a cell nucleus; for very low-energy ions, it has been defined locally within thin slabs. The simulations show that protons and helium ions induce more DNA damage than heavier ions do at the same LET. With increasing LET, less DNA strand breaks are formed per unit dose, but due to their clustering the yields of double-strand breaks (DSB) increase, up to saturation around 300 keV/μm. Also individual DSB tend to cluster; DSB clusters peak around 500 keV/μm, while DSB multiplicities per cluster steadily increase with LET. Remarkably similar to patterns known from cell survival studies, LET-dependencies with pronounced maxima around 100–200 keV/μm occur on nanometre scale for sites that contain one or more DSB, and on micrometre scale for megabasepair-sized DNA fragments. PMID:28345622

Spatial dependence and correlation of rainfall in the Danube catchment and its role in flood risk assessment.

NASA Astrophysics Data System (ADS)

Martina, M. L. V.; Vitolo, R.; Todini, E.; Stephenson, D. B.; Cook, I. M.

2009-04-01

The possibility that multiple catastrophic events occur within a given timespan and affect the same portfolio of insured properties may induce enhanced risk. For this reason, in the insurance industry it is of interest to characterise not only the point probability of catastrophic events, but also their spatial structure. As far as floods are concerned it is important to determine the probability of having multiple simultaneous events in different parts of the same basin: in this case, indeed, the loss in a portfolio can be significantly different. Understanding the spatial structure of the precipitation field is a necessary step for the proper modelling of the spatial dependence and correlation of river discharge. Several stochastic models are available in the scientific literature for the multi-site generation of precipitation. Although most models achieve good performance in modelling mean values, temporal variability and inter-site dependence of extremes are still delicate issues. In this work we aim at identifying the main spatial characteristics of the precipitation structure and then at analysing them in a real case. We consider data from a large network of raingauges in the Danube catchment. This catchment is a good example of a large-scale catchment where the spatial correlation of flood events can radically change the effect in term of flood damage.

Pathways of Metabolite-related Damage to A Synthetic p53 Gene Exon 7 Oligonucleotide using Magnetic Enzyme Bioreactor Beads and LC-MS/MS Sequencing.

PubMed

Malla, Spundana; Kadimisetty, Karteek; Jiang, Di; Choudhary, Dharamainder; Rusling, James F

2018-05-11

Reactive metabolites of environmental chemicals and drugs can cause site-specific damage to p53 tumor suppressor gene in a major pathway for genotoxicity. We report here a high throughput, cell-free, 96-well plate magnetic bead-enzyme system interfaced with LC-MS/MS sequencing to bioactivate test chemicals and identify resulting adduction sites on genes. Bioactivated aflatoxin B1 was reacted with a 32 bp exon 7 fragment of the p53 gene using 8 microsomal cyt P450 enzymes from different organs coated on magnetic beads. All cyt P450s converted aflatoxin B1 to aflatoxin B1-8,9-epoxide that adducts guanine (G) in codon 249, with subsequent depurination to give abasic sites, then strand breaks. This is the first demonstration in a cell-free medium that aflatoxin B1 metabolite selectively causes abasic site formation and strand breaks at codon 249 of the p53 probe, corresponding to the chemical pathway and mutations of p53 in human liver cells and tumors. Molecular modeling supports the view that binding of aflatoxin B1-8,9-epoxide to G in codon 249 precedes the SN2 adduction reaction. Among a range of metabolic enzymes characteristic of different organs, human liver microsomes and cyt P450 3A5 supersomes showed the highest bioactivation rate for p53 exon 7 damage. This method to identify metabolite-related gene damage sites may facilitate predictions of organ-specific cancers for test chemicals via correlations with mutation sites.

Characterization of a genotoxicity biomarker in three-spined stickleback (Gasterosteus aculeatus L.): Biotic variability and integration in a battery of biomarkers for environmental monitoring.

PubMed

Santos, Raphael; Joyeux, Aude; Palluel, Olivier; Palos-Ladeiro, Mélissa; Besnard, Aurélien; Blanchard, Christophe; Porcher, Jean Marc; Bony, Sylvie; Devaux, Alain; Sanchez, Wilfried

2016-04-01

As a large array of hazardous substances exhibiting genotoxicity are discharged into surface water, this work aimed at assessing the relevance of adding a genotoxicity biomarker in a battery of biomarkers recently developed in the model fish three-spined stickleback (Gasterosteus aculeatus). First the confounding influence of gender, body length, and season (used as a proxy of age and of the fish reproductive status, respectively) on the level of primary DNA damage in erythrocytes was investigated in wild sticklebacks. Then, the genotoxity biomarker was included in a large battery of biomarkers assessing xenobiotic biotransformation, oxidative stress and neurotoxicity, and implemented in five sites. Gender, age and reproductive status did not influence DNA damage level in fish from the reference site. A significant relationship between the level of primary DNA damage and fish length (as a proxy of age also correlated to the season) was highlighted in the contaminated site. Among all biomarkers investigated in the field, the level of DNA damage was one of the four most discriminating biomarkers with EROD, catalase activity and the level of lipid peroxidation representing together 75.40% of the discriminating power in sampled fish. The level of DNA damage was correlated to the EROD activity and to the level of peroxidation, which mainly discriminated fish from sites under urban pressure. Finally, Integrated Biomarker Response indexes (IBRv2), which were calculated with the whole biomarker response dataset exhibited higher values in the Reveillon (9.62), the Scarpe and Rhonelle contaminated sites (5.11 and 4.90) compared with the two reference sites (2.38 and 2.55). The present work highlights that integration of a genotoxicity biomarker in a multiparametric approach is relevant to assess ecotoxicological risk in freshwater aquatic organisms. © 2014 Wiley Periodicals, Inc.

Amorphous Carbon-Boron Nitride Nanotube Hybrids

NASA Technical Reports Server (NTRS)

Kim, Jae Woo (Inventor); Siochi, Emilie J. (Inventor); Wise, Kristopher E. (Inventor); Lin, Yi (Inventor); Connell, John (Inventor)

2016-01-01

A method for joining or repairing boron nitride nanotubes (BNNTs). In joining BNNTs, the nanotube structure is modified with amorphous carbon deposited by controlled electron beam irradiation to form well bonded hybrid a-C/BNNT structures. In repairing BNNTs, the damaged site of the nanotube structure is modified with amorphous carbon deposited by controlled electron beam irradiation to form well bonded hybrid a-C/BNNT structures at the damage site.

Comparative efficacy of storage bags, storability and damage potential of bruchid beetle.

PubMed

Harish, G; Nataraja, M V; Ajay, B C; Holajjer, Prasanna; Savaliya, S D; Gedia, M V

2014-12-01

Groundnut during storage is attacked by number of stored grain pests and management of these insect pests particularly bruchid beetle, Caryedon serratus (Oliver) is of prime importance as they directly damage the pod and kernels. In this regard different storage bags that could be used and duration up to which we can store groundnut has been studied. Super grain bag recorded minimum number of eggs laid and less damage and minimum weight loss in pods and kernels in comparison to other storage bags. Analysis of variance for multiple regression models were found to be significant in all bags for variables viz, number of eggs laid, damage in pods and kernels, weight loss in pods and kernels throughout the season. Multiple comparison results showed that there was a high probability of eggs laid and pod damage in lino bag, fertilizer bag and gunny bag, whereas super grain bag was found to be more effective in managing the C. serratus owing to very low air circulation.

Fatigue damage assessment of high-usage in-service aircraft fuselage structure

NASA Astrophysics Data System (ADS)

Mosinyi, Bao Rasebolai

As the commercial and military aircraft fleets continue to age, there is a growing concern that multiple-site damage (MSD) can compromise structural integrity. Multiple site damage is the simultaneous occurrence of many small cracks at independent structural locations, and is the natural result of fatigue, corrosion, fretting and other possible damage mechanisms. These MSD cracks may linkup and form a fatigue lead crack of critical length. The presence of MSD also reduces the structure's ability to withstand longer cracks. The objective of the current study is to assess, both experimentally and analytically, MSD formation and growth in the lap joint of curved panels removed from a retired aircraft. A Boeing 727-232 airplane owned and operated by Delta Air Lines, and retired at its design service goal, was selected for the study. Two panels removed from the left-hand side of the fuselage crown, near stringer 4L, were subjected to extended fatigue testing using the Full-Scale Aircraft Structural Test Evaluation and Research (FASTER) facility located at the Federal Aviation Administration (FAA) William J. Hughes Technical Center. The state of MSD was continuously assessed using several nondestructive inspection (NDI) methods. Damage to the load attachment points of the first panel resulted in termination of the fatigue test at 43,500 fatigue cycles, before cracks had developed in the lap joint. The fatigue test for the second panel was initially conducted under simulated in-service loading conditions for 120,000 cycles, and no cracks were detected in the skin of the panel test section. Artificial damage was then introduced into the panel at selected rivets in the critical (lower) rivet row, and the fatigue loads were increased. Visually detectable crack growth from the artificial notches was first seen after 133,000 cycles. The resulting lead crack grew along the lower rivet row, eventually forming an 11.8" long unstable crack after 141,771 cycles, at which point the test was terminated. Posttest fractograpic examinations of the crack surfaces were conducted, revealing the presence of subsurface MSD at the critical rivet row of the lap joint. Special attention was also given to the stringer clips that attach the fuselage frames to the stringers, since they also experienced cracking during the fatigue tests. The performance of the different conventional and emerging NDI methods was also assessed, and some of the emerging NDI methods were quite effective in detecting and measuring the length of subsurface cracks. Delta Air Lines conducted a separate destructive investigation on the state of damage along the right-hand side of the fuselage, near stringer 4R. A comparison of these two studies showed that the lap joint on the left hand-side of the aircraft, along stringer 4L, had better fatigue life than the one on the opposite side, along stringer 4R. The cause of the difference in fatigue life was investigated by close examination of the rivet installation qualities, and was found to be a result of better rivet installation along the lap joint at stringer 4L. Finite element models for both the skin and substructures of the panels were developed and geometrically nonlinear finite element analyses were conducted to verify the loading conditions and to determine near-field parameters governing MSD initiation and growth. Fatigue crack growth predictions based on the NASGRO equation were in good agreement with the experimental crack growth data for through-the-thickness cracks. For subsurface cracks, simulation of crack growth was found to correlate better with fractography data when an empirical crack growth model was used. The results of the study contribute to the understanding of the initiation and growth of MSD in the inner skin layer of a lap joint, and provide valuable data for the evaluation and validation of analytical methodologies to predict MSD initiation and growth and a better understanding on the effect of manufacturing quality on damage accumulation along the lap joint.

Three-Dimensional Characterization and Modeling of Microstructural Weak Links for Spall Damage in FCC Metals

DOE PAGES

Krishnan, Kapil; Brown, Andrew; Wayne, Leda; ...

2014-11-25

Local microstructural weak links for spall damage were investigated using three-dimensional (3-D) characterization in multicrystalline copper samples (grain size ≈ 450 µm) shocked with laser-driven plates at low pressures (2 to 4 GPa). The thickness of samples and flyer plates, approximately 1000 and 500 µm respectively, led to short pressure pulses that allowed isolating microstructure effects on local damage characteristics. Electron Backscattering Diffraction and optical microscopy were used to relate the presence, size, and shape of porosity to local microstructure. The experiments were complemented with 3-D finite element simulations of individual grain boundaries (GBs) that resulted in large damage volumesmore » using crystal plasticity coupled with a void nucleation and growth model. Results from analysis of these damage sites show that the presence of a GB-affected zone, where strain concentration occurs next to a GB, correlates strongly with damage localization at these sites, most likely due to the inability of maintaining strain compatibility across these interfaces, with additional effects due to the inclination of the GB with respect to the shock. Results indicate that strain compatibility plays an important role on intergranular spall damage in metallic materials.« less

PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry.

PubMed

Maréchal, Alexandre; Li, Ju-Mei; Ji, Xiao Ye; Wu, Ching-Shyi; Yazinski, Stephanie A; Nguyen, Hai Dang; Liu, Shizhou; Jiménez, Amanda E; Jin, Jianping; Zou, Lee

2014-01-23

PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). Although the role for PRP19 in splicing is well characterized, its role in the DDR remains elusive. Through a proteomic screen for proteins that interact with RPA-coated single-stranded DNA (RPA-ssDNA), we identified PRP19 as a sensor of DNA damage. PRP19 directly binds RPA and localizes to DNA damage sites via RPA, promoting RPA ubiquitylation in a DNA-damage-induced manner. PRP19 facilitates the accumulation of ATRIP, the regulatory partner of the ataxia telangiectasia mutated and Rad3-related (ATR) kinase, at DNA damage sites. Depletion of PRP19 compromised the phosphorylation of ATR substrates, recovery of stalled replication forks, and progression of replication forks on damaged DNA. Importantly, PRP19 mutants that cannot bind RPA or function as an E3 ligase failed to support the ATR response, revealing that PRP19 drives ATR activation by acting as an RPA-ssDNA-sensing ubiquitin ligase during the DDR. Copyright © 2014 Elsevier Inc. All rights reserved.

Can forest trees compensate for stress-generated growth losses by induced production of volatile compounds?

PubMed

Holopainen, Jarmo K

2011-12-01

Plants produce a variety of volatile organic compounds (VOCs). Under abiotic and biotic stresses, the number and amount of produced compounds can increase. Due to their long life span and large size, trees can produce biogenic VOCs (BVOCs) in much higher amounts than many other plants. It has been suggested that at cellular and tree physiological levels, induced production of VOCs is aimed at improving plant resistance to damage by reactive oxygen species generated by multiple abiotic stresses. In the few reported cases when biosynthesis of plant volatiles is inhibited or enhanced, the observed response to stress can be attributed to plant volatiles. Reported increase, e.g., in photosynthesis has mostly ranged between 5 and 50%. A comprehensive model to explain similar induction of VOCs under multiple biotic stresses is not yet available. As a result of pathogen or herbivore attack on forest trees, the induced production of VOCs is localized to the damage site but systemic induction of emissions has also been detected. These volatiles can affect fungal pathogens and the arrival rate of herbivorous insects on damaged trees, but also act as signalling compounds to maintain the trophic cascades that may improve tree fitness by improved efficiency of herbivore natural enemies. On the forest scale, biotic induction of VOC synthesis and release leads to an amplified flow of BVOCs in atmospheric reactions, which in atmospheres rich in oxides of nitrogen (NOx) results in ozone formation, and in low NOx atmospheres results in oxidation of VOCs, removal in ozone from the troposphere and the resulting formation of biogenic secondary organic aerosol (SOA) particles. I will summarize recent advances in the understanding of stress-induced VOC emissions from trees, with special focus on Populus spp. Particular importance is given to the ecological and atmospheric feedback systems based on BVOCs and biogenic SOA formation.

Monitoring of self-healing composites: a nonlinear ultrasound approach

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

Demonstrating damage tolerance of composite airframes

NASA Technical Reports Server (NTRS)

Poe, Clarence C., Jr.

1993-01-01

Commercial transport aircraft operating in the United States are certified by the Federal Aviation Authority to be damage tolerant. On 28 April 1988, Aloha Airlines Flight 243, a Boeing 727-200 airplane, suffered an explosive decompression of the fuselage but landed safely. This event provides very strong justification for the damage tolerant design criteria. The likely cause of the explosive decompression was the linkup of numerous small fatigue cracks that initiated at adjacent fastener holes in the lap splice joint at the side of the body. Actually, the design should have limited the damage size to less than two frame spacings (about 40 inches), but this type of 'multi-site damage' was not originally taken into account. This cracking pattern developed only in the high-time airplanes (many flights). After discovery in the fleet, a stringent inspection program using eddy current techniques was inaugurated to discover these cracks before they linked up. Because of concerns about safety and the maintenance burden, the lap-splice joints of these high-time airplanes are being modified to remove cracks and prevent new cracking; newer designs account for 'multi-site damage'.

Imaging San Jacinto Fault damage zone structure using dense linear arrays: application of ambient noise tomography, Rayleigh wave ellipticity, and site amplification

NASA Astrophysics Data System (ADS)

Wang, Y.; Lin, F. C.; Allam, A. A.; Ben-Zion, Y.

2017-12-01

The San Jacinto fault is presently the most seismically active component of the San Andreas Transform system in Southern California. To study the damage zone structure, two dense linear geophone arrays (BS and RR) were deployed across the Clark segment of the San Jacinto Fault between Anza and Hemet during winter 2015 and Fall 2016, respectively. Both arrays were 2 km long with 20 m station spacing. Month-long three-component ambient seismic noise data were recorded and used to calculate multi-channel cross-correlation functions. All three-component noise records of each array were normalized simultaneously to retain relative amplitude information between different stations and different components. We observed clear Rayleigh waves and Love waves on the cross-correlations of both arrays at 0.3 - 1 s period. The phase travel times of the Rayleigh waves on both arrays were measured by frequency-time analysis (FTAN), and inverted for Rayleigh wave phase velocity profiles of the upper 500 m depth. For both arrays, we observe prominent asymmetric low velocity zones which narrow with depth. At the BS array near the Hemet Stepover, an approximately 250m wide slow zone is observed to be offset by 75m to the northeast of the surface fault trace. At the RR array near the Anza segment of the fault, a similar low velocity zone width and offset are observed, along with a 10% across-fault velocity contrast. Analyses of Rayleigh wave ellipticity (H/V ratio), Love wave phase travel times, and site amplification are in progress. By using multiple measurements from ambient noise cross-correlations, we can obtain strong constraints on the local damage zone structure of the San Jacinto Fault. The results contribute to improved understanding of rupture directivity, maximum earthquake magnitude and more generally seismic hazard associated with the San Jacinto fault zone.

Genetics Home Reference: UV-sensitive syndrome

MedlinePlus

... damaged, the enzyme that carries out gene transcription (RNA polymerase) gets stuck, and the process stalls. Researchers ... the CSB, CSA, and UVSSA proteins help remove RNA polymerase from the damaged site, so the DNA ...

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.

DNA damage in cells exhibiting radiation-induced genomic instability

DOE PAGES

Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

2015-02-22

Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesismore » that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.« less

Protective effects of buckwheat honey on DNA damage induced by hydroxyl radicals.

PubMed

Zhou, Juan; Li, Peng; Cheng, Ni; Gao, Hui; Wang, Bini; Wei, Yahui; Cao, Wei

2012-08-01

To understand the antioxidant properties of buckwheat honeys, we investigated their antioxidant effects on hydroxyl radical-induced DNA breaks in the non-site-specific and site-specific systems, the physicochemical properties, antioxidant activities (1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical scavenging activity, chelating, and reducing power assays), total phenolic content and individual phenolic acids were also determined. Total phenolic content of buckwheat honeys ranged from 774 to 1694 mg PA/kg, and p-hydroxybenzoic and p-coumaric acids proved to be the main components in buckwheat honeys. All the buckwheat honey samples possess stronger capability to protect DNA in the non-site-specific systems than in the site-specific systems from being damaged by hydroxyl radicals. In the non-site-specific and site-specific system, buckwheat honeys samples prevented ()OH-induced DNA breaks by 21-78% and 5-31% over control value, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Systemic Prenatal Insults Disrupt Telencephalon Development

PubMed Central

Robinson, Shenandoah

2006-01-01

Infants born prematurely are prone to chronic neurologic deficits including cerebral palsy (CP), epilepsy, cognitive delay, behavioral problems, and neurosensory impairments. In affected children, imaging and neuropathological findings demonstrate significant damage to white matter. The extent of cortical damage has been less obvious. Advances in the understanding of telencephalon development provide insights into how systemic intrauterine insults affect the developing white matter, subplate and cortex, and lead to multiple neurologic impairments. In addition to white matter oligodendrocytes and axons, other elements at risk for perinatal brain injury include subplate neurons, GABAergic neurons migrating through white matter and subplate, and afferents of maturing neurotransmitter systems. Common insults including hypoxia-ischemia and infection often affect the developing brain differently than the mature brain, and insults precipitate a cascade of damage to multiple neural lineages. Insights from development can identify potential targets for therapies to repair the damaged neonatal brain before it has matured. PMID:16061421

ILF2 Is a Regulator of RNA Splicing and DNA Damage Response in 1q21-Amplified Multiple Myeloma.

PubMed

Marchesini, Matteo; Ogoti, Yamini; Fiorini, Elena; Aktas Samur, Anil; Nezi, Luigi; D'Anca, Marianna; Storti, Paola; Samur, Mehmet Kemal; Ganan-Gomez, Irene; Fulciniti, Maria Teresa; Mistry, Nipun; Jiang, Shan; Bao, Naran; Marchica, Valentina; Neri, Antonino; Bueso-Ramos, Carlos; Wu, Chang-Jiun; Zhang, Li; Liang, Han; Peng, Xinxin; Giuliani, Nicola; Draetta, Giulio; Clise-Dwyer, Karen; Kantarjian, Hagop; Munshi, Nikhil; Orlowski, Robert; Garcia-Manero, Guillermo; DePinho, Ronald A; Colla, Simona

2017-07-10

Amplification of 1q21 occurs in approximately 30% of de novo and 70% of relapsed multiple myeloma (MM) and is correlated with disease progression and drug resistance. Here, we provide evidence that the 1q21 amplification-driven overexpression of ILF2 in MM promotes tolerance of genomic instability and drives resistance to DNA-damaging agents. Mechanistically, elevated ILF2 expression exerts resistance to genotoxic agents by modulating YB-1 nuclear localization and interaction with the splicing factor U2AF65, which promotes mRNA processing and the stabilization of transcripts involved in homologous recombination in response to DNA damage. The intimate link between 1q21-amplified ILF2 and the regulation of RNA splicing of DNA repair genes may be exploited to optimize the use of DNA-damaging agents in patients with high-risk MM. Copyright © 2017 Elsevier Inc. All rights reserved.

Public health impact of the 1992 Los Angeles civil unrest.

PubMed Central

Evans, C A

1993-01-01

The Los Angeles civil unrest in April 1992 stunned the nation. The days of violence resulted in 53 deaths, 2,325 reported injuries, more than 600 buildings completely destroyed by fire, and approximately $735 million in total damages. The purpose of this paper is to give an overview of the activities of the Public Health Programs and Services Branch of the Los Angeles County Department of Health Services during and after the civil unrest and to illustrate the types of public health issues and problems that may result from large-scale civil disturbance. Public health agencies and jurisdictions should consider these issues in their disaster planning. Public Health Programs and Services Branch activities were directly affected by the violence and destruction. Women, Infants and Children Program vouchering sites and 20 drug program and alcohol recovery sites were damaged or burned and 15 county health centers closed during the unrest. At least 38 private medical and dental offices and 45 pharmacies were destroyed or damaged. County health authorities offered facilities to house relocated private care providers and filled prescriptions for medications where needed. The environmental health impact required the inspection of 2,827 burned and damaged sites for hazardous waste including asbestos; at 9 percent of the inspected sites, waste required special disposal. More than 1,000 food facilities suffered damage and required inspection before reopening. In the 3 months following the unrest, a 20-percent increase in disposal capacity was authorized at four county landfills to accommodate the disposal of debris. Violence was a public health issue of particular concern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8497562

Community-level destruction of hard corals by the sea urchin Diadema setosum.

PubMed

Qiu, Jian-Wen; Lau, Dickey C C; Cheang, Chi-chiu; Chow, Wing-kuen

2014-08-30

Sea urchins are common herbivores and bioeroders of coral ecosystems, but rarely have they been reported as corallivores. We determined the spatial pattern of hard coral damage due to corallivory and bioerosion by the sea urchin Diadema setosum Leske in Hong Kong waters. Coral damage was common at the northeastern sites, with 23.7 - 90.3% colonies being either collapsed or severely damaged with >25% tissue loss. Many genera of corals were impacted by the sea urchin but the damage was most obvious for the structure forming genus Platygyra. The percentage of severely damaged and collapsed coral had significant positive correlation with the abundance of D. setosum, which ranged from 0.01 to 5.2 individuals per coral head or 0.1 - 21.1 individuals m(-2) across the study sites. Remedial management actions such as sea urchin removal are urgently needed to save these fringing coral communities. Copyright © 2013 Elsevier Ltd. All rights reserved.

