Aggressive treatment of early rheumatoid arthritis: recognizing the window of opportunity and treating to target goals.

PubMed

Resman-Targoff, Beth H; Cicero, Marco P

2010-11-01

Evidence supports the use of aggressive therapy for patients with early rheumatoid arthritis (RA). Clinical outcomes in patients with early RA can improve with a treat-to-target approach that sets the goal at disease remission. The current selection of antirheumatic therapies, including conventional and biologic disease-modifying antirheumatic drugs (DMARDs), has made disease remission a realistic target for patients with early RA. The challenge is selecting the optimal antirheumatic drug or combination of drugs for initial and subsequent therapy to balance the clinical benefits, risks, and economic considerations. In some cases, the use of biologic agents as part of the treatment regimen has shown superior results compared with conventional DMARDs alone in halting the progression of disease, especially in reducing radiographic damage. However, the use of biologic agents as initial therapy is challenged by cost-effectiveness analyses, which favor the use of conventional DMARDs. The use of biologic agents may be justified in certain patients with poor prognostic factors or those who experience an inadequate response to conventional DMARDs as a means to slow or halt disease progression and its associated disability. In these cases, the higher cost of treatment with biologic agents may be offset by decreased societal costs, such as lost work productivity, and increased health-related quality of life. Further research is needed to understand optimal strategies for balancing costs, benefits, and risks of antirheumatic drugs. Some key questions are (1) when biologic agents are appropriate for initial therapy, and (2) when to conclude that response to conventional DMARDs is inadequate and biologic agents should be initiated.

Mechanically triggered heterolytic unzipping of a low-ceiling-temperature polymer

NASA Astrophysics Data System (ADS)

Diesendruck, Charles E.; Peterson, Gregory I.; Kulik, Heather J.; Kaitz, Joshua A.; Mar, Brendan D.; May, Preston A.; White, Scott R.; Martínez, Todd J.; Boydston, Andrew J.; Moore, Jeffrey S.

2014-07-01

Biological systems rely on recyclable materials resources such as amino acids, carbohydrates and nucleic acids. When biomaterials are damaged as a result of aging or stress, tissues undergo repair by a depolymerization-repolymerization sequence of remodelling. Integration of this concept into synthetic materials systems may lead to devices with extended lifetimes. Here, we show that a metastable polymer, end-capped poly(o-phthalaldehyde), undergoes mechanically initiated depolymerization to revert the material to monomers. Trapping experiments and steered molecular dynamics simulations are consistent with a heterolytic scission mechanism. The obtained monomer was repolymerized by a chemical initiator, effectively completing a depolymerization-repolymerization cycle. By emulating remodelling of biomaterials, this model system suggests the possibility of smart materials where aging or mechanical damage triggers depolymerization, and orthogonal conditions regenerate the polymer when and where necessary.

Pressure pulse induced-damage in live biological samples

NASA Astrophysics Data System (ADS)

Bo, C.; Balzer, J.; Godfrey, S.; Francois, M.; Saffell, J. L.; Rankin, S. M.; Proud, W. G.; Brown, K. A.

2012-08-01

Developing a cellular and molecular understanding of the nature of traumatic and post-traumatic effects of blast on live biological samples is critical for improving clinical outcomes. To analyze the effects of blast waves upon the cellular structures and the underlying physiological and biochemical changes, we have constructed an experimental platform capable of delivering compression waves, of amplitudes relevant to blast, to cell suspensions in a contained environment. Initial characterization of the system shows that cell cultures can be subjected to high-intensity compression waves up to 15 MPa in pressure and duration of 80 ± 10μs. Studies of mouse mesenchymal stem cells subjected to two different pressure impulses were analysed by cell counting, cell viability assays and microscopic evaluation: the experiments present evidence suggestive of increased levels of damage and loss of cellular integrity compared to uncompressed cell cultures.

Biological tooth replacement

PubMed Central

Sartaj, Rachel; Sharpe, Paul

2006-01-01

Teeth develop from a series of reciprocal interactions that take place between epithelium and mesenchyme during development of the mouth that begin early in mammalian embryogenesis. The molecular control of key processes in tooth development such as initiation, morphogenesis and cytodifferentiation are being increasingly better understood, to the point where this information can be used as the basis for approaches to produce biological replacement teeth (BioTeeth). This review outlines the current approaches, ideas and progress towards the production of BioTeeth that could form an alternative method for replacing lost or damaged teeth. PMID:17005022

Computational Model of the Modulation of Gene Expression Following DNA Damage

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Dicello, J. F.; Nikjoo, H.; Cherubini, R.

2002-01-01

High linear energy transfer (LET) radiation, such as heavy ions or neutrons, has an increased biological effectiveness compared to X rays for gene mutation, genomic instability, and carcinogenesis. In the traditional paradigm, mutations or chromosomal aberrations are causative of late effects. However, in recent years experimental evidence has demonstrated the important role of the description of the modification of gene expression by radiation in understanding the mechanisms of radiation action. In this report, approaches are discussed to the mathematical description of mRNA and protein expression kinetics following DNA damage. Several hypotheses for models of radiation modulation of protein expression are discussed including possible non-linear processes that evolve from the linear dose responses that follow the initial DNA damage produced by radiation.

WE-DE-202-00: Connecting Radiation Physics with Computational Biology

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

NONE

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are themore » most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)« less

Biological effects and epidemiological consequences of arsenic exposure, and reagents that can ameliorate arsenic damage in vivo

PubMed Central

Rao, Chinthalapally V.; Pal, Sanya; Mohammed, Altaf; Farooqui, Mudassir; Doescher, Mark P.; Asch, Adam S.; Yamada, Hiroshi Y.

2017-01-01

Through contaminated diet, water, and other forms of environmental exposure, arsenic affects human health. There are many U.S. and worldwide “hot spots” where the arsenic level in public water exceeds the maximum exposure limit. The biological effects of chronic arsenic exposure include generation of reactive oxygen species (ROS), leading to oxidative stress and DNA damage, epigenetic DNA modification, induction of genomic instability, and inflammation and immunomodulation, all of which can initiate carcinogenesis. High arsenic exposure is epidemiologically associated with skin, lung, bladder, liver, kidney and pancreatic cancer, and cardiovascular, neuronal, and other diseases. This review briefly summarizes the biological effects of arsenic exposure and epidemiological cancer studies worldwide, and provides an overview for emerging rodent-based studies of reagents that can ameliorate the effects of arsenic exposure in vivo. These reagents may be translated to human populations for disease prevention. We propose the importance of developing a biomarker-based precision prevention approach for the health issues associated with arsenic exposure that affects millions of people worldwide. PMID:28915699

WE-DE-202-02: Are Track Structure Simulations Truly Needed for Radiobiology at the Cellular and Tissue Levels?

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

Stewart, R.

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are themore » most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)« less

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

McMahon, S.

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are themore » most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)« less

[The role of the biological damaging factor in the explosive injury].

PubMed

Popov, V L; Kadochnikov, D S; Minaeva, P V

2015-01-01

This article describes the specific features of the action of the biological damaging factors on the human organism associated with the explosive injury. Both the direct action of the damaging agents contained in the biological weapons and their secondary effects in the form of systemic and local infectious complications of the inflicted wounds are considered. The criteria for the evaluation of the degree of harm to the health of the victims of explosion attributable to the action of the biological damaging factor are proposed.

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

NASA Astrophysics Data System (ADS)

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

2016-07-01

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

Atmospheric skin aging-Contributors and inhibitors.

PubMed

McDaniel, David; Farris, Patricia; Valacchi, Giuseppe

2018-04-01

Cutaneous aging is a complex biological process consisting of 2 elements: intrinsic aging, which is primarily determined by genetics, and extrinsic aging, which is largely caused by atmospheric factors, such as exposure to sunlight and air pollution, and lifestyle choices, such as diet and smoking. The role of the solar spectrum, comprised of ultraviolet light, specifically UVB (290-320 nm) and UVA (320-400) in causing skin damage, including skin cancers, has been well documented. In recent years, the contribution of visible light (400-700 nm) and infrared radiation (above 800 nm) in causing skin damage, similar to the photodamage caused by UV light, is also being elucidated. In addition, other atmospheric factors such as air pollution (smog, ozone, particulate matter, etc.) have been implicated in premature skin aging. The skin damage caused by environmental exposure is largely attributable to a complex cascade of reactions inside the skin initiated by the generation of reactive oxygen species (ROS), which causes oxidative damage to cellular components such as proteins, lipids, and nucleic acids. These damaged skin cells initiate inflammatory responses leading to the eventual damage manifested in chronically exposed skin. Novel therapeutic strategies to combat ROS species generation are being developed to prevent the skin damage caused by atmospheric factors. In addition to protecting skin from solar radiation using sunscreens, other approaches using topically applied ingredients, particularly antioxidants that penetrate the skin and protect the skin from within, have also been well documented. This review summarizes current knowledge of atmospheric aggressors, including UVA, UVB, visible light, infrared radiation (IR), and ozone on skin damage, and proposes new avenues for future research in the prevention and treatment of premature skin aging caused by such atmospheric factors. New therapeutic modalities currently being developed are also discussed. © 2018 Wiley Periodicals, Inc.

The Focinator v2-0 - Graphical Interface, Four Channels, Colocalization Analysis and Cell Phase Identification.

PubMed

Oeck, Sebastian; Malewicz, Nathalie M; Hurst, Sebastian; Al-Refae, Klaudia; Krysztofiak, Adam; Jendrossek, Verena

2017-07-01

The quantitative analysis of foci plays an important role in various cell biological methods. In the fields of radiation biology and experimental oncology, the effect of ionizing radiation, chemotherapy or molecularly targeted drugs on DNA damage induction and repair is frequently performed by the analysis of protein clusters or phosphorylated proteins recruited to so called repair foci at DNA damage sites, involving for example γ-H2A.X, 53BP1 or RAD51. We recently developed "The Focinator" as a reliable and fast tool for automated quantitative and qualitative analysis of nuclei and DNA damage foci. The refined software is now even more user-friendly due to a graphical interface and further features. Thus, we included an R-script-based mode for automated image opening, file naming, progress monitoring and an error report. Consequently, the evaluation no longer required the attendance of the operator after initial parameter definition. Moreover, the Focinator v2-0 is now able to perform multi-channel analysis of four channels and evaluation of protein-protein colocalization by comparison of up to three foci channels. This enables for example the quantification of foci in cells of a specific cell cycle phase.

Release, establishment, and initial spread of the fungal pathogen Entomophaga maimaiga in island populations of Lymantria dispar

Treesearch

Patrick C. Tobin; Ann E. Hajek

2012-01-01

Biological invasions represent a major threat to the function and composition of ecosystems. Although the degree of invasion success of a non-native species and the consequent damage it causes can vary among and within invading species, the absence or presence of natural enemies associated with the invader can also play roles in the invasion dynamics. We used newly...

Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage Measured in Metaphase and Interphase Human Lymphocytes

NASA Technical Reports Server (NTRS)

George, Kerry; Durante, Marco; Willingham, Veronica; Wu, Honglu; Yang, Tracy C.; Cucinotta, Francis A.

2003-01-01

Chromosome aberrations were investigated in human lymphocytes after in vitro exposure to 1H-, 3He-, 12C-, 40Ar-, 28Si-, 56Fe-, or 197Au-ion beams, with LET ranging from approximately 0.4-1393 keV/microm in the dose range of 0.075-3 Gy. Dose-response curves for chromosome exchanges, measured at the first mitosis postirradiation using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosomal damage with respect to low- or high-dose-rate gamma rays. Estimates of RBEmax values for mitotic spreads, which ranged from near 0.7 to 11.1 for total exchanges, increased with LET, reaching a maximum at about 150 keV/microm, and decreased with further increase in LET. RBEs for complex aberrations are undefined due to the lack of an initial slope for gamma rays. Additionally, the effect of mitotic delay on RBE values was investigated by measuring chromosome aberrations in interphase after chemically induced premature chromosome condensation (PCC), and values were up to threefold higher than for metaphase analysis.

Effects on DNA Damage and/or Repair Processes as Biological Mechanisms Linking Psychological Stress to Cancer Risk

PubMed Central

Jenkins, Frank J.; Van Houten, Bennett; Bovbjerg, Dana H.

2014-01-01

Considerable research effort in the past several decades has focused on the impact of psychological stress, and stress hormones, on cancer progression. Numerous studies have reported that stress hormone treatment or in vivo stress exposure can enhance the growth of tumor cell lines in vitro, as well as tumors in animal models, and have begun to explore molecular mechanisms. Comparatively little research has focused on the impact of psychological stress and stress hormones on cancer initiation, in part due to inherent methodological challenges, but also because potential underlying biological mechanisms have remained obscure. In this review, we present a testable theoretical model of pathways by which stress may result in cellular transformation and tumorigenesis. This model supports our overarching hypothesis that psychological stress, acting through increased levels of catecholamines and/or cortisol, can increase DNA damage and/or reduce repair mechanisms, resulting in increased risk of DNA mutations leading to carcinogenesis. A better understanding of molecular pathways by which psychological stress can increase the risk of cancer initiation would open new avenues of translational research, bringing together psychologists, neuroscientists, and molecular biologists, potentially resulting in the development of novel approaches for cancer risk reduction at the population level. PMID:24891812

Quantitative Profiling of DNA Damage and Apoptotic Pathways in UV Damaged Cells Using PTMScan Direct

PubMed Central

Stokes, Matthew P.; Silva, Jeffrey C.; Jia, Xiaoying; Lee, Kimberly A.; Polakiewicz, Roberto D.; Comb, Michael J.

2013-01-01

Traditional methods for analysis of peptides using liquid chromatography and tandem mass spectrometry (LC-MS/MS) lack the specificity to comprehensively monitor specific biological processes due to the inherent duty cycle limitations of the MS instrument and the stochastic nature of the analytical platform. PTMScan Direct is a novel, antibody-based method that allows quantitative LC-MS/MS profiling of specific peptides from proteins that reside in the same signaling pathway. New PTMScan Direct reagents have been produced that target peptides from proteins involved in DNA Damage/Cell Cycle and Apoptosis/Autophagy pathways. Together, the reagents provide access to 438 sites on 237 proteins in these signaling cascades. These reagents have been used to profile the response to UV damage of DNA in human cell lines. UV damage was shown to activate canonical DNA damage response pathways through ATM/ATR-dependent signaling, stress response pathways and induce the initiation of apoptosis, as assessed by an increase in the abundance of peptides corresponding to cleaved, activated caspases. These data demonstrate the utility of PTMScan Direct as a multiplexed assay for profiling specific cellular responses to various stimuli, such as UV damage of DNA. PMID:23344034

Microwave Heating of Synthetic Skin Samples for Potential Treatment of Gout Using the Metal-Assisted and Microwave-Accelerated Decrystallization Technique

PubMed Central

2016-01-01

Physical stability of synthetic skin samples during their exposure to microwave heating was investigated to demonstrate the use of the metal-assisted and microwave-accelerated decrystallization (MAMAD) technique for potential biomedical applications. In this regard, optical microscopy and temperature measurements were employed for the qualitative and quantitative assessment of damage to synthetic skin samples during 20 s intermittent microwave heating using a monomode microwave source (at 8 GHz, 2–20 W) up to 120 s. The extent of damage to synthetic skin samples, assessed by the change in the surface area of skin samples, was negligible for microwave power of ≤7 W and more extensive damage (>50%) to skin samples occurred when exposed to >7 W at initial temperature range of 20–39 °C. The initial temperature of synthetic skin samples significantly affected the extent of change in temperature of synthetic skin samples during their exposure to microwave heating. The proof of principle use of the MAMAD technique was demonstrated for the decrystallization of a model biological crystal (l-alanine) placed under synthetic skin samples in the presence of gold nanoparticles. Our results showed that the size (initial size ∼850 μm) of l-alanine crystals can be reduced up to 60% in 120 s without damage to synthetic skin samples using the MAMAD technique. Finite-difference time-domain-based simulations of the electric field distribution of an 8 GHz monomode microwave radiation showed that synthetic skin samples are predicted to absorb ∼92.2% of the microwave radiation. PMID:27917407

On the Use of Biaxial Properties in Modeling Annulus as a Holzapfel–Gasser–Ogden Material

PubMed Central

Momeni Shahraki, Narjes; Fatemi, Ali; Goel, Vijay K.; Agarwal, Anand

2015-01-01

Besides the biology, stresses and strains within the tissue greatly influence the location of damage initiation and mode of failure in an intervertebral disk. Finite element models of a functional spinal unit (FSU) that incorporate reasonably accurate geometry and appropriate material properties are suitable to investigate such issues. Different material models and techniques have been used to model the anisotropic annulus fibrosus, but the abilities of these models to predict damage initiation in the annulus and to explain clinically observed phenomena are unclear. In this study, a hyperelastic anisotropic material model for the annulus with two different sets of material constants, experimentally determined using uniaxial and biaxial loading conditions, were incorporated in a 3D finite element model of a ligamentous FSU. The purpose of the study was to highlight the biomechanical differences (e.g., intradiscal pressure, motion, forces, stresses, strains, etc.) due to the dissimilarity between the two sets of material properties (uniaxial and biaxial). Based on the analyses, the biaxial constants simulations resulted in better agreements with the in vitro and in vivo data, and thus are more suitable for future damage analysis and failure prediction of the annulus under complex multiaxial loading conditions. PMID:26090359

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.

Judicious use of biologicals in juvenile idiopathic arthritis.

PubMed

Zhao, Yongdong; Wallace, Carol

2014-11-01

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disorder that may cause joint destruction. Biological treatments targeting specific cytokines and cell interactions have transformed the outcomes of JIA. This review focuses on the selection of patients for and the timing and selection of biological treatment in JIA. Tumor necrosis factor (TNF) inhibitors remain the first choice for polyarticular JIA, followed by abatacept and tocilizumab. Monoclonal-antibody TNF inhibitors and abatacept are usually chosen for methotrexate-resistant uveitis. Recent clinical trials of canakinumab, rilonacept, and tocilizumab have obtained great improvement in both systemic and arthritic features in chronic systemic JIA patients. Current guidelines support the early use of a short-acting IL-1 antagonist for macrophage activation syndrome, a life-threatening complication. TREAT and ACUTE studies suggest that a therapeutic window of opportunity during early disease may exist in JIA. Early initiation of biological therapy may be associated with slower progression of joint damage and longer remission.

Biological aspects of terrestrial oil spills: USA CRREL oil research in Alaska, 1970--1974. Final report 1970--1974

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

Deneke, F.J.; McCown, B.H.; Coyne, P.I.

1975-12-01

Knowledge concerning the biological effects of oil pollution on arctic and subarctic terrestrial ecosystems is limited. USA CRREL research personnel conducted investigations from 1970 through 1974 to expand information in this field. Objectives were to: (1) define the ecosystems most sensitive to the presence of crude oil or its refined products, (2) quantify and understand the injury response, and (3) establish time frames for manifestation of damage and natural restorative processes in arctic and subarctic regions. This was accomplished through: (1) surveys of natural oil seepages and past accidential spills in the Arctic and Subarctic, (2) initiation of controlled oilmore » spills and (3) detailed laboratory investigations. Results demonstrated that terrestrial oil spills will to some degree be detrimental to both artic and subarctic plant communities. Degree and longevity of damage will be influenced primarily by the magnitude of the spill, season of occurrence and existing soil moisture content. Rapid recovery of plant communities subjected to spills will occur only if root systems remain relatively unaffected. Damage will be more extensive and long-term when root systems are saturated witl oil. Effects of damage will be manifested gradually over several seasons being influenced by winter stresses. Variation does exist in plant species susceptibility. Carex aquatilis a predominant sedge of the arctic is markedly resistant to crude oil damage. In the taiga Picea mariana is very susceptible. Plant recovery can be enhanced through the application of fertilizer. Fertilization, in addition to its direct effect on plant nutrition, will stimulate microbial decomposition of crude oil. (Author)« less

Damage Response in Fluid Flow Networks

NASA Astrophysics Data System (ADS)

Gavrilchenko, Tatyana; Katifori, Eleni

The networks found in biological fluid flow systems such as leaf venation and animal vasculature are characterized by hierarchically nested loops. This structure allows the system to be resilient against fluctuations in the flow of fluid and to be robust against damage. We analytically and computationally investigate how this loopy hierarchy determines the extent of disruption in fluid flow in the vicinity of a damage site. Perturbing the network with the removal of a single edge results in the differential flow as a function of distance from the perturbation decaying as a power law. The power law exponent is generally around -2 in 2D, but we find that it varies due to edge effects, initial edge conductivity, and local topology. We expect that these network flow findings, directly applicable to plant and animal veins, will have analogues in electrical grids, traffic flow and other transport networks.

Variations in the short wavelength cut-off of the solar UV spectra.

PubMed

Parisi, A V; Turner, J

2006-03-01

Cloud and solar zenith angle (SZA) are two major factors that influence the magnitude of the biologically damaging UV (UVBD) irradiances for humans. However, the effect on the short wavelength cut-off due to SZA and due to clouds has not been investigated for biologically damaging UV for cataracts. This research aims to investigate the influence of cloud and SZA on the short wavelength cut-off of the spectral UVBD for cataracts. The spectral biologically damaging UV for cataracts on a horizontal plane was calculated by weighting the spectral UV measured with a spectroradiometer with the action spectrum for the induction of cataracts in a porcine lens. The UV spectra were obtained on an unshaded plane at a latitude of 29.5 degrees S. The cut-off wavelength (lambdac) was defined as the wavelength at which the biologically damaging spectral irradiance was 0.1% of the maximum biologically damaging irradiance for that scan. For the all sky conditions, the short wavelength cut-off ranged by 12 nm for the SZA range of 5 to 80 degrees and the maximum in the spectral UVBD ranged by 15 nm. Similarly, for the cloud free cases, the short wavelength cut-off ranged by 9 nm for the same SZA range. Although, cloud has a large influence on the magnitude of the biologically damaging UV for cataracts, the influence of cloud on the short wavelength cut-off for the biologically damaging UV for cataracts is less than the influence of the solar zenith angle.

Watson-Crick Base Pair Radical Cation as a Model for Oxidative Damage in DNA.

PubMed

Feketeová, Linda; Chan, Bun; Khairallah, George N; Steinmetz, Vincent; Maitre, Philippe; Radom, Leo; O'Hair, Richard A J

2017-07-06

The deleterious cellular effects of ionizing radiation are well-known, but the mechanisms causing DNA damage are poorly understood. The accepted molecular events involve initial oxidation and deprotonation at guanine sites, triggering hydrogen atom abstraction reactions from the sugar moieties, causing DNA strand breaks. Probing the chemistry of the initially formed radical cation has been challenging. Here, we generate, spectroscopically characterize, and examine the reactivity of the Watson-Crick nucleobase pair radical cation in the gas phase. We observe rich chemistry, including proton transfer between the bases and propagation of the radical site in deoxyguanosine from the base to the sugar, thus rupturing the sugar. This first example of a gas-phase model system providing molecular-level details on the chemistry of an ionized DNA base pair paves the way toward a more complete understanding of molecular processes induced by radiation. It also highlights the role of radical propagation in chemistry, biology, and nanotechnology.

On binding specificity of (6-4) photolyase to a T(6-4)T DNA photoproduct*

NASA Astrophysics Data System (ADS)

Jepsen, Katrine Aalbæk; Solov'yov, Ilia A.

2017-06-01

Different factors lead to DNA damage and if it is not repaired in due time, the damaged DNA could initiate mutagenesis and cancer. To avoid this deadly scenario, specific enzymes can scavenge and repair the DNA, but the enzymes have to bind first to the damaged sites. We have investigated this binding for a specific enzyme called (6-4) photolyase, which is capable of repairing certain UV-induced damage in DNA. Through molecular dynamics simulations we describe the binding between photolyase and the DNA and reveal that several charged amino acid residues in the enzyme, such as arginines and lysines turn out to be important. Especially R421 is crucial, as it keeps the DNA strands at the damaged site inside the repair pocket of the enzyme separated. DNA photolyase is structurally highly homologous to a protein called cryptochrome. Both proteins are biologically activated similarly, namely through flavin co-factor photoexcitation. It is, however, striking that cryptochrome cannot repair UV-damaged DNA. The present investigation allowed us to conclude on the small but, apparently, critical differences between photolyase and cryptochrome. The performed analysis gives insight into important factors that govern the binding of UV-damaged DNA and reveal why cryptochrome cannot have this functionality.

Irreparable complex DNA double-strand breaks induce chromosome breakage in organotypic three-dimensional human lung epithelial cell culture

PubMed Central

Asaithamby, Aroumougame; Hu, Burong; Delgado, Oliver; Ding, Liang-Hao; Story, Michael D.; Minna, John D.; Shay, Jerry W.; Chen, David J.

2011-01-01

DNA damage and consequent mutations initiate the multistep carcinogenic process. Differentiated cells have a reduced capacity to repair DNA lesions, but the biological impact of unrepaired DNA lesions in differentiated lung epithelial cells is unclear. Here, we used a novel organotypic human lung three-dimensional (3D) model to investigate the biological significance of unrepaired DNA lesions in differentiated lung epithelial cells. We showed, consistent with existing notions that the kinetics of loss of simple double-strand breaks (DSBs) were significantly reduced in organotypic 3D culture compared to kinetics of repair in two-dimensional (2D) culture. Strikingly, we found that, unlike simple DSBs, a majority of complex DNA lesions were irreparable in organotypic 3D culture. Levels of expression of multiple DNA damage repair pathway genes were significantly reduced in the organotypic 3D culture compared with those in 2D culture providing molecular evidence for the defective DNA damage repair in organotypic culture. Further, when differentiated cells with unrepaired DNA lesions re-entered the cell cycle, they manifested a spectrum of gross-chromosomal aberrations in mitosis. Our data suggest that downregulation of multiple DNA repair pathway genes in differentiated cells renders them vulnerable to DSBs, promoting genome instability that may lead to carcinogenesis. PMID:21421565

Radiation promotes colorectal cancer initiation and progression by inducing senescence-associated inflammatory responses.

PubMed

Kim, S B; Bozeman, R G; Kaisani, A; Kim, W; Zhang, L; Richardson, J A; Wright, W E; Shay, J W

2016-06-30

Proton radiotherapy is becoming more common as protons induce more precise DNA damage at the tumor site with reduced side effects to adjacent normal tissues. However, the long-term biological effects of proton irradiation in cancer initiation compared with conventional photon irradiation are poorly characterized. In this study, using a human familial adenomatous polyposis syndrome susceptible mouse model, we show that whole-body irradiation with protons are more effective in inducing senescence-associated inflammatory responses (SIRs), which are involved in colon cancer initiation and progression. After proton irradiation, a subset of SIR genes (Troy, Sox17, Opg, Faim2, Lpo, Tlr2 and Ptges) and a gene known to be involved in invasiveness (Plat), along with the senescence-associated gene (P19Arf), are markedly increased. Following these changes, loss of Casein kinase Iα and induction of chronic DNA damage and TP53 mutations are increased compared with X-ray irradiation. Proton irradiation also increases the number of colonic polyps, carcinomas and invasive adenocarcinomas. Pretreatment with the non-steroidal anti-inflammatory drug, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid-ethyl amide (CDDO-EA), reduces proton irradiation-associated SIR and tumorigenesis. Thus exposure to proton irradiation elicits significant changes in colorectal cancer initiation and progression that can be mitigated using CDDO-EA.

A systems biology analysis of autophagy in cancer therapy.

PubMed

Shi, Zheng; Li, Chun-yang; Zhao, Si; Yu, Yang; An, Na; Liu, Yong-xi; Wu, Chuan-fang; Yue, Bi-song; Bao, Jin-ku

2013-09-01

Autophagy, which degrades redundant or damaged cellular constituents, is intricately relevant to a variety of human diseases, most notably cancer. Autophagy exerts distinct effects on cancer initiation and progression, due to the intrinsic overlapping of autophagic and cancer signalling pathways. However, due to the complexity of cancer as a systemic disease, the fate of cancer cells is not decided by any one signalling pathway. Numerous autophagic inter-connectivity and cross-talk pathways need to be further clarified at a systems level. In this review, we propose a systems biology perspective for the comprehensive analysis of the autophagy-cancer network, focusing on systems biology analysis in autophagy and cancer therapy. Together, these analyses may not only improve our understanding on autophagy-cancer relationships, but also facilitate cancer drug discovery. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Interactions between low energy electrons and DNA: a perspective from first-principles simulations

NASA Astrophysics Data System (ADS)

Kohanoff, Jorge; McAllister, Maeve; Tribello, Gareth A.; Gu, Bin

2017-09-01

DNA damage caused by irradiation has been studied for many decades. Such studies allow us to better assess the dangers posed by radiation, and to increase the efficiency of the radiotherapies that are used to combat cancer. A full description of the irradiation process involves multiple size and time scales. It starts with the interaction of radiation—either photons or swift ions—and the biological medium, which causes electronic excitation and ionisation. The two main products of ionising radiation are thus electrons and radicals. Both of these species can cause damage to biological molecules, in particular DNA. In the long run, this molecular level damage can prevent cells from replicating and can hence lead to cell death. For a long time it was assumed that the main actors in the damage process were the radicals. However, experiments in a seminal paper by the group of Leon Sanche in 2000 showed that low-energy electrons (LEE), such as those generated when ionising biological targets, can also cause bond breaks in biomolecules, and strand breaks in plasmid DNA in particular (Boudaiffa et al 2000 Science 287 1658-60). These results prompted a significant amount of experimental and theoretical work aimed at elucidating the role played by LEE in DNA damage. In this Topical Review we provide a general overview of the problem. We discuss experimental findings and theoretical results hand in hand with the aim of describing the physics and chemistry that occurs during the process of radiation damage, from the initial stages of electronic excitation, through the inelastic propagation of electrons in the medium, the interaction of electrons with DNA, and the chemical end-point effects on DNA. A very important aspect of this discussion is the consideration of a realistic, physiological environment. The role played by the aqueous solution and the amino acids from the histones in chromatin must be considered. Moreover, thermal fluctuations must be incorporated when studying these phenomena. Hence, a special place in this Topical Review is occupied by our recent first-principles molecular dynamics simulations that address the issue of how the environment favours or prevents LEEs from causing damage to DNA. We finish by summarising the conclusions achieved so far, and by suggesting a number of possible directions for further study.

Interactions between low energy electrons and DNA: a perspective from first-principles simulations.

PubMed

Kohanoff, Jorge; McAllister, Maeve; Tribello, Gareth A; Gu, Bin

2017-09-27

DNA damage caused by irradiation has been studied for many decades. Such studies allow us to better assess the dangers posed by radiation, and to increase the efficiency of the radiotherapies that are used to combat cancer. A full description of the irradiation process involves multiple size and time scales. It starts with the interaction of radiation-either photons or swift ions-and the biological medium, which causes electronic excitation and ionisation. The two main products of ionising radiation are thus electrons and radicals. Both of these species can cause damage to biological molecules, in particular DNA. In the long run, this molecular level damage can prevent cells from replicating and can hence lead to cell death. For a long time it was assumed that the main actors in the damage process were the radicals. However, experiments in a seminal paper by the group of Leon Sanche in 2000 showed that low-energy electrons (LEE), such as those generated when ionising biological targets, can also cause bond breaks in biomolecules, and strand breaks in plasmid DNA in particular (Boudaiffa et al 2000 Science 287 1658-60). These results prompted a significant amount of experimental and theoretical work aimed at elucidating the role played by LEE in DNA damage. In this Topical Review we provide a general overview of the problem. We discuss experimental findings and theoretical results hand in hand with the aim of describing the physics and chemistry that occurs during the process of radiation damage, from the initial stages of electronic excitation, through the inelastic propagation of electrons in the medium, the interaction of electrons with DNA, and the chemical end-point effects on DNA. A very important aspect of this discussion is the consideration of a realistic, physiological environment. The role played by the aqueous solution and the amino acids from the histones in chromatin must be considered. Moreover, thermal fluctuations must be incorporated when studying these phenomena. Hence, a special place in this Topical Review is occupied by our recent first-principles molecular dynamics simulations that address the issue of how the environment favours or prevents LEEs from causing damage to DNA. We finish by summarising the conclusions achieved so far, and by suggesting a number of possible directions for further study.

Advanced glycation end-products: a biological consequence of lifestyle contributing to cancer disparity

PubMed Central

Turner, David P.

