Next generation multi-scale biophysical characterization of high precision cancer particle radiotherapy using clinical proton, helium-, carbon- and oxygen ion beams

PubMed Central

Niklas, Martin; Zimmermann, Ferdinand; Chaudhri, Naved; Krunic, Damir; Tessonnier, Thomas; Ferrari, Alfredo; Parodi, Katia; Jäkel, Oliver; Debus, Jürgen; Haberer, Thomas; Abdollahi, Amir

2016-01-01

The growing number of particle therapy facilities worldwide landmarks a novel era of precision oncology. Implementation of robust biophysical readouts is urgently needed to assess the efficacy of different radiation qualities. This is the first report on biophysical evaluation of Monte Carlo simulated predictive models of prescribed dose for four particle qualities i.e., proton, helium-, carbon- or oxygen ions using raster-scanning technology and clinical therapy settings at HIT. A high level of agreement was found between the in silico simulations, the physical dosimetry and the clonogenic tumor cell survival. The cell fluorescence ion track hybrid detector (Cell-Fit-HD) technology was employed to detect particle traverse per cell nucleus. Across a panel of radiobiological surrogates studied such as late ROS accumulation and apoptosis (caspase 3/7 activation), the relative biological effectiveness (RBE) chiefly correlated with the radiation species-specific spatio-temporal pattern of DNA double strand break (DSB) formation and repair kinetic. The size and the number of residual nuclear γ-H2AX foci increased as a function of linear energy transfer (LET) and RBE, reminiscent of enhanced DNA-damage complexity and accumulation of non-repairable DSB. These data confirm the high relevance of complex DSB formation as a central determinant of cell fate and reliable biological surrogates for cell survival/RBE. The multi-scale simulation, physical and radiobiological characterization of novel clinical quality beams presented here constitutes a first step towards development of high precision biologically individualized radiotherapy. PMID:27494855

Structures to Resist the Effects of Accidental Explosions. Volume 3. Principles of Dynamic Analysis

DTIC Science & Technology

1984-06-01

multi-degree-of-freedom systems) is presented. A step-by-step numerical integration of an element’s motion under dynamic loads using the...structural arrangements; providing closures, and preventing damage to interior portions of structures due to structual motion , shock, and fragment...an element’s motion under dynamic loads utilizing the Acceleration-Impulse- Extrapolation Method or the Average Acceleration Method and design charts

Mechanisms of mononuclear phagocyte recruitment in Alzheimer's disease.

PubMed

Hickman, Suzanne E; El Khoury, Joseph

2010-04-01

Alzheimer's disease (AD) is associated with a significant neuroinflammatory component. Mononuclear phagocytes including monocytes and microglia are the principal cells involved, and they accumulate at perivascular sites of beta-amyloid (Abeta) deposition and in senile plaques. Recent evidence suggests that mononuclear phagocyte accumulation in the AD brain is dependent on chemokines. CCL2, a major monocyte chemokine, is upregulated in the AD brain. Interaction of CCL2 with its receptor CCR2 regulates mononuclear phagocyte accumulation in a mouse model of AD. CCR2 deficiency leads to lower mononuclear phagocyte accumulation and is associated with higher brain Abeta levels, specifically around blood vessels, suggesting that monocytes accumulate at sites of Abeta deposition in an initial attempt to clear these deposits and stop or delay their neurotoxic effects. Indeed, enhancing mononuclear phagocyte accumulation delays progression of AD. Here we review the mechanisms of mononuclear phagocyte accumulation in AD and discuss the potential roles of additional chemokines and their receptors in this process. We also propose a multi-step model for recruitment of mononuclear phagocytes into the brain. The first step involves egress of monocyte/microglial precursors from the bone marrow into the blood. The second step is crossing the blood-brain barrier to the perivascular areas and into the brain parenchyma. The final step includes movement of monocytes/microglia from areas of the brain that lack any amyloid deposition to senile plaques. Understanding the mechanism of recruitment of mononuclear phagocytes to the AD brain is necessary to further understand the role of these cells in the pathogenesis of AD and to identify any potential therapeutic use of these cells for the treatment of this disease.

Evaluation of accuracy in implant site preparation performed in single- or multi-step drilling procedures.

PubMed

Marheineke, Nadine; Scherer, Uta; Rücker, Martin; von See, Constantin; Rahlf, Björn; Gellrich, Nils-Claudius; Stoetzer, Marcus

2018-06-01

Dental implant failure and insufficient osseointegration are proven results of mechanical and thermal damage during the surgery process. We herein performed a comparative study of a less invasive single-step drilling preparation protocol and a conventional multiple drilling sequence. Accuracy of drilling holes was precisely analyzed and the influence of different levels of expertise of the handlers and additional use of drill template guidance was evaluated. Six experimental groups, deployed in an osseous study model, were representing template-guided and freehanded drilling actions in a stepwise drilling procedure in comparison to a single-drill protocol. Each experimental condition was studied by the drilling actions of respectively three persons without surgical knowledge as well as three highly experienced oral surgeons. Drilling actions were performed and diameters were recorded with a precision measuring instrument. Less experienced operators were able to significantly increase the drilling accuracy using a guiding template, especially when multi-step preparations are performed. Improved accuracy without template guidance was observed when experienced operators were executing single-step versus multi-step technique. Single-step drilling protocols have shown to produce more accurate results than multi-step procedures. The outcome of any protocol can be further improved by use of guiding templates. Operator experience can be a contributing factor. Single-step preparations are less invasive and are promoting osseointegration. Even highly experienced surgeons are achieving higher levels of accuracy by combining this technique with template guidance. Hereby template guidance enables a reduction of hands-on time and side effects during surgery and lead to a more predictable clinical diameter.

Multi-Scale Impact and Compression-After-Impact Modeling of Reinforced Benzoxazine/Epoxy Composites using Micromechanics Approach

NASA Astrophysics Data System (ADS)

Montero, Marc Villa; Barjasteh, Ehsan; Baid, Harsh K.; Godines, Cody; Abdi, Frank; Nikbin, Kamran

A multi-scale micromechanics approach along with finite element (FE) model predictive tool is developed to analyze low-energy-impact damage footprint and compression-after-impact (CAI) of composite laminates which is also tested and verified with experimental data. Effective fiber and matrix properties were reverse-engineered from lamina properties using an optimization algorithm and used to assess damage at the micro-level during impact and post-impact FE simulations. Progressive failure dynamic analysis (PFDA) was performed for a two step-process simulation. Damage mechanisms at the micro-level were continuously evaluated during the analyses. Contribution of each failure mode was tracked during the simulations and damage and delamination footprint size and shape were predicted to understand when, where and why failure occurred during both impact and CAI events. The composite laminate was manufactured by the vacuum infusion of the aero-grade toughened Benzoxazine system into the fabric preform. Delamination footprint was measured using C-scan data from the impacted panels and compared with the predicated values obtained from proposed multi-scale micromechanics coupled with FE analysis. Furthermore, the residual strength was predicted from the load-displacement curve and compared with the experimental values as well.

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.

Magnetic Flux Leakage Sensing and Artificial Neural Network Pattern Recognition-Based Automated Damage Detection and Quantification for Wire Rope Non-Destructive Evaluation.

PubMed

Kim, Ju-Won; Park, Seunghee

2018-01-02

In this study, a magnetic flux leakage (MFL) method, known to be a suitable non-destructive evaluation (NDE) method for continuum ferromagnetic structures, was used to detect local damage when inspecting steel wire ropes. To demonstrate the proposed damage detection method through experiments, a multi-channel MFL sensor head was fabricated using a Hall sensor array and magnetic yokes to adapt to the wire rope. To prepare the damaged wire-rope specimens, several different amounts of artificial damages were inflicted on wire ropes. The MFL sensor head was used to scan the damaged specimens to measure the magnetic flux signals. After obtaining the signals, a series of signal processing steps, including the enveloping process based on the Hilbert transform (HT), was performed to better recognize the MFL signals by reducing the unexpected noise. The enveloped signals were then analyzed for objective damage detection by comparing them with a threshold that was established based on the generalized extreme value (GEV) distribution. The detected MFL signals that exceed the threshold were analyzed quantitatively by extracting the magnetic features from the MFL signals. To improve the quantitative analysis, damage indexes based on the relationship between the enveloped MFL signal and the threshold value were also utilized, along with a general damage index for the MFL method. The detected MFL signals for each damage type were quantified by using the proposed damage indexes and the general damage indexes for the MFL method. Finally, an artificial neural network (ANN) based multi-stage pattern recognition method using extracted multi-scale damage indexes was implemented to automatically estimate the severity of the damage. To analyze the reliability of the MFL-based automated wire rope NDE method, the accuracy and reliability were evaluated by comparing the repeatedly estimated damage size and the actual damage size.

Alpha-Recoil Damage Annealing Effecfs on Zircon Crystallinity and He Diffusivity: Improving Damage-Diffusivity Models

NASA Astrophysics Data System (ADS)

Thurston, O. G.; Guenthner, W.; Garver, J. I.

2017-12-01

The effects of radiation damage on He diffusion in zircon has been a major research focus in thermochronology over the past decade. In the zircon-He system, alpha-recoil damage effects He diffusivity in two ways: a decrease in He diffusivity at low radiation damage levels, and an increase in He diffusivity at high radiation damage levels. The radiation damage accumulation process within zircon is well understood; however, the kinetics of annealing of alpha-recoil damage at geologic timescales as they pertain to damage-diffusivity models, and for metamict zircon (i.e. transition from crystalline to amorphous glass via damage accumulation), has not been well constrained. This study aims to develop a more complete model that describes the annealing kinetics for zircon grains with a broad range of pre-annealing, alpha-induced radiation damage. A suite of zircon grains from the Lucerne pluton, ME were chosen for this study due to their simple thermal history (monotonic cooling), notable range of effective uranium (eU, eU = [U] +0.235*[Th]) (15 - 34,239 ppm eU), and large range of radiation damage as measured by Raman shift from crystalline (>1005 cm-1) to metamict (<1000 cm-1). The zircon grains selected represent the full range of eU and radiation damage present in the pluton. The zircon grains were first mapped for overall crystallinity using Raman spectroscopy, then annealed at different time-temperature (t-T) schedules from 1 hr to 24 hrs at temperatures ranging from 700-1100 °C, followed by remapping with Raman spectroscopy to track the total Raman shift for each t-T step. The temperature window selected is at the "roll-over" point established in prior studies (Zhang et al., 2000), at which most laboratory annealing occurs. Our data show that high radiation damage zircon grains show larger Raman shifts than low radiation damage zircon grains when exposed to the same t-T step. The high damage zircon grains typically show a Raman shift of 4 cm-1 toward crystalline, while low radiation damage grains show a shift of 2 cm-1. These shifts suggest that the annealing process occurs at a faster rate in high damage zircon grains, and slower rates in more crystalline grains. That is, the initial level of radiation damage prior to annealing must be considered in damage-diffusivity models that contain thermal histories from zircon-He dates.

Fatigue damage monitoring for basalt fiber reinforced polymer composites using acoustic emission technique

NASA Astrophysics Data System (ADS)

Wang, Wentao; Li, Hui; Qu, Zhi

2012-04-01

Basalt fiber reinforced polymer (BFRP) is a structural material with superior mechanical properties. In this study, unidirectional BFRP laminates with 14 layers are made with the hand lay-up method. Then, the acoustic emission technique (AE) combined with the scanning electronic microscope (SEM) technique is employed to monitor the fatigue damage evolution of the BFRP plates in the fatigue loading tests. Time-frequency analysis using the wavelet transform technique is proposed to analyze the received AE signal instead of the peak frequency method. A comparison between AE signals and SEM images indicates that the multi-frequency peaks picked from the time-frequency curves of AE signals reflect the accumulated fatigue damage evolution and fatigue damage patterns. Furthermore, seven damage patterns, that is, matrix cracking, delamination, fiber fracture and their combinations, are identified from the time-frequency curves of the AE signals.

Multi-Step Time Series Forecasting with an Ensemble of Varied Length Mixture Models.

PubMed

Ouyang, Yicun; Yin, Hujun

2018-05-01

Many real-world problems require modeling and forecasting of time series, such as weather temperature, electricity demand, stock prices and foreign exchange (FX) rates. Often, the tasks involve predicting over a long-term period, e.g. several weeks or months. Most existing time series models are inheritably for one-step prediction, that is, predicting one time point ahead. Multi-step or long-term prediction is difficult and challenging due to the lack of information and uncertainty or error accumulation. The main existing approaches, iterative and independent, either use one-step model recursively or treat the multi-step task as an independent model. They generally perform poorly in practical applications. In this paper, as an extension of the self-organizing mixture autoregressive (AR) model, the varied length mixture (VLM) models are proposed to model and forecast time series over multi-steps. The key idea is to preserve the dependencies between the time points within the prediction horizon. Training data are segmented to various lengths corresponding to various forecasting horizons, and the VLM models are trained in a self-organizing fashion on these segments to capture these dependencies in its component AR models of various predicting horizons. The VLM models form a probabilistic mixture of these varied length models. A combination of short and long VLM models and an ensemble of them are proposed to further enhance the prediction performance. The effectiveness of the proposed methods and their marked improvements over the existing methods are demonstrated through a number of experiments on synthetic data, real-world FX rates and weather temperatures.

Radiation Damage in Si Diodes from Short, Intense Ion Pulses

NASA Astrophysics Data System (ADS)

de Leon, S. J.; Ludewigt, B. A.; Persaud, A.; Seidl, P. A.; Schenkel, T.

2017-10-01

The Neutralized Drift Compression Experiment (NDCX-II) at Berkeley Lab is an induction accelerator studying the effects that concentrated ion beams have on various materials. Charged particle radiation damage was the focus of this research - we have characterized a series of Si diodes using an electrometer and calibrated the diodes response using an 241Am alpha source, both before and after exposing the diodes to 1 MeV He ions in the accelerator. The key part here is that the high intensity pulses from NDCX-II (>1010 ions/cm2 per pulse in <20 ns) enabled a systematic study of dose-rate effects. An example of a dose-rate effect in Si diodes is increased accumulation of defects due to damage from ions that bombard them in a short pulse. This accumulated damage leads to a reduction in the charge collection efficiency and an increase in leakage current. Testing dose-rate effects in Si diodes and other semiconductors is a crucial step in designing sustainable instruments that can encounter high doses of radiation, such as high intensity accelerators, fusion energy experiments and space applications and results from short pulses can inform models of radiation damage evolution. This work was supported by the Office of Science of the US Department of Energy under contract DE-AC0205CH11231.

Use of Modal Acoustic Emission to Monitor Damage Progression in Carbon Fiber/Epoxy Tows and Implications for Composite Structures

NASA Technical Reports Server (NTRS)

Waller, Jess M.; Saulsberry, Regor L.; Nichols, Charles T.; Wentzel, Daniel J.

2010-01-01

This slide presentation reviews the use of Modal Acoustic Emission to monitor damage progression to carbon fiber/epoxy tows. There is a risk for catastrophic failure of composite overwrapped pressure vessels (COPVs) due to burst-before-leak (BBL) stress rupture (SR) failure of carbon-epoxy (C/Ep) COPVs. A lack of quantitative nondestructive evaluation (NDE) is causing problems in current and future spacecraft designs. It is therefore important to develop and demonstrate critical NDE that can be implemented during stages of the design process since the observed rupture can occur with little of no advanced warning. Therefore a program was required to develop quantitative acoustic emission (AE) procedures specific to C/Ep overwraps, but which also have utility for monitoring damage accumulation in composite structure in general, and to lay the groundwork for establishing critical thresholds for accumulated damage in composite structures, such as COPVs, so that precautionary or preemptive engineering steps can be implemented to minimize of obviate the risk of catastrophic failure. A computed Felicity Ratio (FR) coupled with fast Fourier Transform (FFT) frequency analysis shows promise as an analytical pass/fail criterion. The FR analysis and waveform and FFT analysis are reviewed

Multi-layered sensor yarns for in situ monitoring of textile reinforced composites

NASA Astrophysics Data System (ADS)

Haentzsche, E.; Onggar, T.; Nocke, A.; Hund, R. D.; Cherif, Ch

2017-10-01

In this contribution, the characteristic of yarns that have intrinsically conductivity as well as such with coaxial conductive coatings acting as in situ strain sensors are described. The objective of the based research projects is the real-time in situ sensing of both global stresses acting on fibre reinforced plastic (FRP) components and the detection of resulted local microscopic damages due to creep, delamination and micro-cracks in the fibre-matrix interphase of glass fibre (GFRP) and carbon fibre (CFRP) composites. Sensor materials similar to the particular FRP and its mechanical behaviour have been chosen. In the first approach, GF- and aramid-based sensor yarns have been developed with multiple tailored silver layer coating system capable to distinguish multiple scaled damage mechanism due to these effects globally and locally. The second approach bases on the piezoresistive effect of CF rovings for their usage as in situ strain sensors. In the next step, suitable fibre and polymer film-based cleading have been tested and evaluated, granting sufficient electrical isolation to avoid shortcircuits between the conductive sensor layers itself or between the sensor and intrinsically conductive CFRP respectively. Initially, the sensor performance of global strain measurement, means the accumulated strain along the integration length of the sensor yarn, has been evaluated during tensile stressing of FRP with integrated suchlike functionalised sensor yarns.

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

Probing multi-scale mechanical damage in connective tissues using X-ray diffraction.

PubMed

Bianchi, Fabio; Hofmann, Felix; Smith, Andrew J; Thompson, Mark S

2016-11-01

The accumulation of microstructural collagen damage following repetitive loading is linked to painful and debilitating tendon injuries. As a hierarchical, semi-crystalline material, collagen mechanics can be studied using X-ray diffraction. The aim of the study was to describe multi-structural changes in tendon collagen following controlled plastic damage (5% permanent strain). We used small angle X-ray scattering (SAXS) to interrogate the spacing of collagen molecules within a fibril, and wide angle X-ray scattering (WAXS) to measure molecular strains under macroscopic loading. Simultaneous recordings of SAXS and WAXS patterns, together with whole-tissue strain in physiologically hydrated rat-tail tendons were made during increments of in situ tensile loading. Results showed that while tissue level modulus was unchanged, fibril modulus decreased significantly, and molecular modulus significantly increased. Further, analysis of higher order SAXS peaks suggested structural changes in the gap and overlap regions, possibly localising the damage to molecular cross-links. Our results provide new insight into the fundamental damage processes at work in collagenous tissues and point to new directions for their mitigation and repair. This article reports the first in situ loading synchrotron studies on mechanical damage in collagenous tissues. We provide new insight into the nano- and micro-structural mechanisms of damage processes. Pre-damaged tendons showed differential alteration of moduli at macro, micro and nano-scales as measured using X-ray scattering techniques. Detailed analysis of higher order diffraction peaks suggested damage is localised to molecular cross-links. The results are consistent with previous X-ray scattering studies of tendons and also with recent thermal stability studies on damaged material. Detailed understanding of damage mechanisms is essential in the development of new therapies promoting tissue repair. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Changes in circulating cytokines and markers of muscle damage in elite cyclists during a multi-stage competition.

PubMed

Córdova Martínez, Alfredo; Martorell Pons, Miquel; Sureda Gomila, Antoni; Tur Marí, Josep A; Pons Biescas, Antoni

2015-09-01

The purpose of this study was to determine the changes in the basal and post-exercise plasma markers of muscular damage, lipid peroxidation and cytokines in eight male well-trained semiprofessional cyclists, in response to a three consecutive-day cycling competition. Serum markers of oxidative and muscular damage - creatine kinase activity, lactate dehydrogenase activity, myoglobin and malondialdehyde (MDA), creatinine and nitrite levels - followed a sawtooth-type representation throughout the competition. MDA showed an accumulative pattern, evidenced in the post-race values of the third stage which were significantly higher with respect to the values of the first stage. Cortisol levels were significantly influenced by an interaction between the exercise and the stage factors, with higher values on the 4th day. Plasma cytokine levels were only determined before the first stage and post-race, after the third stage. The exercise increased TNFα, IL6, IL2 and IFNγ levels, whereas IL1β was unchanged. In conclusion, cyclist stages induced oxidative and cellular muscle damage which is partially recovered to basal values by the next morning. Repetitive stages during the cycling competition accumulated plasma muscular damage and lipid peroxidation markers and pro-inflammatory cytokines, probably as a result of local inflammatory responses. © 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Combination therapies - the next logical step for the treatment of synucleinopathies?

PubMed Central

Valera, E.; Masliah, E.

2015-01-01

Currently there are no disease-modifying alternatives for the treatment of most neurodegenerative disorders. The available therapies for diseases such as Parkinson’s disease (PD), PD dementia (PDD), Dementia with Lewy bodies (DLB) and Multiple system atrophy (MSA), in which the protein alpha-synuclein (α-syn) accumulates within neurons and glial cells with toxic consequences, are focused on managing the disease symptoms. However, utilizing strategic drug combinations and/or multi-target drugs might increase the treatment efficiency when compared to monotherapies. Synucleinopathies are complex disorders that progress through several stages, and toxic α-syn aggregates exhibit prion-like behavior spreading from cell to cell. Therefore, it follows that these neurodegenerative disorders might require equally complex therapeutic approaches in order to obtain significant and long-lasting results. Hypothetically, therapies aimed at reducing α-syn accumulation and cell-to-cell transfer, such as immunotherapy against α-syn, could be combined with agents that reduce neuroinflammation with potential synergistic outcomes. Here we review the current evidence supporting this type of approach, suggesting that such rational therapy combinations, together with the use of multi-target drugs, may hold promise as the next logical step for the treatment of synucleinopathies. PMID:26388203

Silicon Nitride Deposition for Flexible Organic Electronic Devices by VHF (162 MHz)-PECVD Using a Multi-Tile Push-Pull Plasma Source.

PubMed

Kim, Ki Seok; Kim, Ki Hyun; Ji, You Jin; Park, Jin Woo; Shin, Jae Hee; Ellingboe, Albert Rogers; Yeom, Geun Young

2017-10-19

Depositing a barrier film for moisture protection without damage at a low temperature is one of the most important steps for organic-based electronic devices. In this study, the authors investigated depositing thin, high-quality SiN x film on organic-based electronic devices, specifically, very high-frequency (162 MHz) plasma-enhanced chemical vapor deposition (VHF-PECVD) using a multi-tile push-pull plasma source with a gas mixture of NH 3 /SiH 4 at a low temperature of 80 °C. The thin deposited SiN x film exhibited excellent properties in the stoichiometry, chemical bonding, stress, and step coverage. Thin film quality and plasma damage were investigated by the water vapor transmission rate (WVTR) and by electrical characteristics of organic light-emitting diode (OLED) devices deposited with SiN x , respectively. The thin deposited SiN x film exhibited a low WVTR of 4.39 × 10 -4  g (m 2 · day) -1 for a single thin (430 nm thick) film SiN x and the electrical characteristics of OLED devices before and after the thin SiN x film deposition on the devices did not change, which indicated no electrical damage during the deposition of SiN x on the OLED device.

Phonons, defects and optical damage in crystalline acetanilide

NASA Astrophysics Data System (ADS)

Kosic, Thomas J.; Hill, Jeffrey R.; Dlott, Dana D.

1986-04-01

Intense picosecond pulses cause accumulated optical damage in acetanilide crystals at low temperature. Catastrophic damage to the irradiated volume occurs after an incubation period where defects accumulate. The optical damage is monitored with subanosecond time resolution. The generation of defects is studied with damage-detected picosecond spectroscopy. The accumulation of defects is studied by time-resolved coherent Raman scattering, which is used to measure optical phonon scattering from the accumulating defects.

Hormesis enables cells to handle accumulating toxic metabolites during increased energy flux.

PubMed

Zemva, Johanna; Fink, Christoph Andreas; Fleming, Thomas Henry; Schmidt, Leonard; Loft, Anne; Herzig, Stephan; Knieß, Robert André; Mayer, Matthias; Bukau, Bernd; Nawroth, Peter Paul; Tyedmers, Jens

2017-10-01

Energy production is inevitably linked to the generation of toxic metabolites, such as reactive oxygen and carbonyl species, known as major contributors to ageing and degenerative diseases. It remains unclear how cells can adapt to elevated energy flux accompanied by accumulating harmful by-products without taking any damage. Therefore, effects of a sudden rise in glucose concentrations were studied in yeast cells. This revealed a feedback mechanism initiated by the reactive dicarbonyl methylglyoxal, which is formed non-enzymatically during glycolysis. Low levels of methylglyoxal activate a multi-layered defence response against toxic metabolites composed of prevention, detoxification and damage remission. The latter is mediated by the protein quality control system and requires inducible Hsp70 and Btn2, the aggregase that sequesters misfolded proteins. This glycohormetic mechanism enables cells to pre-adapt to rising energy flux and directly links metabolic to proteotoxic stress. Further data suggest the existence of a similar response in endothelial cells. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Development of a high-throughput screening system for identification of novel reagents regulating DNA damage in human dermal fibroblasts.

PubMed

Bae, Seunghee; An, In-Sook; An, Sungkwan

2015-09-01

Ultraviolet (UV) radiation is a major inducer of skin aging and accumulated exposure to UV radiation increases DNA damage in skin cells, including dermal fibroblasts. In the present study, we developed a novel DNA repair regulating material discovery (DREAM) system for the high-throughput screening and identification of putative materials regulating DNA repair in skin cells. First, we established a modified lentivirus expressing the luciferase and hypoxanthine phosphoribosyl transferase (HPRT) genes. Then, human dermal fibroblast WS-1 cells were infected with the modified lentivirus and selected with puromycin to establish cells that stably expressed luciferase and HPRT (DREAM-F cells). The first step in the DREAM protocol was a 96-well-based screening procedure, involving the analysis of cell viability and luciferase activity after pretreatment of DREAM-F cells with reagents of interest and post-treatment with UVB radiation, and vice versa. In the second step, we validated certain effective reagents identified in the first step by analyzing the cell cycle, evaluating cell death, and performing HPRT-DNA sequencing in DREAM-F cells treated with these reagents and UVB. This DREAM system is scalable and forms a time-saving high-throughput screening system for identifying novel anti-photoaging reagents regulating DNA damage in dermal fibroblasts.

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

Taylor, Caitlin Anne; Bufford, Daniel Charles; Muntifering, Brittany Rana

Materials designed for nuclear reactors undergo microstructural changes resulting from a combination of several environmental factors, including neutron irradiation damage, gas accumulation and elevated temperatures. Typical ion beam irradiation experiments designed for simulating a neutron irradiation environment involve irradiating the sample with a single ion beam and subsequent characterization of the resulting microstructure, often by transmission electron microscopy (TEM). This method does not allow for examination of microstructural effects due to simultaneous gas accumulation and displacement cascade damage, which occurs in a reactor. Sandia’s in situ ion irradiation TEM (I 3TEM) offers the unique ability to observe microstructural changes duemore » to irradiation damage caused by concurrent multi-beam ion irradiation in real time. This allows for time-dependent microstructure analysis. A plethora of additional in situ stages can be coupled with these experiments, e.g., for more accurately simulating defect kinetics at elevated reactor temperatures. As a result, this work outlines experiments showing synergistic effects in Au using in situ ion irradiation with various combinations of helium, deuterium and Au ions, as well as some initial work on materials utilized in tritium-producing burnable absorber rods (TPBARs): zirconium alloys and LiAlO 2.« less

In-Situ NDE Characterization of Kevlar and Carbon Composite Micromechanics for Improved COPV Health Monitoring

NASA Technical Reports Server (NTRS)

Waller, Jess M.; Saulsberry, Regor L.

2009-01-01

This project is a subtask of a multi-center project to advance the state-of-the-art by developing NDE techniques that are capable of evaluating stress rupture (SR) degradation in Kevlar/epoxy (K/Ep) composite overwrapped pressure vessels (COPVs), and damage progression in carbon/epoxy (C/Ep) COPVs. In this subtask, acoustic emission (AE) data acquired during intermittent load hold tensile testing of K/Ep and C/Ep composite tow materials-of-construction used in COPV fabrication were analyzed to monitor progressive damage during the approach to tensile failure. Insight into the progressive damage of composite tow was gained by monitoring AE event rate, energy, source location, and frequency. Source location based on arrival time data was used to discern between significant AE attributable to microstructural damage and spurious AE attributable to background and grip noise. One of the significant findings was the observation of increasing violation of the Kaiser effect (Felicity ratio < 1.0) with damage accumulation.

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

Oshima, Masumi; Kin, Tadahiro; Kimura, Atsushi

Multi-step cascades from the {sup 62}Ni(n{sub cold},{gamma}) {sup 63}Ni reaction were studied via a {gamma}-ray spectroscopy method. With a {gamma}-ray detector array multiple {gamma}-ray coincident events were accumulated. By selecting full cascade events from the capture state to the ground state, we have developed a new computer-based level construction method and it is applied to excited level assignment in {sup 63}Ni.

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.

Critical pathogenic steps to high risk Helicobacter pylori gastritis and gastric carcinogenesis

PubMed Central

Lee, Inchul

2014-01-01

Helicobacter pylori (H. pylori) gastritis may progress to high risk gastropathy and cancer. However, the pathological progression has not been characterized in detail. H. pylori induce persistent inflammatory infiltration. Neutrophils are unique in that they directly infiltrate into foveolar epithelium aiming the proliferative zone specifically. Neutrophilic proliferative zone foveolitis is a critical pathogenic step in H. pylori gastritis inducing intensive epithelial damage. Epithelial cells carrying accumulated genomic damage and mutations show the Malgun (clear) cell change, characterized by large clear nucleus and prominent nucleolus. Malgun cells further undergo atypical changes, showing nuclear folding, coarse chromatin, and multiple nucleoli. The atypical Malgun cell (AMC) change is a novel premalignant condition in high risk gastropathy, which may progress and undergo malignant transformation directly. The pathobiological significance of AMC in gastric carcinogenesis is reviewed. A new diagnosis system of gastritis is proposed based on the critical pathologic steps classifying low and high risk gastritis for separate treatment modality. It is suggested that the regulation of H. pylori-induced neutrophilic foveolitis might be a future therapeutic goal replacing bactericidal antibiotics approach. PMID:24914362

Critical pathogenic steps to high risk Helicobacter pylori gastritis and gastric carcinogenesis.

PubMed

Lee, Inchul

2014-06-07

Helicobacter pylori (H. pylori) gastritis may progress to high risk gastropathy and cancer. However, the pathological progression has not been characterized in detail. H. pylori induce persistent inflammatory infiltration. Neutrophils are unique in that they directly infiltrate into foveolar epithelium aiming the proliferative zone specifically. Neutrophilic proliferative zone foveolitis is a critical pathogenic step in H. pylori gastritis inducing intensive epithelial damage. Epithelial cells carrying accumulated genomic damage and mutations show the Malgun (clear) cell change, characterized by large clear nucleus and prominent nucleolus. Malgun cells further undergo atypical changes, showing nuclear folding, coarse chromatin, and multiple nucleoli. The atypical Malgun cell (AMC) change is a novel premalignant condition in high risk gastropathy, which may progress and undergo malignant transformation directly. The pathobiological significance of AMC in gastric carcinogenesis is reviewed. A new diagnosis system of gastritis is proposed based on the critical pathologic steps classifying low and high risk gastritis for separate treatment modality. It is suggested that the regulation of H. pylori-induced neutrophilic foveolitis might be a future therapeutic goal replacing bactericidal antibiotics approach.

A Microstructurally Inspired Damage Model for Early Venous Thrombus

PubMed Central

Rausch, Manuel K.; Humphrey, Jay D.

2015-01-01

Accumulative damage may be an important contributor to many cases of thrombotic disease progression. Thus, a complete understanding of the pathological role of thrombus requires an understanding of its mechanics and in particular mechanical consequences of damage. In the current study, we introduce a novel microstructurally inspired constitutive model for thrombus that considers a non-uniform distribution of microstructural fibers at various crimp levels and employs one of the distribution parameters to incorporate stretch-driven damage on the microscopic level. To demonstrate its ability to represent the mechanical behavior of thrombus, including a recently reported Mullins type damage phenomenon, we fit our model to uniaxial tensile test data of early venous thrombus. Our model shows an agreement with these data comparable to previous models for damage in elastomers with the added advantages of a microstructural basis and fewer model parameters. We submit that our novel approach marks another important step toward modeling the evolving mechanics of intraluminal thrombus, specifically its damage, and hope it will aid in the study of physiological and pathological thrombotic events. PMID:26523784

Bioenergetic metabolites regulate base excision repair dependent cell death in response to DNA damage

PubMed Central

Tang, Jiang-bo; Goellner, Eva M.; Wang, Xiao-hong; Trivedi, Ram N.; Croix, Claudette M. St; Jelezcova, Elena; Svilar, David; Brown, Ashley R.; Sobol, Robert W.

2009-01-01

Base excision repair (BER) protein expression is important for resistance to DNA damage-induced cytotoxicity. Conversely, BER imbalance (Polß deficiency or repair inhibition) enhances cytotoxicity of radiation and chemotherapeutic DNA-damaging agents. Whereas inhibition of critical steps in the BER pathway result in the accumulation of cytotoxic DNA double-strand breaks, we report that DNA damage-induced cytotoxicity due to deficiency in the BER protein Polß triggers cell death dependent on PARP activation yet independent of poly(ADP-ribose) (PAR)-mediated AIF nuclear translocation or PARG, suggesting that cytotoxicity is not from PAR or PAR-catabolite signaling. Cell death is rescued by the NAD+ metabolite NMN and is synergistic with inhibition of NAD+ biosynthesis, demonstrating that DNA damage-induced cytotoxicity mediated via BER inhibition is primarily dependent on cellular metabolite bioavailability. We offer a mechanistic justification for the elevated alkylation-induced cytotoxicity of Polß deficient cells, suggesting a linkage between DNA repair, cell survival and cellular bioenergetics. PMID:20068071

Dynamical analysis of cellular ageing by modeling of gene regulatory network based attractor landscape.

PubMed

Chong, Ket Hing; Zhang, Xiaomeng; Zheng, Jie

2018-01-01

Ageing is a natural phenomenon that is inherently complex and remains a mystery. Conceptual model of cellular ageing landscape was proposed for computational studies of ageing. However, there is a lack of quantitative model of cellular ageing landscape. This study aims to investigate the mechanism of cellular ageing in a theoretical model using the framework of Waddington's epigenetic landscape. We construct an ageing gene regulatory network (GRN) consisting of the core cell cycle regulatory genes (including p53). A model parameter (activation rate) is used as a measure of the accumulation of DNA damage. Using the bifurcation diagrams to estimate the parameter values that lead to multi-stability, we obtained a conceptual model for capturing three distinct stable steady states (or attractors) corresponding to homeostasis, cell cycle arrest, and senescence or apoptosis. In addition, we applied a Monte Carlo computational method to quantify the potential landscape, which displays: I) one homeostasis attractor for low accumulation of DNA damage; II) two attractors for cell cycle arrest and senescence (or apoptosis) in response to high accumulation of DNA damage. Using the Waddington's epigenetic landscape framework, the process of ageing can be characterized by state transitions from landscape I to II. By in silico perturbations, we identified the potential landscape of a perturbed network (inactivation of p53), and thereby demonstrated the emergence of a cancer attractor. The simulated dynamics of the perturbed network displays a landscape with four basins of attraction: homeostasis, cell cycle arrest, senescence (or apoptosis) and cancer. Our analysis also showed that for the same perturbed network with low DNA damage, the landscape displays only the homeostasis attractor. The mechanistic model offers theoretical insights that can facilitate discovery of potential strategies for network medicine of ageing-related diseases such as cancer.

Probabilistic soil erosion modeling using the Erosion Risk Management Tool (ERMIT) after wildfires

Treesearch

P. R. Robichaud; W. J. Elliot; J. W. Wagenbrenner

2011-01-01

The decision of whether or not to apply post-fire hillslope erosion mitigation treatments, and if so, where these treatments are most needed, is a multi-step process. Land managers must assess the risk of damaging runoff and sediment delivery events occurring on the unrecovered burned hillslope. We developed the Erosion Risk Management Tool (ERMiT) to address this need...

The Possible Crosstalk of MOB2 With NDR1/2 Kinases in Cell Cycle and DNA Damage Signaling.

PubMed

Gundogdu, Ramazan; Hergovich, Alexander

2016-09-06

This article is the authors' opinion of the roles of the signal transducer Mps one binder 2 (MOB2) in the control of cell cycle progression and the DNA Damage Response (DDR). We recently found that endogenous MOB2 is required to prevent the accumulation of endogenous DNA damage in order to prevent the undesired, and possibly detrimental, activation of cell cycle checkpoints. In this regard, it is noteworthy that MOB2 has been linked biochemically to the regulation of the NDR1/2 (aka STK38/STK38L) protein kinases, which themselves have functions at different steps of the cell cycle. Therefore, we are speculating in this article about the possible connections of MOB2 with NDR1/2 kinases in cell cycle and DDR Signaling.

Unique medical issues in adult patients with mucopolysaccharidoses.

PubMed

Mitchell, John; Berger, Kenneth I; Borgo, Andrea; Braunlin, Elizabeth A; Burton, Barbara K; Ghotme, Kemel A; Kircher, Susanne G; Molter, David; Orchard, Paul J; Palmer, James; Pastores, Gregory M; Rapoport, David M; Wang, Raymond Y; White, Klane

2016-10-01

The mucopolysaccharidoses are a group of inherited metabolic diseases caused by deficiencies in enzymes involved in the sequential degradation of glycosaminoglycans (GAGs) leading to substrate accumulation in various tissues and organs. GAG accumulation can cause growth retardation and progressive damage to respiratory, cardiovascular, musculoskeletal, nervous, gastrointestinal, auditory, and visual systems. In the past, few people with severe phenotypic mucopolysaccharidosis (MPS) reached adulthood. However, better methods for diagnosis, multi-disciplinary care, and new therapies have extended lifespan, leading to an increasing number of patients surviving beyond childhood. The growing number of adult MPS patients poses significant challenges for clinicians who may not be familiar with the clinical manifestations of MPS. In addition, as new interventions have changed the natural history of these disorders, it is difficult to anticipate both the impact on life expectancy and other complications that may occur as these patients age. Because the MPS disorders are multi-organ diseases, their management requires a coordinated multi-disciplinary approach. Here we discuss the unique pattern of medical issues and multi-organ involvement in adult patients with MPS and identify the challenges that are associated with management of MPS. This review is based on information from an expert investigator meeting with MPS specialists held October 2-4, 2014 in Dublin, Ireland, as well as on current literature searches focusing on MPS and adults. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

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

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

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

2013-12-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-05-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

Environmental impact of multi-wall carbon nanotubes in a novel model of exposure: systemic distribution, macrophage accumulation, and amyloid deposition

PubMed Central

Albini, Adriana; Pagani, Arianna; Pulze, Laura; Bruno, Antonino; Principi, Elisa; Congiu, Terenzio; Gini, Elisabetta; Grimaldi, Annalisa; Bassani, Barbara; De Flora, Silvio; de Eguileor, Magda; Noonan, Douglas M

2015-01-01

Carbon nanotubes (CNTs) have been extensively investigated and employed for industrial use because of their peculiar physical properties, which make them ideal for many industrial applications. However, rapid growth of CNT employment raises concerns about the potential risks and toxicities for public health, environment, and workers associated with the manufacture and use of these new materials. Here we investigate the main routes of entry following environmental exposure to multi-wall CNTs (MWCNTs; currently the most widely used in industry). We developed a novel murine model that could represent a surrogate of a workplace exposure to MWCNTs. We traced the localization of MWCNTs and their possible role in inducing an innate immune response, inflammation, macrophage recruitment, and inflammatory conditions. Following environmental exposure of CD1 mice, we observed that MWCNTs rapidly enter and disseminate in the organism, initially accumulating in lungs and brain and later reaching the liver and kidney via the bloodstream. Since recent experimental studies show that CNTs are associated with the aggregation process of proteins associated with neurodegenerative diseases, we investigated whether MWCNTs are able to induce amyloid fibril production and accumulation. Amyloid deposits in spatial association with macrophages and MWCNT aggregates were found in the brain, liver, lungs, and kidneys of exposed animals. Our data suggest that accumulation of MWCNTs in different organs is associated with inflammation and amyloid accumulation. In the brain, where we observed rapid accumulation and amyloid fibril deposition, exposure to MWCNTs might enhance progression of neurodegenerative and other amyloid-related diseases. Our data highlight the conclusion that, in a novel rodent model of exposure, MWCNTs may induce macrophage recruitment, activation, and amyloid deposition, causing potential damage to several organs. PMID:26457053

Clinical manifestations and management of Gaucher disease.

PubMed

Linari, Silvia; Castaman, Giancarlo

2015-01-01

Gaucher disease is a rare multi-systemic metabolic disorder caused by the inherited deficiency of the lysosomal enzyme β-glucocerebrosidase, which leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages with damage to haematological, visceral and bone systems. Anaemia, thrombocytopenia, enlargement of liver and/or spleen, skeletal abnormalities (osteopenia, lytic lesions, pathological fractures, chronic bone pain, bone crisis, bone infarcts, osteonecrosis and skeletal deformities) are typical manifestations of the most prevalent form of the disease, the so-called non-neuronopathic type 1. However, severity and coexistence of different symptoms are highly variable. The determination of deficient β-glucocerebrosidase activity in leukocytes or fibroblasts by enzymatic assay is the gold standard for the diagnosis of Gaucher disease. Comprehensive and reproducible evaluation and monitoring of all clinically relevant aspects are fundamental for the effective management of Gaucher disease patients. Enzyme replacement therapy has been shown to be effective in reducing glucocerebroside storage burden and diminishing the deleterious effects caused by its accumulation. Tailored treatment plan for each patient should be directed to symptom relief, general improvement of quality of life, and prevention of irreversible damage.

Removing flicker based on sparse color correspondences in old film restoration

NASA Astrophysics Data System (ADS)

Huang, Xi; Ding, Youdong; Yu, Bing; Xia, Tianran

2018-04-01

In the long history of human civilization, archived film is an indispensable part of it, and using digital method to repair damaged film is also a mainstream trend nowadays. In this paper, we propose a sparse color correspondences based technique to remove fading flicker for old films. Our model, combined with multi frame images to establish a simple correction model, includes three key steps. Firstly, we recover sparse color correspondences in the input frames to build a matrix with many missing entries. Secondly, we present a low-rank matrix factorization approach to estimate the unknown parameters of this model. Finally, we adopt a two-step strategy that divide the estimated parameters into reference frame parameters for color recovery correction and other frame parameters for color consistency correction to remove flicker. Our method combined multi-frames takes continuity of the input sequence into account, and the experimental results show the method can remove fading flicker efficiently.

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.

Towards a More Efficient Detection of Earthquake Induced FAÇADE Damages Using Oblique Uav Imagery

NASA Astrophysics Data System (ADS)

Duarte, D.; Nex, F.; Kerle, N.; Vosselman, G.

2017-08-01

Urban search and rescue (USaR) teams require a fast and thorough building damage assessment, to focus their rescue efforts accordingly. Unmanned aerial vehicles (UAV) are able to capture relevant data in a short time frame and survey otherwise inaccessible areas after a disaster, and have thus been identified as useful when coupled with RGB cameras for façade damage detection. Existing literature focuses on the extraction of 3D and/or image features as cues for damage. However, little attention has been given to the efficiency of the proposed methods which hinders its use in an urban search and rescue context. The framework proposed in this paper aims at a more efficient façade damage detection using UAV multi-view imagery. This was achieved directing all damage classification computations only to the image regions containing the façades, hence discarding the irrelevant areas of the acquired images and consequently reducing the time needed for such task. To accomplish this, a three-step approach is proposed: i) building extraction from the sparse point cloud computed from the nadir images collected in an initial flight; ii) use of the latter as proxy for façade location in the oblique images captured in subsequent flights, and iii) selection of the façade image regions to be fed to a damage classification routine. The results show that the proposed framework successfully reduces the extracted façade image regions to be assessed for damage 6 fold, hence increasing the efficiency of subsequent damage detection routines. The framework was tested on a set of UAV multi-view images over a neighborhood of the city of L'Aquila, Italy, affected in 2009 by an earthquake.

Effect of l-Proline on Sake Brewing and Ethanol Stress in Saccharomyces cerevisiae

PubMed Central

Takagi, Hiroshi; Takaoka, Miki; Kawaguchi, Akari; Kubo, Yoshito

2005-01-01

During the fermentation of sake, cells of Saccharomyces cerevisiae are exposed to high concentrations of ethanol, thereby damaging the cell membrane and functional proteins. l-Proline protects yeast cells from damage caused by freezing or oxidative stress. In this study, we evaluated the role of intracellular l-proline in cells of S. cerevisiae grown under ethanol stress. An l-proline-accumulating laboratory strain carries a mutant allele of PRO1, pro1D154N, which encodes the Asp154Asn mutant γ-glutamyl kinase. This mutation increases the activity of γ-glutamyl kinase and γ-glutamyl phosphate reductase, which catalyze the first two steps of l-proline synthesis and which together may form a complex in vivo. When cultured in liquid medium in the presence of 9% and 18% ethanol under static conditions, the cell viability of the l-proline-accumulating laboratory strain is greater than the cell viability of the parent strain. This result suggests that intracellular accumulation of l-proline may confer tolerance to ethanol stress. We constructed a novel sake yeast strain by disrupting the PUT1 gene, which is required for l-proline utilization, and replacing the wild-type PRO1 allele with the pro1D154N allele. The resultant strain accumulated l-proline and was more tolerant to ethanol stress than was the control strain. We used the strain that could accumulate l-proline to brew sake containing five times more l-proline than what is found in sake brewed with the control strain, without affecting the fermentation profiles. PMID:16332860

Early and Late Damages in Chromosome 3 of Human Lymphocytes After Radiation Exposure

NASA Technical Reports Server (NTRS)

Sunagawa, Mayumi; Mangala, Lingegowda; Zhang, Ye; Kahdim, Munira; Wilson, Bobby; Cucinotta, Francis A.; Wu, Honglu

2011-01-01

Tumor formation in humans or animals is a multi-step process. An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. GI is defined as elevated or persistent genetic damages occurring many generations after the cells are exposed. While early studies have demonstrated radiation-induced GI in several cell types as detected in endpoints such as mutation, apoptosis and damages in chromosomes, the dependence of GI on the quality of radiation remains uncertain. To investigate GI in human lymphocytes induced by both low- and high-LET radiation, we initially exposed white blood cells collected from healthy subjects to gamma rays in vitro, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis post irradiation and at several intervals during the culture period. Among a number of biological endpoints planned for the project, the multi-color banding fluorescent in situ hybridization (mBAND) allows identification of inversions that were expected to be stable. We present here early and late chromosome aberrations detected with mBAND in chromosome 3 after gamma exposure. Comparison of chromosome damages in between human lymphocytes and human epithelial cells is also discussed

Skeletal muscle damage and impaired regeneration due to LPL-mediated lipotoxicity

PubMed Central

Tamilarasan, K P; Temmel, H; Das, S K; Al Zoughbi, W; Schauer, S; Vesely, P W; Hoefler, G

2012-01-01

According to the concept of lipotoxicity, ectopic accumulation of lipids in non-adipose tissue induces pathological changes. The most prominent effects are seen in fatty liver disease, lipid cardiomyopathy, non-insulin-dependent diabetes mellitus, insulin resistance and skeletal muscle myopathy. We used the MCK(m)-hLPL mouse distinguished by skeletal and cardiac muscle-specific human lipoprotein lipase (hLPL) overexpression to investigate effects of lipid overload in skeletal muscle. We were intrigued to find that ectopic lipid accumulation induced proteasomal activity, apoptosis and skeletal muscle damage. In line with these findings we observed reduced Musculus gastrocnemius and Musculus quadriceps mass in transgenic animals, accompanied by severely impaired physical endurance. We suggest that muscle loss was aggravated by impaired muscle regeneration as evidenced by reduced cross-sectional area of regenerating myofibers after cardiotoxin-induced injury in MCK(m)-hLPL mice. Similarly, an almost complete loss of myogenic potential was observed in C2C12 murine myoblasts upon overexpression of LPL. Our findings directly link lipid overload to muscle damage, impaired regeneration and loss of performance. These findings support the concept of lipotoxicity and are a further step to explain pathological effects seen in muscle of obese patients, patients with the metabolic syndrome and patients with cancer-associated cachexia. PMID:22825472

Residual strength and crack propagation tests on C-130 airplane center wings with service-imposed fatigue damage

NASA Technical Reports Server (NTRS)

Snider, H. L.; Reeder, F. L.; Dirkin, W. J.

1972-01-01

Fourteen C-130 airplane center wings, each containing service-imposed fatigue damage resulting from 4000 to 13,000 accumulated flight hours, were tested to determine their fatigue crack propagation and static residual strength characteristics. Eight wings were subjected to a two-step constant amplitude fatigue test prior to static testing. Cracks up to 30 inches long were generated in these tests. Residual static strengths of these wings ranged from 56 to 87 percent of limit load. The remaining six wings containing cracks up to 4 inches long were statically tested as received from field service. Residual static strengths of these wings ranged from 98 to 117 percent of limit load. Damage-tolerant structural design features such as fastener holes, stringers, doublers around door cutouts, and spanwise panel splices proved to be effective in retarding crack propagation.

Deformation history and load sequence effects on cumulative fatigue damage and life predictions

NASA Astrophysics Data System (ADS)

Colin, Julie

Fatigue loading seldom involves constant amplitude loading. This is especially true in the cooling systems of nuclear power plants, typically made of stainless steel, where thermal fluctuations and water turbulent flow create variable amplitude loads, with presence of mean stresses and overloads. These complex loading sequences lead to the formation of networks of microcracks (crazing) that can propagate. As stainless steel is a material with strong deformation history effects and phase transformation resulting from plastic straining, such load sequence and variable amplitude loading effects are significant to its fatigue behavior and life predictions. The goal of this study was to investigate the effects of cyclic deformation on fatigue behavior of stainless steel 304L as a deformation history sensitive material and determine how to quantify and accumulate fatigue damage to enable life predictions under variable amplitude loading conditions for such materials. A comprehensive experimental program including testing under fully-reversed, as well as mean stress and/or mean strain conditions, with initial or periodic overloads, along with step testing and random loading histories was conducted on two grades of stainless steel 304L, under both strain-controlled and load-controlled conditions. To facilitate comparisons with a material without deformation history effects, similar tests were also carried out on aluminum 7075-T6. Experimental results are discussed, including peculiarities observed with stainless steel behavior, such as a phenomenon, referred to as secondary hardening characterized by a continuous increase in the stress response in a strain-controlled test and often leading to runout fatigue life. Possible mechanisms for secondary hardening observed in some tests are also discussed. The behavior of aluminum is shown not to be affected by preloading, whereas the behavior of stainless steel is greatly influenced by prior loading. Mean stress relaxation in strain control and ratcheting in load control and their influence on fatigue life are discussed. Some unusual mean strain test results are presented for stainless steel 304L, where in spite of mean stress relaxation fatigue lives were significantly longer than fully-reversed tests. Prestraining indicated no effect on either deformation or fatigue behavior of aluminum, while it induced considerable hardening in stainless steel 304L and led to different results on fatigue life, depending on the test control mode. In step tests for stainless steel 304L, strong hardening induced by the first step of a high-low sequence significantly affects the fatigue behavior, depending on the test control mode used. For periodic overload tests of stainless steel 340L, hardening due to the overloads was progressive throughout life and more significant than in high-low step tests. For aluminum, no effect on deformation behavior was observed due to periodic overloads. However, the direction of the overloads was found to affect fatigue life, as tensile overloads led to longer lives, while compressive overloads led to shorter lives. Deformation and fatigue behaviors under random loading conditions are also presented and discussed for the two materials. The applicability of a common cumulative damage rule, the linear damage rule, is assessed for the two types of material, and for various loading conditions. While the linear damage rule associated with a strain-life or stress-life curve is shown to be fairly accurate for life predictions for aluminum, it is shown to poorly represent the behavior of stainless steel, especially in prestrained and high-low step tests, in load control. In order to account for prior deformation effects and achieve accurate fatigue life predictions for stainless steel, parameters including both stress and strain terms are required. The Smith-Watson-Topper and Fatemi-Socie approaches, as such parameters, are shown to correlate most test data fairly accurately. For damage accumulation under variable amplitude loading, the linear damage rule associated with strain-life or stress-life curves can lead to inaccurate fatigue life predictions, especially for materials presenting strong deformation memory effect, such as stainless steel 304L. The inadequacy of this method is typically attributed to the linear damage rule itself. On the contrary, this study demonstrates that damage accumulation using the linear damage rule can be accurate, provided that the linear damage rule is used in conjunction with parameters including both stress and strain terms. By including both loading history and response of the material in damage quantification, shortcomings of the commonly used linear damage rule approach can be circumvented in an effective manner. In addition, cracking behavior was also analyzed under various loading conditions. Results on microcrack initiation and propagation are presented in relation to deformation and fatigue behaviors of the materials. Microcracks were observed to form during the first few percent of life, indicating that most of the fatigue life of smooth specimens is spent in microcrack formation and growth. Analyses of fractured specimens showed that microcrack formation and growth is dependent on the loading history, and less important in aluminum than stainless steel 304L, due to the higher toughness of this latter material.

Monitoring and evaluating civil structures using measured vibration

NASA Astrophysics Data System (ADS)

Straser, Erik G.; Kiremidjian, Anne S.

1996-04-01

The need for a rapid assessment of the state of critical and conventional civil structures, such as bridges, control centers, airports, and hospitals, among many, has been amply demonstrated during recent natural disasters. Research is underway at Stanford University to develop a state-of-the-art automated damage monitoring system for long term and extreme event monitoring based on both ambient and forced response measurements. Such research requires a multi-disciplinary approach harnessing the talents and expertise of civil, electrical, and mechanical engineering to arrive at a novel hardware and software solution. Recent advances in silicon micro-machining and microprocessor design allow for the economical integration of sensing, processing, and communication components. Coupling these technological advances with parameter identification algorithms allows for the realization of extreme event damage monitoring systems for civil structures. This paper addresses the first steps toward the development of a near real-time damage diagnostic and monitoring system based on structural response to extreme events. Specifically, micro-electro-mechanical- structures (MEMS) and microcontroller embedded systems (MES) are demonstrated to be an effective platform for the measurement and analysis of civil structures. Experimental laboratory tests with small scale model specimens and a preliminary sensor module are used to evaluate hardware and obtain structural response data from input accelerograms. A multi-step analysis procedure employing ordinary least squares (OLS), extended Kalman filtering (EKF), and a substructuring approach is conducted to extract system characteristics of the model. Results from experimental tests and system identification (SI) procedures as well as fundamental system design issues are presented.

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

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

PubMed

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

2013-12-01

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

Effect of the state of internal boundaries on granite fracture nature under quasi-static compression

NASA Astrophysics Data System (ADS)

Damaskinskaya, E. E.; Panteleev, I. A.; Kadomtsev, A. G.; Naimark, O. B.

2017-05-01

Based on an analysis of the spatial distribution of hypocenters of acoustic emission signal sources and an analysis of the energy distributions of acoustic emission signals, the effect of the liquid phase and a weak electric field on the spatiotemporal nature of granite sample fracture is studied. Experiments on uniaxial compression of granite samples of natural moisture showed that the damage accumulation process is twostage: disperse accumulation of damages is followed by localized accumulation of damages in the formed macrofracture nucleus region. In energy distributions of acoustic emission signals, this transition is accompanied by a change in the distribution shape from exponential to power-law. Granite water saturation qualitatively changes the damage accumulation nature: the process is delocalized until macrofracture with the exponential energy distribution of acoustic emission signals. An exposure to a weak electric field results in a selective change in the damage accumulation nature in the sample volume.

Why pleiotropic interventions are needed for Alzheimer's disease.

PubMed

Frautschy, Sally A; Cole, Greg M

2010-06-01

Alzheimer's disease (AD) involves a complex pathological cascade thought to be initially triggered by the accumulation of beta-amyloid (Abeta) peptide aggregates or aberrant amyloid precursor protein (APP) processing. Much is known of the factors initiating the disease process decades prior to the onset of cognitive deficits, but an unclear understanding of events immediately preceding and precipitating cognitive decline is a major factor limiting the rapid development of adequate prevention and treatment strategies. Multiple pathways are known to contribute to cognitive deficits by disruption of neuronal signal transduction pathways involved in memory. These pathways are altered by aberrant signaling, inflammation, oxidative damage, tau pathology, neuron loss, and synapse loss. We need to develop stage-specific interventions that not only block causal events in pathogenesis (aberrant tau phosphorylation, Abeta production and accumulation, and oxidative damage), but also address damage from these pathways that will not be reversed by targeting prodromal pathways. This approach would not only focus on blocking early events in pathogenesis, but also adequately correct for loss of synapses, substrates for neuroprotective pathways (e.g., docosahexaenoic acid), defects in energy metabolism, and adverse consequences of inappropriate compensatory responses (aberrant sprouting). Monotherapy targeting early single steps in this complicated cascade may explain disappointments in trials with agents inhibiting production, clearance, or aggregation of the initiating Abeta peptide or its aggregates. Both plaque and tangle pathogenesis have already reached AD levels in the more vulnerable brain regions during the "prodromal" period prior to conversion to "mild cognitive impairment (MCI)." Furthermore, many of the pathological events are no longer proceeding in series, but are going on in parallel. By the MCI stage, we stand a greater chance of success by considering pleiotropic drugs or cocktails that can independently limit the parallel steps of the AD cascade at all stages, but that do not completely inhibit the constitutive normal functions of these pathways. Based on this hypothesis, efforts in our laboratories have focused on the pleiotropic activities of omega-3 fatty acids and the anti-inflammatory, antioxidant, and anti-amyloid activity of curcumin in multiple models that cover many steps of the AD pathogenic cascade (Cole and Frautschy, Alzheimers Dement 2:284-286, 2006).

Energy release, beam attenuation radiation damage, gas production and accumulation of long-lived activity in Pb, Pb-Bi and Hg targets

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

Shubin, Yu.N.

1996-06-01

The calculation and analysis of the nuclei concentrations and long-lived residual radioactivity accumulated in Pb, Pb-Bi and Hg targets irradiated by 800 MeV, 30 mA proton beam have been performed. The dominating components to the total radioactivity of radionuclides resulting from fission and spallation reactions and radiative capture by both target nuclei and accumulated radioactive nuclei for various irradiation and cooling times were analyzed. The estimations of spectral component contributions of neutron and proton fluxes to the accumulated activity were carried out. The contributions of fission products to the targets activity and partial activities of main long-lived fission products tomore » the targets activity and partial activities of main long-lived fission products were evaluated. The accumulation of Po isotopes due to reactions induced by secondary alpha-particles were found to be important for the Pb target as compared with two-step radiative capture. The production of Tritium in the targets and its contribution to the total targets activity was considered in detail. It is found that total activities of both targets are close to one another.« less

Creep Life Prediction of Ceramic Components Using the Finite Element Based Integrated Design Program (CARES/Creep)

NASA Technical Reports Server (NTRS)

Jadaan, Osama M.; Powers, Lynn M.; Gyekenyesi, John P.

1997-01-01

The desirable properties of ceramics at high temperatures have generated interest in their use for structural applications such as in advanced turbine systems. Design lives for such systems can exceed 10,000 hours. Such long life requirements necessitate subjecting the components to relatively low stresses. The combination of high temperatures and low stresses typically places failure for monolithic ceramics in the creep regime. The objective of this work is to present a design methodology for predicting the lifetimes of structural components subjected to multiaxial creep loading. This methodology utilizes commercially available finite element packages and takes into account the time varying creep stress distributions (stress relaxation). In this methodology, the creep life of a component is divided into short time steps, during which, the stress and strain distributions are assumed constant. The damage, D, is calculated for each time step based on a modified Monkman-Grant creep rupture criterion. For components subjected to predominantly tensile loading, failure is assumed to occur when the normalized accumulated damage at any point in the component is greater than or equal to unity.

In vivo MRI-based simulation of fatigue process: a possible trigger for human carotid atherosclerotic plaque rupture.

PubMed

Huang, Yuan; Teng, Zhongzhao; Sadat, Umar; He, Jing; Graves, Martin J; Gillard, Jonathan H

2013-04-23

Atherosclerotic plaque is subjected to a repetitive deformation due to arterial pulsatility during each cardiac cycle and damage may be accumulated over a time period causing fibrous cap (FC) fatigue, which may ultimately lead to rupture. In this study, we investigate the fatigue process in human carotid plaques using in vivo carotid magnetic resonance (MR) imaging. Twenty seven patients with atherosclerotic carotid artery disease were included in this study. Multi-sequence, high-resolution MR imaging was performed to depict the plaque structure. Twenty patients were found with ruptured FC or ulceration and 7 without. Modified Paris law was used to govern crack propagation and the propagation direction was perpendicular to the maximum principal stress at the element node located at the vulnerable site. The predicted crack initiations from 20 patients with FC defect all matched with the locations of the in vivo observed FC defect. Crack length increased rapidly with numerical steps. The natural logarithm of fatigue life decreased linearly with the local FC thickness (R(2) = 0.67). Plaques (n=7) without FC defect had a longer fatigue life compared with those with FC defect (p = 0.03). Fatigue process seems to explain the development of cracks in FC, which ultimately lead to plaque rupture.

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

PubMed

Lieberman, Rachel; You, Ming

2017-07-15

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

Health condition identification of multi-stage planetary gearboxes using a mRVM-based method

NASA Astrophysics Data System (ADS)

Lei, Yaguo; Liu, Zongyao; Wu, Xionghui; Li, Naipeng; Chen, Wu; Lin, Jing

2015-08-01

Multi-stage planetary gearboxes are widely applied in aerospace, automotive and heavy industries. Their key components, such as gears and bearings, can easily suffer from damage due to tough working environment. Health condition identification of planetary gearboxes aims to prevent accidents and save costs. This paper proposes a method based on multiclass relevance vector machine (mRVM) to identify health condition of multi-stage planetary gearboxes. In this method, a mRVM algorithm is adopted as a classifier, and two features, i.e. accumulative amplitudes of carrier orders (AACO) and energy ratio based on difference spectra (ERDS), are used as the input of the classifier to classify different health conditions of multi-stage planetary gearboxes. To test the proposed method, seven health conditions of a two-stage planetary gearbox are considered and vibration data is acquired from the planetary gearbox under different motor speeds and loading conditions. The results of three tests based on different data show that the proposed method obtains an improved identification performance and robustness compared with the existing method.

A Dimensionality Reduction-Based Multi-Step Clustering Method for Robust Vessel Trajectory Analysis

PubMed Central

Liu, Jingxian; Wu, Kefeng

2017-01-01

The Shipboard Automatic Identification System (AIS) is crucial for navigation safety and maritime surveillance, data mining and pattern analysis of AIS information have attracted considerable attention in terms of both basic research and practical applications. Clustering of spatio-temporal AIS trajectories can be used to identify abnormal patterns and mine customary route data for transportation safety. Thus, the capacities of navigation safety and maritime traffic monitoring could be enhanced correspondingly. However, trajectory clustering is often sensitive to undesirable outliers and is essentially more complex compared with traditional point clustering. To overcome this limitation, a multi-step trajectory clustering method is proposed in this paper for robust AIS trajectory clustering. In particular, the Dynamic Time Warping (DTW), a similarity measurement method, is introduced in the first step to measure the distances between different trajectories. The calculated distances, inversely proportional to the similarities, constitute a distance matrix in the second step. Furthermore, as a widely-used dimensional reduction method, Principal Component Analysis (PCA) is exploited to decompose the obtained distance matrix. In particular, the top k principal components with above 95% accumulative contribution rate are extracted by PCA, and the number of the centers k is chosen. The k centers are found by the improved center automatically selection algorithm. In the last step, the improved center clustering algorithm with k clusters is implemented on the distance matrix to achieve the final AIS trajectory clustering results. In order to improve the accuracy of the proposed multi-step clustering algorithm, an automatic algorithm for choosing the k clusters is developed according to the similarity distance. Numerous experiments on realistic AIS trajectory datasets in the bridge area waterway and Mississippi River have been implemented to compare our proposed method with traditional spectral clustering and fast affinity propagation clustering. Experimental results have illustrated its superior performance in terms of quantitative and qualitative evaluations. PMID:28777353

True cadence and step accumulation are not equivalent: the effect of intermittent claudication on free-living cadence.

PubMed

Stansfield, B; Clarke, C; Dall, P; Godwin, J; Holdsworth, R; Granat, M

2015-02-01

'True cadence' is the rate of stepping during the period of stepping. 'Step accumulation' is the steps within an epoch of time (e.g. 1min). These terms have been used interchangeably in the literature. These outcomes are compared within a population with intermittent claudication (IC). Multiday, 24h stepping activity of those with IC (30) and controls (30) was measured objectively using the activPAL physical activity monitor. 'True cadence' and 'step accumulation' outcomes were calculated. Those with IC took fewer steps/d 6531±2712 than controls 8692±2945 (P=0.003). However, these steps were taken within approximately the same number of minute epochs (IC 301±100min/d; controls 300±70min/d, P=0.894) with only slightly lower true cadence (IC 69 (IQ 66,72) steps/min; controls 72 (IQ 68,76) steps/min, P=0.026), giving substantially lower step accumulation (IC 22 (IQ 19,24) steps/min; controls 30 (IQ 23,34) steps/min) (P<0.001). However, the true cadence of stepping within the blocks of the 1, 5, 20, 30 and 60min with the maximum number of steps accumulated was lower for those with IC than controls (P<0.05). Those with IC took 1300 steps fewer per day above a true cadence of 90 steps/min. True cadence and step accumulation outcomes were radically different for the outcomes examined. 'True cadence' and 'step accumulation' were not equivalent in those with IC or controls. The measurement of true cadence in the population of people with IC provides information about their stepping rate during the time they are stepping. True cadence should be used to correctly describe the rate of stepping as performed. Copyright © 2014 Elsevier B.V. All rights reserved.

Ammonium Accumulation and Cell Death in a Rat 3D Brain Cell Model of Glutaric Aciduria Type I

PubMed Central

Jafari, Paris; Braissant, Olivier; Zavadakova, Petra; Henry, Hugues; Bonafé, Luisa; Ballhausen, Diana

2013-01-01

Glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency) is an inborn error of metabolism that usually manifests in infancy by an acute encephalopathic crisis and often results in permanent motor handicap. Biochemical hallmarks of this disease are elevated levels of glutarate and 3-hydroxyglutarate in blood and urine. The neuropathology of this disease is still poorly understood, as low lysine diet and carnitine supplementation do not always prevent brain damage, even in early-treated patients. We used a 3D in vitro model of rat organotypic brain cell cultures in aggregates to mimic glutaric aciduria type I by repeated administration of 1 mM glutarate or 3-hydroxyglutarate at two time points representing different developmental stages. Both metabolites were deleterious for the developing brain cells, with 3-hydroxyglutarate being the most toxic metabolite in our model. Astrocytes were the cells most strongly affected by metabolite exposure. In culture medium, we observed an up to 11-fold increase of ammonium in the culture medium with a concomitant decrease of glutamine. We further observed an increase in lactate and a concomitant decrease in glucose. Exposure to 3-hydroxyglutarate led to a significantly increased cell death rate. Thus, we propose a three step model for brain damage in glutaric aciduria type I: (i) 3-OHGA causes the death of astrocytes, (ii) deficiency of the astrocytic enzyme glutamine synthetase leads to intracerebral ammonium accumulation, and (iii) high ammonium triggers secondary death of other brain cells. These unexpected findings need to be further investigated and verified in vivo. They suggest that intracerebral ammonium accumulation might be an important target for the development of more effective treatment strategies to prevent brain damage in patients with glutaric aciduria type I. PMID:23326493

Ammonium accumulation and cell death in a rat 3D brain cell model of glutaric aciduria type I.

PubMed

Jafari, Paris; Braissant, Olivier; Zavadakova, Petra; Henry, Hugues; Bonafé, Luisa; Ballhausen, Diana

2013-01-01

Glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency) is an inborn error of metabolism that usually manifests in infancy by an acute encephalopathic crisis and often results in permanent motor handicap. Biochemical hallmarks of this disease are elevated levels of glutarate and 3-hydroxyglutarate in blood and urine. The neuropathology of this disease is still poorly understood, as low lysine diet and carnitine supplementation do not always prevent brain damage, even in early-treated patients. We used a 3D in vitro model of rat organotypic brain cell cultures in aggregates to mimic glutaric aciduria type I by repeated administration of 1 mM glutarate or 3-hydroxyglutarate at two time points representing different developmental stages. Both metabolites were deleterious for the developing brain cells, with 3-hydroxyglutarate being the most toxic metabolite in our model. Astrocytes were the cells most strongly affected by metabolite exposure. In culture medium, we observed an up to 11-fold increase of ammonium in the culture medium with a concomitant decrease of glutamine. We further observed an increase in lactate and a concomitant decrease in glucose. Exposure to 3-hydroxyglutarate led to a significantly increased cell death rate. Thus, we propose a three step model for brain damage in glutaric aciduria type I: (i) 3-OHGA causes the death of astrocytes, (ii) deficiency of the astrocytic enzyme glutamine synthetase leads to intracerebral ammonium accumulation, and (iii) high ammonium triggers secondary death of other brain cells. These unexpected findings need to be further investigated and verified in vivo. They suggest that intracerebral ammonium accumulation might be an important target for the development of more effective treatment strategies to prevent brain damage in patients with glutaric aciduria type I.

Radiation tolerance of low resistivity, high voltage silicon solar cells

NASA Technical Reports Server (NTRS)

Weizer, V. G.; Weinberg, I.; Swartz, C. K.

1984-01-01

The radiation tolerance of the following three low resistivity, high voltage silicon solar cells was investigated: (1) the COMSAT MSD (multi-step diffused) cell, (2) the MinMIS cell, and (3) the MIND cell. A description of these solar cells is given along with drawings of their configurations. The diffusion length damage coefficients for the cells were calculated and presented. Solar cell spectral response was also discussed. Cells of the MinMIS type were judged to be unsuitable for use in the space radiation environment.