Under What Assumptions Do Site-by-Treatment Instruments Identify Average Causal Effects?

ERIC Educational Resources Information Center

Reardon, Sean F.; Raudenbush, Stephen W.

2011-01-01

The purpose of this paper is to clarify the assumptions that must be met if this--multiple site, multiple mediator--strategy, hereafter referred to as "MSMM," is to identify the average causal effects (ATE) in the populations of interest. The authors' investigation of the assumptions of the multiple-mediator, multiple-site IV model demonstrates…

Inhibition of exportin-1 function results in rapid cell cycle-associated DNA damage in cancer cells

PubMed Central

Burke, Russell T.; Marcus, Joshua M.; Orth, James D.

2017-01-01

Selective inhibitors of nuclear export (SINE) are small molecules in development as anti-cancer agents. The first-in-class SINE, selinexor, is in clinical trials for blood and solid cancers. Selinexor forms a covalent bond with exportin-1 at cysteine-528, and blocks its ability to export cargos. Previous work has shown strong cell cycle effects and drug-induced cell death across many different cancer-derived cell lines. Here, we report strong cell cycle-associated DNA double-stranded break formation upon the treatment of cancer cells with SINE. In multiple cell models, selinexor treatment results in the formation of clustered DNA damage foci in 30-40% of cells within 8 hours that is dependent upon cysteine-528. DNA damage strongly correlates with G1/S-phase and decreased DNA replication. Live cell microscopy reveals an association between DNA damage and cell fate. Cells that form damage in G1-phase more often die or arrest, while those damaged in S/G2-phase frequently progress to cell division. Up to half of all treated cells form damage foci, and most cells that die after being damaged, were damaged in G1-phase. By comparison, non-transformed cell lines show strong cell cycle effects but little DNA damage and less death than cancer cells. Significant drug combination effects occur when selinexor is paired with different classes of agents that either cause DNA damage or that diminish DNA damage repair. These data present a novel effect of exportin-1 inhibition and provide a strong rationale for multiple combination treatments of selinexor with agents that are currently in use for the treatment of different solid cancers. PMID:28467801

Boulder damage symposium annual thin film laser damage competition

DOE PAGES

Stolz, Christopher J.

2012-11-28

Optical instruments and laser systems are often fluence-limited by multilayer thin films deposited on the optical surfaces. When comparing publications within the laser damage literature, there can be confusing and conflicting laser damage results. This is due to differences in testing protocols between research groups studying very different applications. In this series of competitions, samples from multiple vendors are compared under identical testing parameters and a single testing service. Unlike a typical study where a hypothesis is tested within a well-controlled experiment with isolated variables, this competition isolates the laser damage testing variables so that trends can be observed betweenmore » different deposition processes, coating materials, cleaning techniques, and multiple coating suppliers. The resulting series of damage competitions has also been designed to observe general trends of damage morphologies and mechanisms over a wide range of coating types (high reflector and antireflector), wavelengths (193 to 1064 nm), and pulse lengths (180 fs to 13 ns). A double blind test assured sample and submitter anonymity were used in each of the competitions so only a summary of the deposition process, coating materials, layer count and spectral results are presented. Laser resistance was strongly affected by substrate cleaning, coating deposition method, and coating material selection whereas layer count and spectral properties had minimal impact.« less

Cell-based therapeutic strategies for multiple sclerosis

PubMed Central

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A; Atkins, Harold; Banwell, Brenda; Bar-Or, Amit; Bebo, Bruce; Bowen, James; Burt, Richard; Calabresi, Peter; Cohen, Jeffrey; Comi, Giancarlo; Connick, Peter; Cross, Anne; Cutter, Gary; Derfuss, Tobias; Ffrench-Constant, Charles; Freedman, Mark; Galipeau, Jacques; Goldman, Myla; Goldman, Steven; Goodman, Andrew; Green, Ari; Griffith, Linda; Hartung, Hans-Peter; Hemmer, Bernhard; Hyun, Insoo; Iacobaeus, Ellen; Inglese, Matilde; Jubelt, Burk; Karussis, Dimitrios; Küry, Patrick; Landsman, Douglas; Laule, Cornelia; Liblau, Roland; Mancardi, Giovanni; Ann Marrie, Ruth; Miller, Aaron; Miller, Robert; Miller, David; Mowry, Ellen; Muraro, Paolo; Nash, Richard; Ontaneda, Daniel; Pasquini, Marcelo; Pelletier, Daniel; Peruzzotti-Jametti, Luca; Pluchino, Stefano; Racke, Michael; Reingold, Stephen; Rice, Claire; Ringdén, Olle; Rovira, Alex; Saccardi, Riccardo; Sadiq, Saud; Sarantopoulos, Stefanie; Savitz, Sean; Scolding, Neil; Soelberg Sorensen, Per; Pia Sormani, Maria; Stuve, Olaf; Tesar, Paul; Thompson, Alan; Trojano, Maria; Uccelli, Antonio; Uitdehaag, Bernard; Utz, Ursula; Vukusic, Sandra; Waubant, Emmanuelle; Wilkins, Alastair

2017-01-01

Abstract The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. PMID:29053779

Seven Years of Recording from Monkey Cortex with a Chronically Implanted Multiple Microelectrode

PubMed Central

Krüger, Jürgen; Caruana, Fausto; Volta, Riccardo Dalla; Rizzolatti, Giacomo

2010-01-01

A brush of 64 microwires was chronically implanted in the ventral premotor cortex of a macaque monkey. Contrary to common approaches, the wires were inserted from the white matter side. This approach, by avoiding mechanical pressure on the dura and pia mater during penetration, disturbed only minimally the cortical recording site. With this approach isolated potentials and multiunit activity were recorded for more than 7 years in about one-third of electrodes. The indirect insertion method also provided an excellent stability within each recording session, and in some cases even allowed recording from the same neurons for several years. Histological examination of the implanted brain region shows only a very marginal damage to the recording area. Advantages and problems related to long-term recording are discussed. PMID:20577628

[Fascioliasis case in the patient with hepatitis A].

PubMed

Kvitashvili, M A; Dvali, Sh A; Kokaia, I Zh

2005-03-01

There is some portion of patients with clinically manifested acute viral hepatitis, which are seronegative to hepatitis A markers. They have to be differentiated with other patients with B, C, D hepatitis, mechanical jaundice, etc. Such clinical cases make physician to recall the parasitic diseases, such as fascioliasis, which affects hepatobiliary system, causes prolongation of cholestasis and dystrophic changes in the biliary tract and likely to cause liver cirrhosis. In the presented case the initial diagnosis was severe acute Hepatitis A (anti-HAV IgM+), though the peripheral blood examination showed moderate eosinophilia, ultrasound investigation revealed multiple sites of damage in the liver, which made us to consider fascioliasis, the latter was confirmed by the serological analysis. Appropriate medical treatment was effective and the state of the patient has improved.

Comparison of in situ measurements of forest decline symptoms in Vermont (USA) and the Schwarzwald (FRG)

NASA Technical Reports Server (NTRS)

Rock, B. N.; Hoshizaki, T.; Lichtenthaler, H.; Schmuck, G.

1986-01-01

Field analyses were conducted at spruce/fir sites in the U.S. and Germany undergoing forest decline. Data gathered from common branch samples included reflectance curves, fluorescence measurements, and pigment concentrations. Similar reflectance signatures are seen for specimens from all sites. Reflectance spectra from specimens collected from high damage sites in both countries show a characteristic reflectance drop in the near infrared and a shift (5 nm) of the red edge to shorter wavelengths. Fluorescence data suggest altered state of health of photosynthetic pigments only in specimens from German high damage sites, and pigment extraction and analysis indicate a reduction in total chlorophyll, a decrease in chlorophyll b when compared with chlorophyll a, and a relative increase in carotenoids.

Genotoxicity in Atlantic killifish (Fundulus heteroclitus) from a PAH-contaminated Superfund site on the Elizabeth River, Virginia.

PubMed

Jung, Dawoon; Matson, Cole W; Collins, Leonard B; Laban, Geoff; Stapleton, Heather M; Bickham, John W; Swenberg, James A; Di Giulio, Richard T

2011-11-01

The Atlantic Wood Industries Superfund site (AWI) on the Elizabeth River in Portsmouth, VA is heavily contaminated with polycyclic aromatic hydrocarbons (PAHs) from a wood treatment facility. Atlantic killifish, or mummichog (Fundulus heteroclitus), at this Superfund site are exposed to very high concentrations of several carcinogens. In this study, we measured PAH concentrations in both fish tissues and sediments. Concurrently, we assessed different aspects of genotoxicity in the killifish exposed in situ. Both sediment and tissue PAH levels were significantly higher in AWI samples, relative to a reference site, but the chemistry profile was different between sediments and tissues. Killifish at AWI exhibited higher levels of DNA damage compared to reference fish, as measured via the flow cytometric method (FCM), and the damage was consistent with sediment PAH concentrations. Covalent binding of benzo[a]pyrene (BaP) metabolites to DNA, as measured via LC-MS/MS adduct detection methods, were also elevated and could be partially responsible for the DNA damage. Using similar LC-MS/MS methods, we found no evidence that oxidative DNA adducts had a role in observed genotoxicity.

Relationships between common forest metrics and realized impacts of Hurricane Katrina on forest resources in Mississippi

Treesearch

Sonja N. Oswalt; Christopher M. Oswalt

2008-01-01

This paper compares and contrasts hurricane-related damage recorded across the Mississippi landscape in the 2 years following Katrina with initial damage assessments based on modeled parameters by the USDA Forest Service. Logistic and multiple regressions are used to evaluate the influence of stand characteristics on tree damage probability. Specifically, this paper...

Brain and Cognitive-Behavioural Development after Asphyxia at Term Birth

ERIC Educational Resources Information Center

de Haan, Michelle; Wyatt, John S.; Roth, Simon; Vargha-Khadem, Faraneh; Gadian, David; Mishkin, Mortimer

2006-01-01

Perinatal asphyxia occurs in approximately 1-6 per 1000 live full-term births. Different patterns of brain damage can result, though the relation of these patterns to long-term cognitive-behavioural outcome remains under investigation. The hippocampus is one brain region that can be damaged (typically not in isolation), and this site of damage has…

Herbivory and climate interact serially to control monoterpene emissions from pinyon pine forests.

PubMed

Trowbridge, Amy M; Daly, Ryan W; Helmig, Detlev; Stoy, Paul C; Monson, Russell K

2014-06-01

The emission of volatile monoterpenes from coniferous trees impacts the oxidative state of the troposphere and multi-trophic signaling between plants and animals. Previous laboratory studies have revealed that climate anomalies and herbivory alter the rate of tree monoterpene emissions. However, no studies to date have been conducted to test these relations in situ. We conducted a two-year field experiment at two semiarid sites dominated by pinyon pine (Pinus edulis) during outbreaks of a specialist herbivore, the southwestern tiger moth (Lophocampa ingens: Arctiidae). We discovered that during the early spring, when herbivory rates were highest, monoterpene emission rates were approximately two to six times higher from undamaged needles on damaged trees, with this increase in emissions due to alpha-pinene, beta-pinene, and camphene at both sites. During mid-summer, emission rates did not differ between previously damaged and undamaged trees at the site on the Western Slope of the Rocky Mountains, but rather tracked changes in the temperature and precipitation regime characteristic of the region. As the mid-summer drought progressed at the Eastern Slope site, emission rates were low, but differences between previously damaged and undamaged trees were not statistically significant. Despite no difference in emissions, mid-summer tissue monoterpene concentrations were significantly lower in previously damaged trees at both sites. With the onset of monsoon rains during late summer, emission rates from previously damaged trees increased to levels higher than those of undamaged trees despite the lack of herbivory. We conclude that (1) herbivory systemically increases the flux of terpenes to the atmosphere during the spring, (2) drought overrides the effect of past herbivory as the primary control over emissions during the mid-summer, and (3) a release from drought and the onset of late-summer rains is correlated with a secondary increase in emissions, particularly from herbivore-damaged trees, possibly due to a drought-delayed stimulation of induced monoterpene synthesis and/or increases in stomatal conductance. A greater understanding of the interactive effects of seasonality and herbivory on monoterpene emissions provides much needed information regarding the atmospheric and ecological consequences that these compounds will have for semiarid ecosystems.

Evidence for Ancient Mesoamerican Earthquakes

NASA Astrophysics Data System (ADS)

Kovach, R. L.; Garcia, B.

2001-12-01

Evidence for past earthquake damage at Mesoamerican ruins is often overlooked because of the invasive effects of tropical vegetation and is usually not considered as a casual factor when restoration and reconstruction of many archaeological sites are undertaken. Yet the proximity of many ruins to zones of seismic activity would argue otherwise. Clues as to the types of damage which should be soughtwere offered in September 1999 when the M = 7.5 Oaxaca earthquake struck the ruins of Monte Alban, Mexico, where archaeological renovations were underway. More than 20 structures were damaged, 5 of them seriously. Damage features noted were walls out of plumb, fractures in walls, floors, basal platforms and tableros, toppling of columns, and deformation, settling and tumbling of walls. A Modified Mercalli Intensity of VII (ground accelerations 18-34 %b) occurred at the site. Within the diffuse landward extension of the Caribbean plate boundary zone M = 7+ earthquakes occur with repeat times of hundreds of years arguing that many Maya sites were subjected to earthquakes. Damage to re-erected and reinforced stelae, walls, and buildings were witnessed at Quirigua, Guatemala, during an expedition underway when then 1976 M = 7.5 Guatemala earthquake on the Motagua fault struck. Excavations also revealed evidence (domestic pttery vessels and skeleton of a child crushed under fallen walls) of an ancient earthquake occurring about the teim of the demise and abandonment of Quirigua in the late 9th century. Striking evidence for sudden earthquake building collapse at the end of the Mayan Classic Period ~A.D. 889 was found at Benque Viejo (Xunantunich), Belize, located 210 north of Quirigua. It is argued that a M = 7.5 to 7.9 earthquake at the end of the Maya Classic period centered in the vicinity of the Chixoy-Polochic and Motagua fault zones cound have produced the contemporaneous earthquake damage to the above sites. As a consequences this earthquake may have accelerated the collapse of the hiearchical authority at these locations and may have contributed to the end of the Classic culture at other nearby sites in proximity to the Caribbean plate boundary zone.

Combined adaptive multiple subtraction based on optimized event tracing and extended wiener filtering

NASA Astrophysics Data System (ADS)

Tan, Jun; Song, Peng; Li, Jinshan; Wang, Lei; Zhong, Mengxuan; Zhang, Xiaobo

2017-06-01

The surface-related multiple elimination (SRME) method is based on feedback formulation and has become one of the most preferred multiple suppression methods used. However, some differences are apparent between the predicted multiples and those in the source seismic records, which may result in conventional adaptive multiple subtraction methods being barely able to effectively suppress multiples in actual production. This paper introduces a combined adaptive multiple attenuation method based on the optimized event tracing technique and extended Wiener filtering. The method firstly uses multiple records predicted by SRME to generate a multiple velocity spectrum, then separates the original record to an approximate primary record and an approximate multiple record by applying the optimized event tracing method and short-time window FK filtering method. After applying the extended Wiener filtering method, residual multiples in the approximate primary record can then be eliminated and the damaged primary can be restored from the approximate multiple record. This method combines the advantages of multiple elimination based on the optimized event tracing method and the extended Wiener filtering technique. It is an ideal method for suppressing typical hyperbolic and other types of multiples, with the advantage of minimizing damage of the primary. Synthetic and field data tests show that this method produces better multiple elimination results than the traditional multi-channel Wiener filter method and is more suitable for multiple elimination in complicated geological areas.

Replication of damaged DNA in vitro is blocked by p53

PubMed Central

Zhou, Jianmin; Prives, Carol

2003-01-01

The tumor suppressor protein p53 may have other roles and functions in addition to its well-documented ability to serve as a sequence-specific transcriptional activator in response to DNA damage. We showed previously that p53 can block the replication of polyomavirus origin-containing DNA (Py ori-DNA) in vitro when p53 binding sites are present on the late side of the Py ori. Here we have both further extended these observations and have also examined whether p53 might be able to bind directly to and inhibit the replication of damaged DNA. We found that p53 strongly inhibits replication of γ-irradiated Py ori-DNA and such inhibition requires both the central DNA binding domain and the extreme C-terminus of the p53 protein. An endogenous p53 binding site lies within the Py origin and is required for the ability of p53 to block initiation of replication from γ-irradiated Py ori-DNA, suggesting the possibility of DNA looping caused by p53 binding both non-specifically to sites of DNA damage and specifically to the endogenous site in the polyomavirus origin. Our results thus suggest the possibility that under some circumstances p53 might serve as a direct regulator of DNA replication and suggest as well an additional function for cooperation between its two autonomous DNA binding domains. PMID:12853603

Bioinformatic prediction and in vivo validation of residue-residue interactions in human proteins

NASA Astrophysics Data System (ADS)

Jordan, Daniel; Davis, Erica; Katsanis, Nicholas; Sunyaev, Shamil

2014-03-01

Identifying residue-residue interactions in protein molecules is important for understanding both protein structure and function in the context of evolutionary dynamics and medical genetics. Such interactions can be difficult to predict using existing empirical or physical potentials, especially when residues are far from each other in sequence space. Using a multiple sequence alignment of 46 diverse vertebrate species we explore the space of allowed sequences for orthologous protein families. Amino acid changes that are known to damage protein function allow us to identify specific changes that are likely to have interacting partners. We fit the parameters of the continuous-time Markov process used in the alignment to conclude that these interactions are primarily pairwise, rather than higher order. Candidates for sites under pairwise epistasis are predicted, which can then be tested by experiment. We report the results of an initial round of in vivo experiments in a zebrafish model that verify the presence of multiple pairwise interactions predicted by our model. These experimentally validated interactions are novel, distant in sequence, and are not readily explained by known biochemical or biophysical features.

15 CFR 921.33 - Boundary changes, amendments to the management plan, and addition of multiple-site components.

Code of Federal Regulations, 2010 CFR

2010-01-01

... management plan, and addition of multiple-site components. 921.33 Section 921.33 Commerce and Foreign Trade... management plan, and addition of multiple-site components. (a) Changes in the boundary of a Reserve and major... management plan shall address goals and objectives for all components of the multi-site Reserve and the...

[Operative treatment strategies for multiple trauma patients : early total care versus damage control].

PubMed

Klüter, T; Lippross, S; Oestern, S; Weuster, M; Seekamp, A

2013-09-01

The treatment of multiple trauma patients is a great challenge for an interdisciplinary team. After preclinical care and subsequent treatment in the emergency room the order of the interventions is prioritized depending of the individual risk stratification. For planning the surgery management it is essential to distinguish between absolutely essential operations to prevent life-threatening situations for the patient and interventions with shiftable indications, depending on the general condition of the patient. All interventions need to be done without causing significant secondary damage to prohibit hyperinflammation and systemic inflammatory response syndrome. The challenge consists in determination of the appropriate treatment at the right point in time. In general the early primary intervention, early total care, is differentiated from the damage control concept.

Non-covalent Interactions with SUMO and Ubiquitin Orchestrate Distinct Functions of the SLX4 Complex in Genome Maintenance

PubMed Central

Ouyang, Jian; Garner, Elizabeth; Hallet, Alexander; Nguyen, Hai Dang; Rickman, Kimberly A.; Gill, Grace; Smogorzewska, Agata; Zou, Lee

2014-01-01

SLX4, a coordinator of multiple DNA structure-specific endonucleases, is important for several DNA repair pathways. Non-covalent interactions of SLX4 with ubiquitin are required for localizing SLX4 to DNA-interstrand crosslinks (ICLs), yet how SLX4 is targeted to other functional contexts remains unclear. Here, we show that SLX4 binds SUMO-2/3 chains via SUMO-interacting motifs (SIMs). The SIMs of SLX4 are dispensable for ICL repair, but important for processing CPT-induced replication intermediates, suppressing fragile site instability, and localizing SLX4 to ALT telomeres. The localization of SLX4 to laser-induced DNA damage also requires the SIMs, as well as DNA-end resection, UBC9 and MDC1. Furthermore, the SUMO binding of SLX4 enhances its interaction with specific DNA-damage sensors or telomere-binding proteins, including RPA, MRE11-RAD50-NBS1 and TRF2. Thus, the interactions of SLX4 with SUMO and ubiquitin increase its affinity for factors recognizing different DNA lesions or telomeres, helping to direct the SLX4 complex in distinct functional contexts. PMID:25533185

Tributyltin promoted hepatic steatosis in zebrafish (Danio rerio) and the molecular pathogenesis involved.

PubMed

Zhang, Jiliang; Sun, Ping; Kong, Tao; Yang, Fan; Guan, Wenchao

2016-01-01

Endocrine disruptor effects of tributyltin (TBT) are well established in fish. However, the adverse effects on lipid metabolism are less well understood. Since the liver is the predominant site of de novo synthesis of lipids, the present study uses zebrafish (Danio rerio) to examine lipid accumulation in the livers and hepatic gene expression associated with lipid metabolism pathways. After exposure for 90 days, we found that the livers in fish exposed to TBT were yellowish in appearance and with accumulation of lipid droplet, which is consistent with the specific pathological features of steatosis. Molecular analysis revealed that TBT induced hepatic steatosis by increasing the gene expression associated with lipid transport, lipid storage, lipiogenic enzymes and lipiogenic factors in the livers. Moreover, TBT enhanced hepatic caspase-3 activity and up-regulated genes related to apoptosis and cell-death, which indicated steatotic livers of fish exposed to TBT and the subsequent liver damage were likely due to accelerated hepatocyte apoptosis or cell stress. In short, TBT can produce multiple and complex alterations in transcriptional activity of lipid metabolism and cell damage, which provides potential molecular evidence of TBT on hepatic steatosis. Copyright © 2015 Elsevier B.V. All rights reserved.

Protein oxidation and peroxidation

PubMed Central

Davies, Michael J.

2016-01-01

Proteins are major targets for radicals and two-electron oxidants in biological systems due to their abundance and high rate constants for reaction. With highly reactive radicals damage occurs at multiple side-chain and backbone sites. Less reactive species show greater selectivity with regard to the residues targeted and their spatial location. Modification can result in increased side-chain hydrophilicity, side-chain and backbone fragmentation, aggregation via covalent cross-linking or hydrophobic interactions, protein unfolding and altered conformation, altered interactions with biological partners and modified turnover. In the presence of O2, high yields of peroxyl radicals and peroxides (protein peroxidation) are formed; the latter account for up to 70% of the initial oxidant flux. Protein peroxides can oxidize both proteins and other targets. One-electron reduction results in additional radicals and chain reactions with alcohols and carbonyls as major products; the latter are commonly used markers of protein damage. Direct oxidation of cysteine (and less commonly) methionine residues is a major reaction; this is typically faster than with H2O2, and results in altered protein activity and function. Unlike H2O2, which is rapidly removed by protective enzymes, protein peroxides are only slowly removed, and catabolism is a major fate. Although turnover of modified proteins by proteasomal and lysosomal enzymes, and other proteases (e.g. mitochondrial Lon), can be efficient, protein hydroperoxides inhibit these pathways and this may contribute to the accumulation of modified proteins in cells. Available evidence supports an association between protein oxidation and multiple human pathologies, but whether this link is causal remains to be established. PMID:27026395

Gastrointestinal damage caused by swallowing multiple magnets.