2015-01-01

Low income, poor diet, obesity and a lack of exercise are inter-related lifestyle factors that can profoundly alter our biological make-up to increase cancer risk, growth and development. We recently reported a potential mechanistic link between carbohydrate derived metabolites and cancer which may provide a biological consequence of lifestyle that can directly impact tumor biology. Advanced glycation end-products (AGEs) are reactive metabolites produced as a by-product of sugar metabolism. Failure to remove these highly reactive metabolites can lead to protein damage, aberrant cell signaling, increased stress responses, and decreased genetic fidelity. Critically, AGE accumulation is also directly affected by our lifestyle choices and shows a race specific, tumor dependent pattern of accumulation in cancer patients. This review will discuss the contribution of AGEs to the cancer phenotype with a particular emphasis on their biological links with the socioeconomic and environmental risk factors that drive cancer disparity. Given the potential benefits of lifestyle changes and the potential biological role of AGEs in promoting cancer, opportunities exist for collaborations impacting basic, translational, epidemiological and cancer prevention initiatives. PMID:25920350

Advanced glycation end-products: a biological consequence of lifestyle contributing to cancer disparity.

PubMed

Turner, David P

2015-05-15

Low income, poor diet, obesity, and a lack of exercise are interrelated lifestyle factors that can profoundly alter our biologic make up to increase cancer risk, growth, and development. We recently reported a potential mechanistic link between carbohydrate-derived metabolites and cancer, which may provide a biologic consequence of lifestyle that can directly affect tumor biology. Advanced glycation end-products (AGE) are reactive metabolites produced as a by-product of sugar metabolism. Failure to remove these highly reactive metabolites can lead to protein damage, aberrant cell signaling, increased stress responses, and decreased genetic fidelity. Critically, AGE accumulation is also directly affected by our lifestyle choices and shows a race-specific, tumor-dependent pattern of accumulation in cancer patients. This review will discuss the contribution of AGEs to the cancer phenotype, with a particular emphasis on their biologic links with the socioeconomic and environmental risk factors that drive cancer disparity. Given the potential benefits of lifestyle changes and the potential biologic role of AGEs in promoting cancer, opportunities exist for collaborations affecting basic, translational, epidemiologic, and cancer prevention initiatives. ©2015 American Association for Cancer Research.

Nanosecond laser-induced damage at different initial temperatures of Ta{sub 2}O{sub 5} films prepared by dual ion beam sputtering

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

Xu, Cheng, E-mail: xucheng@cumt.edu.cn; Jia, Jiaojiao; Fan, Heliang

2014-08-07

Ta{sub 2}O{sub 5} films were deposited by dual ion beam sputtering method. The nanosecond laser-induced damage threshold (LIDT) at different initial temperatures and time of the films was investigated by an in situ high temperature laser-induced damage testing platform. It was shown that, when the initial temperature increased from 298 K to 383 K, the LIDT at 1064 nm and 12 ns significantly decreased by nearly 14%. Then the LIDT at 1064 nm and 12 ns decreased slower with the same temperature increment. Different damage morphologies were found at different initial temperatures. At low initial temperatures, it was the defects-isolated damage while at high initial temperaturesmore » it was the defects-combined damage. The theoretical calculations based on the defect-induced damage model revealed that both the significant increase of the highest temperature and the duration contributed to the different damage morphologies. With the initial temperature being increased, the thermal-stress coupling damage mechanism transformed gradually to the thermal dominant damage mechanism.« less

Stem cells in drug discovery, tissue engineering, and regenerative medicine: emerging opportunities and challenges.

PubMed

Nirmalanandhan, Victor Sanjit; Sittampalam, G Sitta

2009-08-01

Stem cells, irrespective of their origin, have emerged as valuable reagents or tools in human health in the past 2 decades. Initially, a research tool to study fundamental aspects of developmental biology is now the central focus of generating transgenic animals, drug discovery, and regenerative medicine to address degenerative diseases of multiple organ systems. This is because stem cells are pluripotent or multipotent cells that can recapitulate developmental paths to repair damaged tissues. However, it is becoming clear that stem cell therapy alone may not be adequate to reverse tissue and organ damage in degenerative diseases. Existing small-molecule drugs and biologicals may be needed as "molecular adjuvants" or enhancers of stem cells administered in therapy or adult stem cells in the diseased tissues. Hence, a combination of stem cell-based, high-throughput screening and 3D tissue engineering approaches is necessary to advance the next wave of tools in preclinical drug discovery. In this review, the authors have attempted to provide a basic account of various stem cells types, as well as their biology and signaling, in the context of research in regenerative medicine. An attempt is made to link stem cells as reagents, pharmacology, and tissue engineering as converging fields of research for the next decade.

Estrogens and progression of diabetic kidney damage.

PubMed

Doublier, Sophie; Lupia, Enrico; Catanuto, Paola; Elliot, Sharon J

2011-01-01

It is generally accepted that estrogens affect and modulate the development and progression of chronic kidney diseases (CKD) not related to diabetes. Clinical studies have indeed demonstrated that the severity and rate of progression of renal damage tends to be greater among men, compared with women. Experimental studies also support the notion that female sex is protective and male sex permissive, for the development of CKD in non-diabetics, through the opposing actions of estrogens and testosterone. However, when we consider diabetes-induced kidney damage, in the setting of either type 1 or type 2 diabetes, the contribution of gender to the progression of renal disease is somewhat uncertain. Previous studies on the effects of estrogens in the pathogenesis of progressive kidney damage have primarily focused on mesangial cells. More recently, data on the effects of estrogens on podocytes, the cell type whose role may include initiation of progressive diabetic renal disease, became available. The aim of this review will be to summarize the main clinical and experimental data on the effects of estrogens on the progression of diabetes-induced kidney injury. In particular, we will highlight the possible biological effects of estrogens on podocytes, especially considering those critical for the pathogenesis of diabetic kidney damage.

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

PubMed

Burkitt, M J; Gilbert, B C

1989-01-01

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

Are Mental Disorders Brain Diseases, and What Does This Mean? A Clinical-Neuropsychological Perspective.

PubMed

Frisch, Stefan

Neuroscientific research has substantially increased our knowledge about mental disorders in recent years. Along with these benefits, radical postulates have been articulated according to which understanding and treatment of mental disorders should generally be based on biological terms, such as neurons/brain areas, transmitters, genes etc. Proponents of such a 'biological psychiatry' claim that mental disorders are analogous to neurological disorders and refer to neurology and neuropsychology to corroborate their claims. The present article argues that, from a clinical-neuropsychological perspective, 'biological psychiatry' is based on a mechanistic, 'cerebrocentric' framework of brain (dys-)function which has its roots in experimental neuroscience but runs up against narrow limits in clinical neurology and neuropsychology. In fact, understanding and treating neurological disorders generally demands a systems perspective including brain, organism and environment as intrinsically entangled. In this way, 'biological' characterizes a 'holistic', nonreductionist level of explanation, according to which the significance of particular mechanisms can only be estimated in the context of the organism (or person). This is evident in the common observation that local brain damage does not just lead to an isolated loss of function, but to multiple attempts of reorganization and readaptation; it initiates new developments. Furthermore, treating brain disorders necessarily includes aspects of individuality and subjectivity, a conclusion that contradicts the purely 'objectivist', third-person stance put forward by some proponents of biological psychiatry. In sum, understanding and treating brain damage sequelae in the clinical neurosciences demands a biopsychosocial perspective, for both conceptual and historical reasons. The same may hold for psychiatry when adopting a brain-based view on mental disorders. In such a perspective, biological psychiatry seems an interesting project but falls short of its original claims. © 2016 S. Karger AG, Basel.

Molecular and Cellular Mechanisms that Initiate Pain and Itch

PubMed Central

Luo, Jialie; Feng, Jing; Liu, Shenbin; Walters, Edgar T.

2015-01-01

Somatosensory neurons mediate our sense of touch. They are critically involved in transducing pain and itch sensations under physiological and pathological conditions, along with other skin resident cells. Tissue damage and inflammation can produce a localized or systemic sensitization of our senses of pain and itch, which can facilitate our detection of threats in the environment. Although acute pain and itch protect us from further damage, persistent pain and itch are debilitating. Recent exciting discoveries have significantly advanced our knowledge of the roles of membrane-bound G protein-coupled receptors and ion channels in the encoding of information leading to pain and itch sensations. This review focuses on molecular and cellular events that are important in early stages of the biological processing that culminates in our senses of pain and itch. PMID:25894692

The Demographic and Biomedical Case for Late-Life Interventions in Aging

PubMed Central

Rae, Michael J.; Butler, Robert N.; Campisi, Judith; de Grey, Aubrey D. N. J.; Finch, Caleb E.; Gough, Michael; Martin, George M.; Vijg, Jan; Perrott, Kevin M.; Logan, Barbara J.

2013-01-01

The social and medical costs of the biological aging process are high and will rise rapidly in coming decades, creating an enormous challenge to societies worldwide. In recent decades, researchers have expanded their understanding of the underlying deleterious structural and physiological changes (aging damage) that underlie the progressive functional impairments, declining health, and rising mortality of aging humans and other organisms and have been able to intervene in the process in model organisms, even late in life. To preempt a global aging crisis, we advocate an ambitious global initiative to translate these findings into interventions for aging humans, using three complementary approaches to retard, arrest, and even reverse aging damage, extending and even restoring the period of youthful health and functionality of older people. PMID:20630854

Physical Biology of Axonal Damage.

PubMed

de Rooij, Rijk; Kuhl, Ellen

2018-01-01

Excessive physical impacts to the head have direct implications on the structural integrity at the axonal level. Increasing evidence suggests that tau, an intrinsically disordered protein that stabilizes axonal microtubules, plays a critical role in the physical biology of axonal injury. However, the precise mechanisms of axonal damage remain incompletely understood. Here we propose a biophysical model of the axon to correlate the dynamic behavior of individual tau proteins under external physical forces to the evolution of axonal damage. To propagate damage across the scales, we adopt a consistent three-step strategy: First, we characterize the axonal response to external stretches and stretch rates for varying tau crosslink bond strengths using a discrete axonal damage model. Then, for each combination of stretch rates and bond strengths, we average the axonal force-stretch response of n = 10 discrete simulations, from which we derive and calibrate a homogenized constitutive model. Finally, we embed this homogenized model into a continuum axonal damage model of [1-d]-type in which d is a scalar damage parameter that is driven by the axonal stretch and stretch rate. We demonstrate that axonal damage emerges naturally from the interplay of physical forces and biological crosslinking. Our study reveals an emergent feature of the crosslink dynamics: With increasing loading rate, the axonal failure stretch increases, but axonal damage evolves earlier in time. For a wide range of physical stretch rates, from 0.1 to 10 /s, and biological bond strengths, from 1 to 100 pN, our model predicts a relatively narrow window of critical damage stretch thresholds, from 1.01 to 1.30, which agrees well with experimental observations. Our biophysical damage model can help explain the development and progression of axonal damage across the scales and will provide useful guidelines to identify critical damage level thresholds in response to excessive physical forces.

Compression of thick laminated composite beams with initial impact-like damage

NASA Technical Reports Server (NTRS)

Breivik, N. L.; Guerdal, Z.; Griffin, O. H., Jr.

1992-01-01

While the study of compression after impact of laminated composites has been under consideration for many years, the complexity of the damage initiated by low velocity impact has not lent itself to simple predictive models for compression strength. The damage modes due to non-penetrating, low velocity impact by large diameter objects can be simulated using quasi-static three-point bending. The resulting damage modes are less coupled and more easily characterized than actual impact damage modes. This study includes the compression testing of specimens with well documented initial damage states obtained from three-point bend testing. Compression strengths and failure modes were obtained for quasi-isotropic stacking sequences from 0.24 to 1.1 inches thick with both grouped and interspersed ply stacking. Initial damage prior to compression testing was divided into four classifications based on the type, extent, and location of the damage. These classifications are multiple through-thickness delaminations, isolated delamination, damage near the surface, and matrix cracks. Specimens from each classification were compared to specimens tested without initial damage in order to determine the effects of the initial damage on the final compression strength and failure modes. A finite element analysis was used to aid in the understanding and explanation of the experimental results.

Early development and characterization of a DNA-based radiation dosimeter

NASA Astrophysics Data System (ADS)

Avarmaa, Kirsten A.

It is the priority of first responders to minimize damage to persons and infrastructure in the case of a nuclear emergency due to an accident or deliberate terrorist attack -- if this emergency includes a radioactive hazard, first responders require a simple-to-use, accurate and complete dosimeter for radiation protection purposes in order to minimize the health risk to these individuals and the general population at large. This work consists of the early evaluation of the design and performance of a biologically relevant dosimeter which uses DNA material that can respond to the radiation of any particle type. The construct consists of fluorescently tagged strands of DNA. The signalling components of this dosimeter are also investigated for their sensitivity to radiation damage and light exposure. The dual-labelled dosimeter that is evaluated in this work gave a measurable response to gamma radiation at dose levels of 10 Gy for the given detector design and experimental setup. Further testing outside of this work confirmed this finding and indicated a working range of 100 mGy to 10 Gy using a custom-built fluorimeter as part of a larger CRTI initiative. Characterization of the chromatic components of the dosimeter showed that photobleaching is not expected to have an effect on dosimeter performance, but that radiation can damage the non-DNA signalling components at higher dose levels, although this damage is minimal at lower doses over the expected operating ranges. This work therefore describes the early steps in the quantification of the behaviour of the DNA dosimeter as a potential biologically-based device to measure radiation dose.

[Sea urchin embryo, DNA-damaged cell cycle checkpoint and the mechanisms initiating cancer development].

PubMed

Bellé, Robert; Le Bouffant, Ronan; Morales, Julia; Cosson, Bertrand; Cormier, Patrick; Mulner-Lorillon, Odile

2007-01-01

Cell division is an essential process for heredity, maintenance and evolution of the whole living kingdom. Sea urchin early development represents an excellent experimental model for the analysis of cell cycle checkpoint mechanisms since embryonic cells contain a functional DNA-damage checkpoint and since the whole sea urchin genome is sequenced. The DNA-damaged checkpoint is responsible for an arrest in the cell cycle when DNA is damaged or incorrectly replicated, for activation of the DNA repair mechanism, and for commitment to cell death by apoptosis in the case of failure to repair. New insights in cancer biology lead to two fundamental concepts about the very first origin of cancerogenesis. Cancers result from dysfunction of DNA-damaged checkpoints and cancers appear as a result of normal stem cell (NCS) transformation into a cancer stem cell (CSC). The second aspect suggests a new definition of "cancer", since CSC can be detected well before any clinical evidence. Since early development starts from the zygote, which is a primary stem cell, sea urchin early development allows analysis of the early steps of the cancerization process. Although sea urchins do not develop cancers, the model is alternative and complementary to stem cells which are not easy to isolate, do not divide in a short time and do not divide synchronously. In the field of toxicology and incidence on human health, the sea urchin experimental model allows assessment of cancer risk from single or combined molecules long before any epidemiologic evidence is available. Sea urchin embryos were used to test the worldwide used pesticide Roundup that contains glyphosate as the active herbicide agent; it was shown to activate the DNA-damage checkpoint of the first cell cycle of development. The model therefore allows considerable increase in risk evaluation of new products in the field of cancer and offers a tool for the discovery of molecular markers for early diagnostic in cancer biology. Prevention and early diagnosis are two decisive elements of human cancer therapy.

BRAIN DAMAGE IN CHILDREN, THE BIOLOGICAL AND SOCIAL ASPECTS.

ERIC Educational Resources Information Center

BIRCH, HERBERT G., ED.

PAPERS AND DISCUSSION SUMMARIES ARE PRESENTED FROM A CONFERENCE ON THE BIOLOGICAL AND SOCIAL PROBLEMS OF CHILDHOOD BRAIN DAMAGE, HELD AT THE CHILDREN'S HOSPITAL OF PHILADELPHIA IN NOVEMBER 1962. A VARIETY OF DISCIPLINES IS REPRESENTED, AND THE FOLLOWING TOPICS ARE CONSIDERED--(1) "THE PROBLEM OF 'BRAIN DAMAGE' IN CHILDREN" BY HERBERT G. BIRCH, (2)…

Development of a GCR Event-based Risk Model

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Ponomarev, Artem L.; Plante, Ianik; Carra, Claudio; Kim, Myung-Hee

2009-01-01

A goal at NASA is to develop event-based systems biology models of space radiation risks that will replace the current dose-based empirical models. Complex and varied biochemical signaling processes transmit the initial DNA and oxidative damage from space radiation into cellular and tissue responses. Mis-repaired damage or aberrant signals can lead to genomic instability, persistent oxidative stress or inflammation, which are causative of cancer and CNS risks. Protective signaling through adaptive responses or cell repopulation is also possible. We are developing a computational simulation approach to galactic cosmic ray (GCR) effects that is based on biological events rather than average quantities such as dose, fluence, or dose equivalent. The goal of the GCR Event-based Risk Model (GERMcode) is to provide a simulation tool to describe and integrate physical and biological events into stochastic models of space radiation risks. We used the quantum multiple scattering model of heavy ion fragmentation (QMSFRG) and well known energy loss processes to develop a stochastic Monte-Carlo based model of GCR transport in spacecraft shielding and tissue. We validated the accuracy of the model by comparing to physical data from the NASA Space Radiation Laboratory (NSRL). Our simulation approach allows us to time-tag each GCR proton or heavy ion interaction in tissue including correlated secondary ions often of high multiplicity. Conventional space radiation risk assessment employs average quantities, and assumes linearity and additivity of responses over the complete range of GCR charge and energies. To investigate possible deviations from these assumptions, we studied several biological response pathway models of varying induction and relaxation times including the ATM, TGF -Smad, and WNT signaling pathways. We then considered small volumes of interacting cells and the time-dependent biophysical events that the GCR would produce within these tissue volumes to estimate how GCR event rates mapped to biological signaling induction and relaxation times. We considered several hypotheses related to signaling and cancer risk, and then performed simulations for conditions where aberrant or adaptive signaling would occur on long-duration space mission. Our results do not support the conventional assumptions of dose, linearity and additivity. A discussion on how event-based systems biology models, which focus on biological signaling as the mechanism to propagate damage or adaptation, can be further developed for cancer and CNS space radiation risk projections is given.

Involvement of oxidatively damaged DNA and repair in cancer development and aging

PubMed Central

Tudek, Barbara; Winczura, Alicja; Janik, Justyna; Siomek, Agnieszka; Foksinski, Marek; Oliński, Ryszard

2010-01-01

DNA damage and DNA repair may mediate several cellular processes, like replication and transcription, mutagenesis and apoptosis and thus may be important factors in the development and pathology of an organism, including cancer. DNA is constantly damaged by reactive oxygen species (ROS) and reactive nitrogen species (RNS) directly and also by products of lipid peroxidation (LPO), which form exocyclic adducts to DNA bases. A wide variety of oxidatively-generated DNA lesions are present in living cells. 8-oxoguanine (8-oxoGua) is one of the best known DNA lesions due to its mutagenic properties. Among LPO-derived DNA base modifications the most intensively studied are ethenoadenine and ethenocytosine, highly miscoding DNA lesions considered as markers of oxidative stress and promutagenic DNA damage. Although at present it is impossible to directly answer the question concerning involvement of oxidatively damaged DNA in cancer etiology, it is likely that oxidatively modified DNA bases may serve as a source of mutations that initiate carcinogenesis and are involved in aging (i.e. they may be causal factors responsible for these processes). To counteract the deleterious effect of oxidatively damaged DNA, all organisms have developed several DNA repair mechanisms. The efficiency of oxidatively damaged DNA repair was frequently found to be decreased in cancer patients. The present work reviews the basis for the biological significance of DNA damage, particularly effects of 8-oxoGua and ethenoadduct occurrence in DNA in the aspect of cancer development, drawing attention to the multiplicity of proteins with repair activities. PMID:20589166

Viability and proliferation potential of adipose-derived stem cells following labeling with a positron-emitting radiotracer.

PubMed

Elhami, Esmat; Goertzen, Andrew L; Xiang, Bo; Deng, Jixian; Stillwell, Chris; Mzengeza, Shadreck; Arora, Rakesh C; Freed, Darren; Tian, Ganghong

2011-07-01

Adipose-derived stem cells (ASCs) have promising potential in regenerative medicine and cell therapy. Our objective is to examine the biological function of the labeled stem cells following labeling with a readily available positron emission tomography (PET) tracer, (18)F-fluoro-2-deoxy-D: -glucose (FDG). In this work we characterize labeling efficiency through assessment of FDG uptake and retention by the ASCs and the effect of FDG on cell viability, proliferation, transdifferentiation, and cell function in vitro using rat ASCs. Samples of 10(5) ASCs (from visceral fat tissue) were labeled with concentrations of FDG (1-55 Bq/cell) in 0.75 ml culture medium. Label uptake and retention, as a function of labeling time, FDG concentration, and efflux period were measured to determine optimum cell labeling conditions. Cell viability, proliferation, DNA structure damage, cell differentiation, and other cell functions were examined. Non-labeled ASC samples were used as a control for all experimental groups. Labeled ASCs were injected via tail vein in several healthy rats and initial cell biodistribution was assessed. Our results showed that FDG uptake and retention by the stem cells did not depend on FDG concentration but on labeling and efflux periods and glucose content of the labeling and efflux media. Cell viability, transdifferentiation, and cell function were not greatly affected. DNA damage due to FDG radioactivity was acute, but reversible; cells managed to repair the damage and continue with cell cycles. Over all, FDG (up to 25 Bq/cell) did not impose severe cytotoxicity in rat ASCs. Initial biodistribution of the FDG-labeled ASCs was 80% + retention in the lungs. In the delayed whole-body images (2-3 h postinjection) there was some activity distribution resembling typical FDG uptake patterns. For in vivo cell tracking studies with PET tracers, the parameter of interest is the amount of radiotracer that is present in the cells being labeled and consequent biological effects. From our study we developed a labeling protocol for labeling ASCs with a readily available PET tracer, FDG. Our results indicate that ASCs can be safely labeled with FDG concentration up to 25 Bq/cell, without compromising their biological function. A labeling period of 90 min in glucose-free medium and efflux of 60 min in complete media resulted in optimum label retention, i.e., 60% + by the stem cells. The initial biodistribution of the implanted FDG-labeled stem cells can be monitored using microPET imaging.

Combining wet etching and real-time damage event imaging to reveal the most dangerous laser damage initiator in fused silica.

PubMed

Hu, Guohang; Zhao, Yuanan; Liu, Xiaofeng; Li, Dawei; Xiao, Qiling; Yi, Kui; Shao, Jianda

2013-08-01

A reliable method, combining a wet etch process and real-time damage event imaging during a raster scan laser damage test, has been developed to directly determine the most dangerous precursor inducing low-density laser damage at 355 nm in fused silica. It is revealed that ~16% of laser damage sites were initiated at the place of the scratches, ~49% initiated at the digs, and ~35% initiated at invisible defects. The morphologies of dangerous scratches and digs were compared with those of moderate ones. It is found that local sharp variation at the edge, twist, or inside of a subsurface defect is the most dangerous laser damage precursor.

Characterization of UVC-induced DNA damage in bloodstains: forensic implications.

PubMed

Hall, Ashley; Ballantyne, Jack

2004-09-01

The ability to detect DNA polymorphisms using molecular genetic techniques has revolutionized the forensic analysis of biological evidence. DNA typing now plays a critical role within the criminal justice system, but one of the limiting factors with the technology is that DNA isolated from biological stains recovered from the crime scene is sometimes so damaged as to be intractable to analysis. Potential remedies for damaged DNA are likely to be dependent upon the precise nature of the DNA damage present in any particular sample but, unfortunately, current knowledge of the biochemical nature, and the extent, of such DNA damage in dried biological stains is rudimentary. As a model for DNA damage assessment in biological stains recovered from crime scenes, we have subjected human bloodstains and naked DNA in the hydrated and dehydrated states to varying doses of UVC radiation. It was possible to damage the DNA sufficiently in a bloodstain to cause a standard autosomal short tandem repeat (STR) profile to be lost. However, a detailed analysis of the process, based upon assays developed to detect bipyrimidine photoproducts (BPPPs), single- and double-strand breaks, and DNA-DNA crosslinks, produced some unexpected findings. Contrary to the situation with living tissues or cells in culture, the predominant UVC-induced damage to DNA in bloodstains appears not to be pyrimidine dimers. Although some evidence for the presence of BPPPs and DNA crosslinks was obtained, the major form of UVC damage causing genetic profile loss appeared to be single-strand breaks. It was not possible, however, to preclude the possibility that a combination of damage types was responsible for the profile loss observed. We demonstrate here that a significant measure of protection against UVC-mediated genetic profile loss in dried biological stain material is afforded by the dehydrated state of the DNA and, to a lesser extent, the DNA cellular milieu.

Predicting spillover risk to non-target plants pre-release: Bikasha collaris a potential biological control agent of Chinese tallowtree (Triadica sebifera)

USDA-ARS?s Scientific Manuscript database

Quarantine host range tests accurately predict direct risk of biological control agents to non-target species. However, a well-known indirect effect of biological control of weeds releases is spillover damage to non-target species. Spillover damage may occur when the population of agents achieves ou...

Photoacoustic imaging in both soft and hard biological tissue

NASA Astrophysics Data System (ADS)

Li, T.; Dewhurst, R. J.

2010-03-01

To date, most Photoacoustic (PA) imaging results have been from soft biotissues. In this study, a PA imaging system with a near-infrared pulsed laser source has been applied to obtain 2-D and 3-D images from both soft tissue and post-mortem dental samples. Imaging results showed that the PA technique has the potential to image human oral disease, such as early-stage teeth decay. For non-invasive photoacoustic imaging, the induced temperature and pressure rises within biotissues should not cause physical damage to the tissue. Several simulations based on the thermoelastic effect have been applied to predict initial temperature and pressure fields within a tooth sample. Predicted initial temperature and pressure rises are below corresponding safety limits.

Numerical Simulation of Thawing Process of Biological Tissue

NASA Astrophysics Data System (ADS)

Momose, Noboru; Tada, Yukio; Hayashi, Yujiro

Heat transfer and simplified physicochemical model for thawing of the frozen biological cell element consisting of cell and extracellular region was proposed. The melting of intra-and extra-cellular ice, the water transport through cell membrane and other microscale behavior during thawing process were discussed as a function of temperature. Recovery of the cell volume and change of osmotic pressure difference during thawing were clarified theortically in connection with heating velocity, initial cell volume and membrane permeability. Extending this model, the thawing of cellular tissue consisted of numerous cell elements was also simulated. There was a position where osmotic pressure difference became maximum during thawing. Summarizing these results, the thawing damage due to osmotic stress was discussed in relation with the heating operation and the size effect of tissue.

Phase 2 trial of daily, oral epigallocatechin gallate in patients with light-chain amyloidosis.

PubMed

Meshitsuka, Sohsuke; Shingaki, Sumito; Hotta, Masatoshi; Goto, Miku; Kobayashi, Makoto; Ukawa, Yuuichi; Sagesaka, Yuko M; Wada, Yasuyo; Nojima, Masanori; Suzuki, Kenshi

2017-03-01

Previous studies have suggested that an increase in mitochondrial reactive oxygen species may cause organ damage in patients with light-chain (AL) amyloidosis; however, this damage can be decreased by antioxidant-agent treatment. Epigallocatechin gallate (EGCG), the major natural catechin in green tea, has potent antioxidant activity. Because EGCG has recently been reported to have a favorable toxicity profile for treating amyloidosis, we sought to examine the clinical efficacy and toxicity of EGCG in patients with AL amyloidosis. Fifty-seven patients were randomly assigned to the EGCG and observation groups and observed for six months. There were no increases in grade 3-5 adverse events and EGCG therapy was well tolerated. Although a decrease in the urinary albumin level was found in the EGCG group in patients with obvious albuminuria after treatment initiation, its antioxidant activity may not be sufficient to clarify the potential effect of EGCG in patients with AL amyloidosis. Because some of the biological markers responsible for organ damage were well correlated to the level of antioxidant potential in patients' plasma, the status of oxidative stress in the blood may indicate the extent of organ damage in clinical situations.

Copper toxicity, oxidative stress, and antioxidant nutrients.

PubMed

Gaetke, Lisa M; Chow, Ching Kuang

2003-07-15

Copper (Cu) is an integral part of many important enzymes involved in a number of vital biological processes. Although normally bound to proteins, Cu may be released and become free to catalyze the formation of highly reactive hydroxyl radicals. Data obtained from in vitro and cell culture studies are largely supportive of Cu's capacity to initiate oxidative damage and interfere with important cellular events. Oxidative damage has been linked to chronic Cu-overload and/or exposure to excess Cu caused by accidents, occupational hazards, and environmental contamination. Additionally, Cu-induced oxidative damage has been implicated in disorders associated with abnormal Cu metabolism and neurodegenerative changes. Interestingly, a deficiency in dietary Cu also increases cellular susceptibility to oxidative damage. A number of nutrients have been shown to interact with Cu and alter its cellular effects. Vitamin E is generally protective against Cu-induced oxidative damage. While most in vitro or cell culture studies show that ascorbic acid aggravates Cu-induced oxidative damage, results obtained from available animal studies suggest that the compound is protective. High intakes of ascorbic acid and zinc may provide protection against Cu toxicity by preventing excess Cu uptake. Zinc also removes Cu from its binding site, where it may cause free radical formation. Beta-carotene, alpha-lipoic acid and polyphenols have also been shown to attenuate Cu-induced oxidative damage. Further studies are needed to better understand the cellular effects of this essential, but potentially toxic, trace mineral and its functional interaction with other nutrients.

Applying Petri nets to modeling the chemical stage of radiobiological mechanism

NASA Astrophysics Data System (ADS)

Barilla, J.; Lokajíček, M.; Pisaková, H.; Simr, P.

2015-03-01

The chemical stage represents important part of radiological mechanism as double strand breaks of DNA molecules represent main damages leading to final biological effect. These breaks are formed mainly by water radicals arising in clusters formed by densely ionizing ends of primary or secondary charged particles in neighborhood of a DNA molecule. The given effect may be significantly influenced by other species present in water, which may depend on the size and diffusion of corresponding clusters. We have already proposed a model describing the corresponding process (i.e., the combined effect of cluster diffusion and chemical reactions) running in individual radical clusters and influencing the formation probability of main damages (i.e., DSBs). Now a full number of corresponding species will be considered. With the help of Continuous Petri nets it will then be possible to follow the time evolution of corresponding species in individual clusters, which might be important especially in the case of studying the biological effect of very low-LET radiation. The results in deoxygenated water will be presented; the ratio of final and initial contents of corresponding species being in good agreement with values established experimentally.

Response of thyroid follicular cells to gamma irradiation compared to proton irradiation. I. Initial characterization of DNA damage, micronucleus formation, apoptosis, cell survival, and cell cycle phase redistribution

NASA Technical Reports Server (NTRS)

Green, L. M.; Murray, D. K.; Bant, A. M.; Kazarians, G.; Moyers, M. F.; Nelson, G. A.; Tran, D. T.

2001-01-01

The RBE of protons has been assumed to be equivalent to that of photons. The objective of this study was to determine whether radiation-induced DNA and chromosome damage, apoptosis, cell killing and cell cycling in organized epithelial cells was influenced by radiation quality. Thyroid-stimulating hormone-dependent Fischer rat thyroid cells, established as follicles, were exposed to gamma rays or proton beams delivered acutely over a range of physical doses. Gamma-irradiated cells were able to repair DNA damage relatively rapidly so that by 1 h postirradiation they had approximately 20% fewer exposed 3' ends than their counterparts that had been irradiated with proton beams. The persistence of free ends of DNA in the samples irradiated with the proton beam implies that either more initial breaks or a quantitatively different type of damage had occurred. These results were further supported by an increased frequency of chromosomal damage as measured by the presence of micronuclei. Proton-beam irradiation induced micronuclei at a rate of 2.4% per gray, which at 12 Gy translated to 40% more micronuclei than in comparable gamma-irradiated cultures. The higher rate of micronucleus formation and the presence of larger micronuclei in proton-irradiated cells was further evidence that a qualitatively more severe class of damage had been induced than was induced by gamma rays. Differences in the type of damage produced were detected in the apoptosis assay, wherein a significant lag in the induction of apoptosis occurred after gamma irradiation that did not occur with protons. The more immediate expression of apoptotic cells in the cultures irradiated with the proton beam suggests that the damage inflicted was more severe. Alternatively, the cell cycle checkpoint mechanisms required for recovery from such damage might not have been invoked. Differences based on radiation quality were also evident in the alpha components of cell survival curves (0.05 Gy(-1) for gamma rays, 0.12 Gy(-1) for protons), which suggests that the higher level of survival of gamma-irradiated cells could be attributed to the persistence of nonlethally irradiated thyrocytes and/or the capacity to repair damage more effectively than cells exposed to equal physical doses of protons. The final assessment in this study was radiation-induced cell cycle phase redistribution. Gamma rays and protons produced a similar dose-dependent redistribution toward a predominantly G(2)-phase population. From our cumulative results, it seems likely that a majority of the proton-irradiated cells would not continue to divide. In conclusion, these findings suggest that there are quantitative and qualitative differences in the biological effects of proton beams and gamma rays. These differences could be due to structured energy deposition from the tracks of primary protons and the associated high-LET secondary particles produced in the targets. The results suggest that a simple dose-equivalent approach to dosimetry may be inadequate to compare the biological responses of cells to photons and protons.