Interplay of wavelength, fluence and spot-size in free-electron laser ablation of cornea.

PubMed

Hutson, M Shane; Ivanov, Borislav; Jayasinghe, Aroshan; Adunas, Gilma; Xiao, Yaowu; Guo, Mingsheng; Kozub, John

2009-06-08

Infrared free-electron lasers ablate tissue with high efficiency and low collateral damage when tuned to the 6-microm range. This wavelength-dependence has been hypothesized to arise from a multi-step process following differential absorption by tissue water and proteins. Here, we test this hypothesis at wavelengths for which cornea has matching overall absorption, but drastically different differential absorption. We measure etch depth, collateral damage and plume images and find that the hypothesis is not confirmed. We do find larger etch depths for larger spot sizes--an effect that can lead to an apparent wavelength dependence. Plume imaging at several wavelengths and spot sizes suggests that this effect is due to increased post-pulse ablation at larger spots.

Role of transmethylation reactions in alcoholic liver disease

PubMed Central

Kharbanda, Kusum K

2007-01-01

Alcoholic liver disease is a major health care problem worldwide. Findings from many laboratories, including ours, have demonstrated that ethanol feeding impairs several of the many steps involved in methionine metabolism. Ethanol consumption predominantly results in a decrease in the hepatocyte level of S-adenosylmethionine and the increases in two toxic metabolites, homocysteine and S-adenosylhomocysteine. These changes, in turn, result in serious functional consequences which include decreases in essential methylation reactions via inhibition of various methyltransferases. Of particular interest to our laboratory is the inhibition of three important enzymes, phosphatidylethanolamine methyltransferase, isoprenylcysteine carboxyl methyltransferase and protein L-isoaspartate methyltransferase. Decreased activity of these enzymes results in increased fat deposition, increased apoptosis and increased accumulation of damaged proteins-all of which are hallmark features of alcoholic liver injury. Of all the therapeutic modalities available, betaine has been shown to be the safest, least expensive and most effective in attenuating ethanol-induced liver injury. Betaine, by virtue of aiding in the remethylation of homocysteine, removes both toxic metabolites (homocysteine and S-adenosylhomocysteine), restores S-adenosylmethionine level, and reverses steatosis, apoptosis and damaged proteins accumulation. In conclusion, betaine appears to be a promising therapeutic agent in relieving the methylation and other defects associated with alcoholic abuse. PMID:17854136

Macrodamage Accumulation Model for a Human Femur

PubMed Central

2017-01-01

The objective of this study was to more fully understand the mechanical behavior of bone tissue that is important to find an alternative material to be used as an implant and to develop an accurate model to predict the fracture of the bone. Predicting and preventing bone failure is an important area in orthopaedics. In this paper, the macrodamage accumulation models in the bone tissue have been investigated. Phenomenological models for bone damage have been discussed in detail. In addition, 3D finite element model of the femur prepared from imaging data with both cortical and trabecular structures is delineated using MIMICS and ANSYS® and simulated as a composite structure. The damage accumulation occurring during cyclic loading was analyzed for fatigue scenario. We found that the damage accumulates sooner in the multiaxial than in the uniaxial loading condition for the same number of cycles, and the failure starts in the cortical bone. The damage accumulation behavior seems to follow a three-stage growth: a primary phase, a secondary phase of damage growth marked by linear damage growth, and a tertiary phase that leads to failure. Finally, the stiffness of the composite bone comprising the cortical and trabecular bone was significantly different as expected. PMID:28951659

Dynamic modeling of photothermal interactions for laser-induced interstitial thermotherapy: parameter sensitivity analysis.

PubMed

Jiang, S C; Zhang, X X

2005-12-01

A two-dimensional model was developed to model the effects of dynamic changes in the physical properties on tissue temperature and damage to simulate laser-induced interstitial thermotherapy (LITT) treatment procedures with temperature monitoring. A modified Monte Carlo method was used to simulate photon transport in the tissue in the non-uniform optical property field with the finite volume method used to solve the Pennes bioheat equation to calculate the temperature distribution and the Arrhenius equation used to predict the thermal damage extent. The laser light transport and the heat transfer as well as the damage accumulation were calculated iteratively at each time step. The influences of different laser sources, different applicator sizes, and different irradiation modes on the final damage volume were analyzed to optimize the LITT treatment. The numerical results showed that damage volume was the smallest for the 1,064-nm laser, with much larger, similar damage volumes for the 980- and 850-nm lasers at normal blood perfusion rates. The damage volume was the largest for the 1,064-nm laser with significantly smaller, similar damage volumes for the 980- and 850-nm lasers with temporally interrupted blood perfusion. The numerical results also showed that the variations in applicator sizes, laser powers, heating durations and temperature monitoring ranges significantly affected the shapes and sizes of the thermal damage zones. The shapes and sizes of the thermal damage zones can be optimized by selecting different applicator sizes, laser powers, heating duration times, temperature monitoring ranges, etc.

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

PubMed Central

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

2013-01-01

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

In-process deformation measurements of translucent high speed fibre-reinforced disc rotors

NASA Astrophysics Data System (ADS)

Philipp, Katrin; Filippatos, Angelos; Koukourakis, Nektarios; Kuschmierz, Robert; Leithold, Christoph; Langkamp, Albert; Fischer, Andreas; Czarske, Jürgen

2015-07-01

The high stiffness to weight ratio of glass fibre-reinforced polymers (GFRP) makes them an attractive material for rotors e.g. in the aerospace industry. We report on recent developments towards non-contact, in-situ deformation measurements with temporal resolution up to 200 µs and micron measurement uncertainty. We determine the starting point of damage evolution inside the rotor material through radial expansion measurements. This leads to a better understanding of dynamic material behaviour regarding damage evolution and the prediction of damage initiation and propagation. The measurements are conducted using a novel multi-sensor system consisting of four laser Doppler distance (LDD) sensors. The LDD sensor, a two-wavelength Mach-Zehnder interferometer was already successfully applied for dynamic deformation measurements at metallic rotors. While translucency of the GFRP rotor material limits the applicability of most optical measurement techniques due to speckles from both surface and volume of the rotor, the LDD profits from speckles and is not disturbed by backscattered laser light from the rotor volume. The LDD sensor evaluates only signals from the rotor surface. The anisotropic glass fibre-reinforcement results in a rotationally asymmetric dynamic deformation. A novel signal processing algorithm is applied for the combination of the single sensor signals to obtain the shape of the investigated rotors. In conclusion, the applied multi-sensor system allows high temporal resolution dynamic deformation measurements. First investigations regarding damage evolution inside GFRP are presented as an important step towards a fundamental understanding of the material behaviour and the prediction of damage initiation and propagation.

Review of basic medical results of the Salyut-7-Soyuz-T 8-month manned flight

NASA Astrophysics Data System (ADS)

Gazenko, O. G.; Schulzhenko, E. B.; Grigoriev, A. I.; Atkov, O. Yu.; Egorov, A. D.

This paper presents the results of medical investigations performed in the Salyut-7 8-month mission in which a professional physician took part. The paper contains anthropometric measurements, results of investigating the vestibular function, cardiovascular function at rest and in response to multi-step tests (with emphasis on echocardiographic measurements), metabolic parameters and hormonal status. It also discusses medical aspects of the extravehicular activity. The medical investigations, although some new methods were applied, provided the continuity of methodical approaches and data accumulated in previous missions.

Single-molecule localization microscopy reveals molecular transactions during RAD51 filament assembly at cellular DNA damage sites

PubMed Central

Haas, Kalina T; Lee, MiYoung; Esposito, Alessandro; Venkitaraman, Ashok R

2018-01-01

Abstract RAD51 recombinase assembles on single-stranded (ss)DNA substrates exposed by DNA end-resection to initiate homologous recombination (HR), a process fundamental to genome integrity. RAD51 assembly has been characterized using purified proteins, but its ultrastructural topography in the cell nucleus is unexplored. Here, we combine cell genetics with single-molecule localization microscopy and a palette of bespoke analytical tools, to visualize molecular transactions during RAD51 assembly in the cellular milieu at resolutions approaching 30–40 nm. In several human cell types, RAD51 focalizes in clusters that progressively extend into long filaments, which abut—but do not overlap—with globular bundles of replication protein A (RPA). Extended filaments alter topographically over time, suggestive of succeeding steps in HR. In cells depleted of the tumor suppressor protein BRCA2, or overexpressing its RAD51-binding BRC repeats, RAD51 fails to assemble at damage sites, although RPA accumulates unhindered. By contrast, in cells lacking a BRCA2 carboxyl (C)-terminal region targeted by cancer-causing mutations, damage-induced RAD51 assemblies initiate but do not extend into filaments. We suggest a model wherein RAD51 assembly proceeds concurrently with end-resection at adjacent sites, via an initiation step dependent on the BRC repeats, followed by filament extension through the C-terminal region of BRCA2. PMID:29309696

Controlling the response to DNA damage by the APC/C-Cdh1.

PubMed

de Boer, H Rudolf; Guerrero Llobet, S; van Vugt, Marcel A T M

2016-03-01

Proper cell cycle progression is safeguarded by the oscillating activities of cyclin/cyclin-dependent kinase complexes. An important player in the regulation of mitotic cyclins is the anaphase-promoting complex/cyclosome (APC/C), a multi-subunit E3 ubiquitin ligase. Prior to entry into mitosis, the APC/C remains inactive, which allows the accumulation of mitotic regulators. APC/C activation requires binding to either the Cdc20 or Cdh1 adaptor protein, which sequentially bind the APC/C and facilitate targeting of multiple mitotic regulators for proteasomal destruction, including Securin and Cyclin B, to ensure proper chromosome segregation and mitotic exit. Emerging data have indicated that the APC/C, particularly in association with Cdh1, also functions prior to mitotic entry. Specifically, the APC/C-Cdh1 is activated in response to DNA damage in G2 phase cells. These observations are in line with in vitro and in vivo genetic studies, in which cells lacking Cdh1 expression display various defects, including impaired DNA repair and aberrant cell cycle checkpoints. In this review, we summarize the current literature on APC/C regulation in response to DNA damage, the functions of APC/C-Cdh1 activation upon DNA damage, and speculate how APC/C-Cdh1 can control cell fate in the context of persistent DNA damage.

Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography.

PubMed

Foadi, James; Aller, Pierre; Alguel, Yilmaz; Cameron, Alex; Axford, Danny; Owen, Robin L; Armour, Wes; Waterman, David G; Iwata, So; Evans, Gwyndaf

2013-08-01

The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of <10 µm in size. The increased likelihood of severe radiation damage where microcrystals or particularly sensitive crystals are used forces crystallographers to acquire large numbers of data sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein.

Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography

PubMed Central

Foadi, James; Aller, Pierre; Alguel, Yilmaz; Cameron, Alex; Axford, Danny; Owen, Robin L.; Armour, Wes; Waterman, David G.; Iwata, So; Evans, Gwyndaf

2013-01-01

The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of <10 µm in size. The increased likelihood of severe radiation damage where microcrystals or particularly sensitive crystals are used forces crystallographers to acquire large numbers of data sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein. PMID:23897484

Root Damage under Alkaline Stress Is Associated with Reactive Oxygen Species Accumulation in Rice (Oryza sativa L.)

PubMed Central

Zhang, Hui; Liu, Xiao-Long; Zhang, Rui-Xue; Yuan, Hai-Yan; Wang, Ming-Ming; Yang, Hao-Yu; Ma, Hong-Yuan; Liu, Duo; Jiang, Chang-Jie; Liang, Zheng-Wei

2017-01-01

Alkaline stress (high pH) severely damages root cells, and consequently, inhibits rice (Oryza sativa L.) seedling growth. In this study, we demonstrate the accumulation of reactive oxygen species (ROS) in root cells under alkaline stress. Seedlings of two rice cultivars with different alkaline tolerances, ‘Dongdao-4’ (moderately alkaline-tolerant) and ‘Jiudao-51’ (alkaline-sensitive), were subjected to alkaline stress simulated by 15 mM sodium carbonate (Na2CO3). Alkaline stress greatly reduced seedling survival rate, shoot and root growth, and root vigor. Moreover, severe root cell damage was observed under alkaline stress, as shown by increased membrane injury, malondialdehyde accumulation, and Evan’s Blue staining. The expression of the cell death-related genes OsKOD1, OsHsr203j, OsCP1, and OsNAC4 was consistently upregulated, while that of a cell death-suppressor gene, OsBI1, was downregulated. Analysis of the ROS contents revealed that alkaline stress induced a marked accumulation of superoxide anions (O2•-) and hydrogen peroxide (H2O2) in rice roots. The application of procyanidins (a potent antioxidant) to rice seedlings 24 h prior to alkaline treatment significantly alleviated alkalinity-induced root damage and promoted seedling growth inhibition, which were concomitant with reduced ROS accumulation. These results suggest that root cell damage, and consequently growth inhibition, of rice seedlings under alkaline stress is closely associated with ROS accumulation. The antioxidant activity of superoxide dismutase, catalase, peroxidase, and ascorbate peroxidase increased under alkaline stress in the roots, probably in response to the cellular damage induced by oxidative stress. However, this response mechanism may be overwhelmed by the excess ROS accumulation observed under stress, resulting in oxidative damage to root cells. Our findings provide physiological insights into the molecular mechanisms of alkalinity-induced damage to root cells, and will contribute to the improvement of alkaline stress tolerance in rice plants. PMID:28943882

Root Damage under Alkaline Stress Is Associated with Reactive Oxygen Species Accumulation in Rice (Oryza sativa L.).

PubMed

Zhang, Hui; Liu, Xiao-Long; Zhang, Rui-Xue; Yuan, Hai-Yan; Wang, Ming-Ming; Yang, Hao-Yu; Ma, Hong-Yuan; Liu, Duo; Jiang, Chang-Jie; Liang, Zheng-Wei

2017-01-01

Alkaline stress (high pH) severely damages root cells, and consequently, inhibits rice ( Oryza sativa L.) seedling growth. In this study, we demonstrate the accumulation of reactive oxygen species (ROS) in root cells under alkaline stress. Seedlings of two rice cultivars with different alkaline tolerances, 'Dongdao-4' (moderately alkaline-tolerant) and 'Jiudao-51' (alkaline-sensitive), were subjected to alkaline stress simulated by 15 mM sodium carbonate (Na 2 CO 3 ). Alkaline stress greatly reduced seedling survival rate, shoot and root growth, and root vigor. Moreover, severe root cell damage was observed under alkaline stress, as shown by increased membrane injury, malondialdehyde accumulation, and Evan's Blue staining. The expression of the cell death-related genes OsKOD1 , OsHsr203j , OsCP1 , and OsNAC4 was consistently upregulated, while that of a cell death-suppressor gene, OsBI1 , was downregulated. Analysis of the ROS contents revealed that alkaline stress induced a marked accumulation of superoxide anions ([Formula: see text]) and hydrogen peroxide (H 2 O 2 ) in rice roots. The application of procyanidins (a potent antioxidant) to rice seedlings 24 h prior to alkaline treatment significantly alleviated alkalinity-induced root damage and promoted seedling growth inhibition, which were concomitant with reduced ROS accumulation. These results suggest that root cell damage, and consequently growth inhibition, of rice seedlings under alkaline stress is closely associated with ROS accumulation. The antioxidant activity of superoxide dismutase, catalase, peroxidase, and ascorbate peroxidase increased under alkaline stress in the roots, probably in response to the cellular damage induced by oxidative stress. However, this response mechanism may be overwhelmed by the excess ROS accumulation observed under stress, resulting in oxidative damage to root cells. Our findings provide physiological insights into the molecular mechanisms of alkalinity-induced damage to root cells, and will contribute to the improvement of alkaline stress tolerance in rice plants.

Numerical study of multi-point forming of thick sheet using remeshing procedure

NASA Astrophysics Data System (ADS)

Cherouat, A.; Ma, X.; Borouchaki, H.; Zhang, Q.

2018-05-01

Multi-point forming MPF is an innovative technology of manufacturing complex thick sheet metal products without the need for solid tools. The central component of this system is a pair of the desired discrete matrices of punches, and die surface constructed by changing the positions of the tools though CAD and a control system. Because reconfigurable discrete tools are used, part-manufacturing costs are reduced and manufacturing time is shorten substantially. Firstly, in this work we develop constitutive equations which couples isotropic ductile damage into various flow stress based on the Continuum Damage Mechanic theory. The modified Johnson-Cook flow model fully coupled with an isotropic ductile damage is established using the quasi-unilateral damage evolution for considering both the open and the close of micro-cracks. During the forming processes severe mesh distortion of elements occur after a few incremental forming steps. Secondly, we introduce 3D adaptive remeshing procedure based on linear tetrahedral element and geometrical/physical errors estimation to optimize the element quality, to refine the mesh size in the whole model and to adapt the deformed mesh to the tools geometry. Simulation of the MPF process (see Fig. 1) and the unloading spring-back are carried out using adaptive remeshing scheme using the commercial finite element package ABAQUS and OPTIFORM mesher. Subsequently, influencing factors of MPF spring-back are researched to investigate the MPF spring-back tendency with the proposed remeshing procedure.

Premature aging/senescence in cancer cells facing therapy: good or bad?

PubMed

Gonzalez, Llilians Calvo; Ghadaouia, Sabrina; Martinez, Aurélie; Rodier, Francis

2016-02-01

Normal and cancer cells facing their demise following exposure to radio-chemotherapy can actively participate in choosing their subsequent fate. These programmed cell fate decisions include true cell death (apoptosis-necroptosis) and therapy-induced cellular senescence (TIS), a permanent "proliferative arrest" commonly portrayed as premature cellular aging. Despite a permanent loss of proliferative potential, senescent cells remain viable and are highly bioactive at the microenvironment level, resulting in a prolonged impact on tissue architecture and functions. Cellular senescence is primarily documented as a tumor suppression mechanism that prevents cellular transformation. In the context of normal tissues, cellular senescence also plays important roles in tissue repair, but contributes to age-associated tissue dysfunction when senescent cells accumulate. Theoretically, in multi-step cancer progression models, cancer cells have already bypassed cellular senescence during their immortalization step (see hallmarks of cancer). It is then perhaps surprising to find that cancer cells often retain the ability to undergo TIS, or premature aging. This occurs because cellular senescence results from multiple signalling pathways, some retained in cancer cells, aiming to prevent cell cycle progression in damaged cells. Since senescent cancer cells persist after therapy and secrete an array of cytokines and growth factors that can modulate the tumor microenvironment, these cells may have beneficial and detrimental effects regarding immune modulation and survival of remaining proliferation-competent cancer cells. Similarly, while normal cells undergoing senescence are believed to remain indefinitely growth arrested, whether this is true for senescent cancer cells remains unclear, raising the possibility that these cells may represent a reservoir for cancer recurrence after treatment. This review discusses our current knowledge on cancer cell senescence and highlight questions that must be addressed to fully understand the beneficial and detrimental impacts of cellular senescence during cancer therapy.

Residual strength of GFR/POM as a function of damage

NASA Astrophysics Data System (ADS)

Zachariev, G.; Rudolph, H.-V.; Ivers, H.

2010-07-01

A relation between the residual strength and the dispersed damage accumulated in a short fiber reinforced polyoximethylene (GFR/POM) samples under tension is found. For that purpose dependencies of damage and residual strength on loading percentage are used. Damage as a function of loading percentage is known for the material under study. To find the dependency of residual strength on loading percentage a subsidiary function is introduced and a method is proposed for determination of the parameters in the dependency on the basis of the experimental data. Both damage and residual strength are measured after unloading samples that have been loaded applying different loading percentages. Damage is the accumulation of new internal surfaces that arise under mechanical loading in the whole volume of the material. They are registered by a new original method of X-ray refraction. The analytical relation between the residual strength and damage accumulated is compared to the experimental results found for the residual strength under different damage degrees.

Instantaneous Wavenumber Estimation for Damage Quantification in Layered Plate Structures

NASA Technical Reports Server (NTRS)

Mesnil, Olivier; Leckey, Cara A. C.; Ruzzene, Massimo

2014-01-01

This paper illustrates the application of instantaneous and local wavenumber damage quantification techniques for high frequency guided wave interrogation. The proposed methodologies can be considered as first steps towards a hybrid structural health monitoring/ nondestructive evaluation (SHM/NDE) approach for damage assessment in composites. The challenges and opportunities related to the considered type of interrogation and signal processing are explored through the analysis of numerical data obtained via EFIT simulations of damage in CRFP plates. Realistic damage configurations are modeled from x-ray CT scan data of plates subjected to actual impacts, in order to accurately predict wave-damage interactions in terms of scattering and mode conversions. Simulation data is utilized to enhance the information provided by instantaneous and local wavenumbers and mitigate the complexity related to the multi-modal content of the plate response. Signal processing strategies considered for this purpose include modal decoupling through filtering in the frequency/wavenumber domain, the combination of displacement components, and the exploitation of polarization information for the various modes as evaluated through the dispersion analysis of the considered laminate lay-up sequence. The results presented assess the effectiveness of the proposed wavefield processing techniques as a hybrid SHM/NDE technique for damage detection and quantification in composite, plate-like structures.

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

DOE PAGES

Jin, Ke; Zhang, Yanwen; Bei, Hongbin

2015-09-09

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

Landslide risk analysis: a multi-disciplinary methodological approach

NASA Astrophysics Data System (ADS)

Sterlacchini, S.; Frigerio, S.; Giacomelli, P.; Brambilla, M.

2007-11-01

This study describes an analysis carried out within the European community project "ALARM" (Assessment of Landslide Risk and Mitigation in Mountain Areas, 2004) on landslide risk assessment in the municipality of Corvara in Badia, Italy. This mountainous area, located in the central Dolomites (Italian Alps), poses a significant landslide hazard to several man-made and natural objects. Three parameters for determining risk were analysed as an aid to preparedness and mitigation planning: event occurrence probability, elements at risk, and the vulnerability of these elements. Initially, a landslide hazard scenario was defined; this step was followed by the identification of the potential vulnerable elements, by the estimation of the expected physical effects, due to the occurrence of a damaging phenomenon, and by the analysis of social and economic features of the area. Finally, a potential risk scenario was defined, where the relationships between the event, its physical effects, and its economic consequences were investigated. People and public administrators with training and experience in local landsliding and slope processes were involved in each step of the analysis. A "cause-effect" correlation was applied, derived from the "dose-response" equation initially used in the biological sciences and then adapted by economists for the assessment of environmental risks. The relationship was analysed from a physical point of view and the cause (the natural event) was correlated to the physical effects, i.e. the aesthetic, functional, and structural damage. An economic evaluation of direct and indirect damage was carried out considering the assets in the affected area (i.e., tourist flows, goods, transport and the effect on other social and economic activities). This study shows the importance of indirect damage, which is as significant as direct damage. The total amount of direct damage was estimated in 8 913 000 €; on the contrary, indirect damage ranged considerably from 2 840 000 to 9 350 000 €, depending on the selected temporal scenario and the expected closing time of the potentially affected structures. The multi-disciplinary approach discussed in this study may assist local decision makers in determining the nature and magnitude of the expected losses due to a dangerous event, which can be anticipated in a given study area, during a specified time period. Besides, a preventive knowledge of the prospective physical effects and economic consequences may help local decision makers to choose the best prevention and mitigation options and to decide how to allocate resources properly, so that potential benefits are maximised at an acceptable cost.

Synchronous parallel spatially resolved stochastic cluster dynamics

DOE PAGES

Dunn, Aaron; Dingreville, Rémi; Martínez, Enrique; ...

2016-04-23

In this work, a spatially resolved stochastic cluster dynamics (SRSCD) model for radiation damage accumulation in metals is implemented using a synchronous parallel kinetic Monte Carlo algorithm. The parallel algorithm is shown to significantly increase the size of representative volumes achievable in SRSCD simulations of radiation damage accumulation. Additionally, weak scaling performance of the method is tested in two cases: (1) an idealized case of Frenkel pair diffusion and annihilation, and (2) a characteristic example problem including defect cluster formation and growth in α-Fe. For the latter case, weak scaling is tested using both Frenkel pair and displacement cascade damage.more » To improve scaling of simulations with cascade damage, an explicit cascade implantation scheme is developed for cases in which fast-moving defects are created in displacement cascades. For the first time, simulation of radiation damage accumulation in nanopolycrystals can be achieved with a three dimensional rendition of the microstructure, allowing demonstration of the effect of grain size on defect accumulation in Frenkel pair-irradiated α-Fe.« less

Simulation of Micron-Sized Debris Populations in Low Earth Orbit

NASA Technical Reports Server (NTRS)

Xu, Y.-L.; Hyde, J. L.; Prior, T.; Matney, Mark

2010-01-01

The update of ORDEM2000, the NASA Orbital Debris Engineering Model, to its new version ORDEM2010, is nearly complete. As a part of the ORDEM upgrade, this paper addresses the simulation of micro-debris (greater than 10 m and smaller than 1 mm in size) populations in low Earth orbit. The principal data used in the modeling of the micron-sized debris populations are in-situ hypervelocity impact records, accumulated in post-flight damage surveys on the space-exposed surfaces of returned spacecrafts. The development of the micro-debris model populations follows the general approach to deriving other ORDEM2010-required input populations for various components and types of debris. This paper describes the key elements and major steps in the statistical inference of the ORDEM2010 micro-debris populations. A crucial step is the construction of a degradation/ejecta source model to provide prior information on the micron-sized objects (such as orbital and object-size distributions). Another critical step is to link model populations with data, which is rather involved. It demands detailed information on area-time/directionality for all the space-exposed elements of a shuttle orbiter and damage laws, which relate impact damage with the physical properties of a projectile and impact conditions such as impact angle and velocity. Also needed are model-predicted debris fluxes as a function of object size and impact velocity from all possible directions. In spite of the very limited quantity of the available shuttle impact data, the population-derivation process is satisfactorily stable. Final modeling results obtained from shuttle window and radiator impact data are reasonably convergent and consistent, especially for the debris populations with object-size thresholds at 10 and 100 m.

Simulation of Micron-Sized Debris Populations in Low Earth Orbit

NASA Technical Reports Server (NTRS)

Xu, Y.-L.; Matney, M.; Liou, J.-C.; Hyde, J. L.; Prior, T. G.

2010-01-01

The update of ORDEM2000, the NASA Orbital Debris Engineering Model, to its new version . ORDEM2010, is nearly complete. As a part of the ORDEM upgrade, this paper addresses the simulation of micro-debris (greater than 10 micron and smaller than 1 mm in size) populations in low Earth orbit. The principal data used in the modeling of the micron-sized debris populations are in-situ hypervelocity impact records, accumulated in post-flight damage surveys on the space-exposed surfaces of returned spacecrafts. The development of the micro-debris model populations follows the general approach to deriving other ORDEM2010-required input populations for various components and types of debris. This paper describes the key elements and major steps in the statistical inference of the ORDEM2010 micro-debris populations. A crucial step is the construction of a degradation/ejecta source model to provide prior information on the micron-sized objects (such as orbital and object-size distributions). Another critical step is to link model populations with data, which is rather involved. It demands detailed information on area-time/directionality for all the space-exposed elements of a shuttle orbiter and damage laws, which relate impact damage with the physical properties of a projectile and impact conditions such as impact angle and velocity. Also needed are model-predicted debris fluxes as a function of object size and impact velocity from all possible directions. In spite of the very limited quantity of the available shuttle impact data, the population-derivation process is satisfactorily stable. Final modeling results obtained from shuttle window and radiator impact data are reasonably convergent and consistent, especially for the debris populations with object-size thresholds at 10 and 100 micron.

Potential pharmacological strategies for the improved treatment of organophosphate-induced neurotoxicity.

PubMed

Kaur, Shamsherjit; Singh, Satinderpal; Chahal, Karan Singh; Prakash, Atish

2014-11-01

Organophosphates (OP) are highly toxic compounds that cause cholinergic neuronal excitotoxicity and dysfunction by irreversible inhibition of acetylcholinesterase, resulting in delayed brain damage. This delayed secondary neuronal destruction, which arises primarily in the cholinergic areas of the brain that contain dense accumulations of cholinergic neurons and the majority of cholinergic projection, could be largely responsible for persistent profound neuropsychiatric and neurological impairments such as memory, cognitive, mental, emotional, motor, and sensory deficits in the victims of OP poisoning. The therapeutic strategies for reducing neuronal brain damage must adopt a multifunctional approach to the various steps of brain deterioration: (i) standard treatment with atropine and related anticholinergic compounds; (ii) anti-excitotoxic therapies to prevent cerebral edema, blockage of calcium influx, inhibition of apoptosis, and allow for the control of seizure; (iii) neuroprotection by aid of antioxidants and N-methyl-d-aspartate (NMDA) antagonists (multifunctional drug therapy), to inhibit/limit the secondary neuronal damage; and (iv) therapies targeting chronic neuropsychiatric and neurological symptoms. These neuroprotective strategies may prevent secondary neuronal damage in both early and late stages of OP poisoning, and thus may be a beneficial approach to treating the neuropsychological and neuronal impairments resulting from OP toxicity.

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

MESOSCALE MODELING OF DEFLAGRATION-INDUCED DECONSOLIDATION IN POLYMER-BONDED EXPLOSIVES

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

Springer, H K; Glascoe, E A; Reaugh, J E

Initially undamaged polymer-bonded explosives can transition from conductive burning to more violent convective burning via rapid deconsolidation at higher pressures. The pressure-dependent infiltration of cracks and pores, i.e., damage, by product gases at the burn-front is a key step in the transition to convective burning. However, the relative influence of pre-existing damage and the evolution of deflagration-induced damage during the transition to convective burning is not well understood. The objective of this study is to investigate the role of microstructure and initial pressurization on deconsolidation. We performed simulations using the multi-physics hydrocode, ALE3D. HMX-Viton A served as our model explosive.more » A Prout-Tompkins chemical kinetic model, Vielle's Law pressure-dependent burning, Gruneisen equation-of-state, and simplified strength model were used for the HMX. The propensity for deconsolidation increased with increasing defect size and decreasing initial pressurization, as measured by the increase in burning surface area. These studies are important because they enable the development of continuum-scale damage models and the design of inherently safer explosives.« less

Human Adipose‐Derived Stem Cells Expanded Under Ambient Oxygen Concentration Accumulate Oxidative DNA Lesions and Experience Procarcinogenic DNA Replication Stress

PubMed Central

Renoud, Marie‐Laure; Hoede, Claire; Gonzalez, Ignacio; Jones, Natalie; Longy, Michel; Sensebé, Luc; Cazaux, Christophe

2016-01-01

Abstract Adipose‐derived stem cells (ADSCs) have led to growing interest in cell‐based therapy because they can be easily harvested from an abundant tissue. ADSCs must be expanded in vitro before transplantation. This essential step causes concerns about the safety of adult stem cells in terms of potential transformation. Tumorigenesis is driven in its earliest step by DNA replication stress, which is characterized by the accumulation of stalled DNA replication forks and activation of the DNA damage response. Thus, to evaluate the safety of ADSCs during ex vivo expansion, we monitored DNA replication under atmospheric (21%) or physiologic (1%) oxygen concentration. Here, by combining immunofluorescence and DNA combing, we show that ADSCs cultured under 21% oxygen accumulate endogenous oxidative DNA lesions, which interfere with DNA replication by increasing fork stalling events, thereby leading to incomplete DNA replication and fork collapse. Moreover, we found by RNA sequencing (RNA‐seq) that culture of ADSCs under atmospheric oxygen concentration leads to misexpression of cell cycle and DNA replication genes, which could contribute to DNA replication stress. Finally, analysis of acquired small nucleotide polymorphism shows that expansion of ADSCs under 21% oxygen induces a mutational bias toward deleterious transversions. Overall, our results suggest that expanding ADSCs at a low oxygen concentration could reduce the risk for DNA replication stress‐associated transformation, as occurs in neoplastic tissues. Stem Cells Translational Medicine 2017;6:68–76 PMID:28170194

48 CFR 15.202 - Advisory multi-step process.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Advisory multi-step... Information 15.202 Advisory multi-step process. (a) The agency may publish a presolicitation notice (see 5.204... participate in the acquisition. This process should not be used for multi-step acquisitions where it would...

Atomistic simulation of damage accumulation and amorphization in Ge

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

Gomez-Selles, Jose L., E-mail: joseluis.gomezselles@imdea.org; Martin-Bragado, Ignacio; Claverie, Alain

2015-02-07

Damage accumulation and amorphization mechanisms by means of ion implantation in Ge are studied using Kinetic Monte Carlo and Binary Collision Approximation techniques. Such mechanisms are investigated through different stages of damage accumulation taking place in the implantation process: from point defect generation and cluster formation up to full amorphization of Ge layers. We propose a damage concentration amorphization threshold for Ge of ∼1.3 × 10{sup 22} cm{sup −3} which is independent on the implantation conditions. Recombination energy barriers depending on amorphous pocket sizes are provided. This leads to an explanation of the reported distinct behavior of the damage generated by different ions.more » We have also observed that the dissolution of clusters plays an important role for relatively high temperatures and fluences. The model is able to explain and predict different damage generation regimes, amount of generated damage, and extension of amorphous layers in Ge for different ions and implantation conditions.« less

Cascading processes and interactions in torrent catchments and their influence on the damage pattern

NASA Astrophysics Data System (ADS)

Keiler, Margreth; Gebbers, David

2014-05-01

Research on single geomorphological processes during damaging events has a long history; however, comprehensive documentations and analyses of the events have been conducted not until the late 1980s. Thus, for highly damaging events insights about triggering, the evolution and the impacts of processes during an event and the resulting damage were produced. Though, in the majority of cases the processes were studied in a well-defined procedure of one disciplinary focus. These focused studies neglect mutable influences which may alter the sequence of the process or the event. During damaging events multiple geomorphological processes are active which leads to the assumption that they have a certain impact on each other and the course of damaging effect. Consequently, for a comprehensive hazard and risk analysis all processes of a catchment have to be analysed and evaluated quantitatively and qualitatively (MARZOCCHI, 2007). Although the demand for a sophisticated risk management is increasing, the research on interactions as well as on physical vulnerability to multiple hazards, including the different processes impact effects, is still very limited (KAPPES et al., 2010, 2011). The challenges in this field are the quantity of data needed, and furthermore to conduct this kind of analysis is very complex and complicated (KAPPES et al. 2012). Yet, knowledge about possible interactions and resulting impact effects could significantly contribute to the reduction of risk in a region. The objective of this study is to analyse, i) how geomorphological processes interact with each other and with other factors of the surrounding during a damaging event, ii) what influences those interactions have on the resulting damage of the event and iii) whether or not different events are comparable in terms of those interactions and their impacts. To meet these objectives, 15 damaging torrent events, which occurred between 2000 and 2011 in the Bernese Oberland and the Pennine Alps, Switzerland, were analysed on the basis of event reports and general catchment parameters. The interactions were classified into different categories regarding a process and the interacting counterpart (another process, with structures or disposition) and the temporal and spatial extent in which these interactions occurred. Additionally, positive and negative feedbacks of the processes were considered. First results highlight that some types of interaction can be extracted in several events and that their temporal and spatial extent is comparable. However, the analysis indicates that single interaction exhibits multi-path consequences which are a challenge for general propositions of interactions influencing damage patterns. In the further step of this study, clusters of interactions which could occur in different events in similar ways are analysed in more detail. REFERENCES Kappes, M.S., Papathoma-Köhle, M. & Keiler, M. 2011: Assessing physical vulnerability for multi-hazards using an indicator-based methodology, Applied Geography, 32, 577-590. Kappes, M.S., Keiler, M. & Glade, T. 2010: From single- to multi-hazard risk analyses: a concept addressing emerging challenges. In: Malet, J.-P.; Glade, T. & N. Casagli (eds.) Mountain Risks: bringing science to society. Proceedings of the 'Mountain Risks' International Conference, Firenze, Italy. Strasbourg. CERG Editions: 351-356 Kappes, M. S., Keiler, M., von Eleverfeldt, K., Glade, T. 2012: Challenges of analyzing multi-hazard risk: a review. NAT HAZARDS 64: 1925-1958. Marzocchi, W., Mastellone, M.L., Ruocco, A. 2009: Principles of multi-risk assessment: Interaction amongst natural and man-induced risks. European Commission. Brussels.

Structural damage detection-oriented multi-type sensor placement with multi-objective optimization

NASA Astrophysics Data System (ADS)

Lin, Jian-Fu; Xu, You-Lin; Law, Siu-Seong

2018-05-01

A structural damage detection-oriented multi-type sensor placement method with multi-objective optimization is developed in this study. The multi-type response covariance sensitivity-based damage detection method is first introduced. Two objective functions for optimal sensor placement are then introduced in terms of the response covariance sensitivity and the response independence. The multi-objective optimization problem is formed by using the two objective functions, and the non-dominated sorting genetic algorithm (NSGA)-II is adopted to find the solution for the optimal multi-type sensor placement to achieve the best structural damage detection. The proposed method is finally applied to a nine-bay three-dimensional frame structure. Numerical results show that the optimal multi-type sensor placement determined by the proposed method can avoid redundant sensors and provide satisfactory results for structural damage detection. The restriction on the number of each type of sensors in the optimization can reduce the searching space in the optimization to make the proposed method more effective. Moreover, how to select a most optimal sensor placement from the Pareto solutions via the utility function and the knee point method is demonstrated in the case study.

Characteristics and Concepts of Dynamic Hub Proteins in DNA Processing Machinery from Studies of RPA

PubMed Central

Sugitani, Norie; Chazin, Walter J.

2015-01-01

DNA replication, damage response and repair require the coordinated action of multi-domain proteins operating within dynamic multi-protein machines that act upon the DNA substrate. These modular proteins contain flexible linkers of various lengths, which enable changes in the spatial distribution of the globular domains (architecture) that harbor their essential biochemical functions. This mobile architecture is uniquely suited to follow the evolving substrate landscape present over the course of the specific process performed by the multi-protein machinery. A fundamental advance in understanding of protein machinery is the realization of the pervasive role of dynamics. Not only is the machine undergoing dynamic transformations, but the proteins themselves are flexible and constantly adapting to the progression through the steps of the overall process. Within this dynamic context the activity of the constituent proteins must be coordinated, a role typically played by hub proteins. A number of important characteristics of modular proteins and concepts about the operation of dynamic machinery have been discerned. These provide the underlying basis for the action of the machinery that reads DNA, and responds to and repairs DNA damage. Here, we introduce a number of key characteristics and concepts, including the modularity of the proteins, linkage of weak binding sites, direct competition between sites, and allostery, using the well recognized hub protein replication protein A (RPA). PMID:25542993

DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

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

Marchetti, Francesco; Marchetti, Francesco; Wryobek, Andrew J

The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-inducedmore » heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7- 1 dbf). Analysis of chromosomalaberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.« less

DNA Repair Decline During Mouse Spermiogenesis Results in the Accumulation of Heritable DNA Damage

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

Marchetti, Francesco; Marchetti, Francesco; Wyrobek, Andrew J.

The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-inducedmore » heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7-1 dbf). Analysis of chromosomal aberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.« less

Peripheral vascular damage in systemic lupus erythematosus: data from LUMINA, a large multi-ethnic U.S. cohort (LXIX).

PubMed

Burgos, P I; Vilá, L M; Reveille, J D; Alarcón, G S

2009-12-01

To determine the factors associated with peripheral vascular damage in systemic lupus erythematosus patients and its impact on survival from Lupus in Minorities, Nature versus Nurture, a longitudinal US multi-ethnic cohort. Peripheral vascular damage was defined by the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Factors associated with peripheral vascular damage were examined by univariable and multi-variable logistic regression models and its impact on survival by a Cox multi-variable regression. Thirty-four (5.3%) of 637 patients (90% women, mean [SD] age 36.5 [12.6] [16-87] years) developed peripheral vascular damage. Age and the SDI (without peripheral vascular damage) were statistically significant (odds ratio [OR] = 1.05, 95% confidence interval [CI] 1.01-1.08; P = 0.0107 and OR = 1.30, 95% CI 0.09-1.56; P = 0.0043, respectively) in multi-variable analyses. Azathioprine, warfarin and statins were also statistically significant, and glucocorticoid use was borderline statistically significant (OR = 1.03, 95% CI 0.10-1.06; P = 0.0975). In the survival analysis, peripheral vascular damage was independently associated with a diminished survival (hazard ratio = 2.36; 95% CI 1.07-5.19; P = 0.0334). In short, age was independently associated with peripheral vascular damage, but so was the presence of damage in other organs (ocular, neuropsychiatric, renal, cardiovascular, pulmonary, musculoskeletal and integument) and some medications (probably reflecting more severe disease). Peripheral vascular damage also negatively affected survival.

The theoretical and experimental study of a material structure evolution in gigacyclic fatigue regime

NASA Astrophysics Data System (ADS)

Plekhov, Oleg; Naimark, Oleg; Narykova, Maria; Kadomtsev, Andrey; Betekhtin, Vladimir

2015-10-01

The work is devoted to the study of the metal structure evolution under gigacyclic fatigue (VHCF) regime. The study of the mechanical properties of the samples (Armco iron) with different state of life time existing was carried out on the base of the acoustic resonance method. The damage accumulation (porosity of the samples) was studied by the hydrostatic weighing method. A statistical model of damage accumulation was proposed in order to describe the damage accumulation process. The model describes the influence of the sample surface on the location of fatigue crack initiation.

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.

Evaluating the Magnitude and Duration of Cold Load Pick-up on Residential Distribution Feeders Using Multi-State Load Models

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

Schneider, Kevin P.; Sortomme, Eric; Venkata, S. S.

The increased level of demand that is associated with the restoration of service after an outage, Cold Load Pick-Up (CLPU), can be significantly higher than pre-outage levels, even exceeding the normal distribution feeder peak demand. These high levels of demand can delay restoration efforts and in extreme cases damage equipment. The negative impacts of CLPU can be mitigated with strategies that restore the feeder in sections, minimizing the load current. The challenge for utilities is to manage the current level on critical equipment while minimizing the time to restore service to all customers. Accurately modeling CLPU events is the firstmore » step in developing improved restoration strategies that minimize restoration times. This paper presents a new method for evaluating the magnitude of the CLPU peak, and its duration, using multi-state load models. The use of multi-state load models allows for a more accurate representation of the end-use loads that are present on residential distribution feeders.« less

In vitro investigation of oxide nanoparticle and carbon nanotube toxicity and intracellular accumulation in A549 human pneumocytes.

PubMed

Simon-Deckers, A; Gouget, B; Mayne-L'hermite, M; Herlin-Boime, N; Reynaud, C; Carrière, M

2008-11-20

If released in the environment, nanomaterials might be inhaled by populations and cause damage to the deepest regions of the respiratory tract, i.e., the alveolar compartment. To model this situation, we studied the response of A549 human pneumocytes after exposure to aluminium oxide or titanium oxide nanoparticles, and to multi-walled carbon nanotubes. The influence of size, crystalline structure and chemical composition was investigated. After a detailed identification of nanomaterial physico-chemical characteristics, cells were exposed in vitro and viability and intracellular accumulation were assessed. In our conditions, carbon nanotubes were more toxic than metal oxide nanoparticles. Our results confirmed that both nanotubes and nanoparticles are able to rapidly enter into cells, and distribute in the cytoplasm and intracellular vesicles. Among nanoparticles, we demonstrate significant difference in biological response as a function of size, crystalline phase and chemical composition. Their toxicity was globally lower than nanotubes toxicity. Among nanotubes, the length did not influence cytotoxicity, neither the presence of metal catalyst impurities.

Improving drug accumulation and photothermal efficacy in tumor depending on size of ICG loaded lipid-polymer nanoparticles.

PubMed

Zhao, Pengfei; Zheng, Mingbin; Yue, Caixia; Luo, Zhenyu; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Cai, Lintao

2014-07-01

A key challenge to strengthen anti-tumor efficacy is to improve drug accumulation in tumors through size control. To explore the biodistribution and tumor accumulation of nanoparticles, we developed indocyanine green (ICG) loaded poly (lactic-co-glycolic acid) (PLGA) -lecithin-polyethylene glycol (PEG) core-shell nanoparticles (INPs) with 39 nm, 68 nm and 116 nm via single-step nanoprecipitation. These INPs exhibited good monodispersity, excellent fluorescence and size stability, and enhanced temperature response after laser irradiation. Through cell uptake and photothermal efficiency in vitro, we demonstrated that 39 nm INPs were more easily be absorbed by pancreatic carcinoma tumor cells (BxPC-3) and showed better photothermal damage than that of 68 nm and 116 nm size of INPs. Simultaneously, the fluorescence of INPs offered a real-time imaging monitor for subcellular locating and in vivo metabolic distribution. Near-infrared imaging in vivo and photothermal therapy illustrated that 68 nm INPs showed the strongest efficiency to suppress tumor growth due to abundant accumulation in BxPC-3 xenograft tumor model. The findings revealed that a nontoxic, size-dependent, theranostic INPs model was built for in vivo cancer imaging and photothermal therapy without adverse effect. Copyright © 2014 Elsevier Ltd. All rights reserved.

The application of continuum damage mechanics to solve problems in geodynamics

NASA Astrophysics Data System (ADS)

Manaker, David Martin

Deformation within the Earth's lithosphere is largely controlled by the rheology of the rock. Ductile behavior in rocks is often associated with plasticity due to dislocation motion or diffusion under high pressures and temperatures. However, ductile behavior can also occur in brittle materials. An example would be cataclastic flow associated with folding at shallow crustal levels, steep subduction zones, and large-scale deformation at plate boundaries. Engineers utilize damage mechanics to model the continuum deformation of brittle materials. We utilize a modified form of damage mechanics where damage represents a reduction in frictional strength and includes a yield stress. We use this empirical approach to simulate the bending of the lithosphere. We use numerical simulations to obtain elastostatic solutions for plate bending and where the stress exceeds a yield stress, we apply damage to reduce the elastic moduli. Damage is calculated at each time step by a power-law relationship of the ratio of the yield stress to stress and the yield strain to the strain. To test our method, we apply our damage rheology to a plate deforming under applied shear, a constant bending moment, and a constant load. We simulate a wide range of behaviors from slow relaxation to instantaneous failure, over timescales that span six orders of magnitude. Stress relaxation produces elastic-perfectly plastic behavior in cases where failure does not occur. For cases of failure, we observe a rapid increase in damage leading to failure. The changes in the rate of damage accumulation in failure cases are similar to the changes in b-values of acoustic emissions observed in triaxial compression tests of fractured rock and b-value changes prior to some large earthquakes. Thus continuum damage mechanics can simulate ductile behavior due to brittle mechanisms as well as observations of laboratory experiments and seismicity.

Damage buildup in Ar-ion-irradiated 3 C-SiC at elevated temperatures

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

Wallace, J. B.; Bayu Aji, L. B.; Li, T. T.

Above room temperature, the accumulation of radiation damage in 3 C-SiC is strongly influenced by dynamic defect interaction processes and remains poorly understood. Here, we use a combination of ion channeling and transmission electron microscopy to study lattice disorder in 3 C-SiC irradiated with 500 keV Ar ions in the temperature range of 25–250 °C. Results reveal sigmoidal damage buildup for all the temperatures studied. For 150 °C and below, the damage level monotonically increases with ion dose up to amorphization. Starting at 200 °C, the shape of damage–depth profiles becomes anomalous, with the damage peak narrowing and moving tomore » larger depths and an additional shoulder forming close to the ion end of range. As a result, damage buildup curves for 200 and 250 °C exhibit an anomalous two-step shape, with a damage saturation stage followed by rapid amorphization above a critical ion dose, suggesting a nucleation-limited amorphization behavior. Despite their complexity, all damage buildup curves are well described by a phenomenological model based on an assumption of a linear dependence of the effective amorphization cross section on ion dose. Here, in contrast to the results of previous studies, 3 C-SiC can be amorphized by bombardment with 500 keV Ar ions even at 250 °C with a relatively large dose rate of ~2×10 13 cm -2 s -1, revealing a dominant role of defect interaction dynamics at elevated temperatures.« less

Damage buildup in Ar-ion-irradiated 3 C-SiC at elevated temperatures

DOE PAGES

Wallace, J. B.; Bayu Aji, L. B.; Li, T. T.; ...

2015-09-14

Above room temperature, the accumulation of radiation damage in 3 C-SiC is strongly influenced by dynamic defect interaction processes and remains poorly understood. Here, we use a combination of ion channeling and transmission electron microscopy to study lattice disorder in 3 C-SiC irradiated with 500 keV Ar ions in the temperature range of 25–250 °C. Results reveal sigmoidal damage buildup for all the temperatures studied. For 150 °C and below, the damage level monotonically increases with ion dose up to amorphization. Starting at 200 °C, the shape of damage–depth profiles becomes anomalous, with the damage peak narrowing and moving tomore » larger depths and an additional shoulder forming close to the ion end of range. As a result, damage buildup curves for 200 and 250 °C exhibit an anomalous two-step shape, with a damage saturation stage followed by rapid amorphization above a critical ion dose, suggesting a nucleation-limited amorphization behavior. Despite their complexity, all damage buildup curves are well described by a phenomenological model based on an assumption of a linear dependence of the effective amorphization cross section on ion dose. Here, in contrast to the results of previous studies, 3 C-SiC can be amorphized by bombardment with 500 keV Ar ions even at 250 °C with a relatively large dose rate of ~2×10 13 cm -2 s -1, revealing a dominant role of defect interaction dynamics at elevated temperatures.« less

Effect of n = 3 perturbation field amplitudes below the ELM triggering threshold on edge and SOL transport in NSTX

DOE PAGES

J. M. Canik; Lore, J. D.; Ahn, J. -W.; ...

2013-01-12

Here, the pulsed application of n = 3 magnetic perturbation fields with amplitudes below that which triggers ELMs results in distinct, transient responses observable on several edge and divertor diagnostics in NSTX. We refer to these responses as Sub-Threshold Edge Perturbations (STEPs). An analysis of edge measurements suggests that STEPs result in increased transport in the plasma edge and scrape-off layer, which leads to augmentation of the intrinsic strike point splitting due to error fields, i.e., an intensification of the helical divertor footprint flux pattern. These effects are much smaller in magnitude than those of triggered ELMs, and are observedmore » for the duration of the field perturbation measured internal to the vacuum vessel. In addition, STEPs are correlated with changes to the MHD activity, along with transient reductions in the neutron production rate. Ideally the STEPs could be used to provide density control and prevent impurity accumulation, in the same manner that on-demand ELM triggering is used on NSTX, without the impulsive divertor fluxes and potential for damage to plasma facing components associated with ELMs.« less

Testing and Analysis of Composite Skin/Stringer Debonding Under Multi-Axial Loading

NASA Technical Reports Server (NTRS)

Krueger, Ronald; Cvitkovich, Michael K.; O'Brien, T. Kevin; Minguet, Pierre J.

2000-01-01

A consistent step-wise approach is presented to investigate the damage mechanism in composite bonded skin/stringer constructions under uniaxial and biaxial (in-plane/out-of-plane) loading conditions. The approach uses experiments to detect the failure mechanism, computational stress analysis to determine the location of first matrix cracking and computational fracture mechanics to investigate the potential for delamination growth. In a first step, tests were performed on specimens, which consisted of a tapered composite flange, representing a stringer or frame, bonded onto a composite skin. Tests were performed under monotonic loading conditions in tension, three-point bending, and combined tension/bending to evaluate the debonding mechanisms between the skin and the bonded stringer. For combined tension/bending testing, a unique servohydraulic load frame was used that was capable of applying both in-plane tension and out-of-plane bending loads simultaneously. Specimen edges were examined on the microscope to document the damage occurrence and to identify typical damage patterns. For all three load cases, observed failure initiated in the flange, near the flange tip, causing the flange to almost fully debond from skin. In a second step, a two dimensional plane-strain finite element model was developed to analyze the different test cases using a geometrically nonlinear solution. For all three loading conditions, computed principal stresses exceeded the transverse strength of the material in those areas of the flange where the matrix cracks had developed during the tests. In a third step, delaminations of various lengths were simulated in two locations where delaminations were observed during the tests. The analyses showed that at the loads corresponding to matrix ply crack initiation computed strain energy release rates exceeded the values obtained from a mixed mode failure criterion in one location, Hence. Unstable delamination propagation is likely to occur as observed in the experiments.

Testing and Analysis of Composite Skin/Stringer Debonding under Multi-Axial Loading

NASA Technical Reports Server (NTRS)

Krueger, Ronald; Cvitkovich, Michael; OBrien, Kevin; Minguet, Pierre J.

2000-01-01

A consistent step-wise approach is presented to investigate the damage mechanism in composite bonded skin/stringer constructions under uniaxial and biaxial (in-plane/out-of-plane) loading conditions. The approach uses experiments to detect the failure mechanism, computational stress analysis to determine the location of first matrix cracking and computational fracture mechanics to investigate the potential for delamination growth. In a first step, tests were performed on specimens, which consisted of a tapered composite flange, representing a stringer or frame, bonded onto a composite skin. Tests were performed under monotonic loading conditions in tension, three-point bending, and combined tension/bending to evaluate the debonding mechanisms between the skin and the bonded stringer. For combined tension/bending testing, a unique servohydraulic load frame was used that was capable of applying both in-plane tension and out-of-plane bending loads simultaneously. Specimen edges were examined on the microscope to document the damage occurrence and to identify typical damage patterns. For all three load cases, observed failure initiated in the flange, near the flange tip, causing the flange to almost fully debond from the skin. In a second step, a two-dimensional plane-strain finite element model was developed to analyze the different test cases using a geometrically nonlinear solution. For all three loading conditions, computed principal stresses exceeded the transverse strength of the material in those areas of the flange where the matrix cracks had developed during the tests. In a third step, delaminations of various lengths were simulated in two locations where delaminations were observed during the tests. The analyses showed that at the loads corresponding to matrix ply crack initiation computed strain energy release rates exceeded the values obtained from a mixed mode failure criterion in one location. Hence, unstable delamination propagation is likely to occur as observed in the experiments.

Flexible, multi-measurement guided wave damage detection under varying temperatures

NASA Astrophysics Data System (ADS)

Douglass, Alexander C. S.; Harley, Joel B.

2018-04-01

Temperature compensation in structural health monitoring helps identify damage in a structure by removing data variations due to environmental conditions, such as temperature. Stretch-based methods are one of the most commonly used temperature compensation methods. To account for variations in temperature, stretch-based methods optimally stretch signals in time to optimally match a measurement to a baseline. All of the data is then compared with the single baseline to determine the presence of damage. Yet, for these methods to be effective, the measurement and the baseline must satisfy the inherent assumptions of the temperature compensation method. In many scenarios, these assumptions are wrong, the methods generate error, and damage detection fails. To improve damage detection, a multi-measurement damage detection method is introduced. By using each measurement in the dataset as a baseline, error caused by imperfect temperature compensation is reduced. The multi-measurement method increases the detection effectiveness of our damage metric, or damage indicator, over time and reduces the presence of additional peaks caused by temperature that could be mistaken for damage. By using many baselines, the variance of the damage indicator is reduced and the effects from damage are amplified. Notably, the multi-measurement improves damage detection over single-measurement methods. This is demonstrated through an increase in the maximum of our damage signature from 0.55 to 0.95 (where large values, up to a maximum of one, represent a statistically significant change in the data due to damage).

A multi-step approach for testing non-toxic amphiphilic antifouling coatings against marine microfouling at different levels of biological complexity.

PubMed

Zecher, Karsten; Aitha, Vishwa Prasad; Heuer, Kirsten; Ahlers, Herbert; Roland, Katrin; Fiedel, Michael; Philipp, Bodo

2018-03-01

Marine biofouling on artificial surfaces such as ship hulls or fish farming nets causes enormous economic damage. The time for the developmental process of antifouling coatings can be shortened by reliable laboratory assays. For designing such test systems, it is important that toxic effects can be excluded, that multiple parameters can be addressed simultaneously and that mechanistic aspects can be included. In this study, a multi-step approach for testing antifouling coatings was established employing photoautotrophic biofilm formation of marine microorganisms in micro- and mesoscoms. Degree and pattern of biofilm formation was determined by quantification of chlorophyll fluorescence. For the microcosms, co-cultures of diatoms and a heterotrophic bacterium were exposed to fouling-release coatings. For the mesocosms, a novel device was developed that permits parallel quantification of a multitude of coatings under defined conditions with varying degrees of shear stress. Additionally, the antifouling coatings were tested for leaching of potential compounds and finally tested in sea trials. This multistep-approach revealed that the individual steps led to consistent results regarding antifouling activity of the coatings. Furthermore, the novel mesocosm system can be employed for advanced antifouling analysis including metagenomic approaches for determination of microbial diversity attaching to different coatings under changing shear forces. Copyright © 2018 Elsevier B.V. All rights reserved.

Deformation and reperfusion damages and their accumulation in subcutaneous tissues during loading and unloading: a theoretical modeling of deep tissue injuries.

PubMed

Mak, Arthur F T; Yu, Yanyan; Kwan, Linda P C; Sun, Lei; Tam, Eric W C

2011-11-21

Deep tissue injuries (DTI) involve damages in the subcutaneous tissues under intact skin incurred by prolonged excessive epidermal loadings. This paper presents a new theoretical model for the development of DTI, broadly based on the experimental evidence in the literatures. The model covers the loading damages implicitly inclusive of both the direct mechanical and ischemic injuries, and the additional reperfusion damages and the competing healing processes during the unloading phase. Given the damage accumulated at the end of the loading period, the relative strength of the reperfusion and the healing capacity of the involved tissues system, the model provides a description of the subsequent damage evolution during unloading. The model is used to study parametrically the scenario when reperfusion damage dominates over healing upon unloading and the opposite scenario when the loading and subsequent reperfusion damages remain small relative to the healing capacity of the tissues system. The theoretical model provides an integrated understanding of how tissue damage may further build-up paradoxically even with unloading, how long it would take for the loading and reperfusion damages in the tissues to become fully recovered, and how such loading and reperfusion damages, if not given sufficient time for recovery, may accumulate over multiple loading and unloading cycles, leading to clinical deep tissues ulceration. Copyright © 2011 Elsevier Ltd. All rights reserved.

Managing Occupational Irritant Contact Dermatitis Using a Two-Step Skincare Regimen Designed to Prevent Skin Damage and Support Skin Recovery.

PubMed

von Grote, Erika C; Palaniswarmy, Kiruthi; Meckfessel, Matthew H

2016-12-01

Occupational irritant contact dermatitis (ICD) affecting the hands is a common and difficult-to-manage condition. Occupations that necessitate contact with harsh chemicals, use of alcohol-based disinfectants, and frequent hand washing elevate the risk of ICD. Management strategies that do not adequately prevent accumulated damage and repair skin, can develop into chronic dermatoses which negatively impact work productivity and quality of life. A 2-step skin-care regimen (Excipial Daily Protection Hand Cream (EP) and Excipial Rapid Repair Hand Cream (ER), Galderma Laboratories, L.P.) has been developed as a daily-use management strategy to protect and repair vulnerable hands. The protective barrier cream is formulated with aluminum chlorohydrate and designed for pre-exposure application to enhance the skin's natural protective barrier and minimize excessive moisture while wearing protective gloves. The repair cream, a lipid-rich formulation, is intended for post-exposure application to rehydrate and facilitate the skin's natural healing process. The results of 3 clinical studies highlighted in this review demonstrate how the use of a 2-step skin-care regimen offers a greater protective effect against ICD than the use of barrier cream alone, and also how the formulation of the barrier cream used in these studies helps minimize the occlusion effect caused by gloves and does not interfere with the antibacterial efficacy of an alcohol-based hand sanitizer. This 2-step skin-care regimen is effectively designed to manage and minimize the risk of ICD development in a variety of patients and provides clinicians an additional tool for helping patients manage ICD. J Drugs Dermatol. 2016;15(12):1504-1510.

Cell biological effects of hyperthermia alone or combined with radiation or drugs: a short introduction to newcomers in the field.

PubMed

Kampinga, Harm H

2006-05-01

Hyperthermia results in protein unfolding that, if not properly chaperoned by Heat Shock Proteins (HSP), can lead to irreversible and toxic protein aggregates. Elevating HSP prior to heating makes cells thermotolerant. Hyperthermia also can enhance the sensitivity of cells to radiation and drugs. This sensitization to drugs or radiation is not directly related to altered HSP expression. However, altering HSP expression before heat and radiation or drug treatment will affect the extent of thermal sensitization because the HSP will attenuate the heat-induced protein damage that is responsible for radiation- or drug-sensitization. For thermal radiosensitization, nuclear protein damage is considered to be responsible for hyperthermic effects on DNA repair, in particular base excision repair. Hyperthermic drug sensitization can be seen for a number of anti-cancer drugs, especially of alkylating agents. Synergy between heat and drugs may arise from multiple events such as heat damage to ABC transporters (drug accumulation), intra-cellular drug detoxification pathways and repair of drug-induced DNA adducts. This may be why cells with acquired drug resistance (often multi-factorial) can be made responsive to drugs again by combining the drug treatment with heat.

Hormesis does not make sense except in the light of TOR-driven aging

PubMed Central

Blagosklonny, Mikhail V.

2011-01-01

Weak stresses (including weak oxidative stress, cytostatic agents, heat shock, hypoxia, calorie restriction) may extend lifespan. Known as hormesis, this is the most controversial notion in gerontology. For one, it is believed that aging is caused by accumulation of molecular damage. If so, hormetic stresses (by causing damage) must shorten lifespan. To solve the paradox, it was suggested that, by activating repair, hormetic stresses eventually decrease damage. Similarly, Baron Munchausen escaped from a swamp by pulling himself up by his own hair. Instead, I discuss that aging is not caused by accumulation of molecular damage. Although molecular damage accumulates, organisms do not live long enough to age from this accumulation. Instead, aging is driven by overactivated signal-transduction pathways including the TOR (Target of Rapamycin) pathway. A diverse group of hormetic conditions can be divided into two groups. “Hormesis A” inhibits the TOR pathway. “Hormesis B” increases aging-tolerance, defined as the ability to survive catastrophic complications of aging. Hormesis A includes calorie restriction, resveratrol, rapamycin, p53-inducing agents and, in part, physical exercise, heat shock and hypoxia. Hormesis B includes ischemic preconditioning and, in part, physical exercise, heat shock, hypoxia and medical interventions. PMID:22166724

Demonstration of improvement in the signal-to-noise ratio of Thomson scattering signal obtained by using a multi-pass optical cavity on the Tokyo Spherical Tokamak-2

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

Togashi, H., E-mail: togashi@fusion.k.u-tokyo.ac.jp; Ejiri, A.; Nakamura, K.

2014-11-15

The multi-pass Thomson scattering (TS) scheme enables obtaining many photons by accumulating multiple TS signals. The signal-to-noise ratio (SNR) depends on the accumulation number. In this study, we performed multi-pass TS measurements for ohmically heated plasmas, and the relationship between SNR and the accumulation number was investigated. As a result, improvement of SNR in this experiment indicated similar tendency to that calculated for the background noise dominant situation.

Impact of genomic damage and ageing on stem cell function

PubMed Central

Behrens, Axel; van Deursen, Jan M.; Rudolph, K. Lenhard; Schumacher, Björn

2014-01-01

Impairment of stem cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem cells and cells that comprise the stem cell microenvironment are partly responsible for stem cell dysfunction with ageing. Here, we review the impact of the various types of DNA damage that accumulate with ageing on stem cell functionality, as well as the development of cancer. We discuss DNA-damage-induced cell intrinsic and extrinsic alterations that influence these processes, and review recent advances in understanding systemic adjustments to DNA damage and how they affect stem cells. PMID:24576896

A multi-damages identification method for cantilever beam based on mode shape curvatures and Kriging surrogate model

NASA Astrophysics Data System (ADS)

Xie, Fengle; Jiang, Zhansi; Jiang, Hui

2018-05-01

This paper presents a multi-damages identification method for Cantilever Beam. First, the damage location is identified by using the mode shape curvatures. Second, samples of varying damage severities at the damage location and their corresponding natural frequencies are used to construct the initial Kriging surrogate model. Then a particle swarm optimization (PSO) algorithm is employed to identify the damage severities based on Kriging surrogate model. The simulation study of a double-damaged cantilever beam demonstrated that the proposed method is effective.

Nuclear accumulation and activation of p53 in embryonic stem cells after DNA damage.

PubMed

Solozobova, Valeriya; Rolletschek, Alexandra; Blattner, Christine

2009-06-17

P53 is a key tumor suppressor protein. In response to DNA damage, p53 accumulates to high levels in differentiated cells and activates target genes that initiate cell cycle arrest and apoptosis. Since stem cells provide the proliferative cell pool within organisms, an efficient DNA damage response is crucial. In proliferating embryonic stem cells, p53 is localized predominantly in the cytoplasm. DNA damage-induced nuclear accumulation of p53 in embryonic stem cells activates transcription of the target genes mdm2, p21, puma and noxa. We observed bi-phasic kinetics for nuclear accumulation of p53 after ionizing radiation. During the first wave of nuclear accumulation, p53 levels were increased and the p53 target genes mdm2, p21 and puma were transcribed. Transcription of noxa correlated with the second wave of nuclear accumulation. Transcriptional activation of p53 target genes resulted in an increased amount of proteins with the exception of p21. While p21 transcripts were efficiently translated in 3T3 cells, we failed to see an increase in p21 protein levels after IR in embryonal stem cells. In embryonic stem cells where (anti-proliferative) p53 activity is not necessary, or even unfavorable, p53 is retained in the cytoplasm and prevented from activating its target genes. However, if its activity is beneficial or required, p53 is allowed to accumulate in the nucleus and activates its target genes, even in embryonic stem cells.

OBJECT KINETIC MONTE CARLO SIMULATIONS OF RADIATION DAMAGE ACCUMULATION IN TUNGSTEN

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

Nandipati, Giridhar; Setyawan, Wahyu; Roche, Kenneth J.

2016-09-01

The objective of this work is to understand the accumulation of radiation damage created by primary knock-on atoms (PKAs) of various energies, at 300 K and for a dose rate of 10-4 dpa/s in bulk tungsten using the object kinetic Monte Carlo (OKMC) method.

Continuous Estimates of Surface Density and Annual Snow Accumulation with Multi-Channel Snow/Firn Penetrating Radar in the Percolation Zone, Western Greenland Ice Sheet

NASA Astrophysics Data System (ADS)

Meehan, T.; Marshall, H. P.; Bradford, J.; Hawley, R. L.; Osterberg, E. C.; McCarthy, F.; Lewis, G.; Graeter, K.

2017-12-01

A priority of ice sheet surface mass balance (SMB) prediction is ascertaining the surface density and annual snow accumulation. These forcing data can be supplied into firn compaction models and used to tune Regional Climate Models (RCM). RCMs do not accurately capture subtle changes in the snow accumulation gradient. Additionally, leading RCMs disagree among each other and with accumulation studies in regions of the Greenland Ice Sheet (GrIS) over large distances and temporal scales. RCMs tend to yield inconsistencies over GrIS because of sparse and outdated validation data in the reanalysis pool. Greenland Traverse for Accumulation and Climate Studies (GreenTrACS) implemented multi-channel 500 MHz Radar in multi-offset configuration throughout two traverse campaigns totaling greater than 3500 km along the western percolation zone of GrIS. The multi-channel radar has the capability of continuously estimating snow depth, average density, and annual snow accumulation, expressed at 95% confidence (+-) 0.15 m, (+-) 17 kgm-3, (+-) 0.04 m w.e. respectively, by examination of the primary reflection return from the previous year's summer surface.

Normalized spectral damage of a linear system over different spectral loading patterns

NASA Astrophysics Data System (ADS)

Kim, Chan-Jung

2017-08-01

Spectral fatigue damage is affected by different loading patterns; the damage may be accumulated in a different manner because the spectral pattern has an influence on stresses or strains. The normalization of spectral damage with respect to spectral loading acceleration is a novel solution to compare the accumulated fatigue damage over different spectral loading patterns. To evaluate the sensitivity of fatigue damage over different spectral loading cases, a simple notched specimen is used to conduct a uniaxial vibration test for two representative spectral patterns-random and harmonic-between 30 and 3000 Hz. The fatigue damage to the simple specimen is analyzed for different spectral loading cases using the normalized spectral damage from the measured response data for both acceleration and strain. The influence of spectral loading patterns is discussed based on these analyses.

Local structural change in zircon following radiation damage accumulation. Observation by 29Si nuclear magnetic resonance

NASA Astrophysics Data System (ADS)

Farnan, I.; Trachenko, K.

2003-04-01

29Si nuclear magnetic resonance (NMR) is a one of the most useful probes of the local structure of silicates. One of the results of recent studies of naturally radiation damaged zircons is that there is an evolution of the local structure in both crystalline and amorphous fractions of partially metamict zircon as a function of accumulated α-dose. We have examined the evolution of this local structure within the framework of several models of damage accumulation. The total number of displaced atoms produced per α-decay as function of accumulated dose, as measured by NMR, is not consistent with the idea of multiple overlap events being responsible for the evolution of the total damaged fraction. However, increased connectivity in the damaged region as the number of α-events increases is correlated to the degree of cascade overlap. The results of large scale atomistic (MD) simulations of heavy nuclei recoils at realistic energies (70keV) are consistent with the NMR quantification and also with TEM estimates of the diameters of damaged regions. The local heterogeneity (density and bonding) in the damaged area in the simulations is consistent with the existence of connected silicate tetrahedra. Detailed experiments on the annealing of damaged zircons at 500 and 600^oC have been performed. These show that a significant energetic barrier to the recrystallisation exists at these temperatures once a small fraction of damaged material has been recrystallised. This correlates well with the degree of cascade overlap. Indicating that the more connected SiO_4 tetrahedra present this barrier. A sample with very little cascade overlap can be annealed to ˜97% crystallinity at these temperatures.