PubMed

Liu, Shiqi; Li, Jianhui; Lv, Yi

2012-09-01

Swallowing multiple magnets is not uncommon worldwide and it frequently leads to serious consequences. However, most patients fail to receive timely and correct diagnosis and treatment. A literature search was performed to establish an algorithm for these accidents by the authors to identify relevant articles published from June 1987 to October 2010 in Google, Medline, ISI Web of Knowledge Ovid, CNKI, Korea Med and library document delivery, using search terms "magnet ingestion, " "fistula," and "perforation." A total of 149 patients with ingestion of magnetic foreign bodies from 20 countries and areas were identified. 22 of them were companioned with neurological and psychiatric disorders. Swallowing magnets occurred throughout childhood and adolescent, mostly ranging 2 to 4 years in age. Various gastrointestinal damages such as necrosis and intestinal perforation or fistula were encountered. Damage from swallowing multiple magnets carries a significant risk of morbidity and even mortality throughout childhood to adolescent worldwide. Older children and adults with neurological and psychiatric problems may be at high risk for such accidents. Early intervention is crucial.

Antioxidant responses versus DNA damage and lipid peroxidation in golden grey mullet liver: a field study at Ria de Aveiro (Portugal).

PubMed

Oliveira, M; Ahmad, I; Maria, V L; Pacheco, M; Santos, M A

2010-10-01

The present work aimed to investigate golden grey mullet (Liza aurata) liver protection versus damage responses at a polluted coastal lagoon, Ria de Aveiro (Portugal), as a tool to evaluate the human impacts on environmental health at five critical sites in Ria de Aveiro (Portugal) in comparison to a reference site (Torreira; TOR). Protection was evaluated by measuring non-enzymatic [total glutathione (GSHt) and non-protein thiols (NPT)] and enzymatic [catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR)] antioxidant defenses. Damage was assessed as DNA integrity loss and lipid peroxidation (LPO). No significant differences were found between sites in terms of non-enzymatic defenses (GSHt and NPT). CAT did not display significant differences among sites. However, GPx at Barra (BAR, associated with naval traffic), Gafanha (GAF, harbor and dry-dock activities area), Laranjo (LAR, metal contaminated associated with chlor-alkali plant), and Vagos (VAG, contaminated by polycyclic aromatic hydrocarbons) was significantly lower than the reference site. GST was lower at GAF, Rio Novo do Príncipe (RIO, pulp mill effluent area), LAR, and VAG, whereas GR was lower at RIO. The loss of antioxidant defenses was paralleled by higher LPO levels only at GAF and VAG. However, no DNA integrity loss was found. Results highlight the importance of the adopted multibiomarkers as applied in the liver of L. aurata in coastal water pollution monitoring. The integration of liver antioxidant defense and damage responses can improve the aquatic contamination assessment.

Infiltration performance of engineered surfaces commonly used for distributed stormwater management

NASA Astrophysics Data System (ADS)

Valinski, Nicholas A.

Engineered porous media are commonly used in low impact development (LID) structures to mitigate excess stormwater in urban environments. Differences in infiltrability of these LID systems arise from the wide variety of materials used to create porous surfaces and subsequent maintenance, debris loading, and physical damage. In this study, infiltration capacity of six common materials was tested by multiple replicate experiments with automated mini-disk infiltrometers. The tested materials included porous asphalt, porous concrete, porous brick pavers, flexible porous pavement, engineered soils, and native soils. Porous asphalt, large porous brick pavers, and curb cutout rain gardens showed the greatest infiltration rates. Most engineered porous pavements and soils performed better than the native silt loam soils. Infiltration performance was found to be related more to site design and environmental factors than material choice. Sediment trap zones in both pavements and engineered soil rain gardens were found to be beneficial to the whole site performance. Winter chloride application had a large negative impact on poured in place concrete, making it a poor choice for heavily salted areas.

Water quality of a coastal lagoon (ES, Brazil): abiotic aspects, cytogenetic damage, and phytoplankton dynamics.

PubMed

Duarte, Ian Drumond; Silva, Nayara Heloisa Vieira Fraga; da Costa Souza, Iara; de Oliveira, Larissa Bassani; Rocha, Lívia Dorsch; Morozesk, Mariana; Bonomo, Marina Marques; de Almeida Pereira, Thaís; Dias, Mauro Cesar; de Oliveira Fernandes, Valéria; Matsumoto, Silvia Tamie

2017-04-01

Assessment of water resources requires interdisciplinary studies that include multiple ecosystem aspects. This study evaluated the water quality of Juara Lagoon (ES, Brazil) based on physical and chemical variables, cytogenetic responses in Allium cepa and phytoplankton dynamics. Three sampling sites were defined and water samples were collected during two sampling periods. Analyses such as determination of photic zone, conductivity, and concentrations of nutrients and metals were conducted as well as cytotoxic, mutagenic, and genotoxic potentials using A. cepa test. The main attributes of phytoplankton community, such as total richness, total density, density by class, dominance, and diversity, were also evaluated. Results have revealed that Juara Lagoon has signs of artificial eutrophication at two sampling sites due to high levels of total phosphorus and ammonia nitrogen. Cytotoxic, genotoxic, and mutagenic potentials were detected as well as high concentrations of Fe and Mn. Furthermore, 165 phytoplankton taxa were recorded, with highest richness in Chlorophyceae and Cyanophyceae classes. In addition, Cyanophyceae presented as the highest density class. A. cepa test and phytoplankton community evaluation indicated that the ecological quality of Juara Lagoon is compromised.

Infiltration performance of engineered surfaces commonly used for distributed stormwater management.

PubMed

Valinski, N A; Chandler, D G

2015-09-01

Engineered porous media are commonly used in low impact development (LID) structures to mitigate excess stormwater in urban environments. Differences in infiltrability of these LID systems arise from the wide variety of materials used to create porous surfaces and subsequent maintenance, debris loading, and physical damage. In this study, the infiltration capacity of six common materials was tested by multiple replicate experiments with automated mini-disk infiltrometers. The tested materials included porous asphalt, porous concrete, porous brick pavers, flexible porous pavement, engineered soils, and native soils. Porous asphalt, large porous brick pavers, and curb cutout rain gardens showed the greatest infiltration rates. Most engineered porous pavements and soils performed better than the native silt loam soils. Infiltration performance was found to be related more to site design and environmental factors than material choice. Sediment trap zones in both pavements and engineered soil rain gardens were found to be beneficial to the whole site performance. Winter chloride application had a large negative impact on poured in place concrete, making it a poor choice for heavily salted areas. Copyright © 2015 Elsevier Ltd. All rights reserved.

STS-114: Discovery Day 6 Post MMT Meeting

NASA Technical Reports Server (NTRS)

2005-01-01

Wane Hill, Deputy Manager of the Space Shuttle Program, and Steve Poulos, Manager, Orbiter Project Office discussed damage assessments caused during ascent. Steve further detailed the damage analysis and assessments with chart presentation of composite tile damage and gap filler sites evaluation, protruding ceramic shim, left wing tile damage, comparisons of ground test results versus FD5 focused inspection, and the window 1 blanket. Gap fillers, the STS-73, thermal protection, temperature range, heating and heating range, aerodynamics, aerothermodynamics, risk, foam damage, tile adhesions, and extravehicular activities are topics covered with the News media.

355 nm and 1064 nm-pulse mixing to identify the laser-induced damage mechanisms in KDP

NASA Astrophysics Data System (ADS)

Reyné, Stéphane; Duchateau, Guillaume; Natoli, Jean-Yves; Lamaignère, Laurent

2011-02-01

Nanosecond laser-induced damage (LID) in potassium dihydrogen phosphate (KH2PO4 or KDP) remains an issue for light-frequency converters in large-aperture lasers such as NIF (National Ignition Facility, in USA) LMJ (Laser MegaJoule, in France). In the final optic assembly, converters are simultaneously illuminated by multiple wavelengths during the frequency conversion. In this configuration, the damage resistance of the KDP crystals becomes a crucial problem and has to be improved. In this study, we propose a refined investigation about the LID mechanisms involved in the case of a multiple wavelengths combination. Experiments based on an original pump-pump set-up have been carried out in the nanosecond regime on a KDP crystal. In particular, the impact of a simultaneous mixing of 355 nm and 1064 nm pulses has been experimentally studied and compared to a model based on heat transfer, the Mie theory and a Drude model. This study sheds light on the physical processes implied in the KDP laser damage. In particular, a three-photon ionization mechanism is shown to be responsible for laser damage in KDP.

Quantification of Residual Stress from Photonic Signatures of Fused Silica

NASA Technical Reports Server (NTRS)

Cramer, K. Elliott; Hayward, Maurice; Yost, William E.

2013-01-01

A commercially available grey-field polariscope (GFP) instrument for photoelastic examination is used to assess impact damage inflicted upon the outer-most pane of Space Shuttle windows made from fused silica. A method and apparatus for calibration of the stress-optic coefficient using four-point bending is discussed. The results are validated on known material (acrylic) and are found to agree with literature values to within 6%. The calibration procedure is then applied to fused-silica specimens and the stress-optic coefficient is determined to be 2.43 +/- 0.54 x 10(exp -12)/Pa. Fused silica specimens containing impacts artificially made at NASA's Hypervelocity Impact Technology Facility (HIT-F), to simulate damage typical during space flight, are examined. The damage sites are cored from fused silica window carcasses and examined with the GFP. The calibrated GFP measurements of residual stress patterns surrounding the damage sites are presented. Keywords: Glass, fused silica, photoelasticity, residual stress

The RNA Splicing Response to DNA Damage.

PubMed

Shkreta, Lulzim; Chabot, Benoit

2015-10-29

The number of factors known to participate in the DNA damage response (DDR) has expanded considerably in recent years to include splicing and alternative splicing factors. While the binding of splicing proteins and ribonucleoprotein complexes to nascent transcripts prevents genomic instability by deterring the formation of RNA/DNA duplexes, splicing factors are also recruited to, or removed from, sites of DNA damage. The first steps of the DDR promote the post-translational modification of splicing factors to affect their localization and activity, while more downstream DDR events alter their expression. Although descriptions of molecular mechanisms remain limited, an emerging trend is that DNA damage disrupts the coupling of constitutive and alternative splicing with the transcription of genes involved in DNA repair, cell-cycle control and apoptosis. A better understanding of how changes in splice site selection are integrated into the DDR may provide new avenues to combat cancer and delay aging.

The RNA Splicing Response to DNA Damage

PubMed Central

Shkreta, Lulzim; Chabot, Benoit

2015-01-01

The number of factors known to participate in the DNA damage response (DDR) has expanded considerably in recent years to include splicing and alternative splicing factors. While the binding of splicing proteins and ribonucleoprotein complexes to nascent transcripts prevents genomic instability by deterring the formation of RNA/DNA duplexes, splicing factors are also recruited to, or removed from, sites of DNA damage. The first steps of the DDR promote the post-translational modification of splicing factors to affect their localization and activity, while more downstream DDR events alter their expression. Although descriptions of molecular mechanisms remain limited, an emerging trend is that DNA damage disrupts the coupling of constitutive and alternative splicing with the transcription of genes involved in DNA repair, cell-cycle control and apoptosis. A better understanding of how changes in splice site selection are integrated into the DDR may provide new avenues to combat cancer and delay aging. PMID:26529031

Quantification of residual stress from photonic signatures of fused silica

NASA Astrophysics Data System (ADS)

Cramer, K. Elliott; Hayward, Maurice; Yost, William T.

2014-02-01

A commercially available grey-field polariscope (GFP) instrument for photoelastic examination is used to assess impact damage inflicted upon the outer-most pane of Space Shuttle windows made from fused silica. A method and apparatus for calibration of the stress-optic coefficient using four-point bending is discussed. The results are validated on known material (acrylic) and are found to agree with literature values to within 6%. The calibration procedure is then applied to fused-silica specimens and the stress-optic coefficient is determined to be 2.43 ± 0.54 × 10-12 Pa-1. Fused silica specimens containing impacts artificially made at NASA's Hypervelocity Impact Technology Facility (HIT-F), to simulate damage typical during space flight, are examined. The damage sites are cored from fused silica window carcasses and examined with the GFP. The calibrated GFP measurements of residual stress patterns surrounding the damage sites are presented.

Single α-particle irradiation permits real-time visualization of RNF8 accumulation at DNA damaged sites

NASA Astrophysics Data System (ADS)

Muggiolu, Giovanna; Pomorski, Michal; Claverie, Gérard; Berthet, Guillaume; Mer-Calfati, Christine; Saada, Samuel; Devès, Guillaume; Simon, Marina; Seznec, Hervé; Barberet, Philippe

2017-01-01

As well as being a significant source of environmental radiation exposure, α-particles are increasingly considered for use in targeted radiation therapy. A better understanding of α-particle induced damage at the DNA scale can be achieved by following their tracks in real-time in targeted living cells. Focused α-particle microbeams can facilitate this but, due to their low energy (up to a few MeV) and limited range, α-particles detection, delivery, and follow-up observations of radiation-induced damage remain difficult. In this study, we developed a thin Boron-doped Nano-Crystalline Diamond membrane that allows reliable single α-particles detection and single cell irradiation with negligible beam scattering. The radiation-induced responses of single 3 MeV α-particles delivered with focused microbeam are visualized in situ over thirty minutes after irradiation by the accumulation of the GFP-tagged RNF8 protein at DNA damaged sites.

The effects of Vexar® seedling protectors on the growth and development of lodgepole pine roots

USGS Publications Warehouse

Engeman, Richard M.; Anthony, R. Michael; Krupa, Heather W.; Evans, James

1997-01-01

The effects on the growth and development of lodgepole pine roots from the Vexar® tubes used to protect seedlings from pocket gopher damage were studied in the Targhee National Forest, Idaho and the Deschutes National Forest, Oregon. At each site, Vexar-protected and unprotected seedlings, with and without above-ground gopher damage were examined after six growing seasons for root deformities and growth. Undamaged seedlings exhibited greater growth, reflecting the importance of non-lethal gopher damage as a deterrent to tree growth. Protected seedlings with similar damage history as unprotected seedlings had greater root depth than unprotected seedlings, although unprotected seedlings with no above-ground damage generally had the greatest root weight. In general, the percent of seedlings with root deformities was greater for the unprotected seedlings than for the Vexar-protectd seedlings, although this could be largely due to the greater care required to plant protected seedlings. Acute deformities were more common for unprotected seedlings, whereas root deformities with less severe bending were more common for protected seedlings. The incidence of crossed roots was similar for protected and unprotected seedlings on the Deschutes site, where enough occurrences of this deformity permitted analyses. Protected seedlings were similar in root abundance, root distribution, root size and vigor to the unprotected seedlings, with some indication from the Deshutes study site that root distribution was improved with Vexar protection.

Motility and Chemotaxis Mediate the Preferential Colonization of Gastric Injury Sites by Helicobacter pylori

PubMed Central

Aihara, Eitaro; Closson, Chet; Matthis, Andrea L.; Schumacher, Michael A.; Engevik, Amy C.; Zavros, Yana; Ottemann, Karen M.; Montrose, Marshall H.

2014-01-01

Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (106) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (106) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby biases the injured tissue towards sustained gastric damage. PMID:25033386

Motility and chemotaxis mediate the preferential colonization of gastric injury sites by Helicobacter pylori.

PubMed

Aihara, Eitaro; Closson, Chet; Matthis, Andrea L; Schumacher, Michael A; Engevik, Amy C; Zavros, Yana; Ottemann, Karen M; Montrose, Marshall H

2014-07-01

Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (10(6)) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (10(6)) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby biases the injured tissue towards sustained gastric damage.

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

PubMed

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

2017-10-19

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

On binding specificity of (6-4) photolyase to a T(6-4)T DNA photoproduct*

NASA Astrophysics Data System (ADS)

Jepsen, Katrine Aalbæk; Solov'yov, Ilia A.

2017-06-01

Different factors lead to DNA damage and if it is not repaired in due time, the damaged DNA could initiate mutagenesis and cancer. To avoid this deadly scenario, specific enzymes can scavenge and repair the DNA, but the enzymes have to bind first to the damaged sites. We have investigated this binding for a specific enzyme called (6-4) photolyase, which is capable of repairing certain UV-induced damage in DNA. Through molecular dynamics simulations we describe the binding between photolyase and the DNA and reveal that several charged amino acid residues in the enzyme, such as arginines and lysines turn out to be important. Especially R421 is crucial, as it keeps the DNA strands at the damaged site inside the repair pocket of the enzyme separated. DNA photolyase is structurally highly homologous to a protein called cryptochrome. Both proteins are biologically activated similarly, namely through flavin co-factor photoexcitation. It is, however, striking that cryptochrome cannot repair UV-damaged DNA. The present investigation allowed us to conclude on the small but, apparently, critical differences between photolyase and cryptochrome. The performed analysis gives insight into important factors that govern the binding of UV-damaged DNA and reveal why cryptochrome cannot have this functionality.

7 CFR 624.8 - Assistance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... serious, but not immediate threat to human life; (iii) Sites where buildings, utilities, or other... high value crops is threatened; (D) Sites containing wetlands that would be damaged or destroyed...

The behavior of multiple independent managers and ecological traits interact to determine prevalence of weeds.

PubMed

Coutts, Shaun R; Yokomizo, Hiroyuki; Buckley, Yvonne M

2013-04-01

Management of damaging invasive plants is often undertaken by multiple decision makers, each managing only a small part of the invader's population. As weeds can move between properties and re-infest eradicated sites from unmanaged sources, the dynamics of multiple decision makers plays a significant role in weed prevalence and invasion risk at the landscape scale. We used a spatially explicit agent-based simulation to determine how individual agent behavior, in concert with weed population ecology, determined weed prevalence. We compared two invasive grass species that differ in ecology, control methods, and costs: Nassella trichotoma (serrated tussock) and Eragrostis curvula (African love grass). The way decision makers reacted to the benefit of management had a large effect on the extent of a weed. If benefits of weed control outweighed the costs, and either net benefit was very large or all agents were very sensitive to net benefits, then agents tended to act synchronously, reducing the pool of infested agents available to spread the weed. As N. trichotoma was more damaging than E. curvula and had more effective control methods, agents chose to manage it more often, which resulted in lower prevalence of N. trichotoma. A relatively low number of agents who were intrinsically less motivated to control weeds led to increased prevalence of both species. This was particularly apparent when long-distance dispersal meant each infested agent increased the invasion risk for a large portion of the landscape. In this case, a small proportion of land mangers reluctant to control, regardless of costs and benefits, could lead to the whole landscape being infested, even when local control stopped new infestations. Social pressure was important, but only if it was independent of weed prevalence, suggesting that early access to information, and incentives to act on that information, may be crucial in stopping a weed from infesting large areas. The response of our model to both behavioral and ecological parameters was highly nonlinear. This implies that the outcomes of weed management programs that deal with multiple land mangers could be highly variable in both space and through time.

Remote sensing of changes in morphology and physiology of trees under stress

NASA Technical Reports Server (NTRS)

Olson, C. E., Jr.; Rohde, W. G.; Ward, J. M.

1970-01-01

Results of continuing studies of forest trees subjected to varying types of stress are reported. Both greenhouse and field studies are included. Greenhouse work with tree seedlings exposed to varying levels of NaCl and CaCl2 in the soil indicated that, in the initial stages, palisade cells shrink and the amount of air space in the leaf increases. As the severity of damage increases, the cells of the spongy mesophyll shrink and flatten, and the amount of air space in the leaf decreases. Statistical analysis of foliar reflectance and associated moisture content data led to a series of regression equations for predicting foliar moisture content from reflectance data. Equations were calculated for three species, yellow birch (Betula alleghaniensis Britton), sugar maple (Acer saccharum Marsh.) and white ash (Fraxinus americana L.) having multiple correlation coefficients of 0.98, 0.94 and 0.93 respectively. Interpretation of multispectral imagery of the Ann Arbor Forestry Test Site (NASA Site 190) provided evidence that infections of Fomes annosus can be detected in the early stages. Infections of two needle cast diseases were also detected in conifer plantations in the test site. A study of automatic interpretation of multispectral scanner imagery for tree species recognition provided encouraging results.

Characterization of Bleomycin-Mediated Cleavage of a Hairpin DNA Library

PubMed Central

Segerman, Zachary J.; Roy, Basab; Hecht, Sidney M.

2013-01-01

A study of BLM A5 was conducted using a previously isolated library of hairpin DNAs found to bind strongly to metal free BLM. The ability of Fe(II)•BLM to effect cleavage on both the 3' and 5'-arms of the hairpin DNAs was characterized. The strongly bound DNAs were found to be efficient substrates for Fe•BLM A5-mediated hairpin DNA cleavage. Surprisingly, the most prevalent site of BLM-mediated cleavage was found to be the 5′-AT-3′ dinucleotide sequence. This dinucleotide sequence, and other sequences generally not cleaved well by BLM when examined using arbitrarily chosen DNA substrates, were apparent when examining the library of ten hairpin DNAs. In total, 132 sites of DNA cleavage were produced by exposure of the hairpin DNA library to Fe•BLM A5. The existence of multiple sites of cleavage on both the 3′- and 5′-arms of the hairpin DNAs suggested that some of these might be double-strand cleavage events. Accordingly, an assay was developed with which to test the propensity of the hairpin DNAs to undergo double-strand DNA damage. One hairpin DNA was characterized using this method, and gave results consistent with earlier reports of double-strand DNA cleavage, but with a sequence selectivity different from those reported previously. PMID:23834496

Impact of Hurricane Iniki on native Hawaiian Acacia koa forests: damage and two-year recovery

Treesearch

Robin A. Harrington; James H. Fownes; Paul G. Scowcroft; Cheryl S. Vann

1997-01-01

Damage to Hawaiian Acacia koa forest by Hurricane Iniki was assessed by comparison with our previous measures of stand structure and leaf area index (LAI) at sites along a precipitation/elevation gradient on western Kauai. Reductions in LAI ranged from 29 to 80% and were correlated with pre-hurricane LAI and canopy height. The canopy damage...

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

NASA Astrophysics Data System (ADS)

Messaoudi, Akila; Laouami, Nasser; Mezouar, Nourredine

2017-07-01

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

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

Rapid building damage assessment system using mobile phone technology

NASA Astrophysics Data System (ADS)

Cimellaro, Gian Paolo; Scura, G.; Renschler, C. S.; Reinhorn, A. M.; Kim, H. U.

2014-09-01

One common scenario during disasters such as earthquakes is that the activity of damage field reconnaissance on site is not well-coordinated. For example in Italy the damage assessment of structures after an earthquake is managed from the Italian Emergency Authority, using printed forms (AeDES) which are filled by experts on site generating a lot of confusion in filling and transferring the forms to the Disaster Management Operative Center. Because of this, the paper explores the viability of using mobile communication technologies (smart phones) and the Web to develop response systems that would aid communities after a major disaster, providing channels for allowing residents and responders of uploading and distributing information, related to structural damages coordinating the damage field reconnaissance. A mobile application that can be run by residents on smart phones has been developed, to give an initial damage evaluation of the area, which is going to be very useful when resources (e.g. the number of experts is limited). The mobile application has been tested for the first time during 2012 Emilia earthquake to enhance the emergency response, showing the efficiency of the proposed method in statistical terms comparing the proposed procedure with the standard procedure.

[Embryo-fetal diseases in multiple pregnancies].