Linking Adverse Outcome Pathways to Dynamic Energy Budgets: A Conceptual Model

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

Murphy, Cheryl; Nisbet, Roger; Antczak, Philipp

Ecological risk assessment quantifies the likelihood of undesirable impacts of stressors, primarily at high levels of biological organization. Data used to inform ecological risk assessments come primarily from tests on individual organisms or from suborganismal studies, indicating a disconnect between primary data and protection goals. We know how to relate individual responses to population dynamics using individual-based models, and there are emerging ideas on how to make connections to ecosystem services. However, there is no established methodology to connect effects seen at higher levels of biological organization with suborganismal dynamics, despite progress made in identifying Adverse Outcome Pathways (AOPs) thatmore » link molecular initiating events to ecologically relevant key events. This chapter is a product of a working group at the National Center for Mathematical and Biological Synthesis (NIMBioS) that assessed the feasibility of using dynamic energy budget (DEB) models of individual organisms as a “pivot” connecting suborganismal processes to higher level ecological processes. AOP models quantify explicit molecular, cellular or organ-level processes, but do not offer a route to linking sub-organismal damage to adverse effects on individual growth, reproduction, and survival, which can be propagated to the population level through individual-based models. DEB models describe these processes, but use abstract variables with undetermined connections to suborganismal biology. We propose linking DEB and quantitative AOP models by interpreting AOP key events as measures of damage-inducing processes in a DEB model. Here, we present a conceptual model for linking AOPs to DEB models and review existing modeling tools available for both AOP and DEB.« less

Personal characteristics relating to radium loss over a decade or more in radium dial workers

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

Stebbings, J.H.; Jansen, A.; Kotek, T.J.

1986-01-01

Personal habits and biological characteristics of 42 female Illinois radium workers first employed during the 1920s were analyzed in relationship to radium loss in late adult life. The 42 women met the criteria that they first were examined between 1957 and 1969 and are no longer employed, have had two or more radium body-burden measurements by gamma spectroscopy, 10-year minimum interval exists between initial and final measurements, and exhibit a RaC body burden in 1970 or later of greater than or equal to.137 kBQ. High radium body burdens are associated with decreased rates of radium elimination, as previously described. However,more » the most powerful predictor was coffee/tea consumption, increased consumption being associated with increased rates of radium elimination and explaining approx.35% of the variance. The effect persisted after deletion of smokers and subjects with x-ray evidence of bone damage. Weight/height ratios were positively associated with radium excretion. Individuals smoking cigarettes throughout the study period had significantly low rates of elimination of radium, similar to subjects with x-ray evidence of significant radiation-induced bone damage. Both smokers and subjects with x-ray evidence of radiation damage to bone had low weight/height ratios, suggesting that biological promoters of radiation damage to bone may exist. Rates of radium elimination were significantly associated with (linear) bone density, demonstrating that rates of loss of radium cannot be assumed to be independent of adult or postmenopausal bone density losses. Number of children and age of menopause did not have demonstrable effects on radium elimination. 9 refs., 2 figs., 7 tabs.« less

Study of cell killing effect on S180 by ultrasound activating protoporphyrin IX.

PubMed

Wang, Xiao Bing; Liu, Quan Hong; Wang, Pan; Tang, Wei; Hao, Qiao

2008-04-01

The present study was initiated to investigate the potential biological mechanism of cell killing effect on isolate sarcoma 180 (S180) cells induced by ultrasound activating protoporphyrin IX (PPIX). S180 cells were exposed to ultrasound for 30s duration, at a frequency of 2.2 MHz and an acoustic power of 3 W/cm(2) in the presence of 120 microM PPIX. The viability of cells was evaluated using trypan blue staining. The generation of oxygen free radicals in cell suspensions was detected immediately after treatment using a reactive oxygen detection kit. A copper reagent colorimetry method was used to measure the level of FFAs released into cell suspensions by the process of cell damage induced by ultrasound and PPIX treatment. Oxidative stress was assessed by measuring the activities of key antioxidant enzymes (i.e., SOD, CAT, GSH-PX) in S180 tumor cells. Treatment with ultrasound and PPIX together increased the cell damage rate to 50.91%, while treatment with ultrasound alone gave a cell damage rate to 24.24%, and PPIX alone kept this rate unchanged. Colorimetry and enzymatic chemical methods showed that the level of FFAs in cell suspension increased significantly after the treatment, while the activity of all the above enzymes decreased in tumor cells at different levels, and were associated with the generation of oxygen free radicals in cell suspension after treatment. The results indicate that oxygen free radicals may play an important role in improving the membrane lipid peroxidation, degrading membrane phospholipids to release FFAs, and decreasing the activities of the key antioxidant enzymes in cells. This biological mechanism might be involved in mediating the effects on S180 cells and resulting in the cell damage seen with SDT.

What Combined Measurements From Structures and Imaging Tell Us About DNA Damage Responses

PubMed Central

Brosey, Chris A.; Ahmed, Zamal; Lees-Miller, Susan P.; Tainer, John A.

2017-01-01

DNA damage outcomes depend upon the efficiency and fidelity of DNA damage responses (DDRs) for different cells and damage. As such, DDRs represent tightly regulated prototypical systems for linking nanoscale biomolecular structure and assembly to the biology of genomic regulation and cell signaling. However, the dynamic and multifunctional nature of DDR assemblies can render elusive the correlation between the structures of DDR factors and specific biological disruptions to the DDR when these structures are altered. In this chapter, we discuss concepts and strategies for combining structural, biophysical, and imaging techniques to investigate DDR recognition and regulation, and thus bridge sequence-level structural biochemistry to quantitative biological outcomes visualized in cells. We focus on representative DDR responses from PARP/PARG/AIF damage signaling in DNA single-strand break repair and nonhomologous end joining complexes in double-strand break repair. Methods with exemplary experimental results are considered with a focus on strategies for probing flexibility, conformational changes, and assembly processes that shape a predictive understanding of DDR mechanisms in a cellular context. Integration of structural and imaging measurements promises to provide foundational knowledge to rationally control and optimize DNA damage outcomes for synthetic lethality and for immune activation with resulting insights for biology and cancer interventions. PMID:28668129

Stability Study on Steel Structural Columns with Initial Blast Damage under High Temperatures

NASA Astrophysics Data System (ADS)

Baoxin, Qi; Yan, Shi; Li, Peng

2018-03-01

Blast may bring light-weight steel columns with initial damages, resulting in lowering its critical fire-resistance temperature whose reduced amplitude is relevant to the form and degree of the damages. Finite element analysis software ANSYS was used in the paper to analyze the issue of the fire-resistance temperature of the column with the blast damages, and the coupling method for heat and structure was applied during the simulation. The emphasis was laid on parametric factors of axial compression ratio, the form and the degree of the initial damages, as well as the confined condition at the ends of the columns. The numerical results showed that the fire-resistance temperature will lower as increasing of the axial compression ratio, the form and the degree of the initial damages and it will be also affected by the restraint conditions at the ends of the columns. The critical stress formula with initial bending damage under elevated temperature was set up under flexural small deformation condition, then the stability coefficient was determined and the method for evaluating the limit temperature of the column was put forward. The theoretical result was also compared with that of the finite element method (FEM). The results both showed that the stability capacity for the damaged columns was dramatically reduced as increasing the temperature and the initial damage level.

Ventral aspect of the visual form pathway is not critical for the perception of biological motion

PubMed Central

Gilaie-Dotan, Sharon; Saygin, Ayse Pinar; Lorenzi, Lauren J.; Rees, Geraint; Behrmann, Marlene

2015-01-01

Identifying the movements of those around us is fundamental for many daily activities, such as recognizing actions, detecting predators, and interacting with others socially. A key question concerns the neurobiological substrates underlying biological motion perception. Although the ventral “form” visual cortex is standardly activated by biologically moving stimuli, whether these activations are functionally critical for biological motion perception or are epiphenomenal remains unknown. To address this question, we examined whether focal damage to regions of the ventral visual cortex, resulting in significant deficits in form perception, adversely affects biological motion perception. Six patients with damage to the ventral cortex were tested with sensitive point-light display paradigms. All patients were able to recognize unmasked point-light displays and their perceptual thresholds were not significantly different from those of three different control groups, one of which comprised brain-damaged patients with spared ventral cortex (n > 50). Importantly, these six patients performed significantly better than patients with damage to regions critical for biological motion perception. To assess the necessary contribution of different regions in the ventral pathway to biological motion perception, we complement the behavioral findings with a fine-grained comparison between the lesion location and extent, and the cortical regions standardly implicated in biological motion processing. This analysis revealed that the ventral aspects of the form pathway (e.g., fusiform regions, ventral extrastriate body area) are not critical for biological motion perception. We hypothesize that the role of these ventral regions is to provide enhanced multiview/posture representations of the moving person rather than to represent biological motion perception per se. PMID:25583504

Chemical form of selenium differentially influences DNA repair pathways following exposure to lead nitrate.

PubMed

McKelvey, Shauna M; Horgan, Karina A; Murphy, Richard A

2015-01-01

Lead, an environmental toxin is known to induce a broad range of physiological and biochemical dysfunctions in humans through a number of mechanisms including the deactivation of antioxidants thus leading to generation of reactive oxygen species (ROS) and subsequent DNA damage. Selenium on the other hand has been proven to play an important role in the protection of cells from free radical damage and oxidative stress, though its effects are thought to be form and dose dependent. As the liver is the primary organ required for metabolite detoxification, HepG2 cells were chosen to assess the protective effects of various selenium compounds following exposure to the genotoxic agent lead nitrate. Initially DNA damage was quantified using a comet assay, gene expression patterns associated with DNA damage and signalling were also examined using PCR arrays and the biological pathways which were most significantly affected by selenium were identified. Interestingly, the organic type selenium compounds (selenium yeast and selenomethionine) conferred protection against lead induced DNA damage in HepG2 cells; this is evident by reduction in the quantity of DNA present in the comet tail of cells cultured in their presence with lead. This trend also followed through the gene expression changes noted in DNA damage pathways analysed. These results were in contrast with those of inorganic sodium selenite which promoted lead induced DNA damage evident in both the comet assay results and the gene expression analysis. Over all this study provided valuable insights into the effects which various selenium compounds had on the DNA damage and signalling pathway indicating the potential for using organic forms of selenium such as selenium enriched yeast to protect against DNA damaging agents. Copyright © 2014 Elsevier GmbH. All rights reserved.

TH-AB-207A-01: Contrast-Enhanced CT: Correlation of Radiation Dose and Biological Effect

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

Abadi, E; Sanders, J; Agasthya, G

2016-06-15

Purpose: The potential risk from CT is generally characterized in terms of radiation dose. The presence of iodinated-contrast medium increases radiation dose. However, it is unclear how much of this increase is biologically relevant. The purpose of this study was to establish the contribution of dose increase from iodine to biological effect. Methods: Radiation organ dose was estimated in 58 human (XCAT) phantoms “undergoing” chest CT examination (120 kVp, 9 mGy CTDI) on a simulated CT system (Definition Flash, Siemens) with and without iodinated-contrast agent (62.5 mL of iodine per subject). The dose without and with the presence of iodinemore » was compared to the increase in foci per cell (a surrogate of DNA damage) measured before and after similar CT exams without and with contrast agent (Piechowiak et al. 2015). The data were analyzed to ascertain how the enhancement in biological effect in contrast-enhanced CTs correlated with the increase in dose due to the presence of iodine. Results: The presence of iodinated-contrast in CT increased the organ doses by 2% to 50% on average. Typical values were heart (50%±7%), kidney (19%±7%), and liver (2%±3%). The corresponding increase in the average foci per cell was 107%±19%, indicating biological effect of iodine was greater than what would be anticipated from the iodine-initiated increase in radiation dose alone. Conclusion: Mean foci per cell and organ dose both increase in the presence of contrast agent. The former, however, is at least twice as large as the latter, indicating that iodine contributes to an increase in the probability of DNA damage not only as a consequence of increased x-ray energy deposition but also from other mechanisms. Hence iodine radiation dose, while relevant to be included in estimating the risk associated with contrast-enhanced CT, still can underestimate the biological effects.« less

Vitamin C for stabilising biological lasers (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kar, Ajoy K.; Mackenzie, Mark D.; Cialowicz, Katarzyna I.; Saleeb, Rebecca S.; Duncan, Rory R.

2016-04-01

We report on efforts to improve the lifetime of biological lasers through the use of ascorbic acid (also commonly known as vitamin C). Fluorescent proteins and dyes, used in biological lasers, suffer from photobleaching due to the build-up of reactive oxygen species (ROS) which causes damage leading to a decrease in emission over time. This is an issue both for laser lifetime and cell health. It has previously been shown that ascorbic acid can be effective in reducing ROS levels in a variety of applications. For our experiments human embryonic kidney cells (HEK293), containing the fluorescent dye Calcein AM, were placed between two dielectric plane mirrors to form a laser cavity. The cells were pumped using the output of a Ti:Sapphire femtosecond OPO system, frequency doubled twice in BBO crystals, giving an output of 474 nm. Initial results have shown an increase in laser lifetime when ascorbic acid is added to cells indicating a reduction in the build-up of ROS.

Nutraceuticals, aging, and cognitive dysfunction.

PubMed

Head, Elizabeth; Zicker, Steven C

2004-01-01

Decline in cognitive function that accompanies aging in dogs might have a biological basis, and many of the disorders associated with aging in canines might be preventable through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants might be one class of nutraceutical that benefits aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which can lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes might lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs; however, determining which compounds, combinations, dosage ranges, when to initiate intervention, and long-term effects constitute critical gaps in knowledge about this subject.

Host response biomarkers in the diagnosis of sepsis: a general overview.

PubMed

Parlato, Marianna; Cavaillon, Jean-Marc

2015-01-01

Critically ill patients who display a systemic inflammatory response syndrome (SIRS) are prone to develop nosocomial infections. The challenge remains to distinguish as early as possible among SIRS patients those who are developing sepsis. Following a sterile insult, damage-associated molecular patterns (DAMPs) released by damaged tissues and necrotic cells initiate an inflammatory response close to that observed during sepsis. During sepsis, pathogen-associated molecular patterns (PAMPs) trigger the release of host mediators involved in innate immunity and inflammation through identical receptors as DAMPs. In both clinical settings, a compensatory anti-inflammatory response syndrome (CARS) is concomitantly initiated. The exacerbated production of pro- or anti-inflammatory mediators allows their detection in biological fluids and particularly within the bloodstream. Some of these mediators can be used as biomarkers to decipher among the patients those who developed sepsis, and eventually they can be used as prognosis markers. In addition to plasma biomarkers, the analysis of some surface markers on circulating leukocytes or the study of mRNA and miRNA can be helpful. While there is no magic marker, a combination of few biomarkers might offer a high accuracy for diagnosis.

Fast Biological Modeling for Voxel-based Heavy Ion Treatment Planning Using the Mechanistic Repair-Misrepair-Fixation Model and Nuclear Fragment Spectra.

PubMed

Kamp, Florian; Cabal, Gonzalo; Mairani, Andrea; Parodi, Katia; Wilkens, Jan J; Carlson, David J

2015-11-01

The physical and biological differences between heavy ions and photons have not been fully exploited and could improve treatment outcomes. In carbon ion therapy, treatment planning must account for physical properties, such as the absorbed dose and nuclear fragmentation, and for differences in the relative biological effectiveness (RBE) of ions compared with photons. We combined the mechanistic repair-misrepair-fixation (RMF) model with Monte Carlo-generated fragmentation spectra for biological optimization of carbon ion treatment plans. Relative changes in double-strand break yields and radiosensitivity parameters with particle type and energy were determined using the independently benchmarked Monte Carlo damage simulation and the RMF model to estimate the RBE values for primary carbon ions and secondary fragments. Depth-dependent energy spectra were generated with the Monte Carlo code FLUKA for clinically relevant initial carbon ion energies. The predicted trends in RBE were compared with the published experimental data. Biological optimization for carbon ions was implemented in a 3-dimensional research treatment planning tool. We compared the RBE and RBE-weighted dose (RWD) distributions of different carbon ion treatment scenarios with and without nuclear fragments. The inclusion of fragments in the simulations led to smaller RBE predictions. A validation of RMF against measured cell survival data reported in published studies showed reasonable agreement. We calculated and optimized the RWD distributions on patient data and compared the RMF predictions with those from other biological models. The RBE values in an astrocytoma tumor ranged from 2.2 to 4.9 (mean 2.8) for a RWD of 3 Gy(RBE) assuming (α/β)X = 2 Gy. These studies provide new information to quantify and assess uncertainties in the clinically relevant RBE values for carbon ion therapy based on biophysical mechanisms. We present results from the first biological optimization of carbon ion radiation therapy beams on patient data using a combined RMF and Monte Carlo damage simulation modeling approach. The presented method is advantageous for fast biological optimization. Copyright © 2015 Elsevier Inc. All rights reserved.

LincRNA-p21: Implications in Human Diseases.

PubMed

Tang, Sai-Sai; Zheng, Bi-Ying; Xiong, Xing-Dong

2015-08-11

Long noncoding RNAs (lncRNAs), which lack significant protein-coding capacity, regulate various biological processes through diverse and as yet poorly understood molecular mechanisms. However, a number of studies in the past few years have documented important functions for lncRNAs in human diseases. Among these lncRNAs, lincRNA-p21 has been proposed to be a novel regulator of cell proliferation, apoptosis and DNA damage response, and involved in the initiation and progression of human diseases. In this review, we summarize the current knowledge of lincRNA-p21, mainly focus on the known biological functions and its underlying mechanisms. Moreover, we highlight the growing body of evidences for the importance of lincRNA-p21 in diverse human diseases, which indicate lincRNA-p21 as a potential diagnostic marker and/or a valuable therapeutic target for these diseases.

PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes

PubMed Central

Gupte, Rebecca; Liu, Ziying; Kraus, W. Lee

2017-01-01

The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates. Supporting these advances is a host of methodological approaches from chemical biology, proteomics, genomics, cell biology, and genetics that have propelled new discoveries in the field. New findings on the diverse roles of PARPs in chromatin regulation, transcription, RNA biology, and DNA repair have been complemented by recent advances that link ADP-ribosylation to stress responses, metabolism, viral infections, and cancer. These studies have begun to reveal the promising ways in which PARPs may be targeted therapeutically for the treatment of disease. In this review, we discuss these topics and relate them to the future directions of the field. PMID:28202539

Fatigue loading of tendon

PubMed Central

Shepherd, Jennifer H; Screen, Hazel R C

2013-01-01

Tendon injuries, often called tendinopathies, are debilitating and painful conditions, generally considered to develop as a result of tendon overuse. The aetiology of tendinopathy remains poorly understood, and whilst tendon biopsies have provided some information concerning tendon appearance in late-stage disease, there is still little information concerning the mechanical and cellular events associated with disease initiation and progression. Investigating this in situ is challenging, and numerous models have been developed to investigate how overuse may generate tendon fatigue damage and how this may relate to tendinopathy conditions. This article aims to review these models and our current understanding of tendon fatigue damage. We review the strengths and limitations of different methodologies for characterizing tendon fatigue, considering in vitro methods that adopt both viable and non-viable samples, as well as the range of different in vivo approaches. By comparing data across model systems, we review the current understanding of fatigue damage development. Additionally, we compare these findings with data from tendinopathic tissue biopsies to provide some insights into how these models may relate to the aetiology of tendinopathy. Fatigue-induced damage consistently highlights the same microstructural, biological and mechanical changes to the tendon across all model systems and also correlates well with the findings from tendinopathic biopsy tissue. The multiple testing routes support matrix damage as an important contributor to tendinopathic conditions, but cellular responses to fatigue appear complex and often contradictory. PMID:23837793

In vivo gamma-rays induced initial DNA damage and the effect of famotidine in mouse leukocytes as assayed by the alkaline comet assay.

PubMed

Mozdarani, Hossein; Nasirian, Borzo; Haeri, S Abolghasem

2007-03-01

Ionizing radiation induces a variety of lesions in DNA, each of which can be used as a bio-indicator for biological dosimetry or the study of the radioprotective effects of substances. To assess gamma ray-induced DNA damage in vivo in mouse leukocytes at various doses and the effect of famotidine, blood was collected from Balb/c male mice after irradiation with 4 Gy gamma-rays at different time intervals post-irradiation. To assess the response, mice were irradiated with doses of gamma-rays at 1 to 4 Grays. Famotidine was injected intra-peritoneally (i.p) at a dose of 5 mg/kg at various time intervals before irradiation. Four slides were prepared from each sample and alkaline comet assay was performed using standard protocols. Results obtained show that radiation significantly increases DNA damage in leukocytes in a dose dependent manner (p < 0.01) when using appropriate sampling time after irradiation, because increasing sampling time after irradiation resulted in a time dependent disappearance of DNA damage. Treatment with only 5 mg/kg famotidine before 4 Gy irradiation led to almost 50% reduction in DNA damage when compared with those animals which received radiation alone. The radioprotective capability of famotidine might be attributed to radical scavenging properties and an anti-oxidation mechanism.

[Special mechanisms for reducing life span of cells and organisms, initiated by some weak external signals].

PubMed

Bychkovskaia, I B; Fedortseva, R F

2014-01-01

The study presents the results of many-years research conducted using biological objects of different organization level. It demonstrates special species-nonspecific form of weak external signals negative effect to cells life expectancy reduction caused by program damage of cells populations. This effect is detected after weak radiation, radio-chemical and thermal influences. It leads to faster extinction of postmitotic populations which can be a reason for life expectancy reduction of multicellular organisms. A possibility of such effect inheritance in the asexual and sexual reproduction is shown. Epigenetic mechanisms of this phenomenon are assumed.

The long and short of it: the role of telomeres in fetal origins of adult disease.

PubMed

Hallows, Stephanie E; Regnault, Timothy R H; Betts, Dean H

2012-01-01

Placental insufficiency, maternal malnutrition, and other causes of intrauterine growth restriction (IUGR) can significantly affect short-term growth and long-term health. Following IUGR, there is an increased risk for cardiovascular disease and Type 2 Diabetes. The etiology of these diseases is beginning to be elucidated, and premature aging or cellular senescence through increased oxidative stress and DNA damage to telomeric ends may be initiators of these disease processes. This paper will explore the areas where telomere and telomerase biology can have significant effects on various tissues in the body in IUGR outcomes.

Biological effects of {sup 137}CsCl injected in beagle dogs

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

Nikula, K.J.; Muggenburg, B.A.; Griffith, W.C.

The toxicity of intravenously administered {sup 137}CsCl in the beagle dog was investigated as part of a program to evaluate the biological effects of internally deposited fission-product radionuclides. The intravenous route of exposure was chosen for simplicity and accuracy because it was known that after intravenous injection, inhalation or ingestion, internally deposited {sup 137}CsCl is rapidly absorbed and distributed throughout the body, exposing the whole body to {beta}-particle and {gamma} radiations. Fifty-four dogs were injected intravenously with {sup 137}Cs to provide one group of six dogs with mean initial body burdens of 141 MBq {sup 137}Cs/kg body mass and fourmore » groups of 12 dogs each with mean initial body burdens of 104, 72, 52 and 36 MBq {sup 137}Cs/kg. Twelve dogs were injected with isotonic saline as study controls. Because the number of study controls dogs was small, data from an additional 49 control dogs from other studies at the Inhalation Toxicology Research Institute that were performed over a similar span of years were also used. There was a significant, dose-dependent decrease in survival of the {sup 137}Cs-injected dogs. Eleven {sup 137}Cs-injected dogs, including all six in the highest initial body burden group, died within 81 days after injection, primarily due to hematopoietic cell damage resulting in severe pancytopenia. An additional 25 dogs had transient hematological dyscrasia but survived for long times. All {sup 137}Cs-injected male dogs had marked damage to the germinal epithelium of the testicular seminiferous tubules with azoospermia in the long-term survivors. benign and malignant neoplasms occurred in a variety of organs in {sup 137}Cs-injected dogs, rather than in a single target organ. When individual organs were considered, the incidence of malignant neoplasms was increased in the liver and in the nasal cavity and paranasal sinuses of the {sup 137}Cs-injected dogs. 34 refs., 6 figs., 6 tabs.« less

Summer Research Paper

NASA Technical Reports Server (NTRS)

Patel, Zarana

2011-01-01

Certain populations such as chemotherapy patients and atomic bomb survivors have been exposed to ionizing radiation and experience tissue damage and cancer initiation and progression. One cancer that can be initiated from radiation is esophageal squamous cell carcinoma (ESCC), an epithelial cancer that has a survival rate as low as 20%. Researchers have found that when protein tyrosine kinase receptors (RPTK) activate oncogenes, they can create epithelial tumors and cause deadly cancers like ESCC. The RPTK family has one group, MET, that has only two receptors, MET and RON, present in the human body. MET s ligand is the hepatocyte growth factor (HGF) and RON's ligand is the macrophage-stimulating protein (MSP-1). Both HGF and MSP-1 have been shown to activate their receptors and are implicated in certain processes. Since radiation damages cells throughout the biological system, researchers are investigating whether or not HGF and MSP-1 protects or kills certain normal and cancerous cells by being part of cell recovery processes. One research group recently reviewed that the HGF-MET pathway has an important role in the embryonic development in the liver, migration of myogenic precursor cells, regulation of epithelial morphogenesis and growth, and regeneration and protection in tissues. In addition, since the RON receptor is more commonly expressed in cells of epithelial origin, and when activated is part of epithelial cell matrix invasion, dissociation, and migration processes, scientists conclude that RON might be one of the factors causing epithelial cancer initiation in the biological system. In order to examine HGF and MSP-1 s effect on cancer initiation and progression we used two immortalized esophageal epithelial cell lines. One is a normal human cell line (EPC2-hTERT), while the other had a p53 mutation at the 175th amino acid position (EPC2-hTERT-p53(sup R175H)). For this investigation, we used 0(control), 2, and 4 Gray doses of gamma (Cs137) radiation and selected various concentrations from 0-100 ng/mL of HGF and MSP-1 in our assays. Since the HGF and MSP-1 pathways have proliferative roles in epithelial cells, we conducted the MTT proliferation assay to see if either drug enhances or inhibits cell proliferation over time. Also, a MTT cytotoxicity assay was necessary to observe whether the drugs are protecting the cells from radiation and if a trend is occurring depending upon the amount of dose added. In addition, a wound healing assay was done since both drugs have been to known to promote cell motility. Since cell damage occurs when radiation is added, apoptosis and micronuclei assays are vital to see if HGF and MSP-1 increase or decrease cell death and damage in normal and pre-cancerous cells and by how much based on the radiation dosage. Overall, we used the MTT, wound healing, apoptosis and micronuclei assays to investigate the effects ofHGF and MSP-1 on irradiated esophageal epithelial cells.

Numerical and Experimental Validation of a New Damage Initiation Criterion

NASA Astrophysics Data System (ADS)

Sadhinoch, M.; Atzema, E. H.; Perdahcioglu, E. S.; van den Boogaard, A. H.

2017-09-01

Most commercial finite element software packages, like Abaqus, have a built-in coupled damage model where a damage evolution needs to be defined in terms of a single fracture energy value for all stress states. The Johnson-Cook criterion has been modified to be Lode parameter dependent and this Modified Johnson-Cook (MJC) criterion is used as a Damage Initiation Surface (DIS) in combination with the built-in Abaqus ductile damage model. An exponential damage evolution law has been used with a single fracture energy value. Ultimately, the simulated force-displacement curves are compared with experiments to validate the MJC criterion. 7 out of 9 fracture experiments were predicted accurately. The limitations and accuracy of the failure predictions of the newly developed damage initiation criterion will be discussed shortly.

Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition

PubMed Central

Ferguson, Lynnette R.; Chen, Helen; Collins, Andrew R.; Connell, Marisa; Damia, Giovanna; Dasgupta, Santanu; Malhotra, Meenakshi; Meeker, Alan K.; Amedei, Amedeo; Amin, Amr; Ashraf, S. Salman; Aquilano, Katia; Azmi, Asfar S.; Bhakta, Dipita; Bilsland, Alan; Boosani, Chandra S.; Chen, Sophie; Ciriolo, Maria Rosa; Fujii, Hiromasa; Guha, Gunjan; Halicka, Dorota; Helferich, William G.; Keith, W. Nicol; Mohammed, Sulma I.; Niccolai, Elena; Yang, Xujuan; Honoki, Kanya; Parslow, Virginia R.; Prakash, Satya; Rezazadeh, Sarallah; Shackelford, Rodney E.; Sidransky, David; Tran, Phuoc T.; Yang, Eddy S.; Maxwell, Christopher A.

2015-01-01

Genomic instability can initiate cancer, augment progression, and influence the overall prognosis of the affected patient. Genomic instability arises from many different pathways, such as telomere damage, centrosome amplification, epigenetic modifications, and DNA damage from endogenous and exogenous sources, and can be perpetuating, or limiting, through the induction of mutations or aneuploidy, both enabling and catastrophic. Many cancer treatments induce DNA damage to impair cell division on a global scale but it is accepted that personalized treatments, those that are tailored to the particular patient and type of cancer, must also be developed. In this review, we detail the mechanisms from which genomic instability arises and can lead to cancer, as well as treatments and measures that prevent genomic instability or take advantage of the cellular defects caused by genomic instability. In particular, we identify and discuss five priority targets against genomic instability: (1) prevention of DNA damage; (2) enhancement of DNA repair; (3) targeting deficient DNA repair; (4) impairing centrosome clustering; and, (5) inhibition of telomerase activity. Moreover, we highlight vitamin D and B, selenium, carotenoids, PARP inhibitors, resveratrol, and isothiocyanates as priority approaches against genomic instability. The prioritized target sites and approaches were cross validated to identify potential synergistic effects on a number of important areas of cancer biology. PMID:25869442

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

Induction and repair of HZE induced cytogenetic damage

NASA Technical Reports Server (NTRS)

Brooks, A. L.; Bao, S.; Rithidech, K.; Chrisler, W. B.; Couch, L. A.; Braby, L. A.

2001-01-01

Wistar rats were exposed to high-mass, high energy (HZE) 56Fe particles (1000 GeV/AMU) using the Alternating Gradient Synchrotron (AGS). The animals were sacrificed at 1-5 hours or after a 30-day recovery period. The frequency of micronuclei in the tracheal and the deep lung epithelial cells were evaluated. The relative effectiveness of 56Fe, for the induction of initial chromosome damage in the form of micronuclei, was compared to damage produced in the same biological system exposed to other types of high and low-LET radiation. It was demonstrated that for animals sacrificed at short times after exposure, the tracheal and lung epithelial cells, the 56Fe particles were 3.3 and 1.3 times as effective as 60Co in production of micronuclei, respectively. The effectiveness was also compared to that for exposure to inhaled radon. With this comparison, the 56Fe exposure of the tracheal epithelial cells and the lung epithelial cells were only 0.18 and 0.20 times as effective as radon in the production of the initial cytogenetic damage. It was suggested that the low relative effectiveness was related to potential for 'wasted energy' from the core of the 56Fe particles. When the animals were sacrificed after 30 days, the slopes of the dose-response relationships, which reflect the remaining level of damage, decreased by a factor of 10 for both the tracheal and lung epithelial cells. In both cases, the slope of the dose-response lines were no longer significantly different from zero, and the r2 values were very high. Lung epithelial cells, isolated from the animals sacrificed hours after exposure, were maintained in culture, and the micronuclei frequency evaluated after 4 and 6 subcultures. These cells were harvested at 24 and 36 days after the exposure. There was no dose-response detected in these cultures and no signs of genomic instability at either sample time.

Damage-free vibrational spectroscopy of biological materials in the electron microscope

PubMed Central

Rez, Peter; Aoki, Toshihiro; March, Katia; Gur, Dvir; Krivanek, Ondrej L.; Dellby, Niklas; Lovejoy, Tracy C.; Wolf, Sharon G.; Cohen, Hagai

2016-01-01

Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an ‘aloof' electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies <1 eV can be ‘safely' investigated. To demonstrate the potential of aloof spectroscopy, we record electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C–H, N–H and C=O vibrational signatures with no observable radiation damage. The technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ∼10 nm, simultaneously combined with imaging in the electron microscope. PMID:26961578

Damage-free vibrational spectroscopy of biological materials in the electron microscope.