Acute Doxorubicin Insult in the Mouse Ovary Is Cell- and Follicle-Type Dependent

PubMed Central

Roti Roti, Elon C.; Leisman, Scott K.; Abbott, David H.; Salih, Sana M.

2012-01-01

Primary ovarian insufficiency (POI) is one of the many unintended consequences of chemotherapy faced by the growing number of female cancer survivors. While ovarian repercussions of chemotherapy have long been recognized, the acute insult phase and primary sites of damage are not well-studied, hampering efforts to design effective intervention therapies to protect the ovary. Utilizing doxorubicin (DXR) as a model chemotherapy agent, we defined the acute timeline for drug accumulation, induced DNA damage, and subsequent cellular and follicular demise in the mouse ovary. DXR accumulated first in the core ovarian stroma cells, then redistributed outwards into the cortex and follicles in a time-dependent manner, without further increase in total ovarian drug levels after four hours post-injection. Consistent with early drug accumulation and intimate interactions with the blood supply, stroma cell-enriched populations exhibited an earlier DNA damage response (measurable at 2 hours) than granulosa cells (measurable at 4 hours), as quantified by the comet assay. Granulosa cell-enriched populations were more sensitive however, responding with greater levels of DNA damage. The oocyte DNA damage response was delayed, and not measurable above background until 10–12 hours post-DXR injection. By 8 hours post-DXR injection and prior to the oocyte DNA damage response, the number of primary, secondary, and antral follicles exhibiting TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive granulosa cells plateaued, indicating late-stage apoptosis and suggesting damage to the oocytes is subsequent to somatic cell failure. Primordial follicles accumulate significant DXR by 4 hours post-injection, but do not exhibit TUNEL-positive granulosa cells until 48 hours post-injection, indicating delayed demise. Taken together, the data suggest effective intervention therapies designed to protect the ovary from chemotherapy accumulation and induced insult in the ovary must act almost immediately to prevent acute insult as significant damage was seen in stroma cells within the first two hours. PMID:22876313

High level expression of chorismate pyruvate-lyase (UbiC) and HMG-CoA reductase in hairy root cultures of Lithospermum erythrorhizon.

PubMed

Köhle, Annegret; Sommer, Susanne; Yazaki, Kazufumi; Ferrer, Albert; Boronat, Albert; Li, Shu-Ming; Heide, Lutz

2002-08-01

Shikonin, a red naphthoquinone pigment, is produced by cell cultures of Lithospermum erythrorhizon (Boraginaceae). It is biosynthetically derived from two key precursors, 4-hydroxybenzoate (4HB) and geranyldiphosphate (GPP). The bacterial ubiC gene, encoding chorismate pyruvate-lyase (CPL) which converts chorismate to 4-hydroxybenzoate, was expressed in L. erythrorhizon under the control of the strong (ocs)(3)mas-promoter. This introduced an efficient biosynthetic pathway to 4HB, i.e. a one-step reaction from chorismate, in addition to the endogeneous multi-step phenylpropanoid pathway. Feeding experiments with [1,7-(13)C(2)]shikimic acid showed that in the most active transgenic line, 73% of 4HB was synthesized via the genetically introduced pathway. However, there was no correlation between CPL activity and 4HB glucoside or shikonin accumulation in the transgenic lines. HMG-CoA reductase (HMGR) is involved in the biosynthesis of GPP in L. erythrorhizon. Two forms of HMGR1 of Arabidopsis thaliana were expressed in Lithospermum under control of the (ocs)(3)mas promoter. Only moderate increases in enzyme activity were obtained with the complete enzyme, but high activity was achieved using the soluble cytosolic domain of HMGR1. Shikonin accumulation remained unchanged even upon high expression of soluble HMGR.

Electronic-carrier-controlled photochemical etching process in semiconductor device fabrication

DOEpatents

Ashby, C.I.H.; Myers, D.R.; Vook, F.L.

1988-06-16

An electronic-carrier-controlled photochemical etching process for carrying out patterning and selective removing of material in semiconductor device fabrication includes the steps of selective ion implanting, photochemical dry etching, and thermal annealing, in that order. In the selective ion implanting step, regions of the semiconductor material in a desired pattern are damaged and the remainder of the regions of the material not implanted are left undamaged. The rate of recombination of electrons and holes is increased in the damaged regions of the pattern compared to undamaged regions. In the photochemical dry etching step which follows ion implanting step, the material in the undamaged regions of the semiconductor are removed substantially faster than in the damaged regions representing the pattern, leaving the ion-implanted, damaged regions as raised surface structures on the semiconductor material. After completion of photochemical dry etching step, the thermal annealing step is used to restore the electrical conductivity of the damaged regions of the semiconductor material.

Electronic-carrier-controlled photochemical etching process in semiconductor device fabrication

DOEpatents

Ashby, Carol I. H.; Myers, David R.; Vook, Frederick L.

1989-01-01

An electronic-carrier-controlled photochemical etching process for carrying out patterning and selective removing of material in semiconductor device fabrication includes the steps of selective ion implanting, photochemical dry etching, and thermal annealing, in that order. In the selective ion implanting step, regions of the semiconductor material in a desired pattern are damaged and the remainder of the regions of the material not implanted are left undamaged. The rate of recombination of electrons and holes is increased in the damaged regions of the pattern compared to undamaged regions. In the photochemical dry etching step which follows ion implanting step, the material in the undamaged regions of the semiconductor are removed substantially faster than in the damaged regions representing the pattern, leaving the ion-implanted, damaged regions as raised surface structures on the semiconductor material. After completion of photochemical dry etching step, the thermal annealing step is used to restore the electrical conductivity of the damaged regions of the semiconductor material.

DNA Damage, DNA Repair, Aging, and Neurodegeneration

PubMed Central

Maynard, Scott; Fang, Evandro Fei; Scheibye-Knudsen, Morten; Croteau, Deborah L.; Bohr, Vilhelm A.

2015-01-01

Aging in mammals is accompanied by a progressive atrophy of tissues and organs, and stochastic damage accumulation to the macromolecules DNA, RNA, proteins, and lipids. The sequence of the human genome represents our genetic blueprint, and accumulating evidence suggests that loss of genomic maintenance may causally contribute to aging. Distinct evidence for a role of imperfect DNA repair in aging is that several premature aging syndromes have underlying genetic DNA repair defects. Accumulation of DNA damage may be particularly prevalent in the central nervous system owing to the low DNA repair capacity in postmitotic brain tissue. It is generally believed that the cumulative effects of the deleterious changes that occur in aging, mostly after the reproductive phase, contribute to species-specific rates of aging. In addition to nuclear DNA damage contributions to aging, there is also abundant evidence for a causative link between mitochondrial DNA damage and the major phenotypes associated with aging. Understanding the mechanistic basis for the association of DNA damage and DNA repair with aging and age-related diseases, such as neurodegeneration, would give insight into contravening age-related diseases and promoting a healthy life span. PMID:26385091

Effects of Amplitude Variations on Deformation and Damage Evolution in SnAgCu Solder in Isothermal Cycling

NASA Astrophysics Data System (ADS)

Wentlent, Luke; Alghoul, Thaer M.; Greene, Christopher M.; Borgesen, Peter

2018-02-01

Although apparently simpler than in thermal cycling, the behavior of SnAgCu (SAC) solder joints in cyclic bending or vibration is not currently well understood. The rate of damage has been shown to scale with the inelastic work per cycle, and excursions to higher amplitudes lead to an apparent softening, some of which remains so that damage accumulation is faster in subsequent cycling at lower amplitudes. This frequently leads to a dramatic breakdown of current damage accumulation rules. An empirical damage accumulation rule has been proposed to account for this, but any applicability to the extrapolation of accelerated test results to life under realistic long-term service conditions remains to be validated. This will require a better understanding of the underlying mechanisms. The present work provides experimental evidence to support recent suggestions that the observed behavior is a result of cycling-induced dislocation structures providing for increased diffusion creep. It is argued that this means that the measured work is an indicator of the instantaneous dislocation density, rather than necessarily reflecting the actual work involved in the creation of the damage.

Dose-rate-dependent damage of cerium dioxide in the scanning transmission electron microscope.

PubMed

Johnston-Peck, Aaron C; DuChene, Joseph S; Roberts, Alan D; Wei, Wei David; Herzing, Andrew A

2016-11-01

Beam damage caused by energetic electrons in the transmission electron microscope is a fundamental constraint limiting the collection of artifact-free information. Through understanding the influence of the electron beam, experimental routines may be adjusted to improve the data collection process. Investigations of CeO 2 indicate that there is not a critical dose required for the accumulation of electron beam damage. Instead, measurements using annular dark field scanning transmission electron microscopy and electron energy loss spectroscopy demonstrate that the onset of measurable damage occurs when a critical dose rate is exceeded. The mechanism behind this phenomenon is that oxygen vacancies created by exposure to a 300keV electron beam are actively annihilated as the sample re-oxidizes in the microscope environment. As a result, only when the rate of vacancy creation exceeds the recovery rate will beam damage begin to accumulate. This observation suggests that dose-intensive experiments can be accomplished without disrupting the native structure of the sample when executed using dose rates below the appropriate threshold. Furthermore, the presence of an encapsulating carbonaceous layer inhibits processes that cause beam damage, markedly increasing the dose rate threshold for the accumulation of damage. Published by Elsevier B.V.

Dose-rate-dependent damage of cerium dioxide in the scanning transmission electron microscope

PubMed Central

Johnston-Peck, Aaron C.; DuChene, Joseph S.; Roberts, Alan D.; Wei, Wei David; Herzing, Andrew A.

2016-01-01

Beam damage caused by energetic electrons in the transmission electron microscope is a fundamental constraint limiting the collection of artifact-free information. Through understanding the influence of the electron beam, experimental routines may be adjusted to improve the data collection process. Investigations of CeO2 indicate that there is not a critical dose required for the accumulation of electron beam damage. Instead, measurements using annular dark field scanning transmission electron microscopy and electron energy loss spectroscopy demonstrate that the onset of measurable damage occurs when a critical dose rate is exceeded. The mechanism behind this phenomenon is that oxygen vacancies created by exposure to a 300 keV electron beam are actively annihilated as the sample re-oxidizes in the microscope environment. As a result, only when the rate of vacancy creation exceeds the recovery rate will beam damage begin to accumulate. This observation suggests that dose-intensive experiments can be accomplished without disrupting the native structure of the sample when executed using dose rates below the appropriate threshold. Furthermore, the presence of an encapsulating carbonaceous layer inhibits processes that cause beam damage, markedly increasing the dose rate threshold for the accumulation of damage. PMID:27469265

Investigation on the use of artificial neural networks to overcome the effects of environmental and operational changes on guided waves monitoring

NASA Astrophysics Data System (ADS)

El Mountassir, M.; Yaacoubi, S.; Dahmene, F.

2015-07-01

Intelligent feature extraction and advanced signal processing techniques are necessary for a better interpretation of ultrasonic guided waves signals either in structural health monitoring (SHM) or in nondestructive testing (NDT). Such signals are characterized by at least multi-modal and dispersive components. In addition, in SHM, these signals are closely vulnerable to environmental and operational conditions (EOCs), and can be severely affected. In this paper we investigate the use of Artificial Neural Network (ANN) to overcome these effects and to provide a reliable damage detection method with a minimal of false indications. An experimental case of study (full scale pipe) is presented. Damages sizes have been increased and their shapes modified in different steps. Various parameters such as the number of inputs and the number of hidden neurons were studied to find the optimal configuration of the neural network.

Delayed damage accumulation by athermal suppression of defect production in concentrated solid solution alloys

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

Velişa, G.; Wendler, E.; Zhao, S.

A combined experimental and computational evaluation of damage accumulation in ion-irradiated Ni, NiFe, and NiFeCoCr is presented. Furthermore, a suppressed damage accumulation, at early stages (low-fluence irradiation), is revealed in NiFeCoCr, with a linear dependence as a function of ion fluence, in sharp contrast with Ni and NiFe. This effect, observed at 16 K, is attributed to the complex energy landscape in these alloys that limits defect mobility and therefore enhances defect interaction and recombination. Our results, together with previous room-temperature and high-temperature investigations, suggest "self-healing" as an intrinsic property of complex alloys that is not a thermally activated process.

Delayed damage accumulation by athermal suppression of defect production in concentrated solid solution alloys

DOE PAGES

Velişa, G.; Wendler, E.; Zhao, S.; ...

2017-12-17

A combined experimental and computational evaluation of damage accumulation in ion-irradiated Ni, NiFe, and NiFeCoCr is presented. Furthermore, a suppressed damage accumulation, at early stages (low-fluence irradiation), is revealed in NiFeCoCr, with a linear dependence as a function of ion fluence, in sharp contrast with Ni and NiFe. This effect, observed at 16 K, is attributed to the complex energy landscape in these alloys that limits defect mobility and therefore enhances defect interaction and recombination. Our results, together with previous room-temperature and high-temperature investigations, suggest "self-healing" as an intrinsic property of complex alloys that is not a thermally activated process.

Damage accumulation of bovine bone under variable amplitude loads.

PubMed

Campbell, Abbey M; Cler, Michelle L; Skurla, Carolyn P; Kuehl, Joseph J

2016-12-01

Stress fractures, a painful injury, are caused by excessive fatigue in bone. This study on damage accumulation in bone sought to determine if the Palmgren-Miner rule (PMR), a well-known linear damage accumulation hypothesis, is predictive of fatigue failure in bone. An electromagnetic shaker apparatus was constructed to conduct cyclic and variable amplitude tests on bovine bone specimens. Three distinct damage regimes were observed following fracture. Fractures due to a low cyclic amplitude loading appeared ductile ( 4000 μ ϵ ), brittle due to high cyclic amplitude loading (> 9000 μ ϵ ), and a combination of ductile and brittle from mid-range cyclic amplitude loading (6500 -6750 μ ϵ ). Brittle and ductile fracture mechanisms were isolated and mixed, in a controlled way, into variable amplitude loading tests. PMR predictions of cycles to failure consistently over-predicted fatigue life when mixing isolated fracture mechanisms. However, PMR was not proven ineffective when used with a single damage mechanism.

Rubisco Accumulation Factor 1 from Thermosynechococcus elongatus participates in the final stages of ribulose-1,5-bisphosphate carboxylase/oxygenase assembly in Escherichia coli cells and in vitro.

PubMed

Kolesinski, Piotr; Belusiak, Iwona; Czarnocki-Cieciura, Mariusz; Szczepaniak, Andrzej

2014-09-01

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) biosynthesis is a multi-step process in which specific chaperones are involved. Recently, a novel polypeptide, Rubisco Accumulation Factor 1 (RAF1), has been identified as a protein that is necessary for proper assembly of this enzyme in maize cells (Zea mays). However, neither its specific function nor its mode of action have as yet been determined. The results presented here show that the prokaryotic homolog of RAF1 from Thermosynechococcus elongatus is expressed in cyanobacterial cells and interacts with a large Rubisco subunit (RbcL). Using a heterologous expression system, it was demonstrated that this protein promotes Rubisco assembly in Escherichia coli cells. Moreover, when co-expressed with RbcL alone, a stable RbcL-RAF1 complex is formed. Molecular mass determination for this Rubisco assembly intermediate by size-exclusion chromatography coupled with multi-angle light scattering indicates that it consists of an RbcL dimer and two RAF1 molecules. A purified RbcL-RAF1 complex dissociated upon addition of a small Rubisco subunit (RbcS), leading to formation of the active holoenzyme. Moreover, titration of the octameric (RbcL8) core of Rubisco with RAF1 results in disassembly of such a stucture and creation of an RbcL-RAF1 intermediate. The results presented here are the first attempt to elucidate the role of cyanobacterial Rubisco Accumulation Factor 1 in the Rubisco biosynthesis process. © 2014 FEBS.

Daily physical activity patterns of children living in an American Indian community.

PubMed

Brusseau, Timothy A; Kulinna, Pamela H; Tudor-Locke, Catrine; Ferry, Matthew

2013-01-01

Embracing a physically active lifestyle is especially important for American Indian (AI) children who are at a greater risk for hypokinetic diseases, particularly Type 2 diabetes. The purpose of this study was to describe AI children's pedometer-determined physical activity (PA) segmented into prominent daily activity patterns. Participants included 5th- and 6th-grade children (N = 77) attending school from 1 Southwestern US AI community. Children wore a pedometer (Yamax Digiwalker SW-200) for 7 consecutive days. Boys accumulated 12,621 (± 5385) steps/weekday and girls accumulated 11,640 (± 3695) steps/weekday of which 38% (4,779 ± 1271) and 35% (4,027 ± 1285) were accumulated at school for boys and girls, respectively. Physical education (PE) provided the single largest source of PA during school for both boys (25% or 3117 steps/day) and girls (23% or 2638 steps/day). Lunchtime recess provided 1612 (13%) and 1241 (11%) steps/day for boys and girls, respectively. Children were significantly less active on weekend days, accumulating 8066 ± 1959 (boys) and 6676 ± 1884 (girls). Although children accumulate a majority of their steps outside of school, this study highlights the important contribution of PE to the overall PA accumulation of children living in AI communities. Further, PA programming during the weekend appears to be important for this population.

Gear Damage Detection Using Oil Debris Analysis

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.

2001-01-01

The purpose of this paper was to verify, when using an oil debris sensor, that accumulated mass predicts gear pitting damage and to identify a method to set threshold limits for damaged gears. Oil debris data was collected from 8 experiments with no damage and 8 with pitting damage in the NASA Glenn Spur Gear Fatigue Rig. Oil debris feature analysis was performed on this data. Video images of damage progression were also collected from 6 of the experiments with pitting damage. During each test, data from an oil debris sensor was monitored and recorded for the occurrence of pitting damage. The data measured from the oil debris sensor during experiments with damage and with no damage was used to identify membership functions to build a simple fuzzy logic model. Using fuzzy logic techniques and the oil debris data, threshold limits were defined that discriminate between stages of pitting wear. Results indicate accumulated mass combined with fuzzy logic analysis techniques is a good predictor of pitting damage on spur gears.

Multi-frequency local wavenumber analysis and ply correlation of delamination damage.

PubMed

Juarez, Peter D; Leckey, Cara A C

2015-09-01

Wavenumber domain analysis through use of scanning laser Doppler vibrometry has been shown to be effective for non-contact inspection of damage in composites. Qualitative and semi-quantitative local wavenumber analysis of realistic delamination damage and quantitative analysis of idealized damage scenarios (Teflon inserts) have been performed previously in the literature. This paper presents a new methodology based on multi-frequency local wavenumber analysis for quantitative assessment of multi-ply delamination damage in carbon fiber reinforced polymer (CFRP) composite specimens. The methodology is presented and applied to a real world damage scenario (impact damage in an aerospace CFRP composite). The methodology yields delamination size and also correlates local wavenumber results from multiple excitation frequencies to theoretical dispersion curves in order to robustly determine the delamination ply depth. Results from the wavenumber based technique are validated against a traditional nondestructive evaluation method. Published by Elsevier B.V.

Splenic red pulp macrophages are intrinsically superparamagnetic and contaminate magnetic cell isolates.

PubMed

Franken, Lars; Klein, Marika; Spasova, Marina; Elsukova, Anna; Wiedwald, Ulf; Welz, Meike; Knolle, Percy; Farle, Michael; Limmer, Andreas; Kurts, Christian

2015-08-11

A main function of splenic red pulp macrophages is the degradation of damaged or aged erythrocytes. Here we show that these macrophages accumulate ferrimagnetic iron oxides that render them intrinsically superparamagnetic. Consequently, these cells routinely contaminate splenic cell isolates obtained with the use of MCS, a technique that has been widely used in immunological research for decades. These contaminations can profoundly alter experimental results. In mice deficient for the transcription factor SpiC, which lack red pulp macrophages, liver Kupffer cells take over the task of erythrocyte degradation and become superparamagnetic. We describe a simple additional magnetic separation step that avoids this problem and substantially improves purity of magnetic cell isolates from the spleen.

Adaptations of quaking aspen for defense against damage by herbivores and related environmental agents

Treesearch

Richard L. Lindroth

2001-01-01

Quaking aspen (Populus tremuloides) employs two major systems of defense against damage by environmental agents: chemical defense and tolerance. Aspen accumulates appreciable quantities of phenolic glycosides (salicylates) and condensed tannins in most tissues and accumulates coniferyl benzoate in flower buds. Phenolic glycosides are toxic and/or deterrent to pathogens...

Damage accumulation in ion-irradiated Ni-based concentrated solid-solution alloys

DOE PAGES

Ullah, Mohammad W.; Aidhy, Dilpuneet S.; Zhang, Yanwen; ...

2016-03-05

We investigate Irradiation-induced damage accumulation in Ni 0.8Fe 0.2 and Ni 0.8Cr 0.2 alloys by using molecular dynamics simulations to assess possible enhanced radiation-resistance in these face-centered cubic (fcc), single-phase, concentrated solid-solution alloys, as compared with pure fcc Ni.

Multilevel modeling of damage accumulation processes in metals

NASA Astrophysics Data System (ADS)

Kurmoiartseva, K. A.; Trusov, P. V.; Kotelnikova, N. V.

2017-12-01

To predict the behavior of components and constructions it is necessary to develop the methods and mathematical models which take into account the self-organization of microstructural processes and the strain localization. The damage accumulation processes and the evolution of material properties during deformation are important to take into account. The heterogeneity of the process of damage accumulation is due to the appropriate physical mechanisms at the scale levels, which are lower than the macro-level. The purpose of this work is to develop a mathematical model for analyzing the behavior of polycrystalline materials that allows describing the damage accumulation processes. Fracture is the multistage and multiscale process of the build-up of micro- and mesodefects over the wide range of loading rates. The formation of microcracks by mechanisms is caused by the interactions of the dislocations of different slip systems, barriers, boundaries and the inclusions of the secondary phase. This paper provides the description of some of the most well-known models of crack nucleation and also suggests the structure of a mathematical model based on crystal plasticity and dislocation models of crack nucleation.

Computational simulation of the creep-rupture process in filamentary composite materials

NASA Technical Reports Server (NTRS)

Slattery, Kerry T.; Hackett, Robert M.

1991-01-01

A computational simulation of the internal damage accumulation which causes the creep-rupture phenomenon in filamentary composite materials is developed. The creep-rupture process involves complex interactions between several damage mechanisms. A statistically-based computational simulation using a time-differencing approach is employed to model these progressive interactions. The finite element method is used to calculate the internal stresses. The fibers are modeled as a series of bar elements which are connected transversely by matrix elements. Flaws are distributed randomly throughout the elements in the model. Load is applied, and the properties of the individual elements are updated at the end of each time step as a function of the stress history. The simulation is continued until failure occurs. Several cases, with different initial flaw dispersions, are run to establish a statistical distribution of the time-to-failure. The calculations are performed on a supercomputer. The simulation results compare favorably with the results of creep-rupture experiments conducted at the Lawrence Livermore National Laboratory.

Development and evaluation of an ozone deposition scheme for coupling to a terrestrial biosphere model

NASA Astrophysics Data System (ADS)

Franz, Martina; Simpson, David; Arneth, Almut; Zaehle, Sönke

2017-01-01

Ozone (O3) is a toxic air pollutant that can damage plant leaves and substantially affect the plant's gross primary production (GPP) and health. Realistic estimates of the effects of tropospheric anthropogenic O3 on GPP are thus potentially important to assess the strength of the terrestrial biosphere as a carbon sink. To better understand the impact of ozone damage on the terrestrial carbon cycle, we developed a module to estimate O3 uptake and damage of plants for a state-of-the-art global terrestrial biosphere model called OCN. Our approach accounts for ozone damage by calculating (a) O3 transport from 45 m height to leaf level, (b) O3 flux into the leaf, and (c) ozone damage of photosynthesis as a function of the accumulated O3 uptake over the lifetime of a leaf. A comparison of modelled canopy conductance, GPP, and latent heat to FLUXNET data across European forest and grassland sites shows a general good performance of OCN including ozone damage. This comparison provides a good baseline on top of which ozone damage can be evaluated. In comparison to literature values, we demonstrate that the new model version produces realistic O3 surface resistances, O3 deposition velocities, and stomatal to total O3 flux ratios. A sensitivity study reveals that key metrics of the air-to-leaf O3 transport and O3 deposition, in particular the stomatal O3 uptake, are reasonably robust against uncertainty in the underlying parameterisation of the deposition scheme. Nevertheless, correctly estimating canopy conductance plays a pivotal role in the estimate of cumulative O3 uptake. We further find that accounting for stomatal and non-stomatal uptake processes substantially affects simulated plant O3 uptake and accumulation, because aerodynamic resistance and non-stomatal O3 destruction reduce the predicted leaf-level O3 concentrations. Ozone impacts on GPP and transpiration in a Europe-wide simulation indicate that tropospheric O3 impacts the regional carbon and water cycling less than expected from previous studies. This study presents a first step towards the integration of atmospheric chemistry and ecosystem dynamics modelling, which would allow for assessing the wider feedbacks between vegetation ozone uptake and tropospheric ozone burden.

A continuum model for damage evolution in laminated composites

NASA Technical Reports Server (NTRS)

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

1991-01-01

The accumulation of matrix cracking is examined using continuum damage mechanics lamination theory. A phenomenologically based damage evolutionary relationship is proposed for matrix cracking in continuous fiber reinforced laminated composites. The use of material dependent properties and damage dependent laminate averaged ply stresses in this evolutionary relationship permits its application independently of the laminate stacking sequence. Several load histories are applied to crossply laminates using this model, and the results are compared to published experimental data. The stress redistribution among the plies during the accumulation of matrix damage is also examined. It is concluded that characteristics of the stress redistribution process could assist in the analysis of the progressive failure process in laminated composites.

The opportunity and challenge of spin coat based nanoimprint lithography

NASA Astrophysics Data System (ADS)

Jung, Wooyung; Cho, Jungbin; Choi, Eunhyuk; Lim, Yonghyun; Bok, Cheolkyu; Tsuji, Masatoshi; Kobayashi, Kei; Kono, Takuya; Nakasugi, Tetsuro

2017-03-01

Since multi patterning with spacer was introduced in NAND flash memory1, multi patterning with spacer has been a promising solution to overcome the resolution limit. However, the increase in process cost of multi patterning with spacer must be a serious burden to device manufacturers as half pitch of patterns gets smaller.2, 3 Even though Nano Imprint Lithography (NIL) has been considered as one of strong candidates to avoid cost issue of multi patterning with spacer, there are still negative viewpoints; template damage induced from particles between template and wafer, overlay degradation induced from shear force between template and wafer, and throughput loss induced from dispensing and spreading resist droplet. Jet and Flash Imprint Lithography (J-FIL4, 5, 6) has contributed to throughput improvement, but still has these above problems. J-FIL consists of 5 steps; dispense of resist droplets on wafer, imprinting template on wafer, filling the gap between template and wafer with resist, UV curing, and separation of template from wafer. If dispensing resist droplets by inkjet is replaced with coating resist at spin coater, additional progress in NIL can be achieved. Template damage from particle can be suppressed by thick resist which is spin-coated at spin coater and covers most of particles on wafer, shear force between template and wafer can be minimized with thick resist, and finally additional throughput enhancement can be achieved by skipping dispense of resist droplets on wafer. On the other hand, spin-coat-based NIL has side effect such as pattern collapse which comes from high separation energy of resist. It is expected that pattern collapse can be improved by the development of resist with low separation energy.

Lead facilitates foci formation in a Balb/c-3T3 two-step cell transformation model: role of Ape1 function.

PubMed

Hernández-Franco, Pablo; Silva, Martín; Franco, Rodrigo; Valverde, Mahara; Rojas, Emilio

2018-04-01

Several possible mechanisms have been examined to gain an understanding on the carcinogenic properties of lead, which include among others, mitogenesis, alteration of gene expression, oxidative damage, and inhibition of DNA repair. The aim of the present study was to explore if low concentrations of lead, relevant for human exposure, interfere with Ape1 function, a base excision repair enzyme, and its role in cell transformation in Balb/c-3T3. Lead acetate 5 and 30 μM induced APE1 mRNA and upregulation of protein expression. This increase in mRNA expression is consistent throughout the chronic exposure. Additionally, we also found an impaired function of Ape1 through molecular beacon-based assay. To evaluate the impact of lead on foci formation, a Balb/c-3T3 two-step transformation model was used. Balb/c-3T3 cells were pretreated 1 week with low concentrations of lead before induction of transformation with n-methyl-n-nitrosoguanidine (MNNG) (0.5 μg/mL) and 12-O-tetradecanoylphorbol-13-acetate (TPA) (0.1 μg/mL) (a classical two-step protocol). Morphological cell transformation increased in response to lead pretreatment that was paralleled with an increase in Ape1 mRNA and protein overexpression and an impairment of Ape1 activity and correlating with foci number. In addition, we found that lead pretreatment and MNNG (transformation initiator) increased DNA damage, determined by comet assay. Our data suggest that low lead concentrations (5, 30 μM) could play a facilitating role in cellular transformation, probably through the impaired function of housekeeping genes such as Ape1, leading to DNA damage accumulation and chromosomal instability, one of the most important hallmarks of cancer induced by chronic exposures.

A Prospective Study of the Impact of Current Poverty, History of Poverty, and Exiting Poverty on Accumulation of Disease Damage in Systemic Lupus Erythematosus.

PubMed

Yelin, Edward; Trupin, Laura; Yazdany, Jinoos

2017-08-01

To estimate the effect of current poverty, number of years in poverty, and exiting poverty on disease damage accumulation in systemic lupus erythematosus (SLE). For this study, 783 patients with SLE were followed up from 2003 to 2015 through annual structured interviews. Respondents were categorized in each year by whether they had a household income of ≤125% of the US federal poverty level. Linear and logistic regression analyses were used to assess the impact of poverty in 2009, number of years in poverty between 2003 and 2009, and permanent exits from poverty as of 2009 on the extent of disease damage (according to the Brief Index of Lupus Damage [BILD] score) or accumulation of a clinically meaningful increase in disease damage (defined as a minimum 2-point increase in the BILD damage score) by 2015. After adjustment for sociodemographic features, health care characteristics, and health behaviors, poverty in 2009 was associated with an increased level of accumulated disease damage in 2015 (mean difference in BILD damage score between poor and non-poor 0.62 points, 95% confidence interval [95% CI] 0.25-0.98) and increased odds of a clinically important increase in damage (odds ratio [OR] 1.67, 95% CI 0.98-2.85). Being poor in every year between 2003 and 2009 was associated with greater damage (mean change in BILD score 2.45, 95% CI 1.88-3.01) than being poor for one-half or more of those years (mean change in BILD score 1.45, 95% CI 0.97-1.93), for fewer than one-half of those years (mean change in BILD score 1.49, 95% CI 1.10-1.88), or for none of those years (mean change in BILD score 1.34, 95% CI 1.20-1.49). Those exiting poverty permanently had similar increases in disease damage (mean change in BILD score 1.30, 95% CI 0.90-1.69) as those who were never in poverty (mean change in BILD score 1.36, 95% CI 1.23-1.50) but much less damage than those who remained in poverty (mean change in BILD score 1.98, 95% CI 1.59-2.38). The effects of current poverty, "dose" of poverty, and exiting poverty suggest that poverty plays a critical role in the accumulation of damage in patients with SLE. © 2017, American College of Rheumatology.

D-PSA-K: A Model for Estimating the Accumulated Potential Damage on Kiwifruit Canes Caused by Bacterial Canker during the Growing and Overwintering Seasons.

PubMed

Do, Ki Seok; Chung, Bong Nam; Joa, Jae Ho

2016-12-01

We developed a model, termed D-PSA-K, to estimate the accumulated potential damage on kiwifruit canes caused by bacterial canker during the growing and overwintering seasons. The model consisted of three parts including estimation of the amount of necrotic lesion in a non-frozen environment, the rate of necrosis increase in a freezing environment during the overwintering season, and the amount of necrotic lesion on kiwifruit canes caused by bacterial canker during the overwintering and growing seasons. We evaluated the model's accuracy by comparing the observed maximum disease incidence on kiwifruit canes against the damage estimated using weather and disease data collected at Wando during 1994-1997 and at Seogwipo during 2014-2015. For the Hayward cultivar, D-PSA-K estimated the accumulated damage as approximately nine times the observed maximum disease incidence. For the Hort16A cultivar, the accumulated damage estimated by D-PSA-K was high when the observed disease incidence was high. D-PSA-K could assist kiwifruit growers in selecting optimal sites for kiwifruit cultivation and establishing improved production plans by predicting the loss in kiwifruit production due to bacterial canker, using past weather or future climate change data.

Development of an International Canine Spinal Cord Injury observational registry: a collaborative data-sharing network to optimize translational studies of SCI.

PubMed

Moore, Sarah A; Zidan, Natalia; Spitzbarth, Ingo; Nout-Lomas, Yvette S; Granger, Nicolas; da Costa, Ronaldo C; Levine, Jonathan M; Jeffery, Nick D; Stein, Veronika M; Tipold, Andrea; Olby, Natasha J

2018-05-23

Prospective cross-sectional cohort study. The canine spontaneous model of spinal cord injury (SCI) is as an important pre-clinical platform as it recapitulates key facets of human injury in a naturally occurring context. The establishment of an observational canine SCI registry constitutes a key step in performing epidemiologic studies and assessing the impact of therapeutic strategies to enhance translational research. Further, accumulating information on dogs with SCI may contribute to current "big data" approaches to enhance understanding of the disease using heterogeneous multi-institutional, multi-species datasets from both pre-clinical and human studies. Multiple veterinary academic institutions across the United States and Europe. Common data elements recommended for experimental and human SCI studies were reviewed and adapted for use in a web-based registry, to which all dogs presenting to member veterinary tertiary care facilities were prospectively entered over ~1 year. Analysis of data accumulated during the first year of the registry suggests that 16% of dogs with SCI present with severe, sensorimotor-complete injury and that 15% of cases are seen by a tertiary care facility within 8 h of injury. Similar to the human SCI population, 34% were either overweight or obese. Severity of injury and timing of presentation suggests that neuroprotective studies using the canine clinical model could be conducted efficiently using a multi-institutional approach. Additionally, pet dogs with SCI experience similar comorbidities to people with SCI, in particular obesity, and could serve as an important model to evaluate the effects of this condition.

Characterization of shallow trench isolation CMP process and its application

NASA Astrophysics Data System (ADS)

Li, Helen; Zhang, ChunLei; Liu, JinBing; Liu, ZhengFang; Chen, Kuang Han; Gbondo-Tugbawa, Tamba; Ding, Hua; Li, Flora; Lee, Brian; Gower-Hall, Aaron; Chiu, Yang-Chih

2016-03-01

Chemical mechanical polishing (CMP) has been a critical enabling technology in shallow trench isolation (STI), which is used in current integrated circuit fabrication process to accomplish device isolation. Excessive dishing and erosion in STI CMP processes, however, create device yield concerns. This paper proposes characterization and modeling techniques to address a variety of concerns in STI CMP. In the past, majority of CMP publications have been addressed on interconnect layers in backend- of-line (BEOL) process. However, the number of CMP steps in front-end-of-line (FEOL) has been increasing in more advanced process techniques like 3D-FinFET and replacement metal gate, as a results incoming topography induced by FEOL CMP steps can no longer be ignored as the topography accumulates and stacks up across multiple CMP steps and eventually propagating to BEOL layers. In this paper, we first discuss how to characterize and model STI CMP process. Once STI CMP model is developed, it can be used for screening design and detect possible manufacturing weak spots. We also work with process engineering team to establish hotspot criteria in terms of oxide dishing and nitride loss. As process technologies move from planar transistor to 3D transistor like FinFet and multi-gate, it is important to accurately predict topography in FEOL CMP processes. These incoming topographies when stacked up can have huge impact in BEOL copper processes, where copper pooling becomes catastrophic yield loss. A calibration methodology to characterize STI CMP step is developed as shown in Figure 1; moreover, this STI CMP model is validated from silicon data collected from product chips not used in calibration stage. Additionally, wafer experimental setup and metrology plan are instrumental to an accurate model with high predictive power. After a model is generated, spec limits and threshold to establish hotspots criteria can be defined. Such definition requires working closely with foundry process engineering and integration team and reviewing past failure analysis (FA) to come up a reasonable metrics. Conventionally, a potential STI weak point can be found when nitride residues remains in the active region after nitride strip. Another source of STI hotspots occurs when nitride erosion is too much, and active region can suffer severe damage.

"Boomerang Neuropathology" of Late-Onset Alzheimer's Disease is Shrouded in Harmful "BDDS": Breathing, Diet, Drinking, and Sleep During Aging.

PubMed

Daulatzai, Mak Adam

2015-07-01

Brain damage begins years before substantial neurodegeneration and Alzheimer's dementia. Crucial fundamental activities of life are breathing, eating, drinking, and sleeping. When these pivotal functions are maligned over a prolonged period, they impart escalating dyshomeostasis. The latter may lead to disastrous consequences including cognitive dysfunction and Alzheimer's disease (AD). The current theme here is that multiple pathophysiological derangements are promoted over a prolonged period by the very fundamental activities of life-when "rendered unhealthy." They may converge on several regulating/modulating factors (e.g., mitochondrial energy production, oxidative stress, innate immunity, and vascular function) and promote insidious neuropathology that culminates in cognitive decline in the aged. This is of course associated with the accumulation of amyloid beta and phosphorylated tau in the brain. Epidemiological, biomarker, and neuroimaging studies have provided significant copious evidence on the presence of indolent prodromal AD neuropathology many years prior to symptomatic onset. Progressive oxidative damage to specific gene promoters may result in gene silencing. A mechanistic link may possibly exist between epigenomic state, DNA damage, and chronically unhealthy/dysfunctional body systems. This paper, therefore, addresses and delineates the deleterious pathophysiological impact triggered by dysfunctional breathing, harmful diet, excess of alcohol consumption, and sleep deprivation; indeed, their impact may alter epigenetic state. It is mandatory, therefore, to abrogate cognitive decline and attenuate AD pathology through adoption of a healthy lifestyle, in conjunction with combination therapy with known moderators of cognitive decline. This strategy may thwart multiple concurrent and synergistic pathologies, including epigenetic dysfunction. A multi-factorial therapeutic intervention is required to overcome wide ranging neuropathology and multi-faceted disease process. Such an approach may attenuate neuropathology and ameliorate memory dysfunction.

ATM-dependent E2F1 accumulation in the nucleolus is an indicator of ribosomal stress in early response to DNA damage

PubMed Central

Jin, Ya-Qiong; An, Guo-Shun; Ni, Ju-Hua; Li, Shu-Yan; Jia, Hong-Ti

2014-01-01

The nucleolus plays a major role in ribosome biogenesis. Most genotoxic agents disrupt nucleolar structure and function, which results in the stabilization/activation of p53, inducing cell cycle arrest or apoptosis. Likewise, transcription factor E2F1 as a DNA damage responsive protein also plays roles in cell cycle arrest, DNA repair, or apoptosis in response to DNA damage through transcriptional response and protein–protein interaction. Furthermore, E2F1 is known to be involved in regulating rRNA transcription. However, how E2F1 displays in coordinating DNA damage and nucleolar stress is unclear. In this study, we demonstrate that ATM-dependent E2F1 accumulation in the nucleolus is a characteristic feature of nucleolar stress in early response to DNA damage. We found that at the early stage of DNA damage, E2F1 accumulation in the nucleolus was an ATM-dependent and a common event in p53-suficient and -deficient cells. Increased nucleolar E2F1 was sequestered by the nucleolar protein p14ARF, which repressed E2F1-dependent rRNA transcription initiation, and was coupled with S phase. Our data indicate that early accumulation of E2F1 in the nucleolus is an indicator for nucleolar stress and a component of ATM pathway, which presumably buffers elevation of E2F1 in the nucleoplasm and coordinates the diversifying mechanisms of E2F1 acts in cell cycle progression and apoptosis in early response to DNA damage. PMID:24675884

ATM-dependent E2F1 accumulation in the nucleolus is an indicator of ribosomal stress in early response to DNA damage.

PubMed

Jin, Ya-Qiong; An, Guo-Shun; Ni, Ju-Hua; Li, Shu-Yan; Jia, Hong-Ti

2014-01-01

The nucleolus plays a major role in ribosome biogenesis. Most genotoxic agents disrupt nucleolar structure and function, which results in the stabilization/activation of p53, inducing cell cycle arrest or apoptosis. Likewise, transcription factor E2F1 as a DNA damage responsive protein also plays roles in cell cycle arrest, DNA repair, or apoptosis in response to DNA damage through transcriptional response and protein-protein interaction. Furthermore, E2F1 is known to be involved in regulating rRNA transcription. However, how E2F1 displays in coordinating DNA damage and nucleolar stress is unclear. In this study, we demonstrate that ATM-dependent E2F1 accumulation in the nucleolus is a characteristic feature of nucleolar stress in early response to DNA damage. We found that at the early stage of DNA damage, E2F1 accumulation in the nucleolus was an ATM-dependent and a common event in p53-suficient and -deficient cells. Increased nucleolar E2F1 was sequestered by the nucleolar protein p14ARF, which repressed E2F1-dependent rRNA transcription initiation, and was coupled with S phase. Our data indicate that early accumulation of E2F1 in the nucleolus is an indicator for nucleolar stress and a component of ATM pathway, which presumably buffers elevation of E2F1 in the nucleoplasm and coordinates the diversifying mechanisms of E2F1 acts in cell cycle progression and apoptosis in early response to DNA damage.

46 CFR 76.33-10 - Location and spacing of accumulators.

Code of Federal Regulations, 2012 CFR

2012-10-01

... PROTECTION EQUIPMENT Smoke Detecting System, Details § 76.33-10 Location and spacing of accumulators. (a) Smoke accumulators shall be located overhead in each compartment. Where liable to physical damage, the...

46 CFR 76.33-10 - Location and spacing of accumulators.

Code of Federal Regulations, 2014 CFR

2014-10-01

... PROTECTION EQUIPMENT Smoke Detecting System, Details § 76.33-10 Location and spacing of accumulators. (a) Smoke accumulators shall be located overhead in each compartment. Where liable to physical damage, the...

46 CFR 76.33-10 - Location and spacing of accumulators.

Code of Federal Regulations, 2013 CFR

2013-10-01

... PROTECTION EQUIPMENT Smoke Detecting System, Details § 76.33-10 Location and spacing of accumulators. (a) Smoke accumulators shall be located overhead in each compartment. Where liable to physical damage, the...

46 CFR 76.33-10 - Location and spacing of accumulators.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PROTECTION EQUIPMENT Smoke Detecting System, Details § 76.33-10 Location and spacing of accumulators. (a) Smoke accumulators shall be located overhead in each compartment. Where liable to physical damage, the...

46 CFR 76.33-10 - Location and spacing of accumulators.

Code of Federal Regulations, 2011 CFR

2011-10-01

... PROTECTION EQUIPMENT Smoke Detecting System, Details § 76.33-10 Location and spacing of accumulators. (a) Smoke accumulators shall be located overhead in each compartment. Where liable to physical damage, the...

Hierarchical damage mechanisms in composite materials subjected to fatigue loadings

NASA Astrophysics Data System (ADS)

D'Amore, Alberto; Grassia, Luigi

2018-02-01

The strength degradation of fiber reinforced composites subjected to constant amplitude (CA) fatigue loadings can be described by a two-parameter residual strength model. From the analytical approach it results that under moderate loadings the multiple damage mechanisms develop with different kinetics and manifest their effectiveness at different time scales highlighting the three-Stage hierarchical nature of damage accumulation in composites. The model captures the sequence of damage accumulation mechanisms from diffuse matrix cracking (I), to fiber/matrix interface failure (II) to fiber and ply rupture and delamination (III). Further, by increasing the loading severity it appears that the different mechanisms superpose witnessing their simultaneous co-existence.

Cumulative Disadvantage and Youth Well-Being: A Multi-Domain Examination with Life Course Implications

PubMed Central

Nurius, Paula S.; Prince, Dana M.; Rocha, Anita

2015-01-01

Purpose The accumulation of disadvantage has been shown to increase psychosocial stressors that impact life course well-being. This study tests for significant differences, based on disadvantage exposure, on youths’ emotional and physical health, as well as family supports, peer assets, and academic success, which hold potential for resilience and amelioration of negative health outcomes. Methods A 12 item cumulative disadvantage summed index derived from surveys of a racially and socioeconomically diverse sample of urban high school seniors (n=9,658) was used to distinguish youth at low, moderate, and high levels. Results Findings supported hypothesized stepped patterns such that as multiple disadvantages accumulate, a concomitant decline is evident across the assessed outcome variables (except positive academic identity). Post-hoc tests indicated a pattern of groups being significantly different from one another. Discussion Overall, results lend support for an additive stress load associated with stacked disadvantage, with implications for continuing trends into adulthood as well as preventive interventions PMID:26617431

Lifestyle impacts on the aging associated expression of biomarkers of DNA damage and telomere dysfunction in human blood

PubMed Central

Song, Zhangfa; von Figura, Guido; Liu, Yan; Kraus, Johann M.; Torrice, Chad; Dillon, Patric; Rudolph-Watabe, Masami; Ju, Zhenyu; Kestler, Hans A.; Sanoff, Hanna; Rudolph, K. Lenhard

2010-01-01

Summary Cellular aging is characterised by telomere shortening, which can lead to uncapping of chromosome ends (telomere dysfunction) and that activation of DNA damage responses. There is some evidence the DNA damage accumulates during human aging and that lifestyle factors contribute to the accumulation of DNA damage. Recent studies have identified a set of serum markers that are induced by telomere dysfunction and DNA damage and these markers showed an increased expression in blood during human aging. Here, we investigated the influence of lifestyle factors (such as exercise, smoking, body mass) on the aging associated expression of serum markers of DNA damage (CRAMP, EF-1α, Stathmin, n-acetyl-glucosaminidase, and chitinase) in comparison to other described markers of cellular aging (p16INK4a upregulation and telomere shortening) in human peripheral blood. The study shows that lifestyle factors have an age-independent impact on the expression level of biomarkers of DNA damage. Smoking and increased body mass indices were associated with elevated levels of biomarkers of DNA damage independent of the age of the individuals. In contrast, exercise was associated with an age-independent reduction in the expression of biomarkers of DNA damage in human blood. The expression of biomarkers of DNA damage correlated positively with p16INK4a expression and negatively with telomere length in peripheral blood T-lymphocytes. Together, these data provide experimental evidence that both aging and lifestyle impact on the accumulation of DNA damage during human aging. PMID:20560902

Use of Acoustic Emission to Monitor Progressive Damage Accumulation in KEVLAR® 49 Composites

NASA Astrophysics Data System (ADS)

Waller, J. M.; Andrade, E.; Saulsberry, R. L.

2010-02-01

Acoustic emission (AE) data acquired during intermittent load hold tensile testing of epoxy impregnated Kevlar® 49 (K/Ep) composite strands were analyzed to monitor progressive damage during the approach to tensile failure. Insight into the progressive damage of K/Ep strands was gained by monitoring AE event rate and energy. Source location based on energy attenuation and arrival time data was used to discern between significant AE attributable to microstructural damage and spurious AE attributable to noise. One of the significant findings was the observation of increasing violation of the Kaiser effect (Felicity ratio <1.0) with damage accumulation. The efficacy of three different intermittent load hold stress schedules that allowed the Felicity ratio to be determined analytically is discussed.

Analysis of dynamic accumulative damage about the lining structure of high speed railway’s tunnel based on ultrasonic testing technology

NASA Astrophysics Data System (ADS)

Wang, Xiang-qiu; Zhang, Huojun; Xie, Wen-xi

2017-08-01

Based on the similar material model test of full tunnel, the theory of elastic wave propagation and the testing technology of intelligent ultrasonic wave had been used to research the dynamic accumulative damage characteristics of tunnel’s lining structure under the dynamic loads of high speed train. For the more, the dynamic damage variable of lining structure of high speed railway’s tunnel was obtained. The results shown that the dynamic cumulative damage of lining structure increases nonlinearly with the times of cumulative vibration, the weakest part of dynamic cumulative damage is the arch foot of tunnel. Much more attention should be paid to the design and operation management of high speed railway’s tunnel.

Fast fluorescence techniques for crystallography beamlines

PubMed Central

Stepanov, Sergey; Hilgart, Mark; Yoder, Derek W.; Makarov, Oleg; Becker, Michael; Sanishvili, Ruslan; Ogata, Craig M.; Venugopalan, Nagarajan; Aragão, David; Caffrey, Martin; Smith, Janet L.; Fischetti, Robert F.

2011-01-01

This paper reports on several developments of X-ray fluorescence techniques for macromolecular crystallography recently implemented at the National Institute of General Medical Sciences and National Cancer Institute beamlines at the Advanced Photon Source. These include (i) three-band on-the-fly energy scanning around absorption edges with adaptive positioning of the fine-step band calculated from a coarse pass; (ii) on-the-fly X-ray fluorescence rastering over rectangular domains for locating small and invisible crystals with a shuttle-scanning option for increased speed; (iii) fluorescence rastering over user-specified multi-segmented polygons; and (iv) automatic signal optimization for reduced radiation damage of samples. PMID:21808424

77 FR 45981 - Airworthiness Directives; Bombardier, Inc. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-02

... the affected parking brake hydraulic accumulator, and relocating the parking brake accumulator, on the... parking brake hydraulic accumulator, which could result in damage to the airplane's primary structures... (P/N) 08-60197-001 (Parking Brake Accumulator), are installed on the aeroplanes listed in the...

Progressive Damage Analysis of Laminated Composite (PDALC) (A Computational Model Implemented in the NASA COMET Finite Element Code). 2.0

NASA Technical Reports Server (NTRS)

Coats, Timothy W.; Harris, Charles E.; Lo, David C.; Allen, David H.

1998-01-01

A method for analysis of progressive failure in the Computational Structural Mechanics Testbed is presented in this report. The relationship employed in this analysis describes the matrix crack damage and fiber fracture via kinematics-based volume-averaged damage variables. Damage accumulation during monotonic and cyclic loads is predicted by damage evolution laws for tensile load conditions. The implementation of this damage model required the development of two testbed processors. While this report concentrates on the theory and usage of these processors, a complete listing of all testbed processors and inputs that are required for this analysis are included. Sample calculations for laminates subjected to monotonic and cyclic loads were performed to illustrate the damage accumulation, stress redistribution, and changes to the global response that occurs during the loading history. Residual strength predictions made with this information compared favorably with experimental measurements.

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

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

NASA Astrophysics Data System (ADS)

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

2015-06-01

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

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

Bates, Robert; McConnell, Elizabeth

Machining methods across many industries generally require multiple operations to machine and process advanced materials, features with micron precision, and complex shapes. The resulting multiple machining platforms can significantly affect manufacturing cycle time and the precision of the final parts, with a resultant increase in cost and energy consumption. Ultrafast lasers represent a transformative and disruptive technology that removes material with micron precision and in a single step manufacturing process. Such precision results from athermal ablation without modification or damage to the remaining material which is the key differentiator between ultrafast laser technologies and traditional laser technologies or mechanical processes.more » Athermal ablation without modification or damage to the material eliminates post-processing or multiple manufacturing steps. Combined with the appropriate technology to control the motion of the work piece, ultrafast lasers are excellent candidates to provide breakthrough machining capability for difficult-to-machine materials. At the project onset in early 2012, the project team recognized that substantial effort was necessary to improve the application of ultrafast laser and precise motion control technologies (for micromachining difficult-to-machine materials) to further the aggregate throughput and yield improvements over conventional machining methods. The project described in this report advanced these leading-edge technologies thru the development and verification of two platforms: a hybrid enhanced laser chassis and a multi-application testbed.« less

Parallel Multi-Step/Multi-Rate Integration of Two-Time Scale Dynamic Systems

NASA Technical Reports Server (NTRS)

Chang, Johnny T.; Ploen, Scott R.; Sohl, Garett. A,; Martin, Bryan J.

2004-01-01

Increasing demands on the fidelity of simulations for real-time and high-fidelity simulations are stressing the capacity of modern processors. New integration techniques are required that provide maximum efficiency for systems that are parallelizable. However many current techniques make assumptions that are at odds with non-cascadable systems. A new serial multi-step/multi-rate integration algorithm for dual-timescale continuous state systems is presented which applies to these systems, and is extended to a parallel multi-step/multi-rate algorithm. The superior performance of both algorithms is demonstrated through a representative example.

77 FR 26158 - Airworthiness Directives; Saab AB, Saab Aerosystems Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-03

... of hydraulic accumulator failure. This AD requires replacing certain hydraulic accumulators with stainless steel hydraulic accumulators, and structural modifications in the nose landing gear bay. We are issuing this AD to prevent failure of hydraulic accumulators, which may result in damage to the airplane...

Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data

PubMed Central

2011-01-01

Background Deregulation between two different cell populations manifests itself in changing gene expression patterns and changing regulatory interactions. Accumulating knowledge about biological networks creates an opportunity to study these changes in their cellular context. Results We analyze re-wiring of regulatory networks based on cell population-specific perturbation data and knowledge about signaling pathways and their target genes. We quantify deregulation by merging regulatory signal from the two cell populations into one score. This joint approach, called JODA, proves advantageous over separate analysis of the cell populations and analysis without incorporation of knowledge. JODA is implemented and freely available in a Bioconductor package 'joda'. Conclusions Using JODA, we show wide-spread re-wiring of gene regulatory networks upon neocarzinostatin-induced DNA damage in Human cells. We recover 645 deregulated genes in thirteen functional clusters performing the rich program of response to damage. We find that the clusters contain many previously characterized neocarzinostatin target genes. We investigate connectivity between those genes, explaining their cooperation in performing the common functions. We review genes with the most extreme deregulation scores, reporting their involvement in response to DNA damage. Finally, we investigate the indirect impact of the ATM pathway on the deregulated genes, and build a hypothetical hierarchy of direct regulation. These results prove that JODA is a step forward to a systems level, mechanistic understanding of changes in gene regulation between different cell populations. PMID:21693013

Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data.

PubMed

Szczurek, Ewa; Markowetz, Florian; Gat-Viks, Irit; Biecek, Przemysław; Tiuryn, Jerzy; Vingron, Martin

2011-06-21

Deregulation between two different cell populations manifests itself in changing gene expression patterns and changing regulatory interactions. Accumulating knowledge about biological networks creates an opportunity to study these changes in their cellular context. We analyze re-wiring of regulatory networks based on cell population-specific perturbation data and knowledge about signaling pathways and their target genes. We quantify deregulation by merging regulatory signal from the two cell populations into one score. This joint approach, called JODA, proves advantageous over separate analysis of the cell populations and analysis without incorporation of knowledge. JODA is implemented and freely available in a Bioconductor package 'joda'. Using JODA, we show wide-spread re-wiring of gene regulatory networks upon neocarzinostatin-induced DNA damage in Human cells. We recover 645 deregulated genes in thirteen functional clusters performing the rich program of response to damage. We find that the clusters contain many previously characterized neocarzinostatin target genes. We investigate connectivity between those genes, explaining their cooperation in performing the common functions. We review genes with the most extreme deregulation scores, reporting their involvement in response to DNA damage. Finally, we investigate the indirect impact of the ATM pathway on the deregulated genes, and build a hypothetical hierarchy of direct regulation. These results prove that JODA is a step forward to a systems level, mechanistic understanding of changes in gene regulation between different cell populations.

Modeling of thermo-mechanical fatigue and damage in shape memory alloy axial actuators

NASA Astrophysics Data System (ADS)

Wheeler, Robert W.; Hartl, Darren J.; Chemisky, Yves; Lagoudas, Dimitris C.

2015-04-01

The aerospace, automotive, and energy industries have seen the potential benefits of using shape memory alloys (SMAs) as solid state actuators. Thus far, however, these actuators are generally limited to non-critical components or over-designed due to a lack of understanding regarding how SMAs undergo thermomechanical or actuation fatigue and the inability to accurately predict failure in an actuator during use. The purpose of this study was to characterize the actuation fatigue response of Nickel-Titanium-Hafnium (NiTiHf) axial actuators and, in turn, use this characterization to predict failure and monitor damage in dogbone actuators undergoing various thermomechanical loading paths. Calibration data was collected from constant load, full cycle tests ranging from 200-600MPa. Subsequently, actuator lifetimes were predicted for four additional loading paths. These loading paths consisted of linearly varying load with full transformation (300-500MPa) and step loads which transition from zero stress to 300-400MPa at various martensitic volume fractions. Thermal cycling was achieved via resistive heating and convective cooling and was controlled via a state machine developed in LabVIEW. A previously developed fatigue damage model, which is formulated such that the damage accumulation rate is general in terms of its dependence on current and local stress and actuation strain states, was utilized. This form allows the model to be utilized for specimens undergoing complex loading paths. Agreement between experiments and simulations is discussed.

Flat Surface Damage Detection System (FSDDS)

NASA Technical Reports Server (NTRS)

Williams, Martha; Lewis, Mark; Gibson, Tracy; Lane, John; Medelius, Pedro; Snyder, Sarah; Ciarlariello, Dan; Parks, Steve; Carrejo, Danny; Rojdev, Kristina

2013-01-01

The Flat Surface Damage Detection system (FSDDS} is a sensory system that is capable of detecting impact damages to surfaces utilizing a novel sensor system. This system will provide the ability to monitor the integrity of an inflatable habitat during in situ system health monitoring. The system consists of three main custom designed subsystems: the multi-layer sensing panel, the embedded monitoring system, and the graphical user interface (GUI). The GUI LABVIEW software uses a custom developed damage detection algorithm to determine the damage location based on the sequence of broken sensing lines. It estimates the damage size, the maximum depth, and plots the damage location on a graph. Successfully demonstrated as a stand alone technology during 2011 D-RATS. Software modification also allowed for communication with HDU avionics crew display which was demonstrated remotely (KSC to JSC} during 2012 integration testing. Integrated FSDDS system and stand alone multi-panel systems were demonstrated remotely and at JSC, Mission Operations Test using Space Network Research Federation (SNRF} network in 2012. FY13, FSDDS multi-panel integration with JSC and SNRF network Technology can allow for integration with other complementary damage detection systems.

The role of nickel in radiation damage of ferritic alloys

DOE PAGES

Osetsky, Y.; Anento, Napoleon; Serra, Anna; ...

2014-11-26

According to modern theory, damage evolution under neutron irradiation depends on the fraction of self-interstitial atoms (SIAs) produced in the form of one-dimensional glissile clusters. These clusters, having a low interaction cross-section with other defects, are absorbed mainly by grain boundaries and dislocations, creating the so-called production bias. It is known empirically that the addition of certain alloying elements influences many radiation effects, including swelling; however, the mechanisms are unknown in many cases. In this study, we report the results of an extensive multi-technique atomistic level modeling study of SIA clusters mobility in body-centered cubic Fe–Ni alloys. We have foundmore » that Ni interacts strongly with the periphery of clusters, affecting their mobility. The total effect is defined by the number of Ni atoms interacting with the cluster at the same time and can be significant, even in low-Ni alloys. Thus a 1 nm (37SIAs) cluster is practically immobile at T < 500 K in the Fe–0.8 at.% Ni alloy. Increasing cluster size and Ni content enhances cluster immobilization. Finally, this effect should have quite broad consequences in void swelling, matrix damage accumulation and radiation induced hardening and the results obtained help to better understand and predict the effects of radiation in Fe–Ni ferritic alloys.« less

[Increasing oxidative stress in aging].

PubMed

Shimosawa, Tatsuo

2005-06-01

The balance between reactive oxigen species (ROS) production and degradation is important in defining oxidative stress. In aging process, ROS production increases and degradation is impaired and thus oxidative stress is accumulated. Oxidative stress damages organs both directly and indirectly. Protein, lipid, as well as DNA are directly react with ROS, more over, ROS interact with intracellular signaling system. It is reported that several transcription factors such as NF-kappaB, AP-1 and ASK-1 and also it interferes MAPK activity. Besides these signaling, we recently showed that insulin resistance is induced by accumulated oxidative stress in aged mice. Adrenomedullin deficient mice accumulate higher oxidative stress and insulin resistance developed in aging. Oxidative stress in aging relates not only direct organ damage but also induce risk factors for vascular damage such as metabolic syndrome.

Mesoscale Modeling of Deflagration-Induced Deconsolidation in Polymer-Bonded Explosives

NASA Astrophysics Data System (ADS)

Springer, H. Keo; Reaugh, J. E.; Glascoe, E. A.; Kercher, J. R.; Friedman, G.

2011-06-01

Initially intact polymer-bonded explosives can transition from conductive burning to more violent convective burning via rapid deconsolidation at higher pressures. The pressure-dependent infiltration of cracks and pores, i.e., damage, by product gases at the burn-front is a key step in the transition to convective burning. However, the relative influence of pre-existing damage and deflagration-induced damage on the transition to convective burning is not well understood. The objective of this study is to investigate the role of explosive constituent properties, microstructure, and deflagration velocity on deconsolidation. We performed simulations using the multi-physics hydrocode, ALE3D. HMX was used as the model energetic grain. We used a JWL form for the unreacted and reacted equation-of-state of the HMX. Simplified strength and failure models were used for the HMX and the binder. The propensity for deconsolidation increased with increasing grain volume fraction, increasing porosity, decreasing binder strength, and increasing deflagration velocity. These studies are important because they enable the development of deflagration-induced damage models, as well as the design of inherently safer explosives. This work performed under the auspices of the U.S. DOE by LLNL under Contract DE-AC52-07NA27344. This work was funded by the Joint DoD/DOE Munitions Technology Development Program.

Accrual of organ damage over time in patients with systemic lupus erythematosus.

PubMed

Gladman, Dafna D; Urowitz, Murray B; Rahman, Proton; Ibañez, Dominique; Tam, Lai-Shan

2003-09-01

To determine the pattern of accumulation of damage in an inception cohort of patients with systemic lupus erythematosus (SLE) followed yearly for at least 15 years, and to identify damage items that might be related to corticosteroid therapy. An inception cohort was identified from among patients with SLE followed prospectively in the University of Toronto Lupus Clinic. Only patients who had at least yearly evaluations and were followed for at least 15 years were included. Using the SLICC/ACR damage index (SDI) accumulated damage was calculated at yearly intervals. Each new organ system involved was designated as either definitely, possibly, or not at all related to corticosteroid therapy. Of the 73 patients, 85% were women and 87.7% were Caucasian. Their mean age at diagnosis was 34.9 years. The mean (range) SLEDAI at presentation was 11.9 (0-37). Prednisone was used by 87.7% of the patients (mean maximum dose 37.7 mg/day, mean cumulative dose 36.8 g) for a mean of 117.1 months. Antimalarial drugs were used by 70% of the patients and 50% were taking immunosuppressive agents. The mean SDI for the whole cohort increased over time from 0.33 (0.89) during the first year to 1.90 (1.99) at 15 years. A significant proportion of the damage both early and late could be attributed to corticosteroid therapy, and this damage accumulated over time such that it constituted most of the damage at 15 years. While the overall accrual of damage is gradual, the specific systems demonstrate varying patterns of damage accrual.

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

NASA Astrophysics Data System (ADS)

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

2016-07-01

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

A procedure for utilization of a damage-dependent constitutive model for laminated composites

NASA Technical Reports Server (NTRS)

Lo, David C.; Allen, David H.; Harris, Charles E.

1992-01-01

Described here is the procedure for utilizing a damage constitutive model to predict progressive damage growth in laminated composites. In this model, the effects of the internal damage are represented by strain-like second order tensorial damage variables and enter the analysis through damage dependent ply level and laminate level constitutive equations. The growth of matrix cracks due to fatigue loading is predicted by an experimentally based damage evolutionary relationship. This model is incorporated into a computer code called FLAMSTR. This code is capable of predicting the constitutive response and matrix crack damage accumulation in fatigue loaded laminated composites. The structure and usage of FLAMSTR are presented along with sample input and output files to assist the code user. As an example problem, an analysis of crossply laminates subjected to two stage fatigue loading was conducted and the resulting damage accumulation and stress redistribution were examined to determine the effect of variations in fatigue load amplitude applied during the first stage of the load history. It was found that the model predicts a significant loading history effect on damage evolution.

Damage to urban buildings in zones of intensities VIII and VII during the Wenchuan earthquake and discussion on some typical damages

NASA Astrophysics Data System (ADS)

Sun, Jingjiang; Tang, Yuhong; Zheng, Chao; Shi, Hongbin; Lin, Lin; Sun, Zhongxian

2009-04-01

The outline and typical characteristics of damages to building in Jiangyou city and Anxian county (intensity VIII), Mianyang city and Deyang city (intensity VII) are introduced in the paper. The damage ratios, based on the sample statistics of multi-story brick buildings together with multi-story brick buildings with RC frame at first story (BBF), are presented. Then some typical damages, such as horizontal cricks of brick masonry buildings, X-shaped cricks on the walls under windows, the damages to columns, beams and infill walls of frame buildings and the damage to half circle-shaped masonry walls, are discussed.

[Preliminary study of rabbit experiment modality for evaluating cardiac fatigue].

PubMed

Yan, Xiaobo; Luo, Linmei; Liu, Leichu; Xiao, Shouzhong; Deng, Suyuan; Xiang, Lingli; Zhang, Cong

2013-04-01

This paper presents a preliminary study of rabbit experiment modality incorporating a new indicator for evaluating cardiac function changes, providing a basis for subsequent study of cardiac fatigue. Using only biochemical indicators, such as troponins, is difficult to make a distinction between exercise-induced cardiac fatigue (EICF) and exercise-induced cardiac damage (EICD). Therefore, some new indicators are needed to evaluate cardiac fatigue synthetically. In our study, we used New Zealand white rabbits to conduct a multi-step swimming experiments with load. We made the rabbits reach an exhaustive state to evaluate whether the amplitude ratio of the first to second heart sound (S1/S2) and heart rate (HR) during the exhaustive exercise would be decreased and whether they would be able to recover after the exhaustive exercise for 24 hours. During the first phase of swimming, S1/S2 and HR were increased, and then decreased at exhaustive state. They were recovered after the exhaustive exercise for 24 hours. Overloading led to deaths of three rabbis, and new phenomena from overloading and related to this kind of death were observed. The experiments proved that Multi-steps swimming experiments with loads by using New Zealand white rabbit is useful for studying cardiac fatigue and premonition of sudden cardiac death.

Multi-electrolyte-step anodic aluminum oxide method for the fabrication of self-organized nanochannel arrays

PubMed Central

2012-01-01

Nanochannel arrays were fabricated by the self-organized multi-electrolyte-step anodic aluminum oxide [AAO] method in this study. The anodization conditions used in the multi-electrolyte-step AAO method included a phosphoric acid solution as the electrolyte and an applied high voltage. There was a change in the phosphoric acid by the oxalic acid solution as the electrolyte and the applied low voltage. This method was used to produce self-organized nanochannel arrays with good regularity and circularity, meaning less power loss and processing time than with the multi-step AAO method. PMID:22333268

High-fluence ion implantation in silicon carbide for fabrication of a compliant substrate

NASA Astrophysics Data System (ADS)

Lioubtchenko, Mikhail

GaN and related nitrides are promising materials for applications as UV/blue light emitters and in high-power, high-temperature electonic devices. Unfortunately, the vast potential of these materials cannot be realized effectively due to a large density of threading dislocations, arising from large lattice mismatch between GaN and utilized substrates. Therefore, a new approach to the heteroepitaxial growth is desirable, and a compliant substrate might help to remedy the situation. A modified model for the compliant substrate consisting of the compliant membrane glued to a thick handling substrate by a soft layer was proposed. We have chosen 6H-SiC as a starting substrate and ion implantation as a means of creating a buried layer. High fluence ion implantation of different species in 6H-SiC was performed at elevated temperatures and damage removal/accumulation was studied. It was found that temperatures around 1600°C are necessary to successfully recrystallize the radiation damage for Ti, Ga, Si and C implantations, but no damage removal was monitored for In implantation. In order to minimize the damage produced during ion implantation, it was decided to employ a multistep process in which each implantation step was followed by annealing. This approach was realized for 125 keV Ti++ and 300 keV Ga+ implantations up to a total dose of 1.8 x 1017 cm--2. Ti-implanted substrates were shown to retain good quality in the top layer, whereas Ga implantation preserves the quality of the near-surface region only at lower doses. The implanted species concentration was monitored after each step using Rutherford Backscattering (RBS). GaN films were grown on the prepared substrates and a control SiC sample by MOCVD. TEM and photoluminescence measurements have demonstrated that the quality of GaN films improves upon growth on compliant substrates.

A general solution strategy of modified power method for higher mode solutions

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

Zhang, Peng; Lee, Hyunsuk; Lee, Deokjung, E-mail: deokjung@unist.ac.kr

2016-01-15

A general solution strategy of the modified power iteration method for calculating higher eigenmodes has been developed and applied in continuous energy Monte Carlo simulation. The new approach adopts four features: 1) the eigen decomposition of transfer matrix, 2) weight cancellation for higher modes, 3) population control with higher mode weights, and 4) stabilization technique of statistical fluctuations using multi-cycle accumulations. The numerical tests of neutron transport eigenvalue problems successfully demonstrate that the new strategy can significantly accelerate the fission source convergence with stable convergence behavior while obtaining multiple higher eigenmodes at the same time. The advantages of the newmore » strategy can be summarized as 1) the replacement of the cumbersome solution step of high order polynomial equations required by Booth's original method with the simple matrix eigen decomposition, 2) faster fission source convergence in inactive cycles, 3) more stable behaviors in both inactive and active cycles, and 4) smaller variances in active cycles. Advantages 3 and 4 can be attributed to the lower sensitivity of the new strategy to statistical fluctuations due to the multi-cycle accumulations. The application of the modified power method to continuous energy Monte Carlo simulation and the higher eigenmodes up to 4th order are reported for the first time in this paper. -- Graphical abstract: -- Highlights: •Modified power method is applied to continuous energy Monte Carlo simulation. •Transfer matrix is introduced to generalize the modified power method. •All mode based population control is applied to get the higher eigenmodes. •Statistic fluctuation can be greatly reduced using accumulated tally results. •Fission source convergence is accelerated with higher mode solutions.« less

Use of Acoustic Emission to Monitor Progressive Damage Accumulation in Kevlar (R) 49 Composites

NASA Technical Reports Server (NTRS)

Waller, Jess M.; Saulsberry, Regor L.; Andrade, Eduardo

2009-01-01

Acoustic emission (AE) data acquired during intermittent load hold tensile testing of epoxy impregnated Kevlar(Registeres TradeMark) 49 (K/Ep) composite strands were analyzed to monitor progressive damage during the approach to tensile failure. Insight into the progressive damage of K/Ep strands was gained by monitoring AE event rate and energy. Source location based on energy attenuation and arrival time data was used to discern between significant AE attributable to microstructural damage and spurious AE attributable to noise. One of the significant findings was the observation of increasing violation of the Kaiser effect (Felicity ratio < 1.0) with damage accumulation. The efficacy of three different intermittent load hold stress schedules that allowed the Felicity ratio to be determined analytically is discussed.