PubMed

Colla, F; Alba, E; Grio, R

2001-04-01

Embryo-fetal diseases are the consequence of prenatal (progenetic and metagenetic or environmental) and intranatal (of a traumatic, infective, toxic nature) pathological factors. In multiple pregnancies this complex etiopathogenesis also includes an altered didymous embriogenesis. This study aimed to evaluate the pathologies affecting the fetus in multiple pregnancy, a special biological situation leading to the potential onset of severe fetal and neonatal damage. The authors studied 205 patients with multiple pregnancies, including 199 bigeminal, 5 trigeminal and 1 quadrigeminal, admitted to the Department B of the Obstetrics and Gynecological Clinic of Turin University between 1989-1999. Possible embyro-fetal damage was examined using a chronological criterion: namely following the development of the multiple fetuses from the zygotic to the neonatal phase. Pregnancies were biamniotic bichorionic in 54% of cases, biamniotic monochorionic in 45% and monochorionic monoamniotic in 1%. There were a total of 154 (79.38%) premature births out of 194 and neonatal birth weight was always SGA (small for gestational age). 66.84% of newborns were LBW (<2500 g) and 7.14% were VLBW (<1500 g). Fetal mortality (2.29%) was higher than early neonatal mortality (1.53%). Perinatal mortality (3.82%) was three times higher than in all neonates from the same period (1.03%). The severe embryo-fetal and neonatal damage found in multiple pregnancies is a clinical reality that calls for adequate diagnostic and therapeutic measures, and above all specific medical and social prevention to limit maternal pathogenic risks.

Modelling the influence of predicted future climate change on the risk of wind damage within New Zealand's planted forests.

PubMed

Moore, John R; Watt, Michael S

2015-08-01

Wind is the major abiotic disturbance in New Zealand's planted forests, but little is known about how the risk of wind damage may be affected by future climate change. We linked a mechanistic wind damage model (ForestGALES) to an empirical growth model for radiata pine (Pinus radiata D. Don) and a process-based growth model (cenw) to predict the risk of wind damage under different future emissions scenarios and assumptions about the future wind climate. The cenw model was used to estimate site productivity for constant CO2 concentration at 1990 values and for assumed increases in CO2 concentration from current values to those expected during 2040 and 2090 under the B1 (low), A1B (mid-range) and A2 (high) emission scenarios. Stand development was modelled for different levels of site productivity, contrasting silvicultural regimes and sites across New Zealand. The risk of wind damage was predicted for each regime and emission scenario combination using the ForestGALES model. The sensitivity to changes in the intensity of the future wind climate was also examined. Results showed that increased tree growth rates under the different emissions scenarios had the greatest impact on the risk of wind damage. The increase in risk was greatest for stands growing at high stand density under the A2 emissions scenario with increased CO2 concentration. The increased productivity under this scenario resulted in increased tree height, without a corresponding increase in diameter, leading to more slender trees that were predicted to be at greater risk from wind damage. The risk of wind damage was further increased by the modest increases in the extreme wind climate that are predicted to occur. These results have implications for the development of silvicultural regimes that are resilient to climate change and also indicate that future productivity gains may be offset by greater losses from disturbances. © 2015 John Wiley & Sons Ltd.

Effects of Military activity and habitat quality on DNA damage and oxidative stress in the largest population of the Federally threatened gopher tortoise.

PubMed

Theodorakis, Christopher W; Adams, S Marshall; Smith, Chandra; Rotter, Jamie; Hay, Ashley; Eslick, Joy

2017-12-01

Department of Defense lands are essential for providing important habitat for threatened, endangered, and at-risk species (TER-S). However, there is little information on the effects of military-related contaminants on TER-S on these lands in field situations. Thus, this study examined genotoxicity and oxidative stress in gopher tortoises (Gopherus polyphemus) on Camp Shelby, MS-the largest known population of this species, which is listed as an "endangered species" in Mississippi and a "threatened species" by the U.S. government. Blood was collected from tortoises at 19 different sites on the base with different levels of habitat quality (high-quality and low-quality habitat) and military activity (high, low, and no military activity). Oxidative stress was quantified as lipid peroxidation and GSSG/GSH ratios, while DNA damage was determined using flow cytometry. Our results suggest that: (1) for tortoises residing in low-quality habitats, oxidative stress and DNA damage increased with increasing military activity, while in high-quality habitats, oxidative stress and DNA damage decreased with increasing military activity; (2) in the absence of military activity, tortoises in high-quality habitat had higher levels of oxidative stress and DNA damage than those in low-quality habitat, and (3) there were interactions between military activity, habitat quality, and landuse in terms of the amount of observable DNA damage and oxidative stress. In particular, on high-quality habitat, tortoises from areas with high levels of military activity had lower levels of oxidative stress and DNA damage biomarkers than on reference sites. This may represent a compensatory or hormetic response. Conversely, on low-quality habitats, the level of oxidative stress and DNA damage was lower on the reference sites. Thus, tortoises on higher-quality habitats may have a greater capacity for compensatory responses. In terms of management implications, it is suggested that low quality habitats should be a higher priority for remediation, and lower priority for conducting military activities.

The prion-like domain of FUS is multiphosphorylated following DNA damage without altering nuclear localization.

PubMed

Rhoads, Shannon N; Monahan, Zachary T; Yee, Debra S; Leung, Andrew Y; Newcombe, Cameron G; O'Meally, Robert N; Cole, Robert N; Shewmaker, Frank P

2018-06-13

FUS is an abundant, predominantly nuclear protein involved in RNA processing. Under various conditions, FUS functionally associates with RNA and other macromolecules to form distinct, reversible phase-separated liquid structures. Persistence of the phase-separated state and increased cytoplasmic localization are both hypothesized to predispose FUS to irreversible aggregation, which is a pathological hallmark of subtypes of amyotrophic lateral sclerosis and frontotemporal dementia. We previously showed that phosphorylation of FUS's prion-like domain suppressed phase separation and toxic aggregation, proportionally to the number of added phosphates. However, phosphorylation of FUS's prion-like domain was previously reported to promote its cytoplasmic localization, potentially favoring pathological behavior. Here, we used mass spectrometry and human cell models to further identify phosphorylation sites within FUS's prion-like domain, specifically following DNA-damaging stress. In total, 28 putative sites have been identified, about half of which are DNA-dependent protein kinase (DNA-PK) consensus sites. Custom antibodies were developed to confirm the phosphorylation of two of these sites (Ser26 and Ser30). Both sites were usually phosphorylated in a sub-population of cellular FUS following a variety of DNA-damaging stresses, but not necessarily equally or simultaneously. Importantly, we found DNA-PK-dependent multi-phosphorylation of FUS's prion-like domain does not cause cytoplasmic localization.

Characteristics of plasma scalds in multilayer dielectric films

NASA Astrophysics Data System (ADS)

Liu, Xiaofeng; Zhao, Yuan'an; Li, Dawei; Hu, Guohang; Gao, Yanqi; Fan, Zhengxiu; Shao, Jianda

2011-07-01

Plasma scalding is one of the most typical laser damage morphologies induced by a nanosecond laser with a wavelength of 1053nm in HfO2/SiO2 multilayer films. In this paper, the characteristics of plasma scalds are systematically investigated with multiple methods. The scalding behaves as surface discoloration under a microscope. The shape is nearly circular when the laser incidence angle is close to normal incidence and is elliptical at oblique incidence. The nodular-ejection pit is in the center of the scalding region when the laser irradiates at the incidence angle close to normal incidence and in the right of the scalding region when the laser irradiates from left to right at oblique incidence. The maximum damage size of the scalding increases with laser energy. The edge of the scalding is high compared with the unirradiated film surface, and the region tending to the center is concave. Plasma scald is proved to be surface damage. The maximum depth of a scald increases with its size. Tiny pits of nanometer scale can be seen in the scalding film under a scanning electronic microscope at a higher magnification. The absorptions of the surface plasma scalds tend to be approximately the same as the lower absorptions of test sites without laser irradiation. Scalds do not grow during further illumination pulses until 65J/cm2. The formation of surface plasma scalding may be related to the occurrence of the laser-supported detonation wave.

PARP Inhibitors in Reproductive System Cancers: Current Use and Developments.

PubMed

O'Sullivan Coyne, Geraldine; Chen, Alice P; Meehan, Robert; Doroshow, James H

2017-02-01

The repair of DNA damage is a critical cellular process governed by multiple biochemical pathways that are often found to be defective in cancer cells. The poly(ADP-ribose) polymerase (PARP) family of proteins controls response to single-strand DNA breaks by detecting these damaged sites and recruiting the proper factors for repair. Blocking this pathway forces cells to utilize complementary mechanisms to repair DNA damage. While PARP inhibition may not, in itself, be sufficient to cause tumor cell death, inhibition of DNA repair with PARP inhibitors is an effective cytotoxic strategy when it is used in patients who carry other defective DNA-repair mechanisms, such as mutations in the genes BRCA 1 and 2. This discovery has supported the development of PARP inhibitors (PARPi), agents that have proven effective against various types of tumors that carry BRCA mutations. With the application of next-generation sequencing of tumors, there is increased interest in looking beyond BRCA mutations to identify genetic and epigenetic aberrations that might lead to similar defects in DNA repair, conferring susceptibility to PARP inhibition. Identification of these genetic lesions and the development of screening assays for their detection may allow for the selection of patients most likely to respond to this class of anticancer agents. This article provides an overview of clinical trial results obtained with PARPi and describes the companion diagnostic assays being established for patient selection. In addition, we review known mechanisms for resistance to PARPi and potential strategies for combining these agents with other types of therapy.

Overview of the Special Issue: A Multi-Model Framework to Achieve Consistent Evaluation of Climate Change Impacts in the United States

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

Waldhoff, Stephanie T.; Martinich, Jeremy; Sarofim, Marcus

2015-07-01

The Climate Change Impacts and Risk Analysis (CIRA) modeling exercise is a unique contribution to the scientific literature on climate change impacts, economic damages, and risk analysis that brings together multiple, national-scale models of impacts and damages in an integrated and consistent fashion to estimate climate change impacts, damages, and the benefits of greenhouse gas (GHG) mitigation actions in the United States. The CIRA project uses three consistent socioeconomic, emissions, and climate scenarios across all models to estimate the benefits of GHG mitigation policies: a Business As Usual (BAU) and two policy scenarios with radiative forcing (RF) stabilization targets ofmore » 4.5 W/m2 and 3.7 W/m2 in 2100. CIRA was also designed to specifically examine the sensitivity of results to uncertainties around climate sensitivity and differences in model structure. The goals of CIRA project are to 1) build a multi-model framework to produce estimates of multiple risks and impacts in the U.S., 2) determine to what degree risks and damages across sectors may be lowered from a BAU to policy scenarios, 3) evaluate key sources of uncertainty along the causal chain, and 4) provide information for multiple audiences and clearly communicate the risks and damages of climate change and the potential benefits of mitigation. This paper describes the motivations, goals, and design of the CIRA modeling exercise and introduces the subsequent papers in this special issue.« less

Localized grey matter damage in early primary progressive multiple sclerosis contributes to disability.

PubMed

Khaleeli, Z; Cercignani, M; Audoin, B; Ciccarelli, O; Miller, D H; Thompson, A J

2007-08-01

Disability in primary progressive multiple sclerosis (PPMS) has been correlated with damage to the normal appearing brain tissues. Magnetization transfer ratio (MTR) and volume changes indicate that much of this damage occurs in the normal appearing grey matter, but the clinical significance of this remains uncertain. We aimed to localize these changes to distinct grey matter regions, and investigate the clinical impact of the MTR changes. 46 patients with early PPMS and 23 controls underwent MT and high-resolution T1-weighted imaging. Patients were scored on the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite and subtests (Nine-Hole Peg Test, Timed Walk Test, Paced Auditory Serial Addition Test [PASAT]). Grey matter volume and MTR were compared between patients and controls, adjusting for age. Mean MTR for significant regions within the motor network and in areas relevant to PASAT performance were correlated with appropriate clinical scores, adjusting for grey matter volume. Patients showed reduced MTR and atrophy in the right pre- and left post-central gyri, right middle frontal gyrus, left insula, and thalamus bilaterally. Reduced MTR without significant atrophy occurred in the left pre-central gyrus, left superior frontal gyri, bilateral superior temporal gyri, right insula and visual cortex. Higher EDSS correlated with lower MTR in the right primary motor cortex (BA 4). In conclusion, localized grey matter damage occurs in early PPMS, and MTR change is more widespread than atrophy. Damage demonstrated by reduced MTR is clinically eloquent.

High Incidence of HPV-Associated Head and Neck Cancers in FA Deficient Mice Is Associated with E7’s Induction of DNA Damage through Its Inactivation of Pocket Proteins

PubMed Central

Park, Jung Wook; Shin, Myeong-Kyun; Pitot, Henry C.; Lambert, Paul F.

2013-01-01

Fanconi anemia (FA) patients are highly susceptible to solid tumors at multiple anatomical sites including head and neck region. A subset of head and neck cancers (HNCs) is associated with ‘high-risk’ HPVs, particularly HPV16. However, the correlation between HPV oncogenes and cancers in FA patients is still unclear. We previously learned that FA deficiency in mice predisposes HPV16 E7 transgenic mice to HNCs. To address HPV16 E6’s oncogenic potential under FA deficiency in HNCs, we utilized HPV16 E6-transgenic mice (K14E6) and HPV16 E6/E7-bi-transgenic mice (K14E6E7) on genetic backgrounds sufficient or deficient for one of the fanc genes, fancD2 and monitored their susceptibility to HNCs. K14E6 mice failed to develop tumor. However, E6 and fancD2-deficiency accelerated E7-driven tumor development in K14E6E7 mice. The increased tumor incidence was more correlated with E7-driven DNA damage than proliferation. We also found that deficiency of pocket proteins, pRb, p107, and p130 that are well-established targets of E7, could recapitulate E7’s induction of DNA damage. Our findings support the hypothesis that E7 induces HPV-associated HNCs by promoting DNA damage through the inactivation of pocket proteins, which explains why a deficiency in DNA damage repair would increase susceptibility to E7-driven cancer. Our results further demonstrate the unexpected finding that FA deficiency does not predispose E6 transgenic mice to HNCs, indicating a specificity in the synergy between FA deficiency and HPV oncogenes in causing HNCs. PMID:24086435

Curcumin-Mediated HDAC Inhibition Suppresses the DNA Damage Response and Contributes to Increased DNA Damage Sensitivity

PubMed Central

Wang, Shu-Huei; Lin, Pei-Ya; Chiu, Ya-Chen; Huang, Ju-Sui; Kuo, Yi-Tsen; Wu, Jen-Chine; Chen, Chin-Chuan

2015-01-01

Chemo- and radiotherapy cause multiple forms of DNA damage and lead to the death of cancer cells. Inhibitors of the DNA damage response are candidate drugs for use in combination therapies to increase the efficacy of such treatments. In this study, we show that curcumin, a plant polyphenol, sensitizes budding yeast to DNA damage by counteracting the DNA damage response. Following DNA damage, the Mec1-dependent DNA damage checkpoint is inactivated and Rad52 recombinase is degraded by curcumin, which results in deficiencies in double-stand break repair. Additive effects on damage-induced apoptosis and the inhibition of damage-induced autophagy by curcumin were observed. Moreover, rpd3 mutants were found to mimic the curcumin-induced suppression of the DNA damage response. In contrast, hat1 mutants were resistant to DNA damage, and Rad52 degradation was impaired following curcumin treatment. These results indicate that the histone deacetylase inhibitor activity of curcumin is critical to DSB repair and DNA damage sensitivity. PMID:26218133

Prevalence of feral swine disturbance at important archaeological sites over a large landscape in Florida

NASA Astrophysics Data System (ADS)

Engeman, Richard M.; Meyer, Joseph S.; Allen, John B.

2017-01-01

Feral swine are globally known as one of the most destructive invasive vertebrates, damaging native habitats, native plants and animals, agriculture, infrastructure, spreading diseases. There has been little quantification on their disturbance to archaeological sites across a broad landscape. Over 6 years we inspected 293 significant archaeological sites for swine disturbance across a vast area. We found a 42% prevalence of swine disturbance among all sites, with prevalence not distinguishable among prehistoric sites, historic sites, and sites with both components. The areas of disturbance mapped within three historic homestead sites showed 5-26% of total site surface area rooted. Disturbance was not evident upon re-inspection of one of these sites after 18 months, indicating how evidence of disturbance can be obscured in this environment. Thus, our observed 42% prevalence of disturbance should be considered a minimum for disturbance occurring through time. Artifacts depths were <10 cm of the surface at 85% of the sites and <20 cm of the surface for 90% of the sites. Feral swine rooting commonly exceeds 20 cm in depth, especially in soft sandy substrates typical of Florida, making the great majority of the studied sites highly vulnerable to artifact damage or displacement.

DamaGIS: a multisource geodatabase for collection of flood-related damage data

NASA Astrophysics Data System (ADS)

Saint-Martin, Clotilde; Javelle, Pierre; Vinet, Freddy

2018-06-01

Every year in France, recurring flood events result in several million euros of damage, and reducing the heavy consequences of floods has become a high priority. However, actions to reduce the impact of floods are often hindered by the lack of damage data on past flood events. The present paper introduces a new database for collection and assessment of flood-related damage. The DamaGIS database offers an innovative bottom-up approach to gather and identify damage data from multiple sources, including new media. The study area has been defined as the south of France considering the high frequency of floods over the past years. This paper presents the structure and contents of the database. It also presents operating instructions in order to keep collecting damage data within the database. This paper also describes an easily reproducible method to assess the severity of flood damage regardless of the location or date of occurrence. A first analysis of the damage contents is also provided in order to assess data quality and the relevance of the database. According to this analysis, despite its lack of comprehensiveness, the DamaGIS database presents many advantages. Indeed, DamaGIS provides a high accuracy of data as well as simplicity of use. It also has the additional benefit of being accessible in multiple formats and is open access. The DamaGIS database is available at https://doi.org/10.5281/zenodo.1241089.

Thin-Film Module Reverse-Bias Breakdown Sites Identified by Thermal Imaging: Preprint

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

Johnston, Steven; Sulas, Dana; Guthrey, Harvey L

Thin-film module sections are stressed under reverse bias to simulate partial shading conditions. Such stresses can cause permanent damage in the form of 'wormlike' defects due to thermal runaway. When large reverse biases with limited current are applied to the cells, dark lock-in thermography (DLIT) can detect where spatially-localized breakdown initiates before thermal runaway leads to permanent damage. Predicted breakdown defect sites have been identified in both CIGS and CdTe modules using DLIT. These defects include small pinholes, craters, or voids in the absorber layer of the film that lead to built-in areas of weakness where high current densities maymore » cause thermal damage in a partial-shading event.« less

Thin-Film Module Reverse-Bias Breakdown Sites Identified by Thermal Imaging

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

Johnston, Steven; Sulas, Dana; Guthrey, Harvey L

Thin-film module sections are stressed under reverse bias to simulate partial shading conditions. Such stresses can cause permanent damage in the form of 'wormlike' defects due to thermal runaway. When large reverse biases with limited current are applied to the cells, dark lock-in thermography (DLIT) can detect where spatially-localized breakdown initiates before thermal runaway leads to permanent damage. Predicted breakdown defect sites have been identified in both CIGS and CdTe modules using DLIT. These defects include small pinholes, craters, or voids in the absorber layer of the film that lead to built-in areas of weakness where high current densities maymore » cause thermal damage in a partial-shading event.« less

A Uniform Fault Zone Diffusivity Structure in the Simi Valley Based on Water Level Tidal and Barometric Response

NASA Astrophysics Data System (ADS)

Xue, L.; Brodsky, E. E.; Allègre, V.; Parker, B. L.; Cherry, J. A.

2016-12-01

Water levels inside conventional water wells can tap an artesian aquifer response to pressure head disturbances caused by the Earth tides and surface atmospheric loading. The fluctuation of water levels can measure the hydrogeologic properties of the formation surrounding these wells. Specifically, the amplitude of water level oscillation is determined by formation specific storage, and the phase shift between the water level oscillation and the pressure head disturbance is determined by formation permeability. We utilized 36 wells completed in fractured, interbedded sandstone of turbidite origin in an upland area of southern California to measure the in-situ hydrogeologic properties by combining the water level tidal and barometric responses. This site experiences north-south shortening and it has groups of NE-SW and east-west conjugate faults. The site has been intensively characterized and monitored hydrologically since the 1980's because of the groundwater contamination. Hence, this study provides a good opportunity to measure the in-situ hydrogeologic properties for comparison to other test types and scales. Most of the observed water level tidal responses have a lead phase response, which cannot be interpreted either by the water level response in a confined aquifer or the water level response in an unconfined aquifer. To interpret these observations, we utilized the water level response in a partially confined aquifer, resulting in both positive and negative phase information when fully considering all the observations. Due to the different mechanisms for tidal versus barometric water level responses, the combination can give better constraints on the inverted hydrologic properties. The range of the measured permeability is 10-15-10-13 m2 and the range of the specific storage is 10-7-10-5 1/m. The resulting diffusivity is within 10-2-10-1 m2/s which is relatively uniform. This indicates the fault damages in the site are relatively homogeneous at the scale of measurement and there is no major fault-guided hydrogeological channel at the site. Such homogenous by fault zone damage is possible in a region of multiple strands and copious secondary faulting.

A risk assessment method for multi-site damage

NASA Astrophysics Data System (ADS)

Millwater, Harry Russell, Jr.

This research focused on developing probabilistic methods suitable for computing small probabilities of failure, e.g., 10sp{-6}, of structures subject to multi-site damage (MSD). MSD is defined as the simultaneous development of fatigue cracks at multiple sites in the same structural element such that the fatigue cracks may coalesce to form one large crack. MSD is modeled as an array of collinear cracks with random initial crack lengths with the centers of the initial cracks spaced uniformly apart. The data used was chosen to be representative of aluminum structures. The structure is considered failed whenever any two adjacent cracks link up. A fatigue computer model is developed that can accurately and efficiently grow a collinear array of arbitrary length cracks from initial size until failure. An algorithm is developed to compute the stress intensity factors of all cracks considering all interaction effects. The probability of failure of two to 100 cracks is studied. Lower bounds on the probability of failure are developed based upon the probability of the largest crack exceeding a critical crack size. The critical crack size is based on the initial crack size that will grow across the ligament when the neighboring crack has zero length. The probability is evaluated using extreme value theory. An upper bound is based on the probability of the maximum sum of initial cracks being greater than a critical crack size. A weakest link sampling approach is developed that can accurately and efficiently compute small probabilities of failure. This methodology is based on predicting the weakest link, i.e., the two cracks to link up first, for a realization of initial crack sizes, and computing the cycles-to-failure using these two cracks. Criteria to determine the weakest link are discussed. Probability results using the weakest link sampling method are compared to Monte Carlo-based benchmark results. The results indicate that very small probabilities can be computed accurately in a few minutes using a Hewlett-Packard workstation.

15 CFR 921.10 - General.

Code of Federal Regulations, 2011 CFR

2011-01-01

... ESTUARINE RESEARCH RESERVE SYSTEM REGULATIONS Site Selection, Post Site Selection and Management Plan... of site selection, preparation of documents specified in § 921.13 (draft management plan (DMP) and... recovered as a result of damage to natural resources located in the coastal zone, such assistance may be...

15 CFR 921.10 - General.

Code of Federal Regulations, 2010 CFR

2010-01-01

... ESTUARINE RESEARCH RESERVE SYSTEM REGULATIONS Site Selection, Post Site Selection and Management Plan... of site selection, preparation of documents specified in § 921.13 (draft management plan (DMP) and... recovered as a result of damage to natural resources located in the coastal zone, such assistance may be...