PubMed

Rez, Peter; Aoki, Toshihiro; March, Katia; Gur, Dvir; Krivanek, Ondrej L; Dellby, Niklas; Lovejoy, Tracy C; Wolf, Sharon G; Cohen, Hagai

2016-03-10

Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an 'aloof' electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies <1 eV can be 'safely' investigated. To demonstrate the potential of aloof spectroscopy, we record electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C-H, N-H and C=O vibrational signatures with no observable radiation damage. The technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ∼10 nm, simultaneously combined with imaging in the electron microscope.

Wavelength dependence of biological damage induced by UV radiation on bacteria.

PubMed

Santos, Ana L; Oliveira, Vanessa; Baptista, Inês; Henriques, Isabel; Gomes, Newton C M; Almeida, Adelaide; Correia, António; Cunha, Ângela

2013-01-01

The biological effects of UV radiation of different wavelengths (UVA, UVB and UVC) were assessed in nine bacterial isolates displaying different UV sensitivities. Biological effects (survival and activity) and molecular markers of oxidative stress [DNA strand breakage (DSB), generation of reactive oxygen species (ROS), oxidative damage to proteins and lipids, and the activity of antioxidant enzymes catalase and superoxide dismutase] were quantified and statistically analyzed in order to identify the major determinants of cell inactivation under the different spectral regions. Survival and activity followed a clear wavelength dependence, being highest under UVA and lowest under UVC. The generation of ROS, as well as protein and lipid oxidation, followed the same pattern. DNA damage (DSB) showed the inverse trend. Multiple stepwise regression analysis revealed that survival under UVA, UVB and UVC wavelengths was best explained by DSB, oxidative damage to lipids, and intracellular ROS levels, respectively.

Damage-free vibrational spectroscopy of biological materials in the electron microscope

DOE PAGES

Rez, Peter; Aoki, Toshihiro; March, Katia; ...

2016-03-10

Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an ‘aloof’ electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies o1 eV can be ‘safely’ investigated. To demonstrate the potential of aloof spectroscopy, we record electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C–H, N–H and C=O vibrational signatures with nomore » observable radiation damage. Furthermore, the technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ~10nm, simultaneously combined with imaging in the electron microscope.« less

Damage-free vibrational spectroscopy of biological materials in the electron microscope

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

Rez, Peter; Aoki, Toshihiro; March, Katia

Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an ‘aloof’ electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies o1 eV can be ‘safely’ investigated. To demonstrate the potential of aloof spectroscopy, we record electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C–H, N–H and C=O vibrational signatures with nomore » observable radiation damage. Furthermore, the technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ~10nm, simultaneously combined with imaging in the electron microscope.« less

The Biological Effectiveness of Four Energies of Neon Ions for the Induction of Chromosome Damage in Human Lymphocytes

NASA Technical Reports Server (NTRS)

George, Kerry; Hada, Megumi; Cucinotta, F. A.

2011-01-01

Chromosomal aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to neon ions at energies of 64, 89, 142, or 267. The corresponding LET values for these energies of neon ranged from 38-103 keV/micrometers and doses delivered were in the 10 to 80 cGy range. Chromosome exchanges were assessed in metaphase and G2 phase cells at first division after exposure using fluorescence in situ hybridization (FISH) with whole chromosome probes and dose response curves were generated for different types of chromosomal exchanges. The yields of total chromosome exchanges were similar for the 64, 89, and 142 MeV exposures, whereas the 267 MeV/u neon with LET of 38 keV/micrometers produced about half as many exchanges per unit dose. The induction of complex type chromosome exchanges (exchanges involving three or more breaks and two or more chromosomes) showed a clear LET dependence for all energies. The ratio of simple to complex type exchanges increased with LET from 18 to 51%. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose response curve for chromosome damage with respect to gamma-rays. The RBE(sub max) values for total chromosome exchanges for the 64 MeV/u was around 30.

Compression of laminated composite beams with initial damage

NASA Technical Reports Server (NTRS)

Breivik, Nicole L.; Gurdal, Zafer; Griffin, O. H., Jr.

1993-01-01

The effect of isolated damage modes on the compressive strength and failure characteristics of laminated composite test specimens were evaluated experimentally and numerically. In addition to specimens without initial damage, specimens with three types of initial damage were considered: (1) specimens with short delaminations distributed evenly through the specimen thickness, (2) specimens with few long delaminations, and (3) specimens with local fiber damage in the surface plies under the three-point bend contact point. It was found that specimens with short multiple delamination experienced the greatest reduction in compression strength compared to the undamaged specimens. Single delaminations far from the specimen surface had little effect on the final compression strength, and moderate strength reduction was observed for specimens with localized surface ply damage.

Modeling electrical power absorption and thermally-induced biological tissue damage.

PubMed

Zohdi, T I

2014-01-01

This work develops a model for thermally induced damage from high current flow through biological tissue. Using the first law of thermodynamics, the balance of energy produced by the current and the energy absorbed by the tissue are investigated. The tissue damage is correlated with an evolution law that is activated upon exceeding a temperature threshold. As an example, the Fung material model is used. For certain parameter choices, the Fung material law has the ability to absorb relatively significant amounts of energy, due to its inherent exponential response character, thus, to some extent, mitigating possible tissue damage. Numerical examples are provided to illustrate the model's behavior.

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.

A Computational Efficient Physics Based Methodology for Modeling Ceramic Matrix Composites (Preprint)

DTIC Science & Technology

2011-11-01

elastic range, and with some simple forms of progressing damage . However, a general physics-based methodology to assess the initial and lifetime... damage evolution in the RVE for all possible load histories. Microstructural data on initial configuration and damage progression in CMCs were...the damaged elements will have changed, hence, a progressive damage model. The crack opening for each crack type in each element is stored as a

Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Katz, Robert; Wilson, John W.; Townsend, Lawrence W.; Nealy, John E.; Shinn, Judy L.

1991-01-01

The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space.

A spatial-dynamic value transfer model of economic losses from a biological invasion

Treesearch

Thomas P. Holmes; Andrew M. Liebhold; Kent F. Kovacs; Betsy Von Holle

2010-01-01

Rigorous assessments of the economic impacts of introduced species at broad spatial scales are required to provide credible information to policy makers. We propose that economic models of aggregate damages induced by biological invasions need to link microeconomic analyses of site-specific economic damages with spatial-dynamic models of value change associated with...

LincRNA-p21: Implications in Human Diseases

PubMed Central

Tang, Sai-Sai; Zheng, Bi-Ying; Xiong, Xing-Dong

2015-01-01

Long noncoding RNAs (lncRNAs), which lack significant protein-coding capacity, regulate various biological processes through diverse and as yet poorly understood molecular mechanisms. However, a number of studies in the past few years have documented important functions for lncRNAs in human diseases. Among these lncRNAs, lincRNA-p21 has been proposed to be a novel regulator of cell proliferation, apoptosis and DNA damage response, and involved in the initiation and progression of human diseases. In this review, we summarize the current knowledge of lincRNA-p21, mainly focus on the known biological functions and its underlying mechanisms. Moreover, we highlight the growing body of evidences for the importance of lincRNA-p21 in diverse human diseases, which indicate lincRNA-p21 as a potential diagnostic marker and/or a valuable therapeutic target for these diseases. PMID:26270659

Oxidative stress, free radicals and protein peroxides.

PubMed

Gebicki, Janusz M

2016-04-01

Primary free radicals generated under oxidative stress in cells and tissues produce a cascade of reactive secondary radicals, which attack biomolecules with efficiency determined by the reaction rate constants and target concentration. Proteins are prominent targets because they constitute the bulk of the organic content of cells and tissues and react readily with many of the secondary radicals. The reactions commonly lead to the formation of carbon-centered radicals, which generally convert in vivo to peroxyl radicals and finally to semistable hydroperoxides. All of these intermediates can initiate biological damage. This article outlines the advantages of the application of ionizing radiations to studies of radicals, with particular reference to the generation of desired radicals, studies of the kinetics of their reactions and correlating the results with events in biological systems. In one such application, formation of protein hydroperoxides in irradiated cells was inhibited by the intracellular ascorbate and glutathione. Copyright © 2015 Elsevier Inc. All rights reserved.

PARPs and ADP-Ribosylation: 50 Years … and Counting.

PubMed

Kraus, W Lee

2015-06-18

Over 50 years ago, the discovery of poly(ADP-ribose) (PAR) set a new field of science in motion-the field of poly(ADP-ribosyl) transferases (PARPs) and ADP-ribosylation. The field is still flourishing today. The diversity of biological processes now known to require PARPs and ADP-ribosylation was practically unimaginable even two decades ago. From an initial focus on DNA damage detection and repair in response to genotoxic stresses, the field has expanded to include the regulation of chromatin structure, gene expression, and RNA processing in a wide range of biological systems, including reproduction, development, aging, stem cells, inflammation, metabolism, and cancer. This special focus issue of Molecular Cell includes a collection of three Reviews, three Perspectives, and a SnapShot, which together summarize the current state of the field and suggest where it may be headed. Copyright © 2015 Elsevier Inc. All rights reserved.

Bioterrorism for the respiratory physician.

PubMed

Waterer, Grant W; Robertson, Hannah

2009-01-01

Terrorist attacks by definition are designed to cause fear and panic. There is no question that a terrorist attack using biological agents would present a grave threat to stability of the society in which they were released. Early recognition of such a bioterrorist attack is crucial to containing the damage they could cause. As many of the most likely bioterrorism agents present with pulmonary disease, respiratory physicians may be crucial in the initial recognition and diagnosis phase, and certainly would be drawn into treatment of affected individuals. This review focuses on the biological agents thought most likely to be used by terrorists that have predominantly respiratory presentations. The primary focus of this review is on anthrax, plague, tularaemia, ricin, and Staphylococcal enterotoxin B. The pathogenesis, clinical manifestations and treatment of these agents will be discussed as well as historical examples of their use. Other potential bioterrorism agents with respiratory manifestations will also be discussed briefly.

Astrophysical and biological constraints on radiopanspermia.

PubMed

Secker, J; Wesson, P S; Lepock, J R

1996-08-01

We have carried out a series of calculations involving bacteria and viruses embedded in dust grains, which are ejected from our solar system by radiation pressure and travel through space to other star systems. Under many conditions this type of panspermia is impractical, primarily because the ultraviolet (UV) radiation of the present Sun inactivates the micro-organisms. However, if the organisms are shielded by an absorbing material like carbon and if ejection takes place in the red-giant phase of a one solar mass star like our Sun, there is a significant probability that the micro-organisms can reach another star system alive (i.e. with only sub-lethal damage from UV and ionizing radiation). In addition to panspermia with viable micro-organisms, it is possible to seed the Galaxy with inactivated ones whose DNA and RNA fragments may provide the initial information necessary to start biological evolution in favourable environments.

Numerical investigation of contact stresses for fretting fatigue damage initiation

NASA Astrophysics Data System (ADS)

Bhatti, N. A.; Abdel Wahab, M.

2017-05-01

Fretting fatigue phenomena occurs due to interaction between contacting bodies under application of cyclic and normal loads. In addition to environmental conditions and material properties, the response at the contact interface highly depends on the combination of applied loads. High stress concentration is present at the contact interface, which can start the damage nucleation process. At the culmination of nucleation process several micro cracks are initiated, ultimately leading to the structural failure. In this study, effect of ratio of tangential to normal load on contact stresses, slip amplitude and damage initiation is studied using finite element analysis. The results are evaluated for Ruiz parameter as it involves the slip amplitude which in an important factor in fretting fatigue conditions. It is observed that tangential to normal load ratio influences the stick zone size and damage initiation life. Furthermore, it is observed that tensile stress is the most important factor that drives the damage initiation to failure for the cases where failure occurs predominantly in mode I manner.

Biological characterization of a novel in vitro cell irradiator

PubMed Central

Fowler, Tyler L.; Fisher, Michael M.; Bailey, Alison M.; Bednarz, Bryan P.

2017-01-01

To evaluate the overall robustness of a novel cellular irradiator we performed a series of well-characterized, dose-responsive assays to assess the consequences of DNA damage. We used a previously described novel irradiation system and a traditional 137Cs source to irradiate a cell line. The generation of reactive oxygen species was assessed using chloromethyl-H2DCFDA dye, the induction of DNA DSBs was observed using the comet assay, and the initiation of DNA break repair was assessed through γH2AX image cytometry. A high correlation between physical absorbed dose and biologic dose was seen for the production of intracellular reactive oxygen species, physical DNA double strand breaks, and modulation of the cellular double stand break pathway. The results compared favorably to irradiation with a traditional 137Cs source. The rapid, straightforward tests described form a reasonable approach for biologic characterization of novel irradiators. These additional testing metrics go beyond standard physics testing such as Monte Carlo simulation and thermo-luminescent dosimeter evaluation to confirm that a novel irradiator can produce the desired dose effects in vitro. Further, assessment of these biological metrics confirms that the physical handling of the cells during the irradiation process results in biologic effects that scale appropriately with dose. PMID:29232400

A Hybrid Approach to Composite Damage and Failure Analysis Combining Synergistic Damage Mechanics and Peridynamics

DTIC Science & Technology

2016-03-31

fiber distributions. Task 2.1 is concerned with damage evolution in a peridynamic model of poroelastic materials. Initial results for both tasks are...distributions. Task 2.1 is concerned with damage evolution in a peridynamic model of poroelastic materials. Initial results for both tasks are reported and...Task 2.1: Damage evolution in a peridynamic model of poroelastic materials. Background and Motivation In order to model the presence of pores and

The role of TGF-β/SMAD4 signaling in cancer.

PubMed

Zhao, Ming; Mishra, Lopa; Deng, Chu-Xia

2018-01-01

Transforming growth factor β (TGF-β) signaling pathway plays important roles in many biological processes, including cell growth, differentiation, apoptosis, migration, as well as cancer initiation and progression. SMAD4, which serves as the central mediator of TGF-β signaling, is specifically inactivated in over half of pancreatic duct adenocarcinoma, and varying degrees in many other types of cancers. In the past two decades, multiple studies have revealed that SMAD4 loss on its own does not initiate tumor formation, but can promote tumor progression initiated by other genes, such as KRAS activation in pancreatic duct adenocarcinoma and APC inactivation in colorectal cancer. In other cases, such as skin cancer, loss of SMAD4 plays an important initiating role by disrupting DNA damage response and repair mechanisms and enhance genomic instability, suggesting its distinct roles in different types of tumors. This review lists SMAD4 mutations in various types of cancer and summarizes recent advances on SMAD4 with focuses on the function, signaling pathway, and the possibility of SMAD4 as a prognostic indicator.

The role of TGF-β/SMAD4 signaling in cancer

PubMed Central

Zhao, Ming; Mishra, Lopa; Deng, Chu-Xia

2018-01-01

Transforming growth factor β (TGF-β) signaling pathway plays important roles in many biological processes, including cell growth, differentiation, apoptosis, migration, as well as cancer initiation and progression. SMAD4, which serves as the central mediator of TGF-β signaling, is specifically inactivated in over half of pancreatic duct adenocarcinoma, and varying degrees in many other types of cancers. In the past two decades, multiple studies have revealed that SMAD4 loss on its own does not initiate tumor formation, but can promote tumor progression initiated by other genes, such as KRAS activation in pancreatic duct adenocarcinoma and APC inactivation in colorectal cancer. In other cases, such as skin cancer, loss of SMAD4 plays an important initiating role by disrupting DNA damage response and repair mechanisms and enhance genomic instability, suggesting its distinct roles in different types of tumors. This review lists SMAD4 mutations in various types of cancer and summarizes recent advances on SMAD4 with focuses on the function, signaling pathway, and the possibility of SMAD4 as a prognostic indicator. PMID:29483830

Progressive Fracture of Fiber Composite Builtup Structures

NASA Technical Reports Server (NTRS)

Gotsis, Pascal K.; Chamis, Christos C.; Minnetyan, Levon

1996-01-01

The damage progression and fracture of builtup composite structures was evaluated by using computational simulation to examine the behavior and response of a stiffened composite (0 +/- 45/90)(sub s6) laminate panel subjected to a bending load. The damage initiation, growth, accumulation, progression, and propagation to structural collapse were simulated. An integrated computer code (CODSTRAN) was augmented for the simulation of the progressive damage and fracture of builtup composite structures under mechanical loading. Results showed that damage initiation and progression have a significant effect on the structural response. Also investigated was the influence of different types of bending load on the damage initiation, propagation, and final fracture of the builtup composite panel.

The Effect of a Mars Mission on Chromosome Damage in the Blood Lymphocytes of Astronauts

NASA Technical Reports Server (NTRS)

George, Kerry A.; Durante, M.; Cucinnotta, F. A.

2006-01-01

The radiation environment encountered during a manned mission to Mars will lead to significant elevation of biological damage in astronauts. Here we present estimates of the increased frequencies of chromosome aberrations in the peripheral blood lymphocytes of astronauts after a hypothetical Mars mission using radiation dose estimations and lymphocyte biology. Results will incorporate previously published data on in vivo induced chromosome damage in the blood lymphocytes of crewmembers after ISS and Mir missions, along with recent findings on the time dependant decay of chromosome aberrations after space flight.

Induction and repair of DNA strand breaks in bovine lens epithelial cells after high LET irradiation

NASA Astrophysics Data System (ADS)

Baumstark-Khan, C.; Heilmann, J.; Rink, H.

The lens epithelium is the initiation site for the development of radiation induced cataracts. Radiation in the cortex and nucleus interacts with proteins, while in the epithelium, experimental results reveal mutagenic and cytotoxic effects. It is suggested that incorrectly repaired DNA damage may be lethal in terms of cellular reproduction and also may initiate the development of mutations or transformations in surviving cells. The occurrence of such genetically modified cells may lead to lens opacification. For a quantitative risk estimation for astronauts and space travelers it is necessary to know the relative biological effectiveness (RBE), because the spacial and temporal distribution of initial physical damage induced by cosmic radiation differ significantly from that of X-rays. RBEs for the induction of DNA strand breaks and the efficiency of repair of these breaks were measured in cultured diploid bovine lens epithelial cells exposed to different LET irradiation to either 300 kV X-rays or to heavy ions at the UNILAC accelerator at GSI. Accelerated ions from Z=8 (O) to Z=92 (U) were used. Strand breaks were measured by hydroxyapatite chromatography of alkaline unwound DNA (overall strand breaks). Results showed that DNA damage occurs as a function of dose, of kinetic energy and of LET. For particles having the same LET the severity of the DNA damage increases with dose. For a given particle dose, as the LET rises, the numbers of DNA strand breaks increase to a maximum and then reach a plateau or decrease. Repair kinetics depend on the fluence (irradiation dose). At any LET value, repair is much slower after heavy ion exposure than after X-irradiation. For ions with an LET of less than 10,000 keV μ -1 more than 90 percent of the strand breaks induced are repaired within 24 hours. At higher particle fluences, especially for low energetic particles with a very high local density of energy deposition within the particle track, a higher proportion of non-rejoined breaks is found, even after prolonged periods of incubation. At the highest LET value (16,300 keV μ -1 no significant repair is observed. These LET-dependencies are consistent with the current mechanistic model for radiation induced cataractogenesis which postulates that genomic damage to the surviving fraction of epithelial cells is responsible for lens opacification.

Direct observation of ultrafast-electron-transfer reactions unravels high effectiveness of reductive DNA damage

PubMed Central

Nguyen, Jenny; Ma, Yuhan; Luo, Ting; Bristow, Robert G.; Jaffray, David A.; Lu, Qing-Bin

2011-01-01

Both water and electron-transfer reactions play important roles in chemistry, physics, biology, and the environment. Oxidative DNA damage is a well-known mechanism, whereas the relative role of reductive DNA damage is unknown. The prehydrated electron (), a novel species of electrons in water, is a fascinating species due to its fundamental importance in chemistry, biology, and the environment. is an ideal agent to observe reductive DNA damage. Here, we report both the first in situ femtosecond time-resolved laser spectroscopy measurements of ultrafast-electron-transfer (UET) reactions of with various scavengers (KNO3, isopropanol, and dimethyl sulfoxide) and the first gel electrophoresis measurements of DNA strand breaks induced by and OH• radicals co-produced by two-UV-photon photolysis of water. We strikingly found that the yield of reductive DNA strand breaks induced by each is twice the yield of oxidative DNA strand breaks induced by each OH• radical. Our results not only unravel the long-standing mystery about the relative role of radicals in inducing DNA damage under ionizing radiation, but also challenge the conventional notion that oxidative damage is the main pathway for DNA damage. The results also show the potential of femtomedicine as a new transdisciplinary frontier and the broad significance of UET reactions of in many processes in chemistry, physics, biology, and the environment. PMID:21730183

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

NASA Astrophysics Data System (ADS)

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

1999-07-01

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

Laser damage initiation and growth of antireflection coated S-FAP crystal surfaces prepared by pitch lap and magnetorheological finishing

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

Stolz, C J; Menapace, J A; Schaffers, K I

Antireflection (AR) coatings typically damage at the interface between the substrate and coating. Therefore the substrate finishing technology can have an impact on the laser resistance of the coating. For this study, AR coatings were deposited on Yb:S-FAP [Yb{sup 3+}:Sr{sub 5}(PO{sub 4}){sub 3}F] crystals that received a final polish by both conventional pitch lap finishing as well as magnetorheological finishing (MRF). SEM images of the damage morphology reveals laser damage originates at scratches and at substrate coating interfacial absorbing defects. Previous damage stability tests on multilayer mirror coatings and bare surfaces revealed damage growth can occur at fluences below themore » initiation fluence. The results from this study suggest the opposite trend for AR coatings. Investigation of unstable HR and uncoated surface damage morphologies reveals significant radial cracking that is not apparent with AR damage due to AR delamination from the coated surface with few apparent cracks at the damage boundary. Damage stability tests show that coated Yb:S-FAP crystals can operate at 1057 nm at fluences around 20 J/cm{sup 2} at 10 ns; almost twice the initiation damage threshold.« less

Evaluation of a contraction flow field on hydrodynamic damage to entomopathogenic nematodes-A biological pest control agent.

PubMed

Fife, Jane P; Derksen, Richard C; Ozkan, H Erdal; Grewal, Parwinder S; Chalmers, Jeffrey J; Krause, Charles R

2004-04-05

Mechanized production and delivery of biological pesticides presents challenges because the biological agents must remain viable during these processes. This study evaluates the effect of flow through an abrupt contraction, where flow characteristics similar to that found within bioprocesses and spray equipment are developed, on damage to a benchmark biological pest control agent, entomopathogenic nematodes (EPNs). An opposed-pistons, contraction flow device generated volumetric flow rates ranging between 8.26 cm(3)/s and 41.3 cm(3)/s. Four EPN species were evaluated: Heterorhabditis bacteriophora, Heterorhabditis megidis, Steinernema carpocapsae, and Steinernema glaseri. Damage was quantified by counting living and dead EPNs. Optical and cold field emission scanning electron microscope (CFE-SEM) images provided qualitative information to describe how the damage occurred. The experimental flow field was completely described using FLUENT, a computational fluid dynamics program. Local flow parameters computed in FLUENT were compared to EPN damage. The type and extent of damage varied between EPN species. Damaged Heterorhabditis spp. generally remained whole with an internal rupture located near the center of the body, while Steinernema spp. most often broke into several pieces. The fast-transient stress field generated at the entrance to the contraction caused a momentary tensile loading and then relaxation that damaged the EPNs. At high flow rates, the tensile stresses became large enough to cause failure of the EPN structural membrane. The relative elasticity of the EPN structural membrane may explain the differences in damage observed between the species. It is speculated that the internal rupture of the Heterorhabditis spp. occurred during the processes of stretching and relaxing at the contraction entrance. Appreciable damage was observed at lower average energy dissipation rates for H. bacteriophora (1.23E + 8 W/m(3)), H. megidis (1.72E + 8 W/m(3)), and S. glaseri (2.89E + 8 W/m(3)) compared to S. carpocapsae (3.70E + 8 W/m(3)). Energy dissipation rates within an equipment component should be kept below 1E + 8 W/m(3) to avoid hydrodynamic damage to EPNs. The relationship between average energy dissipation and EPN damage provides important information for future simulation efforts of actual spray equipment components. Copyright 2004 Wiley Periodicals, Inc.

The Hypoxic Testicle: Physiology and Pathophysiology

PubMed Central

Reyes, Juan G.; Farias, Jorge G.; Henríquez-Olavarrieta, Sebastián; Madrid, Eva; Parraga, Mario; Zepeda, Andrea B.; Moreno, Ricardo D.

2012-01-01

Mammalian spermatogenesis is a complex biological process occurring in the seminiferous tubules in the testis. This process represents a delicate balance between cell proliferation, differentiation, and apoptosis. In most mammals, the testicles are kept in the scrotum 2 to 7°C below body core temperature, and the spermatogenic process proceeds with a blood and oxygen supply that is fairly independent of changes in other vascular beds in the body. Despite this apparently well-controlled local environment, pathologies such as varicocele or testicular torsion and environmental exposure to low oxygen (hypoxia) can result in changes in blood flow, nutrients, and oxygen supply along with an increased local temperature that may induce adverse effects on Leydig cell function and spermatogenesis. These conditions may lead to male subfertility or infertility. Our literature analyses and our own results suggest that conditions such as germ cell apoptosis and DNA damage are common features in hypoxia and varicocele and testicular torsion. Furthermore, oxidative damage seems to be present in these conditions during the initiation stages of germ cell damage and apoptosis. Other mechanisms like membrane-bound metalloproteinases and phospholipase A2 activation could also be part of the pathophysiological consequences of testicular hypoxia. PMID:23056665

Response of an invasive liana to simulated herbivory: implications for its biological control

NASA Astrophysics Data System (ADS)

Raghu, S.; Dhileepan, K.; Treviño, M.

2006-05-01

Pre-release evaluation of the efficacy of biological control agents is often not possible in the case of many invasive species targeted for biocontrol. In such circumstances simulating herbivory could yield significant insights into plant response to damage, thereby improving the efficiency of agent prioritisation, increasing the chances of regulating the performance of invasive plants through herbivory and minimising potential risks posed by release of multiple herbivores. We adopted this approach to understand the weaknesses herbivores could exploit, to manage the invasive liana, Macfadyena unguis-cati. We simulated herbivory by damaging the leaves, stem, root and tuber of the plant, in isolation and in combination. We also applied these treatments at multiple frequencies. Plant response in terms of biomass allocation showed that at least two severe defoliation treatments were required to diminish this liana's climbing habit and reduce its allocation to belowground tuber reserves. Belowground damage appears to have negligible effect on the plant's biomass production and tuber damage appears to trigger a compensatory response. Plant response to combinations of different types of damage did not differ significantly to that from leaf damage. This suggests that specialist herbivores in the leaf-feeding guild capable of removing over 50% of the leaf tissue may be desirable in the biological control of this invasive species.

From Snow to Hill to ALS: An epidemiological odyssey in search of ALS causation.

PubMed

Armon, Carmel

2018-05-21

Establishing mechanisms of disease causation in neurodegenerative diseases has long seemed to be beyond the pale of traditional epidemiological tools. Establishing a plausible mechanism for initiation of amyotrophic lateral sclerosis (ALS) has appeared a particularly elusive goal. This review shows that a likely mechanism for ALS initiation may be inferred by applying classical methods of epidemiological inference. Advances in characterizing the biology of ALS suggest that most cases of ALS are cortically-generated, part of the ALS-FTD spectrum, with focal onset and spread by contiguity within the motor super-network. Evidence-based methods identified the most credible exogenous risk factor - smoking. AB Hill's nine viewpoints to inferring causation from association were invoked. The most likely mechanism consistent with smoking being a risk factor for ALS was inferred: cumulative DNA damage, akin to cumulative somatic mutations in carcinogenesis. Focal onset supports the concept that these changes, occurring in a single cell, may trigger the cascade leading to clinical ALS. The plausibility of this mechanism was affirmed by its coherence/consistency with other observations in sporadic, familial and western Pacific ALS. Application of traditional epidemiological reasoning suggests that cumulative DNA damage may contribute to disease onset in ALS. Copyright © 2018 Elsevier B.V. All rights reserved.

Biological damage induced by ionizing cosmic rays in dry Arabidopsis seeds.

PubMed

Kranz, A R; Bork, U; Bucker, H; Reitz, G

1990-01-01

In September 1987 dry seeds containing embryos of the crucifer plant Arabidopsis thaliana (L.) Heynh, were flown in orbit for 13 days on the Kosmos 1887 satellite. The seeds were fixed on CNd detectors and stored in units of Biorack type I/O. One unit was exposed inside, another one outside the satellite. The temperature profile of the flown seeds inside the satellite was simulated on earth in an identical backup control sample (BC). An additional control (SC) was studied with the original seeds sample. By use of the CNd-detector, HZE-tracks were measured with a PC-assisted microscope. The biological damages were investigated by growing the seeds under controlled climatic conditions. The following biological endpoints of the cosmic radiation damage were studied: germination, radicle length, sublethality, morphological aberrations, flower development, tumorization, embryo lethality inside the siliques. The summarized damage (D) and the mutation frequencies of embyronic lethal genes were calculated. The following results were obtained: the damages increase significantly in orbit at all biological endpoints; germination and fiowerings especially, as well as embryo lethality of fruits and lethal mutation frequency, were maximum mostly for HZE-hit seeds. Additionally, an increase of damage was observed for the seeds of the outside-exposed Biorack in comparison to the inside ones, which was probably caused by less radiation shielding and free space vacuum. The significance of the results obtained is discussed with respect to stress and risk and, thus, the quality of the RBE-factors and heavy ionizing radiation all needed for the very definition of radiation protection standards in space.

Higher Initial DNA Damage and Persistent Cell Cycle Arrest after Carbon Ion Irradiation Compared to X-irradiation in Prostate and Colon Cancer Cells

PubMed Central

Suetens, Annelies; Konings, Katrien; Moreels, Marjan; Quintens, Roel; Verslegers, Mieke; Soors, Els; Tabury, Kevin; Grégoire, Vincent; Baatout, Sarah

2016-01-01

The use of charged-particle beams, such as carbon ions, is becoming a more and more attractive treatment option for cancer therapy. Given the precise absorbed dose-localization and an increased biological effectiveness, this form of therapy is much more advantageous compared to conventional radiotherapy, and is currently being used for treatment of specific cancer types. The high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. In order to better understand the underlying mechanisms responsible for the increased biological effectiveness, we investigated the DNA damage and repair kinetics and cell cycle progression in two p53 mutant cell lines, more specifically a prostate (PC3) and colon (Caco-2) cancer cell line, after exposure to different radiation qualities. Cells were irradiated with various absorbed doses (0, 0.5, and 2 Gy) of accelerated 13C-ions at the Grand Accélérateur National d’Ions Lourds facility (Caen, France) or with X-rays (0, 0.1, 0.5, 1, 2, and 5 Gy). Microscopic analysis of DNA double-strand breaks showed dose-dependent increases in γ-H2AX foci numbers and foci occupancy after exposure to both types of irradiation, in both cell lines. However, 24 h after exposure, residual damage was more pronounced after lower doses of carbon ion irradiation compared to X-irradiation. Flow cytometric analysis showed that carbon ion irradiation induced a permanent G2/M arrest in PC3 cells at lower doses (2 Gy) compared to X-rays (5 Gy), while in Caco-2 cells the G2/M arrest was transient after irradiation with X-rays (2 and 5 Gy) but persistent after exposure to carbon ions (2 Gy). PMID:27148479

Metabolite damage and repair in metabolic engineering design.

PubMed

Sun, Jiayi; Jeffryes, James G; Henry, Christopher S; Bruner, Steven D; Hanson, Andrew D

2017-11-01

The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects. Copyright © 2017 International Metabolic Engineering Society. All rights reserved.

Metabolite damage and repair in metabolic engineering design

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

Sun, Jiayi; Jeffryes, James G.; Henry, Christopher S.