Accelerated age-related cognitive decline and neurodegeneration, caused by deficient DNA repair.

PubMed

Borgesius, Nils Z; de Waard, Monique C; van der Pluijm, Ingrid; Omrani, Azar; Zondag, Gerben C M; van der Horst, Gijsbertus T J; Melton, David W; Hoeijmakers, Jan H J; Jaarsma, Dick; Elgersma, Ype

2011-08-31

Age-related cognitive decline and neurodegenerative diseases are a growing challenge for our societies with their aging populations. Accumulation of DNA damage has been proposed to contribute to these impairments, but direct proof that DNA damage results in impaired neuronal plasticity and memory is lacking. Here we take advantage of Ercc1(Δ/-) mutant mice, which are impaired in DNA nucleotide excision repair, interstrand crosslink repair, and double-strand break repair. We show that these mice exhibit an age-dependent decrease in neuronal plasticity and progressive neuronal pathology, suggestive of neurodegenerative processes. A similar phenotype is observed in mice where the mutation is restricted to excitatory forebrain neurons. Moreover, these neuron-specific mutants develop a learning impairment. Together, these results suggest a causal relationship between unrepaired, accumulating DNA damage, and age-dependent cognitive decline and neurodegeneration. Hence, accumulated DNA damage could therefore be an important factor in the onset and progression of age-related cognitive decline and neurodegenerative diseases.

Mechanical and Metallurgical Evolution of Stainless Steel 321 in a Multi-step Forming Process

NASA Astrophysics Data System (ADS)

Anderson, M.; Bridier, F.; Gholipour, J.; Jahazi, M.; Wanjara, P.; Bocher, P.; Savoie, J.

2016-04-01

This paper examines the metallurgical evolution of AISI Stainless Steel 321 (SS 321) during multi-step forming, a process that involves cycles of deformation with intermediate heat treatment steps. The multi-step forming process was simulated by implementing interrupted uniaxial tensile testing experiments. Evolution of the mechanical properties as well as the microstructural features, such as twins and textures of the austenite and martensite phases, was studied as a function of the multi-step forming process. The characteristics of the Strain-Induced Martensite (SIM) were also documented for each deformation step and intermediate stress relief heat treatment. The results indicated that the intermediate heat treatments considerably increased the formability of SS 321. Texture analysis showed that the effect of the intermediate heat treatment on the austenite was minor and led to partial recrystallization, while deformation was observed to reinforce the crystallographic texture of austenite. For the SIM, an Olson-Cohen equation type was identified to analytically predict its formation during the multi-step forming process. The generated SIM was textured and weakened with increasing deformation.

Engineering multi-stage nanovectors for controlled degradation and tunable release kinetics

PubMed Central

Martinez, Jonathan O.; Chiappini, Ciro; Ziemys, Arturas; Faust, Ari M.; Kojic, Milos; Liu, Xuewu; Ferrari, Mauro; Tasciotti, Ennio

2013-01-01

Nanovectors hold substantial promise in abating the off-target effects of therapeutics by providing a means to selectively accumulate payloads at the target lesion, resulting in an increase in the therapeutic index. A sophisticated understanding of the factors that govern the degradation and release dynamics of these nanovectors is imperative to achieve these ambitious goals. In this work, we elucidate the relationship that exists between variations in pore size and the impact on the degradation, loading, and release of multistage nanovectors. Larger pored vectors displayed faster degradation and higher loading of nanoparticles, while exhibiting the slowest release rate. The degradation of these particles was characterized to occur in a multi-step progression where they initially decreased in size leaving the porous core isolated, while the pores gradually increased in size. Empirical loading and release studies of nanoparticles along with diffusion modeling revealed that this prolonged release was modulated by the penetration within the porous core of the vectors regulated by their pore size. PMID:23911070

How does damage affect rupture propagation across a fault stepover?

NASA Astrophysics Data System (ADS)

Cooke, M. L.; Savage, H. M.

2011-12-01

We investigate the potential for fault damage to influence earthquake rupture at fault step-overs using a mechanical numerical model that explicitly includes the generation of cracks around faults. We compare the off-fault fracture patterns and slip profiles generated along faults with a variety of frictional slip-weakening distances and step-over geometry. Models with greater damage facilitate the transfer of slip to the second fault. Increasing separation and decreasing the overlap distance reduces the transfer of slip across the step over. This is consistent with observations of rupture stopping at step-over separation greater than 4 km (Wesnousky, 2006). In cases of slip transfer, rupture is often passed to the second fault before the damage zone cracks of the first fault reach the second fault. This implies that stresses from the damage fracture tips are transmitted elastically to the second fault to trigger the onset of slip along the second fault. Consequently, the growth of damage facilitates transfer of rupture from one fault to another across the step-over. In addition, the rupture propagates along the damage-producing fault faster than along the rougher fault that does not produce damage. While this result seems counter to our understanding that damage slows rupture propagation, which is documented in our models with pre-existing damage, these model results are suggesting an additional process. The slip along the newly created damage may unclamp portions of the fault ahead of the rupture and promote faster rupture. We simulate the M7.1 Hector Mine Earthquake and compare the generated fracture patterns to maps of surface damage. Because along with the detailed damage pattern, we also know the stress drop during the earthquake, we may begin to constrain parameters like the slip-weakening distance along portions of the faults that ruptured in the Hector Mine earthquake.

Endothelial and smooth muscle cells from abdominal aortic aneurysm have increased oxidative stress and telomere attrition.

PubMed

Cafueri, Giuseppe; Parodi, Federica; Pistorio, Angela; Bertolotto, Maria; Ventura, Francesco; Gambini, Claudio; Bianco, Paolo; Dallegri, Franco; Pistoia, Vito; Pezzolo, Annalisa; Palombo, Domenico

2012-01-01

Abdominal aortic aneurysm (AAA) is a complex multi-factorial disease with life-threatening complications. AAA is typically asymptomatic and its rupture is associated with high mortality rate. Both environmental and genetic risk factors are involved in AAA pathogenesis. Aim of this study was to investigate telomere length (TL) and oxidative DNA damage in paired blood lymphocytes, aortic endothelial cells (EC), vascular smooth muscle cells (VSMC), and epidermal cells from patients with AAA in comparison with matched controls. TL was assessed using a modification of quantitative (Q)-FISH in combination with immunofluorescence for CD31 or α-smooth muscle actin to detect EC and VSMC, respectively. Oxidative DNA damage was investigated by immunofluorescence staining for 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG). Telomeres were found to be significantly shortened in EC, VSMC, keratinocytes and blood lymphocytes from AAA patients compared to matched controls. 8-oxo-dG immunoreactivity, indicative of oxidative DNA damage, was detected at higher levels in all of the above cell types from AAA patients compared to matched controls. Increased DNA double strand breaks were detected in AAA patients vs controls by nuclear staining for γ-H2AX histone. There was statistically significant inverse correlation between TL and accumulation of oxidative DNA damage in blood lymphocytes from AAA patients. This study shows for the first time that EC and VSMC from AAA have shortened telomeres and oxidative DNA damage. Similar findings were obtained with circulating lymphocytes and keratinocytes, indicating the systemic nature of the disease. Potential translational implications of these findings are discussed.

Renal accumulation of pentosidine in non-diabetic proteinuria-induced renal damage in rats.

PubMed

Waanders, Femke; Greven, Wendela L; Baynes, John W; Thorpe, Suzanne R; Kramer, Andrea B; Nagai, Ryoji; Sakata, Noriyuki; van Goor, Harry; Navis, Gerjan

2005-10-01

Advanced glycation end-products (AGEs) contribute to the pathogenesis of diabetic glomerulopathy. The role of AGEs in non-diabetic renal damage is not well characterized. First, we studied whether renal AGE accumulation occurs in non-diabetic proteinuria-induced renal damage and whether this is ameliorated by renoprotective treatment. Secondly, we investigated whether renal AGE accumulation was due to intrarenal effects of local protein trafficking. Pentosidine was measured (by high-performance liquid chromatography) in rats with chronic bilateral adriamycin nephropathy (AN), untreated and treated with lisinopril. Age-matched healthy rats served as negative controls. Secondly, we compared renal pentosidine in mild proteinuric and non-proteinuric kidneys of unilateral AN and in age-matched controls at 12 and 30 weeks. Intrarenal localization of pentosidine was studied by immunohistochemistry. Renal pentosidine was elevated in untreated AN (0.14+/-0.04 micromol/mol valine) vs healthy controls (0.04+/-0.01 micromol/mol valine, P<0.01). In lisinopril-treated AN, pentosidine was lower (0.09+/-0.02 micromol/mol valine) than in untreated AN (P<0.05). In unilateral proteinuria, pentosidine was similar in non-proteinuric and proteinuric kidneys. After 30 weeks of unilateral proteinuria, pentosidine was increased in both kidneys (0.26+/-0.10 micromol/mol valine) compared with controls (0.18+/-0.06 micromol/mol valine, P<0.05). Pentosidine (AN, week 30) was also increased compared with AN at week 12 (0.16+/-0.06 micromol/mol valine, P<0.01). In control and diseased kidneys, pentosidine was present in the collecting ducts. In proteinuric kidneys, in addition, pentosidine was present in the brush border and cytoplasm of dilated tubular structures, i.e. at sites of proteinuria-induced tubular damage. Pentosidine accumulates in non-diabetic proteinuric kidneys in damaged tubules, and renoprotective treatment by angiotensin-converting enzyme (ACE) inhibitors inhibits AGE accumulation, supporting a relationship between abnormal renal protein trafficking, proteinuria-induced tubular damage and tubular pentosidine accumulation. Future studies, applying specific AGE inhibitors, should be conducted to provide insight into the pathophysiological significance of renal AGEs in non-diabetic renal disease.

Progressive Damage Analysis of Laminated Composite (PDALC)-A Computational Model Implemented in the NASA COMET Finite Element Code

NASA Technical Reports Server (NTRS)

Lo, David C.; Coats, Timothy W.; Harris, Charles E.; Allen, David H.

1996-01-01

A method for analysis of progressive failure in the Computational Structural Mechanics Testbed is presented in this report. The relationship employed in this analysis describes the matrix crack damage and fiber fracture via kinematics-based volume-averaged variables. Damage accumulation during monotonic and cyclic loads is predicted by damage evolution laws for tensile load conditions. The implementation of this damage model required the development of two testbed processors. While this report concentrates on the theory and usage of these processors, a complete list of all testbed processors and inputs that are required for this analysis are included. Sample calculations for laminates subjected to monotonic and cyclic loads were performed to illustrate the damage accumulation, stress redistribution, and changes to the global response that occur during the load history. Residual strength predictions made with this information compared favorably with experimental measurements.

A Lattice-Misfit-Dependent Damage Model for Non-linear Damage Accumulations Under Monotonous Creep in Single Crystal Superalloys

NASA Astrophysics Data System (ADS)

le Graverend, J.-B.

2018-05-01

A lattice-misfit-dependent damage density function is developed to predict the non-linear accumulation of damage when a thermal jump from 1050 °C to 1200 °C is introduced somewhere in the creep life. Furthermore, a phenomenological model aimed at describing the evolution of the constrained lattice misfit during monotonous creep load is also formulated. The response of the lattice-misfit-dependent plasticity-coupled damage model is compared with the experimental results obtained at 140 and 160 MPa on the first generation Ni-based single crystal superalloy MC2. The comparison reveals that the damage model is well suited at 160 MPa and less at 140 MPa because the transfer of stress to the γ' phase occurs for stresses above 150 MPa which leads to larger variations and, therefore, larger effects of the constrained lattice misfit on the lifetime during thermo-mechanical loading.

Effects of hydromechanical loading history and antecedent soil mechanical damage on shallow landslide triggering

NASA Astrophysics Data System (ADS)

Fan, Linfeng; Lehmann, Peter; Or, Dani

2015-10-01

Evidence suggests that the sudden triggering of rainfall-induced shallow landslides is preceded by accumulation of local internal failures in the soil mantle before their abrupt coalescence into a landslide failure plane. The mechanical status of a hillslope at any given time reflects competition between local damage accumulated during antecedent rainfall events and rates of mechanical healing (e.g., rebonding of microcracks and root regrowth). This dynamic interplay between damage accumulation and healing rates determines the initial mechanical state for landslide modeling. We evaluated the roles of these dynamic processes on landslide characteristics and patterns using a hydromechanical landslide-triggering model for a sequence of rainfall scenarios. The progressive nature of soil failure was represented by the fiber bundle model formalism that considers threshold strength of mechanical bonds linking adjacent soil columns and bedrock. The antecedent damage induced by prior rainfall events was expressed by the fraction of broken fibers that gradually regain strength or mechanically heal at rates specific to soil and roots. Results indicate that antecedent damage accelerates landslide initiation relative to pristine (undamaged) hillslopes. The volumes of first triggered landslides increase with increasing antecedent damage; however, for heavily damaged hillslopes, landslide volumes tend to decrease. Elapsed time between rainfall events allows mechanical healing that reduces the effects of antecedent damage. This study proposed a quantitative framework for systematically incorporating hydromechanical loading history and information on precursor events (e.g., such as recorded by acoustic emissions) into shallow landslide hazard assessment.

Effects of fatigue induced damage on the longitudinal fracture resistance of cortical bone.

PubMed

Fletcher, Lloyd; Codrington, John; Parkinson, Ian

2014-07-01

As a composite material, cortical bone accumulates fatigue microdamage through the repetitive loading of everyday activity (e.g. walking). The accumulation of fatigue microdamage is thought to contribute to the occurrence of fragility fractures in older people. Therefore it is beneficial to understand the relationship between microcrack accumulation and the fracture resistance of cortical bone. Twenty longitudinally orientated compact tension fracture specimens were machined from a single bovine femur, ten specimens were assigned to both the control and fatigue damaged groups. The damaged group underwent a fatigue loading protocol to induce microdamage which was assessed via fluorescent microscopy. Following fatigue loading, non-linear fracture resistance tests were undertaken on both the control and damaged groups using the J-integral method. The interaction of the crack path with the fatigue induced damage and inherent toughening mechanisms were then observed using fluorescent microscopy. The results of this study show that fatigue induced damage reduces the initiation toughness of cortical bone and the growth toughness within the damage zone by three distinct mechanisms of fatigue-fracture interaction. Further analysis of the J-integral fracture resistance showed both the elastic and plastic component were reduced in the damaged group. For the elastic component this was attributed to a decreased number of ligament bridges in the crack wake while for the plastic component this was attributed to the presence of pre-existing fatigue microcracks preventing energy absorption by the formation of new microcracks.

Biomarkers of aging in Drosophila.

PubMed

Jacobson, Jake; Lambert, Adrian J; Portero-Otín, Manuel; Pamplona, Reinald; Magwere, Tapiwanashe; Miwa, Satomi; Driege, Yasmine; Brand, Martin D; Partridge, Linda

2010-08-01

Low environmental temperature and dietary restriction (DR) extend lifespan in diverse organisms. In the fruit fly Drosophila, switching flies between temperatures alters the rate at which mortality subsequently increases with age but does not reverse mortality rate. In contrast, DR acts acutely to lower mortality risk; flies switched between control feeding and DR show a rapid reversal of mortality rate. Dietary restriction thus does not slow accumulation of aging-related damage. Molecular species that track the effects of temperatures on mortality but are unaltered with switches in diet are therefore potential biomarkers of aging-related damage. However, molecular species that switch upon instigation or withdrawal of DR are thus potential biomarkers of mechanisms underlying risk of mortality, but not of aging-related damage. Using this approach, we assessed several commonly used biomarkers of aging-related damage. Accumulation of fluorescent advanced glycation end products (AGEs) correlated strongly with mortality rate of flies at different temperatures but was independent of diet. Hence, fluorescent AGEs are biomarkers of aging-related damage in flies. In contrast, five oxidized and glycated protein adducts accumulated with age, but were reversible with both temperature and diet, and are therefore not markers either of acute risk of dying or of aging-related damage. Our approach provides a powerful method for identification of biomarkers of aging.

Biomarkers of ageing in Drosophila

PubMed Central

Jacobson, Jake; Portero-Otín, Manuel; Pamplona, Reinald; Magwere, Tapiwanashe; Miwa, Satomi; Driege, Yasmine; Brand, Martin D.; Partridge, Linda

2015-01-01

Summary Low environmental temperature and dietary restriction (DR) extend lifespan in diverse organisms. In the fruit fly Drosophila, switching flies between temperatures alters the rate at which mortality subsequently increases with age but does not reverse mortality rate. In contrast, DR acts acutely to lower mortality risk; flies switched between control feeding and DR show a rapid reversal of mortality rate. DR thus does not slow accumulation of ageing-related damage. Molecular species that track the effects of temperatures on mortality but are unaltered with switches in diet are therefore potential biomarkers of ageing-related damage. However, molecular species that switch upon instigation or withdrawal of DR are thus potential biomarkers of mechanisms underlying risk of mortality, but not of ageing-related damage. Using this approach, we assessed several commonly used biomarkers of ageing-related damage. Accumulation of fluorescent advanced glycation end products (AGEs) correlated strongly with mortality rate of flies at different temperatures but was independent of diet. Hence fluorescent AGEs are biomarkers of ageing-related damage in flies. In contrast, five oxidised and glycated protein adducts accumulated with age, but were reversible with both temperature and diet, and are therefore not markers either of acute risk of dying or of ageing-related damage. Our approach provides a powerful method for identification of biomarkers of ageing. PMID:20367621

Microstructural evaluation of cumulative fatigue damage in a plant component sample

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

Fukuoka, C.; Nakagawa, Y.G.; Yoshida, K.

1996-12-31

Fatigue damage accumulated in a real plant was evaluated in terms of microstructural conditioning. Microstructural damage induced in laboratory by cyclic deformation near and below the fatigue limit was also examined. A Transmission Electron Microscopy (TEM) technique called the Selected Area Diffraction (SAD) method was employed in this study. In earlier studies, it was found that the SAD value indicating a magnitude of crystallographic misorientation in the substructure (dislocation cells) was increasing with the increase of fatigue damage accumulation. Small samples removed from PWR feed water nozzle welds were examined by the SAD. It was found that the damage statemore » measured by the SAD well agreed with the morphological evidence. Cyclic stresses near or below the fatigue limit were applied to samples taken from a SA508 steel plate at various stresses. The SAD value increased even below the fatigue limit, but there was no sign of microstructural conditioning below the stresses of 50% of the fatigue limit. These results suggested that at stresses below the current design curve (below half the fatigue limit) no microstructural conditioning proceeded. It was concluded that the microstructural method was effective to evaluate damage accumulation in real plant components, and also that the current design curve was adequate in terms of microstructural conditioning state.« less

Fractal dimension based damage identification incorporating multi-task sparse Bayesian learning

NASA Astrophysics Data System (ADS)

Huang, Yong; Li, Hui; Wu, Stephen; Yang, Yongchao

2018-07-01

Sensitivity to damage and robustness to noise are critical requirements for the effectiveness of structural damage detection. In this study, a two-stage damage identification method based on the fractal dimension analysis and multi-task Bayesian learning is presented. The Higuchi’s fractal dimension (HFD) based damage index is first proposed, directly examining the time-frequency characteristic of local free vibration data of structures based on the irregularity sensitivity and noise robustness analysis of HFD. Katz’s fractal dimension is then presented to analyze the abrupt irregularity change of the spatial curve of the displacement mode shape along the structure. At the second stage, the multi-task sparse Bayesian learning technique is employed to infer the final damage localization vector, which borrow the dependent strength of the two fractal dimension based damage indication information and also incorporate the prior knowledge that structural damage occurs at a limited number of locations in a structure in the absence of its collapse. To validate the capability of the proposed method, a steel beam and a bridge, named Yonghe Bridge, are analyzed as illustrative examples. The damage identification results demonstrate that the proposed method is capable of localizing single and multiple damages regardless of its severity, and show superior robustness under heavy noise as well.

Multi-Material ALE with AMR for Modeling Hot Plasmas and Cold Fragmenting Materials

NASA Astrophysics Data System (ADS)

Alice, Koniges; Nathan, Masters; Aaron, Fisher; David, Eder; Wangyi, Liu; Robert, Anderson; David, Benson; Andrea, Bertozzi

2015-02-01

We have developed a new 3D multi-physics multi-material code, ALE-AMR, which combines Arbitrary Lagrangian Eulerian (ALE) hydrodynamics with Adaptive Mesh Refinement (AMR) to connect the continuum to the microstructural regimes. The code is unique in its ability to model hot radiating plasmas and cold fragmenting solids. New numerical techniques were developed for many of the physics packages to work efficiently on a dynamically moving and adapting mesh. We use interface reconstruction based on volume fractions of the material components within mixed zones and reconstruct interfaces as needed. This interface reconstruction model is also used for void coalescence and fragmentation. A flexible strength/failure framework allows for pluggable material models, which may require material history arrays to determine the level of accumulated damage or the evolving yield stress in J2 plasticity models. For some applications laser rays are propagating through a virtual composite mesh consisting of the finest resolution representation of the modeled space. A new 2nd order accurate diffusion solver has been implemented for the thermal conduction and radiation transport packages. One application area is the modeling of laser/target effects including debris/shrapnel generation. Other application areas include warm dense matter, EUV lithography, and material wall interactions for fusion devices.

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

PubMed

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

2016-12-12

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

Stochastic modelling of animal movement.

PubMed

Smouse, Peter E; Focardi, Stefano; Moorcroft, Paul R; Kie, John G; Forester, James D; Morales, Juan M

2010-07-27

Modern animal movement modelling derives from two traditions. Lagrangian models, based on random walk behaviour, are useful for multi-step trajectories of single animals. Continuous Eulerian models describe expected behaviour, averaged over stochastic realizations, and are usefully applied to ensembles of individuals. We illustrate three modern research arenas. (i) Models of home-range formation describe the process of an animal 'settling down', accomplished by including one or more focal points that attract the animal's movements. (ii) Memory-based models are used to predict how accumulated experience translates into biased movement choices, employing reinforced random walk behaviour, with previous visitation increasing or decreasing the probability of repetition. (iii) Lévy movement involves a step-length distribution that is over-dispersed, relative to standard probability distributions, and adaptive in exploring new environments or searching for rare targets. Each of these modelling arenas implies more detail in the movement pattern than general models of movement can accommodate, but realistic empiric evaluation of their predictions requires dense locational data, both in time and space, only available with modern GPS telemetry.

Loss of Homogentisate 1,2-Dioxygenase Activity in Bacillus anthracis Results in Accumulation of Protective Pigment

PubMed Central

Han, Hesong; Iakovenko, Liudmyla; Wilson, Adam C.

2015-01-01

Melanin production is important to the pathogenicity and survival of some bacterial pathogens. In Bacillus anthracis, loss of hmgA, encoding homogentisate 1,2-dioxygenase, results in accumulation of a melanin-like pigment called pyomelanin. Pyomelanin is produced in the mutant as a byproduct of disrupted catabolism of L-tyrosine and L-phenylalanine. Accumulation of pyomelanin protects B. anthracis cells from UV damage but not from oxidative damage. Neither loss of hmgA nor accumulation of pyomelanin alter virulence gene expression, sporulation or germination. This is the first investigation of homogentisate 1,2-dioxygenase activity in the Gram-positive bacteria, and these results provide insight into a conserved aspect of bacterial physiology. PMID:26047497

Studying damage accumulation in martensitic corrosion-resistant steel under cold radial reduction

NASA Astrophysics Data System (ADS)

Karamyshev, A. P.; Nekrasov, I. I.; Nesterenko, A. V.; Parshin, V. S.; Smirnov, S. V.; Shveikin, V. P.; Fedulov, A. A.

2017-12-01

Cold radial reduction of specimens made of the Kh17N2 corrosion-resistant martensitic steel is studied on a lever-type radial-forging machine (RFM). The mechanical properties of the deformed specimens, the "damage accumulation - strain" relation in the specimens are obtained with the application of hydrostatic and fractographic methods for fractured specimens. The damage of the Kh17N2 corrosion-resistant steel is evaluated as a result of an experimental study considering the data of simulation by a complex finite element model of cold deformation on a lever-type RFM.

The fatigue evaluation method for a structural stainless steel using the magnetic sensor composed of three pancake coils

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

Oka, M.; Tsuchida, Y.; Enokizono, M.

May metallic structural materials, such as stainless steels, are currently used in our surroundings. If external force is repeatedly added for many years, it is thought that fatigue damage accumulates in stainless steels. When excessive fatigue damage accumulates in these metals, there is a possibility that they are destroyed by fatigue damage accumulation. Therefore, it is important to know the amount of the fatigue damage they have suffered in order to prevent them from being destroyed. We are developing the fatigue evaluation method for stainless steels with a magnetic sensor composed of three pancake type coils. In this research, themore » inspection object is ferritic stainless steels such as SUS430. The method of fatigue evaluation for ferritic stainless steels uses the three coil type sensor, and shows a good correlation between the number of stress cycles and the output signal of the sensor, even though the correlation between the output signal and an added stress is not completely accurate. This paper describes the evaluation method of fatigue damage in ferritic stainless steel using a magnetic sensor composed of three pancake-type coils.« less

Surface Modified Particles By Multi-Step Addition And Process For The Preparation Thereof

DOEpatents

Cook, Ronald Lee; Elliott, Brian John; Luebben, Silvia DeVito; Myers, Andrew William; Smith, Bryan Matthew

2006-01-17

The present invention relates to a new class of surface modified particles and to a multi-step surface modification process for the preparation of the same. The multi-step surface functionalization process involves two or more reactions to produce particles that are compatible with various host systems and/or to provide the particles with particular chemical reactivities. The initial step comprises the attachment of a small organic compound to the surface of the inorganic particle. The subsequent steps attach additional compounds to the previously attached organic compounds through organic linking groups.

Experimental study of crack initiation and propagation in high- and gigacycle fatigue in titanium alloys

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

Bannikov, Mikhail, E-mail: mbannikov@icmm.ru, E-mail: oborin@icmm.ru, E-mail: naimark@icmm.ru; Oborin, Vladimir, E-mail: mbannikov@icmm.ru, E-mail: oborin@icmm.ru, E-mail: naimark@icmm.ru; Naimark, Oleg, E-mail: mbannikov@icmm.ru, E-mail: oborin@icmm.ru, E-mail: naimark@icmm.ru

Fatigue (high- and gigacycle) crack initiation and its propagation in titanium alloys with coarse and fine grain structure are studied by fractography analysis of fracture surface. Fractured specimens were analyzed by interferometer microscope and SEM to improve methods of monitoring of damage accumulation during fatigue test and to verify the models for fatigue crack kinetics. Fatigue strength was estimated for high cycle fatigue regime using the Luong method [1] by “in-situ” infrared scanning of the sample surface for the step-wise loading history for different grain size metals. Fine grain alloys demonstrated higher fatigue resistance for both high cycle fatigue andmore » gigacycle fatigue regimes. Fracture surface analysis for plane and cylindrical samples was carried out using optical and electronic microscopy method. High resolution profilometry (interferometer-profiler New View 5010) data of fracture surface roughness allowed us to estimate scale invariance (the Hurst exponent) and to establish the existence of two characteristic areas of damage localization (different values of the Hurst exponent). Area 1 with diameter ∼300 μm has the pronounced roughness and is associated with damage localization hotspot. Area 2 shows less amplitude roughness, occupies the rest fracture surface and considered as the trace of the fatigue crack path corresponding to the Paris kinetics.« less

Microstructure Design of Tempered Martensite by Atomistically Informed Full-Field Simulation: From Quenching to Fracture

PubMed Central

Borukhovich, Efim; Du, Guanxing; Stratmann, Matthias; Boeff, Martin; Shchyglo, Oleg; Hartmaier, Alexander; Steinbach, Ingo

2016-01-01

Martensitic steels form a material class with a versatile range of properties that can be selected by varying the processing chain. In order to study and design the desired processing with the minimal experimental effort, modeling tools are required. In this work, a full processing cycle from quenching over tempering to mechanical testing is simulated with a single modeling framework that combines the features of the phase-field method and a coupled chemo-mechanical approach. In order to perform the mechanical testing, the mechanical part is extended to the large deformations case and coupled to crystal plasticity and a linear damage model. The quenching process is governed by the austenite-martensite transformation. In the tempering step, carbon segregation to the grain boundaries and the resulting cementite formation occur. During mechanical testing, the obtained material sample undergoes a large deformation that leads to local failure. The initial formation of the damage zones is observed to happen next to the carbides, while the final damage morphology follows the martensite microstructure. This multi-scale approach can be applied to design optimal microstructures dependent on processing and materials composition. PMID:28773791

Multi-level damage identification with response reconstruction

NASA Astrophysics Data System (ADS)

Zhang, Chao-Dong; Xu, You-Lin

2017-10-01

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

Failure Analysis Study and Long-Term Reliability of Optical Assemblies with End-Face Damage

NASA Technical Reports Server (NTRS)

Kichak, Robert A.; Ott, Melanie N.; Leidecker, Henning W.; Chuska, Richard F.; Greenwell, Christopher J.

2008-01-01

In June 2005, the NESC received a multi-faceted request to determine the long term reliability of fiber optic termini on the ISS that exhibited flaws not manufactured to best workmanship practices. There was a lack of data related to fiber optic workmanship as it affects the long term reliability of optical fiber assemblies in a harsh environment. A fiber optic defect analysis was requested which would find and/or create various types of chips, spalls, scratches, etc., that were identified by the ISS personnel. Once the defects and causes were identified the next step would be to perform long term reliability testing of similar assemblies with similar defects. The goal of the defect analysis would be for the defects to be observed and documented for deterioration of fiber optic performance. Though this report mostly discusses what has been determined as evidence of poor manufacturing processes, it also concludes the majority of the damage could have been avoided with a rigorous process in place.

Multi Resolution In-Situ Testing and Multiscale Simulation for Creep Fatigue Damage Analysis of Alloy 617

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

Liu, Yongming; Oskay, Caglar

This report outlines the research activities that were carried out for the integrated experimental and simulation investigation of creep-fatigue damage mechanism and life prediction of Nickel-based alloy, Inconel 617 at high temperatures (950° and 850°). First, a novel experimental design using a hybrid control technique is proposed. The newly developed experimental technique can generate different combinations of creep and fatigue damage by changing the experimental design parameters. Next, detailed imaging analysis and statistical data analysis are performed to quantify the failure mechanisms of the creep fatigue of alloy 617 at high temperatures. It is observed that the creep damage ismore » directly associated with the internal voids at the grain boundaries and the fatigue damage is directly related to the surface cracking. It is also observed that the classical time fraction approach does not has a good correlation with the experimental observed damage features. An effective time fraction parameter is seen to have an excellent correlation with the material microstructural damage. Thus, a new empirical damage interaction diagram is proposed based on the experimental observations. Following this, a macro level viscoplastic model coupled with damage is developed to simulate the stress/strain response under creep fatigue loadings. A damage rate function based on the hysteresis energy and creep energy is proposed to capture the softening behavior of the material and a good correlation with life prediction and material hysteresis behavior is observed. The simulation work is extended to include the microstructural heterogeneity. A crystal plasticity finite element model considering isothermal and large deformation conditions at the microstructural scale has been developed for fatigue, creep-fatigue as well as creep deformation and rupture at high temperature. The model considers collective dislocation glide and climb of the grains and progressive damage accumulation of the grain boundaries. The glide model incorporates a slip resistance evolution model that characterizes the solute-drag creep effects and can capture well the stress-strain and stress time response of fatigue and creep-fatigue tests at various strain ranges and hold times. In order to accurately capture the creep strains that accumulate particularly at relatively low stress levels, a dislocation climb model has been incorporated into the crystal plasticity modeling framework. The dislocation climb model parameters are calibrated and verified through experimental creep tests performed at 950°. In addition, a cohesive zone model has been fully implemented in the context of the crystal plasticity finite element model to capture the intergranular creep damage. The parameters of the cohesive zone model have been calibrated using available experimental data. The numerical simulations illustrate the capability of the proposed model in capturing damage initiation and growth under creep loads as compared to the experimental observations. The microscale analysis sheds light on the crack initiation sites and propagation patterns within the microstructure. The model is also utilized to investigate the hybrid-controlled creep-fatigue tests and has been found to capture reasonably well the stress-strain response with different hold times and hold stress magnitudes.« less

Tracking Virus Particles in Fluorescence Microscopy Images Using Multi-Scale Detection and Multi-Frame Association.

PubMed

Jaiswal, Astha; Godinez, William J; Eils, Roland; Lehmann, Maik Jorg; Rohr, Karl

2015-11-01

Automatic fluorescent particle tracking is an essential task to study the dynamics of a large number of biological structures at a sub-cellular level. We have developed a probabilistic particle tracking approach based on multi-scale detection and two-step multi-frame association. The multi-scale detection scheme allows coping with particles in close proximity. For finding associations, we have developed a two-step multi-frame algorithm, which is based on a temporally semiglobal formulation as well as spatially local and global optimization. In the first step, reliable associations are determined for each particle individually in local neighborhoods. In the second step, the global spatial information over multiple frames is exploited jointly to determine optimal associations. The multi-scale detection scheme and the multi-frame association finding algorithm have been combined with a probabilistic tracking approach based on the Kalman filter. We have successfully applied our probabilistic tracking approach to synthetic as well as real microscopy image sequences of virus particles and quantified the performance. We found that the proposed approach outperforms previous approaches.

Understanding and simulating the material behavior during multi-particle irradiations

PubMed Central

Mir, Anamul H.; Toulemonde, M.; Jegou, C.; Miro, S.; Serruys, Y.; Bouffard, S.; Peuget, S.

2016-01-01

A number of studies have suggested that the irradiation behavior and damage processes occurring during sequential and simultaneous particle irradiations can significantly differ. Currently, there is no definite answer as to why and when such differences are seen. Additionally, the conventional multi-particle irradiation facilities cannot correctly reproduce the complex irradiation scenarios experienced in a number of environments like space and nuclear reactors. Therefore, a better understanding of multi-particle irradiation problems and possible alternatives are needed. This study shows ionization induced thermal spike and defect recovery during sequential and simultaneous ion irradiation of amorphous silica. The simultaneous irradiation scenario is shown to be equivalent to multiple small sequential irradiation scenarios containing latent damage formation and recovery mechanisms. The results highlight the absence of any new damage mechanism and time-space correlation between various damage events during simultaneous irradiation of amorphous silica. This offers a new and convenient way to simulate and understand complex multi-particle irradiation problems. PMID:27466040

A Multi-Level Decision Fusion Strategy for Condition Based Maintenance of Composite Structures

PubMed Central

Sharif Khodaei, Zahra; Aliabadi, M.H.

2016-01-01

In this work, a multi-level decision fusion strategy is proposed which weighs the Value of Information (VoI) against the intended functions of a Structural Health Monitoring (SHM) system. This paper presents a multi-level approach for three different maintenance strategies in which the performance of the SHM systems is evaluated against its intended functions. Level 1 diagnosis results in damage existence with minimum sensors covering a large area by finding the maximum energy difference for the guided waves propagating in pristine structure and the post-impact state; Level 2 diagnosis provides damage detection and approximate localization using an approach based on Electro-Mechanical Impedance (EMI) measures, while Level 3 characterizes damage (exact location and size) in addition to its detection by utilising a Weighted Energy Arrival Method (WEAM). The proposed multi-level strategy is verified and validated experimentally by detection of Barely Visible Impact Damage (BVID) on a curved composite fuselage panel. PMID:28773910

Involvement of the Reparative DNA Polymerase Pol X of African Swine Fever Virus in the Maintenance of Viral Genome Stability In Vivo

PubMed Central

Redrejo-Rodríguez, Modesto; Rodríguez, Javier M.; Suárez, Cristina; Salas, José

2013-01-01

The function of the African swine fever virus (ASFV) reparative DNA polymerase, Pol X, was investigated in the context of virus infection. Pol X is a late structural protein that localizes at cytoplasmic viral factories during DNA replication. Using an ASFV deletion mutant lacking the Pol X gene, we have shown that Pol X is not required for virus growth in Vero cells or swine macrophages under one-step growth conditions. However, at a low multiplicity of infection, when multiple rounds of replication occur, the growth of the mutant virus is impaired in swine macrophages but not in Vero cells, suggesting that Pol X is needed to repair the accumulated DNA damage. The replication of the mutant virus in Vero cells presents sensitivity to oxidative damage, and mutational analysis of viral DNA shows that deletion of Pol X results in an increase in the mutation frequency in macrophages. Therefore, our data reveal a biological role for ASFV Pol X in the context of the infected cell in the preservation of viral genetic information. PMID:23824796

Lightning Damage of Carbon Fiber/Epoxy Laminates with Interlayers Modified by Nickel-Coated Multi-Walled Carbon Nanotubes

NASA Astrophysics Data System (ADS)

Dong, Qi; Wan, Guoshun; Xu, Yongzheng; Guo, Yunli; Du, Tianxiang; Yi, Xiaosu; Jia, Yuxi

2017-12-01

The numerical model of carbon fiber reinforced polymer (CFRP) laminates with electrically modified interlayers subjected to lightning strike is constructed through finite element simulation, in which both intra-laminar and inter-laminar lightning damages are considered by means of coupled electrical-thermal-pyrolytic analysis method. Then the lightning damage extents including the damage volume and maximum damage depth are investigated. The results reveal that the simulated lightning damages could be qualitatively compared to the experimental counterparts of CFRP laminates with interlayers modified by nickel-coated multi-walled carbon nanotubes (Ni-MWCNTs). With higher electrical conductivity of modified interlayer and more amount of modified interlayers, both damage volume and maximum damage depth are reduced. This work provides an effective guidance to the anti-lightning optimization of CFRP laminates.

Post-treatment of biologically treated wastewater containing organic contaminants using a sequence of H2O2 based advanced oxidation processes: photolysis and catalytic wet oxidation.

PubMed

Rueda-Márquez, J J; Sillanpää, M; Pocostales, P; Acevedo, A; Manzano, M A

2015-03-15

In this paper the feasibility of a multi-barrier treatment (MBT) for the regeneration of synthetic industrial wastewater (SIWW) was evaluated. Industrial pollutants (orange II, phenol, 4-chlorophenol and phenanthrene) were added to the effluent of municipal wastewater treatment plant. The proposed MBT begins with a microfiltration membrane pretreatment (MF), followed by hydrogen peroxide photolysis (H2O2/UVC) and finishing, as a polishing step, with catalytic wet peroxide oxidation (CWPO) using granular activated carbon (GAC) at ambient conditions. During the microfiltration step (0.7 μm) the decrease of suspended solids concentration, turbidity and Escherichia coli in treated water were 88, 94 and 99%, respectively. Also, the effluent's transmittance (254 nm) was increased by 14.7%. Removal of more than 99.9% of all added pollutants, mineralization of 63% of organic compounds and complete disinfection of total coliforms were reached during the H2O2/UVC treatment step (H2O2:TOC w/w ratio = 5 and an UVC average dose accumulated by wastewater 8.80 WUVC s cm(-2)). The power and efficiency of the lamp, the water transmittance and photoreactor geometry are taken into account and a new equation to estimate the accumulated dose in water is suggested. Remaining organic pollutants with a higher oxidation state of carbon atoms (+0.47) and toxic concentration of residual H2O2 were present in the effluent of the H2O2/UVC process. After 2.3 min of contact time with GAC at CWPO step, 90 and 100% of total organic carbon and residual H2O2 were removed, respectively. Also, the wastewater toxicity was studied using Vibrio fischeri and Sparus aurata larvae. The MBT operational and maintenance costs (O&M) was estimated to be 0.59 € m(-3). Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular Clues to Physiological and Premature Ageing Revealed | Center for Cancer Research

Cancer.gov

There are many theories about the molecular basis of ageing. One of the most popular ones postulates that organisms age by accumulating damage to their tissues, cells, and molecules. On the cellular level, ageing is associated with progressive changes in chromatin (a combination of DNA and proteins that makes up chromosomes). These changes include loss of chromatin structure, loss and/or modification of essential proteins, and accumulation of DNA damage.

Acoustic Emission and Damage Accumulation for Various Woven C/SiC Composites Tested in Tension at Room Temperature

NASA Technical Reports Server (NTRS)

Morscher, Gregory; Petko, Jeanne; Kiser, James D.

2002-01-01

Modal acoustic emission (AE) has proven to be an excellent technique to monitor damage accumulation in ceramic matrix composites. In this study, AE was used to monitor tensile load-unload-reload hysteresis tests for a variety of C fiber reinforced, Sic matrix composites. C/SiC composites were reinforced with T-300 and IM7 fibers, had C, multilayer, or pseudo-porous C interphases, and had chemical vapor infiltrated Sic or melt-infiltrated SiC matrices. All of the composites exhibited considerable AE during testing. The extent and nature of the AE activity will be analyzed and discussed in light of matrix cracking and the variety of composite constituents. It is hoped that understanding the nature of stress-dependent damage accumulation in these materials can be of use in life-modeling for these types of composites.

Acoustic Emission and Damage Accumulation for Various Woven C/SiC Composites Tested in Tension at Room Temperature

NASA Technical Reports Server (NTRS)

Morscher, Gregory N.; Petko, Jeanne; Kiser, James D.; Gray, Hugh R. (Technical Monitor)

2002-01-01

Modal acoustic emission (AE) has proven to be an excellent technique to monitor damage accumulation in ceramic matrix composites. In this study, AE was used to monitor tensile load-unload-reload hysteresis tests for a variety of C fiber reinforced, SiC matrix composites. C/SiC composites were reinforced with T300 and IM7 fibers, had C, multilayer, or pseudo-porous C interphases, and had chemical vapor infiltrated SiC or melt-infiltrated SiC matrices. All of the composites exhibited considerable AE during testing. The extent and nature of the AE activity will be analyzed and discussed in light of matrix cracking and the variety of composite constituents. It is hoped that understanding the nature of stress dependent damage accumulation in these materials can be of use in life modeling for these types of composites.

DNA damage leads to progressive replicative decline but extends the life span of long-lived mutant animals.

PubMed

Lans, H; Lindvall, J M; Thijssen, K; Karambelas, A E; Cupac, D; Fensgård, O; Jansen, G; Hoeijmakers, J H J; Nilsen, H; Vermeulen, W

2013-12-01

Human-nucleotide-excision repair (NER) deficiency leads to different developmental and segmental progeroid symptoms of which the pathogenesis is only partially understood. To understand the biological impact of accumulating spontaneous DNA damage, we studied the phenotypic consequences of DNA-repair deficiency in Caenorhabditis elegans. We find that DNA damage accumulation does not decrease the adult life span of post-mitotic tissue. Surprisingly, loss of functional ERCC-1/XPF even further extends the life span of long-lived daf-2 mutants, likely through an adaptive activation of stress signaling. Contrariwise, NER deficiency leads to a striking transgenerational decline in replicative capacity and viability of proliferating cells. DNA damage accumulation induces severe, stochastic impairment of development and growth, which is most pronounced in NER mutants that are also impaired in their response to ionizing radiation and inter-strand crosslinks. These results suggest that multiple DNA-repair pathways can protect against replicative decline and indicate that there might be a direct link between the severity of symptoms and the level of DNA-repair deficiency in patients.

Cross-country transferability of multi-variable damage models

NASA Astrophysics Data System (ADS)

Wagenaar, Dennis; Lüdtke, Stefan; Kreibich, Heidi; Bouwer, Laurens

2017-04-01

Flood damage assessment is often done with simple damage curves based only on flood water depth. Additionally, damage models are often transferred in space and time, e.g. from region to region or from one flood event to another. Validation has shown that depth-damage curve estimates are associated with high uncertainties, particularly when applied in regions outside the area where the data for curve development was collected. Recently, progress has been made with multi-variable damage models created with data-mining techniques, i.e. Bayesian Networks and random forest. However, it is still unknown to what extent and under which conditions model transfers are possible and reliable. Model validations in different countries will provide valuable insights into the transferability of multi-variable damage models. In this study we compare multi-variable models developed on basis of flood damage datasets from Germany as well as from The Netherlands. Data from several German floods was collected using computer aided telephone interviews. Data from the 1993 Meuse flood in the Netherlands is available, based on compensations paid by the government. The Bayesian network and random forest based models are applied and validated in both countries on basis of the individual datasets. A major challenge was the harmonization of the variables between both datasets due to factors like differences in variable definitions, and regional and temporal differences in flood hazard and exposure characteristics. Results of model validations and comparisons in both countries are discussed, particularly in respect to encountered challenges and possible solutions for an improvement of model transferability.

Creep Life of Ceramic Components Using a Finite-Element-Based Integrated Design Program (CARES/CREEP)

NASA Technical Reports Server (NTRS)

Powers, L. M.; Jadaan, O. M.; Gyekenyesi, J. P.

1998-01-01

The desirable properties of ceramics at high temperatures have generated interest in their use for structural application such as in advanced turbine engine systems. Design lives for such systems can exceed 10,000 hours. The long life requirement necessitates subjecting the components to relatively low stresses. The combination of high temperatures and low stresses typically places failure for monolithic ceramics in the creep regime. The objective of this paper is to present a design methodology for predicting the lifetimes of structural components subjected to creep rupture conditions. This methodology utilizes commercially available finite element packages and takes into account the time-varying creep strain distributions (stress relaxation). The creep life, of a component is discretized into short time steps, during which the stress and strain distributions are assumed constant. The damage is calculated for each time step based on a modified Monkman-Grant creep rupture criterion. Failure is assumed to occur when the normalized accumulated damage at any point in the component is greater than or equal to unity. The corresponding time will be the creep rupture life for that component. Examples are chosen to demonstrate the Ceramics Analysis and Reliability Evaluation of Structures/CREEP (CARES/CREEP) integrated design program, which is written for the ANSYS finite element package. Depending on the component size and loading conditions, it was found that in real structures one of two competing failure modes (creep or slow crack growth) will dominate. Applications to benchmark problems and engine components are included.

Creep Life of Ceramic Components Using a Finite-Element-Based Integrated Design Program (CARES/CREEP)

NASA Technical Reports Server (NTRS)

Gyekenyesi, J. P.; Powers, L. M.; Jadaan, O. M.

1998-01-01

The desirable properties of ceramics at high temperatures have generated interest in their use for structural applications such as in advanced turbine systems. Design lives for such systems can exceed 10,000 hours. The long life requirement necessitates subjecting the components to relatively low stresses. The combination of high temperatures and low stresses typically places failure for monolithic ceramics in the creep regime. The objective of this paper is to present a design methodology for predicting the lifetimes of structural components subjected to creep rupture conditions. This methodology utilized commercially available finite element packages and takes into account the time-varying creep strain distributions (stress relaxation). The creep life of a component is discretized into short time steps, during which the stress and strain distributions are assumed constant. The damage is calculated for each time step based on a modified Monkman-Grant creep rupture criterion. Failure is assumed to occur when the normalized accumulated damage at any point in the component is greater than or equal to unity. The corresponding time will be the creep rupture life for that component. Examples are chosen to demonstrate the CARES/CREEP (Ceramics Analysis and Reliability Evaluation of Structures/CREEP) integrated design programs, which is written for the ANSYS finite element package. Depending on the component size and loading conditions, it was found that in real structures one of two competing failure modes (creep or slow crack growth) will dominate. Applications to benechmark problems and engine components are included.

Mitigation effects of silicon rich amendments on heavy metal accumulation in rice (Oryza sativa L.) planted on multi-metal contaminated acidic soil

USDA-ARS?s Scientific Manuscript database

The mechanisms of stabilization by silicon-rich amendments of cadmium, zinc, copper and lead in a multi-metal contaminated acidic soil and the mitigation of metal accumulation in rice were investigated in this study. The results from a pot experiment indicated that the application of fly ash (20 and...

Rotary drum separator system

NASA Technical Reports Server (NTRS)

Barone, Michael R. (Inventor); Murdoch, Karen (Inventor); Scull, Timothy D. (Inventor); Fort, James H. (Inventor)

2009-01-01

A rotary phase separator system generally includes a step-shaped rotary drum separator (RDS) and a motor assembly. The aspect ratio of the stepped drum minimizes power for both the accumulating and pumping functions. The accumulator section of the RDS has a relatively small diameter to minimize power losses within an axial length to define significant volume for accumulation. The pumping section of the RDS has a larger diameter to increase pumping head but has a shorter axial length to minimize power losses. The motor assembly drives the RDS at a low speed for separating and accumulating and a higher speed for pumping.

Effect of Surface Preparation on Residual Stresses in Multilayer Coatings and the Consequences for Disbondment Following Construction Damage and Exposure to In-Service Stress

DOT National Transportation Integrated Search

2009-01-01

Underground pipelines are protected by a combination of cathodic protection and a protective coating. Multi-layer coatings offer protection against corrosion and from mechanical damage during construction or during service. Multi-layer coatings are w...

Damage Accumulation in Cyclically-Loaded Glass-Ceramic Matrix Composites Monitored by Acoustic Emission

PubMed Central

Aggelis, D. G.; Dassios, K. G.; Kordatos, E. Z.; Matikas, T. E.

2013-01-01

Barium osumilite (BMAS) ceramic matrix composites reinforced with SiC-Tyranno fibers are tested in a cyclic loading protocol. Broadband acoustic emission (AE) sensors are used for monitoring the occurrence of different possible damage mechanisms. Improved use of AE indices is proposed by excluding low-severity signals based on waveform parameters, rather than only threshold criteria. The application of such improvements enhances the accuracy of the indices as accumulated damage descriptors. RA-value, duration, and signal energy follow the extension cycles indicating moments of maximum or minimum strain, while the frequency content of the AE signals proves very sensitive to the pull-out mechanism. PMID:24381524

High-sensitivity x-ray mask damage studies employing holographic gratings and phase-shifting interferometry

NASA Astrophysics Data System (ADS)

Hansen, Matthew E.; Cerrina, Franco

1994-05-01

A high-sensitivity holographic and interferometric metrology developed at the Center for X- ray Lithography (CXrL) has been employed to investigate in-plane distortions (IPD) produced in x-ray mask materials. This metrology has been applied to characterize damage to x-ray mask materials exposed to synchrotron radiation. X-ray mask damage and accelerated mask damage studies on silicon nitride and silicon carbide were conducted on the Aladdin ES-1 and ES-2 beamline exposure stations, respectively. Accumulated in-plane distortions due to x-ray irradiation were extracted from the incremental interferometric phase maps to yield IPD vs. dose curves for silicon nitride mask blanks. Silicon carbide mask blanks were subjected to accelerated mask damage in the high flux 2 mm X 2 mm beam of the ES-2 exposure station. An accelerated damage study of silicon carbide has shown no in-plane distortion for an accumulated dose of 800 kJ/cm2 with a measurement sensitivity of less than 5 nm.

Acoustic Emission Analysis of Damage during Compressive Deformation of Amorphous Zr-Based Foams with Aligned, Elongated Pores

NASA Astrophysics Data System (ADS)

Cox, Marie E.; Dunand, David C.

2013-07-01

Acoustic emission methods are used to investigate the evolution of internal microfractural damage during uniaxial compression of amorphous Zr-based foams with aligned, elongated pores. The foams are fabricated by means of densifying a blend of crystalline W powders and amorphous Zr-based powders with two oxygen contents (0.078 and 0.144 wt pct) by warm equal channel angular extrusion, followed by dissolution of the elongated W phase from the fully densified amorphous matrix. For the high-oxygen foams, prior powder boundaries in the amorphous struts promote damage that accumulates during compression, resulting in energy-absorbing properties comparable with the low-oxygen foams without stress-concentrating powder boundaries. The influence of pore orientation on the evolution of microfracture damage and the ability of the foams to accumulate damage without catastrophic failure is also investigated: pores oriented from 24 to 68 deg to the loading direction promote wall bending, resulting in foams with more diffuse damage and better energy-absorbing properties.

Detection and localization of damage using empirical mode decomposition and multilevel support vector machine

NASA Astrophysics Data System (ADS)

Dushyanth, N. D.; Suma, M. N.; Latte, Mrityanjaya V.

2016-03-01

Damage in the structure may raise a significant amount of maintenance cost and serious safety problems. Hence detection of the damage at its early stage is of prime importance. The main contribution pursued in this investigation is to propose a generic optimal methodology to improve the accuracy of positioning of the flaw in a structure. This novel approach involves a two-step process. The first step essentially aims at extracting the damage-sensitive features from the received signal, and these extracted features are often termed the damage index or damage indices, serving as an indicator to know whether the damage is present or not. In particular, a multilevel SVM (support vector machine) plays a vital role in the distinction of faulty and healthy structures. Formerly, when a structure is unveiled as a damaged structure, in the subsequent step, the position of the damage is identified using Hilbert-Huang transform. The proposed algorithm has been evaluated in both simulation and experimental tests on a 6061 aluminum plate with dimensions 300 mm × 300 mm × 5 mm which accordingly yield considerable improvement in the accuracy of estimating the position of the flaw.

An extended diffraction tomography method for quantifying structural damage using numerical Green's functions.

PubMed

Chan, Eugene; Rose, L R Francis; Wang, Chun H

2015-05-01

Existing damage imaging algorithms for detecting and quantifying structural defects, particularly those based on diffraction tomography, assume far-field conditions for the scattered field data. This paper presents a major extension of diffraction tomography that can overcome this limitation and utilises a near-field multi-static data matrix as the input data. This new algorithm, which employs numerical solutions of the dynamic Green's functions, makes it possible to quantitatively image laminar damage even in complex structures for which the dynamic Green's functions are not available analytically. To validate this new method, the numerical Green's functions and the multi-static data matrix for laminar damage in flat and stiffened isotropic plates are first determined using finite element models. Next, these results are time-gated to remove boundary reflections, followed by discrete Fourier transform to obtain the amplitude and phase information for both the baseline (damage-free) and the scattered wave fields. Using these computationally generated results and experimental verification, it is shown that the new imaging algorithm is capable of accurately determining the damage geometry, size and severity for a variety of damage sizes and shapes, including multi-site damage. Some aspects of minimal sensors requirement pertinent to image quality and practical implementation are also briefly discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Ca2+-Permeable AMPARs Mediate Glutamatergic Transmission and Excitotoxic Damage at the Hair Cell Ribbon Synapse.

PubMed

Sebe, Joy Y; Cho, Soyoun; Sheets, Lavinia; Rutherford, Mark A; von Gersdorff, Henrique; Raible, David W

2017-06-21

We report functional and structural evidence for GluA2-lacking Ca 2+ -permeable AMPARs (CP-AMPARs) at the mature hair cell ribbon synapse. By using the methodological advantages of three species (of either sex), we demonstrate that CP-AMPARs are present at the hair cell synapse in an evolutionarily conserved manner. Via a combination of in vivo electrophysiological and Ca 2+ imaging approaches in the larval zebrafish, we show that hair cell stimulation leads to robust Ca 2+ influx into afferent terminals. Prolonged application of AMPA caused loss of afferent terminal responsiveness, whereas blocking CP-AMPARs protects terminals from excitotoxic swelling. Immunohistochemical analysis of AMPAR subunits in mature rat cochlea show regions within synapses lacking the GluA2 subunit. Paired recordings from adult bullfrog auditory synapses demonstrate that CP-AMPARs mediate a major component of glutamatergic transmission. Together, our results support the importance of CP-AMPARs in mediating transmission at the hair cell ribbon synapse. Further, excess Ca 2+ entry via CP-AMPARs may underlie afferent terminal damage following excitotoxic challenge, suggesting that limiting Ca 2+ levels in the afferent terminal may protect against cochlear synaptopathy associated with hearing loss. SIGNIFICANCE STATEMENT A single incidence of noise overexposure causes damage at the hair cell synapse that later leads to neurodegeneration and exacerbates age-related hearing loss. A first step toward understanding cochlear neurodegeneration is to identify the cause of initial excitotoxic damage to the postsynaptic neuron. Using a combination of immunohistochemical, electrophysiological, and Ca 2+ imaging approaches in evolutionarily divergent species, we demonstrate that Ca 2+ -permeable AMPARs (CP-AMPARs) mediate glutamatergic transmission at the adult auditory hair cell synapse. Overexcitation of the terminal causes Ca 2+ accumulation and swelling that can be prevented by blocking CP-AMPARs. We demonstrate that CP-AMPARs mediate transmission at this first-order sensory synapse and that limiting Ca 2+ accumulation in the terminal may protect against hearing loss. Copyright © 2017 the authors 0270-6474/17/376162-14$15.00/0.

Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes

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

Doherty, Kimberly R., E-mail: kimberly.doherty@quintiles.com; Wappel, Robert L.; Talbert, Dominique R.

2013-10-01

Tyrosine kinase inhibitors (TKi) have greatly improved the treatment and prognosis of multiple cancer types. However, unexpected cardiotoxicity has arisen in a subset of patients treated with these agents that was not wholly predicted by pre-clinical testing, which centers around animal toxicity studies and inhibition of the human Ether-à-go-go-Related Gene (hERG) channel. Therefore, we sought to determine whether a multi-parameter test panel assessing the effect of drug treatment on cellular, molecular, and electrophysiological endpoints could accurately predict cardiotoxicity. We examined how 4 FDA-approved TKi agents impacted cell viability, apoptosis, reactive oxygen species (ROS) generation, metabolic status, impedance, and ion channelmore » function in human cardiomyocytes. The 3 drugs clinically associated with severe cardiac adverse events (crizotinib, sunitinib, nilotinib) all proved to be cardiotoxic in our in vitro tests while the relatively cardiac-safe drug erlotinib showed only minor changes in cardiac cell health. Crizotinib, an ALK/MET inhibitor, led to increased ROS production, caspase activation, cholesterol accumulation, disruption in cardiac cell beat rate, and blockage of ion channels. The multi-targeted TKi sunitinib showed decreased cardiomyocyte viability, AMPK inhibition, increased lipid accumulation, disrupted beat pattern, and hERG block. Nilotinib, a second generation Bcr-Abl inhibitor, led to increased ROS generation, caspase activation, hERG block, and an arrhythmic beat pattern. Thus, each drug showed a unique toxicity profile that may reflect the multiple mechanisms leading to cardiotoxicity. This study demonstrates that a multi-parameter approach can provide a robust characterization of drug-induced cardiomyocyte damage that can be leveraged to improve drug safety during early phase development. - Highlights: • TKi with known adverse effects show unique cardiotoxicity profiles in this panel. • Crizotinib increases ROS, apoptosis, and cholesterol as well as alters beat rate. • Sunitinib inhibits AMPK, increases lipids and alters the cardiac beat pattern. • Nilotinib causes ROS and caspase activation, decreased lipids and arrhythmia. • Erlotinib did not impact ROS, caspase, or lipid levels or affect the beat pattern.« less

Automating the evaluation of flood damages: methodology and potential gains

NASA Astrophysics Data System (ADS)

Eleutério, Julian; Martinez, Edgar Daniel

2010-05-01

The evaluation of flood damage potential consists of three main steps: assessing and processing data, combining data and calculating potential damages. The first step consists of modelling hazard and assessing vulnerability. In general, this step of the evaluation demands more time and investments than the others. The second step of the evaluation consists of combining spatial data on hazard with spatial data on vulnerability. Geographic Information System (GIS) is a fundamental tool in the realization of this step. GIS software allows the simultaneous analysis of spatial and matrix data. The third step of the evaluation consists of calculating potential damages by means of damage-functions or contingent analysis. All steps demand time and expertise. However, the last two steps must be realized several times when comparing different management scenarios. In addition, uncertainty analysis and sensitivity test are made during the second and third steps of the evaluation. The feasibility of these steps could be relevant in the choice of the extent of the evaluation. Low feasibility could lead to choosing not to evaluate uncertainty or to limit the number of scenario comparisons. Several computer models have been developed over time in order to evaluate the flood risk. GIS software is largely used to realise flood risk analysis. The software is used to combine and process different types of data, and to visualise the risk and the evaluation results. The main advantages of using a GIS in these analyses are: the possibility of "easily" realising the analyses several times, in order to compare different scenarios and study uncertainty; the generation of datasets which could be used any time in future to support territorial decision making; the possibility of adding information over time to update the dataset and make other analyses. However, these analyses require personnel specialisation and time. The use of GIS software to evaluate the flood risk requires personnel with a double professional specialisation. The professional should be proficient in GIS software and in flood damage analysis (which is already a multidisciplinary field). Great effort is necessary in order to correctly evaluate flood damages, and the updating and the improvement of the evaluation over time become a difficult task. The automation of this process should bring great advance in flood management studies over time, especially for public utilities. This study has two specific objectives: (1) show the entire process of automation of the second and third steps of flood damage evaluations; and (2) analyse the induced potential gains in terms of time and expertise needed in the analysis. A programming language is used within GIS software in order to automate hazard and vulnerability data combination and potential damages calculation. We discuss the overall process of flood damage evaluation. The main result of this study is a computational tool which allows significant operational gains on flood loss analyses. We quantify these gains by means of a hypothetical example. The tool significantly reduces the time of analysis and the needs for expertise. An indirect gain is that sensitivity and cost-benefit analyses can be more easily realized.

The Study of the Relationship between Probabilistic Design and Axiomatic Design Methodology. Volume 3

NASA Technical Reports Server (NTRS)

Onwubiko, Chin-Yere; Onyebueke, Landon

1996-01-01

Structural failure is rarely a "sudden death" type of event, such sudden failures may occur only under abnormal loadings like bomb or gas explosions and very strong earthquakes. In most cases, structures fail due to damage accumulated under normal loadings such as wind loads, dead and live loads. The consequence of cumulative damage will affect the reliability of surviving components and finally causes collapse of the system. The cumulative damage effects on system reliability under time-invariant loadings are of practical interest in structural design and therefore will be investigated in this study. The scope of this study is, however, restricted to the consideration of damage accumulation as the increase in the number of failed components due to the violation of their strength limits.

Genome-wide RNAi screening identifies protein damage as a regulator of osmoprotective gene expression.

PubMed

Lamitina, Todd; Huang, Chunyi George; Strange, Kevin

2006-08-08

The detection, stabilization, and repair of stress-induced damage are essential requirements for cellular life. All cells respond to osmotic stress-induced water loss with increased expression of genes that mediate accumulation of organic osmolytes, solutes that function as chemical chaperones and restore osmotic homeostasis. The signals and signaling mechanisms that regulate osmoprotective gene expression in animal cells are poorly understood. Here, we show that gpdh-1 and gpdh-2, genes that mediate the accumulation of the organic osmolyte glycerol, are essential for survival of the nematode Caenorhabditis elegans during osmotic stress. Expression of GFP driven by the gpdh-1 promoter (P(gpdh-1)::GFP) is detected only during hypertonic stress but is not induced by other stressors. Using P(gpdh-1)::GFP expression as a phenotype, we screened approximately 16,000 genes by RNAi feeding and identified 122 that cause constitutive activation of gpdh-1 expression and glycerol accumulation. Many of these genes function to regulate protein translation and cotranslational protein folding and to target and degrade denatured proteins, suggesting that the accumulation of misfolded proteins functions as a signal to activate osmoprotective gene expression and organic osmolyte accumulation in animal cells. Consistent with this hypothesis, 73% of these protein-homeostasis genes have been shown to slow age-dependent protein aggregation in C. elegans. Because diverse environmental stressors and numerous disease states result in protein misfolding, mechanisms must exist that discriminate between osmotically induced and other forms of stress-induced protein damage. Our findings provide a foundation for understanding how these damage-selectivity mechanisms function.

Genome-wide RNAi screening identifies protein damage as a regulator of osmoprotective gene expression

PubMed Central

Lamitina, Todd; Huang, Chunyi George; Strange, Kevin

2006-01-01

The detection, stabilization, and repair of stress-induced damage are essential requirements for cellular life. All cells respond to osmotic stress-induced water loss with increased expression of genes that mediate accumulation of organic osmolytes, solutes that function as chemical chaperones and restore osmotic homeostasis. The signals and signaling mechanisms that regulate osmoprotective gene expression in animal cells are poorly understood. Here, we show that gpdh-1 and gpdh-2, genes that mediate the accumulation of the organic osmolyte glycerol, are essential for survival of the nematode Caenorhabditis elegans during osmotic stress. Expression of GFP driven by the gpdh-1 promoter (Pgpdh-1::GFP) is detected only during hypertonic stress but is not induced by other stressors. Using Pgpdh-1::GFP expression as a phenotype, we screened ≈16,000 genes by RNAi feeding and identified 122 that cause constitutive activation of gpdh-1 expression and glycerol accumulation. Many of these genes function to regulate protein translation and cotranslational protein folding and to target and degrade denatured proteins, suggesting that the accumulation of misfolded proteins functions as a signal to activate osmoprotective gene expression and organic osmolyte accumulation in animal cells. Consistent with this hypothesis, 73% of these protein-homeostasis genes have been shown to slow age-dependent protein aggregation in C. elegans. Because diverse environmental stressors and numerous disease states result in protein misfolding, mechanisms must exist that discriminate between osmotically induced and other forms of stress-induced protein damage. Our findings provide a foundation for understanding how these damage-selectivity mechanisms function. PMID:16880390

Prediction of failure in notched carbon-fibre-reinforced-polymer laminates under multi-axial loading.

PubMed

Tan, J L Y; Deshpande, V S; Fleck, N A

2016-07-13

A damage-based finite-element model is used to predict the fracture behaviour of centre-notched quasi-isotropic carbon-fibre-reinforced-polymer laminates under multi-axial loading. Damage within each ply is associated with fibre tension, fibre compression, matrix tension and matrix compression. Inter-ply delamination is modelled by cohesive interfaces using a traction-separation law. Failure envelopes for a notch and a circular hole are predicted for in-plane multi-axial loading and are in good agreement with the observed failure envelopes from a parallel experimental study. The ply-by-ply (and inter-ply) damage evolution and the critical mechanisms of ultimate failure also agree with the observed damage evolution. It is demonstrated that accurate predictions of notched compressive strength are obtained upon employing the band broadening stress for microbuckling, highlighting the importance of this damage mode in compression. This article is part of the themed issue 'Multiscale modelling of the structural integrity of composite materials'. © 2016 The Author(s).

Multi-step routes of capuchin monkeys in a laser pointer traveling salesman task.

PubMed

Howard, Allison M; Fragaszy, Dorothy M

2014-09-01

Prior studies have claimed that nonhuman primates plan their routes multiple steps in advance. However, a recent reexamination of multi-step route planning in nonhuman primates indicated that there is no evidence for planning more than one step ahead. We tested multi-step route planning in capuchin monkeys using a pointing device to "travel" to distal targets while stationary. This device enabled us to determine whether capuchins distinguish the spatial relationship between goals and themselves and spatial relationships between goals and the laser dot, allocentrically. In Experiment 1, two subjects were presented with identical food items in Near-Far (one item nearer to subject) and Equidistant (both items equidistant from subject) conditions with a laser dot visible between the items. Subjects moved the laser dot to the items using a joystick. In the Near-Far condition, one subject demonstrated a bias for items closest to self but the other subject chose efficiently. In the second experiment, subjects retrieved three food items in similar Near-Far and Equidistant arrangements. Both subjects preferred food items nearest the laser dot and showed no evidence of multi-step route planning. We conclude that these capuchins do not make choices on the basis of multi-step look ahead strategies. © 2014 Wiley Periodicals, Inc.

77 FR 65617 - Airworthiness Directives; Bombardier, Inc. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-30

... part number and replacing the affected parking brake hydraulic accumulator, and relocating the parking brake accumulator, on the subject airplanes. We are issuing this AD to prevent failure of the screw caps and/or end caps of the parking brake hydraulic accumulator, which could result in damage to the...

Multi-objective optimization of process parameters of multi-step shaft formed with cross wedge rolling based on orthogonal test

NASA Astrophysics Data System (ADS)

Han, S. T.; Shu, X. D.; Shchukin, V.; Kozhevnikova, G.

2018-06-01

In order to achieve reasonable process parameters in forming multi-step shaft by cross wedge rolling, the research studied the rolling-forming process multi-step shaft on the DEFORM-3D finite element software. The interactive orthogonal experiment was used to study the effect of the eight parameters, the first section shrinkage rate φ1, the first forming angle α1, the first spreading angle β1, the first spreading length L1, the second section shrinkage rate φ2, the second forming angle α2, the second spreading angle β2 and the second spreading length L2, on the quality of shaft end and the microstructure uniformity. By using the fuzzy mathematics comprehensive evaluation method and the extreme difference analysis, the influence degree of the process parameters on the quality of the multi-step shaft is obtained: β2>φ2L1>α1>β1>φ1>α2L2. The results of the study can provide guidance for obtaining multi-stepped shaft with high mechanical properties and achieving near net forming without stub bar in cross wedge rolling.

Discovery of multi-ring basins - Gestalt perception in planetary science

NASA Technical Reports Server (NTRS)

Hartmann, W. K.