Interplay between Ubiquitin, SUMO, and Poly(ADP-Ribose) in the Cellular Response to Genotoxic Stress

PubMed Central

Pellegrino, Stefania; Altmeyer, Matthias

2016-01-01

Cells employ a complex network of molecular pathways to cope with endogenous and exogenous genotoxic stress. This multilayered response ensures that genomic lesions are efficiently detected and faithfully repaired in order to safeguard genome integrity. The molecular choreography at sites of DNA damage relies heavily on post-translational modifications (PTMs). Protein modifications with ubiquitin and the small ubiquitin-like modifier SUMO have recently emerged as important regulatory means to coordinate DNA damage signaling and repair. Both ubiquitylation and SUMOylation can lead to extensive chain-like protein modifications, a feature that is shared with yet another DNA damage-induced PTM, the modification of proteins with poly(ADP-ribose) (PAR). Chains of ubiquitin, SUMO, and PAR all contribute to the multi-protein assemblies found at sites of DNA damage and regulate their spatio-temporal dynamics. Here, we review recent advancements in our understanding of how ubiquitin, SUMO, and PAR coordinate the DNA damage response and highlight emerging examples of an intricate interplay between these chain-like modifications during the cellular response to genotoxic stress. PMID:27148359

Specific association of mouse MDC1/NFBD1 with NBS1 at sites of DNA-damage.

PubMed

Lee, Alicia C; Fernandez-Capetillo, Oscar; Pisupati, Venkat; Jackson, Stephen P; Nussenzweig, André

2005-01-01

Human MDC1/NFBD1 has been found to interact with key players of the DNA-damage response machinery. Here, we identify and describe a functional homologue of MDC1/ NFBD1 in Mus musculus. The mouse homologue, mMDC1, retains the key motifs identified in the human protein and in response to ionizing radiation forms foci that co-localize with the MRE11-RAD50-NBS1 (MRN) complex and factors such as gammaH2AX and 53BP1. In addition, mMDC1 is associated with DNA damage sites generated during meiotic recombination as well as the X and Y chromosomes during the late stages of meiotic prophase I. Finally, whereas MDC1 shows strong colocalization with the MRN complex in response to DNA damage it does not co-localize with the MRN complex on replicating chromatin. These data suggest that mMDC1 is a marker for both exogenously and endogenously generated DNA double-stranded breaks and that its interaction with the MRN complex is initiated exclusively by DNA damage.

Narrative discourse in children with early focal brain injury.

PubMed

Reilly, J S; Bates, E A; Marchman, V A

1998-02-15

Children with early brain damage, unlike adult stroke victims, often go on to develop nearly normal language. However, the route and extent of their linguistic development are still unclear, as is the relationship between lesion site and patterns of delay and recovery. Here we address these questions by examining narratives from children with early brain damage. Thirty children (ages 3:7-10:10) with pre- or perinatal unilateral focal brain damage and their matched controls participated in a storytelling task. Analyses focused on linguistic proficiency and narrative competence. Overall, children with brain damage scored significantly lower than their age-matched controls on both linguistic (morphological and syntactic) indices and those targeting broader narrative qualities. Rather than indicating that children with brain damage fully catch up, these data suggest that deficits in linguistic abilities reassert themselves as children face new linguistic challenges. Interestingly, after age 5, site of lesion does not appear to be a significant factor and the delays we have witnessed do not map onto the lesion profiles observed in adults with analogous brain injuries.

Nandrolone decanoate induces genetic damage in multiple organs of rats.

PubMed

Pozzi, Renan; Fernandes, Kelly Rosseti; de Moura, Carolina Foot Gomes; Ferrari, Raquel Agnelli Mesquita; Fernandes, Kristianne Porta Santos; Renno, Ana Claudia Muniz; Ribeiro, Daniel Araki

2013-04-01

To evaluate the impact potential of nandrolone decanoate on DNA damage in multiple organs of Wistar rats by means of single-cell gel (comet) assay and micronucleus test. A total of 15 animals were distributed into three groups of five animals each as follows: control group = animal not exposed to nandrolone decanoate; experimental group = animals exposed to nandrolone decanoate for 24 h at 5 mg/kg subcutaneously; and experimental group = animals exposed to nandrolone decanoate for 24 h at 15 mg/kg subcutaneously. Significant statistical differences (p < 0.05) were noted in peripheral blood, liver, and heart cells exposed to nandrolone decanoate at the two doses evaluated. A clear dose-response relationship was observed between groups. Kidney cells showed genetic damage at only the highest dose (15 mg/kg) used. However, micronucleus data did not show remarkable differences among groups. In conclusion, the present study indicates that nandrolone decanoate induces genetic damage in rat blood, liver, heart, and kidney cells as shown by single-cell gel (comet) assay results.

High EDSS can predict risk for upper urinary tract damage in patients with multiple sclerosis.

PubMed

Ineichen, Benjamin V; Schneider, Marc P; Hlavica, Martin; Hagenbuch, Niels; Linnebank, Michael; Kessler, Thomas M

2018-04-01

Neurogenic lower urinary tract dysfunction (NLUTD) is very common in patients with multiple sclerosis (MS), and it might jeopardize renal function and thereby increase mortality. Although there are well-known urodynamic risk factors for upper urinary tract damage, no clinical prediction parameters are available. We aimed to assess clinical parameters potentially predicting urodynamic risk factors for upper urinary tract damage. A consecutive series of 141 patients with MS referred from neurologists for primary neuro-urological work-up including urodynamics were prospectively evaluated. Clinical parameters taken into account were age, sex, duration, and clinical course of MS and Expanded Disability Status Scale (EDSS). Multivariate modeling revealed EDSS as a clinical parameter significantly associated with urodynamic risk factors for upper urinary tract damage (odds ratio = 1.34, 95% confidence interval (CI) = 1.06-1.71, p = 0.02). Using receiver operator characteristic (ROC) curves, an EDSS of 5.0 as cutoff showed a sensitivity of 86%-87% and a specificity of 52% for at least one urodynamic risk factor for upper urinary tract damage. High EDSS is significantly associated with urodynamic risk factors for upper urinary tract damage and allows a risk-dependent stratification in daily neurological clinical practice to identify MS patients requiring further neuro-urological assessment and treatment.

Response of an invasive liana to simulated herbivory: implications for its biological control

NASA Astrophysics Data System (ADS)

Raghu, S.; Dhileepan, K.; Treviño, M.

2006-05-01

Pre-release evaluation of the efficacy of biological control agents is often not possible in the case of many invasive species targeted for biocontrol. In such circumstances simulating herbivory could yield significant insights into plant response to damage, thereby improving the efficiency of agent prioritisation, increasing the chances of regulating the performance of invasive plants through herbivory and minimising potential risks posed by release of multiple herbivores. We adopted this approach to understand the weaknesses herbivores could exploit, to manage the invasive liana, Macfadyena unguis-cati. We simulated herbivory by damaging the leaves, stem, root and tuber of the plant, in isolation and in combination. We also applied these treatments at multiple frequencies. Plant response in terms of biomass allocation showed that at least two severe defoliation treatments were required to diminish this liana's climbing habit and reduce its allocation to belowground tuber reserves. Belowground damage appears to have negligible effect on the plant's biomass production and tuber damage appears to trigger a compensatory response. Plant response to combinations of different types of damage did not differ significantly to that from leaf damage. This suggests that specialist herbivores in the leaf-feeding guild capable of removing over 50% of the leaf tissue may be desirable in the biological control of this invasive species.

Spectroscopic sensitivity of real-time, rapidly induced phytochemical change in response to damage.

PubMed

Couture, John J; Serbin, Shawn P; Townsend, Philip A

2013-04-01

An ecological consequence of plant-herbivore interactions is the phytochemical induction of defenses in response to insect damage. Here, we used reflectance spectroscopy to characterize the foliar induction profile of cardenolides in Asclepias syriaca in response to damage, tracked in vivo changes and examined the influence of multiple plant traits on cardenolide concentrations. Foliar cardenolide concentrations were measured at specific time points following damage to capture their induction profile. Partial least-squares regression (PLSR) modeling was employed to calibrate cardenolide concentrations to reflectance spectroscopy. In addition, subsets of plants were either repeatedly sampled to track in vivo changes or modified to reduce latex flow to damaged areas. Cardenolide concentrations and the induction profile of A. syriaca were well predicted using models derived from reflectance spectroscopy, and this held true for repeatedly sampled plants. Correlations between cardenolides and other foliar-related variables were weak or not significant. Plant modification for latex reduction inhibited an induced cardenolide response. Our findings show that reflectance spectroscopy can characterize rapid phytochemical changes in vivo. We used reflectance spectroscopy to identify the mechanisms behind the production of plant secondary metabolites, simultaneously characterizing multiple foliar constituents. In this case, cardenolide induction appears to be largely driven by enhanced latex delivery to leaves following damage. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Initiation and growth of multiple-site damage in the riveted lap joint of a curved stiffened fuselage panel: An experimental and analytical study

NASA Astrophysics Data System (ADS)

Ahmed, Abubaker Ali

As part of the structural integrity research of the National Aging Aircraft Research Program, a comprehensive study on multiple-site damage (MSD) initiation and growth in a pristine lap-joint fuselage panel has been conducted. The curved stiffened fuselage panel was tested at the Full-Scale Aircraft Structural Test Evaluation and Research (FASTER) facility located at the Federal Aviation Administration William J. Hughes Technical Center. A strain survey test was conducted to verify proper load application. The panel was then subjected to a fatigue test with constant-amplitude cyclic loading. The applied loading spectrum included underload marker cycles so that crack growth history could be reconstructed from post-test fractographic examinations. Crack formation and growth were monitored via nondestructive and high-magnification visual inspections. Strain gage measurements recorded during the strain survey tests indicated that the inner surface of the skin along the upper rivet row of the lap joint experienced high tensile stresses due to local bending. During the fatigue loading, cracks were detected by eddy-current inspections at multiple rivet holes along the upper rivet row. Through-thickness cracks were detected visually after about 80% of the fatigue life. Once MSD cracks from two adjacent rivet holes linked up, there was a quick deterioration in the structural integrity of the lap joint. The linkup resulted in a 2.87" (72.9-mm) lead fatigue crack that rapidly propagated across 12 rivet holes and crossed over into the next skin bay, at which stage the fatigue test was terminated. A post-fatigue residual strength test was then conducted by loading the panel quasi-statically up to final failure. The panel failed catastrophically when the crack extended instantaneously across three additional bays. Post-test fractographic examinations of the fracture surfaces in the lap joint of the fuselage panel were conducted to characterize subsurface crack initiation and growth. Results showed evidence of fretting damage and crack initiation at multiple locations near the rivet holes along the faying surface of the skin. The subsurface cracks grew significantly along the faying surface before reaching the outer surface of the skin, forming elliptical crack fronts. A finite element model (FE) of the panel was constructed and geometrically-nonlinear analyses conducted to determine strain distribution under the applied loads. The FE model was validated by comparing the analysis results with the strain gage measurements recorded during the strain survey test. The validated FE model was then used to determine stress-intensity factors at the crack tips. Stress-intensity factor results indicated that crack growth in the lap joint was under mixed-mode; however, the opening-mode stress intensity factor was dominant. The stress-intensity factors computed from the FE analysis were used to conduct cycle-by-cycle integration of fatigue crack growth. In the cycle-by-cycle integration, the NASGRO crack growth model was used with its parameters selected to account for the effects of plasticity-induced crack closure and the test environment on crack growth rate. Fatigue crack growth predictions from cycle-by-cycle computation were in good agreement with the experimental measured crack growth data. The results of the study provide key insights into the natural development and growth of MSD cracks in the pristine lap joint. The data provided by the study represent a valuable source for the evaluation and validation of analytical methodologies used for predicting MSD crack initiation and growth.

Site Features

EPA Pesticide Factsheets

This dataset consists of various site features from multiple Superfund sites in U.S. EPA Region 8. These data were acquired from multiple sources at different times and were combined into one region-wide layer.

Genotoxicity in Atlantic killifish (Fundulus heteroclitus) from a PAH-contaminated Superfund site on the Elizabeth River, Virginia

PubMed Central

Jung, Dawoon; Matson, Cole W.; Collins, Leonard B.; Laban, Geoff; Stapleton, Heather M.; Bickham, John W.; Swenberg, James A.; Giulio, Richard T. Di

2011-01-01

The Atlantic Wood Industries Superfund site (AWI) on the Elizabeth River in Portsmouth, VA is heavily contaminated with polycyclic aromatic hydrocarbons (PAHs) from a wood treatment facility. Atlantic killifish, or mummichog (Fundulus heteroclitus), at this Superfund site are exposed to very high concentrations of several carcinogens. In this study, we measured PAH concentrations in both fish tissues and sediments. Concurrently, we assessed different aspects of genotoxicity in the killifish exposed in situ. Both sediment and tissue PAH levels were significantly higher in AWI samples, relative to a reference site, but the chemistry profile was different between sediments and tissues. Killifish at AWI exhibited higher levels of DNA damage compared to reference fish, as measured via the flow cytometric method (FCM), and the damage was consistent with sediment PAH concentrations. Covalent binding of benzo[a]pyrene (BaP) metabolites to DNA, as measured via LC-MS/MS adduct detection methods, were also elevated and could be partially responsible for the DNA damage. Using similar LC-MS/MS methods, we found no evidence that oxidative DNA adducts had a role in observed genotoxicity. PMID:21706406

Recognition of DNA abasic site nanocavity by fluorophore-switched probe: Suitable for all sequence environments

NASA Astrophysics Data System (ADS)

Wang, Ying; Hu, Yuehua; Wu, Tao; Zhang, Lihua; Liu, Hua; Zhou, Xiaoshun; Shao, Yong

2016-01-01

Removal of a damaged base in DNA produces an abasic site (AP site) nanocavity. If left un-repaired in vivo by the specific enzyme, this nanocavity will result in nucleotide mutation in the following DNA replication. Therefore, selective recognition of AP site nanocavity by small molecules is important for identification of such DNA damage and development of genetic drugs. In this work, we investigate the fluorescence behavior of isoquinoline alkaloids including palmatine (PAL), berberine (BER), epiberberine (EPI), jatrorrhizine (JAT), coptisine (COP), coralyne (COR), worenine (WOR), berberrubine (BEU), sanguinarine (SAN), chelerythrine (CHE), and nitidine (NIT) upon binding with the AP nanocavity. PAL is screened out as the most efficient fluorophore-switched probe to recognize the AP nanocavity over the fully matched DNA. Its fluorescence enhancement occurs for all of the AP nanocavity sequence environments, which has not been achieved by the previously used probes. The bridged π conjugation effect should partially contribute to the AP nanocavity-specific fluorescence, as opposed to the solvent effect. Due to the strong binding with the AP nanocavity, PAL will find wide applications in the DNA damage recognition and sensor development.

Human T-cell leukemia virus-I tax oncoprotein functionally targets a subnuclear complex involved in cellular DNA damage-response.

PubMed

Haoudi, Abdelali; Daniels, Rodney C; Wong, Eric; Kupfer, Gary; Semmes, O John

2003-09-26

The virally encoded oncoprotein Tax has been implicated in HTLV-1-mediated cellular transformation. The exact mechanism by which this protein contributes to the oncogenic process is not known. However, it has been hypothesized that Tax induces genomic instability via repression of cellular DNA repair. We examined the effect of de novo Tax expression upon the cell cycle, because appropriate activation of cell cycle checkpoints is essential to a robust damage-repair response. Upon induction of tax expression, Jurkat T-cells displayed a pronounced accumulation in G2/M that was reversible by caffeine. We examined the G2-specific checkpoint signaling response in these cells and found activation of the ATM/chk2-mediated pathway, whereas the ATR/chk1-mediated response was unaffected. Immunoprecipitation with anti-chk2 antibody results in co-precipitation of Tax demonstrating a direct interaction of Tax with a chk2-containing complex. We also show that Tax targets a discrete nuclear site and co-localizes with chk2 and not chk1. This nuclear site, previously identified as Tax Speckled Structures (TSS), also contains the early damage response factor 53BP1. The recruitment of 53BP1 to TSS is dependent upon ATM signaling and requires expression of Tax. Specifically, Tax expression induces redistribution of diffuse nuclear 53BP1 to the TSS foci. Taken together these data suggest that the TSS describe a unique nuclear site involved in DNA damage recognition, repair response, and cell cycle checkpoint activation. We suggest that association of Tax with this multifunctional subnuclear site results in disruption of a subset of the site-specific activities and contributes to cellular genomic instability.

Cell-based therapeutic strategies for multiple sclerosis.

PubMed

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A

2017-11-01

The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

[Effects of different multiple cropping systems on paddy field weed community under long term paddy-upland rotation].

PubMed

Yang, Bin-Juan; Huang, Guo-Qin; Xu, Ning; Wang, Shu-Bin

2013-09-01

Based on a long term field experiment, this paper studied the effects of different multiple cropping systems on the weed community composition and species diversity under paddy-upland rotation. The multiple cropping rotation systems could significantly decrease weed density and inhibited weed growth. Among the rotation systems, the milk vetch-early rice-late maize --> milk vetchearly maize intercropped with early soybean-late rice (CCSR) had the lowest weed species dominance, which inhibited the dominant weeds and decreased their damage. Under different multiple cropping systems, the main weed community was all composed of Monochoia vaginalis, Echinochloa crusgalli, and Sagittaria pygmae, and the similarity of weed community was higher, with the highest similarity appeared in milk vetch-early rice-late maize intercropped with late soybean --> milk vetch-early maize-late rice (CSCR) and in CCSR. In sum, the multiple cropping rotations in paddy field could inhibit weeds to a certain extent, but attentions should be paid to the damage of some less important weeds.

Multiple pathways from three types of sugar receptor sites to metabotropic transduction pathways of the blowfly: study by the whole cell-clamp experiments.

PubMed

Kan, Hideko; Kataoka-Shirasugi, Naoko; Amakawa, Taisaku

2011-09-01

Multiple pathways from three types of multiple receptor sites to three types of metabotropic signal transduction pathways were investigated in the whole cell-clamp experiments using isolated labellar sugar receptor neurons (cells) of the adult blowfly, Phormia regina. First, the concentration-response curves of three types of sweet taste components specialized to multiple receptor sites were obtained: sucrose for the pyranose sites (P-sites), fructose for the furanose sites (F-sites), and l-valine for the alkyl sites (R-sites). Next, the effects of inhibitors such as 2', 5'-dideoxyadenosine on adenylyl cyclase in the cAMP pathway, LY 83583 on guanylyl cyclase in the cGMP pathway, and U-73122 on phospholipase C in the IP₃ pathway were examined. The results showed that all of the inhibitors affected each specific target in the second-messenger transduction pathways. The obtained results verified that the P-site corresponded to the cAMP, the F-site to the cGMP, and the R-site to the IP₃ transduction pathway, and that these three signal pathways did not have crossing points. Copyright © 2011 Elsevier Inc. All rights reserved.

Report: No Significant Residual Contamination Found at Deleted Superfund Sites, But Security Fences Were Damaged at Some Sites

EPA Pesticide Factsheets

Report #15-P-0013, November 10, 2014. Continued security breaches at some sites could impair the effectiveness of the remedy to protect human health and the environment and could expose trespassers to safety or health risks.

Engineering Evaluation of International Low Impact Docking System Latch Hooks

NASA Technical Reports Server (NTRS)

Martinez, J.; Patin, R.; Figert, J.

2013-01-01

The international Low Impact Docking System (iLIDS) provides a structural arrangement that allows for visiting vehicles to dock with the International Space Station (ISS) (Fig 1). The iLIDS docking units are mechanically joined together by a series of active and passive latch hooks. In order to preserve docking capability at the existing Russian docking interfaces, the iLIDS latch hooks are required to conform to the existing Russian design. The latch hooks are classified as being fail-safe. Since the latch hooks are fail-safe, the hooks are not fracture critical and a fatigue based service life assessment will satisfy the structural integrity requirements. Constant amplitude fatigue testing to failure on four sets of active/passive iLIDS latch hooks was performed at load magnitudes of 10, 11, and 12 kips. Failure analysis of the hook fatigue failures identified multi-site fatigue initiation that was effectively centered about the hook mid-plane (consistent with the 3D model results). The fatigue crack initiation distribution implies that the fatigue damage accumulation effectively results in a very low aspect ratio surface crack (which can be simulated as thru-thickness crack). Fatigue damage progression resulted in numerous close proximity fatigue crack initiation sites. It was not possible to determine if fatigue crack coalescence occurs during cyclic loading or as result of the fast fracture response. The presence of multiple fatigue crack initiation sites on different planes will result in the formation of ratchet marks as the cracks coalesce. Once the stable fatigue crack becomes unstable and the fast fracture advances across the remaining ligament and the plane stress condition at a free-surface will result in failure along a 45 deg. shear plane (slant fracture) and the resulting inclined edge is called a shear lip. The hook thickness on the plane of fatigue crack initiation is 0.787". The distance between the shear lips on this plane was on the order of 0.48" and it was effectively centered about the mid-plane of the section. The numerous ratchet marks between the shear lips on the fracture initiation plane are indicative of multiple fatigue initiation sites within this region. The distribution of the fatigue damage about the centerline of the hook is consistent with the analytical results that demonstrate peak stress/strain response at the mid-plane that decreases in the direction of the hook outer surfaces. Scanning electron microscope images of the failed sections detected fatigue crack striations in close proximity to the free surface of the hook radius. These findings were documented at three locations on the fracture surface : 1) adjacent to the left shear lip, 2) adjacent to the right shear lip, and 3) near the centerline of the section. The features of the titanium fracture surface did not allow for a determination of a critical crack size via identification of the region where the fatigue crack propagation became unstable. The fracture based service life projections where benchmarked with strain-life analyses. The strainrange response in the hook radius was defined via the correlated finite element models and the modified method of universal slopes was incorporated to define the strain-life equation for the titanium alloy. The strain-life assessment confirmed that the fracture based projections were reasonable for the loading range of interest. Based upon the analysis and component level fatigue test data a preliminary service life capability for the iLIDS active and passive hooks of 2 lifetimes is projected (includes a scatter factor of 4).

Outer organic layer and internal repair mechanism protects pteropod Limacina helicina from ocean acidification

NASA Astrophysics Data System (ADS)

Peck, Victoria L.; Tarling, Geraint A.; Manno, Clara; Harper, Elizabeth M.; Tynan, Eithne

2016-05-01

Scarred shells of polar pteropod Limacina helicina collected from the Greenland Sea in June 2012 reveal a history of damage, most likely failed predation, in earlier life stages. Evidence of shell fracture and subsequent re-growth is commonly observed in specimens recovered from the sub-Arctic and further afield. However, at one site within sea-ice on the Greenland shelf, shells that had been subject to mechanical damage were also found to exhibit considerable dissolution. It was evident that shell dissolution was localised to areas where the organic, periostracal sheet that covers the outer shell had been damaged at some earlier stage during the animal's life. Where the periostracum remained intact, the shell appeared pristine with no sign of dissolution. Specimens which appeared to be pristine following collection were incubated for four days. Scarring of shells that received periostracal damage during collection only became evident in specimens that were incubated in waters undersaturated with respect to aragonite, ΩAr≤1. While the waters from which the damaged specimens were collected at the Greenland Sea sea-ice margin were not ΩAr≤1, the water column did exhibit the lowest ΩAr values observed in the Greenland and Barents Seas, and was likely to have approached ΩAr≤1 during the winter months. We demonstrate that L. helicina shells are only susceptible to dissolution where both the periostracum has been breached and the aragonite beneath the breach is exposed to waters of ΩAr≤1. Exposure of multiple layers of aragonite in areas of deep dissolution indicate that, as with many molluscs, L. helicina is able to patch up dissolution damage to the shell by secreting additional aragonite internally and maintain their shell. We conclude that, unless breached, the periostracum provides an effective shield for pteropod shells against dissolution in waters ΩAr≤1, and when dissolution does occur the animal has an effective means of self-repair. We suggest that future studies of pteropod shell condition are undertaken on specimens from which the periostracum has not been removed in preparation.