The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields,more » and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects.« less

Oxidative Stress, Aging and CNS disease in the Canine Model of Human Brain Aging

PubMed Central

Head, Elizabeth; Rofina, Jaime; Zicker, Steven

2008-01-01

SYNOPSIS Decline in cognitive functions that accompany aging in dogs may have a biological basis, and many of the disorders associated with aging in canines may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of both laboratory and clinical studies – antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs. However, determining all effective compounds and combinations, dosage ranges, as well as when to initiate intervention and long term effects constitute gaps in our current knowledge. PMID:18249248

DNA fragmentation induced by Fe ions in human cells: shielding influence on spatially correlated damage

NASA Technical Reports Server (NTRS)

Antonelli, F.; Belli, M.; Campa, A.; Chatterjee, A.; Dini, V.; Esposito, G.; Rydberg, B.; Simone, G.; Tabocchini, M. A.

2004-01-01

Outside the magnetic field of the Earth, high energy heavy ions constitute a relevant part of the biologically significant dose to astronauts during the very long travels through space. The typical pattern of energy deposition in the matter by heavy ions on the microscopic scale is believed to produce spatially correlated damage in the DNA which is critical for radiobiological effects. We have investigated the influence of a lucite shielding on the initial production of very small DNA fragments in human fibroblasts irradiated with 1 GeV/u iron (Fe) ions. We also used gamma rays as reference radiation. Our results show: (1) a lower effect per incident ion when the shielding is used; (2) an higher DNA Double Strand Breaks (DSB) induction by Fe ions than by gamma rays in the size range 1-23 kbp; (3) a non-random DNA DSB induction by Fe ions. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

Cellular characterization of compression induced-damage in live biological samples

NASA Astrophysics Data System (ADS)

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

2011-06-01

Understanding the dysfunctions that high-intensity compression waves induce in human tissues is critical to impact on acute-phase treatments and requires the development of experimental models of traumatic damage in biological samples. In this study we have developed an experimental system to directly assess the impact of dynamic loading conditions on cellular function at the molecular level. Here we present a confinement chamber designed to subject live cell cultures in liquid environment to compression waves in the range of tens of MPa using a split Hopkinson pressure bars system. Recording the loading history and collecting the samples post-impact without external contamination allow the definition of parameters such as pressure and duration of the stimulus that can be related to the cellular damage. The compression experiments are conducted on Mesenchymal Stem Cells from BALB/c mice and the damage analysis are compared to two control groups. Changes in Stem cell viability, phenotype and function are assessed flow cytometry and with in vitro bioassays at two different time points. Identifying the cellular and molecular mechanisms underlying the damage caused by dynamic loading in live biological samples could enable the development of new treatments for traumatic injuries.

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

NASA Astrophysics Data System (ADS)

Saito, Takeshi; Fujii, Noriko

2014-05-01

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

Effect of mechanical damage on emission of volatile organic compounds from plant leaves and implications for evaluation of host plant specificity of prospective biological control agents of weeds

USDA-ARS?s Scientific Manuscript database

Assessment of host plant specificity is a critical step in the evaluation of classical biological control agents of weeds, which is necessary for avoiding possible damage to nontarget plants. Volatile organic compounds (VOC) emitted by plants likely play an important role in determining which plant...

Novel platinum black electroplating technique improving mechanical stability.

PubMed

Kim, Raeyoung; Nam, Yoonkey

2013-01-01

Platinum black microelectrodes are widely used as an effective neural signal recording sensor. The simple fabrication process, high quality signal recording and proper biocompatibility are the main advantages of platinum black microelectrodes. When microelectrodes are exposed to actual biological system, various physical stimuli are applied. However, the porous structure of platinum black is vulnerable to external stimuli and destroyed easily. The impedance level of the microelectrode increases when the microelectrodes are damaged resulting in decreased recording performance. In this study, we developed mechanically stable platinum black microelectrodes by adding polydopamine. The polydopamine layer was added between the platinum black structures by electrodeposition method. The initial impedance level of platinum black only microelectrodes and polydopamine added microelectrodes were similar but after applying ultrasonication the impedance value dramatically increased for platinum black only microelectrodes, whereas polydopamine added microelectrodes showed little increase which were nearly retained initial values. Polydopamine added platinum black microelectrodes are expected to extend the availability as neural sensors.

Biophysical and biological factors determining the ability to achieve long-term cryobiological preservation

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

Mazur, P.

1997-12-01

The BESTCapsule will maintain appropriate biological specimens for decades or centuries at cryogenic temperatures in the living state. Maintenance at temperatures below {approximately} {minus}140 C is not a problem. No ordinary chemical reactions in aqueous solutions can occur. The only source of damage will be the slow accumulation of physical damage to DNA from background ionizing radiation. But this source of damage should not become serious in less than a millennium. Rather, the main problem in cryopreservation is to devise procedures for cooling the biological specimens to {minus}196 C and returning them to normal temperatures without inflicting lethal injury. Regardlessmore » of the cell type, there are certain encompassing biophysical factors and constraints that determine whether they will survive or die during freezing and thawing. Superimposed on these may be special biological factors that apply to specific cell types. This paper will emphasize the former and give illustrative examples of the latter.« less

Solar Irradiance Changes And Photobiological Effects At Earth's Surface Following Astrophysical Ionizing Radiation Events

NASA Astrophysics Data System (ADS)

Thomas, Brian; Neale, Patrick

2016-01-01

Astrophysical ionizing radiation events have been recognized as a potential threat to life on Earth for decades. Although there is some direct biological damage on the surface from redistributed radiation several studies have indicated that the greatest long term threat is from ozone depletion and subsequent heightened solar ultraviolet (UV) radiation. It is known that organisms exposed to this irradiation experience harmful effects such as sunburn and even direct damage to DNA, proteins, or other cellular structures. Simulations of the atmospheric effects of a variety of events (such as supernovae, gamma-ray bursts, and solar proton events) have been previously published, along with estimates of biological damage at Earth's surface. In the present work, we employed a radiative transfer model to expand and improve calculations of surface-level irradiance and biological impacts following an ionizing radiation event. We considered changes in surface-level UVB, UVA, and photosynthetically active radiation (visible light). Using biological weighting functions we have considered a wide range of effects, including: erythema and skin cancer in humans; inhibition of photosynthesis in the diatom Phaeodactylum sp. and dinoflagellate Prorocentrum micans inhibition of carbon fixation in Antarctic phytoplankton; inhibition of growth of oat (Avena sativa L. cv. Otana) seedlings; and cataracts. We found that past work overestimated UVB irradiance, but that relative estimates for increase in exposure to DNA damaging radiation are still similar to our improved calculations. We also found that the intensity of biologically damaging radiation varies widely with organism and specific impact considered; these results have implications for biosphere-level damage following astrophysical ionizing radiation events. When considering changes in surface-level visible light irradiance, we found that, contrary to previous assumptions, a decrease in irradiance is only present for a short time in very limited geographical areas; instead we found a net increase for most of the modeled time-space region. This result has implications for proposed climate changes associated with ionizing radiation events.

Damage development under compression-compression fatigue loading in a stitched uniwoven graphite/epoxy composite material

NASA Technical Reports Server (NTRS)

Vandermey, Nancy E.; Morris, Don H.; Masters, John E.

1991-01-01

Damage initiation and growth under compression-compression fatigue loading were investigated for a stitched uniweave material system with an underlying AS4/3501-6 quasi-isotropic layup. Performance of unnotched specimens having stitch rows at either 0 degree or 90 degrees to the loading direction was compared. Special attention was given to the effects of stitching related manufacturing defects. Damage evaluation techniques included edge replication, stiffness monitoring, x-ray radiography, residual compressive strength, and laminate sectioning. It was found that the manufacturing defect of inclined stitches had the greatest adverse effect on material performance. Zero degree and 90 degree specimen performances were generally the same. While the stitches were the source of damage initiation, they also slowed damage propagation both along the length and across the width and affected through-the-thickness damage growth. A pinched layer zone formed by the stitches particularly affected damage initiation and growth. The compressive failure mode was transverse shear for all specimens, both in static compression and fatigue cycling effects.

Postbuckling Investigations of Piezoelectric Microdevices Considering Damage Effects

PubMed Central

Sun, Zhigang; Wang, Xianqiao

2014-01-01

Piezoelectric material has been emerging as a popular building block in MEMS devices owing to its unique mechanical and electrical material properties. However, the reliability of MEMS devices under buckling deformation environments remains elusive and needs to be further explored. Based on the Talreja's tensor valued internal state damage variables as well as the Helmhotlz free energy of piezoelectric material, a constitutive model of piezoelectric materials with damage is presented. The Kachanvo damage evolution law under in-plane compressive loads is employed. The model is applied to the specific case of the postbuckling analysis of the piezoelectric plate with damage. Then, adopting von Karman's plate theory, the nonlinear governing equations of the piezoelectric plates with initial geometric deflection including damage effects under in-plane compressive loads are established. By using the finite difference method and the Newmark scheme, the damage evolution for damage accumulation is developed and the finite difference procedure for postbuckling equilibrium path is simultaneously employed. Numerical results show the postbuckling behaviors of initial flat and deflected piezoelectric plates with damage or no damage under different sets of electrical loading conditions. The effects of applied voltage, aspect ratio of plate, thick-span ratio of plate, damage as well as initial geometric deflections on the postbuckling behaviors of the piezoelectric plate are discussed. PMID:24618774

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

DOEpatents

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

2004-03-16

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

General Biology and Current Management Approaches of Soft Scale Pests (Hemiptera: Coccidae).

PubMed

Camacho, Ernesto Robayo; Chong, Juang-Horng

We summarize the economic importance, biology, and management of soft scales, focusing on pests of agricultural, horticultural, and silvicultural crops in outdoor production systems and urban landscapes. We also provide summaries on voltinism, crawler emergence timing, and predictive models for crawler emergence to assist in developing soft scale management programs. Phloem-feeding soft scale pests cause direct (e.g., injuries to plant tissues and removal of nutrients) and indirect damage (e.g., reduction in photosynthesis and aesthetic value by honeydew and sooty mold). Variations in life cycle, reproduction, fecundity, and behavior exist among congenerics due to host, environmental, climatic, and geographical variations. Sampling of soft scale pests involves sighting the insects or their damage, and assessing their abundance. Crawlers of most univoltine species emerge in the spring and the summer. Degree-day models and plant phenological indicators help determine the initiation of sampling and treatment against crawlers (the life stage most vulnerable to contact insecticides). The efficacy of cultural management tactics, such as fertilization, pruning, and irrigation, in reducing soft scale abundance is poorly documented. A large number of parasitoids and predators attack soft scale populations in the field; therefore, natural enemy conservation by using selective insecticides is important. Systemic insecticides provide greater flexibility in application method and timing, and have longer residual longevity than contact insecticides. Application timing of contact insecticides that coincides with crawler emergence is most effective in reducing soft scale abundance.

Role of defects in laser-induced modifications of silica coatings and fused silica using picosecond pulses at 1053 nm: II Scaling laws and the density of precursors

DOE PAGES

Laurence, T. A.; Negres, R. A.; Ly, S.; ...

2017-06-22

Here, we investigate the role of defects in laser-induced damage of fused silica and of silica coatings produced by e-beam and PIAD processes which are used in damage resistant, multi-layer dielectric, reflective optics. We perform experiments using 1053 nm, 1–60 ps laser pulses with varying beam size, number of shots, and pulse widths in order to understand the characteristics of defects leading to laser-induced damage. This pulse width range spans a transition in mechanisms from intrinsic material ablation for short pulses to defect-dominated damage for longer pulses. We show that for pulse widths as short as 10 ps, laser-induced damagemore » properties of fused silica and silica films are dominated by isolated absorbers. The density of these precursors and their fluence dependence of damage initiation suggest a single photon process for initial energy absorption in these precursors. Higher density precursors that initiate close to the ablation threshold at shorter pulse widths are also observed in fused silica, whose fluence and pulse width scaling suggest a multiphoton initiation process. We also show that these initiated damage sites grow with subsequent laser pulses. We show that scaling laws obtained in more conventional ways depend on the beam size and on the definition of damage for ps pulses. For this reason, coupling scaling laws with the density of precursors are critical to understanding the damage limitations of optics in the ps regime.« less

Role of defects in laser-induced modifications of silica coatings and fused silica using picosecond pulses at 1053 nm: II Scaling laws and the density of precursors

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

Laurence, T. A.; Negres, R. A.; Ly, S.

Here, we investigate the role of defects in laser-induced damage of fused silica and of silica coatings produced by e-beam and PIAD processes which are used in damage resistant, multi-layer dielectric, reflective optics. We perform experiments using 1053 nm, 1–60 ps laser pulses with varying beam size, number of shots, and pulse widths in order to understand the characteristics of defects leading to laser-induced damage. This pulse width range spans a transition in mechanisms from intrinsic material ablation for short pulses to defect-dominated damage for longer pulses. We show that for pulse widths as short as 10 ps, laser-induced damagemore » properties of fused silica and silica films are dominated by isolated absorbers. The density of these precursors and their fluence dependence of damage initiation suggest a single photon process for initial energy absorption in these precursors. Higher density precursors that initiate close to the ablation threshold at shorter pulse widths are also observed in fused silica, whose fluence and pulse width scaling suggest a multiphoton initiation process. We also show that these initiated damage sites grow with subsequent laser pulses. We show that scaling laws obtained in more conventional ways depend on the beam size and on the definition of damage for ps pulses. For this reason, coupling scaling laws with the density of precursors are critical to understanding the damage limitations of optics in the ps regime.« less

Yields of biologically significant damage produced in mammalian DNA by irradiation associated with radon decay. Final progress report

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

Ward, J.F.

1994-03-01

The objective of this project was to characterize the difference between damage to DNA caused by alpha particles and by low LET radiation. Estimation of the risk posed by exposure to high LET radiation (such as that from radon) relies at present on epidemiological data, and is therefore largely empirical. This empiricism is evident from the concepts of quality factor or RBE that find use for describing the biological effects of high LET radiation. The author argues that some effort should be made to address the mechanisms of DNA damage by high and low LET forms of radiation, and howmore » these mechanisms might relate to the biological endpoints. This report summarizes the results of the author`s investigations and the current understanding of these mechanisms.« less

Effective protection of biological membranes against photo-oxidative damage: Polymeric antioxidant forming a protecting shield over the membrane.

PubMed

Mertins, Omar; Mathews, Patrick D; Gomide, Andreza B; Baptista, Mauricio S; Itri, Rosangela

2015-10-01

We have prepared a chitosan polymer modified with gallic acid in order to develop an efficient protection strategy biological membranes against photodamage. Lipid bilayers were challenged with photoinduced damage by photosensitization with methylene blue, which usually causes formation of hydroperoxides, increasing area per lipid, and afterwards allowing leakage of internal materials. The damage was delayed by a solution of gallic acid in a concentration dependent manner, but further suppressed by the polymer at very low concentrations. The membrane of giant unilamellar vesicles was covered with this modified macromolecule leading to a powerful shield against singlet oxygen and thus effectively protecting the lipid membrane from oxidative stress. The results have proven the discovery of a promising strategy for photo protection of biological membranes. Copyright © 2015 Elsevier B.V. All rights reserved.

Magnetic Field Triggered Multicycle Damage Sensing and Self Healing.

PubMed

Ahmed, Anansa S; Ramanujan, R V

2015-09-08

Multifunctional materials inspired by biological structures have attracted great interest, e.g. for wearable/ flexible "skin" and smart coatings. A current challenge in this area is to develop an artificial material which mimics biological skin by simultaneously displaying color change on damage as well as self healing of the damaged region. Here we report, for the first time, the development of a damage sensing and self healing magnet-polymer composite (Magpol), which actively responds to an external magnetic field. We incorporated reversible sensing using mechanochromic molecules in a shape memory thermoplastic matrix. Exposure to an alternating magnetic field (AMF) triggers shape recovery and facilitates damage repair. Magpol exhibited a linear strain response upto 150% strain and complete recovery after healing. We have demonstrated the use of this concept in a reusable biomedical device i.e., coated guidewires. Our findings offer a new synergistic method to bestow multifunctionality for applications ranging from medical device coatings to adaptive wing structures.

Laser-induced damage of intrinsic and extrinsic defects by picosecond pulses on multilayer dielectric coatings for petawatt-class lasers

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

Negres, Raluca A.; Carr, Christopher W.; Laurence, Ted A.

2016-08-01

Here, we describe a damage testing system and its use in investigating laser-induced optical damage initiated by both intrinsic and extrinsic precursors on multilayer dielectric coatings suitable for use in high-energy, large-aperture petawatt-class lasers. We employ small-area damage test methodologies to evaluate the intrinsic damage resistance of various coatings as a function of deposition methods and coating materials under simulated use conditions. In addition, we demonstrate that damage initiation by raster scanning at lower fluences and growth threshold testing are required to probe the density of extrinsic defects, which will limit large-aperture optics performance.

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

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

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

Relevance of impacter shape to nonvisible damage and residual tensile strength of a thick graphite/epoxy laminate

NASA Technical Reports Server (NTRS)

Poe, Clarence C., Jr.

1991-01-01

A study was made to determine the relevance of impacter shape to nonvisible damage and tensile residual strength of a 36 mm thick graphite/epoxy motor case. The shapes of the impacters were as follows: 12.7 mm and 25.4 mm diameter hemispheres, a sharp corner, and a 6.3 mm diameter bolt-like rod. The investigation revealed that damage initiated when the contact pressure exceeded a critical level. However, the damage was not visible on the surface until an even higher pressure was exceeded. The impact energy to initiate damage or cause visible damage on the surface increased approximately with impacter diameter to the third power. The reduction in strength for nonvisible damage increased with increasing diameter, 9 and 30 percent for the 12.7 mm and 25.4 mm diameter hemispheres, respectively. The corner impacter made visible damage on the surface for even the smallest impact energy. The rod impacter acted like a punch and sliced through the composite. Even so, the critical level of pressure to initiate damage was the same for the rod and hemispherical impacters. Factors of safety for nonvisible damage increased with increasing kinetic energy of impact. The effects of impacter shape on impact force, damage size, damage visibility, and residual tensile strength were predicted quite well assuming Hertzian contact and using maximum stress criteria and a surface crack analysis.

The role of electron transfer in DNA building blocks: Evaluation of strand breaks and their implications

NASA Astrophysics Data System (ADS)

Almeida, Diogo Alexandre Fialho de

Radiation-induced damage to biological systems, both direct and indirect processes, has increasingly come under scrutiny by the international scientific community due to recent findings that electrons are a very effective agent in damaging DNA/RNA. Indeed, much remains to be discovered regarding the exact physico-chemical processes that occur in the nascent stages of DNA/RNA damage by incident radiation. However, it is also known that electrons do not exist freely in the physiological medium, but rather solvated and/or pre-solvated states. This leads to the need for new techniques that can better explore the damaging role of "bound" electrons to DNA/RNA. The work presented in this thesis consists on the study of electron transfer in collisions of atomic species with molecules of biological relevance. In order to study these processes, two experimental setups were used. One setup consists of a crossed beam experiment where a neutral potassium beam is created and made to collide with an effusive molecular target beam. The anionic products that stem from electron transfer in potassium atom to the molecular target collisions are then extracted and time-of-flight (TOF) mass analysed. In the second setup a beam of anionic species is formed and made to collide with a molecular target. Collisions with three different anionic beams were performed (H-, O- and OH-), as well as with different simple organic molecules, by measuring the positive and negative ion fragmentation patterns with a quadrupole mass spectrometer (QMS). A comparison between these two collisional systems can greatly help to understand the underlying mechanisms of the electron transfer processes. Finally, studies of potassium collisions with sugar surrogates D-Ribose and THF were performed. These studies show very different fragmentation patterns from DEA, although in the case of THF, it is suggested that the initially accessed states are the same as in DEA. With these studies was also possible to show for the first time collision induced site and bond selectivity breaking, where the electron is transferred into a given state of the acceptor molecule and the resulting fragmentation pathways are exclusive to the initial anionic state. Furthermore, the role of the potassium cation post collisionwas explored and indeed its presence is suggested to induce at least partial suppression of auto-detachment. The implications that ensue from this degradation are analysed in the light of the obtained fragmentation patterns.

Depleted uranium dust from fired munitions: physical, chemical and biological properties.

PubMed

Mitchel, R E J; Sunder, S

2004-07-01

This paper reports physical, chemical and biological analyses of samples of dust resulting from munitions containing depleted uranium (DU) that had been live-fired and had impacted an armored target. Mass spectroscopic analysis indicated that the average atom% of U was 0.198 +/- 0.10, consistent with depleted uranium. Other major elements present were iron, aluminum, and silicon. About 47% of the total mass was particles with diameters <300 microm, of which about 14% was <10 microm. X-ray diffraction analysis indicated that the uranium was present in the sample as uranium oxides-mainly U3O7 (47%), U3O8 (44%) and UO2 (9%). Depleted uranium dust, instilled into the lungs or implanted into the muscle of rats, contained a rapidly soluble uranium component and a more slowly soluble uranium component. The fraction that underwent dissolution in 7 d declined exponentially with increasing initial burden. At the lower lung burdens tested (<15 microg DU dust/lung) about 14% of the uranium appeared in urine within 7 d. At the higher lung burdens tested (~80-200 microg DU dust/lung) about 5% of the DU appeared in urine within 7 d. In both cases about 50% of that total appeared in urine within the first day. DU implanted in muscle similarly showed that about half of the total excreted within 7 d appeared in the first day. At the lower muscle burdens tested (<15 microg DU dust/injection site) about 9% was solubilized within 7 d. At muscle burdens >35 microg DU dust/injection site about 2% appeared in urine within 7 d. Natural uranium (NU) ore dust was instilled into rat lungs for comparison. The fraction dissolving in lung showed a pattern of exponential decline with increasing initial burden similar to DU. However, the decline was less steep, with about 14% appearing in urine for lung burdens up to about 200 microg NU dust/lung and 5% at lung burdens >1,100 microg NU dust/lung. NU also showed both a fast and a more slowly dissolving component. At the higher lung burdens of both DU and NU that showed lowered urine excretion rates, histological evidence of kidney damage was seen. Kidney damage was not seen with the muscle burdens tested. DU dust produced kidney damage at lower lung burdens and lower urine uranium levels than NU dust, suggesting that other toxic metals in DU dust may contribute to the damage.

Biologically based multistage modeling of radiation effects

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

William Hazelton; Suresh Moolgavkar; E. Georg Luebeck

2005-08-30

This past year we have made substantial progress in modeling the contribution of homeostatic regulation to low-dose radiation effects and carcinogenesis. We have worked to refine and apply our multistage carcinogenesis models to explicitly incorporate cell cycle states, simple and complex damage, checkpoint delay, slow and fast repair, differentiation, and apoptosis to study the effects of low-dose ionizing radiation in mouse intestinal crypts, as well as in other tissues. We have one paper accepted for publication in ''Advances in Space Research'', and another manuscript in preparation describing this work. I also wrote a chapter describing our combined cell-cycle and multistagemore » carcinogenesis model that will be published in a book on stochastic carcinogenesis models edited by Wei-Yuan Tan. In addition, we organized and held a workshop on ''Biologically Based Modeling of Human Health Effects of Low dose Ionizing Radiation'', July 28-29, 2005 at Fred Hutchinson Cancer Research Center in Seattle, Washington. We had over 20 participants, including Mary Helen Barcellos-Hoff as keynote speaker, talks by most of the low-dose modelers in the DOE low-dose program, experimentalists including Les Redpath (and Mary Helen), Noelle Metting from DOE, and Tony Brooks. It appears that homeostatic regulation may be central to understanding low-dose radiation phenomena. The primary effects of ionizing radiation (IR) are cell killing, delayed cell cycling, and induction of mutations. However, homeostatic regulation causes cells that are killed or damaged by IR to eventually be replaced. Cells with an initiating mutation may have a replacement advantage, leading to clonal expansion of these initiated cells. Thus we have focused particularly on modeling effects that disturb homeostatic regulation as early steps in the carcinogenic process. There are two primary considerations that support our focus on homeostatic regulation. First, a number of epidemiologic studies using multistage carcinogenesis models that incorporate the ''initiation, promotion, and malignant conversion'' paradigm of carcinogenesis are indicating that promotion of initiated cells is the most important cellular mechanism driving the shape of the age specific hazard for many types of cancer. Second, we have realized that many of the genes that are modified in early stages of the carcinogenic process contribute to one or more of four general cellular pathways that confer a promotional advantage to cells when these pathways are disrupted.« less

Nanobubbles, cavitation, shock waves and traumatic brain injury.

PubMed

Adhikari, Upendra; Goliaei, Ardeshir; Berkowitz, Max L

2016-12-07

Collapse of bubbles, microscopic or nanoscopic, due to their interaction with the impinging pressure wave produces a jet of particles moving in the direction of the wave. If there is a surface nearby, the high-speed jet particles hit it, and as a result damage to the surface is produced. This cavitation effect is well known and intensely studied in case of microscopic sized bubbles. It can be quite damaging to materials, including biological tissues, but it can also be beneficial when controlled, like in case of sonoporation of biological membranes for the purpose of drug delivery. Here we consider recent simulation work performed to study collapse of nanobubbles exposed to shock waves, in order to understand the detailed mechanism of the cavitation induced damage to soft materials, such as biological membranes. We also discuss the connection of the cavitation effect with the traumatic brain injury caused by blasts. Specifically, we consider possible damage to model membranes containing lipid bilayers, bilayers with embedded ion channel proteins like the ones found in neural cells and also protein assemblies found in the tight junction of the blood brain barrier.

A Review: Some biological effects of high LET radiations

NASA Technical Reports Server (NTRS)

Wiley, A., Jr.

1972-01-01

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

Models for integrated pest control and their biological implications.

PubMed

Tang, Sanyi; Cheke, Robert A

2008-09-01

Successful integrated pest management (IPM) control programmes depend on many factors which include host-parasitoid ratios, starting densities, timings of parasitoid releases, dosages and timings of insecticide applications and levels of host-feeding and parasitism. Mathematical models can help us to clarify and predict the effects of such factors on the stability of host-parasitoid systems, which we illustrate here by extending the classical continuous and discrete host-parasitoid models to include an IPM control programme. The results indicate that one of three control methods can maintain the host level below the economic threshold (ET) in relation to different ET levels, initial densities of host and parasitoid populations and host-parasitoid ratios. The effects of host intrinsic growth rate and parasitoid searching efficiency on host mean outbreak period can be calculated numerically from the models presented. The instantaneous pest killing rate of an insecticide application is also estimated from the models. The results imply that the modelling methods described can help in the design of appropriate control strategies and assist management decision-making. The results also indicate that a high initial density of parasitoids (such as in inundative releases) and high parasitoid inter-generational survival rates will lead to more frequent host outbreaks and, therefore, greater economic damage. The biological implications of this counter intuitive result are discussed.

Biological properties

Treesearch

Rebecca E. Ibach

2005-01-01

There are numerous biological degradations that wood is exposed to in various environments. Biological damage occurs when a log, sawn product, or final product is not stored, handled, or designed properly. Biological organisms, such as bacteria, mold, stain, decay fungi, insects, and marine borers, depend heavily on temperature and moisture conditions to grow. A higher...

Evaluation of Late Effects of Heavy-Ion Radiation on Mesenchymal Stem Cells

NASA Technical Reports Server (NTRS)

Gonda, S.R.; Behravesh, E.; Huff, J.L.; Johnson, F.

2005-01-01

The overall objective of this recently funded study is to utilize well-characterized model test systems to assess the impact of pluripotent stem cell differentiation on biological effects associated with high-energy charged particle radiation. These stem cells, specifically mesenchymal stem cells (MSCs), have the potential for differentiation into bone, cartilage, fat, tendons, and other tissue types. The characterization of the regulation mechanisms of MSC differentiation to the osteoblastic lineage by transcription factors, such as Runx2/Cbfa1 and Osterix, and osteoinductive proteins such as members of the bone morphogenic protein family are well established. More importantly, for late biological effects, MSCs have been shown to contribute to tissue restructuring and repair after tissue injury. The complex regulation of and interactions between inflammation and repair determine the eventual outcome of the responses to tissue injury, for which MSCs play a crucial role. Additionally, MSCs have been shown to respond to reactive oxygen species, a secondary effector of radiation, by differentiating. With this, we hypothesized that differentiation of MSCs can alter or exacerbate the damage initiated by radiation, which can ultimately lead to late biological effects of misrepair/fibrosis which may ultimately lead to carcinogenesis. Currently, studies are underway to examine high-energy X-ray radiation at low and high doses, approximately 20 and 200 Rad, respectively, on cytogenetic damage and gene modulation of isolated MSCs. These cells, positive for MSC surface markers, were obtained from three persons. In vitro cell samples were harvested during cellular proliferation and after both cellular recovery and differentiation. Future work will use established in vitro models of increasing complexity to examine the value of traditional 2D tissue-culture techniques, and utilize 3D in vitro tissue culture techniques that can better assess late effects associated with radiation.

Biomarkers for Uranium Risk Assessment for the Development of the CURE (Concerted Uranium Research in Europe) Molecular Epidemiological Protocol.

PubMed

Guéguen, Yann; Roy, Laurence; Hornhardt, Sabine; Badie, Christophe; Hall, Janet; Baatout, Sarah; Pernot, Eileen; Tomasek, Ladislav; Laurent, Olivier; Ebrahimian, Teni; Ibanez, Chrystelle; Grison, Stephane; Kabacik, Sylwia; Laurier, Dominique; Gomolka, Maria

2017-01-01

Despite substantial experimental and epidemiological research, there is limited knowledge of the uranium-induce health effects after chronic low-dose exposures in humans. Biological markers can objectively characterize pathological processes or environmental responses to uranium and confounding agents. The integration of such biological markers into a molecular epidemiological study would be a useful approach to improve and refine estimations of uranium-induced health risks. To initiate such a study, Concerted Uranium Research in Europe (CURE) was established, and involves biologists, epidemiologists and dosimetrists. The aims of the biological work package of CURE were: 1. To identify biomarkers and biological specimens relevant to uranium exposure; 2. To define standard operating procedures (SOPs); and 3. To set up a common protocol (logistic, questionnaire, ethical aspects) to perform a large-scale molecular epidemiologic study in uranium-exposed cohorts. An intensive literature review was performed and led to the identification of biomarkers related to: 1. retention organs (lungs, kidneys and bone); 2. other systems/organs with suspected effects (cardiovascular system, central nervous system and lympho-hematopoietic system); 3. target molecules (DNA damage, genomic instability); and 4. high-throughput methods for the identification of new biomarkers. To obtain high-quality biological materials, SOPs were established for the sampling and storage of different biospecimens. A questionnaire was developed to assess potential confounding factors. The proposed strategy can be adapted to other internal exposures and should improve the characterization of the biological and health effects that are relevant for risk assessment.

Integrated assessment of oil pollution using biological monitoring and chemical fingerprinting.

PubMed

Lewis, Ceri; Guitart, Carlos; Pook, Chris; Scarlett, Alan; Readman, James W; Galloway, Tamara S

2010-06-01

A full assessment of the impact of oil and chemical spills at sea requires the identification of both the polluting chemicals and the biological effects they cause. Here, a combination of chemical fingerprinting of surface oils, tissue residue analysis, and biological effects measures was used to explore the relationship between spilled oil and biological impact following the grounding of the MSC Napoli container ship in Lyme Bay, England in January 2007. Initially, oil contamination remained restricted to a surface slick in the vicinity of the wreck, and there was no chemical evidence to link biological impairment of animals (the common limpet, Patella vulgata) on the shore adjacent to the oil spill. Secondary oil contamination associated with salvage activities in July 2007 was also assessed. Chemical analyses of aliphatic hydrocarbons and terpanes in shell swabs taken from limpet shells provided an unequivocal match with the fuel oil carried by the ship. Corresponding chemical analysis of limpet tissues revealed increased concentrations of polycyclic aromatic hydrocarbons (PAHs) dominated by phenanthrene and C1 to C3 phenanthrenes with smaller contributions from heavier molecular weight PAHs. Concurrent ecotoxicological tests indicated impairment of cellular viability (p < 0.001), reduced immune function (p < 0.001), and damage to DNA (Comet assay, p < 0.001) in these animals, whereas antioxidant defenses were elevated relative to un-oiled animals. These results illustrate the value of combining biological monitoring with chemical fingerprinting for the rapid identification of spilled oils and their sublethal impacts on biota in situ. Copyright 2010 SETAC.

Perspective on the pipeline of drugs being developed with modulation of DNA damage as a target.

PubMed

Plummer, Ruth

2010-09-15

Inhibitors of various elements of the DNA repair pathways have entered clinical development or are in late preclinical stages of drug development. It was initially considered that agents targeting DNA repair would act to overcome tumor resistance to chemotherapy and radiotherapy. More recent data have shown that targeting DNA repair pathways can be effective in selected tumors via a synthetically lethal route, with single agent activity having been shown with poly-ADP ribose polymerase (PARP) inhibitors. An increased understanding of the biology and interaction of the DNA repair pathways also means that rational combination of DNA repair inhibitors may also give great benefit in the clinic. ©2010 AACR.