1981-01-01

Early selenographers resolved individual structural components of multi-ring basin systems but missed the underlying large-scale multi-ring basin patterns. The recognition of multi-ring basins as a general class of planetary features can be divided into five steps. Gilbert (1893) took a first step in recognizing radial 'sculpture' around the Imbrium basin system. Several writers through the 1940's rediscovered the radial sculpture and extended this concept by describing concentric rings around several circular maria. Some reminiscences are given about the fourth step - discovery of the Orientale basin and other basin systems by rectified lunar photography at the University of Arizona in 1961-62. Multi-ring basins remained a lunar phenomenon until the fifth step - discovery of similar systems of features on other planets, such as Mars (1972), Mercury (1974), and possibly Callisto and Ganymede (1979). This sequence is an example of gestalt recognition whose implications for scientific research are discussed.

Neuroprotective Role of a Brain-Enriched Tyrosine Phosphatase, STEP, in Focal Cerebral Ischemia

PubMed Central

Deb, Ishani; Manhas, Namratta; Poddar, Ranjana; Rajagopal, Sathyanarayanan; Allan, Andrea M.; Lombroso, Paul J.; Rosenberg, Gary A.; Candelario-Jalil, Eduardo

2013-01-01

The striatal-enriched phosphatase (STEP) is a component of the NMDA-receptor-mediated excitotoxic signaling pathway, which plays a key role in ischemic brain injury. Using neuronal cultures and a rat model of ischemic stroke, we show that STEP plays an initial role in neuroprotection, during the insult, by disrupting the p38 MAPK pathway. Degradation of active STEP during reperfusion precedes ischemic brain damage and is associated with secondary activation of p38 MAPK. Application of a cell-permeable STEP-derived peptide that is resistant to degradation and binds to p38 MAPK protects cultured neurons from hypoxia-reoxygenation injury and reduces ischemic brain damage when injected up to 6 h after the insult. Conversely, genetic deletion of STEP in mice leads to sustained p38 MAPK activation and exacerbates brain injury and neurological deficits after ischemia. Administration of the STEP-derived peptide at the onset of reperfusion not only prevents the sustained p38 MAPK activation but also reduces ischemic brain damage in STEP KO mice. The findings indicate a neuroprotective role of STEP and suggest a potential role of the STEP-derived peptide in stroke therapy. PMID:24198371

The influence of rock strength on erosion processes and river morphology in central Arizona: the accumulation of damage from macro-abrasion

NASA Astrophysics Data System (ADS)

Larimer, J. E.; Yanites, B.

2017-12-01

River morphology reflects the interaction between the driving forces of erosion and the resisting properties of bedrock that limit erosion. Changes in energy dissipation at the riverbed are indicated by differences in channel geometry. To erode at the same rate, stronger rocks require more energy, and thus, an adjustment in river slope or width is necessary to accomplish this work. Therefore, morphological changes should reflect differences in the rock strength properties most relevant to the dominant erosion process. We investigate this hypothesis by comparing river morphology and rock-strength properties of reaches subject to different processes. Streams in Prescott National Forest, AZ expose bedrock through a variety of lithologies, which provides a natural testing ground. Measurements include channel geometry, surface P-wave velocity, fracture spacing, and bedload grain size distribution of 150 individual reaches, as well as 260 tensile and compressive-strength tests and P-wave velocity of cores up to depths of 20 cm. Based on observations, we infer that fluvial erosion processes in this region generally fall into three domains: (1) grain by grain abrasion, (2) progressive failure by damage accumulation due to bedload impacts or `macro-abrasion', and (3) `plucking' of jointed rocks. We focus analyses on the accumulation of damage from sub-critical stresses that weakens the surface of the bedrock, potentially leading to macroscopic fractures, fatigue, and rock failure. This plays a dual role facilitating the ease with which abrasion removes material and increasing the rate of production of pluck-able particles. We estimate the `damage potential' of saltating bedload using water discharge time-series, sediment transport models and grain size distribution. To determine the resistance to damage accumulation among different rocks, we measure the evolution of damage in core samples under uniaxial loading using strain energy and inherent flaw theory. Preliminary results suggest that tensile strength is a good predictor of channel morphology in abrasion dominated reaches, morphology is better predicted through a damage perspective in macro-abrasion dominated reaches, and reduction in P-wave velocity near the surface correlates with damage susceptibility.

Raster microdiffraction with synchrotron radiation of hydrated biopolymers with nanometre step-resolution: case study of starch granules

PubMed Central

Riekel, C.; Burghammer, M.; Davies, R. J.; Di Cola, E.; König, C.; Lemke, H.T.; Putaux, J.-L.; Schöder, S.

2010-01-01

X-ray radiation damage propagation is explored for hydrated starch granules in order to reduce the step resolution in raster-microdiffraction experiments to the nanometre range. Radiation damage was induced by synchrotron radiation microbeams of 5, 1 and 0.3 µm size with ∼0.1 nm wavelength in B-type potato, Canna edulis and Phajus grandifolius starch granules. A total loss of crystallinity of granules immersed in water was found at a dose of ∼1.3 photons nm−3. The temperature dependence of radiation damage suggests that primary radiation damage prevails up to about 120 K while secondary radiation damage becomes effective at higher temperatures. Primary radiation damage remains confined to the beam track at 100 K. Propagation of radiation damage beyond the beam track at room temperature is assumed to be due to reactive species generated principally by water radiolysis induced by photoelectrons. By careful dose selection during data collection, raster scans with 500 nm step-resolution could be performed for granules immersed in water. PMID:20975219

77 FR 35304 - Airworthiness Directives; Costruzioni Aeronautiche Tecnam srl Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-13

... the LG emergency accumulator and the LG retraction/extension system. You may obtain further... 300 hours TIS, inspect the LG emergency accumulator and the LG retraction/extension system for damage...

77 FR 56991 - Airworthiness Directives; Costruzioni Aeronautiche Tecnam srl Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-17

... as to inspect after the installation the LG emergency accumulator and the LG retraction/extension... the LG emergency accumulator and the LG retraction/extension system for damage and leakage following...

A Space-Based Perspective of the 2017 Hurricane Season from the Global Precipitation Measurement (GPM) Mission

NASA Astrophysics Data System (ADS)

Skofronick Jackson, G.; Petersen, W. A.; Huffman, G. J.; Kirschbaum, D.; Wolff, D. B.; Tan, J.; Zavodsky, B.

2017-12-01

The Global Precipitation Measurement (GPM) mission collected unique, near real time 3-D satellite-based views of hurricanes in 2017 together with estimated precipitation accumulation using merged satellite data for scientific studies and societal applications. Central to GPM is the NASA-JAXA GPM Core Observatory (CO). The GPM-CO carries an advanced dual-frequency precipitation radar (DPR) and a well-calibrated, multi-frequency passive microwave radiometer that together serve as an on orbit reference for precipitation measurements made by the international GPM satellite constellation. GPM-CO overpasses of major Hurricanes such as Harvey, Irma, Maria, and Ophelia revealed intense convective structures in DPR radar reflectivity together with deep ice-phase microphysics in both the eyewalls and outer rain bands. Of considerable scientific interest, and yet to be determined, will be DPR-diagnosed characteristics of the rain drop size distribution as a function of convective structure, intensity and microphysics. The GPM-CO active/passive suite also provided important decision support information. For example, the National Hurricane Center used GPM-CO observations as a tool to inform track and intensity estimates in their forecast briefings. Near-real-time rainfall accumulation from the Integrated Multi-satellitE Retrievals for GPM (IMERG) was also provided via the NASA SPoRT team to Puerto Rico following Hurricane Maria when ground-based radar systems on the island failed. Comparisons between IMERG, NOAA Multi-Radar Multi-Sensor data, and rain gauge rainfall accumulations near Houston, Texas during Hurricane Harvey revealed spatial biases between ground and IMERG satellite estimates, and a general underestimation of IMERG rain accumulations associated with infrared observations, collectively illustrating the difficulty of measuring rainfall in hurricanes.GPM data continue to advance scientific research on tropical cyclone intensification and structure, and contribute to societal and operational applications for improving storm forecasting. Precipitation accumulations from the multi-satellite product IMERG also contribute to a better understanding of rainfall accumulation, inland flooding, and landslide susceptibility during the passage of these major events.

Preliminary Results of Earthquake-Induced Building Damage Detection with Object-Based Image Classification

NASA Astrophysics Data System (ADS)

Sabuncu, A.; Uca Avci, Z. D.; Sunar, F.

2016-06-01

Earthquakes are the most destructive natural disasters, which result in massive loss of life, infrastructure damages and financial losses. Earthquake-induced building damage detection is a very important step after earthquakes since earthquake-induced building damage is one of the most critical threats to cities and countries in terms of the area of damage, rate of collapsed buildings, the damage grade near the epicenters and also building damage types for all constructions. Van-Ercis (Turkey) earthquake (Mw= 7.1) was occurred on October 23th, 2011; at 10:41 UTC (13:41 local time) centered at 38.75 N 43.36 E that places the epicenter about 30 kilometers northern part of the city of Van. It is recorded that, 604 people died and approximately 4000 buildings collapsed or seriously damaged by the earthquake. In this study, high-resolution satellite images of Van-Ercis, acquired by Quickbird-2 (Digital Globe Inc.) after the earthquake, were used to detect the debris areas using an object-based image classification. Two different land surfaces, having homogeneous and heterogeneous land covers, were selected as case study areas. As a first step of the object-based image processing, segmentation was applied with a convenient scale parameter and homogeneity criterion parameters. As a next step, condition based classification was used. In the final step of this preliminary study, outputs were compared with streetview/ortophotos for the verification and evaluation of the classification accuracy.

Impact of user influence on information multi-step communication in a micro-blog

NASA Astrophysics Data System (ADS)

Wu, Yue; Hu, Yong; He, Xiao-Hai; Deng, Ken

2014-06-01

User influence is generally considered as one of the most critical factors that affect information cascading spreading. Based on this common assumption, this paper proposes a theoretical model to examine user influence on the information multi-step communication in a micro-blog. The multi-steps of information communication are divided into first-step and non-first-step, and user influence is classified into five dimensions. Actual data from the Sina micro-blog is collected to construct the model by means of an approach based on structural equations that uses the Partial Least Squares (PLS) technique. Our experimental results indicate that the dimensions of the number of fans and their authority significantly impact the information of first-step communication. Leader rank has a positive impact on both first-step and non-first-step communication. Moreover, global centrality and weight of friends are positively related to the information non-first-step communication, but authority is found to have much less relation to it.

Amyloid and intracellular accumulation of BRI2.

PubMed

Garringer, Holly J; Sammeta, Neeraja; Oblak, Adrian; Ghetti, Bernardino; Vidal, Ruben

2017-04-01

Familial British dementia (FBD) and familial Danish dementia (FDD) are caused by mutations in the BRI 2 gene. These diseases are characterized clinically by progressive dementia and ataxia and neuropathologically by amyloid deposits and neurofibrillary tangles. Herein, we investigate BRI 2 protein accumulation in FBD, FDD, Alzheimer disease and Gerstmann-Sträussler-Scheinker disease. In FBD and FDD, we observed reduced processing of the mutant BRI 2 pro-protein, which was found accumulating intracellularly in the Golgi of neurons and glial cells. In addition, we observed an accumulation of a mature form of BRI 2 protein in dystrophic neurites, surrounding amyloid cores. Accumulation of BRI 2 was also observed in dystrophic neurites of Alzheimer disease and Gerstmann-Sträussler-Scheinker disease cases. Although it remains to be determined whether intracellular accumulation of BRI 2 may lead to cell damage in these degenerative diseases, our study provides new insights into the role of mutant BRI 2 in the pathogenesis of FBD and FDD and implicates BRI 2 as a potential indicator of neuritic damage in diseases characterized by cerebral amyloid deposition. Copyright © 2016 Elsevier Inc. All rights reserved.

Amyloid and intracellular accumulation of BRI2

PubMed Central

Garringer, Holly J.; Sammeta, Neeraja; Oblak, Adrian; Ghetti, Bernardino; Vidal, Ruben

2016-01-01

Familial British dementia (FBD) and familial Danish dementia (FDD) are caused by mutations in the BRI2 gene. These diseases are characterized clinically by progressive dementia and ataxia and neuropathologically by amyloid deposits and neurofibrillary tangles. Herein, we investigate BRI2 protein accumulation in FBD, FDD, Alzheimer disease and Gerstmann-Sträussler-Scheinker disease. In FBD and FDD, we observed reduced processing of the mutant BRI2 pro-protein, which was found accumulating intracellularly in the Golgi of neurons and glial cells. In addition, we observed an accumulation of a mature form of BRI2 protein in dystrophic neurites, surrounding amyloid cores. Accumulation of BRI2 was also observed in dystrophic neurites of Alzheimer disease and Gerstmann-Sträussler-Scheinker disease cases. Although it remains to be determined whether intracellular accumulation of BRI2 may lead to cell damage in these degenerative diseases, our study provides new insights into the role of mutant BRI2 in the pathogenesis of FBD and FDD and implicates BRI2 as a potential indicator of neuritic damage in diseases characterized by cerebral amyloid deposition. PMID:28131015

Earthquake Vulnerability Assessment for Hospital Buildings Using a Gis-Based Group Multi Criteria Decision Making Approach: a Case Study of Tehran, Iran

NASA Astrophysics Data System (ADS)

Delavar, M. R.; Moradi, M.; Moshiri, B.

2015-12-01

Nowadays, urban areas are threatened by a number of natural hazards such as flood, landslide and earthquake. They can cause huge damages to buildings and human beings which necessitates disaster mitigation and preparation. One of the most important steps in disaster management is to understand all impacts and effects of disaster on urban facilities. Given that hospitals take care of vulnerable people reaction of hospital buildings against earthquake is vital. In this research, the vulnerability of hospital buildings against earthquake is analysed. The vulnerability of buildings is related to a number of criteria including age of building, number of floors, the quality of materials and intensity of the earthquake. Therefore, the problem of seismic vulnerability assessment is a multi-criteria assessment problem and multi criteria decision making methods can be used to address the problem. In this paper a group multi criteria decision making model is applied because using only one expert's judgments can cause biased vulnerability maps. Sugeno integral which is able to take into account the interaction among criteria is employed to assess the vulnerability degree of buildings. Fuzzy capacities which are similar to layer weights in weighted linear averaging operator are calculated using particle swarm optimization. Then, calculated fuzzy capacities are included into the model to compute a vulnerability degree for each hospital.

Answering the ultimate question "what is the proximal cause of aging?".

PubMed

Blagosklonny, Mikhail V

2012-12-01

Recent discoveries suggest that aging is neither driven by accumulation of molecular damage of any cause, nor by random damage of any kind. Some predictions of a new theory, quasi-programmed hyperfunction, have already been confirmed and a clinically-available drug slows aging and delays diseases in animals. The relationship between diseases and aging becomes easily apparent. Yet, the essence of aging turns out to be so startling that the theory cannot be instantly accepted and any possible arguments are raised for its disposal. I discuss that these arguments actually support a new theory. Are any questions remaining? And might accumulation of molecular damage still play a peculiar role in aging?

Answering the ultimate question “What is the Proximal Cause of Aging?”

PubMed Central

Blagosklonny, Mikhail V.

2012-01-01

Recent discoveries suggest that aging is neither driven by accumulation of molecular damage of any cause, nor by random damage of any kind. Some predictions of a new theory, quasi-programmed hyperfunction, have already been confirmed and a clinically-available drug slows aging and delays diseases in animals. The relationship between diseases and aging becomes easily apparent. Yet, the essence of aging turns out to be so startling that the theory cannot be instantly accepted and any possible arguments are raised for its disposal. I discuss that these arguments actually support a new theory. Are any questions remaining? And might accumulation of molecular damage still play a peculiar role in aging? PMID:23425777

OBJECT KINETIC MONTE CARLO SIMULATIONS OF RADIATION DAMAGE IN BULK TUNGSTEN

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

Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard L.

2015-09-22

We used our recently developed lattice based OKMC code; KSOME [1] to carryout simulations of radiation damage in bulk W. We study the effect of dimensionality of self interstitial atom (SIA) diffusion i.e. 1D versus 3D on the defect accumulation during irradiation with a primary knock-on atom (PKA) energy of 100 keV at 300 K for the dose rates of 10-5 and 10-6 dpa/s. As expected 3D SIA diffusion significantly reduces damage accumulation due to increased probability of recombination events. In addition, dose rate, over the limited range examined here, appears to have no effect in both cases of SIAmore » diffusion.« less

Kinetics of Accumulation of Damage in Surface Layers of Lithium-Containing Aluminum Alloys in Fatigue Tests with Rigid Loading Cycle and Corrosive Effect of Environment

NASA Astrophysics Data System (ADS)

Morozova, L. V.; Zhegina, I. P.; Grigorenko, V. B.; Fomina, M. A.

2017-07-01

High-resolution methods of metal physics research including electron, laser and optical microscopy are used to study the kinetics of the accumulation of slip lines and bands and the corrosion damage in the plastic zone of specimens of aluminum-lithium alloys 1441 and B-1469 in rigid-cycle fatigue tests under the joint action of applied stresses and corrosive environment. The strain parameters (the density of slip bands, the sizes of plastic zones near fracture, the surface roughness in singled-out zones) and the damage parameters (the sizes of pits and the pitting area) are evaluated.

Advanced Mitigation Process (AMP) for Improving Laser Damage Threshold of Fused Silica Optics

NASA Astrophysics Data System (ADS)

Ye, Xin; Huang, Jin; Liu, Hongjie; Geng, Feng; Sun, Laixi; Jiang, Xiaodong; Wu, Weidong; Qiao, Liang; Zu, Xiaotao; Zheng, Wanguo

2016-08-01

The laser damage precursors in subsurface of fused silica (e.g. photosensitive impurities, scratches and redeposited silica compounds) were mitigated by mineral acid leaching and HF etching with multi-frequency ultrasonic agitation, respectively. The comparison of scratches morphology after static etching and high-frequency ultrasonic agitation etching was devoted in our case. And comparison of laser induce damage resistance of scratched and non-scratched fused silica surfaces after HF etching with high-frequency ultrasonic agitation were also investigated in this study. The global laser induce damage resistance was increased significantly after the laser damage precursors were mitigated in this case. The redeposition of reaction produce was avoided by involving multi-frequency ultrasonic and chemical leaching process. These methods made the increase of laser damage threshold more stable. In addition, there is no scratch related damage initiations found on the samples which were treated by Advanced Mitigation Process.

Advanced Mitigation Process (AMP) for Improving Laser Damage Threshold of Fused Silica Optics

PubMed Central

Ye, Xin; Huang, Jin; Liu, Hongjie; Geng, Feng; Sun, Laixi; Jiang, Xiaodong; Wu, Weidong; Qiao, Liang; Zu, Xiaotao; Zheng, Wanguo

2016-01-01

The laser damage precursors in subsurface of fused silica (e.g. photosensitive impurities, scratches and redeposited silica compounds) were mitigated by mineral acid leaching and HF etching with multi-frequency ultrasonic agitation, respectively. The comparison of scratches morphology after static etching and high-frequency ultrasonic agitation etching was devoted in our case. And comparison of laser induce damage resistance of scratched and non-scratched fused silica surfaces after HF etching with high-frequency ultrasonic agitation were also investigated in this study. The global laser induce damage resistance was increased significantly after the laser damage precursors were mitigated in this case. The redeposition of reaction produce was avoided by involving multi-frequency ultrasonic and chemical leaching process. These methods made the increase of laser damage threshold more stable. In addition, there is no scratch related damage initiations found on the samples which were treated by Advanced Mitigation Process. PMID:27484188

Aluminum and Alzheimer's disease: after a century of controversy, is there a plausible link?

PubMed

Tomljenovic, Lucija

2011-01-01

The brain is a highly compartmentalized organ exceptionally susceptible to accumulation of metabolic errors. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of the elderly and is characterized by regional specificity of neural aberrations associated with higher cognitive functions. Aluminum (Al) is the most abundant neurotoxic metal on earth, widely bioavailable to humans and repeatedly shown to accumulate in AD-susceptible neuronal foci. In spite of this, the role of Al in AD has been heavily disputed based on the following claims: 1) bioavailable Al cannot enter the brain in sufficient amounts to cause damage, 2) excess Al is efficiently excreted from the body, and 3) Al accumulation in neurons is a consequence rather than a cause of neuronal loss. Research, however, reveals that: 1) very small amounts of Al are needed to produce neurotoxicity and this criterion is satisfied through dietary Al intake, 2) Al sequesters different transport mechanisms to actively traverse brain barriers, 3) incremental acquisition of small amounts of Al over a lifetime favors its selective accumulation in brain tissues, and 4) since 1911, experimental evidence has repeatedly demonstrated that chronic Al intoxication reproduces neuropathological hallmarks of AD. Misconceptions about Al bioavailability may have misled scientists regarding the significance of Al in the pathogenesis of AD. The hypothesis that Al significantly contributes to AD is built upon very solid experimental evidence and should not be dismissed. Immediate steps should be taken to lessen human exposure to Al, which may be the single most aggravating and avoidable factor related to AD.

Laser Scanning Holographic Lithography for Flexible 3D Fabrication of Multi-Scale Integrated Nano-structures and Optical Biosensors

PubMed Central

Yuan, Liang (Leon); Herman, Peter R.

2016-01-01

Three-dimensional (3D) periodic nanostructures underpin a promising research direction on the frontiers of nanoscience and technology to generate advanced materials for exploiting novel photonic crystal (PC) and nanofluidic functionalities. However, formation of uniform and defect-free 3D periodic structures over large areas that can further integrate into multifunctional devices has remained a major challenge. Here, we introduce a laser scanning holographic method for 3D exposure in thick photoresist that combines the unique advantages of large area 3D holographic interference lithography (HIL) with the flexible patterning of laser direct writing to form both micro- and nano-structures in a single exposure step. Phase mask interference patterns accumulated over multiple overlapping scans are shown to stitch seamlessly and form uniform 3D nanostructure with beam size scaled to small 200 μm diameter. In this way, laser scanning is presented as a facile means to embed 3D PC structure within microfluidic channels for integration into an optofluidic lab-on-chip, demonstrating a new laser HIL writing approach for creating multi-scale integrated microsystems. PMID:26922872

Developing the snow component of a distributed hydrological model: a step-wise approach based on multi-objective analysis

NASA Astrophysics Data System (ADS)

Dunn, S. M.; Colohan, R. J. E.

1999-09-01

A snow component has been developed for the distributed hydrological model, DIY, using an approach that sequentially evaluates the behaviour of different functions as they are implemented in the model. The evaluation is performed using multi-objective functions to ensure that the internal structure of the model is correct. The development of the model, using a sub-catchment in the Cairngorm Mountains in Scotland, demonstrated that the degree-day model can be enhanced for hydroclimatic conditions typical of those found in Scotland, without increasing meteorological data requirements. An important element of the snow model is a function to account for wind re-distribution. This causes large accumulations of snow in small pockets, which are shown to be important in sustaining baseflows in the rivers during the late spring and early summer, long after the snowpack has melted from the bulk of the catchment. The importance of the wind function would not have been identified using a single objective function of total streamflow to evaluate the model behaviour.

Decomposing properties of phosphogypsum with iron addition under two-step cycle multi-atmosphere control in fluidised bed.

PubMed

Zheng, Dalong; Ma, Liping; Wang, Rongmou; Yang, Jie; Dai, Quxiu

2018-02-01

Phosphogypsum is a solid industry by-product generated when sulphuric acid is used to process phosphate ore into fertiliser. Phosphogypsum stacks without pretreatment are often piled on the land surface or dumped in the sea, causing significant environmental damage. This study examined the reaction characteristics of phosphogypsum, when decomposed in a multi-atmosphere fluidised bed. Phosphogypsum was first dried, sieved and mixed proportionally with lignite at the mass ratio of 10:1, it was then immersed in 0.8 [Formula: see text] with a solid-liquid ratio of 8:25. The study included a two-step cycle of multi-atmosphere control. First, a reducing atmosphere was provided to allow phosphogypsum decomposition through partial lignite combustion. After the reduction stage reaction was completed, the reducing atmosphere was changed into an air-support oxidising atmosphere at the constant temperature. Each atmosphere cycle had a conversion time of 30 min to ensure a sufficient reaction. The decomposing properties of phosphogypsum were obtained in different atmosphere cycles, at different reaction temperatures, different heating rates and different fluidised gas velocities, using experimental results combined with a theoretical analysis using FactSage 7.0 Reaction module. The study revealed that the optimum reaction condition was to circulate the atmosphere twice at a temperature of 1100 °C. The heating rate above 800 °C was 5 [Formula: see text], and the fluidised gas velocity was 0.40 [Formula: see text]. The procedure proposed in this article can serve as a phosphogypsum decomposition solution, and can support the future management of this by-product, resulting in more sustainable production.

Surface Modified Particles By Multi-Step Michael-Type Addition And Process For The Preparation Thereof

DOEpatents

Cook, Ronald Lee; Elliott, Brian John; Luebben, Silvia DeVito; Myers, Andrew William; Smith, Bryan Matthew

2005-05-03

A new class of surface modified particles and a multi-step Michael-type addition surface modification process for the preparation of the same is provided. The multi-step Michael-type addition surface modification process involves two or more reactions to compatibilize particles with various host systems and/or to provide the particles with particular chemical reactivities. The initial step comprises the attachment of a small organic compound to the surface of the inorganic particle. The subsequent steps attach additional compounds to the previously attached organic compounds through reactive organic linking groups. Specifically, these reactive groups are activated carbon—carbon pi bonds and carbon and non-carbon nucleophiles that react via Michael or Michael-type additions.

Development of a Corrosion Sensor for AN Aircraft Vehicle Health Monitoring System

NASA Astrophysics Data System (ADS)

Scott, D. A.; Price, D. C.; Edwards, G. C.; Batten, A. B.; Kolmeder, J.; Muster, T. H.; Corrigan, P.; Cole, I. S.

2010-02-01

A Rayleigh-wave-based sensor has been developed to measure corrosion damage in aircraft. This sensor forms an important part of a corrosion monitoring system being developed for a major aircraft manufacturer. This system measures the corrosion rate at the location of its sensors, and through a model predicts the corrosion rates in nearby places on an aircraft into which no sensors can be placed. In order to calibrate this model, which yields corrosion rates rather than the accumulated effect, an absolute measure of the damage is required. In this paper the development of a surface wave sensor capable of measuring accumulated damage will be described in detail. This sensor allows the system to measure material loss due to corrosion regardless of the possible loss of historical corrosion rate data, and can provide, at any stage, a benchmark for the predictive model that would allow a good estimate of the accumulated corrosion damage in similar locations on an aircraft. This system may obviate the need for costly inspection of difficult-to-access places in aircraft, where presently the only way to check for corrosion is by periodic dismantling and reassembly.

Impact of multi-resolution analysis of artificial intelligence models inputs on multi-step ahead river flow forecasting

NASA Astrophysics Data System (ADS)

Badrzadeh, Honey; Sarukkalige, Ranjan; Jayawardena, A. W.

2013-12-01

Discrete wavelet transform was applied to decomposed ANN and ANFIS inputs.Novel approach of WNF with subtractive clustering applied for flow forecasting.Forecasting was performed in 1-5 step ahead, using multi-variate inputs.Forecasting accuracy of peak values and longer lead-time significantly improved.

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.

Knowledge of damage identification about tensegrities via flexibility disassembly

NASA Astrophysics Data System (ADS)

Jiang, Ge; Feng, Xiaodong; Du, Shigui

2017-12-01

Tensegrity structures composing of continuous cables and discrete struts are under tension and compression, respectively. In order to determine the damage extents of tensegrity structures, a new method for tensegrity structural damage identification is presented based on flexibility disassembly. To decompose a tensegrity structural flexibility matrix into the matrix represention of the connectivity between degress-of-freedoms and the diagonal matrix comprising of magnitude informations. Step 1: Calculate perturbation flexibility; Step 2: Compute the flexibility connectivity matrix and perturbation flexibility parameters; Step 3: Calculate the perturbation stiffness parameters. The efficiency of the proposed method is demonstrated by a numeical example comprising of 12 cables and 4 struts with pretensioned. Accurate identification of local damage depends on the availability of good measured data, an accurate and reasonable algorithm.

Multi-walled carbon nanotubes: biodegradation by gastric agents in vitro and effect on murine intestinal system

NASA Astrophysics Data System (ADS)

Masyutin, A.; Erokhina, M.; Sychevskaya, K.; Gusev, A.; Vasyukova, I.; Smirnova, E.; Onishchenko, G.

2015-11-01

One of the main questions limiting application of fibrous carbon nanomaterials (CNM) in medicine and food industry concerns presumptive degradation of CNM in living organisms. In this study, we have investigated biodegradation of multi-walled carbon nanotubes (MWCNTs) by gastric agents in vitro and influence of ingested MWCNTs on murine intestine. Using scanning, conventional transmission and analytical electron microscopy, we demonstrated that industrial MWCNTs treated in vitro by 0.1 M hydrochloric acid (pH=1) and gastric juice (pH=2-3) isolated from murine stomach, are subjected to incomplete degradation. After 30 days of oral administration to experimental mice, we did find MWCNTs in the cells of small intestine, and it may indicate that agglomerates of MWCNTs do not penetrate into colon epithelia and do not accumulate in enterocytes. However, we observed local areas of necrotic damages of intestinal villi. It seems likely, therefore, that MWCNTs end up leaving gastrointestinal tract by excretion with the feces. Our results suggest that MWCNTs do not undergo complete degradation in gastrointestinal tract of mice, and passing through non-degraded particles may negatively affect intestinal system.

Mutant tamm-horsfall glycoprotein accumulation in endoplasmic reticulum induces apoptosis reversed by colchicine and sodium 4-phenylbutyrate.

PubMed

Choi, Sung Won; Ryu, Ok Hee; Choi, Sun Jin; Song, In Sun; Bleyer, Anthony J; Hart, Thomas C

2005-10-01

As a consequence of uromodulin gene mutations, individuals develop precocious hyperuricemia, gout, and progressive renal failure. In vitro studies suggest that pathologic accumulation of uromodulin/Tamm-Horsfall glycoprotein (THP) occurs in the endoplasmic reticulum (ER), but the pathophysiology of renal damage is unclear. It was hypothesized that programmed cell death triggered by accumulation of misfolded THP in the ER causes progressive renal disease. Stably transfected human embryonic kidney 293 cells and immortalized thick ascending limb of Henle's loop cells with wild-type and mutated uromodulin cDNA were evaluated to test this hypothesis. Immunocytochemistry, ELISA, and deglycosylation studies indicated that accumulation of mutant THP occurred in the ER. FACS analyses showed a significant increase in early apoptosis signal in human embryonic kidney 293 and thick ascending limb of Henle's loop cells that were transfected with mutant uromodulin constructs. Colchicine and sodium 4-phenylbutyrate treatment increased secretion of THP from the ER to the cell membrane and into the culture media and significantly improved cell viability. These findings indicate that intracellular accumulation of THP facilitates apoptosis and that this may provide the pathologic mechanism responsible for the progressive renal damage associated with uromodulin gene mutations. Colchicine and sodium 4-phenylbutyrate reverse these processes and could potentially be beneficial in ameliorating the progressive renal damage in uromodulin-associated kidney diseases.

THE SOURCE OF LIPID ACCUMULATION IN L CELLS

PubMed Central

Bensch, Klaus G.; King, Donald W.; Socolow, Edward L.

1961-01-01

Strain L cells accumulate lipid, concurrent with cessation of protein synthesis, in the stationary phase of growth from the extracellular medium and as a result of de novo synthesis. Cells which have been more severely damaged with an amino acid analogue also accumulate lipid from the extracellular medium, but synthesize very little lipid from labeled acetate. The possible roles which lipid accumulation may play in the cell are discussed. PMID:19866577

A Micro-Mechanism-Based Continuum Corrosion Fatigue Damage Model for Steels

NASA Astrophysics Data System (ADS)

Sun, Bin; Li, Zhaoxia

2018-05-01

A micro-mechanism-based corrosion fatigue damage model is developed for studying the high-cycle corrosion fatigue of steel from multi-scale viewpoint. The developed physical corrosion fatigue damage model establishes micro-macro relationships between macroscopic continuum damage evolution and collective evolution behavior of microscopic pits and cracks, which can be used to describe the multi-scale corrosion fatigue process of steel. As a case study, the model is used to predict continuum damage evolution and number density of the corrosion pit and short crack of steel component in 5% NaCl water under constant stress amplitude at 20 kHz, and the numerical results are compared with experimental results. It shows that the model is effective and can be used to evaluate the continuum macroscopic corrosion fatigue damage and study microscopic corrosion fatigue mechanisms of steel.

A Micro-Mechanism-Based Continuum Corrosion Fatigue Damage Model for Steels

NASA Astrophysics Data System (ADS)

Sun, Bin; Li, Zhaoxia

2018-04-01

A micro-mechanism-based corrosion fatigue damage model is developed for studying the high-cycle corrosion fatigue of steel from multi-scale viewpoint. The developed physical corrosion fatigue damage model establishes micro-macro relationships between macroscopic continuum damage evolution and collective evolution behavior of microscopic pits and cracks, which can be used to describe the multi-scale corrosion fatigue process of steel. As a case study, the model is used to predict continuum damage evolution and number density of the corrosion pit and short crack of steel component in 5% NaCl water under constant stress amplitude at 20 kHz, and the numerical results are compared with experimental results. It shows that the model is effective and can be used to evaluate the continuum macroscopic corrosion fatigue damage and study microscopic corrosion fatigue mechanisms of steel.

Impaired tRNA nuclear export links DNA damage and cell-cycle checkpoint.

PubMed

Ghavidel, Ata; Kislinger, Thomas; Pogoutse, Oxana; Sopko, Richelle; Jurisica, Igor; Emili, Andrew

2007-11-30

In response to genotoxic stress, cells evoke a plethora of physiological responses collectively aimed at enhancing viability and maintaining the integrity of the genome. Here, we report that unspliced tRNA rapidly accumulates in the nuclei of yeast Saccharomyces cerevisiae after DNA damage. This response requires an intact MEC1- and RAD53-dependent signaling pathway that impedes the nuclear export of intron-containing tRNA via differential relocalization of the karyopherin Los1 to the cytoplasm. The accumulation of unspliced tRNA in the nucleus signals the activation of Gcn4 transcription factor, which, in turn, contributes to cell-cycle arrest in G1 in part by delaying accumulation of the cyclin Cln2. The regulated nucleocytoplasmic tRNA trafficking thus constitutes an integral physiological adaptation to DNA damage. These data further illustrate how signal-mediated crosstalk between distinct functional modules, namely, tRNA nucleocytoplasmic trafficking, protein synthesis, and checkpoint execution, allows for functional coupling of tRNA biogenesis and cell-cycle progression.

Accumulation of senescent cells in mitotic tissue of aging primates.

PubMed

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

2007-01-01

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

Causal relationship of hepatic fat with liver damage and insulin resistance in nonalcoholic fatty liver.

PubMed

Dongiovanni, P; Stender, S; Pietrelli, A; Mancina, R M; Cespiati, A; Petta, S; Pelusi, S; Pingitore, P; Badiali, S; Maggioni, M; Mannisto, V; Grimaudo, S; Pipitone, R M; Pihlajamaki, J; Craxi, A; Taube, M; Carlsson, L M S; Fargion, S; Romeo, S; Kozlitina, J; Valenti, L

2018-04-01

Nonalcoholic fatty liver disease is epidemiologically associated with hepatic and metabolic disorders. The aim of this study was to examine whether hepatic fat accumulation has a causal role in determining liver damage and insulin resistance. We performed a Mendelian randomization analysis using risk alleles in PNPLA3, TM6SF2, GCKR and MBOAT7, and a polygenic risk score for hepatic fat, as instruments. We evaluated complementary cohorts of at-risk individuals and individuals from the general population: 1515 from the liver biopsy cohort (LBC), 3329 from the Swedish Obese Subjects Study (SOS) and 4570 from the population-based Dallas Heart Study (DHS). Hepatic fat was epidemiologically associated with liver damage, insulin resistance, dyslipidemia and hypertension. The impact of genetic variants on liver damage was proportional to their effect on hepatic fat accumulation. Genetically determined hepatic fat was associated with aminotransferases, and with inflammation, ballooning and fibrosis in the LBC. Furthermore, in the LBC, the causal association between hepatic fat and fibrosis was independent of disease activity, suggesting that a causal effect of long-term liver fat accumulation on liver disease is independent of inflammation. Genetically determined hepatic steatosis was associated with insulin resistance in the LBC and SOS. However, this association was dependent on liver damage severity. Genetically determined hepatic steatosis was associated with liver fibrosis/cirrhosis and with a small increase in risk of type 2 diabetes in publicly available databases. These data suggest that long-term hepatic fat accumulation plays a causal role in the development of chronic liver disease. © 2017 The Authors Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

Purification of melt-spun metallurgical grade silicon micro-flakes through a multi-step segregation procedure

NASA Astrophysics Data System (ADS)

Martinsen, F. A.; Nordstrand, E. F.; Gibson, U. J.

2013-01-01

Melt-spun metallurgical grade (MG) micron dimension silicon flakes have been purified into near solar grade (SG) quality through a multi-step melting and re-solidification procedure. A wet oxidation-applied thermal oxide maintained the sample morphology during annealing while the interiors were melted and re-solidified. The small thickness of the flakes allowed for near elimination of in-plane grain boundaries, with segregation enhanced accumulation of impurities at the object surface and in the few remaining grain boundaries. A subsequent etch in 48% hydrofluoric acid (HF) removed the impure oxide layer, and part of the contamination at the oxide-silicon interface, as shown by electron dispersive spectroscopy (EDS) and backscattered electron imaging (BEI). The sample grains were investigated by electron back-scattered diffraction (EBSD) after varying numbers of oxidation-annealing-etch cycles, and were observed to grow from ˜5 μm to ˜200 μm. The concentration of iron, titanium, copper and aluminium were shown by secondary ion mass spectroscopy (SIMS) and inductively coupled plasma mass spectroscopy (ICPMS) to drop between five and six orders of magnitude. The concentration of boron was observed to drop approximately one order of magnitude. A good correlation was observed between impurity removal rates and segregation models, indicating that the purification effect is mainly caused by segregation. Deviations from these models could be explained by the formation of oxides and hydroxides later removed through etching.

Fatigue damage behavior of a surface-mount electronic package under different cyclic applied loads

NASA Astrophysics Data System (ADS)

Ren, Huai-Hui; Wang, Xi-Shu

2014-04-01

This paper studies and compares the effects of pull-pull and 3-point bending cyclic loadings on the mechanical fatigue damage behaviors of a solder joint in a surface-mount electronic package. The comparisons are based on experimental investigations using scanning electron microscopy (SEM) in-situ technology and nonlinear finite element modeling, respectively. The compared results indicate that there are different threshold levels of plastic strain for the initial damage of solder joints under two cyclic applied loads; meanwhile, fatigue crack initiation occurs at different locations, and the accumulation of equivalent plastic strain determines the trend and direction of fatigue crack propagation. In addition, simulation results of the fatigue damage process of solder joints considering a constitutive model of damage initiation criteria for ductile materials and damage evolution based on accumulating inelastic hysteresis energy are identical to the experimental results. The actual fatigue life of the solder joint is almost the same and demonstrates that the FE modeling used in this study can provide an accurate prediction of solder joint fatigue failure.

Neuro-fuzzy computing for vibration-based damage localization and severity estimation in an experimental wind turbine blade with superimposed operational effects

NASA Astrophysics Data System (ADS)

Hoell, Simon; Omenzetter, Piotr

2016-04-01

Fueled by increasing demand for carbon neutral energy, erections of ever larger wind turbines (WTs), with WT blades (WTBs) with higher flexibilities and lower buckling capacities lead to increasing operation and maintenance costs. This can be counteracted with efficient structural health monitoring (SHM), which allows scheduling maintenance actions according to the structural state and preventing dramatic failures. The present study proposes a novel multi-step approach for vibration-based structural damage localization and severity estimation for application in operating WTs. First, partial autocorrelation coefficients (PACCs) are estimated from vibrational responses. Second, principal component analysis is applied to PACCs from the healthy structure in order to calculate scores. Then, the scores are ranked with respect to their ability to differentiate different damage scenarios. This ranking information is used for constructing hierarchical adaptive neuro-fuzzy inference systems (HANFISs), where cross-validation is used to identify optimal numbers of hierarchy levels. Different HANFISs are created for the purposes of structural damage localization and severity estimation. For demonstrating the applicability of the approach, experimental data are superimposed with signals from numerical simulations to account for characteristics of operational noise. For the physical experiments, a small scale WTB is excited with a domestic fan and damage scenarios are introduced non-destructively by attaching small masses. Numerical simulations are also performed for a representative fully functional small WT operating in turbulent wind. The obtained results are promising for future applications of vibration-based SHM to facilitate improved safety and reliability of WTs at lower costs.

Sorafenib-induced defective autophagy promotes cell death by necroptosis.

PubMed

Kharaziha, Pedram; Chioureas, Dimitris; Baltatzis, George; Fonseca, Pedro; Rodriguez, Patricia; Gogvadze, Vladimir; Lennartsson, Lena; Björklund, Ann-Charlotte; Zhivotovsky, Boris; Grandér, Dan; Egevad, Lars; Nilsson, Sten; Panaretakis, Theocharis

2015-11-10

Autophagy is one of the main cytoprotective mechanisms that cancer cells deploy to withstand the cytotoxic stress and survive the lethal damage induced by anti-cancer drugs. However, under specific conditions, autophagy may, directly or indirectly, induce cell death. In our study, treatment of the Atg5-deficient DU145 prostate cancer cells, with the multi-tyrosine kinase inhibitor, sorafenib, induces mitochondrial damage, autophagy and cell death. Molecular inhibition of autophagy by silencing ULK1 and Beclin1 rescues DU145 cells from cell death indicating that, in this setting, autophagy promotes cell death. Re-expression of Atg5 restores the lipidation of LC3 and rescues DU145 and MEF atg5-/- cells from sorafenib-induced cell death. Despite the lack of Atg5 expression and LC3 lipidation, DU145 cells form autophagosomes as demonstrated by transmission and immuno-electron microscopy, and the formation of LC3 positive foci. However, the lack of cellular content in the autophagosomes, the accumulation of long-lived proteins, the presence of GFP-RFP-LC3 positive foci and the accumulated p62 protein levels indicate that these autophagosomes may not be fully functional. DU145 cells treated with sorafenib undergo a caspase-independent cell death that is inhibited by the RIPK1 inhibitor, necrostatin-1. Furthermore, treatment with sorafenib induces the interaction of RIPK1 with p62, as demonstrated by immunoprecipitation and a proximity ligation assay. Silencing of p62 decreases the RIPK1 protein levels and renders necrostatin-1 ineffective in blocking sorafenib-induced cell death. In summary, the formation of Atg5-deficient autophagosomes in response to sorafenib promotes the interaction of p62 with RIPK leading to cell death by necroptosis.

Cobalt distribution in keratinocyte cells indicates nuclear and perinuclear accumulation and interaction with magnesium and zinc homeostasis.

PubMed

Ortega, Richard; Bresson, Carole; Fraysse, Aurélien; Sandre, Caroline; Devès, Guillaume; Gombert, Clémentine; Tabarant, Michel; Bleuet, Pierre; Seznec, Hervé; Simionovici, Alexandre; Moretto, Philippe; Moulin, Christophe

2009-07-10

Cobalt is known to be toxic at high concentration, to induce contact dermatosis, and occupational radiation skin damage because of its use in nuclear industry. We investigated the intracellular distribution of cobalt in HaCaT human keratinocytes as a model of skin cells, and its interaction with endogenous trace elements. Direct micro-chemical imaging based on ion beam techniques was applied to determine the quantitative distribution of cobalt in HaCaT cells. In addition, synchrotron radiation X-ray fluorescence microanalysis in tomography mode was performed, for the first time on a single cell, to determine the 3D intracellular distribution of cobalt. Results obtained with these micro-chemical techniques were compared to a more classical method based on cellular fractionation followed by inductively coupled plasma atomic emission spectrometry (ICP-AES) measurements. Cobalt was found to accumulate in the cell nucleus and in perinuclear structures indicating the possible direct interaction with genomic DNA, and nuclear proteins. The perinuclear accumulation in the cytosol suggests that cobalt could be stored in the endoplasmic reticulum or the Golgi apparatus. The multi-elemental analysis revealed that cobalt exposure significantly decreased magnesium and zinc content, with a likely competition of cobalt for magnesium and zinc binding sites in proteins. Overall, these data suggest a multiform toxicity of cobalt related to interactions with genomic DNA and nuclear proteins, and to the alteration of zinc and magnesium homeostasis.

Critical and subcritical damage monitoring of bonded composite repairs using innovative non-destructive techniques

NASA Astrophysics Data System (ADS)

Grammatikos, S. A.; Kordatos, E. Z.; Aggelis, D. G.; Matikas, T. E.; Paipetis, A. S.

2012-04-01

Infrared Thermography (IrT) has been shown to be capable of detecting and monitoring service induced damage of repair composite structures. Full-field imaging, along with portability are the primary benefits of the thermographic technique. On-line lock-in thermography has been reported to successfully monitor damage propagation or/and stress concentration in composite coupons, as mechanical stresses in structures induce heat concentration phenomena around flaws. During mechanical fatigue, cyclic loading plays the role of the heating source and this allows for critical and subcritical damage identification and monitoring using thermography. The Electrical Potential Change Technique (EPCT) is a new method for damage identification and monitoring during loading. The measurement of electrical potential changes at specific points of Carbon Fiber Reinforced Polymers (CFRPs) under load are reported to enable the monitoring of strain or/and damage accumulation. Along with the aforementioned techniques Finally, Acoustic Emission (AE) method is well known to provide information about the location and type of damage. Damage accumulation due to cyclic loading imposes differentiation of certain parameters of AE like duration and energy. Within the scope of this study, infrared thermography is employed along with AE and EPCT methods in order to assess the integrity of bonded repair patches on composite substrates and to monitor critical and subcritical damage induced by the mechanical loading. The combined methodologies were effective in identifying damage initiation and propagation of bonded composite repairs.

Modeling damage in concrete pavements and bridges.

DOT National Transportation Integrated Search

2010-09-01

This project focused on micromechanical modeling of damage in concrete under general, multi-axial loading. A : continuum-level, three-dimensional constitutive model based on micromechanics was developed. The model : accounts for damage in concrete by...

Reducing sedimentation of depressional wetlands in agricultural landscapes

USGS Publications Warehouse

Skagen, S.K.; Melcher, Cynthia; Haukos, D.A.

2008-01-01

Depressional wetlands in agricultural landscapes are easily degraded by sediments and contaminants accumulated from their watersheds. Several best management practices can reduce transport of sediments into wetlands, including the establishment of vegetative buffers. We summarize the sources, transport dynamics, and effect of sediments, nutrients, and contaminants that threaten wetlands and the current knowledge of design and usefulness of grass buffers for protecting isolated wetlands. Buffer effectiveness is dependent on several factors, including vegetation structure, buffer width, attributes of the surrounding watershed (i.e., area, vegetative cover, slope and topography, soil type and structure, soil moisture, amount of herbicides and pesticides applied), and intensity and duration of rain events. To reduce dissolved contaminants from runoff, the water must infiltrate the soil where microbes or other processes can break down or sequester contaminants. But increasing infiltration also diminishes total water volume entering a wetland, which presents threats to wetland hydrology in semi-arid regions. Buffer effectiveness may be enhanced significantly by implementing other best management practices (e.g., conservation tillage, balancing input with nutrient requirements for livestock and crops, precision application of chemicals) in the surrounding watershed to diminish soil erosion and associated contaminant runoff. Buffers require regular maintenance to remove sediment build-up and replace damaged or over-mature vegetation. Further research is needed to establish guidelines for effective buffer width and structure, and such efforts should entail a coordinated, regional, multi-scale, multidisciplinary approach to evaluate buffer effectiveness and impacts. Direct measures in "real-world" systems and field validations of buffer-effectiveness models are crucial next steps in evaluating how grass buffers will impact the abiotic and biotic variables attributes that characterize small, isolated wetlands. ?? 2008 The Society of Wetland Scientists.

Modeling the roles of damage accumulation and mechanical healing on rainfall-induced landslides

NASA Astrophysics Data System (ADS)

Fan, Linfeng; Lehmann, Peter; Or, Dani

2014-05-01

The abrupt release of rainfall-induced shallow landslides is preceded by local failures that may abruptly coalesce and form a continuous failure plane within a hillslope. The mechanical status of hillslopes reflects a competition between the extent of severity of accumulated local damage during prior rainfall events and the rates of mechanically healing (i.e. regaining of strength) by closure of micro-cracks, regrowth of roots, etc. The interplay of these processes affects the initial conditions for landslide modeling and shapes potential failure patterns during future rainfall events. We incorporated these competing mechanical processes in a hydro-mechanical landslide triggering model subjected to a sequence of rainfall scenarios. The model employs the Fiber Bundle Model (FBM) with bonds (fiber bundle) with prescribed threshold linking adjacent soil columns and soil to bedrock. Prior damage was represented by a fraction of broken fibers during previous rainfall events, and the healing of broken fibers was described by strength regaining models for soil and roots at different characteristic time scales. Results show that prior damage and healing introduce highly nonlinear response to landslide triggering. For small prior damage, mechanical bonds at soil-bedrock interface may fail early in next rainfall event but lead to small perturbations onto lateral bonds without triggering a landslide. For more severe damage weakening lateral bonds, excess load due to failure at soil-bedrock interface accumulates at downslope soil columns resulting in early soil failure with patterns strongly correlated with prior damage distribution. Increasing prior damage over the hillslope decreases the volume of first landslide and prolongs the time needed to trigger the second landslide due to mechanical relaxation of the system. The mechanical healing of fibers diminishes effects of prior damage on the time of failure, and shortens waiting time between the first and second landslides. These findings highlight the need to improve definition of initial conditions and the shortcomings of assuming pristine hillslopes.

AVO Analysis of a Shallow Gas Accumulation in the Marmara Sea

NASA Astrophysics Data System (ADS)

Er, M.; Dondurur, D.; Çifçi, G.

2012-04-01

In recent years, Amplitude versus Offset-AVO analysis is widely used in determination and classification of gas anomalies from wide-offset seismic data. Bright spots which are among the significant factors in determining the hydrocarbon accumulations, can also be determined sucessfully using AVO analysis. A bright spot anomaly were identified on the multi-channel seismic data collected by R/V K. Piri Reis research vessel in the Marmara Sea in 2008. On prestack seismic data, the associated AVO anomalies are clearly identified on the supergathers. Near- and far-offset stack sections are plotted to show the amplitudes changes at different offsets and the bright amplitudes were observed on the far-offset stack. AVO analysis was applied to the observed bright spot anomaly following the standart data processing steps. The analysis includes the preparation of Intercept, Gradient and Fluid Factor sections of AVO attribues. Top and base boundaries of gas bearing sediment were shown by intercept - gradient crossplot method. 1D modelling was also performed to show AVO classes and models were compared with the analysis results. It is interpreted that the bright spot anomaly arises from a shallow gas accumulation. In addition, the gas saturation from P-wave velocity was also estimated by the analysis. AVO analysis indicated Class 3 and Class 4 AVO anomalies observed on the bright spot anomaly.

Chalcone isomerase cDNA cloning and mRNA induction by fungal elicitor, wounding and infection

PubMed Central

Mehdy, Mona C.; Lamb, Christopher J.

1987-01-01

The environmentally regulated synthesis of phenylpropanoid natural products was studied by examining the expression of the gene encoding chalcone isomerase (CHI). This enzyme catalyzes a step common to the synthesis of flavonoid pigments and isoflavonoid phytoalexins. A λgt11 library was constructed using mRNA from cell cultures of bean (Phaseolus vulgaris L.) treated with fungal elicitor. Two positive clones were obtained by screening 105 recombinants with an antiserum to purified bean CHI. The identity of the cloned sequences was confirmed by hybrid-select translation and the production of antigenic polypeptides from transcripts synthesized in vitro. Addition of elicitor to cell cultures resulted in the rapid accumulation of CHI mRNA, with maximum levels achieved 3–4 h after elicitation. CHI mRNA also accumulated during the natural infection of hypocotyls with the fungal pathogen Colletotrichum lindemuthianum, and in mechanically wounded hypocotyls. The kinetics of accumulation of CHI mRNA in response to these environmental signals were strikingly similar to those of mRNAs encoding two other phenylpropanoid pathway enzymes, phenylalanine ammonialyase and chalcone synthase. In contrast to the multi-gene families encoding these two enzymes, chalcone isomerase is encoded by a single gene which is regulated by several environmental stimuli. ImagesFig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6.Fig. 9. PMID:16453768

The influence of artificial radiation damage and thermal annealing on helium diffusion kinetics in apatite

NASA Astrophysics Data System (ADS)

Shuster, David L.; Farley, Kenneth A.

2009-01-01

Recent work [Shuster D. L., Flowers R. M. and Farley K. A. (2006) The influence of natural radiation damage on helium diffusion kinetics in apatite. Earth Planet. Sci. Lett.249(3-4), 148-161] revealing a correlation between radiogenic 4He concentration and He diffusivity in natural apatites suggests that helium migration is retarded by radiation-induced damage to the crystal structure. If so, the He diffusion kinetics of an apatite is an evolving function of time and the effective uranium concentration in a cooling sample, a fact which must be considered when interpreting apatite (U-Th)/He ages. Here we report the results of experiments designed to investigate and quantify this phenomenon by determining He diffusivities in apatites after systematically adding or removing radiation damage. Radiation damage was added to a suite of synthetic and natural apatites by exposure to between 1 and 100 h of neutron irradiation in a nuclear reactor. The samples were then irradiated with a 220 MeV proton beam and the resulting spallogenic 3He used as a diffusant in step-heating diffusion experiments. In every sample, irradiation increased the activation energy ( E a) and the frequency factor ( D o/ a2) of diffusion and yielded a higher He closure temperature ( T c) than the starting material. For example, 100 h in the reactor caused the He closure temperature to increase by as much as 36 °C. For a given neutron fluence the magnitude of increase in closure temperature scales negatively with the initial closure temperature. This is consistent with a logarithmic response in which the neutron damage is additive to the initial damage present. In detail, the irradiations introduce correlated increases in E a and ln( D o/a 2) that lie on the same array as found in natural apatites. This strongly suggests that neutron-induced damage mimics the damage produced by U and Th decay in natural apatites. To investigate the potential consequences of annealing of radiation damage, samples of Durango apatite were heated in vacuum to temperatures up to 550 °C for between 1 and 350 h. After this treatment the samples were step-heated using the remaining natural 4He as the diffusant. At temperatures above 290 °C a systematic change in T c was observed, with values becoming lower with increasing temperature and time. For example, reduction of T c from the starting value of 71 to ˜52 °C occurred in 1 h at 375 °C or 10 h at 330 °C. The observed variations in T c are strongly correlated with the fission track length reduction predicted from the initial holding time and temperature. Furthermore, like the neutron irradiated apatites, these samples plot on the same E a - ln( D o/ a2) array as natural samples, suggesting that damage annealing is simply undoing the consequences of damage accumulation in terms of He diffusivity. Taken together these data provide unequivocal evidence that at these levels, radiation damage acts to retard He diffusion in apatite, and that thermal annealing reverses the process. The data provide support for the previously described radiation damage trapping kinetic model of Shuster et al. (2006) and can be used to define a model which fully accommodates damage production and annealing.

Shape memory polyurethanes with oxidation-induced degradation: In vivo and in vitro correlations for endovascular material applications.

PubMed

Weems, Andrew C; Wacker, Kevin T; Carrow, James K; Boyle, Anthony J; Maitland, Duncan J

2017-09-01

The synthesis of thermoset shape memory polymer (SMP) polyurethanes from symmetric, aliphatic alcohols and diisocyanates has previously demonstrated excellent biocompatibility in short term in vitro and in vivo studies, although long term stability has not been investigated. Here we demonstrate that while rapid oxidation occurs in these thermoset SMPs, facilitated by the incorporation of multi-functional, branching amino groups, byproduct analysis does not indicate toxicological concern for these materials. Through complex multi-step chemical reactions, chain scission begins from the amines in the monomeric repeat units, and results, ultimately, in the formation of carboxylic acids, secondary and primary amines; the degradation rate and product concentrations were confirmed using liquid chromatography mass spectrometry, in model compound studies, yielding a previously unexamined degradation mechanism for these biomaterials. The rate of degradation is dependent on the hydrogen peroxide concentration, and comparison of explanted samples reveals a much slower rate in vivo compared to the widely accepted literature in vitro real-time equivalent of 3% H 2 O 2 . Cytotoxicity studies of the material surface, and examination of the degradation product accumulations, indicate that degradation has negligible impact on cytotoxicity of these materials. This paper presents an in-depth analysis on the degradation of porous, shape memory polyurethanes (SMPs), including traditional surface characterization as well as model degradation compounds with absolute quantification. This combination of techniques allows for determination of rates of degradation as well as accumulation of individual degradation products. These behaviors are used for in vivo-in vitro comparisons for determination of real time degradation rates. Previous studies have primarily been limited to surface characterization without examination of degradation products and accumulation rates. To our knowledge, our work presents a unique example where a range of material scales (atomistic-scale model compounds along with macroscopic porous SMPs) are used in conjunction with ex planted samples for calculation of degradation rates and toxicological risk. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Displacement prediction of Baijiabao landslide based on empirical mode decomposition and long short-term memory neural network in Three Gorges area, China

NASA Astrophysics Data System (ADS)

Xu, Shiluo; Niu, Ruiqing

2018-02-01

Every year, landslides pose huge threats to thousands of people in China, especially those in the Three Gorges area. It is thus necessary to establish an early warning system to help prevent property damage and save peoples' lives. Most of the landslide displacement prediction models that have been proposed are static models. However, landslides are dynamic systems. In this paper, the total accumulative displacement of the Baijiabao landslide is divided into trend and periodic components using empirical mode decomposition. The trend component is predicted using an S-curve estimation, and the total periodic component is predicted using a long short-term memory neural network (LSTM). LSTM is a dynamic model that can remember historical information and apply it to the current output. Six triggering factors are chosen to predict the periodic term using the Pearson cross-correlation coefficient and mutual information. These factors include the cumulative precipitation during the previous month, the cumulative precipitation during a two-month period, the reservoir level during the current month, the change in the reservoir level during the previous month, the cumulative increment of the reservoir level during the current month, and the cumulative displacement during the previous month. When using one-step-ahead prediction, LSTM yields a root mean squared error (RMSE) value of 6.112 mm, while the support vector machine for regression (SVR) and the back-propagation neural network (BP) yield values of 10.686 mm and 8.237 mm, respectively. Meanwhile, the Elman network (Elman) yields an RMSE value of 6.579 mm. In addition, when using multi-step-ahead prediction, LSTM obtains an RMSE value of 8.648 mm, while SVR, BP and the Elman network obtains RSME values of 13.418 mm, 13.014 mm, and 13.370 mm. The predicted results indicate that, to some extent, the dynamic model (LSTM) achieves results that are more accurate than those of the static models (i.e., SVR and BP). LSTM even displays better performance than the Elman network, which is also a dynamic method.

Regulations and guidelines governing stem cell based products: Clinical considerations

PubMed Central

George, Bobby

2011-01-01

The use of stem cells as medicines is a promising and upcoming area of research as they may be able to help the body to regenerate damaged or lost tissue in a host of diseases like Parkinson′s, multiple sclerosis, heart disease, liver disease, spinal cord damage, cancer and many more. Translating basic stem cell research into routine therapies is a complex multi-step process which entails the challenge related to managing the expected therapeutic benefits with the potential risks while complying with the existing regulations and guidelines. While in the United States (US) and European Union (EU) regulations are in place, in India, we do not have a well-defined regulatory framework for “stem cell based products (SCBP)”. There are several areas that need to be addressed as it is quite different from that of pharmaceuticals. These range from establishing batch consistency, product stability to product safety and efficacy through pre-clinical, clinical studies and marketing authorization. This review summarizes the existing regulations/guidelines in US, EU, India, and the associated challenges in developing SCBP with emphasis on clinical aspects. PMID:21897884

Omega-3 fatty acid supplementation decreases DNA damage in brain of rats subjected to a chemically induced chronic model of Tyrosinemia type II.

PubMed

Carvalho-Silva, Milena; Gomes, Lara M; Scaini, Giselli; Rebelo, Joyce; Damiani, Adriani P; Pereira, Maiara; Andrade, Vanessa M; Gava, Fernanda F; Valvassori, Samira S; Schuck, Patricia F; Ferreira, Gustavo C; Streck, Emilio L

2017-08-01

Tyrosinemia type II is an inborn error of metabolism caused by a mutation in a gene encoding the enzyme tyrosine aminotransferase leading to an accumulation of tyrosine in the body, and is associated with neurologic and development difficulties in numerous patients. Because the accumulation of tyrosine promotes oxidative stress and DNA damage, the main aim of this study was to investigate the possible antioxidant and neuroprotective effects of omega-3 treatment in a chemically-induced model of Tyrosinemia type II in hippocampus, striatum and cerebral cortex of rats. Our results showed chronic administration of L-tyrosine increased the frequency and the index of DNA damage, as well as the 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the hippocampus, striatum and cerebral cortex. Moreover, omega-3 fatty acid treatment totally prevented increased DNA damage in the striatum and hippocampus, and partially prevented in the cerebral cortex, whereas the increase in 8-OHdG levels was totally prevented by omega-3 fatty acid treatment in hippocampus, striatum and cerebral cortex. In conclusion, the present study demonstrated that the main accumulating metabolite in Tyrosinemia type II induce DNA damage in hippocampus, striatum and cerebral cortex, possibly mediated by free radical production, and the supplementation with omega-3 fatty acids was able to prevent this damage, suggesting that could be involved in the prevention of oxidative damage to DNA in this disease. Thus, omega-3 fatty acids supplementation to Tyrosinemia type II patients may represent a new therapeutic approach and a possible adjuvant to the curren t treatment of this disease.

MAP kinase-signaling controls nuclear translocation of tripeptidyl-peptidase II in response to DNA damage and oxidative stress

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

Preta, Giulio; Klark, Rainier de; Chakraborti, Shankhamala

2010-08-27

Research highlights: {yields} Nuclear translocation of TPPII occurs in response to different DNA damage inducers. {yields} Nuclear accumulation of TPPII is linked to ROS and anti-oxidant enzyme levels. {yields} MAPKs control nuclear accumulation of TPPII. {yields} Inhibited nuclear accumulation of TPPII decreases DNA damage-induced {gamma}-H2AX expression. -- Abstract: Reactive oxygen species (ROS) are a continuous hazard in eukaroytic cells by their ability to cause damage to biomolecules, in particular to DNA. Previous data indicated that the cytosolic serine peptidase tripeptidyl-peptidase II (TPPII) translocates into the nucleus of most tumor cell lines in response to {gamma}-irradiation and ROS production; an eventmore » that promoted p53 expression as well as caspase-activation. We here observed that nuclear translocation of TPPII was dependent on signaling by MAP kinases, including p38MAPK. Further, this was caused by several types of DNA-damaging drugs, a DNA cross-linker (cisplatinum), an inhibitor of topoisomerase II (etoposide), and to some extent also by nucleoside-analogues (5-fluorouracil, hydroxyurea). In the minority of tumor cell lines where TPPII was not translocated into the nucleus in response to DNA damage we observed reduced intracellular ROS levels, and the expression levels of redox defense systems were increased. Further, treatment with the ROS-inducer {gamma}-hexa-chloro-cyclohexane ({gamma}-HCH, lindane), an inhibitor of GAP junctions, restored nuclear translocation of TPPII in these cell lines upon {gamma}-irradiation. Moreover, blocking nuclear translocation of TPPII in etoposide-treated cells, by using a peptide-derived inhibitor (Z-Gly-Leu-Ala-OH), attenuated expression of {gamma}-H2AX in {gamma}-irradiated melanoma cells. Our results indicated a role for TPPII in MAPK-dependent DNA damage signaling.« less

Probabilistic flood damage modelling at the meso-scale

NASA Astrophysics Data System (ADS)

Kreibich, Heidi; Botto, Anna; Schröter, Kai; Merz, Bruno

2014-05-01

Decisions on flood risk management and adaptation are usually based on risk analyses. Such analyses are associated with significant uncertainty, even more if changes in risk due to global change are expected. Although uncertainty analysis and probabilistic approaches have received increased attention during the last years, they are still not standard practice for flood risk assessments. Most damage models have in common that complex damaging processes are described by simple, deterministic approaches like stage-damage functions. Novel probabilistic, multi-variate flood damage models have been developed and validated on the micro-scale using a data-mining approach, namely bagging decision trees (Merz et al. 2013). In this presentation we show how the model BT-FLEMO (Bagging decision Tree based Flood Loss Estimation MOdel) can be applied on the meso-scale, namely on the basis of ATKIS land-use units. The model is applied in 19 municipalities which were affected during the 2002 flood by the River Mulde in Saxony, Germany. The application of BT-FLEMO provides a probability distribution of estimated damage to residential buildings per municipality. Validation is undertaken on the one hand via a comparison with eight other damage models including stage-damage functions as well as multi-variate models. On the other hand the results are compared with official damage data provided by the Saxon Relief Bank (SAB). The results show, that uncertainties of damage estimation remain high. Thus, the significant advantage of this probabilistic flood loss estimation model BT-FLEMO is that it inherently provides quantitative information about the uncertainty of the prediction. Reference: Merz, B.; Kreibich, H.; Lall, U. (2013): Multi-variate flood damage assessment: a tree-based data-mining approach. NHESS, 13(1), 53-64.

Shadowing effects on multi-step Langmuir probe array on HL-2A tokamak

NASA Astrophysics Data System (ADS)

Ke, R.; Xu, M.; Nie, L.; Gao, Z.; Wu, Y.; Yuan, B.; Chen, J.; Song, X.; Yan, L.; Duan, X.

2018-05-01

Multi-step Langmuir probe arrays have been designed and installed on the HL-2A tokamak [1]–[2] to study the turbulent transport in the edge plasma, especially for the measurement of poloidal momentum flux, Reynolds stress Rs. However, except the probe tips on the top step, all other tips on lower steps are shadowed by graphite skeleton. It is necessary to estimate the shadowing effects on equilibrium and fluctuation measurement. In this paper, comparison of shadowed tips to unshadowed ones is presented. The results show that shadowing can strongly reduce the ion and electron effective collection area. However, its effect is negligible for the turbulence intensity and coherence measurement, confirming that the multi-step LP array is proper for the turbulent transport measurement.

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.

Optical and electrical properties of indium tin oxide films near their laser damage threshold [Electrical and optical properties of indium tin oxide films under multi-pulse laser irradiation at 1064 nm

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

Yoo, Jae -Hyuck; Lange, Andrew; Bude, Jeff

In this paper, we investigated whether the optical and electrical properties of indium tin oxide (ITO) films are degraded under laser irradiation below their laser ablation threshold. While performing multi-pulse laser damage experiments on a single ITO film (4.7 ns, 1064 nm, 10 Hz), we examined the optical and electrical properties in situ. A decrease in reflectance was observed prior to laser damage initiation. However, under sub-damage threshold irradiation, conductivity and reflectance of the film were maintained without measurable degradation. This indicates that ITO films in optoelectronic devices may be operated below their lifetime laser damage threshold without noticeable performancemore » degradation.« less

Optical and electrical properties of indium tin oxide films near their laser damage threshold [Electrical and optical properties of indium tin oxide films under multi-pulse laser irradiation at 1064 nm

DOE PAGES

Yoo, Jae -Hyuck; Lange, Andrew; Bude, Jeff; ...

2017-02-10

In this paper, we investigated whether the optical and electrical properties of indium tin oxide (ITO) films are degraded under laser irradiation below their laser ablation threshold. While performing multi-pulse laser damage experiments on a single ITO film (4.7 ns, 1064 nm, 10 Hz), we examined the optical and electrical properties in situ. A decrease in reflectance was observed prior to laser damage initiation. However, under sub-damage threshold irradiation, conductivity and reflectance of the film were maintained without measurable degradation. This indicates that ITO films in optoelectronic devices may be operated below their lifetime laser damage threshold without noticeable performancemore » degradation.« less

A Geometrically Nonlinear Phase Field Theory of Brittle Fracture

DTIC Science & Technology

2014-10-01

of crack propagation. Philos Mag 91:75–95 Sun X, Khaleel M (2004) Modeling of glass fracture damage using continuum damage mechanics -static spherical...elastic fracture mechanics ). Engineering finite element (FE) simula- tions often invoke continuum damage mechanics the- ories, wherein the tangent...stiffness of a material ele- ment degrades as “damage” accumulates.Conventional continuum damage mechanics theories (Clayton and McDowell 2003, 2004; Sun and

NF-κB inhibition delays DNA damage–induced senescence and aging in mice

PubMed Central

Tilstra, Jeremy S.; Robinson, Andria R.; Wang, Jin; Gregg, Siobhán Q.; Clauson, Cheryl L.; Reay, Daniel P.; Nasto, Luigi A.; St Croix, Claudette M.; Usas, Arvydas; Vo, Nam; Huard, Johnny; Clemens, Paula R.; Stolz, Donna B.; Guttridge, Denis C.; Watkins, Simon C.; Garinis, George A.; Wang, Yinsheng; Niedernhofer, Laura J.; Robbins, Paul D.