Uplifting behavior of shallow buried pipe in liquefiable soil by dynamic centrifuge test.

PubMed

Huang, Bo; Liu, Jingwen; Lin, Peng; Ling, Daosheng

2014-01-01

Underground pipelines are widely applied in the so-called lifeline engineerings. It shows according to seismic surveys that the damage from soil liquefaction to underground pipelines was the most serious, whose failures were mainly in the form of pipeline uplifting. In the present study, dynamic centrifuge model tests were conducted to study the uplifting behaviors of shallow-buried pipeline subjected to seismic vibration in liquefied sites. The uplifting mechanism was discussed through the responses of the pore water pressure and earth pressure around the pipeline. Additionally, the analysis of force, which the pipeline was subjected to before and during vibration, was introduced and proved to be reasonable by the comparison of the measured and the calculated results. The uplifting behavior of pipe is the combination effects of multiple forces, and is highly dependent on the excess pore pressure.

Effects of Condensation on Peri-implant Bone Density and Remodeling

PubMed Central

Wang, L.; Wu, Y.; Perez, K.C.; Hyman, S.; Brunski, J.B.; Tulu, U.; Bao, C.; Salmon, B.; Helms, J.A.

2017-01-01

Bone condensation is thought to densify interfacial bone and thus improve implant primary stability, but scant data substantiate either claim. We developed a murine oral implant model to test these hypotheses. Osteotomies were created in healed maxillary extraction sites 1) by drilling or 2) by drilling followed by stepwise condensation with tapered osteotomes. Condensation increased interfacial bone density, as measured by a significant change in bone volume/total volume and trabecular spacing, but it simultaneously damaged the bone. On postimplant day 1, the condensed bone interface exhibited microfractures and osteoclast activity. Finite element modeling, mechanical testing, and immunohistochemical analyses at multiple time points throughout the osseointegration period demonstrated that condensation caused very high interfacial strains, marginal bone resorption, and no improvement in implant stability. Collectively, these multiscale analyses demonstrate that condensation does not positively contribute to implant stability. PMID:28048963

Effects of Condensation on Peri-implant Bone Density and Remodeling.

PubMed

Wang, L; Wu, Y; Perez, K C; Hyman, S; Brunski, J B; Tulu, U; Bao, C; Salmon, B; Helms, J A

2017-04-01

Bone condensation is thought to densify interfacial bone and thus improve implant primary stability, but scant data substantiate either claim. We developed a murine oral implant model to test these hypotheses. Osteotomies were created in healed maxillary extraction sites 1) by drilling or 2) by drilling followed by stepwise condensation with tapered osteotomes. Condensation increased interfacial bone density, as measured by a significant change in bone volume/total volume and trabecular spacing, but it simultaneously damaged the bone. On postimplant day 1, the condensed bone interface exhibited microfractures and osteoclast activity. Finite element modeling, mechanical testing, and immunohistochemical analyses at multiple time points throughout the osseointegration period demonstrated that condensation caused very high interfacial strains, marginal bone resorption, and no improvement in implant stability. Collectively, these multiscale analyses demonstrate that condensation does not positively contribute to implant stability.

Site-specific management of nematodes pitfalls and practicalities.

PubMed

Evans, Ken; Webster, Richard M; Halford, Paul D; Barker, Anthony D; Russell, Michael D

2002-09-01

The greatest constraint to potato production in the United Kingdom (UK) is damage by the potato cyst nematodes (PCN) Globodera pallida and G. rostochiensis. Management of PCN depends heavily on nematicides, which are costly. Of all the inputs in UK agriculture, nematicides offer the largest potential cost savings from spatially variable application, and these savings would be accompanied by environmental benefits. We mapped PCN infestations in potato fields and monitored the changes in population density and distribution that occurred when susceptible potato crops were grown. The inverse relationship between population density before planting and multiplication rate of PCN makes it difficult to devise reliable spatial nematicide application procedures, especially when the pre-planting population density is just less than the detection threshold. Also, the spatial dependence found suggests that the coarse sampling grids used commercially are likely to produce misleading distribution maps.

Combining wet etching and real-time damage event imaging to reveal the most dangerous laser damage initiator in fused silica.

PubMed

Hu, Guohang; Zhao, Yuanan; Liu, Xiaofeng; Li, Dawei; Xiao, Qiling; Yi, Kui; Shao, Jianda

2013-08-01

A reliable method, combining a wet etch process and real-time damage event imaging during a raster scan laser damage test, has been developed to directly determine the most dangerous precursor inducing low-density laser damage at 355 nm in fused silica. It is revealed that ~16% of laser damage sites were initiated at the place of the scratches, ~49% initiated at the digs, and ~35% initiated at invisible defects. The morphologies of dangerous scratches and digs were compared with those of moderate ones. It is found that local sharp variation at the edge, twist, or inside of a subsurface defect is the most dangerous laser damage precursor.

An Integrated Approach to Damage Accommodation in Flight Control

NASA Technical Reports Server (NTRS)

Boskovic, Jovan D.; Knoebel, Nathan; Mehra, Raman K.; Gregory, Irene

2008-01-01

In this paper we present an integrated approach to in-flight damage accommodation in flight control. The approach is based on Multiple Models, Switching and Tuning (MMST), and consists of three steps: In the first step the main objective is to acquire a realistic aircraft damage model. Modeling of in-flight damage is a highly complex problem since there is a large number of issues that need to be addressed. One of the most important one is that there is strong coupling between structural dynamics, aerodynamics, and flight control. These effects cannot be studied separately due to this coupling. Once a realistic damage model is available, in the second step a large number of models corresponding to different damage cases are generated. One possibility is to generate many linear models and interpolate between them to cover a large portion of the flight envelope. Once these models have been generated, we will implement a recently developed-Model Set Reduction (MSR) technique. The technique is based on parameterizing damage in terms of uncertain parameters, and uses concepts from robust control theory to arrive at a small number of "centered" models such that the controllers corresponding to these models assure desired stability and robustness properties over a subset in the parametric space. By devising a suitable model placement strategy, the entire parametric set is covered with a relatively small number of models and controllers. The third step consists of designing a Multiple Models, Switching and Tuning (MMST) strategy for estimating the current operating regime (damage case) of the aircraft, and switching to the corresponding controller to achieve effective damage accommodation and the desired performance. In the paper present a comprehensive approach to damage accommodation using Model Set Design,MMST, and Variable Structure compensation for coupling nonlinearities. The approach was evaluated on a model of F/A-18 aircraft dynamics under control effector damage, augmented by nonlinear cross-coupling terms and a structural dynamics model. The proposed approach achieved excellent performance under severe damage effects.

Thermal damage produced by high-irradiance continuous wave CO2 laser cutting of tissue.

PubMed

Schomacker, K T; Walsh, J T; Flotte, T J; Deutsch, T F

1990-01-01

Thermal damage produced by continuous wave (cw) CO2 laser ablation of tissue in vitro was measured for irradiances ranging from 360 W/cm2 to 740 kW/cm2 in order to investigate the extent to which ablative cooling can limit tissue damage. Damage zones thinner than 100 microns were readily produced using single pulses to cut guinea pig skin as well as bovine cornea, aorta, and myocardium. Multiple pulses can lead to increased damage. However, a systematic decrease in damage with irradiance, predicted theoretically by an evaporation model of ablation, was not observed. The damage-zone thickness was approximately constant around the periphery of the cut, consistent with the existence of a liquid layer which stores heat and leads to tissue damage, and with a model of damage and ablation recently proposed by Zweig et al.

Monitoring damage growth in titanium matrix composites using acoustic emission

NASA Technical Reports Server (NTRS)

Bakuckas, J. G., Jr.; Prosser, W. H.; Johnson, W. S.

1993-01-01

The application of the acoustic emission (AE) technique to locate and monitor damage growth in titanium matrix composites (TMC) was investigated. Damage growth was studied using several optical techniques including a long focal length, high magnification microscope system with image acquisition capabilities. Fracture surface examinations were conducted using a scanning electron microscope (SEM). The AE technique was used to locate damage based on the arrival times of AE events between two sensors. Using model specimens exhibiting a dominant failure mechanism, correlations were established between the observed damage growth mechanisms and the AE results in terms of the events amplitude. These correlations were used to monitor the damage growth process in laminates exhibiting multiple modes of damage. Results revealed that the AE technique is a viable and effective tool to monitor damage growth in TMC.

Endogenous Task Shift Processes in Relapsing-Remitting Multiple Sclerosis

ERIC Educational Resources Information Center

Stablum, F.; Meligrana, L.; Sgaramella, T.; Bortolon, F.; Toso, V.

2004-01-01

This paper reports a study that was aimed to evaluate executive functions in relapsing-remitting multiple sclerosis patients. The groups tested comprised 22 relapsing-remitting multiple sclerosis patients, and 22 non-brain damaged controls. When one is engaged in two speeded tasks, not simultaneously but with some form of alternation, it is slower…

Moisture migration, microstructure damage and protein structure changes in porcine longissimus muscle as influenced by multiple freeze-thaw cycles.

PubMed

Zhang, Mingcheng; Li, Fangfei; Diao, Xinping; Kong, Baohua; Xia, Xiufang

2017-11-01

This study investigated the effects of multiple freeze-thaw (F-T) cycles on water mobility, microstructure damage and protein structure changes in porcine longissimus muscle. The transverse relaxation time T 2 increased significantly when muscles were subjected to multiple F-T cycles (P<0.05), which means that immobile water shifted to free water and the free water mobility increased. Multiple F-T cycles caused sarcomere shortening, Z line fractures, and I band weakening and also led to microstructural destruction of muscle tissue. The decreased free amino group content and increased dityrosine in myofibrillar protein (MP) revealed that multiple F-T cycles caused protein cross-linking and oxidation. In addition, the results of size exclusion chromatography, circular dichroism spectra, UV absorption spectra, and intrinsic fluorescence spectroscopy indirectly proved that multiple F-T cycles could cause protein aggregation and degradation, α-helix structure disruption, hydrophobic domain exposure, and conformational changes of MP. Overall, repeated F-T cycles changed the protein structure and water distribution within meat. Copyright © 2017 Elsevier Ltd. All rights reserved.

Involvement of Matrin 3 and SFPQ/NONO in the DNA damage response.

PubMed

Salton, Maayan; Lerenthal, Yaniv; Wang, Shih-Ya; Chen, David J; Shiloh, Yosef

2010-04-15

The DNA damage response (DDR) is a complex signaling network that is induced by DNA lesions and vigorously activated by double strand breaks (DSBs). The DSB response is mobilized by the nuclear protein kinase ATM, which phosphorylates key players in its various branches. SFPQ (PSF) and NONO (p54) are nuclear proteins that interact with each other and have diverse roles in nucleic acids metabolism. The SFPQ/NONO heterodimer was previously found to enhance DNA strand break rejoining in vitro. Our attention was drawn to these two proteins as they interact with the nuclear matrix protein Matrin 3 (MATR3), which we found to be a novel ATM target. We asked whether SFPQ and NONO too are involved in the DSB response. Proteins that function at the early phase of this response are often recruited to the damaged sites. We observed rapid recruitment of SFPQ/NONO to sites of DNA damage induced by laser microbeam. In MATR3 knockdown cells SFPQ/NONO retention at DNA damage sites was prolonged. SFPQ and MATR3 depletion led to abnormal accumulation of cells at the S-phase of the cell cycle following treatment with the radiomimetic chemical neocarzinostatin. Notably, proteins involved in DSB repair via nonhomologous end-joining co-immunoprecipitated with NONO; SFPQ depletion delayed DSB repair. Collectively the data suggest that SFPQ, NONO and MATR3 are involved in the early stage of the DSB response, setting the scene for DSB repair.

Chromosomal damage and EROD induction in tree swallows (Tachycineta bicolor) along the Upper Mississippi River, Minnesota, USA

USGS Publications Warehouse

Emilie Bigorgne,; Custer, Thomas W.; Dummer, Paul; Erickson, Richard A.; Karouna-Renier, Natalie K.; Schultz, Sandra; Custer, Christine M.; Thogmartin, Wayne E.; Cole W. Matson,

2015-01-01

The health of tree swallows, Tachycineta bicolor, on the Upper Mississippi River (UMR) was assessed in 2010 and 2011 using biomarkers at six sites downriver of Minneapolis/St. Paul, MN metropolitan area, a tributary into the UMR, and a nearby lake. Chromosomal damage was evaluated in nestling blood by measuring the coefficient of variation of DNA content (DNA CV) using flow cytometry. Cytochrome P450 1A activity in nestling liver was measured using the ethoxyresorufin-O-dealkylase (EROD) assay, and oxidative stress was estimated in nestling livers via determination of thiobarbituric acid reacting substances (TBARS), reduced glutathione (GSH), oxidized glutathione (GSSG), the ratio GSSG/GSH, total sulfhydryl, and protein bound sulfhydryl (PBSH). A multilevel regression model (DNA CV) and simple regressions (EROD and oxidative stress) were used to evaluate biomarker responses for each location. Chromosomal damage was significantly elevated at two sites on the UMR (Pigs Eye and Pool 2) relative to the Green Mountain Lake reference site, while the induction of EROD activity was only observed at Pigs Eye. No measures of oxidative stress differed among sites. Multivariate analysis confirmed an increased DNA CV at Pigs Eye and Pool 2, and elevated EROD activity at Pigs Eye. These results suggest that the health of tree swallows has been altered at the DNA level at Pigs Eye and Pool 2 sites, and at the physiological level at Pigs Eye site only.

The impact of organochlorines and metals on wild fish living in a tropical hydroelectric reservoir: bioaccumulation and histopathological biomarkers.

PubMed

Paulino, Marcelo Gustavo; Benze, Tayrine Paschoaletti; Sadauskas-Henrique, Helen; Sakuragui, Marise Margareth; Fernandes, João Batista; Fernandes, Marisa Narciso

2014-11-01

This study evaluates the contaminants in water and their bioaccumulation in the gills and liver of two ecologically distinct fish species, Astyanax fasciatus and Pimelodus maculatus, living in the reservoir of the Furnas hydroelectric power station located in Minas Gerais in the southeastern Brazil. The histological alterations in these organs are also examined. Water and fish were collected in June and December from five sites (site 1: FU10, site 2: FU20, site 3: FU30, site 4: FU40 and site 5: FU50) in the reservoir, and agrochemicals and metals selected based on their use in the field crops surrounding the reservoir were analyzed in the water and in the fish gills and livers. The concentrations of the organochlorines aldrin/dieldrin, endosulfan and heptachlor/heptachlor epoxide as well as the metals copper, chromium, iron and zinc in the gills and livers of both fish species were higher in June than in December; the liver accumulated higher concentrations of contaminants than the gills. The organochlorine metolachlor was detected only in the liver. The histological pattern of changes was similar in both species with regard to contaminant accumulation in the gills and liver. Fish from FU10, the least contaminated site, exhibited normal gill structure and moderate to heavy liver damage. Fish collected at FU20 to FU50, which were contaminated with organochlorines and metals, showed slight to moderate gill damage in June and irreparable liver damage in the livers in June and December. The histological changes in the gills and liver were suitable to distinguishing contaminated field sites and are therefore useful biomarkers for environmental contamination representing a biological end-point of exposure. Copyright © 2014 Elsevier B.V. All rights reserved.

Quantitative percussion diagnostics as an indicator of the level of the structural pathology of teeth: Retrospective follow-up investigation of high-risk sites that remained pathological after restorative treatment.

PubMed

Sheets, Cherilyn G; Wu, Jean C; Earthman, James C

2017-11-29

Structural damage may remain even after a tooth is restored. Conventional diagnostic aids do not quantify the severity of structural damage or allow the monitoring of structural changes after restoration. The purpose of this retrospective clinical study was to provide an in-depth analysis of 9 high-risk sites after restoration. The analysis followed structural defects found upon disassembly, restorative materials used, therapeutic procedures provided, current longevity, and long-term quantitative percussion diagnostics (QPD) to monitor results. The hypothesis was that QPD can be used to quantify positive and negative changes in structural stability. Sixty sites requiring restoration were part of an institutional review board-approved clinical study. Each participant was examined comprehensively, including QPD testing, at each follow-up. Long-term changes in normal fit error (NFE) values after restoration were evaluated according to a pathology rating system established in an earlier publication. Nine highly compromised sites were chosen for further analysis and monitored for an additional 6 years. Of the 9 high-risk sites (NFE>0.04), 7 sites improved and 2 sites deteriorated. Potential causes for each trend were documented. The data support the hypothesis that QPD can be used to monitor changes in structural stability after restoration. Knowledge of changes in advance of any symptoms allows further preventive or therapeutic intervention before serious structural damage can occur. Follow-up QPD indications of site improvement can also assure the clinician of the desired structural outcome. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Multiple trauma in children: critical care overview.

PubMed

Wetzel, Randall C; Burns, R Cartland

2002-11-01

Multiple trauma is more than the sum of the injuries. Management not only of the physiologic injury but also of the pathophysiologic responses, along with integration of the child's emotional and developmental needs and the child's family, forms the basis of trauma care. Multiple trauma in children also elicits profound psychological responses from the healthcare providers involved with these children. This overview will address the pathophysiology of multiple trauma in children and the general principles of trauma management by an integrated trauma team. Trauma is a systemic disease. Multiple trauma stimulates the release of multiple inflammatory mediators. A lethal triad of hypothermia, acidosis, and coagulopathy is the direct result of trauma and secondary injury from the systemic response to trauma. Controlling and responding to the secondary pathophysiologic sequelae of trauma is the cornerstone of trauma management in the multiply injured, critically ill child. Damage control surgery is a new, rational approach to the child with multiple trauma. The selection of children for damage control surgery depends on the severity of injury. Major abdominal vascular injuries and multiple visceral injuries are best considered for this approach. The effective management of childhood multiple trauma requires a combined team approach, consideration of the child and family, an organized trauma system, and an effective quality assurance and improvement mechanism.

Ultraviolet Shadowing of RNA Can Cause Significant Chemical Damage in Seconds

PubMed Central

Kladwang, Wipapat; Hum, Justine; Das, Rhiju

2012-01-01

Chemical purity of RNA samples is important for high-precision studies of RNA folding and catalytic behavior, but photodamage accrued during ultraviolet (UV) shadowing steps of sample preparation can reduce this purity. Here, we report the quantitation of UV-induced damage by using reverse transcription and single-nucleotide-resolution capillary electrophoresis. We found photolesions in a dozen natural and artificial RNAs; across multiple sequence contexts, dominantly at but not limited to pyrimidine doublets; and from multiple lamps recommended for UV shadowing. Irradiation time-courses revealed detectable damage within a few seconds of exposure for 254 nm lamps held at a distance of 5 to 10 cm from 0.5-mm thickness gels. Under these conditions, 200-nucleotide RNAs subjected to 20 seconds of UV shadowing incurred damage to 16-27% of molecules; and, due to a ‘skin effect’, the molecule-by-molecule distribution of lesions gave 4-fold higher variance than a Poisson distribution. Thicker gels, longer wavelength lamps, and shorter exposure times reduced but did not eliminate damage. These results suggest that RNA biophysical studies should report precautions taken to avoid artifactual heterogeneity from UV shadowing. PMID:22816040

Ion Plume Damage in Formation Flight Regimes

NASA Astrophysics Data System (ADS)

Young, Jarred Alexander

This effort examines the potential for damage from plume impingement from an electric propulsion system within spacecraft missions that utilize a formation flight architecture. Specifically, the potential erosion of a structural material (Aluminum) and anti-reflective coatings for solar cell coverglass are explored. Sputter yields for the materials of Aluminum, Magnesium Fluoride, and Indium Tin Oxide are experimentally validated using an electrostatic ion source at energies varying from 500-1500 eV. Erosion depths are analyzed using white-light optical profilometry to measure potential depths up to 1 microm. This erosion data was then utilized to create (or augment) Bohdansky and Yamamura theoretical curve fits for multiple incidence angles to look at theoretical sputter effects within formation flight regimes at multiple formation distances from 50-1000 m. The damage from these electric propulsion plumes is explored throughout multiple orbital conditions from LEO, Sun-Synchronous, and GEO. Factors affecting erosion are: plume density, local geomagnetic field environment and incidence angles of target surfaces. Results from this simulated study show significant erosion with GEO with minor erosion in some LEO and all Sun-Synchronous cases.

43 CFR 11.24 - Preassessment screen-information on the site.

Code of Federal Regulations, 2011 CFR

2011-10-01

... to grant the permit or license authorizes such commitment of natural resources, and that the facility... site. 11.24 Section 11.24 Public Lands: Interior Office of the Secretary of the Interior NATURAL RESOURCE DAMAGE ASSESSMENTS Preassessment Phase § 11.24 Preassessment screen—information on the site. (a...

43 CFR 11.24 - Preassessment screen-information on the site.

Code of Federal Regulations, 2010 CFR

2010-10-01

... to grant the permit or license authorizes such commitment of natural resources, and that the facility... site. 11.24 Section 11.24 Public Lands: Interior Office of the Secretary of the Interior NATURAL RESOURCE DAMAGE ASSESSMENTS Preassessment Phase § 11.24 Preassessment screen—information on the site. (a...

Documenting the Density of Subtidal Marine Debris across Multiple Marine and Coastal Habitats

PubMed Central

Smith, Stephen D. A.; Edgar, Robert J.

2014-01-01

Marine debris is recognised globally as a key threatening process to marine life, but efforts to address the issue are hampered by the lack of data for many marine habitats. By developing standardised protocols and providing training in their application, we worked with >300 volunteer divers from 11 underwater research groups to document the scale of the subtidal marine debris problem at 120 sites across >1000 km of the coast of NSW, Australia. Sampling consisted of replicated 25×5 m transects in which all debris was identified, counted, and, where appropriate, removed. Sites ranged from estuarine settings adjacent to major population centres, to offshore islands within marine parks. Estuaries and embayments were consistently found to be the most contaminated habitats. Fishing-related items (and especially monofilament and braided fishing line) were most prevalent at the majority of sites, although food and drink items were important contributors at sites adjacent to population centres. The results identified damaging interactions between marine debris and marine biota at some key locations, highlighting the need for management intervention to ensure habitat sustainability. This study reinforces the important contribution that volunteers can make to assessing conservation issues requiring broad-scale data collection. In this case, citizen scientists delivered data that will inform, and help to prioritise, management approaches at both statewide and local scales. These initial data also provide an important baseline for longer-term, volunteer-based monitoring programs. PMID:24743690

In situ FTIR microspectroscopy of extravasated blood-damaged brain tissue

NASA Astrophysics Data System (ADS)

Wetzel, David L.; Le Vine, Steven M.

1994-01-01

Fourier transform infrared (FT-IR) microspectroscopy enables the collection of infrared spectra from microscopic regions of tissue sections. The objectives of this study were to utilize FT-IR microspectroscopy to analyze the spatial distribution of chemical changes that result from the extravasation of blood into the brain and to determine if products of free radical damage are associated with the damaged areas. An animal model that involves the injection of blood into the white matter of rat brains was used. Maps depicting the relative concentrations of chemical functional groups of lesioned sites and surrounding areas were made. Significant decreases were observed for CH2, C equals O, P equals O, and HO-C-H functional groups at the lesioned site and penumbra regions compared to the neighboring normal tissue areas.

October 1, 1989 tornado at the Savannah River Site

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

Parker, M.J.; Kurzeja, R.J.