Fatigue Damage Mechanisms in Advanced Hybrid Titanium Composite Laminates

NASA Technical Reports Server (NTRS)

Johnson, W. Steven; Rhymer, Donald W.; St.Clair, Terry L. (Technical Monitor)

2000-01-01

Hybrid Titanium Composite Laminates (HTCL) are a type of hybrid composite laminate with promise for high-speed aerospace applications, specifically designed for improved damage tolerance and strength at high-temperature (350 F, 177 C). However, in previous testing, HTCL demonstrated a propensity to excessive delamination at the titanium/PMC interface following titanium cracking. An advanced HTCL has been constructed with an emphasis on strengthening this interface, combining a PETI-5/IM7 PMC with Ti-15-3 foils prepared with an alkaline-perborate surface treatment. This paper discusses how the fatigue capabilities of the "advanced" HTCL compare to the first generation HTCL which was not modified for interface optimization, in both tension-tension (R = 0.1) and tension-compression (R=-0.2). The advanced HTCL under did not demonstrate a significant improvement in fatigue life, in either tension-tension or tension-compression loading. However, the advanced HTCL proved much more damage tolerant. The R = 0.1 tests revealed the advanced HTCL to increase the fatigue life following initial titanium ply damage up to 10X that of the initial HTCL at certain stress levels. The damage progression following the initial ply damage demonstrated the effect of the strengthened PMC/titanium interface. Acetate film replication of the advanced HTCL edges showed a propensity for some fibers in the adjacent PMC layers to fail at the point of titanium crack formation, suppressing delamination at the Ti/PMC interface. The inspection of failure surfaces validated these findings, revealing PMC fibers bonded to the majority of the titanium surfaces. Tension compression fatigue (R = -0.2) demonstrated the same trends in cycles between initial damage and failure, damage progression, and failure surfaces. Moreover, in possessing a higher resistance to delamination, the advanced HTCL did not exhibit buckling following initial titanium ply cracking under compression unlike the initial HTCL.

Electrical Stimulation of Coleopteran Muscle for Initiating Flight.

PubMed

Choo, Hao Yu; Li, Yao; Cao, Feng; Sato, Hirotaka

2016-01-01

Some researchers have long been interested in reconstructing natural insects into steerable robots or vehicles. However, until recently, these so-called cyborg insects, biobots, or living machines existed only in science fiction. Owing to recent advances in nano/micro manufacturing, data processing, and anatomical and physiological biology, we can now stimulate living insects to induce user-desired motor actions and behaviors. To improve the practicality and applicability of airborne cyborg insects, a reliable and controllable flight initiation protocol is required. This study demonstrates an electrical stimulation protocol that initiates flight in a beetle (Mecynorrhina torquata, Coleoptera). A reliable stimulation protocol was determined by analyzing a pair of dorsal longitudinal muscles (DLMs), flight muscles that oscillate the wings. DLM stimulation has achieved with a high success rate (> 90%), rapid response time (< 1.0 s), and small variation (< 0.33 s; indicating little habituation). Notably, the stimulation of DLMs caused no crucial damage to the free flight ability. In contrast, stimulation of optic lobes, which was earlier demonstrated as a successful flight initiation protocol, destabilized the beetle in flight. Thus, DLM stimulation is a promising secure protocol for inducing flight in cyborg insects or biobots.

Electrical Stimulation of Coleopteran Muscle for Initiating Flight

PubMed Central

Choo, Hao Yu; Li, Yao; Cao, Feng; Sato, Hirotaka

2016-01-01

Some researchers have long been interested in reconstructing natural insects into steerable robots or vehicles. However, until recently, these so-called cyborg insects, biobots, or living machines existed only in science fiction. Owing to recent advances in nano/micro manufacturing, data processing, and anatomical and physiological biology, we can now stimulate living insects to induce user-desired motor actions and behaviors. To improve the practicality and applicability of airborne cyborg insects, a reliable and controllable flight initiation protocol is required. This study demonstrates an electrical stimulation protocol that initiates flight in a beetle (Mecynorrhina torquata, Coleoptera). A reliable stimulation protocol was determined by analyzing a pair of dorsal longitudinal muscles (DLMs), flight muscles that oscillate the wings. DLM stimulation has achieved with a high success rate (> 90%), rapid response time (< 1.0 s), and small variation (< 0.33 s; indicating little habituation). Notably, the stimulation of DLMs caused no crucial damage to the free flight ability. In contrast, stimulation of optic lobes, which was earlier demonstrated as a successful flight initiation protocol, destabilized the beetle in flight. Thus, DLM stimulation is a promising secure protocol for inducing flight in cyborg insects or biobots. PMID:27050093

Comparison of Model Calculations of Biological Damage from Exposure to Heavy Ions with Measurements

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Hada, Megumi; Cucinotta, Francis A.; Wu, Honglu

2014-01-01

The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET gamma or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. Dose delivered by the charged particle increases sharply at the Bragg peak. However, the Bragg curve does not necessarily represent the biological damage along the particle path since biological effects are influenced by the track structures of both primary and secondary particles. Therefore, the ''biological Bragg curve'' is dependent on the energy and the type of the primary particle and may vary for different biological end points. Measurements of the induction of micronuclei (MN) have made across the Bragg curve in human fibroblasts exposed to energetic silicon and iron ions in vitro at two different energies, 300 MeV/nucleon and 1 GeV/nucleon. Although the data did not reveal an increased yield of MN at the location of the Bragg peak, the increased inhibition of cell progression, which is related to cell death, was found at the Bragg peak location. These results are compared to the calculations of biological damage using a stochastic Monte-Carlo track structure model, Galactic Cosmic Ray Event-based Risk Model (GERM) code (Cucinotta, et al., 2011). The GERM code estimates the basic physical properties along the passage of heavy ions in tissue and shielding materials, by which the experimental set-up can be interpreted. The code can also be used to describe the biophysical events of interest in radiobiology, cancer therapy, and space exploration. The calculation has shown that the severely damaged cells at the Bragg peak are more likely to go through reproductive death, the so called "overkill".

A macrophage response to Mycobacterium leprae phenolic glycolipid initiates nerve damage in leprosy

PubMed Central

Madigan, Cressida A.; Cambier, C.J.; Kelly-Scumpia, Kindra M.; Scumpia, Philip O.; Cheng, Tan-Yun; Zailaa, Joseph; Bloom, Barry R.; Moody, D. Branch; Smale, Stephen T.; Sagasti, Alvaro; Modlin, Robert L.; Ramakrishnan, Lalita

2018-01-01

SUMMARY Mycobacterium leprae causes leprosy, and is unique among mycobacterial diseases in producing peripheral neuropathy. This debilitating morbidity is attributed to axon demyelination resulting from direct interactions of the M. leprae-specific phenolic glycolipid 1 (PGL-1) with myelinating glia, and their subsequent infection. Here, we use transparent zebrafish larvae to visualize the earliest events of M. leprae-induced nerve damage. We find that demyelination and axonal damage are not directly initiated by M. leprae but by infected macrophages that patrol axons; demyelination occurs in areas of intimate contact. PGL-1 confers this neurotoxic response on macrophages: macrophages infected with M. marinum expressing PGL-1 also damage axons. PGL-1 induces nitric oxide synthase in infected macrophages, and the resultant increase in reactive nitrogen species damages axons by injuring their mitochondria and inducing demyelination. Our findings implicate the response of innate macrophages to M. leprae PGL-1 in initiating nerve damage in leprosy. PMID:28841420

A Macrophage Response to Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage in Leprosy.

PubMed

Madigan, Cressida A; Cambier, C J; Kelly-Scumpia, Kindra M; Scumpia, Philip O; Cheng, Tan-Yun; Zailaa, Joseph; Bloom, Barry R; Moody, D Branch; Smale, Stephen T; Sagasti, Alvaro; Modlin, Robert L; Ramakrishnan, Lalita

2017-08-24

Mycobacterium leprae causes leprosy and is unique among mycobacterial diseases in producing peripheral neuropathy. This debilitating morbidity is attributed to axon demyelination resulting from direct interaction of the M. leprae-specific phenolic glycolipid 1 (PGL-1) with myelinating glia and their subsequent infection. Here, we use transparent zebrafish larvae to visualize the earliest events of M. leprae-induced nerve damage. We find that demyelination and axonal damage are not directly initiated by M. leprae but by infected macrophages that patrol axons; demyelination occurs in areas of intimate contact. PGL-1 confers this neurotoxic response on macrophages: macrophages infected with M. marinum-expressing PGL-1 also damage axons. PGL-1 induces nitric oxide synthase in infected macrophages, and the resultant increase in reactive nitrogen species damages axons by injuring their mitochondria and inducing demyelination. Our findings implicate the response of innate macrophages to M. leprae PGL-1 in initiating nerve damage in leprosy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Healing of damaged metal by a pulsed high-energy electromagnetic field

NASA Astrophysics Data System (ADS)

Kukudzhanov, K. V.; Levitin, A. L.

2018-04-01

The processes of defect (intergranular micro-cracks) transformation are investigated for metal samples in a high-energy short-pulsed electromagnetic field. This investigation is based on a numerical coupled model of the impact of high-energy electromagnetic field on the pre-damaged thermal elastic-plastic material with defects. The model takes into account the melting and evaporation of the metal and the dependence of its physical and mechanical properties on the temperature. The system of equations is solved numerically by finite element method with an adaptive mesh using the arbitrary Euler–Lagrange method. The calculations show that the welding of the crack and the healing of micro-defects under treatment by short pulses of the current takes place. For the macroscopic description of the healing process, the healing and damage parameters of the material are introduced. The healing of micro-cracks improves the material healing parameter and reduces its damage. The micro-crack shapes practically do not affect the time-dependence of the healing and damage under the treatment by the current pulses. These changes are affected only by the value of the initial damage of the material and the initial length of the micro-crack. The time-dependence of the healing and the damage is practically the same for all different shapes of micro-defects, provided that the initial lengths of micro-cracks and the initial damages are the same for these different shapes of defects.

Thermal injury models for optical treatment of biological tissues: a comparative study.

PubMed

Fanjul-Velez, Felix; Ortega-Quijano, Noe; Salas-Garcia, Irene; Arce-Diego, Jose L

2010-01-01

The interaction of optical radiation with biological tissues causes an increase in the temperature that, depending on its magnitude, can provoke a thermal injury process in the tissue. The establishment of laser irradiation pathological limits constitutes an essential task, as long as it enables to fix and delimit a range of parameters that ensure a safe treatment in laser therapies. These limits can be appropriately described by kinetic models of the damage processes. In this work, we present and compare several models for the study of thermal injury in biological tissues under optical illumination, particularly the Arrhenius thermal damage model and the thermal dosimetry model based on CEM (Cumulative Equivalent Minutes) 43°C. The basic concepts that link the temperature and exposition time with the tissue injury or cellular death are presented, and it will be shown that they enable to establish predictive models for the thermal damage in laser therapies. The results obtained by both models will be compared and discussed, highlighting the main advantages of each one and proposing the most adequate one for optical treatment of biological tissues.

Examination of Deteriogenic Biofilms on Building Facades with Scanning Electron Microscopy / Badanie Deteriogennych Nalotów Biologicznych Na Elewacjach Budynków Metodą Elektronowej Mikroskopii Skaningowej

NASA Astrophysics Data System (ADS)

Piontek, Marlena; Lechów, Hanna; Paradowska, Ewa; Nycz, Marta

2016-03-01

Destruction of facades is a complex process in which technical material changes its properties, and which is caused by depositing biological agents. The examination of biofilms from building facades is difficult because sampling for tests may result in the damage to the structure of the facade's material. Also biological analysis of the material obtained from a biofilm is arduous. Some species of microorganisms are impossible to be isolated and their pure cultures cannot be cultivated in laboratory conditions. It is multispecies cultures that most frequently develop on the surfaces of the facade's technical material. Clustered in a group, they cooperate with each other and reveal different features than single cells. It is essential to identify organisms present in the biofilms, since they may initiate deterioration processes. The aim of the research was the observation of the biofilm, collected from two facades, in a micrometer scale with the use of a scanning electron microscope.

Constitutive role of the Fanconi anemia D2 gene in the replication stress response.

PubMed

Tian, Yanyan; Shen, Xi; Wang, Rui; Klages-Mundt, Naeh L; Lynn, Erica J; Martin, Sara K; Ye, Yin; Gao, Min; Chen, Junjie; Schlacher, Katharina; Li, Lei

2017-12-08

In response to DNA cross-linking damage, the Fanconi anemia (FA) core complex activates the FA pathway by monoubiquitinating Fanconi anemia complementation group D2 (FANCD2) for the initiation of the nucleolytic processing of the DNA cross-links and stabilization of stalled replication forks. Given that all the classic FA proteins coordinately monoubiquitinate FANCD2, it is unclear why losses of individual classic FA genes yield varying cellular sensitivities to cross-linking damage. To address this question, we generated cellular knock-out models of FA core complex components and FANCD2 and found that FANCD2-null mutants display higher levels of spontaneous chromosomal damage and hypersensitivity to replication-blocking lesions than Fanconi anemia complementation group L (FANCL)-null mutants, suggesting that FANCD2 provides a basal level of DNA protection countering endogenous lesions in the absence of monoubiquitination. FANCD2's ubiquitination-independent function is likely involved in optimized recruitment of nucleolytic activities for the processing and protection of stressed replication forks. Our results reveal that FANCD2 has a ubiquitination-independent role in countering endogenous levels of replication stress, a function that is critical for the maintenance of genomic stability. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Progressive Fracture of [0/90/ + or - Theta]s Composite Structure Under Uniform Pressure Load

NASA Technical Reports Server (NTRS)

Gotsis, Pascalis K.; Chamis, Christos C.; Gotsis, Christos K.; Mouratidis, Ericos

2007-01-01

S-Glass/epoxy [0/90/plus or minus theta]s for theta =45 deg., 60 deg., and 75 deg. laminated fiber-reinforced composite stiffened plate was simulated to investigated for damage and fracture progression under uniform pressure. An integrated computer code was augmented for the simulation of the damage initiation, growth, accumulation, and propagation to fracture and to structural collapse. Results show in detail the damage progression sequence and structural fracture resistance during different degradation stages. Damage through the thickness of the laminate initiated first at [0/90/plus or minus 45]s at 15.168 MPa (2200 psi), followed by [0/90/plus or minus 60]s at 16.96 MPa (2460 psi) and finally by [0/90/plus or minus 75]s at 19.3 MPa (2800 psi). After damage initiation happened the cracks propagate rapidly to structural fracture.

Induction and repair of DNA strand breaks in bovine lens epithelial cells after high LET irradiation.

PubMed

Baumstark-Khan, C; Heilmann, J; Rink, H

2003-01-01

The lens epithelium is the initiation site for the development of radiation induced cataracts. Radiation in the cortex and nucleus interacts with proteins, while in the epithelium, experimental results reveal mutagenic and cytotoxic effects. It is suggested that incorrectly repaired DNA damage may be lethal in terms of cellular reproduction and also may initiate the development of mutations or transformations in surviving cells. The occurrence of such genetically modified cells may lead to lens opacification. For a quantitative risk estimation for astronauts and space travelers it is necessary to know the relative biological effectiveness (RBE), because the spacial and temporal distribution of initial physical damage induced by cosmic radiation differ significantly from that of X-rays. RBEs for the induction of DNA strand breaks and the efficiency of repair of these breaks were measured in cultured diploid bovine lens epithelial cells exposed to different LET irradiation to either 300 kV X-rays or to heavy ions at the UNILAC accelerator at GSI. Accelerated ions from Z=8 (O) to Z=92 (U) were used. Strand breaks were measured by hydroxyapatite chromatography of alkaline unwound DNA (overall strand breaks). Results showed that DNA damage occurs as a function of dose, of kinetic energy and of LET. For particles having the same LET the severity of the DNA damage increases with dose. For a given particle dose, as the LET rises, the numbers of DNA strand breaks increase to a maximum and then reach a plateau or decrease. Repair kinetics depend on the fluence (irradiation dose). At any LET value, repair is much slower after heavy ion exposure than after X-irradiation. For ions with an LET of less than 10,000 keV micrometers-1 more than 90 percent of the strand breaks induced are repaired within 24 hours. At higher particle fluences, especially for low energetic particles with a very high local density of energy deposition within the particle track, a higher proportion of non-rejoined breaks is found, even after prolonged periods of incubation. At the highest LET value (16,300 keV micrometers-1) no significant repair is observed. These LET-dependencies are consistent with the current mechanistic model for radiation induced cataractogenesis which postulates that genomic damage to the surviving fraction of epithelial cells is responsible for lens opacification. c2003 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Oxidative DNA damage background estimated by a system model of base excision repair

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

Sokhansanj, B A; Wilson, III, D M

Human DNA can be damaged by natural metabolism through free radical production. It has been suggested that the equilibrium between innate damage and cellular DNA repair results in an oxidative DNA damage background that potentially contributes to disease and aging. Efforts to quantitatively characterize the human oxidative DNA damage background level based on measuring 8-oxoguanine lesions as a biomarker have led to estimates varying over 3-4 orders of magnitude, depending on the method of measurement. We applied a previously developed and validated quantitative pathway model of human DNA base excision repair, integrating experimentally determined endogenous damage rates and model parametersmore » from multiple sources. Our estimates of at most 100 8-oxoguanine lesions per cell are consistent with the low end of data from biochemical and cell biology experiments, a result robust to model limitations and parameter variation. Our results show the power of quantitative system modeling to interpret composite experimental data and make biologically and physiologically relevant predictions for complex human DNA repair pathway mechanisms and capacity.« less

Imaging and radiation effects of gold nanoparticles in tumour cells

PubMed Central

McQuaid, Harold N.; Muir, Mark F.; Taggart, Laura E.; McMahon, Stephen J.; Coulter, Jonathan A.; Hyland, Wendy B.; Jain, Suneil; Butterworth, Karl T.; Schettino, Giuseppe; Prise, Kevin M.; Hirst, David G.; Botchway, Stanley W.; Currell, Fred J.

2016-01-01

Gold nanoparticle radiosensitization represents a novel technique in enhancement of ionising radiation dose and its effect on biological systems. Variation between theoretical predictions and experimental measurement is significant enough that the mechanism leading to an increase in cell killing and DNA damage is still not clear. We present the first experimental results that take into account both the measured biodistribution of gold nanoparticles at the cellular level and the range of the product electrons responsible for energy deposition. Combining synchrotron-generated monoenergetic X-rays, intracellular gold particle imaging and DNA damage assays, has enabled a DNA damage model to be generated that includes the production of intermediate electrons. We can therefore show for the first time good agreement between the prediction of biological outcomes from both the Local Effect Model and a DNA damage model with experimentally observed cell killing and DNA damage induction via the combination of X-rays and GNPs. However, the requirement of two distinct models as indicated by this mechanistic study, one for short-term DNA damage and another for cell survival, indicates that, at least for nanoparticle enhancement, it is not safe to equate the lethal lesions invoked in the local effect model with DNA damage events. PMID:26787230

Chapter 5:Biological Properties of Wood

Treesearch

Rebecca E. Ibach

2013-01-01

There are numerous biological degradations that wood is exposed to in various environments. Biological damage occurs when a log, sawn product, or final product is not stored, handled, or designed properly. Biological organisms such as bacteria, mold, stain, decay fungi, insects, and marine borers depend heavily on temperature and moisture conditions to grow. Figure 5.1...

Division of Biological and Medical Research annual technical report, 1981

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

Rosenthal, M.W.

1982-06-01

This report summarizes research during 1981 in the Division of Biological and Medical Research, Argonne National Laboratory. Studies in Low Level Radiation include comparison of lifetime effects in mice of low level neutron and gamma irradiation, delineation of the responses of dogs to continuous low level gamma irradiation, elucidation of mechanisms of radiation damage and repair in mammalian cells, and study of the genetic effects of high LET radiations. Carcinogenesis research addresses mechanisms of tumor initiation and promotion in rat liver, chemical carcinogenesis in cultured mammalian cells, and molecular and genetic mechanisms of chemical and ultraviolet mutagenesis in bacteria. Researchmore » in Toxicology uses a variety of cellular, whole animal, and chronobiological end points, chemical separations, and statistical models to evaluate the hazards and mechanisms of actions of metals, coal gasification by products, and other energy-related pollutants. Human Protein Index studies develop two-dimensional electrophoresis systems for diagnosis and detection of cancer and other disease. Biophysics research includes fundamental structural and biophysical investigations of immunoglobulins and key biological molecules using NMR, crystallographic, and x-ray and neutron small-angle scattering techniques. The final sections cover support facilities, educational activities, seminars, staff talks, staff, and funding agencies.« less

Characteristics and mechanism of laser-induced surface damage initiated by metal contaminants

NASA Astrophysics Data System (ADS)

Shi, Shuang; Sun, Mingying; Shi, Shuaixu; Li, Zhaoyan; Zhang, Ya-nan; Liu, Zhigang

2015-08-01

In high power laser facility, contaminants on optics surfaces reduce damage resistance of optical elements and then decrease their lifetime. By damage test experiments, laser damage induced by typical metal particles such as stainless steel 304 is studied. Optics samples with metal particles of different sizes on surfaces are prepared artificially based on the file and sieve. Damage test is implemented in air using a 1-on-1 mode. Results show that damage morphology and mechanism caused by particulate contamination on the incident and exit surfaces are quite different. Contaminants on the incident surface absorb laser energy and generate high temperature plasma during laser irradiation which can ablate optical surface. Metal particles melt and then the molten nano-particles redeposit around the initial particles. Central region of the damaged area bears the same outline as the initial particle because of the shielding effect. However, particles on the exit surface absorb a mass of energy, generate plasma and splash lots of smaller particles, only a few of them redeposit at the particle coverage area on the exit surface. Most of the laser energy is deposited at the interface of the metal particle and the sample surface, and thus damage size on the exit surface is larger than that on the incident surface. The areas covered by the metal particle are strongly damaged. And the damage sites are more serious than that on the incident surface. Besides damage phenomenon also depends on coating and substrate materials.

Ionizing Radiation: The issue of radiation quality

NASA Astrophysics Data System (ADS)

Prise, Kevin; Schettino, Giuseppe

Types of Ionising radiations are differentiated from each other by fundamental characteristics of their energy deposition patterns when they interact with biological materials. At the level of the DNA these non-random patterns drive differences in the yields and distributions of DNA damage patterns and specifically the production of clustered damage or complex lesions. The complex radiation fields found in space bring significant challenges for developing a mechanistic understanding of radiation effects from the perspective of radiation quality as these consist of a diverse range of particle and energy types unique to the space environment. Linear energy transfer, energy deposited per unit track length in units of keV per micron, has long been used as a comparator for different types of radiation but has limitations in that it is an average value. Difference in primary core ionizations relative to secondary delta ray ranges vary significantly with particle mass and energy leading to complex interrelationships with damage production at the cellular level. At the cellular level a greater mechanistic understanding is necessary, linking energy deposition patterns to DNA damage patterns and cellular response, to build appropriate biophysical models that are predictive for different radiation qualities and mixed field exposures. Defined studies using monoenergetic beams delivered under controlled conditions are building quantitative data sets of both initial and long term changes in cells as a basis for a great mechanistic understanding of radiation quality effects of relevance to not only space exposures but clinical application of ion-beams.

Initial stages of cavitation damage and erosion on copper and brass tested in a rotating disk device

NASA Technical Reports Server (NTRS)

Rao, P. V.; Rao, B. C. S.; Rao, N. S. L.

1982-01-01

In view of the differences in flow and experimental conditions, there has been a continuing debate as to whether or not the ultrasonic method of producing cavitation damage is similar to the damage occurring in cavitating flow systems, namely, venturi and rotating disk devices. In this paper, the progress of cavitation damage during incubation periods on polycrystalline copper and brass tested in a rotating disk device is presented. The results indicate several similarities and differences in the damage mechanism encountered in a rotating disk device (which simulates field rotary devices) and a magnetostriction apparatus. The macroscopic erosion appears similar to that in the vibratory device except for nonuniform erosion and apparent plastic flow during the initial damage phase.

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

PubMed

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

2017-06-01

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

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

PubMed Central

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

2017-01-01

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

Radiographic progression of large joint damage in patients with rheumatoid arthritis treated with biological disease-modifying anti-rheumatic drugs.

PubMed

Nakajima, Arata; Aoki, Yasuchika; Sonobe, Masato; Takahashi, Hiroshi; Saito, Masahiko; Terayama, Keiichiro; Nakagawa, Koichi

2016-07-01

Radiographic progression of damage to the small joints in patients with rheumatoid arthritis (RA) is well known; however, it has not been studied fully in the large joints. In this study, we looked at the prevalence of radiographic progression of large joint damage in patients with RA treated with biological disease-modifying anti-rheumatic drugs (bDMARDs). A total of 273 large joints in the upper and lower extremities of 67 patients with RA treated with bDMARDs were investigated. Radiographs for tender and/or swollen large joints were taken at least twice during the study period (mean 18.6 months), and the progression of damage was evaluated. Progressive damage was found in 20.9% of patients and 6.2% of joints. A multivariate analysis revealed that the Larsen grade (LG) alone was a risk factor for progressive damage. The LG cutoff value was determined to be 2.5 (sensitivity: 0.529, specificity: 0.805). The only factor to predict progressive damage was the LG of the joints with symptoms, and the damage must be stopped within LG II. Regular radiographic examinations for large joints should be performed in addition to routine examinations for small joints, such as the hand and foot.

Magnetic Field Triggered Multicycle Damage Sensing and Self Healing

NASA Astrophysics Data System (ADS)

Ahmed, Anansa S.; Ramanujan, R. V.

2015-09-01

Multifunctional materials inspired by biological structures have attracted great interest, e.g. for wearable/ flexible “skin” and smart coatings. A current challenge in this area is to develop an artificial material which mimics biological skin by simultaneously displaying color change on damage as well as self healing of the damaged region. Here we report, for the first time, the development of a damage sensing and self healing magnet-polymer composite (Magpol), which actively responds to an external magnetic field. We incorporated reversible sensing using mechanochromic molecules in a shape memory thermoplastic matrix. Exposure to an alternating magnetic field (AMF) triggers shape recovery and facilitates damage repair. Magpol exhibited a linear strain response upto 150% strain and complete recovery after healing. We have demonstrated the use of this concept in a reusable biomedical device i.e., coated guidewires. Our findings offer a new synergistic method to bestow multifunctionality for applications ranging from medical device coatings to adaptive wing structures.

Magnetic Field Triggered Multicycle Damage Sensing and Self Healing

PubMed Central

Ahmed, Anansa S.; Ramanujan, R. V.

2015-01-01

Multifunctional materials inspired by biological structures have attracted great interest, e.g. for wearable/ flexible “skin” and smart coatings. A current challenge in this area is to develop an artificial material which mimics biological skin by simultaneously displaying color change on damage as well as self healing of the damaged region. Here we report, for the first time, the development of a damage sensing and self healing magnet-polymer composite (Magpol), which actively responds to an external magnetic field. We incorporated reversible sensing using mechanochromic molecules in a shape memory thermoplastic matrix. Exposure to an alternating magnetic field (AMF) triggers shape recovery and facilitates damage repair. Magpol exhibited a linear strain response upto 150% strain and complete recovery after healing. We have demonstrated the use of this concept in a reusable biomedical device i.e., coated guidewires. Our findings offer a new synergistic method to bestow multifunctionality for applications ranging from medical device coatings to adaptive wing structures. PMID:26348284

Relevance of impacter shape to nonvisible damage and residual tensile strength of a thick graphite/epoxy laminate

NASA Technical Reports Server (NTRS)

Poe, C. C., Jr.

1990-01-01

A study was made to determine the relevance of impacter shape to nonvisible damage and tensile residual strength of a 36 mm (1.4 in.) thick graphite/epoxy motor case. The shapes of the impacters were as follows: 12.7 mm (0.5 in.) and 25.4 mm (1.0 in.) diameter hemispheres, a sharp corner, and a 6.3 mm (0.25 in.) diameter bolt-like rod. The investigation revealed that damage initiated when the contact pressure exceeded a critical level. However, the damage was not visible on the surface until an even higher pressure was exceeded. The damage on the surface consisted of a crater shaped like the impacter, and the damage below the surface consisted of broken fibers. The impact energy to initiate damage or cause visible damage on the surface increased approximately with impacter diameter to the third power. The reduction in strength for nonvisible damage increased with increasing diameter, 9 and 30 percent for the 12.7 mm (0.5 in.) and 25.4 mm (1.0 in.) diameter hemispheres, respectively. The corner impacter made visible damage on the surface for even the smallest impact energy. The rod impacter acted like a punch and sliced through the composite. Even so, the critical level of pressure to initiate damage was the same for the rod and hemispherical impacters. Factors of safety for nonvisible damage increased with increasing kinetic energy of impact. The effects of impacter shape on impact force, damage size, damage visibility, and residual tensile strength were predicted quite well assuming Hertzian contact and using maximum stress criteria and a surface crack analysis.

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.

Influence of interface ply orientation on fatigue damage of adhesively bonded composite joints

NASA Technical Reports Server (NTRS)

Johnson, W. S.; Mall, S.

1985-01-01

An experimental study of cracked-lap-shear specimens was conducted to determine the influence of adherend stacking sequence on debond initiation and damage growth in a composite-to-composite bonded joint. Specimens consisted of quasi-isotropic graphite/epoxy adherends bonded together with either FM-300 or EC 3445 adhesives. The stacking sequence of the adherends was varied such that 0 deg, 45 deg, or 90 deg plies were present at the adherend-adhesive interfaces. Fatigue damage initiated in the adhesive layer in those specimens with 0 deg nd 45 deg interface plies. Damage initiated in the form of ply cracking in the strap adherend for the specimens with 90 deg interface plies. The fatigue-damage growth was in the form of delamination within the composite adherends for specimens with the 90 deg and 45 deg plies next to the adhesive, while debonding in the adhesive resulted for the specimens with 0 deg plies next to the adhesive. Those joints with the 0 deg and 45 deg plies next to either adhesive has essentially the same fatigue-damage-initiation stress levels. These stress levels were 13 and 71 percent higher, respectively, than those for specimens with 90 deg plies next to the EC 3445 and FM-300 adhesives.

Diagnosis of retrofit fatigue crack re-initiation and growth in steel-girder bridges for proactive repair and emergency planning.

DOT National Transportation Integrated Search

2014-07-01

This report presents a vibration : - : based damage : - : detection methodology that is capable of effectively capturing crack growth : near connections and crack re : - : initiation of retrofitted connections. The proposed damage detection algorithm...

Material heterogeneity in cancellous bone promotes deformation recovery after mechanical failure.

PubMed

Torres, Ashley M; Matheny, Jonathan B; Keaveny, Tony M; Taylor, David; Rimnac, Clare M; Hernandez, Christopher J

2016-03-15

Many natural structures use a foam core and solid outer shell to achieve high strength and stiffness with relatively small amounts of mass. Biological foams, however, must also resist crack growth. The process of crack propagation within the struts of a foam is not well understood and is complicated by the foam microstructure. We demonstrate that in cancellous bone, the foam-like component of whole bones, damage propagation during cyclic loading is dictated not by local tissue stresses but by heterogeneity of material properties associated with increased ductility of strut surfaces. The increase in surface ductility is unexpected because it is the opposite pattern generated by surface treatments to increase fatigue life in man-made materials, which often result in reduced surface ductility. We show that the more ductile surfaces of cancellous bone are a result of reduced accumulation of advanced glycation end products compared with the strut interior. Damage is therefore likely to accumulate in strut centers making cancellous bone more tolerant of stress concentrations at strut surfaces. Hence, the structure is able to recover more deformation after failure and return to a closer approximation of its original shape. Increased recovery of deformation is a passive mechanism seen in biology for setting a broken bone that allows for a better approximation of initial shape during healing processes and is likely the most important mechanical function. Our findings suggest a previously unidentified biomimetic design strategy in which tissue level material heterogeneity in foams can be used to improve deformation recovery after failure.