2012-01-01

The accumulation of cellular damage, including DNA damage, is thought to contribute to aging-related degenerative changes, but how damage drives aging is unknown. XFE progeroid syndrome is a disease of accelerated aging caused by a defect in DNA repair. NF-κB, a transcription factor activated by cellular damage and stress, has increased activity with aging and aging-related chronic diseases. To determine whether NF-κB drives aging in response to the accumulation of spontaneous, endogenous DNA damage, we measured the activation of NF-κB in WT and progeroid model mice. As both WT and progeroid mice aged, NF-κB was activated stochastically in a variety of cell types. Genetic depletion of one allele of the p65 subunit of NF-κB or treatment with a pharmacological inhibitor of the NF-κB–activating kinase, IKK, delayed the age-related symptoms and pathologies of progeroid mice. Additionally, inhibition of NF-κB reduced oxidative DNA damage and stress and delayed cellular senescence. These results indicate that the mechanism by which DNA damage drives aging is due in part to NF-κB activation. IKK/NF-κB inhibitors are sufficient to attenuate this damage and could provide clinical benefit for degenerative changes associated with accelerated aging disorders and normal aging. PMID:22706308

Chronic Oxidative Damage together with Genome Repair Deficiency in the Neurons is a Double Whammy for Neurodegeneration: Is Damage Response Signaling a Potential Therapeutic Target?

PubMed Central

Wang, Haibo; Dharmalingam, Prakash; Vasquez, Velmarini; Mitra, Joy; Boldogh, Istvan; Rao, K. S.; Kent, Thomas A.; Mitra, Sankar; Hegde, Muralidhar L.

2016-01-01

A foremost challenge for the neurons, which are among the most oxygenated cells, is the genome damage caused by chronic exposure to endogenous reactive oxygen species (ROS), formed as cellular respiratory byproducts. Strong metabolic activity associated with high transcriptional levels in these long lived post-mitotic cells render them vulnerable to oxidative genome damage, including DNA strand breaks and mutagenic base lesions. There is growing evidence for the accumulation of unrepaired DNA lesions in the central nervous system (CNS) during accelerated ageing and progressive neurodegeneration. Several germ line mutations in DNA repair or DNA damage response (DDR) signaling genes are uniquely manifested in the phenotype of neuronal dysfunction and are etiologically linked to many neurodegenerative disorders. Studies in our lab and elsewhere revealed that pro-oxidant metals, ROS and misfolded amyloidogenic proteins not only contribute to genome damage in CNS, but also impede their repair/DDR signaling leading to persistent damage accumulation, a common feature in sporadic neurodegeneration. Here, we have reviewed recent advances in our understanding of the etiological implications of DNA damage vs. repair imbalance, abnormal DDR signaling in triggering neurodegeneration and potential of DDR as a target for the amelioration of neurodegenerative diseases. PMID:27663141

Lagrangian methods for blood damage estimation in cardiovascular devices--How numerical implementation affects the results.

PubMed

Marom, Gil; Bluestein, Danny

2016-01-01

This paper evaluated the influence of various numerical implementation assumptions on predicting blood damage in cardiovascular devices using Lagrangian methods with Eulerian computational fluid dynamics. The implementation assumptions that were tested included various seeding patterns, stochastic walk model, and simplified trajectory calculations with pathlines. Post processing implementation options that were evaluated included single passage and repeated passages stress accumulation and time averaging. This study demonstrated that the implementation assumptions can significantly affect the resulting stress accumulation, i.e., the blood damage model predictions. Careful considerations should be taken in the use of Lagrangian models. Ultimately, the appropriate assumptions should be considered based the physics of the specific case and sensitivity analysis, similar to the ones presented here, should be employed.

Simulation and experiment of thermal fatigue in the CPV die attach

NASA Astrophysics Data System (ADS)

Bosco, Nick; Silverman, Timothy; Kurtz, Sarah

2012-10-01

FEM simulation and accelerated thermal cycling have been performed for the CPV die attach. Trends in fatigue damage accumulation and equivalent test time are explored and found to be most sensitive to temperature ramp rate. Die attach crack growth is measured through cycling and found to be in excellent agreement with simulations of the inelastic strain energy accumulated. Simulations of an entire year of weather data provides for the relative ranking of fatigue damage between four cities as well as their equivalent accelerated test time.

Deferoxamine inhibits microglial activation, attenuates blood-brain barrier disruption, rescues dendritic damage, and improves spatial memory in a mouse model of microhemorrhages.

PubMed

He, Xiao-Fei; Lan, Yue; Zhang, Qun; Liu, Dong-Xu; Wang, Qinmei; Liang, Feng-Ying; Zeng, Jin-Sheng; Xu, Guang-Qing; Pei, Zhong

2016-08-01

Cerebral microbleeds are strongly linked to cognitive dysfunction in the elderly. Iron accumulation plays an important role in the pathogenesis of intracranial hemorrhage. Deferoxamine (DFX), a metal chelator, removes iron overload and protects against brain damage in intracranial hemorrhage. In this study, the protective effects of DFX against microhemorrhage were examined in mice. C57BL6 and Thy-1 green fluorescent protein transgenic mice were subjected to perforating artery microhemorrhages on the right posterior parietal cortex using two-photon laser irradiation. DFX (100 mg/kg) was administered 6 h after microhemorrhage induction, followed by every 12 h for three consecutive days. The water maze task was conducted 7 days after induction of microhemorrhages, followed by measurement of blood-brain barrier permeability, iron deposition, microglial activation, and dendritic damage. Laser-induced multiple microbleeds in the right parietal cortex clearly led to spatial memory disruption, iron deposits, microglial activation, and dendritic damage, which were significantly attenuated by DFX, supporting the targeting of iron overload as a therapeutic option and the significant potential of DFX in microhemorrhage treatment. Irons accumulation after intracranial hemorrhage induced a serious secondary damage to the brain. We proposed that irons accumulation after parietal microhemorrhages impaired spatial cognition. After parietal multiple microhemorrhages, increased irons and ferritin contents induced blood-brain barrier disruption, microglial activation, and further induced dendrites loss, eventually impaired the water maze, deferoxamine treatment protected from these damages. © 2016 International Society for Neurochemistry.

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.

Damage Assessment of Heat Resistant Steels through Electron BackScatter Diffraction Strain Analysis under Creep and Creep-Fatigue Conditions

NASA Astrophysics Data System (ADS)

Fujiyama, Kazunari; Kimachi, Hirohisa; Tsuboi, Toshiki; Hagiwara, Hiroyuki; Ogino, Shotaro; Mizutani, Yoshiki

EBSD(Electron BackScatter Diffraction) analyses were conducted for studying the quantitative microstructural metrics of creep and creep-fatigue damage for austenitic SUS304HTB boiler tube steel and ferritic Mod.9Cr piping steel. KAM(Kernel Average Misorientation) maps and GOS(Grain Orientation Spread) maps were obtained for these samples and the area averaged values KAMave and GOSave were obtained. While the increasing trends of these misorientation metrics were observed for SUS304HTB steel, the decreasing trends were observed for damaged Mod.9Cr steel with extensive recovery of subgrain structure. To establish more universal parameter representing the accumulation of damage to compensate these opposite trends, the EBSD strain parameters were introduced for converting the misorientation changes into the quantities representing accumulated permanent strains during creep and creep-fatigue damage process. As KAM values were dependent on the pixel size (inversely proportional to the observation magnification) and the permanent strain could be expressed as the shear strain which was the product of dislocation density, Burgers vector and dislocation movement distance, two KAM strain parameters MεKAMnet and MεδKAMave were introduced as the sum of product of the noise subtracted KAMnet and the absolute change from initial value δKAMave with dislocation movement distance divided by pixel size. MεδKAMave parameter showed better relationship both with creep strain in creep tests and accumulated creep strain range in creep-fatigue tests. This parameter can be used as the strain-based damage evaluation and detector of final failure.

Ultra-fast consensus of discrete-time multi-agent systems with multi-step predictive output feedback

NASA Astrophysics Data System (ADS)

Zhang, Wenle; Liu, Jianchang

2016-04-01

This article addresses the ultra-fast consensus problem of high-order discrete-time multi-agent systems based on a unified consensus framework. A novel multi-step predictive output mechanism is proposed under a directed communication topology containing a spanning tree. By predicting the outputs of a network several steps ahead and adding this information into the consensus protocol, it is shown that the asymptotic convergence factor is improved by a power of q + 1 compared to the routine consensus. The difficult problem of selecting the optimal control gain is solved well by introducing a variable called convergence step. In addition, the ultra-fast formation achievement is studied on the basis of this new consensus protocol. Finally, the ultra-fast consensus with respect to a reference model and robust consensus is discussed. Some simulations are performed to illustrate the effectiveness of the theoretical results.

Multi-off-grid methods in multi-step integration of ordinary differential equations

NASA Technical Reports Server (NTRS)

Beaudet, P. R.

1974-01-01

Description of methods of solving first- and second-order systems of differential equations in which all derivatives are evaluated at off-grid locations in order to circumvent the Dahlquist stability limitation on the order of on-grid methods. The proposed multi-off-grid methods require off-grid state predictors for the evaluation of the n derivatives at each step. Progressing forward in time, the off-grid states are predicted using a linear combination of back on-grid state values and off-grid derivative evaluations. A comparison is made between the proposed multi-off-grid methods and the corresponding Adams and Cowell on-grid integration techniques in integrating systems of ordinary differential equations, showing a significant reduction in the error at larger step sizes in the case of the multi-off-grid integrator.

Retro-peritoneal cooling for kidney preservation from multi-organ cadaver donors.

PubMed

Salazar-Bañuelos, Anastasio; Monroy-Cuadros, Mauricio; Henriquez-Cooper, Hoover

2018-05-01

Minimizing ischemia is paramount in the procurement of kidneys for transplantation. A fast cooling and expeditious removal is ideal to minimize damage from warm ischemia, however, since the removal of kidneys is delayed in cadaver donation until all other organs are harvested, the risk of kidney damage increases due to contact with the warmer soft body tissues. Surgical techniques that expedite organ retrieval were developed to avoid organ damage. We test a modification of Thomas Starzl's improved technique for multi-organ harvesting by interposing an ice bag between the posterior aspect of the kidney and the psoas muscle in a randomized trial with 21 multi-organ cadaver donors. The modified technique decreases the extraction temperature of the kidneys significantly in comparison with the controls, p < .001. This simple technique improves the preservation of kidneys from cadaver donors, and can potentially have more impact on multi-organ donation after cardiac death. Copyright © 2018 Elsevier Inc. All rights reserved.

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN): Could Retinoids Play a Causative Role?

PubMed Central

Mawson, Anthony R.; Eriator, Ike; Karre, Sridhar

2015-01-01

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are overlapping manifestations on a spectrum of acute drug-induced conditions associated with severe blistering, skin peeling, and multi-organ damage. TEN is an eruption resembling severe scalding, with ≥30% skin detachment. SJS is a mild form of TEN, characterized histologically by epidermal keratinocyte apoptosis with dermo-epidermal separation and extensive small blisters with <10% body surface skin detachment. The syndrome can be induced by numerous medications and typically occurs 1–4 weeks after the initiation of therapy. Granulysin is found in the lesions of patients with SJS/TEN and plays a significant pathogenic role in the condition, but the overall mechanisms linking medications, granulysin, and disease manifestations remain obscure. This paper reviews evidence suggesting that the different medications implicated in SJS/TEN have the common property of interacting and synergizing with endogenous retinoids (vitamin A and its congeners), in many instances causing the latter to accumulate in and damage the liver, the main storage organ for vitamin A. It is hypothesized that liver damage leads to the spillage of toxic retinoid compounds into the circulation, resulting in an endogenous form of hypervitaminosis A and cytotoxicity with widespread apoptosis, mediated by granulysin and recognized as SJS/TEN. Subject to testing, the model suggests that symptom worsening could be arrested at onset by lowering the concentration of circulating retinoids and/or granulysin via phlebotomy or plasmapheresis or by pharmacological measures to limit their expression. PMID:25579087

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN): could retinoids play a causative role?

PubMed

Mawson, Anthony R; Eriator, Ike; Karre, Sridhar

2015-01-12

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are overlapping manifestations on a spectrum of acute drug-induced conditions associated with severe blistering, skin peeling, and multi-organ damage. TEN is an eruption resembling severe scalding, with ≥30% skin detachment. SJS is a mild form of TEN, characterized histologically by epidermal keratinocyte apoptosis with dermo-epidermal separation and extensive small blisters with <10% body surface skin detachment. The syndrome can be induced by numerous medications and typically occurs 1-4 weeks after the initiation of therapy. Granulysin is found in the lesions of patients with SJS/TEN and plays a significant pathogenic role in the condition, but the overall mechanisms linking medications, granulysin, and disease manifestations remain obscure. This paper reviews evidence suggesting that the different medications implicated in SJS/TEN have the common property of interacting and synergizing with endogenous retinoids (vitamin A and its congeners), in many instances causing the latter to accumulate in and damage the liver, the main storage organ for vitamin A. It is hypothesized that liver damage leads to the spillage of toxic retinoid compounds into the circulation, resulting in an endogenous form of hypervitaminosis A and cytotoxicity with widespread apoptosis, mediated by granulysin and recognized as SJS/TEN. Subject to testing, the model suggests that symptom worsening could be arrested at onset by lowering the concentration of circulating retinoids and/or granulysin via phlebotomy or plasmapheresis or by pharmacological measures to limit their expression.

Application of pulsed multi-ion irradiations in radiation damage research: A stochastic cluster dynamics simulation study

NASA Astrophysics Data System (ADS)

Hoang, Tuan L.; Nazarov, Roman; Kang, Changwoo; Fan, Jiangyuan

2018-07-01

Under the multi-ion irradiation conditions present in accelerated material-testing facilities or fission/fusion nuclear reactors, the combined effects of atomic displacements with radiation products may induce complex synergies in the structural materials. However, limited access to multi-ion irradiation facilities and the lack of computational models capable of simulating the evolution of complex defects and their synergies make it difficult to understand the actual physical processes taking place in the materials under these extreme conditions. In this paper, we propose the application of pulsed single/dual-beam irradiation as replacements for the expensive steady triple-beam irradiation to study radiation damages in materials under multi-ion irradiation.

DELLAs Regulate Chlorophyll and Carotenoid Biosynthesis to Prevent Photooxidative Damage during Seedling Deetiolation in Arabidopsis[C][W

PubMed Central

Cheminant, Soizic; Wild, Michael; Bouvier, Florence; Pelletier, Sandra; Renou, Jean-Pierre; Erhardt, Mathieu; Hayes, Scott; Terry, Matthew J.; Genschik, Pascal; Achard, Patrick

2011-01-01

In plants, light represents an important environmental signal that triggers the production of photosynthetically active chloroplasts. This developmental switch is critical for plant survival because chlorophyll precursors that accumulate in darkness can be extremely destructive when illuminated. Thus, plants have evolved mechanisms to adaptively control plastid development during the transition into light. Here, we report that the gibberellin (GA)-regulated DELLA proteins play a crucial role in the formation of functional chloroplasts during deetiolation. We show that Arabidopsis thaliana DELLAs accumulating in etiolated cotyledons derepress chlorophyll and carotenoid biosynthetic pathways in the dark by repressing the transcriptional activity of the phytochrome-interacting factor proteins. Accordingly, dark-grown GA-deficient ga1-3 mutants (that accumulate DELLAs) display a similar gene expression pattern to wild-type seedlings grown in the light. Consistent with this, ga1-3 seedlings accumulate higher amounts of protochlorophyllide (a phototoxic chlorophyll precursor) in darkness but, surprisingly, are substantially more resistant to photooxidative damage following transfer into light. This is due to the DELLA-dependent upregulation of the photoprotective enzyme protochlorophyllide oxidoreductase (POR) in the dark. Our results emphasize the role of DELLAs in regulating the levels of POR, protochlorophyllide, and carotenoids in the dark and in protecting etiolated seedlings against photooxidative damage during initial light exposure. PMID:21571951

Catastrophic optical bulk degradation in high-power single- and multi-mode InGaAs-AlGaAs strained QW lasers: part II

NASA Astrophysics Data System (ADS)

Sin, Yongkun; Ayvazian, Talin; Brodie, Miles; Lingley, Zachary

2018-03-01

High-power single-mode (SM) and multi-mode (MM) InGaAs-AlGaAs strained quantum well (QW) lasers are critical components for both terrestrial and space satellite communications systems. Since these lasers predominantly fail by catastrophic and sudden degradation due to catastrophic optical damage (COD), it is especially crucial for space satellite applications to investigate reliability, failure modes, precursor signatures of failure, and degradation mechanisms of these lasers. Our group reported a new failure mode in MM and SM InGaAs-AlGaAs strained QW lasers in 2009 and 2016, respectively. Our group also reported in 2017 that bulk failure due to catastrophic optical bulk damage (COBD) is the dominant failure mode of both SM and MM lasers that were subject to long-term life-tests. For the present study, we continued our physics of failure investigation by performing long-term life-tests followed by failure mode analysis (FMA) using nondestructive and destructive micro-analytical techniques. We performed long-term accelerated life-tests on state-of-the-art SM and MM InGaAs- AlGaAs strained QW lasers under ACC mode. Our life-tests have accumulated over 25,000 test hours for SM lasers and over 35,000 test hours for MM lasers. We first employed electron beam induced current (EBIC) technique to identify failure modes of degraded SM lasers by observing dark line defects. All the SM failures that we studied showed catastrophic and sudden degradation and all of these failures were bulk failures. Since degradation mechanisms responsible for COBD are still not well understood, we also employed other techniques including focused ion beam (FIB) and high-resolution TEM to further study dark line defects and dislocations in post-aged lasers. Keywor

BN-FLEMOps pluvial - A probabilistic multi-variable loss estimation model for pluvial floods

NASA Astrophysics Data System (ADS)

Roezer, V.; Kreibich, H.; Schroeter, K.; Doss-Gollin, J.; Lall, U.; Merz, B.

2017-12-01

Pluvial flood events, such as in Copenhagen (Denmark) in 2011, Beijing (China) in 2012 or Houston (USA) in 2016, have caused severe losses to urban dwellings in recent years. These floods are caused by storm events with high rainfall rates well above the design levels of urban drainage systems, which lead to inundation of streets and buildings. A projected increase in frequency and intensity of heavy rainfall events in many areas and an ongoing urbanization may increase pluvial flood losses in the future. For an efficient risk assessment and adaptation to pluvial floods, a quantification of the flood risk is needed. Few loss models have been developed particularly for pluvial floods. These models usually use simple waterlevel- or rainfall-loss functions and come with very high uncertainties. To account for these uncertainties and improve the loss estimation, we present a probabilistic multi-variable loss estimation model for pluvial floods based on empirical data. The model was developed in a two-step process using a machine learning approach and a comprehensive database comprising 783 records of direct building and content damage of private households. The data was gathered through surveys after four different pluvial flood events in Germany between 2005 and 2014. In a first step, linear and non-linear machine learning algorithms, such as tree-based and penalized regression models were used to identify the most important loss influencing factors among a set of 55 candidate variables. These variables comprise hydrological and hydraulic aspects, early warning, precaution, building characteristics and the socio-economic status of the household. In a second step, the most important loss influencing variables were used to derive a probabilistic multi-variable pluvial flood loss estimation model based on Bayesian Networks. Two different networks were tested: a score-based network learned from the data and a network based on expert knowledge. Loss predictions are made through Bayesian inference using Markov chain Monte Carlo (MCMC) sampling. With the ability to cope with incomplete information and use expert knowledge, as well as inherently providing quantitative uncertainty information, it is shown that loss models based on BNs are superior to deterministic approaches for pluvial flood risk assessment.

Antioxidant Properties of Proanthocyanidins Attenuate Carbon Tetrachloride (CCl4)–Induced Steatosis and Liver Injury in Rats via CYP2E1 Regulation

PubMed Central

Zou, Yuan; Zhu, Lei; Wang, Hui-Fang; Dai, Mu-Gen

2014-01-01

Abstract Liver steatosis is characterized by lipid dysregulation and fat accumulation in the liver and can lead to oxidative stress in liver. Since proanthocyanidins are present in plant-based foods and have powerful antioxidant properties, we investigated whether proanthocyanidins can prevent oxidative stress and subsequent liver injury. Carbon tetrachloride (CCl4) treatment can cause steatosis in rats that models both alcoholic and non-alcoholic fatty liver disease in humans. We pre-treated rats by oral administration of proanthocyanidins extracted from grape seeds 7 days prior to intragastrically administering CCl4. Proanthocyanidin treatment continued for an additional 2 weeks, after which time liver and serum were harvested, and mediators of liver injury, oxidative stress, and histological features were evaluated. CCl4-treated rats exhibited significant increases in the following parameters as compared to non-treated rats: fat droplets in the liver, liver injury (ALT, AST), and DNA damage (8-OHdG). Additionally, CCl4 treatment decreased antioxidant enzymes SOD, GSH, GPX, and CAT in the liver due to their rapid depletion after battling against oxidative stress. Compared to CCl4-treated rats, treatment with proanthocyanidins effectively suppressed lipid accumulation, liver injury, DNA damage, as well as restored antioxidant enzyme levels. Further investigation revealed that proanthocyanidins treatment also inhibited expression of CYP2E1 in liver, which prevented the initial step of generating free radicals from CCl4. The data presented here show that treatment with orally administered proanthocyanidins prevented liver injury in the CCl4-induced steatosis model, likely through exerting antioxidant actions to suppress oxidative stress and inhibiting the free radical–generating CYP2E1 enzyme. PMID:24712752

Antioxidant properties of proanthocyanidins attenuate carbon tetrachloride (CCl4)-induced steatosis and liver injury in rats via CYP2E1 regulation.

PubMed

Dai, Ning; Zou, Yuan; Zhu, Lei; Wang, Hui-Fang; Dai, Mu-Gen

2014-06-01

Liver steatosis is characterized by lipid dysregulation and fat accumulation in the liver and can lead to oxidative stress in liver. Since proanthocyanidins are present in plant-based foods and have powerful antioxidant properties, we investigated whether proanthocyanidins can prevent oxidative stress and subsequent liver injury. Carbon tetrachloride (CCl4) treatment can cause steatosis in rats that models both alcoholic and non-alcoholic fatty liver disease in humans. We pre-treated rats by oral administration of proanthocyanidins extracted from grape seeds 7 days prior to intragastrically administering CCl4. Proanthocyanidin treatment continued for an additional 2 weeks, after which time liver and serum were harvested, and mediators of liver injury, oxidative stress, and histological features were evaluated. CCl4-treated rats exhibited significant increases in the following parameters as compared to non-treated rats: fat droplets in the liver, liver injury (ALT, AST), and DNA damage (8-OHdG). Additionally, CCl4 treatment decreased antioxidant enzymes SOD, GSH, GPX, and CAT in the liver due to their rapid depletion after battling against oxidative stress. Compared to CCl4-treated rats, treatment with proanthocyanidins effectively suppressed lipid accumulation, liver injury, DNA damage, as well as restored antioxidant enzyme levels. Further investigation revealed that proanthocyanidins treatment also inhibited expression of CYP2E1 in liver, which prevented the initial step of generating free radicals from CCl4. The data presented here show that treatment with orally administered proanthocyanidins prevented liver injury in the CCl4-induced steatosis model, likely through exerting antioxidant actions to suppress oxidative stress and inhibiting the free radical-generating CYP2E1 enzyme.

ATM-activated autotaxin (ATX) propagates inflammation and DNA damage in lung epithelial cells: a new mode of action for silica-induced DNA damage?

PubMed

Zheng, Huiyuan; Högberg, Johan; Stenius, Ulla

2017-12-07

Silica exposure is a common risk factor for lung cancer. It has been claimed that key elements in cancer development are activation of inflammatory cells that indirectly induce DNA damage and proliferative stimuli in respiratory epithelial cells. We studied DNA damage induced by silica particles in respiratory epithelial cells and focused the role of the signaling enzyme autotaxin (ATX). A549 and 16 bronchial epithelial cells (16HBE) lung epithelial cells were exposed to silica particles. Reactive oxygen species (ROS), NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome activation, ATX, ataxia telangiectasia mutated (ATM), and DNA damage (γH2AX, pCHK1, pCHK2, comet assay) were end points. Low doses of silica induced NLRP3 activation, DNA damage accumulation, and ATM phosphorylation. A novel finding was that ATM induced ATX generation and secretion. Not only silica but also rotenone, camptothecin and H2O2 activated ATX via ATM, suggesting that ATX is part of a generalized ATM response to double-strand breaks (DSBs). Surprisingly, ATX inhibition mitigated DNA damage accumulation at later time points (6-16 h), and ATX transfection caused NLRP3 activation and DNA damage. Furthermore, the product of ATX enzymatic activity, lysophosphatidic acid, recapitulated the effects of ATX transfection. These data indicate an ATM-ATX-dependent loop that propagates inflammation and DSB accumulation, making low doses of silica effective inducers of DSBs in epithelial cells. We conclude that an ATM-ATX axis interconnects DSBs with silica-induced inflammation and propagates these effects in epithelial cells. Further studies of this adverse outcome pathway may give an accurate assessment of the lowest doses of silica that causes cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Zoledronate Attenuates Accumulation of DNA Damage in Mesenchymal Stem Cells and Protects Their Function

PubMed Central

Misra, Juhi; Mohanty, Sindhu T.; Madan, Sanjeev; Fernandes, James A.; Hal Ebetino, F.; Russell, R. Graham G.

2015-01-01

Abstract Mesenchymal stem cells (MSCs) undergo a decline in function following ex vivo expansion and exposure to irradiation. This has been associated with accumulation of DNA damage and has important implications for tissue engineering approaches or in patients receiving radiotherapy. Therefore, interventions, which limit accumulation of DNA damage in MSC, are of clinical significance. We were intrigued by findings showing that zoledronate (ZOL), an anti‐resorptive nitrogen containing bisphosphonate, significantly extended survival in patients affected by osteoporosis. The effect was too large to be simply due to the prevention of fractures. Moreover, in combination with statins, it extended the lifespan in a mouse model of Hutchinson Gilford Progeria Syndrome. Therefore, we asked whether ZOL was able to extend the lifespan of human MSC and whether this was due to reduced accumulation of DNA damage, one of the important mechanisms of aging. Here, we show that this was the case both following expansion and irradiation, preserving their ability to proliferate and differentiate in vitro. In addition, administration of ZOL before irradiation protected the survival of mesenchymal progenitors in mice. Through mechanistic studies, we were able to show that inhibition of mTOR signaling, a pathway involved in longevity and cancer, was responsible for these effects. Our data open up new opportunities to protect MSC from the side effects of radiotherapy in cancer patients and during ex vivo expansion for regenerative medicine approaches. Given that ZOL is already in clinical use with a good safety profile, these opportunities can be readily translated for patient benefit. Stem Cells 2016;34:756–767 PMID:26679354

Zoledronate Attenuates Accumulation of DNA Damage in Mesenchymal Stem Cells and Protects Their Function.

PubMed

Misra, Juhi; Mohanty, Sindhu T; Madan, Sanjeev; Fernandes, James A; Hal Ebetino, F; Russell, R Graham G; Bellantuono, Ilaria

2016-03-01

Mesenchymal stem cells (MSCs) undergo a decline in function following ex vivo expansion and exposure to irradiation. This has been associated with accumulation of DNA damage and has important implications for tissue engineering approaches or in patients receiving radiotherapy. Therefore, interventions, which limit accumulation of DNA damage in MSC, are of clinical significance. We were intrigued by findings showing that zoledronate (ZOL), an anti-resorptive nitrogen containing bisphosphonate, significantly extended survival in patients affected by osteoporosis. The effect was too large to be simply due to the prevention of fractures. Moreover, in combination with statins, it extended the lifespan in a mouse model of Hutchinson Gilford Progeria Syndrome. Therefore, we asked whether ZOL was able to extend the lifespan of human MSC and whether this was due to reduced accumulation of DNA damage, one of the important mechanisms of aging. Here, we show that this was the case both following expansion and irradiation, preserving their ability to proliferate and differentiate in vitro. In addition, administration of ZOL before irradiation protected the survival of mesenchymal progenitors in mice. Through mechanistic studies, we were able to show that inhibition of mTOR signaling, a pathway involved in longevity and cancer, was responsible for these effects. Our data open up new opportunities to protect MSC from the side effects of radiotherapy in cancer patients and during ex vivo expansion for regenerative medicine approaches. Given that ZOL is already in clinical use with a good safety profile, these opportunities can be readily translated for patient benefit. © 2015 AlphaMed Press.

Mitochondria and mitochondrial DNA as relevant targets for environmental contaminants.

PubMed

Roubicek, Deborah A; Souza-Pinto, Nadja C de

2017-11-01

The mitochondrial DNA (mtDNA) is a closed circular molecule that encodes, in humans, 13 polypeptides components of the oxidative phosphorylation complexes. Integrity of the mitochondrial genome is essential for mitochondrial function and cellular homeostasis, and mutations and deletions in the mtDNA lead to oxidative stress, mitochondrial dysfunction and cell death. In vitro and in situ studies suggest that when exposed to certain genotoxins, mtDNA accumulates more damage than nuclear DNA, likely owing to its organization and localization in the mitochondrial matrix, which tends to accumulate lipophilic, positively charged molecules. In that regard, several relevant environmental and occupational contaminants have physical-chemical characteristics that indicate that they might accumulate in mitochondria and target mtDNA. Nonetheless, very little is known so far about mtDNA damage and mitochondrial dysfunction due to environmental exposure, either in model organisms or in humans. In this article, we discuss some of the characteristics of mtDNA which render it a potentially relevant target for damage by environmental contaminants, as well as possible functional consequences of damage/mutation accumulation. In addition, we review the data available in the literature focusing on mitochondrial effects of the most common classes of environmental pollutants. From that, we conclude that several lines of experimental evidence support the idea that mitochondria and mtDNA are susceptible and biologically relevant targets for pollutants, and more studies, including mechanistic ones, are needed to shed more light into the contribution of mitochondrial dysfunction to the environmental and human health effects of chemical exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

TOPICAL REVIEW: Smart aggregates: multi-functional sensors for concrete structures—a tutorial and a review

NASA Astrophysics Data System (ADS)

Song, Gangbing; Gu, Haichang; Mo, Yi-Lung

2008-06-01

This paper summarizes the authors' recent pioneering research work in piezoceramic-based smart aggregates and their innovative applications in concrete civil structures. The basic operating principle of smart aggregates is first introduced. The proposed smart aggregate is formed by embedding a waterproof piezoelectric patch with lead wires into a small concrete block. The proposed smart aggregates are multi-functional and can perform three major tasks: early-age concrete strength monitoring, impact detection and structural health monitoring. The proposed smart aggregates are embedded into the desired location before the casting of the concrete structure. The concrete strength development is monitored by observing the high frequency harmonic wave response of the smart aggregate. Impact on the concrete structure is detected by observing the open-circuit voltage of the piezoceramic patch in the smart aggregate. For structural health monitoring purposes, a smart aggregate-based active sensing system is designed for the concrete structure. Wavelet packet analysis is used as a signal-processing tool to analyze the sensor signal. A damage index based on the wavelet packet analysis is used to determine the structural health status. To better describe the time-history and location information of damage, two types of damage index matrices are proposed: a sensor-history damage index matrix and an actuator-sensor damage index matrix. To demonstrate the multi-functionality of the proposed smart aggregates, different types of concrete structures have been used as test objects, including concrete bridge bent-caps, concrete cylinders and a concrete frame. Experimental results have verified the effectiveness and the multi-functionality of the proposed smart aggregates. The multi-functional smart aggregates have the potential to be applied to the comprehensive monitoring of concrete structures from their earliest stages and throughout their lifetime.

Mathematical Methods for Studying DNA and Protein Interactions

NASA Astrophysics Data System (ADS)

LeGresley, Sarah

Deoxyribnucleic Acid (DNA) damage can lead to health related issues such as developmental disorders, aging, and cancer. It has been estimated that damage rates may be as high as 100,000 per cell per day. Because of the devastating effects that DNA damage can have, DNA repair mechanisms are of great interest yet are not completely understood. To gain a better understanding of possible DNA repair mechanisms, my dissertation focused on mathematical methods for understanding the interactions between DNA and proteins. I developed a damaged DNA model to estimate the probabilities of damaged DNA being located at specific positions. Experiments were then performed that suggested that the damaged DNA may be repositioned. These experimental results were consistent with the model's prediction that damaged DNA has preferred locations. To study how proteins might be moving along the DNA, I studied the use of the uniform motion "n-step" model. The n-step model has been used to determine the kinetics parameters (e.g. rates at which a protein moves along the DNA, how much energy is required to move a protein along a specified amount of DNA, etc.) of proteins moving along the DNA. Monte Carlo methods were used to simulate proteins moving with different types of non-uniform motion (e.g. backward, jumping, etc.) along the DNA. Estimates for the kinetics parameters in the n-step model were found by fitting of the Monte Carlo simulation data. Analysis indicated that non-uniform motion of the protein may lead to over or underestimation of the kinetic parameters of this n-step model.

Regulatory effects of curcumin on lipid accumulation in monocytes/macrophages

USDA-ARS?s Scientific Manuscript database

Recent evidence suggests potential benefits from phytochemicals and micronutrients in protecting against oxidative and lipid-mediated damage, but the molecular mechanisms of these actions are still unclear. Here we investigated whether the dietary polyphenol curcumin can modulate the accumulation of...

Multi-step prediction for influenza outbreak by an adjusted long short-term memory.

PubMed

Zhang, J; Nawata, K

2018-05-01

Influenza results in approximately 3-5 million annual cases of severe illness and 250 000-500 000 deaths. We urgently need an accurate multi-step-ahead time-series forecasting model to help hospitals to perform dynamical assignments of beds to influenza patients for the annually varied influenza season, and aid pharmaceutical companies to formulate a flexible plan of manufacturing vaccine for the yearly different influenza vaccine. In this study, we utilised four different multi-step prediction algorithms in the long short-term memory (LSTM). The result showed that implementing multiple single-output prediction in a six-layer LSTM structure achieved the best accuracy. The mean absolute percentage errors from two- to 13-step-ahead prediction for the US influenza-like illness rates were all <15%, averagely 12.930%. To the best of our knowledge, it is the first time that LSTM has been applied and refined to perform multi-step-ahead prediction for influenza outbreaks. Hopefully, this modelling methodology can be applied in other countries and therefore help prevent and control influenza worldwide.

Interacting effects of early dietary conditions and reproductive effort on the oxidative costs of reproduction

PubMed Central

2017-01-01

The hypothesis that oxidative damage accumulation can mediate the trade-off between reproduction and lifespan has recently been questioned. However, in captive conditions, studies reporting no evidence in support of this hypothesis have usually provided easy access to food which may have mitigated the cost of reproduction. Here, I test the hypothesis that greater investment in reproduction should lead to oxidative damage accumulation and telomere loss in domestic zebra finches Taeniopygia guttata. Moreover, since the change or fluctuation in diet composition between early and late postnatal period can impair the ability to produce antioxidant defences in zebra finches, I also tested if early nutritional conditions (constant vs fluctuating early diet) influenced the magnitude of any subsequent costs of reproduction (e.g., oxidative damage and/or telomere shortening). In comparison to pairs with reduced broods, the birds that had to feed enlarged broods showed a higher level of oxidative DNA damage (8-OHdG), but brood size had no effect on telomeres. Fluctuating early diet composition reduced the capacity to maintain the activity of endogenous antioxidants (GPx), particularly when reproductive costs were increased (enlarged brood). The decline in GPx in birds feeding enlarged broods was accompanied by a change in bill colouration. This suggests that birds with lower endogenous antioxidant defences might have strategically increased the mobilization of antioxidants previously stored in other tissues (i.e., bill and liver) and thus, preventing an excessive accumulation of damage during reproduction. PMID:28316895

From monoscale to multiscale modeling of fatigue crack growth: Stress and energy density factor

NASA Astrophysics Data System (ADS)

Sih, G. C.

2014-01-01

The formalism of the earlier fatigue crack growth models is retained to account for multiscaling of the fatigue process that involves the creation of macrocracks from the accumulation of micro damage. The effects of at least two scales, say micro to macro, must be accounted for. The same data can thus be reinterpreted by the invariancy of the transitional stress intensity factors such that the microcracking and macrocracking data would lie on a straight line. The threshold associated with the sigmoid curve disappears. Scale segmentation is shown to be a necessity for addressing multiscale energy dissipative processes such as fatigue and creep. Path independency and energy release rate are monoscale criteria that can lead to unphysical results, violating the first principles. Application of monoscale failure or fracture criteria to nanomaterials is taking toll at the expense of manufacturing super strength and light materials and structural components. This brief view is offered in the spirit of much needed additional research for the reinforcement of materials by creating nanoscale interfaces with sustainable time in service. The step by step consideraton at the different scales may offer a better understanding of the test data and their limitations with reference to space and time.

SIRT3 Links Oxidative Stress with Aging and Cancer | Center for Cancer Research

Cancer.gov

When cells produce energy, they also form reactive oxygen molecules capable of damaging proteins and DNA. Normally, these molecules are neutralized by a protein called superoxide dismutase, or SOD. However, as a cell ages, oxidative damage accumulates. The increase in oxidative cellular damage as people age may provide a mechanistic connection between aging and carcinogenesis.

Statistical Models of Fracture Relevant to Nuclear-Grade Graphite: Review and Recommendations

NASA Technical Reports Server (NTRS)

Nemeth, Noel N.; Bratton, Robert L.

2011-01-01

The nuclear-grade (low-impurity) graphite needed for the fuel element and moderator material for next-generation (Gen IV) reactors displays large scatter in strength and a nonlinear stress-strain response from damage accumulation. This response can be characterized as quasi-brittle. In this expanded review, relevant statistical failure models for various brittle and quasi-brittle material systems are discussed with regard to strength distribution, size effect, multiaxial strength, and damage accumulation. This includes descriptions of the Weibull, Batdorf, and Burchell models as well as models that describe the strength response of composite materials, which involves distributed damage. Results from lattice simulations are included for a physics-based description of material breakdown. Consideration is given to the predicted transition between brittle and quasi-brittle damage behavior versus the density of damage (level of disorder) within the material system. The literature indicates that weakest-link-based failure modeling approaches appear to be reasonably robust in that they can be applied to materials that display distributed damage, provided that the level of disorder in the material is not too large. The Weibull distribution is argued to be the most appropriate statistical distribution to model the stochastic-strength response of graphite.

Measurement of intrahepatic pressure during radiofrequency ablation in porcine liver.

PubMed

Kawamoto, Chiaki; Yamauchi, Atsushi; Baba, Yoko; Kaneko, Keiko; Yakabi, Koji

2010-04-01

To identify the most effective procedures to avoid increased intrahepatic pressure during radiofrequency ablation, we evaluated different ablation methods. Laparotomy was performed in 19 pigs. Intrahepatic pressure was monitored using an invasive blood pressure monitor. Radiofrequency ablation was performed as follows: single-step standard ablation; single-step at 30 W; single-step at 70 W; 4-step at 30 W; 8-step at 30 W; 8-step at 70 W; and cooled-tip. The array was fully deployed in single-step methods. In the multi-step methods, the array was gradually deployed in four or eight steps. With the cooled-tip, ablation was performed by increasing output by 10 W/min, starting at 40 W. Intrahepatic pressure was as follows: single-step standard ablation, 154.5 +/- 30.9 mmHg; single-step at 30 W, 34.2 +/- 20.0 mmHg; single-step at 70 W, 46.7 +/- 24.3 mmHg; 4-step at 30 W, 42.3 +/- 17.9 mmHg; 8-step at 30 W, 24.1 +/- 18.2 mmHg; 8-step at 70 W, 47.5 +/- 31.5 mmHg; and cooled-tip, 114.5 +/- 16.6 mmHg. The radiofrequency ablation-induced area was spherical with single-step standard ablation, 4-step at 30 W, and 8-step at 30 W. Conversely, the ablated area was irregular with single-step at 30 W, single-step at 70 W, and 8-step at 70 W. The ablation time was significantly shorter for the multi-step method than for the single-step method. Increased intrahepatic pressure could be controlled using multi-step methods. From the shapes of the ablation area, 30-W 8-step expansions appear to be most suitable for radiofrequency ablation.

In Pursuit of Improving Airburst and Ground Damage Predictions: Recent Advances in Multi-Body Aerodynamic Testing and Computational Tools Validation

NASA Technical Reports Server (NTRS)

Venkatapathy, Ethiraj; Gulhan, Ali; Aftosmis, Michael; Brock, Joseph; Mathias, Donovan; Need, Dominic; Rodriguez, David; Seltner, Patrick; Stern, Eric; Wiles, Sebastian

2017-01-01

An airburst from a large asteroid during entry can cause significant ground damage. The damage depends on the energy and the altitude of airburst. Breakup of asteroids into fragments and their lateral spread have been observed. Modeling the underlying physics of fragmented bodies interacting at hypersonic speeds and the spread of fragments is needed for a true predictive capability. Current models use heuristic arguments and assumptions such as pancaking or point source explosive energy release at pre-determined altitude or an assumed fragmentation spread rate to predict airburst damage. A multi-year collaboration between German Aerospace Center (DLR) and NASA has been established to develop validated computational tools to address the above challenge.

Immune response is required for the control of in vivo translocation and chronic toxicity of graphene oxide

NASA Astrophysics Data System (ADS)

Wu, Qiuli; Zhao, Yunli; Fang, Jianpeng; Wang, Dayong

2014-05-01

Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO toxicity and accumulation in the intestine and maintained the relatively normal immune response of animals. The severe accumulation of OP50 in the intestine might be partially due to the damage by GO on the development and function of AVL and DVB neurons controlling defecation behavior. Reduction of chronic GO toxicity by PEG surface modification largely resulted from the inhibition of OP50 accumulation in the intestine and the maintenance of normal immune response. Our results highlight the key role of innate immunity in regulating in vivo chronic GO toxicity, which will be helpful for our understanding of the interactions between nanomaterials and biological systems during the long-term development of animals.Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO toxicity and accumulation in the intestine and maintained the relatively normal immune response of animals. The severe accumulation of OP50 in the intestine might be partially due to the damage by GO on the development and function of AVL and DVB neurons controlling defecation behavior. Reduction of chronic GO toxicity by PEG surface modification largely resulted from the inhibition of OP50 accumulation in the intestine and the maintenance of normal immune response. Our results highlight the key role of innate immunity in regulating in vivo chronic GO toxicity, which will be helpful for our understanding of the interactions between nanomaterials and biological systems during the long-term development of animals. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr00699b

Modeling of karst deformation and analysis of acoustic emission during sinkhole formation

NASA Astrophysics Data System (ADS)

Bakeev, R. A.; Stefanov, Yu. P.; Duchkov, A. A.; Myasnikov, A. V.

2017-12-01

In this paper, the fracture pattern and formation of a sinkhole are estimated depending on the rock properties. The possibility of using geophysical methods for recording and analyzing acoustic emission to monitor and predict the state of the medium is considered. The problem of deformation of the sedimentary cover over the growing karst cavity is solved on the basis of the elastoplastic Drucker-Prager-Nikolaevsky model and the equation of damage accumulation. The specified kinetics of accumulation of damages allows us to describe slow processes of degradation of the strength of the medium under stresses that are low for the development of inelastic deformations. The results are obtained for different values of the strength of karst rock; we show the influence of the kinetic parameters of damage accumulation on the shape of collapse depressions. We also model acoustic emission caused by the material fracture. One can follow different stages of the karst development by looking at patterns of cells which fail at a given time. Our observations show the relation between the intensity of material fracture and the intensity of seismic emission.

Accumulation of Senescent Cells in Mitotic Tissue of Aging Primates

PubMed Central

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

2013-01-01

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

Damage Tolerance of Large Shell Structures

NASA Technical Reports Server (NTRS)

Minnetyan, L.; Chamis, C. C.

1999-01-01

Progressive damage and fracture of large shell structures is investigated. A computer model is used for the assessment of structural response, progressive fracture resistance, and defect/damage tolerance characteristics. Critical locations of a stiffened conical shell segment are identified. Defective and defect-free computer models are simulated to evaluate structural damage/defect tolerance. Safe pressurization levels are assessed for the retention of structural integrity at the presence of damage/ defects. Damage initiation, growth, accumulation, and propagation to fracture are included in the simulations. Damage propagation and burst pressures for defective and defect-free shells are compared to evaluate damage tolerance. Design implications with regard to defect and damage tolerance of a large steel pressure vessel are examined.

Lagrangian methods for blood damage estimation in cardiovascular devices - How numerical implementation affects the results

PubMed Central

Marom, Gil; Bluestein, Danny

2016-01-01

Summary This paper evaluated the influence of various numerical implementation assumptions on predicting blood damage in cardiovascular devices using Lagrangian methods with Eulerian computational fluid dynamics. The implementation assumptions that were tested included various seeding patterns, stochastic walk model, and simplified trajectory calculations with pathlines. Post processing implementation options that were evaluated included single passage and repeated passages stress accumulation and time averaging. This study demonstrated that the implementation assumptions can significantly affect the resulting stress accumulation, i.e., the blood damage model predictions. Careful considerations should be taken in the use of Lagrangian models. Ultimately, the appropriate assumptions should be considered based the physics of the specific case and sensitivity analysis, similar to the ones presented here, should be employed. PMID:26679833

An Examination of Four Traditional School Physical Activity Models on Children's Step Counts and MVPA.

PubMed

Brusseau, Timothy A; Kulinna, Pamela H

2015-03-01

Schools have been identified as primary societal institutions for promoting children's physical activity (PA); however, limited evidence exists demonstrating which traditional school-based PA models maximize children's PA. The purpose of this study was to compare step counts and moderate-to-vigorous physical activity (MVPA) across 4 traditional school PA modules. Step count and MVPA data were collected on 5 consecutive school days from 298 children (Mage = 10.0 ± 0.6 years; 55% female) in Grade 5. PA was measured using the NL-1000 piezoelectric pedometer. The 4 models included (a) recess only, (b) multiple recesses, (c) recess and physical education (PE), and (d) multiple recesses and PE. Children accumulated the greatest PA on days that they had PE and multiple recess opportunities (5,242 ± 1,690 steps; 15.3 ± 8.8 min of MVPA). Children accumulated the least amount of PA on days with only 1 recess opportunity (3,312 ± 445 steps; 7.1 ± 2.3 min of MVPA). Across all models, children accumulated an additional 1,140 steps and 4.1 min of MVPA on PE days. It appears that PE is the most important school PA opportunity for maximizing children's PA. However, on days without PE, a 2nd recess can increase school PA by 20% (Δ = 850 steps; 3.8 min of MVPA).

Long-term strength and damage accumulation in laminates

NASA Astrophysics Data System (ADS)

Dzenis, Yuris A.; Joshi, Shiv P.

1993-04-01

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

Black soybean seed coat polyphenols prevent AAPH-induced oxidative DNA-damage in HepG2 cells

PubMed Central

Yoshioka, Yasukiyo; Li, Xiu; Zhang, Tianshun; Mitani, Takakazu; Yasuda, Michiko; Nanba, Fumio; Toda, Toshiya; Yamashita, Yoko; Ashida, Hitoshi

2017-01-01

Black soybean seed coat extract (BE), which contains abundant polyphenols such as procyanidins, cyanidin 3-glucoside, (+)-catechin, and (−)­epicatechin, has been reported on health beneficial functions such as antioxidant activity, anti-inflammatory, anti-obesity, and anti-diabetic activities. In this study, we investigated that prevention of BE and its polyphenols on 2,2'-azobis(2-methylpropionamide) dihydrochloride (AAPH)-induced oxidative DNA damage, and found that these polyphenols inhibited AAPH-induced formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a biomarker for oxidative DNA damage in HepG2 cells. Under the same conditions, these polyphenols also inhibited AAPH-induced accumulation of reactive oxygen species (ROS) in the cells. Inhibition of ROS accumulation was observed in both cytosol and nucleus. It was confirmed that these polyphenols inhibited formation of AAPH radical using oxygen radical absorbance capacity assay under the cell-free conditions. These results indicate that polyphenols in BE inhibit free radical-induced oxidative DNA damages by their potent antioxidant activity. Thus, BE is an effective food material for prevention of oxidative stress and oxidative DNA damages. PMID:28366989

Integrative Sparse K-Means With Overlapping Group Lasso in Genomic Applications for Disease Subtype Discovery

PubMed Central

Huo, Zhiguang; Tseng, George

2017-01-01

Cancer subtypes discovery is the first step to deliver personalized medicine to cancer patients. With the accumulation of massive multi-level omics datasets and established biological knowledge databases, omics data integration with incorporation of rich existing biological knowledge is essential for deciphering a biological mechanism behind the complex diseases. In this manuscript, we propose an integrative sparse K-means (is-K means) approach to discover disease subtypes with the guidance of prior biological knowledge via sparse overlapping group lasso. An algorithm using an alternating direction method of multiplier (ADMM) will be applied for fast optimization. Simulation and three real applications in breast cancer and leukemia will be used to compare is-K means with existing methods and demonstrate its superior clustering accuracy, feature selection, functional annotation of detected molecular features and computing efficiency. PMID:28959370

Integrative Sparse K-Means With Overlapping Group Lasso in Genomic Applications for Disease Subtype Discovery.

PubMed

Huo, Zhiguang; Tseng, George

2017-06-01

Cancer subtypes discovery is the first step to deliver personalized medicine to cancer patients. With the accumulation of massive multi-level omics datasets and established biological knowledge databases, omics data integration with incorporation of rich existing biological knowledge is essential for deciphering a biological mechanism behind the complex diseases. In this manuscript, we propose an integrative sparse K -means (is- K means) approach to discover disease subtypes with the guidance of prior biological knowledge via sparse overlapping group lasso. An algorithm using an alternating direction method of multiplier (ADMM) will be applied for fast optimization. Simulation and three real applications in breast cancer and leukemia will be used to compare is- K means with existing methods and demonstrate its superior clustering accuracy, feature selection, functional annotation of detected molecular features and computing efficiency.

In vivo imaging of spinal cord in contusion injury model mice by multi-photon microscopy

NASA Astrophysics Data System (ADS)

Oshima, Y.; Horiuchi, H.; Ogata, T.; Hikita, A.; Miura, H.; Imamura, T.

2014-03-01

Fluorescent imaging technique is a promising method and has been developed for in vivo applications in cellular biology. In particular, nonlinear optical imaging technique, multi-photon microscopy has make it possible to analyze deep portion of tissues in living animals such as axons of spinal code. Traumatic spinal cord injuries (SCIs) are usually caused by contusion damages. Therefore, observation of spinal cord tissue after the contusion injury is necessary for understanding cellular dynamics in response to traumatic SCI and development of the treatment for traumatic SCI. Our goal is elucidation of mechanism for degeneration of axons after contusion injuries by establishing SCI model and chronic observation of injured axons in the living animals. Firstly we generated and observed acute SCI model by contusion injury. By using a multi-photon microscope, axons in dorsal cord were visualized approximately 140 micron in depth from the surface. Immediately after injury, minimal morphological change of spinal cord was observed. At 3 days after injury, spinal cord was swelling and the axons seem to be fragmented. At 7 days after injury, increased degradation of axons could be observed, although the image was blurred due to accumulation of the connective tissue. In the present study, we successfully observed axon degeneration after the contusion SCI in a living animal in vivo. Our final goal is to understand molecular mechanisms and cellular dynamics in response to traumatic SCIs in acute and chronic stage.

Mathematical Modeling of Nitrous Oxide Production during Denitrifying Phosphorus Removal Process.

PubMed

Liu, Yiwen; Peng, Lai; Chen, Xueming; Ni, Bing-Jie

2015-07-21

A denitrifying phosphorus removal process undergoes frequent alternating anaerobic/anoxic conditions to achieve phosphate release and uptake, during which microbial internal storage polymers (e.g., Polyhydroxyalkanoate (PHA)) could be produced and consumed dynamically. The PHA turnovers play important roles in nitrous oxide (N2O) accumulation during the denitrifying phosphorus removal process. In this work, a mathematical model is developed to describe N2O dynamics and the key role of PHA consumption on N2O accumulation during the denitrifying phosphorus removal process for the first time. In this model, the four-step anoxic storage of polyphosphate and four-step anoxic growth on PHA using nitrate, nitrite, nitric oxide (NO), and N2O consecutively by denitrifying polyphosphate accumulating organisms (DPAOs) are taken into account for describing all potential N2O accumulation steps in the denitrifying phosphorus removal process. The developed model is successfully applied to reproduce experimental data on N2O production obtained from four independent denitrifying phosphorus removal study reports with different experimental conditions. The model satisfactorily describes the N2O accumulation, nitrogen reduction, phosphate release and uptake, and PHA dynamics for all systems, suggesting the validity and applicability of the model. The results indicated a substantial role of PHA consumption in N2O accumulation due to the relatively low N2O reduction rate by using PHA during denitrifying phosphorus removal.

UWALK: the development of a multi-strategy, community-wide physical activity program.

PubMed

Jennings, Cally A; Berry, Tanya R; Carson, Valerie; Culos-Reed, S Nicole; Duncan, Mitch J; Loitz, Christina C; McCormack, Gavin R; McHugh, Tara-Leigh F; Spence, John C; Vallance, Jeff K; Mummery, W Kerry

2017-03-01

UWALK is a multi-strategy, multi-sector, theory-informed, community-wide approach using e and mHealth to promote physical activity in Alberta, Canada. The aim of UWALK is to promote physical activity, primarily via the accumulation of steps and flights of stairs, through a single over-arching brand. This paper describes the development of the UWALK program. A social ecological model and the social cognitive theory guided the development of key strategies, including the marketing and communication activities, establishing partnerships with key stakeholders, and e and mHealth programs. The program promotes the use of physical activity monitoring devices to self-monitor physical activity. This includes pedometers, electronic devices, and smartphone applications. In addition to entering physical activity data manually, the e and mHealth program provides the function for objective data to be automatically uploaded from select electronic devices (Fitbit®, Garmin and the smartphone application Moves) The RE-AIM framework is used to guide the evaluation of UWALK. Funding for the program commenced in February 2013. The UWALK brand was introduced on April 12, 2013 with the official launch, including the UWALK website on September 20, 2013. This paper describes the development and evaluation framework of a physical activity promotion program. This program has the potential for population level dissemination and uptake of an ecologically valid physical activity promotion program that is evidence-based and theoretically framed.

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

Dynamic Modeling of the Main Blow in Basic Oxygen Steelmaking Using Measured Step Responses

NASA Astrophysics Data System (ADS)

Kattenbelt, Carolien; Roffel, B.

2008-10-01

In the control and optimization of basic oxygen steelmaking, it is important to have an understanding of the influence of control variables on the process. However, important process variables such as the composition of the steel and slag cannot be measured continuously. The decarburization rate and the accumulation rate of oxygen, which can be derived from the generally measured waste gas flow and composition, are an indication of changes in steel and slag composition. The influence of the control variables on the decarburization rate and the accumulation rate of oxygen can best be determined in the main blow period. In this article, the measured step responses of the decarburization rate and the accumulation rate of oxygen to step changes in the oxygen blowing rate, lance height, and the addition rate of iron ore during the main blow are presented. These measured step responses are subsequently used to develop a dynamic model for the main blow. The model consists of an iron oxide and a carbon balance and an additional equation describing the influence of the lance height and the oxygen blowing rate on the decarburization rate. With this simple dynamic model, the measured step responses can be explained satisfactorily.

A transition from using multi-step procedures to a fully integrated system for performing extracorporeal photopheresis: A comparison of costs and efficiencies.

PubMed

Azar, Nabih; Leblond, Veronique; Ouzegdouh, Maya; Button, Paul

2017-12-01

The Pitié Salpêtrière Hospital Hemobiotherapy Department, Paris, France, has been providing extracorporeal photopheresis (ECP) since November 2011, and started using the Therakos ® CELLEX ® fully integrated system in 2012. This report summarizes our single-center experience of transitioning from the use of multi-step ECP procedures to the fully integrated ECP system, considering the capacity and cost implications. The total number of ECP procedures performed 2011-2015 was derived from department records. The time taken to complete a single ECP treatment using a multi-step technique and the fully integrated system at our department was assessed. Resource costs (2014€) were obtained for materials and calculated for personnel time required. Time-driven activity-based costing methods were applied to provide a cost comparison. The number of ECP treatments per year increased from 225 (2012) to 727 (2015). The single multi-step procedure took 270 min compared to 120 min for the fully integrated system. The total calculated per-session cost of performing ECP using the multi-step procedure was greater than with the CELLEX ® system (€1,429.37 and €1,264.70 per treatment, respectively). For hospitals considering a transition from multi-step procedures to fully integrated methods for ECP where cost may be a barrier, time-driven activity-based costing should be utilized to gain a more comprehensive understanding the full benefit that such a transition offers. The example from our department confirmed that there were not just cost and time savings, but that the time efficiencies gained with CELLEX ® allow for more patient treatments per year. © 2017 The Authors Journal of Clinical Apheresis Published by Wiley Periodicals, Inc.

Low-Cycle Fatigue Behavior of Die-Cast Mg Alloy AZ91

NASA Astrophysics Data System (ADS)

Rettberg, Luke; Anderson, Warwick; Jones, J. Wayne

An investigation has been conducted on the influence of microstructure and artificial aging response (T6) on the low-cycle fatigue behavior of super vacuum die-cast (SVDC) AZ91. Fatigue lifetimes were determined from total strain-controlled fatigue tests for strain amplitudes of 0.2%, 0.4% and 0.6%, under fully reversed loading at a frequency of 5 Hz. Cyclic stress-strain behavior was determined using incremental step test (IST) methods. Two locations in a prototype casting with different thicknesses and, therefore, solidification rates, microstructure and porosity, were examined. In general., at all total strain amplitudes fatigue life was unaffected by microstructure refinement and was attributed to significant levels of porosity. Cyclic softening and a subsequent increased cyclic hardening rate, compared to monotonic tests, were observed, independent of microstructure. These results, fractography and damage accumulation processes, determined from metallographic sectioning, are discussed.

Mechanism of O2 diffusion and reduction in FeFe hydrogenases

NASA Astrophysics Data System (ADS)

Kubas, Adam; Orain, Christophe; de Sancho, David; Saujet, Laure; Sensi, Matteo; Gauquelin, Charles; Meynial-Salles, Isabelle; Soucaille, Philippe; Bottin, Hervé; Baffert, Carole; Fourmond, Vincent; Best, Robert B.; Blumberger, Jochen; Léger, Christophe

2017-01-01

FeFe hydrogenases are the most efficient H2-producing enzymes. However, inactivation by O2 remains an obstacle that prevents them being used in many biotechnological devices. Here, we combine electrochemistry, site-directed mutagenesis, molecular dynamics and quantum chemical calculations to uncover the molecular mechanism of O2 diffusion within the enzyme and its reactions at the active site. We propose that the partial reversibility of the reaction with O2 results from the four-electron reduction of O2 to water. The third electron/proton transfer step is the bottleneck for water production, competing with formation of a highly reactive OH radical and hydroxylated cysteine. The rapid delivery of electrons and protons to the active site is therefore crucial to prevent the accumulation of these aggressive species during prolonged O2 exposure. These findings should provide important clues for the design of hydrogenase mutants with increased resistance to oxidative damage.

Fatigue injury risk in anterior cruciate ligament of target side knee during golf swing.

PubMed

Purevsuren, Tserenchimed; Kwon, Moon Seok; Park, Won Man; Kim, Kyungsoo; Jang, Seung Ho; Lim, Young-Tae; Kim, Yoon Hyuk

2017-02-28

A golf-related ACL injury can be linked with excessive golf play or practice because such over-use by repetitive golf swing motions can increase damage accumulation to the ACL bundles. In this study, joint angular rotations, forces, and moments, as well as the forces and strains on the ACL of the target-side knee joint, were investigated for ten professional golfers using the multi-body lower extremity model. The fatigue life of the ACL was also predicted by assuming the estimated ACL force as a cyclic load. The ACL force and strain reached their maximum values within a short time just after ball-impact in the follow-through phase. The smaller knee flexion, higher internal tibial rotation, increase of the joint compressive force and knee abduction moment in the follow-through phase were shown as to lead an increased ACL loading. The number of cycles to fatigue failure (fatigue life) in the ACL might be several thousands. It is suggested that the excessive training or practice of swing motion without enough rest may be one of factors to lead to damage or injury in the ACL by the fatigue failure. The present technology can provide fundamental information to understand and prevent the ACL injury for golf players. Copyright © 2017. Published by Elsevier Ltd.

Dissolvable fluidic time delays for programming multi-step assays in instrument-free paper diagnostics.

PubMed

Lutz, Barry; Liang, Tinny; Fu, Elain; Ramachandran, Sujatha; Kauffman, Peter; Yager, Paul

2013-07-21

Lateral flow tests (LFTs) are an ingenious format for rapid and easy-to-use diagnostics, but they are fundamentally limited to assay chemistries that can be reduced to a single chemical step. In contrast, most laboratory diagnostic assays rely on multiple timed steps carried out by a human or a machine. Here, we use dissolvable sugar applied to paper to create programmable flow delays and present a paper network topology that uses these time delays to program automated multi-step fluidic protocols. Solutions of sucrose at different concentrations (10-70% of saturation) were added to paper strips and dried to create fluidic time delays spanning minutes to nearly an hour. A simple folding card format employing sugar delays was shown to automate a four-step fluidic process initiated by a single user activation step (folding the card); this device was used to perform a signal-amplified sandwich immunoassay for a diagnostic biomarker for malaria. The cards are capable of automating multi-step assay protocols normally used in laboratories, but in a rapid, low-cost, and easy-to-use format.

Dissolvable fluidic time delays for programming multi-step assays in instrument-free paper diagnostics

PubMed Central

Lutz, Barry; Liang, Tinny; Fu, Elain; Ramachandran, Sujatha; Kauffman, Peter; Yager, Paul

2013-01-01

Lateral flow tests (LFTs) are an ingenious format for rapid and easy-to-use diagnostics, but they are fundamentally limited to assay chemistries that can be reduced to a single chemical step. In contrast, most laboratory diagnostic assays rely on multiple timed steps carried out by a human or a machine. Here, we use dissolvable sugar applied to paper to create programmable flow delays and present a paper network topology that uses these time delays to program automated multi-step fluidic protocols. Solutions of sucrose at different concentrations (10-70% of saturation) were added to paper strips and dried to create fluidic time delays spanning minutes to nearly an hour. A simple folding card format employing sugar delays was shown to automate a four-step fluidic process initiated by a single user activation step (folding the card); this device was used to perform a signal-amplified sandwich immunoassay for a diagnostic biomarker for malaria. The cards are capable of automating multi-step assay protocols normally used in laboratories, but in a rapid, low-cost, and easy-to-use format. PMID:23685876

The design of a multi-harmonic step-tunable gyrotron

NASA Astrophysics Data System (ADS)

Qi, Xiang-Bo; Du, Chao-Hai; Zhu, Juan-Feng; Pan, Shi; Liu, Pu-Kun

2017-03-01

The theoretical study of a step-tunable gyrotron controlled by successive excitation of multi-harmonic modes is presented in this paper. An axis-encircling electron beam is employed to eliminate the harmonic mode competition. Physics images are depicted to elaborate the multi-harmonic interaction mechanism in determining the operating parameters at which arbitrary harmonic tuning can be realized by magnetic field sweeping to achieve controlled multiband frequencies' radiation. An important principle is revealed that a weak coupling coefficient under a high-harmonic interaction can be compensated by a high Q-factor. To some extent, the complementation between the high Q-factor and weak coupling coefficient makes the high-harmonic mode potential to achieve high efficiency. Based on a previous optimized magnetic cusp gun, the multi-harmonic step-tunable gyrotron is feasible by using harmonic tuning of first-to-fourth harmonic modes. Multimode simulation shows that the multi-harmonic gyrotron can operate on the 34 GHz first-harmonic TE11 mode, 54 GHz second-harmonic TE21 mode, 74 GHz third-harmonic TE31 mode, and 94 GHz fourth-harmonic TE41 mode, corresponding to peak efficiencies of 28.6%, 35.7%, 17.1%, and 11.4%, respectively. The multi-harmonic step-tunable gyrotron provides new possibilities in millimeter-terahertz source development especially for advanced terahertz applications.

Micromechanical modeling of short glass-fiber reinforced thermoplastics-Isotropic damage of pseudograins

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

Kammoun, S.; Brassart, L.; Doghri, I.

A micromechanical damage modeling approach is presented to predict the overall elasto-plastic behavior and damage evolution in short fiber reinforced composite materials. The practical use of the approach is for injection molded thermoplastic parts reinforced with short glass fibers. The modeling is proceeded as follows. The representative volume element is decomposed into a set of pseudograins, the damage of which affects progressively the overall stiffness and strength up to total failure. Each pseudograin is a two-phase composite with aligned inclusions having same aspect ratio. A two-step mean-field homogenization procedure is adopted. In the first step, the pseudograins are homogenized individuallymore » according to the Mori-Tanaka scheme. The second step consists in a self-consistent homogenization of homogenized pseudograins. An isotropic damage model is applied at the pseudograin level. The model is implemented as a UMAT in the finite element code ABAQUS. Model is shown to reproduce the strength and the anisotropy (Lankford coefficient) during uniaxial tensile tests on samples cut under different directions relative to the injection flow direction.« less

Micromechanical modeling of short glass-fiber reinforced thermoplastics-Isotropic damage of pseudograins

NASA Astrophysics Data System (ADS)

Kammoun, S.; Brassart, L.; Robert, G.; Doghri, I.; Delannay, L.

2011-05-01

A micromechanical damage modeling approach is presented to predict the overall elasto-plastic behavior and damage evolution in short fiber reinforced composite materials. The practical use of the approach is for injection molded thermoplastic parts reinforced with short glass fibers. The modeling is proceeded as follows. The representative volume element is decomposed into a set of pseudograins, the damage of which affects progressively the overall stiffness and strength up to total failure. Each pseudograin is a two-phase composite with aligned inclusions having same aspect ratio. A two-step mean-field homogenization procedure is adopted. In the first step, the pseudograins are homogenized individually according to the Mori-Tanaka scheme. The second step consists in a self-consistent homogenization of homogenized pseudograins. An isotropic damage model is applied at the pseudograin level. The model is implemented as a UMAT in the finite element code ABAQUS. Model is shown to reproduce the strength and the anisotropy (Lankford coefficient) during uniaxial tensile tests on samples cut under different directions relative to the injection flow direction.

Improved perovskite phototransistor prepared using multi-step annealing method

NASA Astrophysics Data System (ADS)

Cao, Mingxuan; Zhang, Yating; Yu, Yu; Yao, Jianquan

2018-02-01

Organic-inorganic hybrid perovskites with good intrinsic physical properties have received substantial interest for solar cell and optoelectronic applications. However, perovskite film always suffers from a low carrier mobility due to its structural imperfection including sharp grain boundaries and pinholes, restricting their device performance and application potential. Here we demonstrate a straightforward strategy based on multi-step annealing process to improve the performance of perovskite photodetector. Annealing temperature and duration greatly affects the surface morphology and optoelectrical properties of perovskites which determines the device property of phototransistor. The perovskite films treated with multi-step annealing method tend to form highly uniform, well-crystallized and high surface coverage perovskite film, which exhibit stronger ultraviolet-visible absorption and photoluminescence spectrum compare to the perovskites prepared by conventional one-step annealing process. The field-effect mobilities of perovskite photodetector treated by one-step direct annealing method shows mobility as 0.121 (0.062) cm2V-1s-1 for holes (electrons), which increases to 1.01 (0.54) cm2V-1s-1 for that treated with muti-step slow annealing method. Moreover, the perovskite phototransistors exhibit a fast photoresponse speed of 78 μs. In general, this work focuses on the influence of annealing methods on perovskite phototransistor, instead of obtains best parameters of it. These findings prove that Multi-step annealing methods is feasible to prepared high performance based photodetector.

Apatite (U-Th)/He thermochronometry using a radiation damage accumulation and annealing model

NASA Astrophysics Data System (ADS)

Flowers, Rebecca M.; Ketcham, Richard A.; Shuster, David L.; Farley, Kenneth A.

2009-04-01

Helium diffusion from apatite is a sensitive function of the volume fraction of radiation damage to the crystal, a quantity that varies over the lifetime of the apatite. Using recently published laboratory data we develop and investigate a new kinetic model, the radiation damage accumulation and annealing model (RDAAM), that adopts the effective fission-track density as a proxy for accumulated radiation damage. This proxy incorporates creation of crystal damage proportional to α-production from U and Th decay, and the elimination of that damage governed by the kinetics of fission-track annealing. The RDAAM is a version of the helium trapping model (HeTM; Shuster D. L., Flowers R. M. and Farley K. A. (2006) The influence of natural radiation damage on helium diffusion kinetics in apatite. Earth Planet. Sci. Lett.249, 148-161), calibrated by helium diffusion data in natural and partially annealed apatites. The chief limitation of the HeTM, now addressed by RDAAM, is its use of He concentration as the radiation damage proxy for circumstances in which radiation damage and He are not accumulated and lost proportionately from the crystal. By incorporating the RDAAM into the HeFTy computer program, we explore its implications for apatite (U-Th)/He thermochronometry. We show how (U-Th)/He dates predicted from the model are sensitive to both effective U concentration (eU) and details of the temperature history. The RDAAM predicts an effective He closure temperature of 62 °C for a 28 ppm eU apatite of 60 μm radius that experienced a 10 °C/Ma monotonic cooling rate; this is 8 °C lower than the 70 °C effective closure temperature predicted using commonly assumed Durango diffusion kinetics. Use of the RDAAM is most important for accurate interpretation of (U-Th)/He data for apatite suites that experienced moderate to slow monotonic cooling (1-0.1 °C/Ma), prolonged residence in the helium partial retention zone, or a duration at temperatures appropriate for radiation damage accumulation followed by reheating and partial helium loss. Under common circumstances the RDAAM predicts (U-Th)/He dates that are older, sometimes much older, than corresponding fission-track dates. Nonlinear positive correlations between apatite (U-Th)/He date and eU in apatites subjected to the same temperature history are a diagnostic signature of the RDAAM for many but not all thermal histories. Observed date-eU correlations in four different localities can be explained with the RDAAM using geologically reasonable thermal histories consistent with independent fission-track datasets. The existence of date-eU correlations not only supports a radiation damage based kinetic model, but can significantly limit the range of acceptable time-temperature paths that account for the data. In contrast, these datasets are inexplicable using the Durango diffusion model. The RDAAM helps reconcile enigmatic data in which apatite (U-Th)/He dates are older than expected using the Durango model when compared with thermal histories based on apatite fission-track data or other geological constraints. It also has the potential to explain at least some cases in which (U-Th)/He dates are actually older than the corresponding fission-track dates.