1990-01-01

A tornado with wind speeds in the 113 to 157 mph range struck the southern portion of the Savannah River Site near Aiken, SC at around 7:30 pm on October 1, 1989. The tornado was spawned from a severe thunderstorm with a height of 57,000 ft in a warm and humid air mass. Two million dollars in timber damage occurred over 2,500 acres along a ten-mile swath, but no onsite structural damage or personal injury occurred. Tree-fall patterns indicated that some of this damage was the result of thunderstorm downbursts which accompanied the tornado. Ground-based and aerial photography showed bothmore » snapped and mowed over trees which indicate that the tornado was elevated at times. 4 refs., 25 figs., 2 tabs.« less

Hurricane Andrew Damage in Relation to Wood Decay Fungi and Insects in Bottomland Hardwoods of the Atchafalaya Basin, Louisiana

Treesearch

Theodor D. Leininger; A. Dan Wilson; Donald G. Lester

1997-01-01

Hurricane Andrew caused damage to more than 780 sq.km of bottomland hardwood and cypress-tupelo forests in the Atchafalaya Basin of Louisiana in August 1992. Trees in bottomland hardwood sites were examined, in early May 1994, for signs and symptoms of wood decay fungi, and for insect damage, ostensibly present before the hurricane, which may have predisposed trees to...

Timing matters: error-prone gap filling and translesion synthesis in immunoglobulin gene hypermutation

PubMed Central

Sale, Julian E.; Batters, Christopher; Edmunds, Charlotte E.; Phillips, Lara G.; Simpson, Laura J.; Szüts, Dávid

2008-01-01

By temporarily deferring the repair of DNA lesions encountered during replication, the bypass of DNA damage is critical to the ability of cells to withstand genomic insults. Damage bypass can be achieved either by recombinational mechanisms that are generally accurate or by a process called translesion synthesis. Translesion synthesis involves replacing the stalled replicative polymerase with one of a number of specialized DNA polymerases whose active sites are able to tolerate a distorted or damaged DNA template. While this property allows the translesion polymerases to synthesize across damaged bases, it does so with the trade-off of an increased mutation rate. The deployment of these enzymes must therefore be carefully regulated. In addition to their important role in general DNA damage tolerance and mutagenesis, the translesion polymerases play a crucial role in converting the products of activation induced deaminase-catalysed cytidine deamination to mutations during immunoglobulin gene somatic hypermutation. In this paper, we specifically consider the control of translesion synthesis in the context of the timing of lesion bypass relative to replication fork progression and arrest at sites of DNA damage. We then examine how recent observations concerning the control of translesion synthesis might help refine our view of the mechanisms of immunoglobulin gene somatic hypermutation. PMID:19008194

DNA Damage Repair and the Emerging Role of Poly(ADP-ribose) Polymerase Inhibition in Cancer Therapeutics.

PubMed

Rabenau, Karen; Hofstatter, Erin

2016-07-01

As a result of improved understanding of DNA repair mechanisms, poly(ADP-ribose) polymerase inhibitors (PARPi) are increasingly recognized to play an important therapeutic role in the treatment of cancer. The aim of this article is to provide a review of PARPi function in DNA damage repair and synthetic lethality and to demonstrate how these mechanisms can be exploited to provide new PARPi-based therapies to patients with solid tumors. Literature from a range of sources, including PubMed and MEDLINE, were searched to identify recent reports regarding DNA damage repair and PARPi. DNA damage repair is central to cellular viability. The family of poly(ADP-ribose) polymerase proteins play multiple intracellular roles in DNA repair, but function primarily in the resolution of repair of single-strand DNA breaks. Insights through the discovery of germline BRCA1/2 mutations led to the understanding of synthetic lethality and the potential therapeutic role of PARPi in the treatment of cancer. Further understanding of DNA damage repair and the concept of BRCA-like tumors have catalyzed PARPi clinical investigation in multiple oncologic settings. PARPi hold great promise in the treatment of solid tumors, both as monotherapy and in combination with other cancer therapeutics. Multiple PARPi clinical trials are currently underway. Further understanding of aberrant DNA repair mechanisms in the germline and in the tumor genome will allow clinicians and researchers to apply PARPi most strategically in the era of personalized medicine. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

DNA DAMAGE AND EXTERNAL LESIONS IN BROWN BULLHEADS FROM CONTAMINATED HABITATS

EPA Science Inventory

The Comet assay was used to compare levels of DNA damage in brown bullheads (Ameiurus nebulosus) collected from three known contaminated locations, the Cuyahoga River, Ashtabula River, and Ashumet Pond (Cape Cod), with brown bullheads collected from three paired reference sites, ...

Compression of laminated composite beams with initial damage

NASA Technical Reports Server (NTRS)

Breivik, Nicole L.; Gurdal, Zafer; Griffin, O. H., Jr.

1993-01-01

The effect of isolated damage modes on the compressive strength and failure characteristics of laminated composite test specimens were evaluated experimentally and numerically. In addition to specimens without initial damage, specimens with three types of initial damage were considered: (1) specimens with short delaminations distributed evenly through the specimen thickness, (2) specimens with few long delaminations, and (3) specimens with local fiber damage in the surface plies under the three-point bend contact point. It was found that specimens with short multiple delamination experienced the greatest reduction in compression strength compared to the undamaged specimens. Single delaminations far from the specimen surface had little effect on the final compression strength, and moderate strength reduction was observed for specimens with localized surface ply damage.

Geospatial optimization of siting large-scale solar projects

USGS Publications Warehouse

Macknick, Jordan; Quinby, Ted; Caulfield, Emmet; Gerritsen, Margot; Diffendorfer, James E.; Haines, Seth S.

2014-01-01

guidelines by being user-driven, transparent, interactive, capable of incorporating multiple criteria, and flexible. This work provides the foundation for a dynamic siting assistance tool that can greatly facilitate siting decisions among multiple stakeholders.

An overview of road damages due to flooding: Case study in Kedah state, Malaysia

NASA Astrophysics Data System (ADS)

Ismail, Muhd Shahril Nizam; Ghani, Abdul Naser Abdul

2017-10-01

Flooding occurs frequently in many countries including Malaysia. Floods in Malaysia are usually due to heavy and prolonged rainfall, uncontrolled development, and drainage systems that are not being monitored. Road damage due to flooding event can cause huge expenditures for the post-flooding rehabilitation and maintenance. The required maintenance and rehabilitation could upset the original life cycle cost estimations. Data on road statistics were obtained from the Highway Planning Division, Ministry of Works Malaysia and data on flooding was collected from the Department of Irrigation and Drainage Malaysia for events between 2012 and 2015. The pilot sites were selected based on its historical cases of floods that caused road damages in Kedah. The pilot site indicated that the impact of flooding on road infrastructures systems can be used to plan better road design and maintenances. It also revealed that it costs more than RM 1 million to reinstate roads damaged by flooding in a typical district annually.

Quantification of residual stress from photonic signatures of fused silica

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

Cramer, K. Elliott; Yost, William T.; Hayward, Maurice

2014-02-18

A commercially available grey-field polariscope (GFP) instrument for photoelastic examination is used to assess impact damage inflicted upon the outer-most pane of Space Shuttle windows made from fused silica. A method and apparatus for calibration of the stress-optic coefficient using four-point bending is discussed. The results are validated on known material (acrylic) and are found to agree with literature values to within 6%. The calibration procedure is then applied to fused-silica specimens and the stress-optic coefficient is determined to be 2.43 ± 0.54 × 10{sup −12} Pa{sup −1}. Fused silica specimens containing impacts artificially made at NASA’s Hypervelocity Impact Technologymore » Facility (HIT-F), to simulate damage typical during space flight, are examined. The damage sites are cored from fused silica window carcasses and examined with the GFP. The calibrated GFP measurements of residual stress patterns surrounding the damage sites are presented.« less

Array automated assembly, phase 2

NASA Technical Reports Server (NTRS)

Taylor, W. E.

1978-01-01

An analysis was made of cost tradeoffs for shaping modified square wafers from cylindrical crystals. Tests were conducted of the effectiveness of texture etching for removal of surface damage on sawed wafers. A single step texturing etch appeared adequate for removal of surface damage on wafers cut with multiple blade reciprocating slurry saws.

An improved EMD method for modal identification and a combined static-dynamic method for damage detection

NASA Astrophysics Data System (ADS)

Yang, Jinping; Li, Peizhen; Yang, Youfa; Xu, Dian

2018-04-01

Empirical mode decomposition (EMD) is a highly adaptable signal processing method. However, the EMD approach has certain drawbacks, including distortions from end effects and mode mixing. In the present study, these two problems are addressed using an end extension method based on the support vector regression machine (SVRM) and a modal decomposition method based on the characteristics of the Hilbert transform. The algorithm includes two steps: using the SVRM, the time series data are extended at both endpoints to reduce the end effects, and then, a modified EMD method using the characteristics of the Hilbert transform is performed on the resulting signal to reduce mode mixing. A new combined static-dynamic method for identifying structural damage is presented. This method combines the static and dynamic information in an equilibrium equation that can be solved using the Moore-Penrose generalized matrix inverse. The combination method uses the differences in displacements of the structure with and without damage and variations in the modal force vector. Tests on a four-story, steel-frame structure were conducted to obtain static and dynamic responses of the structure. The modal parameters are identified using data from the dynamic tests and improved EMD method. The new method is shown to be more accurate and effective than the traditional EMD method. Through tests with a shear-type test frame, the higher performance of the proposed static-dynamic damage detection approach, which can detect both single and multiple damage locations and the degree of the damage, is demonstrated. For structures with multiple damage, the combined approach is more effective than either the static or dynamic method. The proposed EMD method and static-dynamic damage detection method offer improved modal identification and damage detection, respectively, in structures.

Multiple-Use Site Demand Analysis: An Application to the Boundary Waters Canoe Area Wilderness.

ERIC Educational Resources Information Center

Peterson, George L.; And Others

1982-01-01

A single-site, multiple-use model for analyzing trip demand is derived from a multiple site regional model based on utility maximizing choice theory. The model is used to analyze and compare trips to the Boundary Waters Canoe Area Wilderness for several types of use. Travel cost elasticities of demand are compared and discussed. (Authors/JN)

Forced Ambiguity of the Leucine Codons for Multiple-Site-Specific Incorporation of a Noncanonical Amino Acid

PubMed Central

Kwon, Inchan; Choi, Eun Sil

2016-01-01

Multiple-site-specific incorporation of a noncanonical amino acid into a recombinant protein would be a very useful technique to generate multiple chemical handles for bioconjugation and multivalent binding sites for the enhanced interaction. Previously combination of a mutant yeast phenylalanyl-tRNA synthetase variant and the yeast phenylalanyl-tRNA containing the AAA anticodon was used to incorporate a noncanonical amino acid into multiple UUU phenylalanine (Phe) codons in a site-specific manner. However, due to the less selective codon recognition of the AAA anticodon, there was significant misincorporation of a noncanonical amino acid into unwanted UUC Phe codons. To enhance codon selectivity, we explored degenerate leucine (Leu) codons instead of Phe degenerate codons. Combined use of the mutant yeast phenylalanyl-tRNA containing the CAA anticodon and the yPheRS_naph variant allowed incorporation of a phenylalanine analog, 2-naphthylalanine, into murine dihydrofolate reductase in response to multiple UUG Leu codons, but not to other Leu codon sites. Despite the moderate UUG codon occupancy by 2-naphthylalaine, these results successfully demonstrated that the concept of forced ambiguity of the genetic code can be achieved for the Leu codons, available for multiple-site-specific incorporation. PMID:27028506

Forced Ambiguity of the Leucine Codons for Multiple-Site-Specific Incorporation of a Noncanonical Amino Acid.

PubMed

Kwon, Inchan; Choi, Eun Sil

2016-01-01

Multiple-site-specific incorporation of a noncanonical amino acid into a recombinant protein would be a very useful technique to generate multiple chemical handles for bioconjugation and multivalent binding sites for the enhanced interaction. Previously combination of a mutant yeast phenylalanyl-tRNA synthetase variant and the yeast phenylalanyl-tRNA containing the AAA anticodon was used to incorporate a noncanonical amino acid into multiple UUU phenylalanine (Phe) codons in a site-specific manner. However, due to the less selective codon recognition of the AAA anticodon, there was significant misincorporation of a noncanonical amino acid into unwanted UUC Phe codons. To enhance codon selectivity, we explored degenerate leucine (Leu) codons instead of Phe degenerate codons. Combined use of the mutant yeast phenylalanyl-tRNA containing the CAA anticodon and the yPheRS_naph variant allowed incorporation of a phenylalanine analog, 2-naphthylalanine, into murine dihydrofolate reductase in response to multiple UUG Leu codons, but not to other Leu codon sites. Despite the moderate UUG codon occupancy by 2-naphthylalaine, these results successfully demonstrated that the concept of forced ambiguity of the genetic code can be achieved for the Leu codons, available for multiple-site-specific incorporation.

Causes, effects and connectivity changes in MS-related cognitive decline.

PubMed

Rimkus, Carolina de Medeiros; Steenwijk, Martijn D; Barkhof, Frederik

2016-01-01

Cognitive decline is a frequent but undervalued aspect of multiple sclerosis (MS). Currently, it remains unclear what the strongest determinants of cognitive dysfunction are, with grey matter damage most directly related to cognitive impairment. Multi-parametric studies seem to indicate that individual factors of MS-pathology are highly interdependent causes of grey matter atrophy and permanent brain damage. They are associated with intermediate functional effects (e.g. in functional MRI) representing a balance between disconnection and (mal) adaptive connectivity changes. Therefore, a more comprehensive MRI approach is warranted, aiming to link structural changes with functional brain organization. To better understand the disconnection syndromes and cognitive decline in MS, this paper reviews the associations between MRI metrics and cognitive performance, by discussing the interactions between multiple facets of MS pathology as determinants of brain damage and how they affect network efficiency.

Total Internal Reflection Microscopy (TIRM) as a nondestructive surface damage assessment tool

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

Liao, Z.M.; Cohen, S.J.; Taylor, J.R.

1994-10-01

An easy to use, nondestructive, method for evaluating subsurface damage in polished substrates has been established at LLNL. Subsurface damage has been related to laser damage in coated optical components used in high power, high repetition rate laser systems. Total Internal Reflection Microscopy (TIRM) has been shown to be a viable nondestructive technique in analyzing subsurface damage in optical components. A successful TIRM system has been established for evaluating subsurface damage on fused silica components. Laser light scattering from subsurface damage sites is collected through a Nomarski microscope. These images are then captured by a CCD camera for analysis onmore » a computer. A variety of optics, including components with intentional subsurface damage due to grinding and polishing, have been analyzed and their TIRM images compared to an existing destructive etching method. Methods for quantitative measurement of subsurface damage are also discussed.« less

Transcriptional Regulation of Brain-Derived Neurotrophic Factor (BDNF) by Methyl CpG Binding Protein 2 (MeCP2): a Novel Mechanism for Re-Myelination and/or Myelin Repair Involved in the Treatment of Multiple Sclerosis (MS).

PubMed

KhorshidAhmad, Tina; Acosta, Crystal; Cortes, Claudia; Lakowski, Ted M; Gangadaran, Surendiran; Namaka, Michael

2016-03-01

Multiple sclerosis (MS) is a chronic progressive, neurological disease characterized by the targeted immune system-mediated destruction of central nervous system (CNS) myelin. Autoreactive CD4+ T helper cells have a key role in orchestrating MS-induced myelin damage. Once activated, circulating Th1-cells secrete a variety of inflammatory cytokines that foster the breakdown of blood-brain barrier (BBB) eventually infiltrating into the CNS. Inside the CNS, they become reactivated upon exposure to the myelin structural proteins and continue to produce inflammatory cytokines such as tumor necrosis factor α (TNFα) that leads to direct activation of antibodies and macrophages that are involved in the phagocytosis of myelin. Proliferating oligodendrocyte precursors (OPs) migrating to the lesion sites are capable of acute remyelination but unable to completely repair or restore the immune system-mediated myelin damage. This results in various permanent clinical neurological disabilities such as cognitive dysfunction, fatigue, bowel/bladder abnormalities, and neuropathic pain. At present, there is no cure for MS. Recent remyelination and/or myelin repair strategies have focused on the role of the neurotrophin brain-derived neurotrophic factor (BDNF) and its upstream transcriptional repressor methyl CpG binding protein (MeCP2). Research in the field of epigenetic therapeutics involving histone deacetylase (HDAC) inhibitors and lysine acetyl transferase (KAT) inhibitors is being explored to repress the detrimental effects of MeCP2. This review will address the role of MeCP2 and BDNF in remyelination and/or myelin repair and the potential of HDAC and KAT inhibitors as novel therapeutic interventions for MS.

Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering.

PubMed

Nims, Robert J; Durney, Krista M; Cigan, Alexander D; Dusséaux, Antoine; Hung, Clark T; Ateshian, Gerard A

2016-02-06

This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process.

Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering

PubMed Central

Nims, Robert J.; Durney, Krista M.; Cigan, Alexander D.; Hung, Clark T.; Ateshian, Gerard A.

2016-01-01

This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process. PMID:26855751

Method for assaying clustered DNA damages

DOEpatents

Sutherland, Betsy M.

2004-09-07

Disclosed is a method for detecting and quantifying clustered damages in DNA. In this method, a first aliquot of the DNA to be tested for clustered damages with one or more lesion-specific cleaving reagents under conditions appropriate for cleavage of the DNA to produce single-strand nicks in the DNA at sites of damage lesions. The number average molecular length (Ln) of double stranded DNA is then quantitatively determined for the treated DNA. The number average molecular length (Ln) of double stranded DNA is also quantitatively determined for a second, untreated aliquot of the DNA. The frequency of clustered damages (.PHI..sub.c) in the DNA is then calculated.

Structural damage diagnostics via wave propagation-based filtering techniques

NASA Astrophysics Data System (ADS)

Ayers, James T., III

Structural health monitoring (SHM) of aerospace components is a rapidly emerging field due in part to commercial and military transport vehicles remaining in operation beyond their designed life cycles. Damage detection strategies are sought that provide real-time information of the structure's integrity. One approach that has shown promise to accurately identify and quantify structural defects is based on guided ultrasonic wave (GUW) inspections, where low amplitude attenuation properties allow for long range and large specimen evaluation. One drawback to GUWs is that they exhibit a complex multi-modal response, such that each frequency corresponds to at least two excited modes, and thus intelligent signal processing is required for even the simplest of structures. In addition, GUWs are dispersive, whereby the wave velocity is a function of frequency, and the shape of the wave packet changes over the spatial domain, requiring sophisticated detection algorithms. Moreover, existing damage quantification measures are typically formulated as a comparison of the damaged to undamaged response, which has proven to be highly sensitive to changes in environment, and therefore often unreliable. As a response to these challenges inherent to GUW inspections, this research develops techniques to locate and estimate the severity of the damage. Specifically, a phase gradient based localization algorithm is introduced to identify the defect position independent of excitation frequency and damage size. Mode separation through the filtering technique is central in isolating and extracting single mode components, such as reflected, converted, and transmitted modes that may arise from the incident wave impacting a damage. Spatially-integrated single and multiple component mode coefficients are also formulated with the intent to better characterize wave reflections and conversions and to increase the signal to noise ratios. The techniques are applied to damaged isotropic finite element plate models and experimental data obtained from Scanning Laser Doppler Vibrometry tests. Numerical and experimental parametric studies are conducted, and the current strengths and weaknesses of the proposed approaches are discussed. In particular, limitations to the damage profiling characterization are shown for low ultrasonic frequency regimes, whereas the multiple component mode conversion coefficients provide excellent noise mitigation. Multiple component estimation relies on an experimental technique developed for the estimation of Lamb wave polarization using a 1D Laser Vibrometer. Lastly, suggestions are made to apply the techniques to more structurally complex geometries.

Two-stage damage diagnosis based on the distance between ARMA models and pre-whitening filters

NASA Astrophysics Data System (ADS)

Zheng, H.; Mita, A.

2007-10-01

This paper presents a two-stage damage diagnosis strategy for damage detection and localization. Auto-regressive moving-average (ARMA) models are fitted to time series of vibration signals recorded by sensors. In the first stage, a novel damage indicator, which is defined as the distance between ARMA models, is applied to damage detection. This stage can determine the existence of damage in the structure. Such an algorithm uses output only and does not require operator intervention. Therefore it can be embedded in the sensor board of a monitoring network. In the second stage, a pre-whitening filter is used to minimize the cross-correlation of multiple excitations. With this technique, the damage indicator can further identify the damage location and severity when the damage has been detected in the first stage. The proposed methodology is tested using simulation and experimental data. The analysis results clearly illustrate the feasibility of the proposed two-stage damage diagnosis methodology.

Damage threshold from large retinal spot size repetitive-pulse laser exposures.

PubMed

Lund, Brian J; Lund, David J; Edsall, Peter R

2014-10-01

The retinal damage thresholds for large spot size, multiple-pulse exposures to a Q-switched, frequency doubled Nd:YAG laser (532 nm wavelength, 7 ns pulses) have been measured for 100 μm and 500 μm retinal irradiance diameters. The ED50, expressed as energy per pulse, varies only weakly with the number of pulses, n, for these extended spot sizes. The previously reported threshold for a multiple-pulse exposure for a 900 μm retinal spot size also shows the same weak dependence on the number of pulses. The multiple-pulse ED50 for an extended spot-size exposure does not follow the n dependence exhibited by small spot size exposures produced by a collimated beam. Curves derived by using probability-summation models provide a better fit to the data.

Surface crack analysis applied to impact damage in a thick graphite-epoxy composite

NASA Technical Reports Server (NTRS)

Poe, C. C., Jr.; Harris, C. E.; Morris, D. H.

1988-01-01

The residual tensile strength of a thick graphite/epoxy composite with impact damage was predicted using surface crack analysis. The damage was localized to a region directly beneath the impact site and extended only part way through the laminate. The damaged region contained broken fibers, and the locus of breaks in each layer resembled a crack perpendicular to the direction of the fibers. In some cases, the impacts broke fibers without making a visible crater. The impact damage was represented as a semi-elliptical surface crack with length and depth equal to that of the impact damage. The maximum length and depth of the damage were predicted with a stress analysis and a maximum shear stress criterion. The predictions and measurements of strength were in good agreement.

Surface crack analysis applied to impact damage in a thick graphite/epoxy composite

NASA Technical Reports Server (NTRS)

Poe, Clarence C., Jr.; Harris, Charles E.; Morris, Don H.

1990-01-01

The residual tensile strength of a thick graphite/epoxy composite with impact damage was predicted using surface crack analysis. The damage was localized to a region directly beneath the impact site and extended only part way through the laminate. The damaged region contained broken fibers, and the locus of breaks in each layer resembled a crack perpendicular to the direction of the fibers. In some cases, the impacts broke fibers without making a visible crater. The impact damage was represented as a semi-elliptical surface crack with length and depth equal to that of the impact damage. The maximum length and depth of the damage were predicted with a stress analysis and a maximum shear stress criterion. The predictions and measurements of strength were in good agreement.

Constraining ground motion parameters and determining the historic earthquake that damaged the vaults underneath the Old City of Jerusalem

NASA Astrophysics Data System (ADS)

Yagoda-Biran, G.; Hatzor, Y. H.

2013-12-01

Evidence for seismically induced damage are preserved in historic masonry structures below the Old City of Jerusalem at a site known locally as the 'Western Wall Tunnels' complex, possibly one of the most important tourist attractions in the world. In the tunnels, structures dated to 500 BC and up until modern times have been uncovered by recent archeological excavation. One of the interesting findings is a 100 m long bridge, composed of two rows of barrel vaults, believed to have been constructed during the 3rd century AD to allow easy access to the Temple Mount. In one of the vaults a single masonry block is displaced 7 cm downward with respect to its neighbors (see figure below). Since the damage seems seismically driven, back analysis of the damage with the numerical Discontinuous Deformation Analysis (DDA) method was performed, in order to constrain the peak ground acceleration (PGA) that had caused the damage. First the numerical method used for back analysis was verified with an analytical solution for the case of a rocking monolithic column, then validated with experimental results for site response analysis. The verification and validation prove the DDA is capable of handling dynamic and wave propagation problems. Next, the back analysis was performed. Results of the dynamic numerical simulations suggest that the damage observed at the vault was induced by seismic vibrations that must have taken place before the bridge was buried underground, namely when it was still in service. We find that the PGA required for causing the observed damage was high - between 1.5 and 2 g. The PGA calculated for Jerusalem on the basis of established attenuation relationships for historic earthquakes that struck the region during the relevant time period is about one order of magnitude lower: 0.14 and 0.48 g, for the events that took place at 362 and 746 AD, respectively. This discrepancy is explained by local site effects that must have amplified bedrock ground motions by a factor of up to 10. This result clearly illustrates the significance of incorporating local site effects when assessing the seismic hazard associated with specific regions in general, and particularly in cities where soft layers separate between the bedrock and the ground surface. The displaced block in Vault 21 in the Western Wall Tunnels.