General Biology and Current Management Approaches of Soft Scale Pests (Hemiptera: Coccidae)

PubMed Central

Camacho, Ernesto Robayo; Chong, Juang-Horng

2015-01-01

We summarize the economic importance, biology, and management of soft scales, focusing on pests of agricultural, horticultural, and silvicultural crops in outdoor production systems and urban landscapes. We also provide summaries on voltinism, crawler emergence timing, and predictive models for crawler emergence to assist in developing soft scale management programs. Phloem-feeding soft scale pests cause direct (e.g., injuries to plant tissues and removal of nutrients) and indirect damage (e.g., reduction in photosynthesis and aesthetic value by honeydew and sooty mold). Variations in life cycle, reproduction, fecundity, and behavior exist among congenerics due to host, environmental, climatic, and geographical variations. Sampling of soft scale pests involves sighting the insects or their damage, and assessing their abundance. Crawlers of most univoltine species emerge in the spring and the summer. Degree-day models and plant phenological indicators help determine the initiation of sampling and treatment against crawlers (the life stage most vulnerable to contact insecticides). The efficacy of cultural management tactics, such as fertilization, pruning, and irrigation, in reducing soft scale abundance is poorly documented. A large number of parasitoids and predators attack soft scale populations in the field; therefore, natural enemy conservation by using selective insecticides is important. Systemic insecticides provide greater flexibility in application method and timing, and have longer residual longevity than contact insecticides. Application timing of contact insecticides that coincides with crawler emergence is most effective in reducing soft scale abundance. PMID:26823990

The Influence of Shielding on the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damages

NASA Technical Reports Server (NTRS)

George, K.; Cucinotta, F. A.

2006-01-01

Chromosome damage was assessed in human peripheral blood lymphocytes after in vitro exposure to the either Si-28 (490 or 600 MeV/n), Ti-48 (1000 MeV/n), or Fe-56 (600, 1000, or 5000 MeV/n). LET values for these ions ranged from approximately 50 to 174 keV/micrometers and doses ranged from 10 to 200 cGy. The effect of either aluminum or polyethylene shielding on the induction of chromosome aberrations was investigated for each ion. Chromosome exchanges were measured using fluorescence in situ hybridization (FISH) with whole chromosome probes in cells collected 48-56 hours after irradiation using a chemical-induced premature chromosome condensation (PCC) technique. The yield of chromosomal aberrations increased linearly with dose and the relative biological effectiveness (RBE) for the primary beams, estimated from the initial slope of the dose response curve for total chromosomal exchanges with respect to gamma-rays, ranged from 14 to 35. The RBE values increased with LET, reaching a maximum for the 1 GeV/n Fe ions with LET of 150 keV/micrometers, and decreased with further increases in LET. When LET of the primary beam was in the region of increasing RBE (i.e. below approximately 100 keV/micrometers), the addition of shielding material increased the effectiveness per unit dose. Whereas shielding decreased the effectiveness per unit dose when the LET of the primary particle beam was higher than 150 keV/micrometers.

Micromechanics Based Failure Analysis of Heterogeneous Materials

NASA Astrophysics Data System (ADS)

Sertse, Hamsasew M.

In recent decades, heterogeneous materials are extensively used in various industries such as aerospace, defense, automotive and others due to their desirable specific properties and excellent capability of accumulating damage. Despite their wide use, there are numerous challenges associated with the application of these materials. One of the main challenges is lack of accurate tools to predict the initiation, progression and final failure of these materials under various thermomechanical loading conditions. Although failure is usually treated at the macro and meso-scale level, the initiation and growth of failure is a complex phenomena across multiple scales. The objective of this work is to enable the mechanics of structure genome (MSG) and its companion code SwiftComp to analyze the initial failure (also called static failure), progressive failure, and fatigue failure of heterogeneous materials using micromechanics approach. The initial failure is evaluated at each numerical integration point using pointwise and nonlocal approach for each constituent of the heterogeneous materials. The effects of imperfect interfaces among constituents of heterogeneous materials are also investigated using a linear traction-displacement model. Moreover, the progressive and fatigue damage analyses are conducted using continuum damage mechanics (CDM) approach. The various failure criteria are also applied at a material point to analyze progressive damage in each constituent. The constitutive equation of a damaged material is formulated based on a consistent irreversible thermodynamics approach. The overall tangent modulus of uncoupled elastoplastic damage for negligible back stress effect is derived. The initiation of plasticity and damage in each constituent is evaluated at each numerical integration point using a nonlocal approach. The accumulated plastic strain and anisotropic damage evolution variables are iteratively solved using an incremental algorithm. The damage analyses are performed for both brittle failure/high cycle fatigue (HCF) for negligible plastic strain and ductile failure/low cycle fatigue (LCF) for large plastic strain. The proposed approach is incorporated in SwiftComp and used to predict the initial failure envelope, stress-strain curve for various loading conditions, and fatigue life of heterogeneous materials. The combined effects of strain hardening and progressive fatigue damage on the effective properties of heterogeneous materials are also studied. The capability of the current approach is validated using several representative examples of heterogeneous materials including binary composites, continuous fiber-reinforced composites, particle-reinforced composites, discontinuous fiber-reinforced composites, and woven composites. The predictions of MSG are also compared with the predictions obtained using various micromechanics approaches such as Generalized Methods of Cells (GMC), Mori-Tanaka (MT), and Double Inclusions (DI) and Representative Volume Element (RVE) Analysis (called as 3-dimensional finite element analysis (3D FEA) in this document). This study demonstrates that a micromechanics based failure analysis has a great potential to rigorously and more accurately analyze initiation and progression of damage in heterogeneous materials. However, this approach requires material properties specific to damage analysis, which are needed to be independently calibrated for each constituent.

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.

DNA Damage Levels Determine Cyclobutyl Pyrimidine Dimer Repair Mechanisms in Alfalfa Seedlings.

PubMed Central

Quaite, F. E.; Takayanagi, S.; Ruffini, J.; Sutherland, J. C.; Sutherland, B. M.

1994-01-01

Ultraviolet radiation in sunlight damages DNA in plants, but little is understood about the types, lesion capacity, and coordination of repair pathways. We challenged intact alfalfa seedlings with UV doses that induced different initial levels of cyclobutyl pyrimidine dimers and measured repair by excision and photoreactivation. By using alkaline gel electrophoresis of nonradioactive DNAs treated with a cyclobutyl pyrimidine dimer-specific UV endonuclease, we quantitated ethidium-stained DNA by electronic imaging and calculated lesion frequencies from the number average molecular lengths. At low initial dimer frequencies (less than ~30 dimers per million bases), the seedlings used only photoreactivation to repair dimers; excision repair was not significant. At higher damage levels, both excision and photorepair contributed significantly. This strategy would allow plants with low damage levels to use error-free repair requiring only an external light energy source, whereas seedlings subjected to higher damage frequencies could call on additional repair processes requiring cellular energy. Characterization of repair in plants thus requires an investigation of a range of conditions, including the level of initial damage. PMID:12244228

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

PubMed Central

Orlova, Anna; Wingelhofer, Bettina; Neubauer, Heidi A.; Maurer, Barbara; Berger-Becvar, Angelika; Keserű, György Miklós; Gunning, Patrick T.; Valent, Peter; Moriggl, Richard

2018-01-01

ABSTRACT Introduction: Hematopoietic neoplasms are often driven by gain-of-function mutations of the JAK-STAT pathway together with mutations in chromatin remodeling and DNA damage control pathways. The interconnection between the JAK-STAT pathway, epigenetic regulation or DNA damage control is still poorly understood in cancer cell biology. Areas covered: Here, we focus on a broader description of mutational insights into myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas, since sequencing efforts have identified similar combinations of driver mutations in these diseases covering different lineages. We summarize how these pathways might be interconnected in normal or cancer cells, which have lost differentiation capacity and drive oncogene transcription. Expert opinion: Due to similarities in driver mutations including epigenetic enzymes, JAK-STAT pathway activation and mutated checkpoint control through TP53, we hypothesize that similar therapeutic approaches could be of benefit in these diseases. We give an overview of how driver mutations in these malignancies contribute to hematopoietic cancer initiation or progression, and how these pathways can be targeted with currently available tools. PMID:29148847

Terrorism in Spain: emergency medical aspects.

PubMed

García-Castrillo Riesgo, Luis; García Merino, Antonio

2003-01-01

A terrorism movement has been active in Spain during the last 20 years, with a painful number of victims. Civil Defense is in charge of the coordination of all the structures that are implicated in a terrorist incident. There are three typical patterns of attacks: (1) individual attacks; (2) group attacks; and (3) mass attacks. The individual attacks are done with guns, usually 9 mm, fired from a short distance; victims die from serious intracranial damage. Collective attacks are done using explosives under vehicles, tramp bombs, or "bomb vehicles;" victims are of different severity with wounds, burns, and blast injuries. With mass attacks with "bomb vehicles" in buildings or crowded public places, the numbers of victims are elevated and produce brutal social consequences. Emergency Medical Services integrated in to "Civil Defense" try to minimize the damage by initializing treatment on-scene and with the rapid provision of definitive care. During the last year, post-traumatic stress disorder treatment groups have been providing care to the victims and personnel. Chemical or biological weapons have not been used, although this is a great concern to the authorities.

Numerical Modeling of S-Wave Generation by Fracture Damage in Underground Nuclear Explosions

DTIC Science & Technology

2009-09-30

Element Package, ABAQUS. A user -defined subroutine , VUMAT, was written that incorporates the micro-mechanics based damage constitutive law described...dynamic damage evolution on the elastic and anelastic response. 2) whereas the Ashby/Sammis model was only applicable to the case where the initial cracks ...are all parallel and the same size, we can now include a specified distribution of initial crack sizes with random azimuthal orientation about the

Role of isolated and clustered DNA damage and the post-irradiating repair process in the effects of heavy ion beam irradiation.

PubMed

Tokuyama, Yuka; Furusawa, Yoshiya; Ide, Hiroshi; Yasui, Akira; Terato, Hiroaki

2015-05-01

Clustered DNA damage is a specific type of DNA damage induced by ionizing radiation. Any type of ionizing radiation traverses the target DNA molecule as a beam, inducing damage along its track. Our previous study showed that clustered DNA damage yields decreased with increased linear energy transfer (LET), leading us to investigate the importance of clustered DNA damage in the biological effects of heavy ion beam radiation. In this study, we analyzed the yield of clustered base damage (comprising multiple base lesions) in cultured cells irradiated with various heavy ion beams, and investigated isolated base damage and the repair process in post-irradiation cultured cells. Chinese hamster ovary (CHO) cells were irradiated by carbon, silicon, argon and iron ion beams with LETs of 13, 55, 90 and 200 keV µm(-1), respectively. Agarose gel electrophoresis of the cells with enzymatic treatments indicated that clustered base damage yields decreased as the LET increased. The aldehyde reactive probe procedure showed that isolated base damage yields in the irradiated cells followed the same pattern. To analyze the cellular base damage process, clustered DNA damage repair was investigated using DNA repair mutant cells. DNA double-strand breaks accumulated in CHO mutant cells lacking Xrcc1 after irradiation, and the cell viability decreased. On the other hand, mouse embryonic fibroblast (Mef) cells lacking both Nth1 and Ogg1 became more resistant than the wild type Mef. Thus, clustered base damage seems to be involved in the expression of heavy ion beam biological effects via the repair process. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Bisphenol A Promotes Cell Survival Following Oxidative DNA Damage in Mouse Fibroblasts

PubMed Central

Gassman, Natalie R.; Coskun, Erdem; Stefanick, Donna F.; Horton, Julie K.; Jaruga, Pawel; Dizdaroglu, Miral; Wilson, Samuel H.

2015-01-01

Bisphenol A (BPA) is a biologically active industrial chemical used in production of consumer products. BPA has become a target of intense public scrutiny following concerns about its association with human diseases such as obesity, diabetes, reproductive disorders, and cancer. Recent studies link BPA with the generation of reactive oxygen species, and base excision repair (BER) is responsible for removing oxidatively induced DNA lesions. Yet, the relationship between BPA and BER has yet to be examined. Further, the ubiquitous nature of BPA allows continuous exposure of the human genome concurrent with the normal endogenous and exogenous insults to the genome, and this co-exposure may impact the DNA damage response and repair. To determine the effect of BPA exposure on base excision repair of oxidatively induced DNA damage, cells compromised in double-strand break repair were treated with BPA alone or co-exposed with either potassium bromate (KBrO3) or laser irradiation as oxidative damaging agents. In experiments with KBrO3, co-treatment with BPA partially reversed the KBrO3-induced cytotoxicity observed in these cells, and this was coincident with an increase in guanine base lesions in genomic DNA. The improvement in cell survival and the increase in oxidatively induced DNA base lesions were reminiscent of previous results with alkyl adenine DNA glycosylase-deficient cells, suggesting that BPA may prevent initiation of repair of oxidized base lesions. With laser irradiation-induced DNA damage, treatment with BPA suppressed DNA repair as revealed by several indicators. These results are consistent with the hypothesis that BPA can induce a suppression of oxidized base lesion DNA repair by the base excision repair pathway. PMID:25693136

Free radicals and low-level photon emission in human pathogenesis: state of the art.

PubMed

Van Wijk, Roeland; Van Wijk, Eduard P A; Wiegant, Fred A C; Ives, John

2008-05-01

Convincing evidence supports a role for oxidative stress in the pathogenesis of many chronic diseases. The model includes the formation of radical oxygen species (ROS) and the misassembly and aggregation of proteins when three tiers of cellular defence are insufficient: (a) direct antioxidative systems, (b) molecular damage repairing systems, and (c) compensatory chaperone synthesis. The aim of the present overview is to introduce (a) the basics of free radical and antioxidant metabolism, (b) the role of the protein quality control system in protecting cells from free radical damage and its relation to chronic diseases, (c) the basics of the ultraweak luminescence as marker of the oxidant status of biological systems, and (d) the research in human photon emission as a non-invasive marker of oxidant status in relation to chronic diseases. In considering the role of free radicals in disease, both their generation and their control by the antioxidant system are part of the story. Excessive free radical production leads to the production of heat shock proteins and chaperone proteins as a second line of protection against damage. Chaperones at the molecular level facilitate stress regulation vis-à-vis protein quali y control mechanisms. The manifestation of misfolded proteins and aggregates is a hallmark of a range of neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amylotrophic lateral sclerosis, polyglutamine (polyQ) diseases, diabetes and many others. Each of these disorders exhibits aging-dependent onset and a progressive, usually fatal clinical course. The second part reviews the current status of human photon emission techniques and protocols for recording the human oxidative status. Sensitive photomultiplier tubes may provide a tool for non-invasive and continuous monitoring of oxidative metabolism. In that respect, recording ultraweak luminescence has been favored compared to other indirect assays. Several biological models have been used to illustrate the technique in cell cultures and organs in vivo. This initiated practical applications addressing specific human pathological issues. Systematic studies on human emission have presented information on: (a) procedures for reliable measurements, and spectral analysis, (b) anatomic intensity of emission and left-right symmetries, (c) biological rhythms in emission, (d) physical and psychological influences on emission, (e) novel physical characteristics of emission, and (f) the identification of ultraweak photon emission with the staging of ROS-related damage and disease. It is concluded that both patterns and physical properties of ultraweak photon emission hold considerable promise as measure for the oxidative status.

Modeling of Damage Initiation and Progression in a SiC/SiC Woven Ceramic Matrix Composite

NASA Technical Reports Server (NTRS)

Mital, Subodh K.; Goldberg, Robert K.; Bonacuse, Peter J.

2012-01-01

The goal of an ongoing project at NASA Glenn is to investigate the effects of the complex microstructure of a woven ceramic matrix composite and its variability on the effective properties and the durability of the material. Detailed analysis of these complex microstructures may provide clues for the material scientists who `design the material? or to structural analysts and designers who `design with the material? regarding damage initiation and damage propagation. A model material system, specifically a five-harness satin weave architecture CVI SiC/SiC composite composed of Sylramic-iBN fibers and a SiC matrix, has been analyzed. Specimens of the material were serially sectioned and polished to capture the detailed images of fiber tows, matrix and porosity. Open source analysis tools were used to isolate various constituents and finite elements models were then generated from simplified models of those images. Detailed finite element analyses were performed that examine how the variability in the local microstructure affected the macroscopic behavior as well as the local damage initiation and progression. Results indicate that the locations where damage initiated and propagated is linked to specific microstructural features.

Cancer Risk-Assessment of Radiation Damage in Ataxia Telangiectasia Heterozygous Human Breast Epithelial Cell Cultures

NASA Technical Reports Server (NTRS)

Applewhite, Lisa C.

2002-01-01

This paper describes the study of the markers of cellular changes that are found during the onset of carcinogenesis. Several of the biological factors are markers of stress response, oncoprotein expression, and differentiation factors. Oxidative stress response agents such as heat shock proteins (HSPs) protect cells from oxidative stresses such as ionizing radiation. The onocoprotein HER-2/neu, a specific breast cancer marker, indicates early onset of cancer. Additional structural and morphogenetic markers of differentiation were considered in order to determine initial cellular changes at the initial onset of cancer. As an additional consideration, all-trans retinoic acid (RA), a differentiation agent, was considered because of its known role in regulating normal differentiation and inhibiting tumor proliferation via specific nuclear receptors. This paper discusses study and results of the preliminary analyses of gamma irradiation of AT heterozygous human breast epithelial cells (WH). Comparisons are also made of the effects various RA concentrations post-irradiation.

Rhizosphere Colonization and Control of Meloidogyne spp. by Nematode-trapping Fungi

PubMed Central

Persson, Christina; Jansson, Hans-Börje

1999-01-01

The ability of nematode-trapping fungi to colonize the rhizosphere of crop plants has been suggested to be an important factor in biological control of root-infecting nematodes. In this study, rhizosphere colonization was evaluated for 38 isolates of nematode-trapping fungi representing 11 species. In an initial screen, Arthrobotrys dactyloides, A. superba, and Monacrosporium ellipsosporum were most frequently detected in the tomato rhizosphere. In subsequent pot experiments these fungi and the non-root colonizing M. geophyropagum were introduced to soil in a sodium alginate matrix, and further tested both for establishment in the tomato rhizosphere and suppression of root-knot nematodes. The knob-forming M. ellipsosporum showed a high capacity to colonize the rhizosphere both in the initial screen and the pot experiments, with more than twice as many fungal propagules in the rhizosphere as in the root-free soil. However, neither this fungus nor the other nematode-trapping fungi tested reduced nematode damage to tomato plants. PMID:19270886

Reproductive Benefit of Oxidative Damage: An Oxidative Stress “Malevolence”?

PubMed Central

Poljsak, B.; Milisav, I.; Lampe, T.; Ostan, I.

2011-01-01

High levels of reactive oxygen species (ROS) compared to antioxidant defenses are considered to play a major role in diverse chronic age-related diseases and aging. Here we present an attempt to synthesize information about proximate oxidative processes in aging (relevant to free radical or oxidative damage hypotheses of aging) with an evolutionary scenario (credited here to Dawkins hypotheses) involving tradeoffs between the costs and benefits of oxidative stress to reproducing organisms. Oxidative stress may be considered a biological imperfection; therefore, the Dawkins' theory of imperfect adaptation of beings to environment was applied to the role of oxidative stress in processes like famine and infectious diseases and their consequences at the molecular level such as mutations and cell signaling. Arguments are presented that oxidative damage is not necessarily an evolutionary mistake but may be beneficial for reproduction; this may prevail over its harmfulness to health and longevity in evolution. Thus, Dawkins' principle of biological “malevolence” may be an additional biological paradigm for explaining the consequences of oxidative stress. PMID:21969876

Residual perception of biological motion in cortical blindness.

PubMed

Ruffieux, Nicolas; Ramon, Meike; Lao, Junpeng; Colombo, Françoise; Stacchi, Lisa; Borruat, François-Xavier; Accolla, Ettore; Annoni, Jean-Marie; Caldara, Roberto

2016-12-01

From birth, the human visual system shows a remarkable sensitivity for perceiving biological motion. This visual ability relies on a distributed network of brain regions and can be preserved even after damage of high-level ventral visual areas. However, it remains unknown whether this critical biological skill can withstand the loss of vision following bilateral striate damage. To address this question, we tested the categorization of human and animal biological motion in BC, a rare case of cortical blindness after anoxia-induced bilateral striate damage. The severity of his impairment, encompassing various aspects of vision (i.e., color, shape, face, and object recognition) and causing blind-like behavior, contrasts with a residual ability to process motion. We presented BC with static or dynamic point-light displays (PLDs) of human or animal walkers. These stimuli were presented either individually, or in pairs in two alternative forced choice (2AFC) tasks. When confronted with individual PLDs, the patient was unable to categorize the stimuli, irrespective of whether they were static or dynamic. In the 2AFC task, BC exhibited appropriate eye movements towards diagnostic information, but performed at chance level with static PLDs, in stark contrast to his ability to efficiently categorize dynamic biological agents. This striking ability to categorize biological motion provided top-down information is important for at least two reasons. Firstly, it emphasizes the importance of assessing patients' (visual) abilities across a range of task constraints, which can reveal potential residual abilities that may in turn represent a key feature for patient rehabilitation. Finally, our findings reinforce the view that the neural network processing biological motion can efficiently operate despite severely impaired low-level vision, positing our natural predisposition for processing dynamicity in biological agents as a robust feature of human vision. Copyright © 2016 Elsevier Ltd. All rights reserved.

Self-Healing Characteristics of Damaged Rock Salt under Different Healing Conditions

PubMed Central

Chen, Jie; Ren, Song; Yang, Chunhe; Jiang, Deyi; Li, Lin

2013-01-01

Salt deposits are commonly regarded as ideal hosts for geologic energy reservoirs. Underground cavern construction-induced damage in salt is reduced by self-healing. Thus, studying the influencing factors on such healing processes is important. This research uses ultrasonic technology to monitor the longitudinal wave velocity variations of stress-damaged rock salts during self-recovery experiments under different recovery conditions. The influences of stress-induced initial damage, temperature, humidity, and oil on the self-recovery of damaged rock salts are analyzed. The wave velocity values of the damaged rock salts increase rapidly during the first 200 h of recovery, and the values gradually increase toward stabilization after 600 h. The recovery of damaged rock salts is subjected to higher initial damage stress. Water is important in damage recovery. The increase in temperature improves damage recovery when water is abundant, but hinders recovery when water evaporates. The presence of residual hydraulic oil blocks the inter-granular role of water and restrains the recovery under triaxial compression. The results indicate that rock salt damage recovery is related to the damage degree, pore pressure, temperature, humidity, and presence of oil due to the sealing integrity of the jacket material. PMID:28811444

Self-Healing Characteristics of Damaged Rock Salt under Different Healing Conditions.

PubMed

Chen, Jie; Ren, Song; Yang, Chunhe; Jiang, Deyi; Li, Lin

2013-08-12

Salt deposits are commonly regarded as ideal hosts for geologic energy reservoirs. Underground cavern construction-induced damage in salt is reduced by self-healing. Thus, studying the influencing factors on such healing processes is important. This research uses ultrasonic technology to monitor the longitudinal wave velocity variations of stress-damaged rock salts during self-recovery experiments under different recovery conditions. The influences of stress-induced initial damage, temperature, humidity, and oil on the self-recovery of damaged rock salts are analyzed. The wave velocity values of the damaged rock salts increase rapidly during the first 200 h of recovery, and the values gradually increase toward stabilization after 600 h. The recovery of damaged rock salts is subjected to higher initial damage stress. Water is important in damage recovery. The increase in temperature improves damage recovery when water is abundant, but hinders recovery when water evaporates. The presence of residual hydraulic oil blocks the inter-granular role of water and restrains the recovery under triaxial compression. The results indicate that rock salt damage recovery is related to the damage degree, pore pressure, temperature, humidity, and presence of oil due to the sealing integrity of the jacket material.

Evolutionary Tradeoffs between Economy and Effectiveness in Biological Homeostasis Systems

PubMed Central

Szekely, Pablo; Sheftel, Hila; Mayo, Avi; Alon, Uri

2013-01-01

Biological regulatory systems face a fundamental tradeoff: they must be effective but at the same time also economical. For example, regulatory systems that are designed to repair damage must be effective in reducing damage, but economical in not making too many repair proteins because making excessive proteins carries a fitness cost to the cell, called protein burden. In order to see how biological systems compromise between the two tasks of effectiveness and economy, we applied an approach from economics and engineering called Pareto optimality. This approach allows calculating the best-compromise systems that optimally combine the two tasks. We used a simple and general model for regulation, known as integral feedback, and showed that best-compromise systems have particular combinations of biochemical parameters that control the response rate and basal level. We find that the optimal systems fall on a curve in parameter space. Due to this feature, even if one is able to measure only a small fraction of the system's parameters, one can infer the rest. We applied this approach to estimate parameters in three biological systems: response to heat shock and response to DNA damage in bacteria, and calcium homeostasis in mammals. PMID:23950698

Evolutionary tradeoffs between economy and effectiveness in biological homeostasis systems.

PubMed

Szekely, Pablo; Sheftel, Hila; Mayo, Avi; Alon, Uri

2013-01-01

Biological regulatory systems face a fundamental tradeoff: they must be effective but at the same time also economical. For example, regulatory systems that are designed to repair damage must be effective in reducing damage, but economical in not making too many repair proteins because making excessive proteins carries a fitness cost to the cell, called protein burden. In order to see how biological systems compromise between the two tasks of effectiveness and economy, we applied an approach from economics and engineering called Pareto optimality. This approach allows calculating the best-compromise systems that optimally combine the two tasks. We used a simple and general model for regulation, known as integral feedback, and showed that best-compromise systems have particular combinations of biochemical parameters that control the response rate and basal level. We find that the optimal systems fall on a curve in parameter space. Due to this feature, even if one is able to measure only a small fraction of the system's parameters, one can infer the rest. We applied this approach to estimate parameters in three biological systems: response to heat shock and response to DNA damage in bacteria, and calcium homeostasis in mammals.

Update on the use of steroids in rheumatoid arthritis.

PubMed

García-Magallón, Blanca; Silva-Fernández, Lucía; Andreu-Sánchez, José Luis

2013-01-01

Corticosteroids are a mainstay in the therapy of rheumatoid arthritis (RA). In recent years, a number of high-quality controlled clinical trials have shown their effect as a disease-modifying anti-rheumatic drug (DMARD) and a favourable safety profile in recent-onset RA. Despite this, they are more frequently used as bridge therapy while other DMARDs initiate their action than as true disease-modifying agents. Low-dose corticosteroid use during the first two years of disease slows radiologic damage and reduces the need of biologic therapy aimed at reaching a state of clinical remission in recent-onset RA. Thus, their systematic use in this clinical scenario should be considered. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Unaspis lansivora sp. n. (Hemiptera: Diaspididae), a new pest of Lansium domesticum (Meliaceae), and a key to Unaspis species.

PubMed

Watson, Gillian W

2015-01-13

Since 2004, an undescribed species of Unaspis (Hemiptera: Diaspididae) has become a damaging pest on Lansium domesticum Corrêa in the Philippines. Its attack on the leaves causes premature senescence and defoliation, resulting in the production of few, underdeveloped, sour fruit and sometimes killing the trees. The scale was misidentified initially as Lepidosaphes ulmi (Linnaeus) and then as Unaspis citri (Comstock), but further study indicated that it was an undescribed species of potential plant quarantine significance. The pest is described as U. lansivora sp. n. and an identification key to all 19 species of Unaspis is provided. Its distribution, host range and prospects for its biological control are discussed.

Interatomic relaxation processes induced in neon dimers by electron-impact ionization

NASA Astrophysics Data System (ADS)

Yan, S.; Zhang, P.; Stumpf, V.; Gokhberg, K.; Zhang, X. C.; Xu, S.; Li, B.; Shen, L. L.; Zhu, X. L.; Feng, W. T.; Zhang, S. F.; Zhao, D. M.; Ma, X.

2018-01-01

We report an experimental observation of the interatomic Coulombic decay (ICD) and radiative charge-transfer (RCT) processes in a Ne dimer (e ,2 e ) following a 380-eV electron impact. By detecting the N e+-N e+ cation pair and one of the emitted electrons in coincidence, the fingerprint of the ICD process initiated by the inner-valence ionization of Ne is obtained. Furthermore, the experimental results and ab initio calculations together unambiguously confirm the occurrence of the RCT process, and we show that most of the low-energy electrons produced in ionization of the Ne dimers are due to the ICD, which strongly suggests the importance of the ICD in causing radiation damage in a biological medium.

11th International Conference of Radiation Research

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

NONE

1999-07-18

Topics discussed in the conference included the following: Radiation Physics, Radiation Chemistry and modelling--Radiation physics and dosimetry; Electron transfer in biological media; Radiation chemistry; Biophysical and biochemical modelling; Mechanisms of DNA damage; Assays of DNA damage; Energy deposition in micro volumes; Photo-effects; Special techniques and technologies; Oxidative damage. Molecular and cellular effects-- Photobiology; Cell cycle effects; DNA damage: Strand breaks; DNA damage: Bases; DNA damage Non-targeted; DNA damage: other; Chromosome aberrations: clonal; Chromosomal aberrations: non-clonal; Interactions: Heat/Radiation/Drugs; Biochemical effects; Protein expression; Gene induction; Co-operative effects; ``Bystander'' effects; Oxidative stress effects; Recovery from radiation damage. DNA damage and repair -- DNAmore » repair genes; DNA repair deficient diseases; DNA repair enzymology; Epigenetic effects on repair; and Ataxia and ATM.« less

Role of basic biological sciences in clinical orthodontics: a case series.

PubMed

Davidovitch, Ze'ev; Krishnan, Vinod

2009-02-01

Orthodontic therapy is based on interaction between mechanics and biology. Basic biologic research aims at developing a better understanding of the mechanism of transformation of mechanical energy into biologic reactions, and exposing the reasons for iatrogenic tissue damage in orthodontics. Previous research has shown that inflammation is a major part of the biologic response to orthodontic forces. In inflammation, signal molecules that originate in remote diseased organs can reach strained paradental tissues and exacerbate the inflammatory process, leading to tissue damage. Our case series includes 3 patients, each having had systemic diseases and malocclusion. One had diabetes mellitus, Hashimoto's thyroiditis, and depression. Concern about the possible effect of these conditions on the well-being of the teeth and their surrounding tissues compelled the orthodontist to choose not to treat this patient. The other 2 patients had allergies, and 1 also had bronchial asthma and bruises. Although these conditions are thought to be risk factors for root resorption, these patients received orthodontic treatment for 2 and 3.5 years, respectively. At the end of treatment, both had excessive root resorption of many teeth. In 1 patient, this damage led to the loss of most maxillary teeth. Basic research should continue to address questions related to the biologic mechanisms of tooth movement on tissue, cellular, and molecular levels. Moreover, this research should continue to identify risk factors that might jeopardize the longevity of treated teeth. Such basic research should promote the development of new tissue-friendly and patient-friendly therapeutic methods.

Kinetic Modeling of the X-ray-induced Damage to a Metalloprotein

PubMed Central

Davis, Katherine M.; Kosheleva, Irina; Henning, Robert W.; Seidler, Gerald T.; Pushkar, Yulia

2013-01-01

It is well known that biological samples undergo x-ray-induced degradation. One of the fastest occurring x-ray-induced processes involves redox modifications (reduction or oxidation) of redox-active cofactors in proteins. Here we analyze room temperature data on the photoreduction of Mn ions in the oxygen evolving complex (OEC) of photosystem II, one of the most radiation damage sensitive proteins and a key constituent of natural photosynthesis in plants, green algae and cyanobacteria. Time-resolved x-ray emission spectroscopy with wavelength-dispersive detection was used to collect data on the progression of x-ray-induced damage. A kinetic model was developed to fit experimental results, and the rate constant for the reduction of OEC MnIII/IV ions by solvated electrons was determined. From this model, the possible kinetics of x-ray-induced damage at variety of experimental conditions, such as different rates of dose deposition as well as different excitation wavelengths, can be inferred. We observed a trend of increasing dosage threshold prior to the onset of x-ray-induced damage with increasing rates of damage deposition. This trend suggests that experimentation with higher rates of dose deposition is beneficial for measurements of biological samples sensitive to radiation damage, particularly at pink beam and x-ray FEL sources. PMID:23815809

Herbal medicine, radical scavenger and metal detoxification: bioinorganic, complexity and nano science perspectives

NASA Astrophysics Data System (ADS)

Sumitro, Sutiman B.; Alit, Sukmaningsih

2018-03-01

Developing Complexity Science and Nano Biological perspective giving the ideas of interfacing between modern physical and biological sciences for more comprehensive understanding of life. The study of bioinorganic is a trans-disciplinary, and will initiate the way to more comprehensive and better understanding life. We can talk about energy generation, motive forces and energy transfer at the level of macromolecules. We can then develop understanding biological behavior on nano size biological materials and its higher order using modern physics as well as thermodynamic law. This is a necessity to ovoid partial understanding of life that are not match with holism. In animal tissues, the accumulation or overwhelmed production of free radicals can damage cells and are believed to accelerate the progression of cancer, cardiovascular disease, and age-related diseases. Thus a guarded balance of radical species is imperative. Edward Kosower [1] proposed an idea of biradical in an aromatic organic compounds. Each of which having unpaired electrons. The magnetic force of this compound used for making agregation based on their magnetic characters. Bioinorganic low molecular weight complex compounds composing herbal medicine can bind toxic metals. This low molecular weight complex molecules then easily excerted the metals from the body, removing them from their either intracellular or extracellular existences. This bioinorganic chelation potential is now inspiring a new therapeutic strategies.