Suppressed expression of choline monooxygenase in sugar beet on the accumulation of glycine betaine.

PubMed

Yamada, Nana; Takahashi, Hiroyuki; Kitou, Kunihide; Sahashi, Kosuke; Tamagake, Hideto; Tanaka, Yoshito; Takabe, Teruhiro

2015-11-01

Glycine betaine (GB) is an important osmoprotectant and synthesized by two-step oxidation of choline. Choline monooxygenase (CMO) catalyzes the first step of the pathway and is believed to be a rate limiting step for GB synthesis. Recent studies have shown the importance of choline-precursor supply for GB synthesis. In order to investigate the role of CMO for GB accumulation in sugar beet (Beta vulgaris), transgenic plants carrying the antisense BvCMO gene were developed. The antisense BvCMO plants showed the decreased activity of GB synthesis from choline compared to wild-type (WT) plants which is well related to the suppressed level of BvCMO protein. However, GB contents were similar between transgenic and WT plants with the exception of young leaves and storage roots. Transgenic plants showed enhanced susceptibility to salt stress than WT plants. These results suggest the importance of choline-precursor-supply for GB accumulation, and young leaves and storage root are sensitive sites for GB accumulation. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A Novel Approach to Identifying Physical Markers of Cryo-Damage in Bull Spermatozoa

PubMed Central

Yoon, Sung-Jae; Kwon, Woo-Sung; Rahman, Md Saidur; Lee, June-Sub; Pang, Myung-Geol

2015-01-01

Cryopreservation is an efficient way to store spermatozoa and plays a critical role in the livestock industry as well as in clinical practice. During cryopreservation, cryo-stress causes substantial damage to spermatozoa. In present study, the effects of cryo-stress at various cryopreservation steps, such as dilution / cooling, adding cryoprtectant, and freezing were studied in spermatozoa collected from 9 individual bull testes. The motility (%), motion kinematics, capacitation status, mitochondrial activity, and viability of bovine spermatozoa at each step of the cryopreservation process were assessed using computer-assisted sperm analysis, Hoechst 33258/chlortetracycline fluorescence, rhodamine 123 staining, and hypo-osmotic swelling test, respectively. The results demonstrate that the cryopreservation steps reduced motility (%), rapid speed (%), and mitochondrial activity, whereas medium/slow speed (%), and the acrosome reaction were increased (P < 0.05). Differences (Δ) of the acrosome reaction were higher in dilution/cooling step (P < 0.05), whereas differences (Δ) of motility, rapid speed, and non-progressive motility were higher in cryoprotectant and freezing as compared to dilution/cooling (P < 0.05). On the other hand, differences (Δ) of mitochondrial activity, viability, and progressive motility were higher in freezing step (P < 0.05) while the difference (Δ) of the acrosome reaction was higher in dilution/cooling (P < 0.05). Based on these results, we propose that freezing / thawing steps are the most critical in cryopreservation and may provide a logical ground of understanding on the cryo-damage. Moreover, these sperm parameters might be used as physical markers of sperm cryo-damage. PMID:25938413

Brief communication: predatory bird damage to the Taung type-skull of Australopithecus africanus Dart 1925.

PubMed

Berger, Lee R

2006-10-01

In this issue of the Journal, McGraw et al. ([2006] Am. J. Phys. Anthropol. 000:00-00) present new data on the taphonomic signature of bone assemblages accumulated by crowned hawk eagles (Stephanoaetus coronatus), including characteristic talon damage to the inferior orbits of primates preyed upon by these birds. Reexamination of the Taung juvenile hominin specimen (the type specimen of Australopithecus africanus Dart 1925) reveals previously undescribed damage to the orbital floors that is nearly identical to that seen in the crania of monkeys preyed upon by crowned hawk eagles (as reported by McGraw et al., this issue). This new evidence, along with previously described aspects of the nonhominin bone assemblage from Taung and damage to the neurocranium of the hominin specimen itself, strongly supports the hypothesis that a bird of prey was an accumulating agent at Taung, and that the Taung child itself was the victim of a bird of prey.

Surface-structure dependence of healing radiation-damage mechanism in nanoporous tungsten

NASA Astrophysics Data System (ADS)

Duan, Guohua; Li, Xiangyan; Sun, Jingjing; Hao, Congyu; Xu, Yichun; Zhang, Yange; Liu, Wei; Liu, C. S.

2018-01-01

Under nuclear fusion environments, displacement damage in tungsten (W) is usually caused by neutrons irradiation through producing large quantities of vacancies (Vs) and self-interstitial atoms (SIAs). These defects not only affect the mechanical properties of W, but also act as the trap sites for implanted hydrogen isotopes and helium. Nano-porous (NP) W with a high fraction of free surfaces has been developed to mitigate the radiation damage. However, the mechanism of the surface reducing defects accumulation is not well understood. By using multi-scale simulation methods, we investigated the interaction of the SIA and V with different surfaces on across length and time scales. We found that, at a typical operation temperature of 1000 K, surface (1 1 0) preferentially heals radiation damage of W compared with surface (1 0 0) and boundary (3 1 0). On surface (1 1 0), the diffusion barrier for the SIA is only 0.68 eV. The annihilation of the SIA-V happens via the coupled motion of the V segregation towards the surface from the bulk and the two-dimensional diffusion of the SIA on the surface. Such mechanism makes the surface (1 1 0) owe better healing capability. On surface (1 0 0), the diffusion energy barrier for the SIA is 2.48 eV, higher than the diffusion energy barrier of the V in bulk. The annihilation of the SIA-V occurs via the V segregation and recombination. The SIA was found to migrate one-dimensionally along a boundary (3 1 0) with a barrier of 0.21 eV, leading to a lower healing efficiency in the boundary. This study suggested that the on-surface process plays an important role in healing radiation damage of NP W in addition to surface-enhanced diffusion and annihilation near the surface. A certain surface structure renders nano-structured W more radiation-tolerant.

Structures and optical properties of \\text{H}_{2}^{+} -implanted GaN epi-layers

NASA Astrophysics Data System (ADS)

Li, B. S.; Wang, Z. G.

2015-06-01

The implantation damage build-up and optical properties of GaN epitaxial films under \\text{H}2+ ion implantation have been investigated by a combination of Rutherford backscattering in channeling geometry, Raman spectroscopy, UV-visible spectroscopy and transmission electron microscopy. GaN epitaxial films were implanted with 134 keV \\text{H}2+ ions to doses ranging from 3.75   ×   1016 to 1.75   ×   1017 \\text{H}2+  cm-2 at room temperature or the same dose of 1.5   ×   1017 \\text{H}2+  cm-2 at room temperature, 573 and 723 K. The dependence of lattice disorder induced by \\text{H}2+ -implantation on the ion dose can be divided into a three-step damage process. A strong influence of the H concentration on the defect accumulation is discussed. The decrease in relative Ga disorder induced by \\text{H}2+ -implantation is linear with increasing implantation temperature. The absorption coefficient of GaN epitaxial films increases with increasing ion dose, leading to the decrease in Raman scattering spectra of Ga-N vibration. With increasing implantation doses up to 5   ×   1016 \\text{H}2+  cm-2, nanoscale hydrogen bubbles are observed in the H deposition peak region. Interstitial-type dislocation loops are observed in the damaged layer located near the damage peak region, and the geometry of the dislocation loops produced by H implantation is analyzed. The surface layer is almost free of lattice disorder induced by \\text{H}2+ -implantation.

Removal of inorganic mercury from aquatic environments by multi-walled carbon nanotubes.

PubMed

Yaghmaeian, Kamyar; Khosravi Mashizi, Reza; Nasseri, Simin; Mahvi, Amir Hossein; Alimohammadi, Mahmood; Nazmara, Shahrokh

2015-01-01

Mercury is considered as a toxic heavy metal in aquatic environments due to accumulation in bodies of living organisms. Exposure to mercury may lead to different toxic effects in humans including damages to kidneys and nervous system. Multi-walled carbon nanotubes (MWCNTs) were selected as sorbent to remove mercury from aqueous solution using batch technique. ICP instrument was used to determine the amount of mercury in solution. Moreover, pH, contact time and initial concentration of mercury were studied to determine the influence of these parameters on the adsorption conditions. Results indicate that the adsorption strongly depended on pH and the best pH for adsorption is about 7. The rate of adsorption process initially was rapid but it was gradually reduced with increasing of contact time and reached the equilibrium after 120 min. In addition, more than 85 % of initial concentration of 0.1 mg/l was removed at 0.5 g/l concentration of sorbent and contact time of 120 min. Meanwhile, the adsorption process followed the pseudo second-order model and the adsorption isotherms could be described by both the Freundlich and the Langmuir models. This study showed that MWCNTs can effectively remove inorganic mercury from aqueous solutions as adsorbent.

DEVELOPMENT OF PERMANENT MECHANICAL REPAIR SLEEVE FOR PLASTIC PIPE

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

Hitesh Patadia

2005-04-29

The report presents a comprehensive summary of the prototype development process utilized towards the development of a permanent mechanical repair fitting intended to be installed on damaged PE mains under blowing gas conditions. Specifically, the step by step construction approach is presented and the experimental data to support the mitigation of ensuing slow crack growth (SCG) of the damage area.

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

PubMed

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

2016-03-01

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

Robust Rocket Engine Concept

NASA Technical Reports Server (NTRS)

Lorenzo, Carl F.

1995-01-01

The potential for a revolutionary step in the durability of reusable rocket engines is made possible by the combination of several emerging technologies. The recent creation and analytical demonstration of life extending (or damage mitigating) control technology enables rapid rocket engine transients with minimum fatigue and creep damage. This technology has been further enhanced by the formulation of very simple but conservative continuum damage models. These new ideas when combined with recent advances in multidisciplinary optimization provide the potential for a large (revolutionary) step in reusable rocket engine durability. This concept has been named the robust rocket engine concept (RREC) and is the basic contribution of this paper. The concept also includes consideration of design innovations to minimize critical point damage.

A dual role of p21 in stem cell aging.

PubMed

Ju, Zhenyu; Choudhury, Aaheli Roy; Rudolph, K Lenhard

2007-04-01

A decline in adult stem cell function occurs during aging, likely contributing to the decline in organ homeostasis and regeneration with age. An emerging field in aging research is to analyze molecular pathways limiting adult stem cell function in response to macromolecular damage accumulation during aging. Current data suggest that the p21 cell cycle inhibitor has a dual role in stem cell aging: On one hand, p21 protects adult stem cells from acute genotoxic stress by preventing inappropriate cycling of acutely damaged stem cells. On the other hand, p21 activation impairs stem cell function and survival of aging telomere dysfunctional mice indicating that p21 checkpoint function is disadvantageous in the context of chronic and persistent damage, which accumulates during aging. This article focuses on these dual roles of p21 in aging stem cells.

Injection-Molded Long-Fiber Thermoplastic Composites: From Process Modeling to Prediction of Mechanical Properties

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

Nguyen, Ba Nghiep; Kunc, Vlastimil; Jin, Xiaoshi

2013-12-18

This article illustrates the predictive capabilities for long-fiber thermoplastic (LFT) composites that first simulate the injection molding of LFT structures by Autodesk® Simulation Moldflow® Insight (ASMI) to accurately predict fiber orientation and length distributions in these structures. After validating fiber orientation and length predictions against the experimental data, the predicted results are used by ASMI to compute distributions of elastic properties in the molded structures. In addition, local stress-strain responses and damage accumulation under tensile loading are predicted by an elastic-plastic damage model of EMTA-NLA, a nonlinear analysis tool implemented in ABAQUS® via user-subroutines using an incremental Eshelby-Mori-Tanaka approach. Predictedmore » stress-strain responses up to failure and damage accumulations are compared to the experimental results to validate the model.« less

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

PubMed

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

2017-03-01

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

Protective effects of resveratrol and its analogs on age-related macular degeneration in vitro.

PubMed

Kang, Jung-Hwan; Choung, Se-Young

2016-12-01

Damage of retinal pigment epithelial (RPE) cells by A2E may be critical for age-related macular degeneration (AMD) management. Accumulation and photooxidation of A2E are known to be one of the critical causes in AMD. Here, we evaluated the protective effect of resveratrol (RES), piceatannol (PIC) and RES glycones on blue-light-induced RPE cell death caused by A2E photooxidation. A2E treatment followed by blue light exposure caused significant damages on human RPE cells (ARPE-19). But the damages were attenuated by post- and pre-treatment of RES and PIC in our in vitro models. The results of cell free system and FAB-MS analysis clearly showed that the reduction of A2E by blue light exposure was significantly rescued, and that oxidized forms of A2E were significantly reduced by RES or PIC treatment. Besides, RES or PIC inhibited the intracellular accumulation of A2E. Not only RES and PIC but RES glycones showed protection of ARPE-19 cells against A2E and blue-light-induced photo-damage. These findings demonstrate that RES and its analogs may have protective effects against A2E and blue-light-induced ARPE-19 cell death through regulation of A2E accumulation as well as photooxidation of A2E. Thus RES and its analogs may be beneficial for AMD treatment.

Alzheimer’s Toxic Amyloid Beta Oligomers: Unwelcome Visitors to the Na/K ATPase alpha3 Docking Station

PubMed Central

DiChiara, Thomas; DiNunno, Nadia; Clark, Jeffrey; Bu, Riana Lo; Cline, Erika N.; Rollins, Madeline G.; Gong, Yuesong; Brody, David L.; Sligar, Stephen G.; Velasco, Pauline T.; Viola, Kirsten L.; Klein, William L.

2017-01-01

Toxic amyloid beta oligomers (AβOs) are known to accumulate in Alzheimer’s disease (AD) and in animal models of AD. Their structure is heterogeneous, and they are found in both intracellular and extracellular milieu. When given to CNS cultures or injected ICV into non-human primates and other non-transgenic animals, AβOs have been found to cause impaired synaptic plasticity, loss of memory function, tau hyperphosphorylation and tangle formation, synapse elimination, oxidative and ER stress, inflammatory microglial activation, and selective nerve cell death. Memory loss and pathology in transgenic models are prevented by AβO antibodies, while Aducanumab, an antibody that targets AβOs as well as fibrillar Aβ, has provided cognitive benefit to humans in early clinical trials. AβOs have now been investigated in more than 3000 studies and are widely thought to be the major toxic form of Aβ. Although much has been learned about the downstream mechanisms of AβO action, a major gap concerns the earliest steps: How do AβOs initially interact with surface membranes to generate neuron-damaging transmembrane events? Findings from Ohnishi et al (PNAS 2005) combined with new results presented here are consistent with the hypothesis that AβOs act as neurotoxins because they attach to particular membrane protein docks containing Na/K ATPase-α3, where they inhibit ATPase activity and pathologically restructure dock composition and topology in a manner leading to excessive Ca++ build-up. Better understanding of the mechanism that makes attachment of AβOs to vulnerable neurons a neurotoxic phenomenon should open the door to therapeutics and diagnostics targeting the first step of a complex pathway that leads to neural damage and dementia. PMID:28356893

Evaluation of the Potential of NASA Multi-satellite Precipitation Analysis in Global Landslide Hazard Assessment

NASA Technical Reports Server (NTRS)

Hong, Yang; Adler, Robert F.; Huffman, George J.

2007-01-01

Landslides are one of the most widespread natural hazards on Earth, responsible for thousands of deaths and billions of dollars in property damage every year. In the U.S. alone landslides occur in every state, causing an estimated $2 billion in damage and 25- 50 deaths each year. Annual average loss of life from landslide hazards in Japan is 170. The situation is much worse in developing countries and remote mountainous regions due to lack of financial resources and inadequate disaster management ability. Recently, a landslide buried an entire village on the Philippines Island of Leyte on Feb 17,2006, with at least 1800 reported deaths and only 3 houses left standing of the original 300. Intense storms with high-intensity , long-duration rainfall have great potential to trigger rapidly moving landslides, resulting in casualties and property damage across the world. In recent years, through the availability of remotely sensed datasets, it has become possible to conduct global-scale landslide hazard assessment. This paper evaluates the potential of the real-time NASA TRMM-based Multi-satellite Precipitation Analysis (TMPA) system to advance our understanding of and predictive ability for rainfall-triggered landslides. Early results show that the landslide occurrences are closely associated with the spatial patterns and temporal distribution of rainfall characteristics. Particularly, the number of landslide occurrences and the relative importance of rainfall in triggering landslides rely on the influence of rainfall attributes [e.g. rainfall climatology, antecedent rainfall accumulation, and intensity-duration of rainstorms). TMPA precipitation data are available in both real-time and post-real-time versions, which are useful to assess the location and timing of rainfall-triggered landslide hazards by monitoring landslide-prone areas while receiving heavy rainfall. For the purpose of identifying rainfall-triggered landslides, an empirical global rainfall intensity-duration threshold is developed by examining a number of landslide occurrences and their corresponding TMPA precipitation characteristics across the world. These early results , in combination with TRMM real-time precipitation estimation system, may form a starting point for developing an operational early warning system for rainfall-triggered landslides around the globe.

Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates

USDA-ARS?s Scientific Manuscript database

The xanthophyll pigments lutein and zeaxanthin cross the blood-retina barrier to preferentially accumulate in the macular region of the neural retina. There they form macular pigment, protecting the retina from blue light damage and oxidative stress. Lutein and zeaxanthin also accumulate in brain t...

Trichothecene-Genotypes Play a Role in Fusarium Head Blight Disease Spread and Trichothecene Accumulation in Wheat

USDA-ARS?s Scientific Manuscript database

In the current study, we evaluated the impact of the observed North American evolutionary shift in the Fusarium graminearum complex on disease spread, kernel damage, and trichothecene accumulation in resistant and susceptible wheat genotypes. Four inocula were prepared using composites of F. gramin...

Walnut diet reduces accumulation of polyubiquitinated proteins and inflammation in the brain of aged rats

USDA-ARS?s Scientific Manuscript database

An increase in the aggregation of misfolded/damaged polyubiquitinated proteins has been the hallmark of many age-related neurodegenerative diseases. The accumulation of these potentially toxic proteins in brain increases with age, in part due to increased oxidative and inflammatory stresses. Walnuts...

Antioxidant enzymatic activity is linked to waterlogging stress tolerance in citrus.

PubMed

Arbona, Vicent; Hossain, Zahed; López-Climent, María F; Pérez-Clemente, Rosa M; Gómez-Cadenas, Aurelio

2008-04-01

Soil flooding constitutes a seasonal factor that negatively affects plant performance and crop yields. In this work, the relationship between oxidative damage and flooding sensitivity was addressed in three citrus genotypes with different abilities to tolerate waterlogging. We examined leaf visible damage, oxidative damage in terms of malondialdehyde (MDA) concentration, leaf proline concentration, leaf and root ascorbate and glutathione contents and the antioxidant enzyme activities superoxide dismutase (EC 1.15.1.1), ascorbate peroxidase (EC 1.11.1.11), catalase (EC 1.11.1.6) and glutathione reductase (EC 1.8.1.7). No differences in the extent of oxidative damage relative to controls were found among genotypes. However, a different ability to delay the apparition of oxidative damage was associated to a higher tolerance to waterlogging. This ability was linked to an enhanced activated oxygen species' scavenging capacity in terms of an increased antioxidant enzyme activity and higher content in polar antioxidant compounds. Therefore, the existence of a direct relationship between stress sensitivity and the early accumulation of MDA is proposed. In addition, data indicate that the protective role of proline has to be considered minimal as its accumulation was inversely correlated with tolerance to the stress. The positive antioxidant response in Carrizo citrange (Poncirus trifoliata L. Raf. x Citrus sinensis L. Osb.) and Citrumelo CPB 4475 (Poncirus trifoliata L. Raf. x Citrus paradisi L. Macf.) might be responsible for a higher tolerance to flooding stress, whereas in Cleopatra mandarin (Citrus reshni Hort. Ex Tan.), the early accumulation of MDA seems to be associated to an impaired ability for H2O2 scavenging.

A Systems Approach towards an Intelligent and Self-Controlling Platform for Integrated Continuous Reaction Sequences**

PubMed Central

Ingham, Richard J; Battilocchio, Claudio; Fitzpatrick, Daniel E; Sliwinski, Eric; Hawkins, Joel M; Ley, Steven V

2015-01-01

Performing reactions in flow can offer major advantages over batch methods. However, laboratory flow chemistry processes are currently often limited to single steps or short sequences due to the complexity involved with operating a multi-step process. Using new modular components for downstream processing, coupled with control technologies, more advanced multi-step flow sequences can be realized. These tools are applied to the synthesis of 2-aminoadamantane-2-carboxylic acid. A system comprising three chemistry steps and three workup steps was developed, having sufficient autonomy and self-regulation to be managed by a single operator. PMID:25377747

Detection of surface cracking in steel pipes based on vibration data using a multi-class support vector machine classifier

NASA Astrophysics Data System (ADS)

Mustapha, S.; Braytee, A.; Ye, L.

2017-04-01

In this study, we focused at the development and verification of a robust framework for surface crack detection in steel pipes using measured vibration responses; with the presence of multiple progressive damage occurring in different locations within the structure. Feature selection, dimensionality reduction, and multi-class support vector machine were established for this purpose. Nine damage cases, at different locations, orientations and length, were introduced into the pipe structure. The pipe was impacted 300 times using an impact hammer, after each damage case, the vibration data were collected using 3 PZT wafers which were installed on the outer surface of the pipe. At first, damage sensitive features were extracted using the frequency response function approach followed by recursive feature elimination for dimensionality reduction. Then, a multi-class support vector machine learning algorithm was employed to train the data and generate a statistical model. Once the model is established, decision values and distances from the hyper-plane were generated for the new collected data using the trained model. This process was repeated on the data collected from each sensor. Overall, using a single sensor for training and testing led to a very high accuracy reaching 98% in the assessment of the 9 damage cases used in this study.

Multi-stage approach for structural damage detection problem using basis pursuit and particle swarm optimization

NASA Astrophysics Data System (ADS)

Gerist, Saleheh; Maheri, Mahmoud R.

2016-12-01

In order to solve structural damage detection problem, a multi-stage method using particle swarm optimization is presented. First, a new spars recovery method, named Basis Pursuit (BP), is utilized to preliminarily identify structural damage locations. The BP method solves a system of equations which relates the damage parameters to the structural modal responses using the sensitivity matrix. Then, the results of this stage are subsequently enhanced to the exact damage locations and extents using the PSO search engine. Finally, the search space is reduced by elimination of some low damage variables using micro search (MS) operator embedded in the PSO algorithm. To overcome the noise present in structural responses, a method known as Basis Pursuit De-Noising (BPDN) is also used. The efficiency of the proposed method is investigated by three numerical examples: a cantilever beam, a plane truss and a portal plane frame. The frequency response is used to detect damage in the examples. The simulation results demonstrate the accuracy and efficiency of the proposed method in detecting multiple damage cases and exhibit its robustness regarding noise and its advantages compared to other reported solution algorithms.

Padova Charter on personal injury and damage under civil-tort law : Medico-legal guidelines on methods of ascertainment and criteria of evaluation.

PubMed

Ferrara, Santo Davide; Baccino, Eric; Boscolo-Berto, Rafael; Comandè, Giovanni; Domenici, Ranieri; Hernandez-Cueto, Claudio; Gulmen, Mete Korkut; Mendelson, George; Montisci, Massimo; Norelli, Gian Aristide; Pinchi, Vilma; Ranavaya, Mohammed; Shokry, Dina A; Sterzik, Vera; Vermylen, Yvo; Vieira, Duarte Nuno; Viel, Guido; Zoja, Riccardo

2016-01-01

Compensation for personal damage, defined as any pecuniary or non-pecuniary loss causally related to a personal injury under civil-tort law, is strictly based on the local jurisdiction and therefore varies significantly across the world. This manuscript presents the first "International Guidelines on Medico-Legal Methods of Ascertainment and Criteria of Evaluation of Personal Injury and Damage under Civil-Tort Law". This consensus document, which includes a step-by-step illustrated explanation of flow charts articulated in eight sequential steps and a comprehensive description of the ascertainment methodology and the criteria of evaluation, has been developed by an International Working Group composed of juridical and medico-legal experts and adopted as Guidelines by the International Academy of Legal Medicine (IALM).

Synthesis and biological evaluation of ¹⁸F-labeled fluoropropyl tryptophan analogs as potential PET probes for tumor imaging.

PubMed

Chiotellis, Aristeidis; Mu, Linjing; Müller, Adrienne; Selivanova, Svetlana V; Keller, Claudia; Schibli, Roger; Krämer, Stefanie D; Ametamey, Simon M

2013-01-01

In the search for an efficient, fluorine-18 labeled amino acid based radiotracer for tumor imaging with positron emission tomography (PET), two new tryptophan analogs were synthesized and characterized in vitro and in vivo. Both are tryptophan alkyl-derivatives, namely 2-(3-[(18)F]fluoropropyl)-DL-tryptophan ([(18)F]2-FPTRP) and 5-(3-[(18)F]fluoro-propyl)-DL-tryptophan ([(18)F]5-FPTRP). Standard reference compounds and precursors were prepared by multi step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [(18)F]fluorination in 29-34% decay corrected yields with radiochemical purity over 99%. In vitro cell uptake assays showed that both compounds are substrates for amino acid transport and enter small cell lung cancer cells (NCI-H69) most probably almost exclusively via large neutral amino acids transporter(s) (LAT). Small animal PET imaging with xenograft bearing mice revealed high tumor/background ratios for [(18)F]2-FPTRP comparable to the well established tyrosine analog O-(2-[(18)F]fluroethyl)-L-tyrosine ([(18)F]FET). Radiometabolite studies showed no evidence of involvement of a biotransformation step in tumor accumulation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

[Metabolic engineering of edible plant oils].

PubMed

Yue, Ai-Qin; Sun, Xi-Ping; Li, Run-Zhi

2007-12-01

Plant seed oil is the major source of many fatty acids for human nutrition, and also one of industrial feedstocks. Recent advances in understanding of the basic biochemistry of seed oil biosynthesis, coupled with cloning of the genes encoding the enzymes involved in fatty acid modification and oil accumulation, have set the stage for the metabolic engineering of oilseed crops that produce "designer" plant seed oils with the improved nutritional values for human being. In this review we provide an overview of seed oil biosynthesis/regulation and highlight the key enzymatic steps that are targets for gene manipulation. The strategies of metabolic engineering of fatty acids in oilseeds, including overexpression or suppression of genes encoding single or multi-step biosynthetic pathways and assembling the complete pathway for the synthesis of long-chain polyunsaturated fatty acids (e.g. arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid) are described in detail. The current "bottlenecks" in using common oilseeds as "bioreactors" for commercial production of high-value fatty acids are analyzed. It is also discussed that the future research focuses of oilseed metabolic engineering and the prospects in creating renewable sources and promoting the sustainable development of human society and economy.

75 FR 3876 - Mark Edward Leyse; Receipt of Petition for Rulemaking

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-25

... (assembly) severe fuel damage experiments. The petitioner also requests that the NRC promulgate a regulation... aware that data from multi-rod (assembly) severe fuel damage experiments indicates that the current... fuel damage experiments indicates that the current peak cladding temperature limit contained in 10 CFR...

Glaze Damage In 13- To 18-Year-Old, Natural, Even-Aged Stands of Loblolly Pines in Southeastern Arkansas

Treesearch

Michael D. Cain; Michael G. Shelton

2002-01-01

In late December 1998, a severe winter storm deposited 2.1 inches of precipitation on the Crossett Experimental Forest in southeastern Arkansas. Ice, in the form of glaze, accumulated on needles and branches of trees, and resulted in visual damage to sapling and pulpwood-sized pines. Within 60 days after the storm, damage was assessed within naturally regenerated,...

Creep rupture analysis of a beam resting on high temperature foundation

NASA Technical Reports Server (NTRS)

Gu, Randy J.; Cozzarelli, Francis A.

1988-01-01

A simplified uniaxial strain controlled creep damage law is deduced with the use of experimental observation from a more complex strain dependent law. This creep damage law correlates the creep damage, which is interpreted as the density variation in the material, directly with the accumulated creep strain. Based on the deduced uniaxial strain controlled creep damage law, a continuum mechanical creep rupture analysis is carried out for a beam resting on a high temperature elastic (Winkler) foundation. The analysis includes the determination of the nondimensional time for initial rupture, the propagation of the rupture front with the associated thinning of the beam, and the influence of creep damage on the deflection of the beam. Creep damage starts accumulating in the beam as soon as the load is applied, and a creep rupture front develops at and propagates from the point at which the creep damage first reaches its critical value. By introducing a series of fundamental assumptions within the framework of technical Euler-Bernoulli type beam theory, a governing set of integro-differential equations is derived in terms of the nondimensional bending moment and the deflection. These governing equations are subjected to a set of interface conditions at the propagating rupture front. A numerical technique is developed to solve the governing equations together with the interface equations, and the computed results are presented and discussed in detail.

Graphene Oxide/Silver Nanohybrid as Multi-functional Material for Highly Efficient Bacterial Disinfection and Detection of Organic Dye

NASA Astrophysics Data System (ADS)

Tam, Le Thi; Dinh, Ngo Xuan; Van Cuong, Nguyen; Van Quy, Nguyen; Huy, Tran Quang; Ngo, Duc-The; Mølhave, Kristian; Le, Anh-Tuan

2016-10-01

In this work, a multi-functional hybrid system consisting of graphene oxide and silver nanoparticles (GO-Ag NPs) was successfully synthesized by using a two-step chemical process. We firstly demonstrated noticeable bactericidal ability of the GO-Ag hybrid system. We provide more chemo-physical evidence explaining the antibacterial behavior of GO-Ag nanohybrid against Gram-negative Escherichia Coli and Gram-positive Staphylococcus aureus in light of ultrastructural damage analyses and Ag1+ ions release rate onto the cells/medium. A further understanding of the mode of antimicrobial action is very important for designing and developing advanced antimicrobial systems. Secondly, we have also demonstrated that the GO-Ag nanohybrid material could be used as a potential surface enhanced Raman scattering (SERS) substrate to detect and quantify organic dyes, e.g., methylene blue (MB), in aqueous media. Our findings revealed that the GO-Ag hybrid system showed better SERS performance of MB detection than that of pure Ag-NPs. MB could be detected at a concentration as low as 1 ppm. The GO-Ag-based SERS platform can be effectively used to detect trace concentrations of various types of organic dyes in aqueous media. With the aforementioned properties, the GO-Ag hybrid system is found to be very promising as a multi-functional material for advanced biomedicine and environmental monitoring applications.

Analysis on Two Typical Landslide Hazard Phenomena in The Wenchuan Earthquake by Field Investigations and Shaking Table Tests.

PubMed

Yang, Changwei; Zhang, Jianjing; Liu, Feicheng; Bi, Junwei; Jun, Zhang

2015-08-06

Based on our field investigations of landslide hazards in the Wenchuan earthquake, some findings can be reported: (1) the multi-aspect terrain facing empty isolated mountains and thin ridges reacted intensely to the earthquake and was seriously damaged; (2) the slope angles of most landslides was larger than 45°. Considering the above disaster phenomena, the reasons are analyzed based on shaking table tests of one-sided, two-sided and four-sided slopes. The analysis results show that: (1) the amplifications of the peak accelerations of four-sided slopes is stronger than that of the two-sided slopes, while that of the one-sided slope is the weakest, which can indirectly explain the phenomena that the damage is most serious; (2) the amplifications of the peak accelerations gradually increase as the slope angles increase, and there are two inflection points which are the point where the slope angle is 45° and where the slope angle is 50°, respectively, which can explain the seismic phenomenon whereby landslide hazards mainly occur on the slopes whose slope angle is bigger than 45°. The amplification along the slope strike direction is basically consistent, and the step is smooth.

Aprataxin resolves adenylated RNA–DNA junctions to maintain genome integrity

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

Tumbale, Percy; Williams, Jessica S.; Schellenberg, Matthew J.

2013-12-22

Faithful maintenance and propagation of eukaryotic genomes is ensured by three-step DNA ligation reactions used by ATP-dependent DNA ligases. Paradoxically, when DNA ligases encounter nicked DNA structures with abnormal DNA termini, DNA ligase catalytic activity can generate and/or exacerbate DNA damage through abortive ligation that produces chemically adducted, toxic 5'-adenylated (5'-AMP) DNA lesions. Aprataxin (APTX) reverses DNA adenylation but the context for deadenylation repair is unclear. Here we examine the importance of APTX to RNase-H2-dependent excision repair (RER) of a lesion that is very frequently introduced into DNA, a ribonucleotide. We show that ligases generate adenylated 5' ends containing amore » ribose characteristic of RNase H2 incision. APTX efficiently repairs adenylated RNA–DNA, and acting in an RNA–DNA damage response (RDDR), promotes cellular survival and prevents S-phase checkpoint activation in budding yeast undergoing RER. Structure–function studies of human APTX–RNA–DNA–AMP–Zn complexes define a mechanism for detecting and reversing adenylation at RNA–DNA junctions. This involves A-form RNA binding, proper protein folding and conformational changes, all of which are affected by heritable APTX mutations in ataxia with oculomotor apraxia 1. Together, these results indicate that accumulation of adenylated RNA–DNA may contribute to neurological disease.« less

Developing a Malaysia flood model

NASA Astrophysics Data System (ADS)

Haseldine, Lucy; Baxter, Stephen; Wheeler, Phil; Thomson, Tina

2014-05-01

Faced with growing exposures in Malaysia, insurers have a need for models to help them assess their exposure to flood losses. The need for an improved management of flood risks has been further highlighted by the 2011 floods in Thailand and recent events in Malaysia. The increasing demand for loss accumulation tools in Malaysia has lead to the development of the first nationwide probabilistic Malaysia flood model, which we present here. The model is multi-peril, including river flooding for thousands of kilometres of river and rainfall-driven surface water flooding in major cities, which may cause losses equivalent to river flood in some high-density urban areas. The underlying hazard maps are based on a 30m digital surface model (DSM) and 1D/2D hydraulic modelling in JFlow and RFlow. Key mitigation schemes such as the SMART tunnel and drainage capacities are also considered in the model. The probabilistic element of the model is driven by a stochastic event set based on rainfall data, hence enabling per-event and annual figures to be calculated for a specific insurance portfolio and a range of return periods. Losses are estimated via depth-damage vulnerability functions which link the insured damage to water depths for different property types in Malaysia. The model provides a unique insight into Malaysian flood risk profiles and provides insurers with return period estimates of flood damage and loss to property portfolios through loss exceedance curve outputs. It has been successfully validated against historic flood events in Malaysia and is now being successfully used by insurance companies in the Malaysian market to obtain reinsurance cover.

Effect of the processing steps on compositions of table olive since harvesting time to pasteurization.

PubMed

Nikzad, Nasim; Sahari, Mohammad A; Vanak, Zahra Piravi; Safafar, Hamed; Boland-nazar, Seyed A

2013-08-01

Weight, oil, fatty acids, tocopherol, polyphenol, and sterol properties of 5 olive cultivars (Zard, Fishomi, Ascolana, Amigdalolia, and Conservalia) during crude, lye treatment, washing, fermentation, and pasteurization steps were studied. Results showed: oil percent was higher and lower in Ascolana (crude step) and in Fishomi (pasteurization step), respectively; during processing steps, in all cultivars, oleic, palmitic, linoleic, and stearic acids were higher; the highest changes in saturated and unsaturated fatty acids were in fermentation step; the highest and the lowest ratios of ω3 / ω6 were in Ascolana (washing step) and in Zard (pasteurization step), respectively; the highest and the lowest tocopherol were in Amigdalolia and Fishomi, respectively, and major damage occurred in lye step; the highest and the lowest polyphenols were in Ascolana (crude step) and in Zard and Ascolana (pasteurization step), respectively; the major damage among cultivars occurred during lye step, in which the polyphenol reduced to 1/10 of first content; sterol did not undergo changes during steps. Reviewing of olive patents shows that many compositions of fruits such as oil quality, fatty acids, quantity and its fraction can be changed by alteration in cultivar and process.

Axon-glial disruption: the link between vascular disease and Alzheimer's disease?

PubMed

Horsburgh, Karen; Reimer, Michell M; Holland, Philip; Chen, Guiquan; Scullion, Gillian; Fowler, Jill H

2011-08-01

Vascular risk factors play a critical role in the development of cognitive decline and AD (Alzheimer's disease), during aging, and often result in chronic cerebral hypoperfusion. The neurobiological link between hypoperfusion and cognitive decline is not yet defined, but is proposed to involve damage to the brain's white matter. In a newly developed mouse model, hypoperfusion, in isolation, produces a slowly developing and diffuse damage to myelinated axons, which is widespread in the brain, and is associated with a selective impairment in working memory. Cerebral hypoperfusion, an early event in AD, has also been shown to be associated with white matter damage and notably an accumulation of amyloid. The present review highlights some of the published data linking white matter disruption to aging and AD as a result of vascular dysfunction. A model is proposed by which chronic cerebral hypoperfusion, as a result of vascular factors, results in both the generation and accumulation of amyloid and injury to white matter integrity, resulting in cognitive impairment. The generation of amyloid and accumulation in the vasculature may act to perpetuate further vascular dysfunction and accelerate white matter pathology, and as a consequence grey matter pathology and cognitive decline.

X ray attenuation measurements for high-temperature materials characterization and in-situ monitoring of damage accumulation. Ph.D. Thesis - Cleveland State Univ., 1991

NASA Technical Reports Server (NTRS)

Baaklini, George Y.

1992-01-01

The scope of this dissertation is to develop and apply x ray attenuation measurement systems that are capable of: (1) characterizing density variations in high-temperature materials, e.g., monolithic ceramics, ceramic and intermetallic matrix composites, and (2) noninvasively monitoring damage accumulation and failure sequences in ceramic matrix composites under room temperature tensile testing. This dissertation results in the development of: (1) a point scan digital radiography system, and (2) an in-situ x ray material testing system. Radiographic evaluation before, during, and after loading shows the effect of preexisting volume flaws on the fracture behavior of composites. Results show that x ray film radiography can monitor damage accumulation during tensile loading. Matrix cracking, fiber matrix debonding, fiber bridging, and fiber pullout are imaged throughout the tensile loading of the specimens. Further in-situ radiography is found to be a practical technique for estimating interfacial shear strength between the silicon carbide fibers and the reaction bonded silicon nitride matrix. It is concluded that pretest, in-situ, and post test x ray imaging can provide for greater understanding of ceramic matrix composite mechanical behavior.

Gray Matter Pathology in MS: Neuroimaging and Clinical Correlations

PubMed Central

Honce, Justin Morris

2013-01-01

It is abundantly clear that there is extensive gray matter pathology occurring in multiple sclerosis. While attention to gray matter pathology was initially limited to studies of autopsy specimens and biopsies, the development of new MRI techniques has allowed assessment of gray matter pathology in vivo. Current MRI techniques allow the direct visualization of gray matter demyelinating lesions, the quantification of diffuse damage to normal appearing gray matter, and the direct measurement of gray matter atrophy. Gray matter demyelination (both focal and diffuse) and gray matter atrophy are found in the very earliest stages of multiple sclerosis and are progressive over time. Accumulation of gray matter damage has substantial impact on the lives of multiple sclerosis patients; a growing body of the literature demonstrates correlations between gray matter pathology and various measures of both clinical disability and cognitive impairment. The effect of disease modifying therapies on the rate accumulation of gray matter pathology in MS has been investigated. This review focuses on the neuroimaging of gray matter pathology in MS, the effect of the accumulation of gray matter pathology on clinical and cognitive disability, and the effect of disease-modifying agents on various measures of gray matter damage. PMID:23878736

Photothermal damage is correlated to the delivery rate of time-integrated temperature

NASA Astrophysics Data System (ADS)

Denton, Michael L.; Noojin, Gary D.; Gamboa, B. Giovanna; Ahmed, Elharith M.; Rockwell, Benjamin A.

2016-03-01

Photothermal damage rate processes in biological tissues are usually characterized by a kinetics approach. This stems from experimental data that show how the transformation of a specified biological property of cells or biomolecule (plating efficiency for viability, change in birefringence, tensile strength, etc.) is dependent upon both time and temperature. However, kinetic methods require determination of kinetic rate constants and knowledge of substrate or product concentrations during the reaction. To better understand photothermal damage processes we have identified temperature histories of cultured retinal cells receiving minimum lethal thermal doses for a variety of laser and culture parameters. These "threshold" temperature histories are of interest because they inherently contain information regarding the fundamental thermal dose requirements for damage in individual cells. We introduce the notion of time-integrated temperature (Tint) as an accumulated thermal dose (ATD) with units of °C s. Damaging photothermal exposure raises the rate of ATD accumulation from that of the ambient (e.g. 37 °C) to one that correlates with cell death (e.g. 52 °C). The degree of rapid increase in ATD (ΔATD) during photothermal exposure depends strongly on the laser exposure duration and the ambient temperature.

Undulator Radiation Damage Experience at LCLS

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

Nuhn, H. D.; Field, C.; Mao, S.

2015-01-06

The SLAC National Accelerator Laboratory has been running the Linac Coherent Light Source (LCLS), the first x-ray Free Electron Laser since 2009. Undulator magnet damage from radiation, produced by the electron beam traveling through the 133-m long straight vacuum tube, has been and is a concern. A damage measurement experiment has been performed in 2007 in order to obtain dose versus damage calibrations. Radiation reduction and detection devices have been integrated into the LCLS undulator system. The accumulated radiation dose rate was continuously monitored and recorded. In addition, undulator segments have been routinely removed from the beamline to be checkedmore » for magnetic (50 ppm, rms) and mechanic (about 0.25 µm, rms) changes. A reduction in strength of the undulator segments is being observed, at a level, which is now clearly above the noise. Recently, potential sources for the observed integrated radiation levels have been investigated. The paper discusses the results of these investigation as well as comparison between observed damage and measured dose accumulations and discusses, briefly, strategies for the new LCLS-II upgrade, which will be operating at more than 300 times larger beam rate.« less

Simulating irradiation hardening in tungsten under fast neutron irradiation including Re production by transmutation

NASA Astrophysics Data System (ADS)

Huang, Chen-Hsi; Gilbert, Mark R.; Marian, Jaime

2018-02-01

Simulations of neutron damage under fusion energy conditions must capture the effects of transmutation, both in terms of accurate chemical inventory buildup as well as the physics of the interactions between transmutation elements and irradiation defect clusters. In this work, we integrate neutronics, primary damage calculations, molecular dynamics results, Re transmutation calculations, and stochastic cluster dynamics simulations to study neutron damage in single-crystal tungsten to mimic divertor materials. To gauge the accuracy and validity of the simulations, we first study the material response under experimental conditions at the JOYO fast reactor in Japan and the High Flux Isotope Reactor at Oak Ridge National Laboratory, for which measurements of cluster densities and hardening levels up to 2 dpa exist. We then provide calculations under expected DEMO fusion conditions. Several key mechanisms involving Re atoms and defect clusters are found to govern the accumulation of irradiation damage in each case. We use established correlations to translate damage accumulation into hardening increases and compare our results to the experimental measurements. We find hardening increases in excess of 5000 MPa in all cases, which casts doubts about the integrity of W-based materials under long-term fusion exposure.

Method to Improve Indium Bump Bonding via Indium Oxide Removal Using a Multi-Step Plasma Process

NASA Technical Reports Server (NTRS)

Dickie, Matthew R. (Inventor); Nikzad, Shouleh (Inventor); Greer, H. Frank (Inventor); Jones, Todd J. (Inventor); Vasquez, Richard P. (Inventor); Hoenk, Michael E. (Inventor)

2012-01-01

A process for removing indium oxide from indium bumps in a flip-chip structure to reduce contact resistance, by a multi-step plasma treatment. A first plasma treatment of the indium bumps with an argon, methane and hydrogen plasma reduces indium oxide, and a second plasma treatment with an argon and hydrogen plasma removes residual organics. The multi-step plasma process for removing indium oxide from the indium bumps is more effective in reducing the oxide, and yet does not require the use of halogens, does not change the bump morphology, does not attack the bond pad material or under-bump metallization layers, and creates no new mechanisms for open circuits.

Interrogating the Effects of Radiation Damage Annealing on Helium Diffusion Kinetics in Apatite

NASA Astrophysics Data System (ADS)

Willett, C. D.; Fox, M.; Shuster, D. L.

2015-12-01

Apatite (U-Th)/He thermochronology is commonly used to study landscape evolution and potential links between climate, erosion and tectonics. The technique relies on a quantitative understanding of (i) helium diffusion kinetics in apatite, (ii) an evolving 4He concentration, (iii) accumulating damage to the crystal lattice caused by radioactive decay[1], and (iv) the thermal annealing of such damage[2],[3], which are each functions of both time and temperature. Uncertainty in existing models of helium diffusion kinetics has resulted in conflicting conclusions, especially in settings involving burial heating through geologic time. The effects of alpha recoil damage annealing are currently assumed to follow the kinetics of fission track annealing (e.g., reference [3]), although this assumption is difficult to fully validate. Here, we present results of modeling exercises and a suite of experiments designed to interrogate the effects of damage annealing on He diffusivity in apatite that are independent of empirical calibrations of fission track annealing. We use the existing experimental results for Durango apatite[2] to develop and calibrate a new function that predicts the effects of annealing temperature and duration on measured diffusivity. We also present a suite of experiments conducted on apatite from Sierra Nevada, CA granite to establish whether apatites with different chemical compositions have the same behavior as Durango apatite. Crystals were heated under vacuum to temperatures between 250 and 500°C for 1, 10, or 100 hours. The samples were then irradiated with ~220 MeV protons to produce spallogenic 3He, the diffusant then used in step-heating diffusion experiments. We compare the results of these experiments and model calibrations to existing models. Citations: [1]Shuster, D., Flowers R., and Farley K., (2006), EPSL 249(3-4), 148-161; [2]Shuster, D. and Farley, K., (2009), GCA 73 (1), 6183-6196; [3]Flowers, R., Ketcham, R., Shuster, D. and Farley, K., (2009), GCA 73, 2347-2365.

A Bluetooth/PDR Integration Algorithm for an Indoor Positioning System.

PubMed

Li, Xin; Wang, Jian; Liu, Chunyan

2015-09-25

This paper proposes two schemes for indoor positioning by fusing Bluetooth beacons and a pedestrian dead reckoning (PDR) technique to provide meter-level positioning without additional infrastructure. As to the PDR approach, a more effective multi-threshold step detection algorithm is used to improve the positioning accuracy. According to pedestrians' different walking patterns such as walking or running, this paper makes a comparative analysis of multiple step length calculation models to determine a linear computation model and the relevant parameters. In consideration of the deviation between the real heading and the value of the orientation sensor, a heading estimation method with real-time compensation is proposed, which is based on a Kalman filter with map geometry information. The corrected heading can inhibit the positioning error accumulation and improve the positioning accuracy of PDR. Moreover, this paper has implemented two positioning approaches integrated with Bluetooth and PDR. One is the PDR-based positioning method based on map matching and position correction through Bluetooth. There will not be too much calculation work or too high maintenance costs using this method. The other method is a fusion calculation method based on the pedestrians' moving status (direct movement or making a turn) to determine adaptively the noise parameters in an Extended Kalman Filter (EKF) system. This method has worked very well in the elimination of various phenomena, including the "go and back" phenomenon caused by the instability of the Bluetooth-based positioning system and the "cross-wall" phenomenon due to the accumulative errors caused by the PDR algorithm. Experiments performed on the fourth floor of the School of Environmental Science and Spatial Informatics (SESSI) building in the China University of Mining and Technology (CUMT) campus showed that the proposed scheme can reliably achieve a 2-meter precision.

A Bluetooth/PDR Integration Algorithm for an Indoor Positioning System

PubMed Central

Li, Xin; Wang, Jian; Liu, Chunyan

2015-01-01

This paper proposes two schemes for indoor positioning by fusing Bluetooth beacons and a pedestrian dead reckoning (PDR) technique to provide meter-level positioning without additional infrastructure. As to the PDR approach, a more effective multi-threshold step detection algorithm is used to improve the positioning accuracy. According to pedestrians’ different walking patterns such as walking or running, this paper makes a comparative analysis of multiple step length calculation models to determine a linear computation model and the relevant parameters. In consideration of the deviation between the real heading and the value of the orientation sensor, a heading estimation method with real-time compensation is proposed, which is based on a Kalman filter with map geometry information. The corrected heading can inhibit the positioning error accumulation and improve the positioning accuracy of PDR. Moreover, this paper has implemented two positioning approaches integrated with Bluetooth and PDR. One is the PDR-based positioning method based on map matching and position correction through Bluetooth. There will not be too much calculation work or too high maintenance costs using this method. The other method is a fusion calculation method based on the pedestrians’ moving status (direct movement or making a turn) to determine adaptively the noise parameters in an Extended Kalman Filter (EKF) system. This method has worked very well in the elimination of various phenomena, including the “go and back” phenomenon caused by the instability of the Bluetooth-based positioning system and the “cross-wall” phenomenon due to the accumulative errors caused by the PDR algorithm. Experiments performed on the fourth floor of the School of Environmental Science and Spatial Informatics (SESSI) building in the China University of Mining and Technology (CUMT) campus showed that the proposed scheme can reliably achieve a 2-meter precision. PMID:26404277

Tumour-associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug

PubMed Central

Miller, Miles A.; Zheng, Yao-Rong; Gadde, Suresh; Pfirschke, Christina; Zope, Harshal; Engblom, Camilla; Kohler, Rainer H.; Iwamoto, Yoshiko; Yang, Katherine S.; Askevold, Bjorn; Kolishetti, Nagesh; Pittet, Mikael; Lippard, Stephen J.; Farokhzad, Omid C.; Weissleder, Ralph

2015-01-01

Therapeutic nanoparticles (TNPs) aim to deliver drugs more safely and effectively to cancers, yet clinical results have been unpredictable owing to limited in vivo understanding. Here we use single-cell imaging of intratumoral TNP pharmacokinetics and pharmacodynamics to better comprehend their heterogeneous behaviour. Model TNPs comprising a fluorescent platinum(IV) pro-drug and a clinically tested polymer platform (PLGA-b-PEG) promote long drug circulation and alter accumulation by directing cellular uptake toward tumour-associated macrophages (TAMs). Simultaneous imaging of TNP vehicle, its drug payload and single-cell DNA damage response reveals that TAMs serve as a local drug depot that accumulates significant vehicle from which DNA-damaging Pt payload gradually releases to neighbouring tumour cells. Correspondingly, TAM depletion reduces intratumoral TNP accumulation and efficacy. Thus, nanotherapeutics co-opt TAMs for drug delivery, which has implications for TNP design and for selecting patients into trials. PMID:26503691

A coupled weather generator - rainfall-runoff approach on hourly time steps for flood risk analysis

NASA Astrophysics Data System (ADS)

Winter, Benjamin; Schneeberger, Klaus; Dung Nguyen, Viet; Vorogushyn, Sergiy; Huttenlau, Matthias; Merz, Bruno; Stötter, Johann

2017-04-01

The evaluation of potential monetary damage of flooding is an essential part of flood risk management. One possibility to estimate the monetary risk is to analyze long time series of observed flood events and their corresponding damages. In reality, however, only few flood events are documented. This limitation can be overcome by the generation of a set of synthetic, physically and spatial plausible flood events and subsequently the estimation of the resulting monetary damages. In the present work, a set of synthetic flood events is generated by a continuous rainfall-runoff simulation in combination with a coupled weather generator and temporal disaggregation procedure for the study area of Vorarlberg (Austria). Most flood risk studies focus on daily time steps, however, the mesoscale alpine study area is characterized by short concentration times, leading to large differences between daily mean and daily maximum discharge. Accordingly, an hourly time step is needed for the simulations. The hourly metrological input for the rainfall-runoff model is generated in a two-step approach. A synthetic daily dataset is generated by a multivariate and multisite weather generator and subsequently disaggregated to hourly time steps with a k-Nearest-Neighbor model. Following the event generation procedure, the negative consequences of flooding are analyzed. The corresponding flood damage for each synthetic event is estimated by combining the synthetic discharge at representative points of the river network with a loss probability relation for each community in the study area. The loss probability relation is based on exposure and susceptibility analyses on a single object basis (residential buildings) for certain return periods. For these impact analyses official inundation maps of the study area are used. Finally, by analyzing the total event time series of damages, the expected annual damage or losses associated with a certain probability of occurrence can be estimated for the entire study area.

MIR imaging of the transitional disk source Oph IRS48

NASA Astrophysics Data System (ADS)

Honda, Mitsuhiko

2015-06-01

We propose to make 25 mum mid-infrared imaging of the transitional disk around the young star Oph IRS 48 to derive the temperature of the emitting dust in this disk. Recently, ALMA observation revealed the apparent difference of the infrared (18.7 mum) and radio (440 mum) dust continuum of this system and implied that the large mm-sized grains are trapped and accumulated to the local pressure maximum, which may eventually form planetesimals/planets. However, there can be other explanations to such apparent difference in the different wavelengths. To verify such interpretation, new 25 mum imaging can provide some clues, since it is the wavelength between the previous 18.7 mum and the 440 mum observations. Furthermore, multi-wavelength study of the disk is a natural step towards detailed understanding of disk structure, and new 25 mum image can be complemental to forthecoming ALMA and NIR polarimetric data.

MIR imaging of the transitional disk source Oph IRS48

NASA Astrophysics Data System (ADS)

Honda, Mitsuhiko

2014-01-01

We propose to make 25 micron mid-infrared imaging of the transitional disk around the young star Oph IRS 48 to derive the temperature of the emitting dust in this disk. Recently, ALMA observation revealed the apparent difference of the infrared (18.7 micron) and radio (440 micron) dust continuum of this system and implied that the large mm-sized grains are trapped and accumulated to the local pressure maximum, which may eventually form planetesimals/planets. However, there can be other explanations to such apparent difference in the different wavelengths. To verify such interpretation, new 25 micron imaging can provide some clues, since it is the wavelength between previous 18.7 micron and 440 micron observations. Furthermore, multi-wavelength study of the disk is a natural step towards detailed understanding of disk structure, and new 25 micron image can be complemental to forthecoming ALMA and NIR polarimetric data.

Electron correlations and pre-collision in the re-collision picture of high harmonic generation

NASA Astrophysics Data System (ADS)

Mašín, Zdeněk; Harvey, Alex G.; Spanner, Michael; Patchkovskii, Serguei; Ivanov, Misha; Smirnova, Olga

2018-07-01

We discuss the seminal three-step model and the re-collision picture in the context of high harmonic generation in molecules. In particular, we stress the importance of multi-electron correlation during the first and the third of the three steps of the process: (1) the strong-field ionization and (3) the recombination. We point out how an accurate account of multi-electron correlations during the third recombination step allows one to gauge the importance of pre-collision: the term coined by Eberly (n.d. private communication) to describe unusual pathways during the first, ionization, step.

Description of bioremediation of soils using the model of a multistep system of microorganisms

NASA Astrophysics Data System (ADS)

Lubysheva, A. I.; Potashev, K. A.; Sofinskaya, O. A.

2018-01-01

The paper deals with the development of a mathematical model describing the interaction of a multi-step system of microorganisms in soil polluted with oil products. Each step in this system uses products of vital activity of the previous step to feed. Six different models of the multi-step system are considered. The equipping of the models with coefficients was carried out from the condition of minimizing the residual of the calculated and experimental data using an original algorithm based on the Levenberg-Marquardt method in combination with the Monte Carlo method for the initial approximation finding.

Diallel analysis for aflatoxin accumulation and fall armyworm leaf feeding damage in maize

USDA-ARS?s Scientific Manuscript database

Two of the major impediments to profitable maize, Zea mays L., production in the southern United States are losses from feeding by fall armyworm, Spodoptera frugiperda (J.E. Smith), and losses from the production and accumulation of aflatoxin in maize grain. The fall armyworm feeds on all above-grou...

PHYSICAL AND ECONOMIC DAMAGE FUNCTIONS FOR AIR POLLUTANTS BY RECEPTOR

EPA Science Inventory

This study is primarily concerned with evaluating regional economic damages to human health, material, and vegetation and of property soiling resulting from air pollution. This study represents a step forward in methodological development of air pollution damage estimation. It at...

MTOR-driven quasi-programmed aging as a disposable soma theory

PubMed Central

2013-01-01

If life were created by intelligent design, we would indeed age from accumulation of molecular damage. Repair is costly and limited by energetic resources, and we would allocate resources rationally. But, albeit elegant, this design is fictional. Instead, nature blindly selects for short-term benefits of robust developmental growth. “Quasi-programmed” by the blind watchmaker, aging is a wasteful and aimless continuation of developmental growth, driven by nutrient-sensing, growth-promoting signaling pathways such as MTOR (mechanistic target of rapamycin). A continuous post-developmental activity of such gerogenic pathways leads to hyperfunctions (aging), loss of homeostasis, age-related diseases, non-random organ damage and death. This model is consistent with a view that (1) soma is disposable, (2) aging and menopause are not programmed and (3) accumulation of random molecular damage is not a cause of aging as we know it. PMID:23708516

MTOR-driven quasi-programmed aging as a disposable soma theory: blind watchmaker vs. intelligent designer.

PubMed

Blagosklonny, Mikhail V

2013-06-15

If life were created by intelligent design, we would indeed age from accumulation of molecular damage. Repair is costly and limited by energetic resources, and we would allocate resources rationally. But, albeit elegant, this design is fictional. Instead, nature blindly selects for short-term benefits of robust developmental growth. "Quasi-programmed" by the blind watchmaker, aging is a wasteful and aimless continuation of developmental growth, driven by nutrient-sensing, growth-promoting signaling pathways such as MTOR (mechanistic target of rapamycin). A continuous post-developmental activity of such gerogenic pathways leads to hyperfunctions (aging), loss of homeostasis, age-related diseases, non-random organ damage and death. This model is consistent with a view that (1) soma is disposable, (2) aging and menopause are not programmed and (3) accumulation of random molecular damage is not a cause of aging as we know it.

Exogenous calcium improves viability of biocontrol yeasts under heat stress by reducing ROS accumulation and oxidative damage of cellular protein.

PubMed

An, Bang; Li, Boqiang; Qin, Guozheng; Tian, Shiping

2012-08-01

In this article, we investigated the effect of exogenous calcium on improving viability of Debaryomyces hansenii and Pichia membranaefaciens under heat stress, and evaluated the role of calcium in reducing oxidant damage of proteins in the yeast cells. The results indicated that high concentration of exogenous calcium in culture medium was beneficial for enhancing the tolerance of the biocontrol yeasts to heat stress. The possible mechanism of calcium improving the viability of yeasts was attributed to enhancement of antioxidant enzyme activities, decrease in ROS accumulation and reduction of oxidative damage of intracellular protein in yeast cells under heat stress. D. hansenii is more sensitive to calcium as compared to P. membranaefaciens. Our results suggest that application of exogenous calcium combined with biocontrol yeasts is a practical approach for the control of postharvest disease in fruit.

Multi-Step Deep Reactive Ion Etching Fabrication Process for Silicon-Based Terahertz Components

NASA Technical Reports Server (NTRS)

Reck, Theodore (Inventor); Perez, Jose Vicente Siles (Inventor); Lee, Choonsup (Inventor); Cooper, Ken B. (Inventor); Jung-Kubiak, Cecile (Inventor); Mehdi, Imran (Inventor); Chattopadhyay, Goutam (Inventor); Lin, Robert H. (Inventor); Peralta, Alejandro (Inventor)

2016-01-01

A multi-step silicon etching process has been developed to fabricate silicon-based terahertz (THz) waveguide components. This technique provides precise dimensional control across multiple etch depths with batch processing capabilities. Nonlinear and passive components such as mixers and multipliers waveguides, hybrids, OMTs and twists have been fabricated and integrated into a small silicon package. This fabrication technique enables a wafer-stacking architecture to provide ultra-compact multi-pixel receiver front-ends in the THz range.

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'.

He diffusion in zircon: Observations from (U-Th)/He age suites and 4He diffusion experiments and implications for radiation damage and anisotropic effects

NASA Astrophysics Data System (ADS)

Guenthner, W. R.; Reiners, P. W.

2009-12-01

Despite widespread use of zircon (U-Th)/He thermochronometry in many geologic applications, our understanding of the kinetics of He diffusion in this system is rudimentary. Previous studies have shown that both radiation damage and crystallographic anisotropy may strongly influence diffusion kinetics and ages. We present observations of zircon He ages from multiple single-grain analyses from both detrital and bedrock suites from a wide variety of locations, showing relationships consistent with effects arising from the interaction of radiation damage and anisotropy. Individual zircons in each suite have experienced the same post-depositional or exhumational t-T history but grains appear to have experienced differential He loss that is correlated with effective uranium (eU) content, a proxy for the relative extent of radiation damage within each suite. Several suites of zircons heated to partial resetting upon burial or that have experienced slow cooling show positive correlations between age and eU. Examples of partially reset detrital samples include Cretaceous Sevier foreland basin sandstones buried to ~6-8 km depth, with ages ranging from 88-309 Ma across an eU range of 215-1453 ppm, and Apennines and Olympics greywackes heated to >~120 °C, showing similar trends. Some slowly-cooled bedrock samples also show positive age-eU correlations, suggesting increasing closure temperature with higher extents of radiation damage. Conversely, zircons from cratonal bedrock samples with high levels of radiation damage—measured as accumulated alpha dosage (in this case >~10^18 α/g)—generally show negative age-eU correlations. We interpret these contrasting age-eU relationships as a manifestation of the interaction of radiation damage and anisotropic diffusion: at low damage, He diffusivity is relatively high and preferentially through c-axis-parallel channels. As suggested by Farley (2007), however, with increasing damage, channels are progressively blocked and He diffusivity decreases. Eventually, a crystal reaches a threshold level (>~10^18 α/g ) wherein radiation damage is so extensive that damage zones become interconnected and He diffusivity increases once again. In order to evaluate these assertions, we conducted a series of step-heating experiments on several pairs of zircon slabs. Individual slabs were crystallographically oriented either orthogonal or parallel to the c-axis and each pair possessed varying degrees of radiation damage. Results from these experiments provide new closure temperature estimates, explain age-eU correlations within a data set, and allow us to construct diffusion models that more accurately describe the t-T history of a given sample.

Silicon Priming Created an Enhanced Tolerance in Alfalfa (Medicago sativa L.) Seedlings in Response to High Alkaline Stress.

PubMed

Liu, Duo; Liu, Miao; Liu, Xiao-Long; Cheng, Xian-Guo; Liang, Zheng-Wei

2018-01-01

Alkaline stress as a result of higher pH usually triggers more severe physiological damage to plants than that of saline stress with a neutral pH. In the present study, we demonstrated that silicon (Si) priming of alfalfa ( Medicago sativa L.) seedlings increased their tolerance to high alkaline stress situations. Gongnong No. 1 seedlings were subjected to alkaline stress simulated by 25 mM Na 2 CO 3 (pH 11.2). Alkaline stress greatly decreased the biomass and caused severe lodging or wilting of alfalfa seedlings. In contrast, the application of Si to alfalfa seedlings 36 h prior to the alkaline treatment significantly alleviated the damage symptoms and greatly increased the biomass and chlorophyll content. Because of being concomitant with increasing photosynthesis and water use efficiency, decreasing membrane injury and malondialdehyde content, and increasing peroxidase and catalase ascorbate activities in alfalfa leaves, thereby alleviating the triggered oxidative damage by alkaline stress to the plant. Furthermore, Si priming significantly decreased the accumulation of protein and proline content in alfalfa, thus reducing photosynthetic feedback repression. Si priming significantly accumulated more Na in the roots, but led to a decrease of Na accumulation and an increase of K accumulation in the leaves under alkaline stress. Meanwhile, Si priming decreased the accumulation of metal ions such as Mg, Fe, Mn, and Zn in the roots of alfalfa seedlings under alkaline stress. Collectively, these results suggested that Si is involved in the metabolic or physiological changes and has a potent priming effect on the alkaline tolerance of alfalfa seedlings. The present study indicated that Si priming is a new approach to improve the alkaline tolerance in alfalfa and provides increasing information for further exploration of the alkaline stress response at the molecular level in alfalfa.

Progressive failure methodologies for predicting residual strength and life of laminated composites

NASA Technical Reports Server (NTRS)

Harris, Charles E.; Allen, David H.; Obrien, T. Kevin

1991-01-01

Two progressive failure methodologies currently under development by the Mechanics of Materials Branch at NASA Langley Research Center are discussed. The damage tolerance/fail safety methodology developed by O'Brien is an engineering approach to ensuring adequate durability and damage tolerance by treating only delamination onset and the subsequent delamination accumulation through the laminate thickness. The continuum damage model developed by Allen and Harris employs continuum damage laws to predict laminate strength and life. The philosophy, mechanics framework, and current implementation status of each methodology are presented.

Semi-active control of monopile offshore wind turbines under multi-hazards

NASA Astrophysics Data System (ADS)

Sun, C.

2018-01-01

The present paper studies the control of monopile offshore wind turbines subjected to multi-hazards consisting of wind, wave and earthquake. A Semi-active tuned mass damper (STMD) with tunable natural frequency and damping ratio is introduced to control the dynamic response. A new fully coupled analytical model of the monopile offshore wind turbine with an STMD is established. The aerodynamic, hydrodynamic and seismic loading models are derived. Soil effects and damage are considered. The National Renewable Energy Lab monopile 5 MW baseline wind turbine model is employed to examine the performance of the STMD. A passive tuned mass damper (TMD) is utilized for comparison. Through numerical simulation, it is found that before damage occurs, the wind and wave induced response is more dominant than the earthquake induced response. With damage presence in the tower and the foundation, the nacelle and the tower response is increased dramatically and the natural frequency is decreased considerably. As a result, the passive TMD with fixed parameters becomes off-tuned and loses its effectiveness. In comparison, the STMD retuned in real-time demonstrates consistent effectiveness in controlling the dynamic response of the monopile offshore wind turbines under multi-hazards and damage with a smaller stroke.

Novel Platinum (Pt)-Vandetanib Hybrid Compounds: Design, Synthesis and Investigation of Anti-cancer Activity and Mechanism of Action

NASA Astrophysics Data System (ADS)

Fei, Rong

Purpose: Lung cancer is one of the most common cancers and non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancers. 70% of individuals with NSCLC harboring somatic mutations in exons of the epidermal growth factor receptor (EGFR) gene that encode tyrosine kinase domain. EGFR tyrosine kinase inhibitors (TKIs) are promising molecular targeted therapy for NSCLC with sensitizing EGFR mutations. However, secondary mutation of EGFR after treatment of TKIs develops resistance. Vandetanib is introduced to overcome erlotinib resistance as a multi-targeted TKI. However, its anticancer effect is still compromised by EGFR T790M mutation. Therefore, new molecular anticancer strategies are necessarily needed. In this study, vandetanib is incorporated with Pt-based anticancer agents as hybrid compounds, aiming to circumvent TKI resistance. Furthermore, hybrid compounds are investigated in cisplatin resistant problem to expect to overcome resistance by introduction of vandetanib. Methods: Three novel Pt-vandetanib hybrid compounds were synthesized and its physicochemical properties were characterized. Anticancer activity and cytotoxicity were evaluated by sulforhodamine B assay and lactate dehydrogenase release. Docking simulation was performed to investigate the interaction of compounds with EGFR harboring different mutations. Inhibition efficacy of hybrids to kinases was evaluated by kinase inhibition profiling service and cell-free kinase inhibition assay. Mechanistic studies on cytotoxicity activity of the hybrid compounds were carried out. DNA damage response of hybrid compounds was further investigated in KB cells. The cytotoxicity of hybrids was tested in cisplatin resistant KB CP20 cells. Mechanistic of anticancer activity was studied to test inhibition on oncoprotein CIP2Aand DNA damage. Results: Platinum-vandetanib hybrid compounds were synthesized and test to be stable under extracellular condition. Hybrids reacted with 5'-GMP2- and glutathione, and both of them formed mono-dentate adducts. Moreover, hybrid compounds exhibited low toxicity in human normal kidney cells. Compounds maintained the inhibition selectivity towards EGFR from the results of kinase inhibition profiling and cell-free kinase inhibition assay. Hybrids formed strong H-bond at D800 on EGFR. Pt-vandetanib hybrids were highly effective against HCC827 cells harboring sensitizing EGFR mutation. Importantly, relative resistant rate of hybrids were much smaller than vandetanib in H1975 cells. Western blot analysis results revealed that the hybrid compounds could efficiently inhibit EGFR phosphorylation in a dose dependent manner in HCC827. While, inhibition of p-EGFR was not as good as the original TKI in H1975 cells. However, the hybrid compounds induced DNA damage and caused apoptosis of the NSCLC cells. Both of the two pathways were contributed to cancer cell death and overcome vandetanib resistance. Pt-vandetanib hybrids showed little resistance in cisplatin resistant cell line KB-CP20. Drug accumulation evaluation revealed that cisplatin accumulation in CP20 cells decreased to one eighth of that in the parental KB3.1 cells. While hybrids maintained similar drug accumulation extent in both cells lines. Mechanistic study showed that hybrid compounds could induce DNA damage and cause apoptosis, whereas cisplatin failed to cause DNA damage in KB-CP20 cells. Oncoprotein CIP2A was overexpressed in CP20 cell and was ascribed to CDDP resistance. The hybrids inhibited CIP2A expression and downstream AKT phosphorylation. It was hypothesized that downregulation of CIP2A contributed to circumvention platinum resistance. Conclusion: Novel Pt-vandetanib hybrid compounds were able to overcome vandetanib resistance in H1975 cells by maintaining inhibition to the EGFR and inducing DNA damage and apoptosis. Moreover, Pt-vandetanib hybrid compounds behaved low toxicity and overcome cisplatin resistance by being "non-substrate" to efflux transporter and successfully causing DNA damage. Hybrids were found to downregulate oncogene CIP2A expression level. The novel Pt-vandetanib hybrid compounds are potent for further development.