Wilderness Campers' Perception and Evaluation of Campsite Impacts.

ERIC Educational Resources Information Center

Farrell, Tracy; Hall, Troy E.; White, Dave D.

2001-01-01

Interviewed campers regarding their perceptions of impacts to vegetation, soil, and trees, comparing campers' measurements of vegetation loss, mineral soil exposure, tree damage, and site size with managers' evaluations. Most campers noticed vegetation impacts, and about half noticed soil impacts and tree damage. Most commented positively about…

Stink bugs

USDA-ARS?s Scientific Manuscript database

Stink bugs can cause serious damage to apple and pear fruit at harvest. Feeding on the maturing fruit results in a puncture wound with a depressed and discolored blemish on the surface. The fruit flesh under the damage site is brown and corky. There are currently four major species of stink bugs ...

The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis

PubMed Central

Bernstock, Joshua D.; Pluchino, Stefano

2015-01-01

Multiple sclerosis is one of the most common causes of chronic neurological disability beginning in early to middle adult life. Multiple sclerosis is idiopathic in nature, yet increasing correlative evidence supports a strong association between one’s genetic predisposition, the environment and the immune system. Symptoms of multiple sclerosis have primarily been shown to result from a disruption in the integrity of myelinated tracts within the white matter of the central nervous system. However, recent research has also highlighted the hitherto underappreciated involvement of gray matter in multiple sclerosis disease pathophysiology, which may be especially relevant when considering the accumulation of irreversible damage and progressive disability. This review aims at providing a comprehensive overview of the interplay between inflammation, glial/neuronal damage and regeneration throughout the course of multiple sclerosis via the analysis of both white and gray matter lesional pathology. Further, we describe the common pathological mechanisms underlying both relapsing and progressive forms of multiple sclerosis, and analyze how current (as well as future) treatments may interact and/or interfere with its pathology. Understanding the putative mechanisms that drive disease pathogenesis will be key in helping to develop effective therapeutic strategies to prevent, mitigate, and treat the diverse morbidities associated with multiple sclerosis. PMID:25802011

Crack Growth Prediction Methodology for Multi-Site Damage: Layered Analysis and Growth During Plasticity

NASA Technical Reports Server (NTRS)

James, Mark Anthony

1999-01-01

A finite element program has been developed to perform quasi-static, elastic-plastic crack growth simulations. The model provides a general framework for mixed-mode I/II elastic-plastic fracture analysis using small strain assumptions and plane stress, plane strain, and axisymmetric finite elements. Cracks are modeled explicitly in the mesh. As the cracks propagate, automatic remeshing algorithms delete the mesh local to the crack tip, extend the crack, and build a new mesh around the new tip. State variable mapping algorithms transfer stresses and displacements from the old mesh to the new mesh. The von Mises material model is implemented in the context of a non-linear Newton solution scheme. The fracture criterion is the critical crack tip opening displacement, and crack direction is predicted by the maximum tensile stress criterion at the crack tip. The implementation can accommodate multiple curving and interacting cracks. An additional fracture algorithm based on nodal release can be used to simulate fracture along a horizontal plane of symmetry. A core of plane strain elements can be used with the nodal release algorithm to simulate the triaxial state of stress near the crack tip. Verification and validation studies compare analysis results with experimental data and published three-dimensional analysis results. Fracture predictions using nodal release for compact tension, middle-crack tension, and multi-site damage test specimens produced accurate results for residual strength and link-up loads. Curving crack predictions using remeshing/mapping were compared with experimental data for an Arcan mixed-mode specimen. Loading angles from 0 degrees to 90 degrees were analyzed. The maximum tensile stress criterion was able to predict the crack direction and path for all loading angles in which the material failed in tension. Residual strength was also accurately predicted for these cases.

Reduced repair capacity of a DNA clustered damage site comprised of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 2-deoxyribonolactone results in an increased mutagenic potential of these lesions

DOE PAGES

Cunniffe, Siobhan; O’Neill, Peter; Greenberg, Marc M.; ...

2014-04-01

A signature of ionizing radiation is the induction of DNA clustered damaged sites. Non-double strand break (DSB) clustered damage has been shown to compromise the base excision repair pathway, extending the lifetimes of the lesions within the cluster, compared to isolated lesions. This increases the likelihood the lesions persist to replication and thus increasing the mutagenic potential of the lesions within the cluster. Lesions formed by ionizing radiation include 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and 2-deoxyribonolactone (dL). dL poses an additional challenge to the cell as it is not repaired by the short-patch base excision repair pathway. Here we show recalcitrant dL repairmore » is reflected in mutations observed when DNA containing it and a proximal 8-oxodGuo is replicated in Escherichia coli. 8-oxodGuo in close proximity to dL on the opposing DNA strand results in an enhanced frequency of mutation of the lesions within the cluster and a 20 base sequence flanking the clustered damage site in an E. coli based plasmid assay. In vitro repair of a dL lesion is reduced when compared to the repair of an abasic (AP) site and a tetrahydrofuran (THF), and this is due mainly to a reduction in the activity of polymerase β, leading to retarded FEN1 and ligase 1 activities. This study has given insights in to the biological effects of clusters containing dL.« less

Chromosomal aberrations in Sigmodon hispidus from a Superfund site

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

Bowers, B.; McBee, K.; Lochmiller, R.

1995-12-31

Cotton rats (Sigmodon hispidus) were collected from an EPA Superfund site located on an abandoned oil refinery. Three trapping grids were located on the refinery and three similar grids were located at uncontaminated localities which served as reference sites. Bone marrow metaphase chromosome preparations were examined for chromosomal damage. For each individual, 50 cells were scored for six classes of chromosomal lesions. For the fall 1991 trapping period, mean number of aberrant cells per individual was 2.33, 0.85, and 1.50 for the three Superfund grids., Mean number of aberrant cells per individual was 2.55, 2.55, and 2.12 from the referencemore » grids. Mean number of lesions per cell was 2.77, 0.86, and 1.9 from the Superfund grids, and 3.55, 2.77, and 2.50 from the reference grids. For the spring 1992 trapping period, more damage was observed in animals from both Superfund and reference sites; however, animals from Superfund grids had more damage than animals from reference grids. Mean number of aberrant cells per individual was 3.50, 3.25, and 3.70 from the Superfund grids, and 2.40, 2.11, and 1.40 from the reference grids. Mean number of lesions per cell was 4.80, 4.25, and 5.50 from the Superfund grids, and 2.60, 2.33, and 1.50 from the reference grids. These data suggest animals may be more susceptible to chromosomal damage during winter months, and animals from the Superfund grids appear to be more severely affected than animals from reference grids.« less

Simulation-Based Extreme Value Marked Correlations in Fatigue of Advanced Engineering Alloys (PREPRINT)

DTIC Science & Technology

2010-04-01

000 the response of damage dependent processes like fatigue crack formation, a framework is needed that accounts for the extreme value life...many different damage processes (e.g. fatigue, creep, fracture). In this work, multiple material volumes for both IN100 and Ti-6Al-4V are simulated via...polycrystalline P/M Ni-base superalloy IN100 Typically, fatigue damage formation in polycrystalline superalloys has been linked to the existence of

Modulation of inflammation and disease tolerance by DNA damage response pathways.

PubMed

Neves-Costa, Ana; Moita, Luis F

2017-03-01

The accurate replication and repair of DNA is central to organismal survival. This process is challenged by the many factors that can change genetic information such as replication errors and direct damage to the DNA molecule by chemical and physical agents. DNA damage can also result from microorganism invasion as an integral step of their life cycle or as collateral damage from host defense mechanisms against pathogens. Here we review the complex crosstalk of DNA damage response and immune response pathways that might be evolutionarily connected and argue that DNA damage response pathways can be explored therapeutically to induce disease tolerance through the activation of tissue damage control processes. Such approach may constitute the missing pillar in the treatment of critical illnesses caused by multiple organ failure, such as sepsis and septic shock. © 2016 Federation of European Biochemical Societies.

Damage in a Thin Metal Film by High-Power Terahertz Radiation.

PubMed

Agranat, M B; Chefonov, O V; Ovchinnikov, A V; Ashitkov, S I; Fortov, V E; Kondratenko, P S

2018-02-23

We report on the experimental observation of high-power terahertz-radiation-induced damage in a thin aluminum film with a thickness less than a terahertz skin depth. Damage in a thin metal film produced by a single terahertz pulse is observed for the first time. The damage mechanism induced by a single terahertz pulse could be attributed to thermal expansion of the film causing debonding of the film from the substrate, film cracking, and ablation. The damage pattern induced by multiple terahertz pulses at fluences below the damage threshold is quite different from that observed in single-pulse experiments. The observed damage pattern resembles an array of microcracks elongated perpendicular to the in-plane field direction. A mechanism related to microcracks' generation and based on a new phenomenon of electrostriction in thin metal films is proposed.

Damage in a Thin Metal Film by High-Power Terahertz Radiation

NASA Astrophysics Data System (ADS)

Agranat, M. B.; Chefonov, O. V.; Ovchinnikov, A. V.; Ashitkov, S. I.; Fortov, V. E.; Kondratenko, P. S.

2018-02-01

We report on the experimental observation of high-power terahertz-radiation-induced damage in a thin aluminum film with a thickness less than a terahertz skin depth. Damage in a thin metal film produced by a single terahertz pulse is observed for the first time. The damage mechanism induced by a single terahertz pulse could be attributed to thermal expansion of the film causing debonding of the film from the substrate, film cracking, and ablation. The damage pattern induced by multiple terahertz pulses at fluences below the damage threshold is quite different from that observed in single-pulse experiments. The observed damage pattern resembles an array of microcracks elongated perpendicular to the in-plane field direction. A mechanism related to microcracks' generation and based on a new phenomenon of electrostriction in thin metal films is proposed.

Cisplatin Resistance: A Cellular Self-Defense Mechanism Resulting from Multiple Epigenetic and Genetic Changes

PubMed Central

Shen, Ding-Wu; Pouliot, Lynn M.; Hall, Matthew D.

2012-01-01

Cisplatin is one of the most effective broad-spectrum anticancer drugs. Its effectiveness seems to be due to the unique properties of cisplatin, which enters cells via multiple pathways and forms multiple different DNA-platinum adducts while initiating a cellular self-defense system by activating or silencing a variety of different genes, resulting in dramatic epigenetic and/or genetic alternations. As a result, the development of cisplatin resistance in human cancer cells in vivo and in vitro by necessity stems from bewilderingly complex genetic and epigenetic changes in gene expression and alterations in protein localization. Extensive published evidence has demonstrated that pleiotropic alterations are frequently detected during development of resistance to this toxic metal compound. Changes occur in almost every mechanism supporting cell survival, including cell growth-promoting pathways, apoptosis, developmental pathways, DNA damage repair, and endocytosis. In general, dozens of genes are affected in cisplatin-resistant cells, including pathways involved in copper metabolism as well as transcription pathways that alter the cytoskeleton, change cell surface presentation of proteins, and regulate epithelial-to-mesenchymal transition. Decreased accumulation is one of the most common features resulting in cisplatin resistance. This seems to be a consequence of numerous epigenetic and genetic changes leading to the loss of cell-surface binding sites and/or transporters for cisplatin, and decreased fluid phase endocytosis. PMID:22659329

Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes.

PubMed

Shen, Ding-Wu; Pouliot, Lynn M; Hall, Matthew D; Gottesman, Michael M

2012-07-01

Cisplatin is one of the most effective broad-spectrum anticancer drugs. Its effectiveness seems to be due to the unique properties of cisplatin, which enters cells via multiple pathways and forms multiple different DNA-platinum adducts while initiating a cellular self-defense system by activating or silencing a variety of different genes, resulting in dramatic epigenetic and/or genetic alternations. As a result, the development of cisplatin resistance in human cancer cells in vivo and in vitro by necessity stems from bewilderingly complex genetic and epigenetic changes in gene expression and alterations in protein localization. Extensive published evidence has demonstrated that pleiotropic alterations are frequently detected during development of resistance to this toxic metal compound. Changes occur in almost every mechanism supporting cell survival, including cell growth-promoting pathways, apoptosis, developmental pathways, DNA damage repair, and endocytosis. In general, dozens of genes are affected in cisplatin-resistant cells, including pathways involved in copper metabolism as well as transcription pathways that alter the cytoskeleton, change cell surface presentation of proteins, and regulate epithelial-to-mesenchymal transition. Decreased accumulation is one of the most common features resulting in cisplatin resistance. This seems to be a consequence of numerous epigenetic and genetic changes leading to the loss of cell-surface binding sites and/or transporters for cisplatin, and decreased fluid phase endocytosis.

FACTORS INFLUENCING HOST-VIRUS INTERACTIONS

PubMed Central

Boring, William D.; Angevine, D. Murray; Walker, Duard L.

1955-01-01

A study was made of the pathogenesis of infection due to the Conn.-5 strain of Coxsackie virus in 4 to 5 day old infant mice, untreated adult mice, and adult mice treated with cortisone. The quantitative distribution of virus and the evolution of lesions in different tissues were followed for the first 7 days of the infection. Virus dissemination was prompt and widespread via the blood in all groups. In 4 to 5 day old infant mice viral multiplication and cellular injury occurred in many organs and tissues, while in untreated adult mice these processes were largely limited to the pancreas, even though infecting virus appeared to be equally available to other tissues from the blood. Treatment of adult mice with a single injection of 2.5 mg. cortisone resulted in viral multiplication and tissue damage in several sites in addition to the pancreas, the most marked occurring in the liver and heart. In a consideration of possible mechanisms involved, it was thought unlikely that the differences in the course of the disease in the three groups could be attributed solely to differences in the specific immune response. It is suggested that developmental changes in cells and tissues, perhaps related to cellular metabolism and alterable by cortisone administration, are the major factors determining the location and extent of viral multiplication and tissue injury in this infection in mice. PMID:13271687

Public-health assessment for American Creosote Works Inc. , Pensacola, Escambia County, Florida, Region 4. CERCLIS No. FLD008161994. Final report

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

Not Available

1992-07-29

The American Creosote Works, Inc., National Priorities List (NPL) site, is near Pensacola Bay in Pensacola, Florida. American Creosote operated a wood preserving business from 1902 until 1981. Soils, buried sludge, ground water, sediments, and air are contaminated with numerous of chemicals including; pentachlorophenol, polycyclic aromatic hydrocarbons (PAHs), polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and benzene. Children trespassing on the site are likely to be exposed to pentachlorophenol, PAHs, and PCDDs/PCDFs in the soil via incidental ingestion and may suffer chloracne, liver damage, and an increased risk of cancer. Incidental ingestion of off-site soil by children may also increase theirmore » risk of chloracne and liver damage, but actual health effects depend on the frequency and duration of the exposure. Inhalation of benzene in the on-site air may increase the lifetime risk of cancer for children and other site trespassers. The site is a public health hazard due to the risk of adverse health effects from long term exposure to hazardous chemicals in the air, soil, and ground water.« less

UCERF3: A new earthquake forecast for California's complex fault system

USGS Publications Warehouse

Field, Edward H.; ,

2015-01-01

With innovations, fresh data, and lessons learned from recent earthquakes, scientists have developed a new earthquake forecast model for California, a region under constant threat from potentially damaging events. The new model, referred to as the third Uniform California Earthquake Rupture Forecast, or "UCERF" (http://www.WGCEP.org/UCERF3), provides authoritative estimates of the magnitude, location, and likelihood of earthquake fault rupture throughout the state. Overall the results confirm previous findings, but with some significant changes because of model improvements. For example, compared to the previous forecast (Uniform California Earthquake Rupture Forecast 2), the likelihood of moderate-sized earthquakes (magnitude 6.5 to 7.5) is lower, whereas that of larger events is higher. This is because of the inclusion of multifault ruptures, where earthquakes are no longer confined to separate, individual faults, but can occasionally rupture multiple faults simultaneously. The public-safety implications of this and other model improvements depend on several factors, including site location and type of structure (for example, family dwelling compared to a long-span bridge). Building codes, earthquake insurance products, emergency plans, and other risk-mitigation efforts will be updated accordingly. This model also serves as a reminder that damaging earthquakes are inevitable for California. Fortunately, there are many simple steps residents can take to protect lives and property.

A Fracture Decoupling Experiment

NASA Astrophysics Data System (ADS)

Stroujkova, A. F.; Bonner, J. L.; Leidig, M.; Ferris, A. N.; Kim, W.; Carnevale, M.; Rath, T.; Lewkowicz, J.

2012-12-01

Multiple observations made at the Semipalatinsk Test Site suggest that conducting nuclear tests in the fracture zones left by previous explosions results in decreased seismic amplitudes for the second nuclear tests (or "repeat shots"). Decreased seismic amplitudes reduce both the probability of detection and the seismically estimated yield of a "repeat shot". In order to define the physical mechanism responsible for the amplitude reduction and to quantify the degree of the amplitude reduction in fractured rocks, Weston Geophysical Corp., in collaboration with Columbia University's Lamont Doherty Earth Observatory, conducted a multi-phase Fracture Decoupling Experiment (FDE) in central New Hampshire. The FDE involved conducting explosions of various yields in the damage/fracture zones of previously detonated explosions. In order to quantify rock damage after the blasts we performed well logging and seismic cross-hole tomography studies of the source region. Significant seismic velocity reduction was observed around the source regions after the initial explosions. Seismic waves produced by the explosions were recorded at near-source and local seismic networks, as well as several regional stations throughout northern New England. Our analysis confirms frequency dependent seismic amplitude reduction for the repeat shots compared to the explosions in un-fractured rocks. The amplitude reduction is caused by pore closing and/or by frictional losses within the fractured media.

Aberrant T Cell Signaling and Subsets in Systemic Lupus Erythematosus

PubMed Central

Katsuyama, Takayuki; Tsokos, George C.; Moulton, Vaishali R.

2018-01-01

Systemic lupus erythematosus (SLE) is a chronic multi-organ debilitating autoimmune disease, which mainly afflicts women in the reproductive years. A complex interaction of genetics, environmental factors and hormones result in the breakdown of immune tolerance to “self” leading to damage and destruction of multiple organs, such as the skin, joints, kidneys, heart and brain. Both innate and adaptive immune systems are critically involved in the misguided immune response against self-antigens. Dendritic cells, neutrophils, and innate lymphoid cells are important in initiating antigen presentation and propagating inflammation at lymphoid and peripheral tissue sites. Autoantibodies produced by B lymphocytes and immune complex deposition in vital organs contribute to tissue damage. T lymphocytes are increasingly being recognized as key contributors to disease pathogenesis. CD4 T follicular helper cells enable autoantibody production, inflammatory Th17 subsets promote inflammation, while defects in regulatory T cells lead to unchecked immune responses. A better understanding of the molecular defects including signaling events and gene regulation underlying the dysfunctional T cells in SLE is necessary to pave the path for better management, therapy, and perhaps prevention of this complex disease. In this review, we focus on the aberrations in T cell signaling in SLE and highlight therapeutic advances in this field. PMID:29868033

Aberrant T Cell Signaling and Subsets in Systemic Lupus Erythematosus.

PubMed

Katsuyama, Takayuki; Tsokos, George C; Moulton, Vaishali R

2018-01-01

Systemic lupus erythematosus (SLE) is a chronic multi-organ debilitating autoimmune disease, which mainly afflicts women in the reproductive years. A complex interaction of genetics, environmental factors and hormones result in the breakdown of immune tolerance to "self" leading to damage and destruction of multiple organs, such as the skin, joints, kidneys, heart and brain. Both innate and adaptive immune systems are critically involved in the misguided immune response against self-antigens. Dendritic cells, neutrophils, and innate lymphoid cells are important in initiating antigen presentation and propagating inflammation at lymphoid and peripheral tissue sites. Autoantibodies produced by B lymphocytes and immune complex deposition in vital organs contribute to tissue damage. T lymphocytes are increasingly being recognized as key contributors to disease pathogenesis. CD4 T follicular helper cells enable autoantibody production, inflammatory Th17 subsets promote inflammation, while defects in regulatory T cells lead to unchecked immune responses. A better understanding of the molecular defects including signaling events and gene regulation underlying the dysfunctional T cells in SLE is necessary to pave the path for better management, therapy, and perhaps prevention of this complex disease. In this review, we focus on the aberrations in T cell signaling in SLE and highlight therapeutic advances in this field.

Suppressor of gamma response 1 (SOG1) encodes a putative transcription factor governing multiple responses to DNA damage

PubMed Central

Yoshiyama, Kaoru; Conklin, Phillip A.; Huefner, Neil D.; Britt, Anne B.

2009-01-01

The Arabidopsis sog1-1 (suppressor of gamma response) mutant was originally isolated as a second-site suppressor of the radiosensitive phenotype of seeds defective in the repair endonuclease XPF. Here, we report that SOG1 encodes a putative transcription factor. This gene is a member of the NAC domain [petunia NAM (no apical meristem) and Arabidopsis ATAF1, 2 and CUC2] family (a family of proteins unique to land plants). Hundreds of genes are normally up-regulated in Arabidopsis within an hour of treatment with ionizing radiation; the induction of these genes requires the damage response protein kinase ATM, but not the related kinase ATR. Here, we find that SOG1 is also required for this transcriptional up-regulation. In contrast, the SOG1-dependent checkpoint response observed in xpf mutant seeds requires ATR, but does not require ATM. Thus, phenotype of the sog1-1 mutant mimics aspects of the phenotypes of both atr and atm mutants in Arabidopsis, suggesting that SOG1 participates in pathways governed by both of these sensor kinases. We propose that, in plants, signals related to genomic stress are processed through a single, central transcription factor, SOG1. PMID:19549833

Multiple independent regulatory pathways control UBI4 expression after heat shock in Saccharomyces cerevisiae.

PubMed

Simon, J R; Treger, J M; McEntee, K

1999-02-01

Transcription of the polyubiquitin gene UBI4 of Saccharomyces cerevisiae is strongly induced by a variety of environmental stresses, such as heat shock, nutrient depletion and exposure to DNA-damaging agents. This transcriptional response of UBI4 is likely to be the primary mechanism for increasing the pool of ubiquitin for degradation of stress-damaged proteins. Deletion and promoter fusion studies of the 5' regulatory sequences indicated that two different elements, heat shock elements (HSEs) and stress response element (STREs), contributed independently to heat shock regulation of the UBI4 gene. In the absence of HSEs, STRE sequences localized to the intervals -264 to -238 and -215 to -183 were needed for stress control of transcription after heat shock. Site-directed mutagenesis of the STRE (AG4) at -252 to -248 abolished heat shock induction of UBI4 transcription. Northern analysis demonstrated that cells containing either a temperature-sensitive HSF or non-functional Msn2p/Msn4p transcription factors induced high levels of UBI4 transcripts after heat shock. In cells deficient in both heat stress pathways, heat-induced UBI4 transcript levels were considerably lower but not abolished, suggesting a role for another factor(s) in stress control of its expression.