78 FR 33206 - Airworthiness Directives; Bombardier, Inc. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-04

... by reports of failure of a screw cap or end cap of the hydraulic system accumulator while on the ground, which resulted in loss of use of that hydraulic system and high-energy impact damage to adjacent..., resulting in loss of the associated hydraulic system and high-energy impact damage to adjacent systems and...

18 CFR 367.2282 - Account 228.2, Accumulated provision for injuries and damages.

Code of Federal Regulations, 2010 CFR

2010-04-01

... with amounts charged to account 925, Injuries and damages (§ 367.9250), or other appropriate accounts... must be charged to this account and credited to the appropriate current liability account. Details of.... (c) Recoveries or reimbursements for losses charged to this account must be credited to this account...

The Effects of Ecoregion Dynamics on Agroregions for Permanent Crops in the Continental US Under Future Climate Change Scenarios

NASA Astrophysics Data System (ADS)

Maddalena, D. M.; L'Heureux, J.; Hoffman, F. M.

2017-12-01

Fruit and Tree Nut production in the US averaged 14% of total annual production, or roughly $28 billion in total revenue for the most recent 5 year period (2011 - 2015). The success of these crops is highly dependent on environmental conditions. Cold snaps before winter dormancy, early frosts in spring, and lack of sufficient chilling hours can reduce productivity, inflict wood damage, and lead to economic loss. Climate change can increase the likelihood of these threats and may have long-term implications for the areas where these crops are grown due to the migration of ecoregions as climate patters shift. We delineate ecoregions using multi-attribute spatio-temporal clustering and calculate chilling unit accumulation under past, present, and future climate scenarios using measured and modeled data. These results are then compared to current agroregions in the US to calculate risk dynamics, potential economic loss, and to map future agroregion scenarios. Our results offer considerations for food system sustainability under a shifting climate.

Simulation of thermomechanical fatigue in solder joints

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

Fang, H.E.; Porter, V.L.; Fye, R.M.

1997-12-31

Thermomechanical fatigue (TMF) is a very complex phenomenon in electronic component systems and has been identified as one prominent degradation mechanism for surface mount solder joints in the stockpile. In order to precisely predict the TMF-related effects on the reliability of electronic components in weapons, a multi-level simulation methodology is being developed at Sandia National Laboratories. This methodology links simulation codes of continuum mechanics (JAS3D), microstructural mechanics (GLAD), and microstructural evolution (PARGRAIN) to treat the disparate length scales that exist between the macroscopic response of the component and the microstructural changes occurring in its constituent materials. JAS3D is used tomore » predict strain/temperature distributions in the component due to environmental variable fluctuations. GLAD identifies damage initiation and accumulation in detail based on the spatial information provided by JAS3D. PARGRAIN simulates the changes of material microstructure, such as the heterogeneous coarsening in Sn-Pb solder, when the component`s service environment varies.« less

Histone deacetylase inhibitor (HDACI) PCI-24781 enhances chemotherapy induced apoptosis in multidrug resistant sarcoma cell lines

PubMed Central

Yang, Cao; Choy, Edwin; Hornicek, Francis J.; Wood, Kirkham B; Schwab, Joseph H; Liu, Xianzhe; Mankin, Henry; Duan, Zhenfeng

2013-01-01

The anti-tumor activity of histone deacetylase inhibitors (HDACI) on multi-drug resistant sarcoma cell lines has never been previously described. Four multidrug resistant sarcoma cell lines treated with HDACI PCI-24781 resulted in dose-dependent accumulation of acetylated histones, p21 and PARP cleavage products. Growth of these cell lines was inhibited by PCI-24781 at IC50 of 0.43 to 2.7. When we looked for synergy of PCI-24781 with chemotherapeutic agents, we found that PCI-24781 reverses drug resistance in all four multidrug resistant sarcoma cell lines and synergizes with chemotherapeutic agents to enhance caspase-3/7 activity. Expression of RAD51 (a marker for DNA double-strand break repair) was inhibited and the expression of GADD45α (a marker for growth arrest and DNA-damage) was induced by PCI-24781 in multidrug resistant sarcoma cell lines. In conclusion, HDACI PCI-24781 synergizes with chemotherapeutic drugs to induce apoptosis and reverses drug resistance in multidrug resistant sarcoma cell lines. PMID:21508354

Monitoring the Electrochemical Processes in the Lithium–Air Battery by Solid State NMR Spectroscopy

PubMed Central

2013-01-01

A multi-nuclear solid-state NMR approach is employed to investigate the lithium–air battery, to monitor the evolution of the electrochemical products formed during cycling, and to gain insight into processes affecting capacity fading. While lithium peroxide is identified by 17O solid state NMR (ssNMR) as the predominant product in the first discharge in 1,2-dimethoxyethane (DME) based electrolytes, it reacts with the carbon cathode surface to form carbonate during the charging process. 13C ssNMR provides evidence for carbonate formation on the surface of the carbon cathode, the carbonate being removed at high charging voltages in the first cycle, but accumulating in later cycles. Small amounts of lithium hydroxide and formate are also detected in discharged cathodes and while the hydroxide formation is reversible, the formate persists and accumulates in the cathode upon further cycling. The results indicate that the rechargeability of the battery is limited by both the electrolyte and the carbon cathode stability. The utility of ssNMR spectroscopy in directly detecting product formation and decomposition within the battery is demonstrated, a necessary step in the assessment of new electrolytes, catalysts, and cathode materials for the development of a viable lithium–oxygen battery. PMID:24489976

Downregulation of VRK1 by p53 in Response to DNA Damage Is Mediated by the Autophagic Pathway

PubMed Central

Valbuena, Alberto; Castro-Obregón, Susana; Lazo, Pedro A.

2011-01-01

Human VRK1 induces a stabilization and accumulation of p53 by specific phosphorylation in Thr18. This p53 accumulation is reversed by its downregulation mediated by Hdm2, requiring a dephosphorylated p53 and therefore also needs the removal of VRK1 as stabilizer. This process requires export of VRK1 to the cytosol and is inhibited by leptomycin B. We have identified that downregulation of VRK1 protein levels requires DRAM expression, a p53-induced gene. DRAM is located in the endosomal-lysosomal compartment. Induction of DNA damage by UV, IR, etoposide and doxorubicin stabilizes p53 and induces DRAM expression, followed by VRK1 downregulation and a reduction in p53 Thr18 phosphorylation. DRAM expression is induced by wild-type p53, but not by common human p53 mutants, R175H, R248W and R273H. Overexpression of DRAM induces VRK1 downregulation and the opposite effect was observed by its knockdown. LC3 and p62 were also downregulated, like VRK1, in response to UV-induced DNA damage. The implication of the autophagic pathway was confirmed by its requirement for Beclin1. We propose a model with a double regulatory loop in response to DNA damage, the accumulated p53 is removed by induction of Hdm2 and degradation in the proteasome, and the p53-stabilizer VRK1 is eliminated by the induction of DRAM that leads to its lysosomal degradation in the autophagic pathway, and thus permitting p53 degradation by Hdm2. This VRK1 downregulation is necessary to modulate the block in cell cycle progression induced by p53 as part of its DNA damage response. PMID:21386980

Moderate Thermal Stress Causes Active and Immediate Expulsion of Photosynthetically Damaged Zooxanthellae (Symbiodinium) from Corals.

PubMed

Fujise, Lisa; Yamashita, Hiroshi; Suzuki, Go; Sasaki, Kengo; Liao, Lawrence M; Koike, Kazuhiko

2014-01-01

The foundation of coral reef biology is the symbiosis between corals and zooxanthellae (dinoflagellate genus Symbiodinium). Recently, coral bleaching, which often results in mass mortality of corals and the collapse of coral reef ecosystems, has become an important issue around the world as coral reefs decrease in number year after year. To understand the mechanisms underlying coral bleaching, we maintained two species of scleractinian corals (Acroporidae) in aquaria under non-thermal stress (27°C) and moderate thermal stress conditions (30°C), and we compared the numbers and conditions of the expelled Symbiodinium from these corals. Under non-thermal stress conditions corals actively expel a degraded form of Symbiodinium, which are thought to be digested by their host coral. This response was also observed at 30°C. However, while the expulsion rates of Symbiodinium cells remained constant, the proportion of degraded cells significantly increased at 30°C. This result indicates that corals more actively digest and expel damaged Symbiodinium under thermal stress conditions, likely as a mechanism for coping with environmental change. However, the increase in digested Symbiodinium expulsion under thermal stress may not fully keep up with accumulation of the damaged cells. There are more photosynthetically damaged Symbiodinium upon prolonged exposure to thermal stress, and corals release them without digestion to prevent their accumulation. This response may be an adaptive strategy to moderate stress to ensure survival, but the accumulation of damaged Symbiodinium, which causes subsequent coral deterioration, may occur when the response cannot cope with the magnitude or duration of environmental stress, and this might be a possible mechanism underlying coral bleaching during prolonged moderate thermal stress.

Moderate Thermal Stress Causes Active and Immediate Expulsion of Photosynthetically Damaged Zooxanthellae (Symbiodinium) from Corals

PubMed Central

Fujise, Lisa; Yamashita, Hiroshi; Suzuki, Go; Sasaki, Kengo; Liao, Lawrence M.; Koike, Kazuhiko

2014-01-01

The foundation of coral reef biology is the symbiosis between corals and zooxanthellae (dinoflagellate genus Symbiodinium). Recently, coral bleaching, which often results in mass mortality of corals and the collapse of coral reef ecosystems, has become an important issue around the world as coral reefs decrease in number year after year. To understand the mechanisms underlying coral bleaching, we maintained two species of scleractinian corals (Acroporidae) in aquaria under non-thermal stress (27°C) and moderate thermal stress conditions (30°C), and we compared the numbers and conditions of the expelled Symbiodinium from these corals. Under non-thermal stress conditions corals actively expel a degraded form of Symbiodinium, which are thought to be digested by their host coral. This response was also observed at 30°C. However, while the expulsion rates of Symbiodinium cells remained constant, the proportion of degraded cells significantly increased at 30°C. This result indicates that corals more actively digest and expel damaged Symbiodinium under thermal stress conditions, likely as a mechanism for coping with environmental change. However, the increase in digested Symbiodinium expulsion under thermal stress may not fully keep up with accumulation of the damaged cells. There are more photosynthetically damaged Symbiodinium upon prolonged exposure to thermal stress, and corals release them without digestion to prevent their accumulation. This response may be an adaptive strategy to moderate stress to ensure survival, but the accumulation of damaged Symbiodinium, which causes subsequent coral deterioration, may occur when the response cannot cope with the magnitude or duration of environmental stress, and this might be a possible mechanism underlying coral bleaching during prolonged moderate thermal stress. PMID:25493938

A two-step FEM-SEM approach for wave propagation analysis in cable structures

NASA Astrophysics Data System (ADS)

Zhang, Songhan; Shen, Ruili; Wang, Tao; De Roeck, Guido; Lombaert, Geert

2018-02-01

Vibration-based methods are among the most widely studied in structural health monitoring (SHM). It is well known, however, that the low-order modes, characterizing the global dynamic behaviour of structures, are relatively insensitive to local damage. Such local damage may be easier to detect by methods based on wave propagation which involve local high frequency behaviour. The present work considers the numerical analysis of wave propagation in cables. A two-step approach is proposed which allows taking into account the cable sag and the distribution of the axial forces in the wave propagation analysis. In the first step, the static deformation and internal forces are obtained by the finite element method (FEM), taking into account geometric nonlinear effects. In the second step, the results from the static analysis are used to define the initial state of the dynamic analysis which is performed by means of the spectral element method (SEM). The use of the SEM in the second step of the analysis allows for a significant reduction in computational costs as compared to a FE analysis. This methodology is first verified by means of a full FE analysis for a single stretched cable. Next, simulations are made to study the effects of damage in a single stretched cable and a cable-supported truss. The results of the simulations show how damage significantly affects the high frequency response, confirming the potential of wave propagation based methods for SHM.

Role of the ceramide-signaling pathways in ionizing radiation-induced apoptosis.

PubMed

Vit, Jean-Philippe; Rosselli, Filippo

2003-11-27

Ionizing radiations (IR) exposure leads to damage on several cellular targets. How signals from different targets are integrated to determine the cell fate remains a controversial issue. Understanding the pathway(s) responsible(s) for the cell killing effect of the IR exposure is of prime importance in light of using radiations as anticancer agent or as diagnostic tool. In this study, we have established that IR-induced cell damage initiates two independent signaling pathways that lead to a biphasic intracellular ceramide increase. A transitory increase of ceramide is observed within minutes after IR exposure as a consequence of DNA damage-independent acid sphingomyelinase activation. Several hours after irradiation, a second wave of ceramide accumulation is observed depending on the DNA damage-dependent activation of ceramide synthase, which requires a signaling pathway involving ATM. Importantly, we have demonstrated that the late ceramide accumulation is also dependent on the first one and is rate limiting for the apoptotic process induced by IR. In conclusion, our observations suggest that ceramide is a major determinant of the IR-induced apoptotic process at the cross-point of different signal transduction pathways.

Combined effects of radiation damage and He accumulation on bubble nucleation in Gd2Ti2O7

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

Taylor, Caitlin A.; Patel, Maulik K.; Aguiar, Jeffery A.

2016-10-01

Pyrochlores have long been considered as host phases for long-term immobilization of radioactive waste nuclides that would undergo ..alpha..-decay for hundreds of thousands of years. This work utilizes ion-beam irradiations to examine the combined effects of radiation damage and He accumulation on bubble formation in Gd2Ti2O7 over relevant waste-form timescales. Helium bubbles are not observed in pre-damaged Gd2Ti2O7 implanted with 2 x 1016 He/cm2, even after post-implantation irradiations with 7 MeV Au3+ at 300, 500, and 700 K. However, He bubbles with average diameters of 1.5 nm and 2.1 nm are observed in pre-damaged (amorphous) Gd2Ti2O7 and pristine Gd2Ti2O7, respectively,more » after implantation of 2 x 1017 He/cm2. The critical He concentration for bubble nucleation in Gd2Ti2O7 is estimated to be 6 at.% He.« less

A successful backward step correlates with hip flexion moment of supporting limb in elderly people.

PubMed

Takeuchi, Yahiko

2018-01-01

The objective of this study was to determine the positional relationship between the center of mass (COM) and the center of pressure (COP) at the time of step landing, and to examine their relationship with the joint moments exerted by the supporting limb, with regard to factors of the successful backward step response. The study population comprised 8 community-dwelling elderly people that were observed to take successive multi steps after the landing of a backward stepping. Using a motion capture system and force plate, we measured the COM, COP and COM-COP deviation distance on landing during backward stepping. In addition, we measured the moment of the supporting limb joint during backward stepping. The multi-step data were compared with data from instances when only one step was taken (single-step). Variables that differed significantly between the single- and multi-step data were used as objective variables and the joint moments of the supporting limb were used as explanatory variables in single regression analyses. The COM-COP deviation in the anteroposterior was significantly larger in the single-step. A regression analysis with COM-COP deviation as the objective variable obtained a significant regression equation in the hip flexion moment (R2 = 0.74). The hip flexion moment of supporting limb was shown to be a significant explanatory variable in both the PS and SS phases for the relationship with COM-COP distance. This study found that to create an appropriate backward step response after an external disturbance (i.e. the ability to stop after 1 step), posterior braking of the COM by a hip flexion moment are important during the single-limbed standing phase.

Physiological and Metabolic Effects of 5-Aminolevulinic Acid for Mitigating Salinity Stress in Creeping Bentgrass

PubMed Central

Yang, Zhimin; Chang, Zuoliang; Sun, Lihong; Yu, Jingjin; Huang, Bingru

2014-01-01

The objectives of this study were to determine whether foliar application of a chlorophyll precursor, 5-aminolevulinic acid (ALA), could mitigate salinity stress damages in perennial grass species by regulating photosynthetic activities, ion content, antioxidant metabolism, or metabolite accumulation. A salinity-sensitive perennial grass species, creeping bentgrass (Agrostis stolonifera), was irrigated daily with 200 mM NaCl for 28 d, which were foliar sprayed with water or ALA (0.5 mg L−1) weekly during the experiment in growth chamber. Foliar application of ALA was effective in mitigating physiological damage resulting from salinity stress, as manifested by increased turf quality, shoot growth rate, leaf relative water content, chlorophyll content, net photosynthetic rate, stomatal conductance and transpiration rate. Foliar application of ALA also alleviated membrane damages, as shown by lower membrane electrolyte leakage and lipid peroxidation, which was associated with increases in the activities of antioxidant enzymes. Leaf content of Na+ was reduced and the ratio of K+/Na+ was increased with ALA application under salinity stress. The positive effects of ALA for salinity tolerance were also associated with the accumulation of organic acids (α-ketoglutaric acid, succinic acid, and malic acid), amino acids (alanine, 5-oxoproline, aspartic acid, and γ -aminobutyric acid), and sugars (glucose, fructose, galactose, lyxose, allose, xylose, sucrose, and maltose). ALA-mitigation of physiological damages by salinity could be due to suppression of Na+ accumulation and enhanced physiological and metabolic activities related to photosynthesis, respiration, osmotic regulation, and antioxidant defense. PMID:25551443

The potential for non-invasive study of mummies: validation of the use of computerized tomography by post factum dissection and histological examination of a 17th century female Korean mummy

PubMed Central

Lim, Do-Seon; Lee, In Sun; Choi, Ki-Ju; Lee, Soong Deok; Oh, Chang Seok; Kim, Yi-Suk; Bok, Gi Dae; Kim, Myeung Ju; Yi, Yang Su; Lee, Eun-Joo; Shin, Dong Hoon

2008-01-01

The socio-cultural antipathies of some descendants with regard to invasive examinations of age-old human remains make permission for dissection of Korean mummies of the Joseon Dynasty (1392–1910) difficult to obtain. Overcoming this obstacle necessitated the use of non-invasive techniques, such as multi-detector computerized tomography (MDCT) and endoscopic examination, enabling determination of the preservation status of internal organs of mummies without significantly damaging the mummies themselves. However, MDCT alone cannot clearly differentiate specific mummified organs. Therefore, in much the same way as diagnostic radiologists make their MDCT readings on living patients more reliable by means of comparison with accumulated post-factum data from autopsies or histological studies, examinations of mummies by invasive techniques should not be decried as mere destruction of age-old human remains. Rather, providing that due permission from descendants and/or other relevant authorities can be obtained, dissection and histological examination should be performed whenever opportunities arise. Therefore, in this study, we compared the radiological data acquired from a 17th century mummy with our dissection results for the same subject. As accumulation of this kind of data could be very crucial for correct interpretation of MDCT findings on Korean mummies, we will perform similar trials on other Korean mummies found in forthcoming days if conditions permit. PMID:19014355

Use of Chiral Oxazolidinones for a Multi-Step Synthetic Laboratory Module

ERIC Educational Resources Information Center

Betush, Matthew P.; Murphree, S. Shaun

2009-01-01

Chiral oxazolidinone chemistry is used as a framework for an advanced multi-step synthesis lab. The cost-effective and robust preparation of chiral starting materials is presented, as well as the use of chiral auxiliaries in a synthesis scheme that is appropriate for students currently in the second semester of the organic sequence. (Contains 1…

Controllable 3D architectures of aligned carbon nanotube arrays by multi-step processes

NASA Astrophysics Data System (ADS)

Huang, Shaoming

2003-06-01

An effective way to fabricate large area three-dimensional (3D) aligned CNTs pattern based on pyrolysis of iron(II) phthalocyanine (FePc) by two-step processes is reported. The controllable generation of different lengths and selective growth of the aligned CNT arrays on metal-patterned (e.g., Ag and Au) substrate are the bases for generating such 3D aligned CNTs architectures. By controlling experimental conditions 3D aligned CNT arrays with different lengths/densities and morphologies/structures as well as multi-layered architectures can be fabricated in large scale by multi-step pyrolysis of FePc. These 3D architectures could have interesting properties and be applied for developing novel nanotube-based devices.

Adaptive Finite Element Methods for Continuum Damage Modeling

NASA Technical Reports Server (NTRS)

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

1995-01-01

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

A novel multi-target ligand (JM-20) protects mitochondrial integrity, inhibits brain excitatory amino acid release and reduces cerebral ischemia injury in vitro and in vivo.

PubMed

Nuñez-Figueredo, Yanier; Ramírez-Sánchez, Jeney; Hansel, Gisele; Simões Pires, Elisa Nicoloso; Merino, Nelson; Valdes, Odalys; Delgado-Hernández, René; Parra, Alicia Lagarto; Ochoa-Rodríguez, Estael; Verdecia-Reyes, Yamila; Salbego, Christianne; Costa, Silvia L; Souza, Diogo O; Pardo-Andreu, Gilberto L

2014-10-01

We previously showed that JM-20, a novel 1,5-benzodiazepine fused to a dihydropyridine moiety, possessed an anxiolytic profile similar to diazepam and strong neuroprotective activity in different cell models relevant to cerebral ischemia. Here, we investigated whether JM-20 protects against ischemic neuronal damage in vitro and in vivo. The effects of JM-20 were evaluated on hippocampal slices subjected to oxygen and glucose deprivation (OGD). For in vivo studies, Wistar rats were subjected 90 min of middle cerebral artery occlusion (MCAo) and oral administration of JM-20 at 2, 4 and 8 mg/kg 1 h following reperfusion. Twenty-four hours after cerebral blood flow restoration, neurological deficits were scored, and the infarct volume, histopathological changes in cortex, number of hippocampal and striatal neurons, and glutamate/aspartate concentrations in the cerebrospinal fluid were measured. Susceptibility to brain mitochondrial swelling, membrane potential dissipation, H2O2 generation, cytochrome c release, Ca2+ accumulation, and morphological changes in the organelles were assessed 24 h post-ischemia. In vitro, JM-20 (1 and 10 μM) administered during reperfusion significantly reduced cell death in hippocampal slices subjected to OGD. In vivo, JM-20 treatment (4 and 8 mg/kg) significantly decreased neurological deficit scores, edema formation, total infarct volumes and histological alterations in different brain regions. JM-20 treatment also protected brain mitochondria from ischemic damage, most likely by preventing Ca2+ accumulation in organelles. Moreover, an 8-mg/kg JM-20 dose reduced glutamate and aspartate concentrations in cerebrospinal fluid and the deleterious effects of MCAo even when delivered 8 h after blood flow restoration. These results suggest that in rats, JM-20 is a robust neuroprotective agent against ischemia/reperfusion injury with a wide therapeutic window. Our findings support the further examination of potential clinical JM-20 use to treat acute ischemic stroke. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nuclear Shield: A Multi-Enzyme Task-Force for Nucleus Protection

PubMed Central

Pallottini, Valentina; Canuti, Lorena; De Canio, Michele; Urbani, Andrea; Marzano, Valeria; Cornetta, Tommaso; Stano, Pasquale; Giovanetti, Anna; Stella, Lorenzo; Canini, Antonella; Federici, Giorgio; Ricci, Giorgio

2010-01-01

Background In eukaryotic cells the nuclear envelope isolates and protects DNA from molecules that could damage its structure or interfere with its processing. Moreover, selected protection enzymes and vitamins act as efficient guardians against toxic compounds both in the nucleoplasm and in the cytosol. The observation that a cytosolic detoxifying and antioxidant enzyme i.e. glutathione transferase is accumulated in the perinuclear region of the rat hepatocytes suggests that other unrecognized modalities of nuclear protection may exist. Here we show evidence for the existence of a safeguard enzyme machinery formed by an hyper-crowding of cationic enzymes and proteins encompassing the nuclear membrane and promoted by electrostatic interactions. Methodology/Principal Findings Electron spectroscopic imaging, zeta potential measurements, isoelectrofocusing, comet assay and mass spectrometry have been used to characterize this surprising structure that is present in the cells of all rat tissues examined (liver, kidney, heart, lung and brain), and that behaves as a “nuclear shield”. In hepatocytes, this hyper-crowding structure is about 300 nm thick, it is mainly formed by cationic enzymes and the local concentration of key protection enzymes, such as glutathione transferase, catalase and glutathione peroxidase is up to seven times higher than in the cytosol. The catalytic activity of these enzymes, when packed in the shield, is not modified and their relative concentrations vary remarkably in different tissues. Removal of this protective shield renders chromosomes more sensitive to damage by oxidative stress. Specific nuclear proteins anchored to the outer nuclear envelope are likely involved in the shield formation and stabilization. Conclusions/Significance The characterization of this previously unrecognized nuclear shield in different tissues opens a new interesting scenario for physiological and protection processes in eukaryotic cells. Selection and accumulation of protection enzymes near sensitive targets represents a new safeguard modality which deeply differs from the adaptive response which is based on expression of specific enzymes. PMID:21170318

Three-Dimensional Analysis of Voids in AM60B Magnesium Tensile Bars Using Computed Tomography Imagery

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

Waters, A M

2001-05-01

In an effort to increase automobile fuel efficiency as well as decrease the output of harmful greenhouse gases, the automotive industry has recently shown increased interest in cast light metals such as magnesium alloys in an effort to increase weight savings. Currently several magnesium alloys such as AZ91 and AM60B are being used in structural applications for automobiles. However, these magnesium alloys are not as well characterized as other commonly used structural metals such as aluminum. This dissertation presents a methodology to nondestructively quantify damage accumulation due to void behavior in three dimensions in die-cast magnesium AM60B tensile bars asmore » a function of mechanical load. Computed tomography data was acquired after tensile bars were loaded up to and including failure, and analyzed to characterize void behavior as it relates to damage accumulation. Signal and image processing techniques were used along with a cluster labeling routine to nondestructively quantify damage parameters in three dimensions. Void analyses were performed including void volume distribution characterization, nearest neighbor distance calculations, shape parameters, and volumetric renderings of voids in the alloy. The processed CT data was used to generate input files for use in finite element simulations, both two- and three-dimensional. The void analyses revealed that the overwhelming source of failure in each tensile bar was a ring of porosity within each bar, possibly due to a solidification front inherent to the casting process. The measured damage parameters related to void nucleation, growth, and coalescence were shown to contribute significantly to total damage accumulation. Void volume distributions were characterized using a Weibull function, and the spatial distributions of voids were shown to be clustered. Two-dimensional finite element analyses of the tensile bars were used to fine-tune material damage models and a three-dimensional mesh of an extracted portion of one tensile bar including voids was generated from CT data and used as input to a finite element analysis.« less

Revealing ionization-induced dynamic recovery in ion-irradiated SrTiO 3

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

Velisa, Gihan; Wendler, Elke; Xue, Haizhou

The lack of fundamental understanding on the coupled effects of energy deposition to electrons and atomic nuclei on defect processes and irradiation response poses a significant roadblock for the design and control of material properties. In this work, SrTiO 3 has been irradiated with various ion species over a wide range of ion fluences at room temperature with a goal to deposit different amounts of energy to target electrons and atomic nuclei by varying the ratio of electronic to nuclear energy loss. Here, the results unambiguously show a dramatic difference in behavior of SrTiO 3 irradiated with light ions (Ne,more » O) compared to heavy ions (Ar). While the damage accumulation and amorphization under Ar ion irradiation are consistent with previous observations and existing models, the damage accumulation under Ne irradiation reveals a quasi-saturation state at a fractional disorder of 0.54 at the damage peak for an ion fluence corresponding to a dose of 0.5 dpa; this is followed by further increases in disorder with increasing ion fluence. In the case of O ion irradiation, the damage accumulation at the damage peak closely follows that for Ne ion irradiation up to a fluence corresponding to a dose of 0.5 dpa, where a quasi-saturation of fractional disorder level occurs at about 0.48; however, in this case, the disorder at the damage peak decreases slightly with further increases in fluence. This behavior is associated with changes in kinetics due to irradiation-enhanced diffusional processes that are dependent on electronic energy loss and the ratio of electronic to nuclear energy dissipation. Lastly, these findings are critical for advancing the fundamental understanding of ion-solid interactions and for a large number of applications in oxide electronics where SrTiO 3 is a foundational material.« less

DNA Damage Response, Redox Status and Hematopoiesis

PubMed Central

Weiss, Cary N.; Ito, Keisuke

2013-01-01

The ability of hematopoietic stem cells (HSCs) to self-renew and differentiate into progenitors is essential for homeostasis of the hematopoietic system. The longevity of HSCs makes them vulnerable to accumulating DNA damage, which may be leukemogenic or result in senescence and cell death. Additionally, the ability of HSCs to self-renew and differentiate allows DNA damage to spread throughout the hematologic system, leaving the organism vulnerable to disease. In this review we discuss cell fate decisions made in the face of DNA damage and other cellular stresses, and the role of reactive oxygen species in the long-term maintenance of HSCs and their DNA damage response. PMID:24041596

Progressive Fracture of Fiber Composite Build-Up Structures

NASA Technical Reports Server (NTRS)

Gotsis, Pascal K.; Chamis, C. C.; Minnetyan, Levon

1997-01-01

Damage progression and fracture of built-up composite structures is evaluated by using computational simulation. The objective is to examine the behavior and response of a stiffened composite (0/ +/- 45/90)(sub s6) laminate panel by simulating the damage initiation, growth, accumulation, progression and propagation to structural collapse. An integrated computer code, CODSTRAN, was augmented for the simulation of the progressive damage and fracture of built-up composite structures under mechanical loading. Results show that damage initiation and progression have significant effect on the structural response. Influence of the type of loading is investigated on the damage initiation, propagation and final fracture of the build-up composite panel.

Progressive Fracture of Fiber Composite Build-Up Structures

NASA Technical Reports Server (NTRS)

Minnetyan, Levon; Gotsis, Pascal K.; Chamis, C. C.

1997-01-01

Damage progression and fracture of built-up composite structures is evaluated by using computational simulation. The objective is to examine the behavior and response of a stiffened composite (0 +/-45/90)(sub s6) laminate panel by simulating the damage initiation, growth, accumulation, progression and propagation to structural collapse. An integrated computer code CODSTRAN was augmented for the simulation of the progressive damage and fracture of built-up composite structures under mechanical loading. Results show that damage initiation and progression to have significant effect on the structural response. Influence of the type of loading is investigated on the damage initiation, propagation and final fracture of the build-up composite panel.

MIMO signal progressing with RLSCMA algorithm for multi-mode multi-core optical transmission system

NASA Astrophysics Data System (ADS)

Bi, Yuan; Liu, Bo; Zhang, Li-jia; Xin, Xiang-jun; Zhang, Qi; Wang, Yong-jun; Tian, Qing-hua; Tian, Feng; Mao, Ya-ya

2018-01-01

In the process of transmitting signals of multi-mode multi-core fiber, there will be mode coupling between modes. The mode dispersion will also occur because each mode has different transmission speed in the link. Mode coupling and mode dispersion will cause damage to the useful signal in the transmission link, so the receiver needs to deal received signal with digital signal processing, and compensate the damage in the link. We first analyzes the influence of mode coupling and mode dispersion in the process of transmitting signals of multi-mode multi-core fiber, then presents the relationship between the coupling coefficient and dispersion coefficient. Then we carry out adaptive signal processing with MIMO equalizers based on recursive least squares constant modulus algorithm (RLSCMA). The MIMO equalization algorithm offers adaptive equalization taps according to the degree of crosstalk in cores or modes, which eliminates the interference among different modes and cores in space division multiplexing(SDM) transmission system. The simulation results show that the distorted signals are restored efficiently with fast convergence speed.

Brain aging in the canine: a diet enriched in antioxidants reduces cognitive dysfunction.

PubMed

Cotman, Carl W; Head, Elizabeth; Muggenburg, Bruce A; Zicker, S; Milgram, Norton W

2002-01-01

Animal models that simulate various aspects of human brain aging are an essential step in the development of interventions to manage cognitive dysfunction in the elderly. Over the past several years we have been studying cognition and neuropathology in the aged-canine (dog). Like humans, canines naturally accumulate deposits of beta-amyloid (Abeta) in the brain with age. Further, canines and humans share the same Abeta sequence and also first show deposits of the longer Abeta1-42 species followed by the deposition of Abeta1-40. Aged canines like humans also show increased oxidative damage. As a function of age, canines show impaired learning and memory on tasks similar to those used in aged primates and humans. The extent of Abeta deposition correlates with the severity of cognitive dysfunction in canines. To test the hypothesis that a cascade of mechanisms centered on oxidative damage and Abeta results in cognitive dysfunction we have evaluated the cognitive effects of an antioxidant diet in aged canines. The diet resulted in a significant improvement in the ability of aged but not young animals to acquire progressively more difficult learning tasks (e.g. oddity discrimination learning). The canine represent a higher animal model to study the earliest declines in the cognitive continuum that includes age associated memory impairments (AAMI) and mild cognitive impairment (MCI) observed in human aging. Thus, studies in the canine model suggest that oxidative damage impairs cognitive function and that antioxidant treatment can result in significant improvements, supporting the need for further human studies. Copyright 2002 Elsevier Science Inc.

Ultraviolet-B-induced DNA damage and ultraviolet-B tolerance mechanisms in species with different functional groups coexisting in subalpine moorlands.

PubMed

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

2016-08-01

High doses of ultraviolet-B (UV-B; 280-315 nm) radiation can have detrimental effects on plants, and especially damage their DNA. Plants have DNA repair and protection mechanisms to prevent UV-B damage. However, it remains unclear how DNA damage and tolerance mechanisms vary among field species. We studied DNA damage and tolerance mechanisms in 26 species with different functional groups coexisting in two moorlands at two elevations. We collected current-year leaves in July and August, and determined accumulation of cyclobutane pyrimidine dimer (CPD) as UV-B damage and photorepair activity (PRA) and concentrations of UV-absorbing compounds (UACs) and carotenoids (CARs) as UV-B tolerance mechanisms. DNA damage was greater in dicot than in monocot species, and higher in herbaceous than in woody species. Evergreen species accumulated more CPDs than deciduous species. PRA was higher in Poaceae than in species of other families. UACs were significantly higher in woody than in herbaceous species. The CPD level was not explained by the mechanisms across species, but was significantly related to PRA and UACs when we ignored species with low CPD, PRA and UACs, implying the presence of another effective tolerance mechanism. UACs were correlated negatively with PRA and positively with CARs. Our results revealed that UV-induced DNA damage significantly varies among native species, and this variation is related to functional groups. DNA repair, rather than UV-B protection, dominates in UV-B tolerance in the field. Our findings also suggest that UV-B tolerance mechanisms vary among species under evolutionary trade-off and synergism.

Identification of damage in composite structures using Gaussian mixture model-processed Lamb waves

NASA Astrophysics Data System (ADS)

Wang, Qiang; Ma, Shuxian; Yue, Dong

2018-04-01

Composite materials have comprehensively better properties than traditional materials, and therefore have been more and more widely used, especially because of its higher strength-weight ratio. However, the damage of composite structures is usually varied and complicated. In order to ensure the security of these structures, it is necessary to monitor and distinguish the structural damage in a timely manner. Lamb wave-based structural health monitoring (SHM) has been proved to be effective in online structural damage detection and evaluation; furthermore, the characteristic parameters of the multi-mode Lamb wave varies in response to different types of damage in the composite material. This paper studies the damage identification approach for composite structures using the Lamb wave and the Gaussian mixture model (GMM). The algorithm and principle of the GMM, and the parameter estimation, is introduced. Multi-statistical characteristic parameters of the excited Lamb waves are extracted, and the parameter space with reduced dimensions is adopted by principal component analysis (PCA). The damage identification system using the GMM is then established through training. Experiments on a glass fiber-reinforced epoxy composite laminate plate are conducted to verify the feasibility of the proposed approach in terms of damage classification. The experimental results show that different types of damage can be identified according to the value of the likelihood function of the GMM.

Circadian Modulation of 8-Oxoguanine DNA Damage Repair

PubMed Central

Manzella, Nicola; Bracci, Massimo; Strafella, Elisabetta; Staffolani, Sara; Ciarapica, Veronica; Copertaro, Alfredo; Rapisarda, Venerando; Ledda, Caterina; Amati, Monica; Valentino, Matteo; Tomasetti, Marco; Stevens, Richard G.; Santarelli, Lory

2015-01-01

The DNA base excision repair pathway is the main system involved in the removal of oxidative damage to DNA such as 8-Oxoguanine (8-oxoG) primarily via the 8-Oxoguanine DNA glycosylase (OGG1). Our goal was to investigate whether the repair of 8-oxoG DNA damage follow a circadian rhythm. In a group of 15 healthy volunteers, we found a daily variation of Ogg1 expression and activity with higher levels in the morning compared to the evening hours. Consistent with this, we also found lower levels of 8-oxoG in morning hours compared to those in the evening hours. Lymphocytes exposed to oxidative damage to DNA at 8:00 AM display lower accumulation of 8-oxoG than lymphocytes exposed at 8:00 PM. Furthermore, altered levels of Ogg1 expression were also observed in a group of shift workers experiencing a deregulation of circadian clock genes compared to a control group. Moreover, BMAL1 knockdown fibroblasts with a deregulated molecular clock showed an abolishment of circadian variation of Ogg1 expression and an increase of OGG1 activity. Our results suggest that the circadian modulation of 8-oxoG DNA damage repair, according to a variation of Ogg1 expression, could render humans less susceptible to accumulate 8-oxoG DNA damage in the morning hours. PMID:26337123

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

PubMed

Gichner, Tomás; Znidar, Irena; Száková, Jirina

2008-04-30

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

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

Interdependence theory of tissue failure: bulk and boundary effects.

PubMed

Suma, Daniel; Acun, Aylin; Zorlutuna, Pinar; Vural, Dervis Can

2018-02-01

The mortality rate of many complex multicellular organisms increases with age, which suggests that net ageing damage is accumulative, despite remodelling processes. But how exactly do these little mishaps in the cellular level accumulate and spread to become a systemic catastrophe? To address this question we present experiments with synthetic tissues, an analytical model consistent with experiments, and a number of implications that follow the analytical model. Our theoretical framework describes how shape, curvature and density influences the propagation of failure in a tissue subjected to oxidative damage. We propose that ageing is an emergent property governed by interaction between cells, and that intercellular processes play a role that is at least as important as intracellular ones.

Interdependence theory of tissue failure: bulk and boundary effects

NASA Astrophysics Data System (ADS)

Suma, Daniel; Acun, Aylin; Zorlutuna, Pinar; Vural, Dervis Can

2018-02-01

The mortality rate of many complex multicellular organisms increases with age, which suggests that net ageing damage is accumulative, despite remodelling processes. But how exactly do these little mishaps in the cellular level accumulate and spread to become a systemic catastrophe? To address this question we present experiments with synthetic tissues, an analytical model consistent with experiments, and a number of implications that follow the analytical model. Our theoretical framework describes how shape, curvature and density influences the propagation of failure in a tissue subjected to oxidative damage. We propose that ageing is an emergent property governed by interaction between cells, and that intercellular processes play a role that is at least as important as intracellular ones.

Fatigue Damage Monitoring of a Composite Step Lap Joint Using Distributed Optical Fibre Sensors

PubMed Central

Wong, Leslie; Chowdhury, Nabil; Wang, John; Chiu, Wing Kong; Kodikara, Jayantha

2016-01-01

Over the past few decades, there has been a considerable interest in the use of distributed optical fibre sensors (DOFS) for structural health monitoring of composite structures. In aerospace-related work, health monitoring of the adhesive joints of composites has become more significant, as they can suffer from cracking and delamination, which can have a significant impact on the integrity of the joint. In this paper, a swept-wavelength interferometry (SWI) based DOFS technique is used to monitor the fatigue in a flush step lap joint composite structure. The presented results will show the potential application of distributed optical fibre sensor for damage detection, as well as monitoring the fatigue crack growth along the bondline of a step lap joint composite structure. The results confirmed that a distributed optical fibre sensor is able to enhance the detection of localised damage in a structure. PMID:28773496

Sarcoidosis Related Novel Candidate Genes Identified by Multi-Omics Integrative Analyses.

PubMed

Hočevar, Keli; Maver, Aleš; Kunej, Tanja; Peterlin, Borut

2018-05-01

Sarcoidosis is a multifactorial systemic disease characterized by granulomatous inflammation and greatly impacting on global public health. The etiology and mechanisms of sarcoidosis are not fully understood. Recent high-throughput biological research has generated vast amounts of multi-omics big data on sarcoidosis, but their significance remains to be determined. We sought to identify novel candidate regions, and genes consistently altered in heterogeneous omics studies so as to reveal the underlying molecular mechanisms. We conducted a comprehensive integrative literature analysis on global data on sarcoidosis, including genomic, transcriptomic, proteomic, and phenomic studies. We performed positional integration analysis of 38 eligible datasets originating from 17 different biological layers. Using the integration interval length of 50 kb, we identified 54 regions reaching significance value p ≤ 0.0001 and 15 regions with significance value p ≤ 0.00001, when applying more stringent criteria. Secondary literature analysis of the top 20 regions, with the most significant accumulation of signals, revealed several novel candidate genes for which associations with sarcoidosis have not yet been established, but have considerable support for their involvement based on omic data. These new plausible candidate genes include NELFE, CFB, EGFL7, AGPAT2, FKBPL, NRC3, and NEU1. Furthermore, annotated data were prepared to enable custom visualization and browsing of these sarcoidosis related omics evidence in the University of California Santa Cruz (UCSC) Genome Browser. Further multi-omics approaches are called for sarcoidosis biomarkers and diagnostic and therapeutic innovation. Our approach for harnessing multi-omics data and the findings presented herein reflect important steps toward understanding the etiology and underlying pathological mechanisms of sarcoidosis.

Unstable vicinal crystal growth from cellular automata

NASA Astrophysics Data System (ADS)

Krasteva, A.; Popova, H.; KrzyŻewski, F.; Załuska-Kotur, M.; Tonchev, V.

2016-03-01

In order to study the unstable step motion on vicinal crystal surfaces we devise vicinal Cellular Automata. Each cell from the colony has value equal to its height in the vicinal, initially the steps are regularly distributed. Another array keeps the adatoms, initially distributed randomly over the surface. The growth rule defines that each adatom at right nearest neighbor position to a (multi-) step attaches to it. The update of whole colony is performed at once and then time increases. This execution of the growth rule is followed by compensation of the consumed particles and by diffusional update(s) of the adatom population. Two principal sources of instability are employed - biased diffusion and infinite inverse Ehrlich-Schwoebel barrier (iiSE). Since these factors are not opposed by step-step repulsion the formation of multi-steps is observed but in general the step bunches preserve a finite width. We monitor the developing surface patterns and quantify the observations by scaling laws with focus on the eventual transition from diffusion-limited to kinetics-limited phenomenon. The time-scaling exponent of the bunch size N is 1/2 for the case of biased diffusion and 1/3 for the case of iiSE. Additional distinction is possible based on the time-scaling exponents of the sizes of multi-step Nmulti, these are 0.36÷0.4 (for biased diffusion) and 1/4 (iiSE).

Isothermal Fatigue, Damage Accumulation, and Life Prediction of a Woven PMC

NASA Technical Reports Server (NTRS)

Gyekenyesi, Andrew L.

1998-01-01

This dissertation focuses on the characterization of the fully reversed fatigue behavior exhibited by a carbon fiber/polyimide resin, woven laminate at room and elevated temperatures. Nondestructive video edge view microscopy and destructive sectioning techniques were used to study the microscopic damage mechanisms that evolved. The residual elastic stiffness was monitored and recorded throughout the fatigue life of the coupon. In addition, residual compressive strength tests were conducted on fatigue coupons with various degrees of damage as quantified by stiffness reduction. Experimental results indicated that the monotonic tensile properties were only minimally influenced by temperature, while the monotonic compressive and fully reversed fatigue properties displayed noticeable reductions due to the elevated temperature. The stiffness degradation, as a function of cycles, consisted of three stages; a short-lived high degradation period, a constant degradation rate segment composing the majority of the life, and a final stage demonstrating an increasing rate of degradation up to failure. Concerning the residual compressive strength tests at room and elevated temperatures, the elevated temperature coupons appeared much more sensitive to damage. At elevated temperatures, coupons experienced a much larger loss in compressive strength when compared to room temperature coupons with equivalent damage. The fatigue damage accumulation law proposed for the model incorporates a scalar representation for damage, but admits a multiaxial, anisotropic evolutionary law. The model predicts the current damage (as quantified by residual stiffness) and remnant life of a composite that has undergone a known load at temperature. The damage/life model is dependent on the applied multiaxial stress state as well as temperature. Comparisons between the model and data showed good predictive capabilities concerning stiffness degradation and cycles to failure.

Multi-Phased, Post-Accident Support of the Fukushima Dai-Ichi Nuclear Power Plant - 12246

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

Gay, Arnaud; Gillet, Philippe; Ytournel, Bertrand

In the wake of the March 11 earthquake and tsunami and the subsequent flooding of several of the Fukushima Dai-Ichi reactors, Japan and the Japanese utility TEPCO faced a crisis situation with incredible challenges: substantial amounts of radioactive mixed seawater and freshwater accumulated in the basements of four reactor and other buildings on the site. This water held varying levels of contamination due to the fact that it had been in contact with damaged fuel elements in the cores and with other contaminated components. The overall water inventory was estimated at around 110,000 tons of water with contamination levels upmore » to the order of 1 Ci/l. Time was of the essence to avoid overflow of this accumulated water into the ocean. AREVA proposed, designed and implemented a water treatment solution using a proven chemical coprecipitation process with ppFeNi reagent, which is currently in use for effluent treatment on several nuclear sites including AREVA sites. In addition to the extremely short schedule the other challenge was to adapt the chemical treatment process to the expected composition of the Fukushima water and, in particular, to evaluate the impact of salinity on process performance. It was also necessary to define operating conditions for the VEOLIA equipment that had been selected for implementation of the process in the future facility. The operation phase began on June 17, and by the end of July more than 30,000 tons of highly radioactive saltwater had been decontaminated - the Decontamination Factor (DF) for Cesium was ∼10{sup 4}. It allowed recycling the contaminated water to cool the reactors while protecting workers and the environment. This paper focuses on the Actiflo{sup TM}-Rad water treatment unit project that was part of the TEPCO general water treatment scheme. It presents a detailed look at the principles of the Actiflo{sup TM}-Rad, related on-the-fly R and D, an explanation of system implementation challenges, and a brief summary of operation results to date. AREVA's response to the Fukushima Dai-Ichi crisis was multi-phased: emergency aid and relief supply was sent within days after the accident; AREVA-Veolia engineering teams designed and implemented a water treatment solution in record time, only 3 months; and AREVA continues to support TEPCO and propose solutions for waste management, soil remediation and decontamination of the Fukushima Dai-Ichi site. Despite the huge challenges, the Actiflo{sup TM}-Rad project has been a success: the water treatment unit started on time and performed as expected. The performance is the result of many key elements: AREVA expertise in radioactive effluents decontamination, Veolia know-how in water treatment equipments in crisis environment, and of course AREVA and Veolia teams' creativity. The project success is also due to AREVA and Veolia teams' reactivity and high level of commitment with engineering teams working 24/7 in Japan, France and Germany. AREVA and Veolia deep knowledge of the Japanese industry ensured that the multi-cultural exchanges were not an issue. Finally the excellent overall project management and execution by TEPCO and other Japanese stakeholders was very efficient. The emergency water treatment was a key step of the roadmap towards restoration from the accident at Fukushima Dai-Ichi that TEPCO designed and keeps executing with success. (authors)« less

Multi-location laser ignition using a spatial light modulator towards improving automotive gasoline engine performance

NASA Astrophysics Data System (ADS)

Kuang, Zheng; Lyon, Elliott; Cheng, Hua; Page, Vincent; Shenton, Tom; Dearden, Geoff

2017-03-01

We report on a study into multi-location laser ignition (LI) with a Spatial Light Modulator (SLM), to improve the performance of a single cylinder automotive gasoline engine. Three questions are addressed: i/ How to deliver a multi-beam diffracted pattern into an engine cylinder, through a small opening, while avoiding clipping? ii/ How much incident energy can a SLM handle (optical damage threshold) and how many simultaneous beam foci could thus be created? ; iii/ Would the multi-location sparks created be sufficiently intense and stable to ignite an engine and, if so, what would be their effect on engine performance compared to single-location LI? Answers to these questions were determined as follows. Multi-beam diffracted patterns were created by applying computer generated holograms (CGHs) to the SLM. An optical system for the SLM was developed via modelling in ZEMAX, to cleanly deliver the multi-beam patterns into the combustion chamber without clipping. Optical damage experiments were carried out on Liquid Crystal on Silicon (LCoS) samples provided by the SLM manufacturer and the maximum safe pulse energy to avoid SLM damage found to be 60 mJ. Working within this limit, analysis of the multi-location laser induced sparks showed that diffracting into three identical beams gave slightly insufficient energy to guarantee 100% sparking, so subsequent engine experiments used 2 equal energy beams laterally spaced by 4 mm. The results showed that dual-location LI gave more stable combustion and higher engine power output than single-location LI, for increasingly lean air-fuel mixtures. The paper concludes by a discussion of how these results may be exploited.

Fabrication of an optical component

DOEpatents

Nichols, Michael A.; Aikens, David M.; Camp, David W.; Thomas, Ian M.; Kiikka, Craig; Sheehan, Lynn M.; Kozlowski, Mark R.

2000-01-01

A method for forming optical parts used in laser optical systems such as high energy lasers, high average power lasers, semiconductor capital equipment and medical devices. The optical parts will not damage during the operation of high power lasers in the ultra-violet light range. A blank is first ground using a fixed abrasive grinding method to remove the subsurface damage formed during the fabrication of the blank. The next step grinds and polishes the edges and forms bevels to reduce the amount of fused-glass contaminants in the subsequent steps. A loose abrasive grind removes the subsurface damage formed during the fixed abrasive or "blanchard" removal process. After repolishing the bevels and performing an optional fluoride etch, the surface of the blank is polished using a zirconia slurry. Any subsurface damage formed during the loose abrasive grind will be removed during this zirconia polish. A post polish etch may be performed to remove any redeposited contaminants. Another method uses a ceria polishing step to remove the subsurface damage formed during the loose abrasive grind. However, any residual ceria may interfere with the optical properties of the finished part. Therefore, the ceria and other contaminants are removed by performing either a zirconia polish after the ceria polish or a post ceria polish etch.

Comparing Multi-Step IMAC and Multi-Step TiO2 Methods for Phosphopeptide Enrichment

PubMed Central

Yue, Xiaoshan; Schunter, Alissa; Hummon, Amanda B.

2016-01-01

Phosphopeptide enrichment from complicated peptide mixtures is an essential step for mass spectrometry-based phosphoproteomic studies to reduce sample complexity and ionization suppression effects. Typical methods for enriching phosphopeptides include immobilized metal affinity chromatography (IMAC) or titanium dioxide (TiO2) beads, which have selective affinity and can interact with phosphopeptides. In this study, the IMAC enrichment method was compared with the TiO2 enrichment method, using a multi-step enrichment strategy from whole cell lysate, to evaluate their abilities to enrich for different types of phosphopeptides. The peptide-to-beads ratios were optimized for both IMAC and TiO2 beads. Both IMAC and TiO2 enrichments were performed for three rounds to enable the maximum extraction of phosphopeptides from the whole cell lysates. The phosphopeptides that are unique to IMAC enrichment, unique to TiO2 enrichment, and identified with both IMAC and TiO2 enrichment were analyzed for their characteristics. Both IMAC and TiO2 enriched similar amounts of phosphopeptides with comparable enrichment efficiency. However, phosphopeptides that are unique to IMAC enrichment showed a higher percentage of multi-phosphopeptides, as well as a higher percentage of longer, basic, and hydrophilic phosphopeptides. Also, the IMAC and TiO2 procedures clearly enriched phosphopeptides with different motifs. Finally, further enriching with two rounds of TiO2 from the supernatant after IMAC enrichment, or further enriching with two rounds of IMAC from the supernatant TiO2 enrichment does not fully recover the phosphopeptides that are not identified with the corresponding multi-step enrichment. PMID:26237447

Multi-contrast MRI registration of carotid arteries based on cross-sectional images and lumen boundaries

NASA Astrophysics Data System (ADS)

Wu, Yu-Xia; Zhang, Xi; Xu, Xiao-Pan; Liu, Yang; Zhang, Guo-Peng; Li, Bao-Juan; Chen, Hui-Jun; Lu, Hong-Bing

2017-02-01

Ischemic stroke has great correlation with carotid atherosclerosis and is mostly caused by vulnerable plaques. It's particularly important to analysis the components of plaques for the detection of vulnerable plaques. Recently plaque analysis based on multi-contrast magnetic resonance imaging has attracted great attention. Though multi-contrast MR imaging has potentials in enhanced demonstration of carotid wall, its performance is hampered by the misalignment of different imaging sequences. In this study, a coarse-to-fine registration strategy based on cross-sectional images and wall boundaries is proposed to solve the problem. It includes two steps: a rigid step using the iterative closest points to register the centerlines of carotid artery extracted from multi-contrast MR images, and a non-rigid step using the thin plate spline to register the lumen boundaries of carotid artery. In the rigid step, the centerline was extracted by tracking the crosssectional images along the vessel direction calculated by Hessian matrix. In the non-rigid step, a shape context descriptor is introduced to find corresponding points of two similar boundaries. In addition, the deterministic annealing technique is used to find a globally optimized solution. The proposed strategy was evaluated by newly developed three-dimensional, fast and high resolution multi-contrast black blood MR imaging. Quantitative validation indicated that after registration, the overlap of two boundaries from different sequences is 95%, and their mean surface distance is 0.12 mm. In conclusion, the proposed algorithm has improved the accuracy of registration effectively for further component analysis of carotid plaques.

Japanese EMRs and IT in Medicine: Expansion, Integration, and Reuse of Data

PubMed Central

Doi, Shunsuke; Suzuki, Takahiro

2011-01-01

Objectives The prevalence of electronic medical record in Japan varies according to the size of the hospital which is 62.5% in major hospitals, 21.7% in medium, 9.1% in small size hospitals, and 16.5% in clinics. The complete paperless system is very limited, though some major hospitals are aiming at this system. Several regional network systems which connect different platforms of EMRs, have been developing in many districts, while the final picture of a regional network has not been clearly proposed. To develop a whole electronic health record or personal health records system from the regional network data, we have several obstacles to overcome such as standardization, a privacy act, unique national health number. Methods Some experimental trials have just been started. The reuse of the accumulated data has also just been initiated. We exploited text mining systems (term frequency-inverse document frequency method) to find similar cases and auto-audit Japanese diagnosis related group (DRG) coding by using discharge summaries. Results The same or even a more extreme phenomenon of huge data accumulation is occurring in genetic research and confluence of multi-disciplines of informatics is the next step, which has an enormous accumulation of data and discoveries of the relations beyond the dimension of each informatics. Conclusions We need another approach to science apart from the conventional method, and data-driven approach with data mining techniques must be brought in for each field. Informaticians have new important roles as coordinators to link up numerous phenomena over dimensions. PMID:22084813

Developmental toxicity of oxidized multi-walled carbon nanotubes on Artemia salina cysts and larvae: Uptake, accumulation, excretion and toxic responses.

PubMed

Zhu, Song; Luo, Fei; Tu, Xiao; Chen, Wei-Chao; Zhu, Bin; Wang, Gao-Xue

2017-10-01

Using Artemia salina (A. salina) cysts (capsulated and decapsulated) and larvae [instar I (0-24 h), II (24-48 h) and III (48-72 h)] as experimental models, developmental toxicity of oxidized multi-walled carbon nanotubes (O-MWCNTs) was evaluated. Results revealed that hatchability of capsulated and decapsulated cysts was significantly decreased (p < 0.01) following exposure to 600 mg/L for 36 h. Mortality rates were 33.8, 55.7 and 40.7% for instar I, II and III larvae in 600 mg/L. The EC 50 values for swimming inhibition of instar I, II and III were 535, 385 and 472 mg/L, respectively. Instar II showed the greatest sensitivity to O-MWCNTs, and followed by instar III, instar I, decapsulated cysts and capsulated cysts. Effects on hatchability, mortality and swimming were accounted for O-MWCNTs rather than metal catalyst impurities. Body length was decreased with the concentrations increased from 0 to 600 mg/L. O-MWCNTs attached onto the cysts, gill and body surface, resulting in irreversible damages. Reactive oxygen species, malondialdehyde content, total antioxidant capacity and antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) activities were increased following exposure, indicating that the effects were related to oxidative stress. O-MWCNTs were ingested and distributed in phagocyte, lipid vesicle and intestine. Most of the accumulated O-MWCNTs were excreted by A. salina at 72 h, but some still remained in the organism. Data of uptake kinetics showed that O-MWCNTs contents in A. salina were gradually increased from 1 to 48 h and followed by rapidly decreased from 48 to 72 h with a range from 5.5 to 28.1 mg/g. These results so far indicate that O-MWCNTs have the potential to affect aquatic organisms when released into the marine ecosystems. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Step changes in leaf oil accumulation via iterative metabolic engineering.

PubMed

Vanhercke, Thomas; Divi, Uday K; El Tahchy, Anna; Liu, Qing; Mitchell, Madeline; Taylor, Matthew C; Eastmond, Peter J; Bryant, Fiona; Mechanicos, Anna; Blundell, Cheryl; Zhi, Yao; Belide, Srinivas; Shrestha, Pushkar; Zhou, Xue-Rong; Ral, Jean-Philippe; White, Rosemary G; Green, Allan; Singh, Surinder P; Petrie, James R

2017-01-01

Synthesis and accumulation of plant oils in the entire vegetative biomass offers the potential to deliver yields surpassing those of oilseed crops. However, current levels still fall well short of those typically found in oilseeds. Here we show how transcriptome and biochemical analyses pointed to a futile cycle in a previously established Nicotiana tabacum line, accumulating up to 15% (dry weight) of the storage lipid triacylglycerol in leaf tissue. To overcome this metabolic bottleneck, we either silenced the SDP1 lipase or overexpressed the Arabidopsis thaliana LEC2 transcription factor in this transgenic background. Both strategies independently resulted in the accumulation of 30-33% triacylglycerol in leaf tissues. Our results demonstrate that the combined optimization of de novo fatty acid biosynthesis, storage lipid assembly and lipid turnover in leaf tissue results in a major overhaul of the plant central carbon allocation and lipid metabolism. The resulting further step changes in oil accumulation in the entire plant biomass offers the possibility of delivering yields that outperform current oilseed crops. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Self-Regulated Strategy Development Instruction for Teaching Multi-Step Equations to Middle School Students Struggling in Math

ERIC Educational Resources Information Center

Cuenca-Carlino, Yojanna; Freeman-Green, Shaqwana; Stephenson, Grant W.; Hauth, Clara

2016-01-01

Six middle school students identified as having a specific learning disability or at risk for mathematical difficulties were taught how to solve multi-step equations by using the self-regulated strategy development (SRSD) model of instruction. A multiple-probe-across-pairs design was used to evaluate instructional effects. Instruction was provided…

OBJECT KINETIC MONTE CARLO SIMULATIONS OF RADIATION DAMAGE IN TUNGSTEN SUBJECTED TO NEUTRON FLUX WITH PKA SPECTRUM CORRESPONDING TO THE HFIR

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

Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard L.

2015-12-31

The objective of this work is to study the damage accumulation in pure tungsten (W) subjected to neutron bombardment with a primary knock-on atom (PKA) spectrum corresponding to the High Flux Isotope Reactor (HFIR), using the object kinetic Monte Carlo (OKMC) method.

cGAS Conducts Micronuclei DNA Surveillance.

PubMed

de Oliveira Mann, Carina C; Kranzusch, Philip J

2017-10-01

DNA damage elicits a potent proinflammatory immune response. A collection of four papers now reveals that micronuclear DNA is a new cell intrinsic immunostimulatory molecule, and that accumulation of the immune sensor cyclic GMP-AMP synthase (cGAS) in micronuclei leads to a cell-cycle-dependent proinflammatory response following DNA damage. Copyright © 2017 Elsevier Ltd. All rights reserved.

Age and gender estimation using Region-SIFT and multi-layered SVM

NASA Astrophysics Data System (ADS)

Kim, Hyunduk; Lee, Sang-Heon; Sohn, Myoung-Kyu; Hwang, Byunghun

2018-04-01

In this paper, we propose an age and gender estimation framework using the region-SIFT feature and multi-layered SVM classifier. The suggested framework entails three processes. The first step is landmark based face alignment. The second step is the feature extraction step. In this step, we introduce the region-SIFT feature extraction method based on facial landmarks. First, we define sub-regions of the face. We then extract SIFT features from each sub-region. In order to reduce the dimensions of features we employ a Principal Component Analysis (PCA) and a Linear Discriminant Analysis (LDA). Finally, we classify age and gender using a multi-layered Support Vector Machines (SVM) for efficient classification. Rather than performing gender estimation and age estimation independently, the use of the multi-layered SVM can improve the classification rate by constructing a classifier that estimate the age according to gender. Moreover, we collect a dataset of face images, called by DGIST_C, from the internet. A performance evaluation of proposed method was performed with the FERET database, CACD database, and DGIST_C database. The experimental results demonstrate that the proposed approach classifies age and performs gender estimation very efficiently and accurately.

The Relationship Between Non-Symbolic Multiplication and Division in Childhood

PubMed Central

McCrink, Koleen; Shafto, Patrick; Barth, Hilary

2016-01-01

Children without formal education in addition and subtraction are able to perform multi-step operations over an approximate number of objects. Further, their performance improves when solving approximate (but not exact) addition and subtraction problems that allow for inversion as a shortcut (e.g., a + b − b = a). The current study examines children’s ability to perform multi-step operations, and the potential for an inversion benefit, for the operations of approximate, non-symbolic multiplication and division. Children were trained to compute a multiplication and division scaling factor (*2 or /2, *4 or /4), and then tested on problems that combined two of these factors in a way that either allowed for an inversion shortcut (e.g., 8 * 4 / 4) or did not (e.g., 8 * 4 / 2). Children’s performance was significantly better than chance for all scaling factors during training, and they successfully computed the outcomes of the multi-step testing problems. They did not exhibit a performance benefit for problems with the a * b / b structure, suggesting they did not draw upon inversion reasoning as a logical shortcut to help them solve the multi-step test problems. PMID:26880261

Alkylation Damage by Lipid Electrophiles Targets Functional Protein Systems*

PubMed Central

Codreanu, Simona G.; Ullery, Jody C.; Zhu, Jing; Tallman, Keri A.; Beavers, William N.; Porter, Ned A.; Marnett, Lawrence J.; Zhang, Bing; Liebler, Daniel C.

2014-01-01

Protein alkylation by reactive electrophiles contributes to chemical toxicities and oxidative stress, but the functional impact of alkylation damage across proteomes is poorly understood. We used Click chemistry and shotgun proteomics to profile the accumulation of proteome damage in human cells treated with lipid electrophile probes. Protein target profiles revealed three damage susceptibility classes, as well as proteins that were highly resistant to alkylation. Damage occurred selectively across functional protein interaction networks, with the most highly alkylation-susceptible proteins mapping to networks involved in cytoskeletal regulation. Proteins with lower damage susceptibility mapped to networks involved in protein synthesis and turnover and were alkylated only at electrophile concentrations that caused significant toxicity. Hierarchical susceptibility of proteome systems to alkylation may allow cells to survive sublethal damage while protecting critical cell functions. PMID:24429493

A study of earthquake-induced building detection by object oriented classification approach

NASA Astrophysics Data System (ADS)

Sabuncu, Asli; Damla Uca Avci, Zehra; Sunar, Filiz

2017-04-01

Among the natural hazards, earthquakes are the most destructive disasters and cause huge loss of lives, heavily infrastructure damages and great financial losses every year all around the world. According to the statistics about the earthquakes, more than a million earthquakes occur which is equal to two earthquakes per minute in the world. Natural disasters have brought more than 780.000 deaths approximately % 60 of all mortality is due to the earthquakes after 2001. A great earthquake took place at 38.75 N 43.36 E in the eastern part of Turkey in Van Province on On October 23th, 2011. 604 people died and about 4000 buildings seriously damaged and collapsed after this earthquake. In recent years, the use of object oriented classification approach based on different object features, such as spectral, textural, shape and spatial information, has gained importance and became widespread for the classification of high-resolution satellite images and orthophotos. The motivation of this study is to detect the collapsed buildings and debris areas after the earthquake by using very high-resolution satellite images and orthophotos with the object oriented classification and also see how well remote sensing technology was carried out in determining the collapsed buildings. In this study, two different land surfaces were selected as homogenous and heterogeneous case study areas. In the first step of application, multi-resolution segmentation was applied and optimum parameters were selected to obtain the objects in each area after testing different color/shape and compactness/smoothness values. In the next step, two different classification approaches, namely "supervised" and "unsupervised" approaches were applied and their classification performances were compared. Object-based Image Analysis (OBIA) was performed using e-Cognition software.

MDC1: The art of keeping things in focus.

PubMed

Jungmichel, Stephanie; Stucki, Manuel

2010-08-01

The chromatin structure is important for recognition and repair of DNA damage. Many DNA damage response proteins accumulate in large chromatin domains flanking sites of DNA double-strand breaks. The assembly of these structures-usually termed DNA damage foci-is primarily regulated by MDC1, a large nuclear mediator/adaptor protein that is composed of several distinct structural and functional domains. Here, we are summarizing the latest discoveries about the mechanisms by which MDC1 mediates DNA damage foci formation, and we are reviewing the considerable efforts taken to understand the functional implication of these structures.

5'-nucleotidase

MedlinePlus

... Use of a liver-damaging drug Risks Slight risks from having blood drawn may include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the skin) Infection ( ...

Assessment of Solder Joint Fatigue Life Under Realistic Service Conditions

NASA Astrophysics Data System (ADS)

Hamasha, Sa'd.; Jaradat, Younis; Qasaimeh, Awni; Obaidat, Mazin; Borgesen, Peter

2014-12-01

The behavior of lead-free solder alloys under complex loading scenarios is still not well understood. Common damage accumulation rules fail to account for strong effects of variations in cycling amplitude, and random vibration test results cannot be interpreted in terms of performance under realistic service conditions. This is a result of the effects of cycling parameters on materials properties. These effects are not yet fully understood or quantitatively predictable, preventing modeling based on parameters such as strain, work, or entropy. Depending on the actual spectrum of amplitudes, Miner's rule of linear damage accumulation has been shown to overestimate life by more than an order of magnitude, and greater errors are predicted for other combinations. Consequences may be particularly critical for so-called environmental stress screening. Damage accumulation has, however, been shown to scale with the inelastic work done, even if amplitudes vary. This and the observation of effects of loading history on subsequent work per cycle provide for a modified damage accumulation rule which allows for the prediction of life. Individual joints of four different Sn-Ag-Cu-based solder alloys (SAC305, SAC105, SAC-Ni, and SACXplus) were cycled in shear at room temperature, alternating between two different amplitudes while monitoring the evolution of the effective stiffness and work per cycle. This helped elucidate general trends and behaviors that are expected to occur in vibrations of microelectronics assemblies. Deviations from Miner's rule varied systematically with the combination of amplitudes, the sequences of cycles, and the strain rates in each. The severity of deviations also varied systematically with Ag content in the solder, but major effects were observed for all the alloys. A systematic analysis was conducted to assess whether scenarios might exist in which the more fatigue-resistant high-Ag alloys would fail sooner than the lower-Ag ones.

GSTP1 Loss results in accumulation of oxidative DNA base damage and promotes prostate cancer cell survival following exposure to protracted oxidative stress.

PubMed

Mian, Omar Y; Khattab, Mohamed H; Hedayati, Mohammad; Coulter, Jonathan; Abubaker-Sharif, Budri; Schwaninger, Julie M; Veeraswamy, Ravi K; Brooks, James D; Hopkins, Lisa; Shinohara, Debika Biswal; Cornblatt, Brian; Nelson, William G; Yegnasubramanian, Srinivasan; DeWeese, Theodore L

2016-02-01

Epigenetic silencing of glutathione S-transferase π (GSTP1) is a hallmark of transformation from normal prostatic epithelium to adenocarcinoma of the prostate. The functional significance of this loss is incompletely understood. The present study explores the effects of restored GSTP1 expression on glutathione levels, accumulation of oxidative DNA damage, and prostate cancer cell survival following oxidative stress induced by protracted, low dose rate ionizing radiation (LDR). GSTP1 protein expression was stably restored in LNCaP prostate cancer cells. The effect of GSTP1 restoration on protracted LDR-induced oxidative DNA damage was measured by GC-MS quantitation of modified bases. Reduced and oxidized glutathione levels were measured in control and GSTP1 expressing populations. Clonogenic survival studies of GSTP1- transfected LNCaP cells after exposure to protracted LDR were performed. Global gene expression profiling and pathway analysis were performed. GSTP1 expressing cells accumulated less oxidized DNA base damage and exhibited decreased survival compared to control LNCaP-Neo cells following oxidative injury induced by protracted LDR. Restoration of GSTP1 expression resulted in changes in modified glutathione levels that correlated with GSTP1 protein levels in response to protracted LDR-induced oxidative stress. Survival differences were not attributable to depletion of cellular glutathione stores. Gene expression profiling and pathway analysis following GSTP1 restoration suggests this protein plays a key role in regulating prostate cancer cell survival. The ubiquitous epigenetic silencing of GSTP1 in prostate cancer results in enhanced survival and accumulation of potentially promutagenic DNA adducts following exposure of cells to protracted oxidative injury suggesting a protective, anti-neoplastic function of GSTP1. The present work provides mechanistic backing to the tumor suppressor function of GSTP1 and its role in prostate carcinogenesis. © 2015 Wiley Periodicals, Inc.