Redox signaling: An evolution from free radicals to aging.

PubMed

Forman, Henry Jay

2016-08-01

Redox biology has evolved from studies of the pathology that involves oxidants to an understanding of how oxidants participate in normal as well as aberrant signal transduction. Although the concept that signal transduction involved changes in the redox state dates from the 1930s, the modern history of redox biology began with the discovery of superoxide dismutase by McCord and Fridovich. The initial focus was on free radicals and damage of macromolecules, which remains an important topic. But, over time it was realized that hydroperoxides, especially H2O2 produced by NADPH oxidases, and electrophiles derived from lipid peroxidation or metabolism, played essential roles in physiologically relevant signaling. The mechanisms through which H2O2 and other electrophiles signal became an important area of study that provided insight into how these reactive molecules were involved in major signaling pathways and regulation of transcription factors. Thus, the field of redox signaling that is the overlap of signal transduction with redox biology was established. Alterations in redox signaling are observed in aging, but we also now know that redox signaling is essential in physiological homeostasis and that sustained deviation from redox homeostasis results in disease. This is a review of the history of redox biology from a personal perspective of nearly fifty years working in this field that hopefully provides some insights for the reader. Copyright © 2016 Elsevier Inc. All rights reserved.

The genetic architecture of sexual conflict: male harm and female resistance in Callosobruchus maculatus.

PubMed

Gay, L; Brown, E; Tregenza, T; Pincheira-Donoso, D; Eady, P E; Vasudev, R; Hunt, J; Hosken, D J

2011-02-01

Males harm females during mating in a range of species. This harm is thought to evolve because it is directly or indirectly beneficial to the male, despite being costly to his mate. The resulting sexually antagonistic selection can cause sexual arms races. For sexually antagonistic co-evolution to occur, there must be genetic variation for traits involved in female harming and susceptibility to harm, but even then intersexual genetic correlations could facilitate or impede sexual co-evolution. Male Callosobruchus maculatus harm their mates during copulation by damaging the female's reproductive tract. However, there have been no investigations of the genetic variation in damage or in female susceptibility to damage, nor has the genetic covariance between these characters been assessed. Here, we use a full-sib/half-sib breeding design to show that male damage is heritable, whereas female susceptibility to damage is much less so. There is also a substantial positive genetic correlation between the two, suggesting that selection favouring damaging males will increase the prevalence of susceptible females. We also provide evidence consistent with intralocus sexual conflict in this species. © 2010 The Authors. Journal of Evolutionary Biology © 2010 European Society For Evolutionary Biology.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-05-01

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

Specialists Meeting on Impact Damage Tolerance of Structures

DTIC Science & Technology

1976-01-01

example, fatigue, timl-de tectIable initial defects and in-fliglht d amalt such aS that inflicted by miilitary weapons or by debris from ’n din tegra t...relative to many types of damaging mechanisms, lncludlig for example: I. Fat Igue 2. Non-detectable Initial defects 3. In-flight damage, such as Inflicted...undetected flaw or defect . In both cases, the benefits of successful design are Improved safety and economics. With respect to In-flight darvqe, tre

Crack initiation modeling of a directionally-solidified nickel-base superalloy

NASA Astrophysics Data System (ADS)

Gordon, Ali Page

Combustion gas turbine components designed for application in electric power generation equipment are subject to periodic replacement as a result of cracking, damage, and mechanical property degeneration that render them unsafe for continued operation. In view of the significant costs associated with inspecting, servicing, and replacing damaged components, there has been much interest in developing models that not only predict service life, but also estimate the evolved microstructural state of the material. This thesis explains manifestations of microstructural damage mechanisms that facilitate fatigue crack nucleation in a newly-developed directionally-solidified (DS) Ni-base superalloy components exposed to elevated temperatures and high stresses. In this study, models were developed and validated for damage and life prediction using DS GTD-111 as the subject material. This material, proprietary to General Electric Energy, has a chemical composition and grain structure designed to withstand creep damage occurring in the first and second stage blades of gas-powered turbines. The service conditions in these components, which generally exceed 600°C, facilitate the onset of one or more damage mechanisms related to fatigue, creep, or environment. The study was divided into an empirical phase, which consisted of experimentally simulating service conditions in fatigue specimens, and a modeling phase, which entailed numerically simulating the stress-strain response of the material. Experiments have been carried out to simulate a variety of thermal, mechanical, and environmental operating conditions endured by longitudinally (L) and transversely (T) oriented DS GTD-111. Both in-phase and out-of-phase thermo-mechanical fatigue tests were conducted. In some cases, tests in extreme environments/temperatures were needed to isolate one or at most two of the mechanisms causing damage. Microstructural examinations were carried out via SEM and optical microscopy. A continuum crystal plasticity model was used to simulate the material behavior in the L and T orientations. The constitutive model was implemented in ABAQUS and a parameter estimation scheme was developed to obtain the material constants. A physically-based model was developed for correlating crack initiation life based on the experimental life data and predictions are made using the crack initiation model. Assuming a unique relationship between the damage fraction and cycle fraction with respect to cycles to crack initiation for each damage mode, the total crack initiation life has been represented in terms of the individual damage components (fatigue, creep-fatigue, creep, and oxidation-fatigue) observed at the end state of crack initiation.

A Novel Technique for Performing Space Based Radiation Dosimetry Using DNA-Results from GRaDEx-I and the Design of GRaDEx-II

NASA Technical Reports Server (NTRS)

Ritter, Joe; Branly, R.; Theodorakis, C.; Bickham, J.; Swartz, C.; Friedfeld, R.; Ackerman, E.; Carruthers, C.; DiGirolamo, A.; Faranda, J.

1999-01-01

Because of the large amounts of cosmic radiation in the space environment relative to that on earth, the effects of radiation on the physiology of astronauts is of major concern. Doses of radiation which can cause acute or chronic biological effects are to be avoided, therefore determination of the amount of radiation exposure encountered during space flight and assessment of its impact on biological systems is critical. Quantifying the radiation dosage and damage to biological systems, especially to humans during repetitive high altitude flight and during long duration space flight is important for several reasons. Radiation can cause altered biosynthesis and long term genotoxicity resulting in cancer and birth defects etc. Radiation damage to biological systems depends in a complex way on incident radiation species and their energy spectra. Typically non-biological, i.e. film or electronic monitoring systems with narrow energy band sensitivity are used to perform dosimetry and then results are extrapolated to biological models. For this reason it may be desirable to perform radiation dosimetry by using biological molecules e.g. DNA or RNA strands as passive sensors. A lightweight genotoxicology experiment was constructed to determine the degree to which in vitro naked DNA extracted from tissues of a variety of vertebrate organisms is damaged by exposure to radiation in a space environment. The DNA is assayed by means of agarose gel electrophoresis to determine damage such as strand breakage caused by high momentum particles and photons, and base oxidation caused by free radicals. The length distribution of DNA fragments is directly correlated with the radiation dose. It is hoped that a low mass, low cost, passive biological system to determine dose response relationship (increase in strand breaks with increase in exposure) can be developed to perform radiation dosimetry in support of long duration space flight, and to predict negative effects on biological systems (e.g. astronauts and greenhouses) in space. The payload was flown in a 2.5 cubic foot Get Away Special (GAS) container through NASA's GAS program. It was subjected to the environment of the space shuttle cargo bay for the duration of the STS-91 mission (9 days). Results of the genotoxicology and radiation dosimetry experiment (GRaDEx-1) as well as the design of an improved follow on payload are presented.

A Novel Technique for Performing Space Based Radiation Dosimetry Using DNA: Results from GRaDEx-I and the Design of GRaDEx-II

NASA Technical Reports Server (NTRS)

Ritter, Joe; Branly, R.; Theodorakis, C.; Bickham, J.; Swartz, C.; Friedfeld, R.; Ackerman, E.; Carruthers, C.; DiGirolamo, A.; Faranda, J.;

Self-healing cable apparatus and methods

NASA Technical Reports Server (NTRS)

Huston, Dryver (Inventor); Esser, Brian (Inventor)

2007-01-01

Self-healing cable apparatus and methods are disclosed. The cable has a central core surrounded by an adaptive cover that can extend over the entire length of the cable or just one or more portions of the cable. The adaptive cover includes a protective layer having an initial damage resistance, and a reactive layer. When the cable is subjected to a localized damaging force, the reactive layer responds by creating a corresponding localized self-healed region. The self-healed region provides the cable with enhanced damage resistance as compared to the cable's initial damage resistance. Embodiments of the invention utilize conventional epoxies or foaming materials in the reactive layer that are released to form the self-healed region when the damaging force reaches the reactive layer.

Neoplastic growth: the consequence of evolutionary malignant resistance to chronic damage for survival of cells (review of a new theory of the origin of cancer).

PubMed

Monceviciūte-Eringiene, E

2005-01-01

In the present review, a new theory that the mechanisms of general evolutionary persistent resistance to damaging factors are closely related to the development of tumour cells is introduced. Evolutionary resistance and its variability have an immense power to drive and control the process of carcinogenesis and the success of microbial and antitumour chemotherapy. First, this phenomenon of adaptation is characteristic of microbial cells whose resistance to antibiotics and other chemotherapeutic drugs is manifested through ATP-dependent transmembrane transporters. The structure and function of some multidrug transporters of resistance are conserved from microorganisms to mammals. When somatic cells are exposed to carcinogens and develop into tumour cells, they also acquire resistance to the toxic effects of carcinogens through these same transmembrane transporters (P-glycoprotein, glutathione S-transferases and other products of evolutionary resistance-related genes arisen for detoxification and exportation of cytotoxic xenobiotics and drugs). Cancerous cells acquire a persistent evolutionary resistance to chemotherapy drugs or irradiation through the same ATP-dependent transporters encountered in prokaryotic and eukaryotic cells. The mechanism of acquired resistance of cells to damaging factors, which becomes manifested during tumorigenic process formation, is a general biological law of primary significance in carcinogenesis. This resistance can be called malignant as, once formed, it does not disappear, as does also a clone of malignant cells. In tumorous cells, the mutagenic processes, morphological and functional modifications are a mechanism of secondary significance in carcinogenesis, contributing to formation of damage-resistant cells. This mechanism characterizes the processes of simplification arising in damage-resistant cells. Such cells acquire parasitic features. To survive under unfavourable conditions, they get adapted as if returning down the evolutionary stairs back to a more primitive stage of atavistic regression, which is characteristic of primitive forms of existence. Therefore they cease obeying the growth-regulating mechanisms in the organism and acquire the potential of unlimited division and accelerated growth (metastases) as do unicellular organisms or their forms resistant to damaging factors in the environment and in the host organism. Thus, cancer is a natural self-protective response of the damaged cells to the biological, physical and chemical damage and oxidative stress. This response has been developed in the process of evolution under the impact of the general biological Darwinian law of nature--to survive through variability and adaptation to the changed environmental conditions. Thus, malignization is the consequence of an evolutionary variety of the general biological resistance of cells to damage and stress in order to survive.

Dynamic Evolution Of Off-Fault Medium During An Earthquake: A Micromechanics Based Model

NASA Astrophysics Data System (ADS)

Thomas, Marion Y.; Bhat, Harsha S.

2018-05-01

Geophysical observations show a dramatic drop of seismic wave speeds in the shallow off-fault medium following earthquake ruptures. Seismic ruptures generate, or reactivate, damage around faults that alter the constitutive response of the surrounding medium, which in turn modifies the earthquake itself, the seismic radiation, and the near-fault ground motion. We present a micromechanics based constitutive model that accounts for dynamic evolution of elastic moduli at high-strain rates. We consider 2D in-plane models, with a 1D right lateral fault featuring slip-weakening friction law. The two scenarios studied here assume uniform initial off-fault damage and an observationally motivated exponential decay of initial damage with fault normal distance. Both scenarios produce dynamic damage that is consistent with geological observations. A small difference in initial damage actively impacts the final damage pattern. The second numerical experiment, in particular, highlights the complex feedback that exists between the evolving medium and the seismic event. We show that there is a unique off-fault damage pattern associated with supershear transition of an earthquake rupture that could be potentially seen as a geological signature of this transition. These scenarios presented here underline the importance of incorporating the complex structure of fault zone systems in dynamic models of earthquakes.

Dynamic Evolution Of Off-Fault Medium During An Earthquake: A Micromechanics Based Model

NASA Astrophysics Data System (ADS)

Thomas, M. Y.; Bhat, H. S.

2017-12-01

Geophysical observations show a dramatic drop of seismic wave speeds in the shallow off-fault medium following earthquake ruptures. Seismic ruptures generate, or reactivate, damage around faults that alter the constitutive response of the surrounding medium, which in turn modifies the earthquake itself, the seismic radiation, and the near-fault ground motion. We present a micromechanics based constitutive model that accounts for dynamic evolution of elastic moduli at high-strain rates. We consider 2D in-plane models, with a 1D right lateral fault featuring slip-weakening friction law. The two scenarios studied here assume uniform initial off-fault damage and an observationally motivated exponential decay of initial damage with fault normal distance. Both scenarios produce dynamic damage that is consistent with geological observations. A small difference in initial damage actively impacts the final damage pattern. The second numerical experiment, in particular, highlights the complex feedback that exists between the evolving medium and the seismic event. We show that there is a unique off-fault damage pattern associated with supershear transition of an earthquake rupture that could be potentially seen as a geological signature of this transition. These scenarios presented here underline the importance of incorporating the complex structure of fault zone systems in dynamic models of earthquakes.

The Effect of Fatty Acids to Protect Forward Osmosis Membranes from Damage

NASA Technical Reports Server (NTRS)

Romero Mangado, Jaione; Parodi, Jurek; Stefanson, Ofir; Lathrop, Cooper; Lewis, Madeleine; Ferrara, Alessandro; Tatum, Simone; Flynn, Michael

2017-01-01

NASA has conducted research and development on forward osmosis (FO) membranes for wastewater reclamation in space since 1993. The lessons learned during operation of the International Space Station and FO based technologies on the ground taught us that reliability is a key limitation. Membranes are susceptible to organic fouling, oxidation and calcium scaling, and these factors tend to damage the membrane reducing their operating life and performance. The development of a Synthetic Biological Membrane (SBM), a membrane that mimics naturally occurring biological processes, will mitigate membrane damage and improve reliability. The SBM is a lipid-based membrane with a protective fatty acid layer configured for use in a FO water purification system. In this configuration, the protective layer on the surface of the lipid membrane is composed of fatty acids (FA). The FA interact with the chemicals found in the wastewater feed, and protect the membrane from damage. In this study, we conducted preliminary experiments to determine the feasibility of using fatty acids to alleviate damage from calcium scaling, oxidation and organic fouling.

Radiation damage to nucleoprotein complexes in macromolecular crystallography

DOE PAGES

Bury, Charles; Garman, Elspeth F.; Ginn, Helen Mary; ...

2015-01-30

Significant progress has been made in macromolecular crystallography over recent years in both the understanding and mitigation of X-ray induced radiation damage when collecting diffraction data from crystalline proteins. Despite the large field that is productively engaged in the study of radiation chemistry of nucleic acids, particularly of DNA, there are currently very few X-ray crystallographic studies on radiation damage mechanisms in nucleic acids. Quantitative comparison of damage to protein and DNA crystals separately is challenging, but many of the issues are circumvented by studying pre-formed biological nucleoprotein complexes where direct comparison of each component can be made under themore » same controlled conditions. A model protein–DNA complex C.Esp1396I is employed to investigate specific damage mechanisms for protein and DNA in a biologically relevant complex over a large dose range (2.07–44.63 MGy). In order to allow a quantitative analysis of radiation damage sites from a complex series of macromolecular diffraction data, a computational method has been developed that is generally applicable to the field. Typical specific damage was observed for both the protein on particular amino acids and for the DNA on, for example, the cleavage of base-sugar N 1—C and sugar-phosphate C—O bonds. Strikingly the DNA component was determined to be far more resistant to specific damage than the protein for the investigated dose range. We observed the protein at low doses and found that they were susceptible to radiation damage while the DNA was far more resistant, damage only being observed at significantly higher doses.« less

DNA damage in outdoor workers occupationally exposed to environmental air pollutants

PubMed Central

Tovalin, H; Valverde, M; Morandi, M T; Blanco, S; Whitehead, L; Rojas, E

2006-01-01

Background Health concerns about the exposure to genotoxic and carcinogenic agents in the air are particularly significant for outdoor workers in less developed countries. Aims To investigate the association between personal exposure to a group of air pollutants and severity of DNA damage in outdoor workers from two Mexican cities. Methods DNA damage (Comet assay) and personal exposure to volatile organic compounds, PM2.5, and ozone were investigated in 55 outdoor and indoor workers from México City and Puebla. Results In México City, outdoor workers had greater DNA damage, reflected by a longer tail length, than indoor workers (median 46.8 v 30.1 μm), and a greater percentage of highly damaged cells (cells with tail length ⩾41 μm); in Puebla, outdoor and indoor workers had similar DNA damage. There were more alkali labile sites in outdoor than indoor workers. The DNA damage magnitude was positively correlated with PM2.5 and ozone exposure. Outdoor and indoor workers with ⩾60% of highly damaged cells (highly damaged workers) had significantly higher exposures to PM2.5, ozone, and some volatile organic compounds. The main factors associated with the highly damaged workers were ozone, PM2.5, and 1‐ethyl‐2‐methyl benzene exposure. Conclusions With this approach, the effects of some air pollutants could be correlated with biological endpoints from the Comet assay. It is suggested that the use of personal exposure assessment and biological endpoints evaluation could be an important tool to generate a more precise assessment of the associated potential health risks. PMID:16556741

A methodology to predict damage initiation, damage growth and residual strength in titanium matrix composites

NASA Technical Reports Server (NTRS)

Bakuckas, J. G., Jr.; Johnson, W. S.

1994-01-01

In this research, a methodology to predict damage initiation, damage growth, fatigue life, and residual strength in titanium matrix composites (TMC) is outlined. Emphasis was placed on micromechanics-based engineering approaches. Damage initiation was predicted using a local effective strain approach. A finite element analysis verified the prevailing assumptions made in the formulation of this model. Damage growth, namely, fiber-bridged matrix crack growth, was evaluated using a fiber bridging (FB) model which accounts for thermal residual stresses. This model combines continuum fracture mechanics and micromechanics analyses yielding stress-intensity factor solutions for fiber-bridged matrix cracks. It is assumed in the FB model that fibers in the wake of the matrix crack are idealized as a closure pressure, and an unknown constant frictional shear stress is assumed to act along the debond length of the bridging fibers. This frictional shear stress was used as a curve fitting parameter to the available experimental data. Fatigue life and post-fatigue residual strength were predicted based on the axial stress in the first intact 0 degree fiber calculated using the FB model and a three-dimensional finite element analysis.

Combined Advanced Finishing and UV-Laser Conditioning for Producing UV-Damage-Resistant Fused Silica Optics

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

Menapace, J A; Penetrante, B; Golini, D

2001-11-01

Laser induced damage initiation on fused silica optics can limit the lifetime of the components when used in high power UV laser environments. Foe example in inertial confinement fusion research applications, the optics can be exposed to temporal laser pulses of about 3-nsec with average fluences of 8 J/cm{sup 2} and peak fluences between 12 and 15 J/cm{sup 2}. During the past year, we have focused on optimizing the damage performance at a wavelength of 355-nm (3{omega}), 3-nsec pulse length, for optics in this category by examining a variety of finishing technologies with a challenge to improve the laser damagemore » initiation density by at least two orders of magnitude. In this paper, we describe recent advances in improving the 3{omega} damage initiation performance of laboratory-scale zirconium oxide and cerium oxide conventionally finished fused silica optics via application of processes incorporating magnetorheological finishing (MRF), wet chemical etching, and UV laser conditioning. Details of the advanced finishing procedures are described and comparisons are made between the procedures based upon large area 3{omega} damage performance, polishing layer contamination, and optical subsurface damage.« less

Track structure model for damage to mammalian cell cultures during solar proton events

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Wilson, J. W.; Townsend, L. W.; Shinn, J. L.; Katz, R.

1992-01-01

Solar proton events (SPEs) occur infrequently and unpredictably, thus representing a potential hazard to interplanetary space missions. Biological damage from SPEs will be produced principally through secondary electron production in tissue, including important contributions due to delta rays from nuclear reaction products. We review methods for estimating the biological effectiveness of SPEs using a high energy proton model and the parametric cellular track model. Results of the model are presented for several of the historically largest flares using typical levels and body shielding.

Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans.

PubMed

Carroll, Judith E; Cole, Steven W; Seeman, Teresa E; Breen, Elizabeth C; Witarama, Tuff; Arevalo, Jesusa M G; Ma, Jeffrey; Irwin, Michael R

2016-01-01

Age-related disease risk has been linked to short sleep duration and sleep disturbances; however, the specific molecular pathways linking sleep loss with diseases of aging are poorly defined. Key cellular events seen with aging, which are thought to contribute to disease, may be particularly sensitive to sleep loss. We tested whether one night of partial sleep deprivation (PSD) would increase leukocyte gene expression indicative of DNA damage responses (DDR), the senescence-associated secretory phenotype (SASP), and senescence indicator p16(INK4a) in older adult humans, who are at increased risk for cellular senescence. Community-dwelling older adults aged 61-86years (n=29; 48% male) underwent an experimental partial sleep deprivation (PSD) protocol over 4 nights, including adaptation, an uninterrupted night of sleep, partial sleep deprivation (sleep restricted 3-7AM), and a subsequent full night of sleep. Blood samples were obtained each morning to assess peripheral blood mononuclear cell (PBMC) gene expression using Illumina HT-12 arrays. Analyses of microarray results revealed that SASP (p<.05) and DDR (p=.08) gene expression were elevated from baseline to PSD nights. Gene expression changes were also observed from baseline to PSD in NFKB2, NBS1 and CHK2 (all p's<.05). The senescence marker p16(INK4a) (CDKN2A) was increased 1day after PSD compared to baseline (p<.01), however confirmatory RT-PCR did not replicate this finding. One night of partial sleep deprivation activates PBMC gene expression patterns consistent with biological aging in this older adult sample. PSD enhanced the SASP and increased the accumulation of damage that initiates cell cycle arrest and promotes cellular senescence. These findings causally link sleep deprivation to the molecular processes associated with biological aging. Copyright © 2015 Elsevier Inc. All rights reserved.

The formation of double-strand breaks at multiply damaged sites is driven by the kinetics of excision/incision at base damage in eukaryotic cells

PubMed Central

Kozmin, Stanislav G.; Sedletska, Yuliya; Reynaud-Angelin, Anne; Gasparutto, Didier; Sage, Evelyne

2009-01-01

It has been stipulated that repair of clustered DNA lesions may be compromised, possibly leading to the formation of double-strand breaks (DSB) and, thus, to deleterious events. Using a variety of model multiply damaged sites (MDS), we investigated parameters that govern the formation of DSB during the processing of MDS. Duplexes carrying MDS were inserted into replicative or integrative vectors, and used to transform yeast Saccharomyces cerevisiae. Formation of DSB was assessed by a relevant plasmid survival assay. Kinetics of excision/incision and DSB formation at MDS was explored using yeast cell extracts. We show that MDS composed of two uracils or abasic sites, were rapidly incised and readily converted into DSB in yeast cells. In marked contrast, none of the MDS carrying opposed oG and hU separated by 3–8 bp gave rise to DSB, despite the fact that some of them contained preexisting single-strand break (a 1-nt gap). Interestingly, the absence of DSB formation in this case correlated with slow excision/incision rates of lesions. We propose that the kinetics of the initial repair steps at MDS is a major parameter that direct towards the conversion of MDS into DSB. Data provides clues to the biological consequences of MDS in eukaryotic cells. PMID:19174565

75 FR 69396 - Availability of an Environmental Assessment for a Biological Control Agent for Arundo donax

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-12

... infestations. The proposed biological control agent, Arundo scale, is one of the most damaging insects to A... feeding on cells that carry out photosynthesis and cellular respiration, resulting over time in gradual... donacis (Hemiptera: Diaspididae), an Insect for Biological Control of Arundo donax (Poaceae) in the...

Managing conflict over biological control: the case of strawberry guava in Hawaii

Treesearch

Tracy Johnson

2016-01-01

Biological control researchers commonly avoid targets with potential for high conflict, but for certain highly damaging invaders with no viable management alternatives, it may be necessary to consider biological control even when it is likely to generate conflict. Discussed here is a case study, strawberry guava (Psidium cattleianum Sabine...

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

NASA Technical Reports Server (NTRS)

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

2011-01-01

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

Damage pattern as a function of radiation quality and other factors.

PubMed

Burkart, W; Jung, T; Frasch, G

1999-01-01

An understanding of damage pattern in critical cellular structures such as DNA is an important prerequisite for a mechanistic assessment of primary radiation damage, its possible repair, and the propagation of residual changes in somatic and germ cells as potential contributors to disease or ageing. Important quantitative insights have been made recently on the distribution in time and space of critical lesions from direct and indirect action of ionizing radiation on mammalian cells. When compared to damage from chemicals or from spontaneous degradation, e.g. depurination or base deamination in DNA, the potential of even low-LET radiation to create local hot spots of damage from single particle tracks is of utmost importance. This has important repercussions on inferences from critical biological effects at high dose and dose rate exposure situations to health risks at chronic, low-level exposures as experienced in environmental and controlled occupational settings. About 10,000 DNA lesions per human cell nucleus and day from spontaneous degradation and chemical attack cause no apparent effect, but a dose of 4 Gy translating into a similar number of direct and indirect DNA breaks induces acute lethality. Therefore, single lesions cannot explain the high efficiency of ionizing radiation in the induction of mutation, transformation and loss of proliferative capacity. Clustered damage leading to poorly repairable double-strand breaks or even more complex local DNA degradation, correlates better with fixed damage and critical biological endpoints. A comparison with other physical, chemical and biological agents indicates that ionizing radiation is indeed set apart from these by its unique micro- and nano-dosimetric traits. Only a few other agents such as bleomycin have a similar potential to cause complex damage from single events. However, in view of the multi-stage mechanism of carcinogenesis, it is still an open question whether dose-effect linearity for complex primary DNA damage and resulting fixed critical cellular lesions translate into linearity for radiation-induced cancer. To solve this enigma, a quantitative assessment of all genotoxic and harmful non-genotoxic agents affecting the human body would be needed.

Linking JNK Activity to the DNA Damage Response

PubMed Central

Picco, Vincent

2013-01-01

The activity of c-Jun N-terminal kinase (JNK) was initially described as ultraviolet- and oncogene-induced kinase activity on c-Jun. Shortly after this initial discovery, JNK activation was reported for a wider variety of DNA-damaging agents, including γ-irradiation and chemotherapeutic compounds. As the DNA damage response mechanisms were progressively uncovered, the mechanisms governing the activation of JNK upon genotoxic stresses became better understood. In particular, a recent set of papers links the physical breakage in DNA, the activation of the transcription factor NF-κB, the secretion of TNF-α, and an autocrine activation of the JNK pathway. In this review, we will focus on the pathway that is initiated by a physical break in the DNA helix, leading to JNK activation and the resultant cellular consequences. The implications of these findings will be discussed in the context of cancer therapy with DNA-damaging agents. PMID:24349633

49 CFR 830.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., search and rescue, law enforcement, aeronautical research, or biological or geological resource..., and which would normally require major repair or replacement of the affected component. Engine failure or damage limited to an engine if only one engine fails or is damaged, bent fairings or cowling...

49 CFR 830.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., search and rescue, law enforcement, aeronautical research, or biological or geological resource..., and which would normally require major repair or replacement of the affected component. Engine failure or damage limited to an engine if only one engine fails or is damaged, bent fairings or cowling...

49 CFR 830.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., search and rescue, law enforcement, aeronautical research, or biological or geological resource..., and which would normally require major repair or replacement of the affected component. Engine failure or damage limited to an engine if only one engine fails or is damaged, bent fairings or cowling...

49 CFR 830.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., search and rescue, law enforcement, aeronautical research, or biological or geological resource..., and which would normally require major repair or replacement of the affected component. Engine failure or damage limited to an engine if only one engine fails or is damaged, bent fairings or cowling...

Commercializing Biological Control

ERIC Educational Resources Information Center

LeLeu, K. L.; Young, M. A.

1973-01-01

Describes the only commercial establishment involved in biological control in Australia. The wasp Aphitis melinus, which parasitizes the insect Red Scale, is bred in large numbers and released in the citrus groves where Red Scale is causing damage to the fruit. (JR)

Corono-radicular biological restoration of maxillary central incisors by direct method.

PubMed

Aggarwal, Sonia; Sahoo, Sujit Ranjan; Pandharkar, Kartik

2014-11-01

This case report refers to the esthetic and functional restorations of extensively damaged maxillary central incisors with dental caries in a 32-year-old woman, with the use of posts and crowns made from natural extracted teeth. Proper restoration of such teeth with the use of natural teeth fragments are known as "biological restoration." Biological restorations can be done by using the fragments of the patients own tooth and if that is not available, tooth fragment can be obtained from an extracted tooth. These biological posts and crowns present a low cost option and an alternative technique for the morphofunctional recovery of extensively damaged teeth. There are limitations with the use of natural extracted teeth (homogenous bonding) for restoration such as the difficulty of finding teeth with a similar color and shape as that of the destroyed element, or patient may refuse to accept a tooth fragment from another patient, which prevents execution of the restoration.

Influence of interface ply orientation on fatigue damage of adhesively bonded composite joints

NASA Technical Reports Server (NTRS)

Johnson, W. S.; Mall, S.

1986-01-01

An experimental study of cracked-lap-shear specimens was conducted to determine the influence of adherend stacking sequence on debond initiation and damage growth in a composite-to-composite bonded joint. Specimens consisted of quasi-isotropic graphite/epoxy adherends bonded together with either FM-300 or EC 3445 adhesives. The stacking sequence of the adherends was varied such that 0 deg, 45 deg, or 90 deg plies were present at the adherend-adhesive interfaces. Fatigue damage initiated in the adhesive layer in those specimens with 0 deg and 45 deg interface plies. Damaage initiated in the form of ply cracking in the strap adherend for the specimens with 90 deg interface plies. The fatigue-damage growth was in the form of delamination within the composite adherends for specimens with the 90 deg and 45 deg plies next to the adhesive, while debonding in the adhesive resulted for the specimens with 0 deg plies next to the adhesive. Those joints with the 0 deg and 45 deg plies next to either adhesive has essentially the same fatigue-damage-initiation stress levels. These stress levels were 13 and 71 percent higher, respectively, than those for specimens with 90 deg plies next to the EC 3445 and FM-300 adhesives.

Tolerance to deer herbivory and resistance to insect herbivores in the common evening primrose (Oenothera biennis).

PubMed

Puentes, A; Johnson, M T J

2016-01-01

The evolution of plant defence in response to herbivory will depend on the fitness effects of damage, availability of genetic variation and potential ecological and genetic constraints on defence. Here, we examine the potential for evolution of tolerance to deer herbivory in Oenothera biennis while simultaneously considering resistance to natural insect herbivores. We examined (i) the effects of deer damage on fitness, (ii) the presence of genetic variation in tolerance and resistance, (iii) selection on tolerance, (iv) genetic correlations with resistance that could constrain evolution of tolerance and (v) plant traits that might predict defence. In a field experiment, we simulated deer damage occurring early and late in the season, recorded arthropod abundances, flowering phenology and measured growth rate and lifetime reproduction. Our study showed that deer herbivory has a negative effect on fitness, with effects being more pronounced for late-season damage. Selection acted to increase tolerance to deer damage, yet there was low and nonsignificant genetic variation in this trait. In contrast, there was substantial genetic variation in resistance to insect herbivores. Resistance was genetically uncorrelated with tolerance, whereas positive genetic correlations in resistance to insect herbivores suggest there exists diffuse selection on resistance traits. In addition, growth rate and flowering time did not predict variation in tolerance, but flowering phenology was genetically correlated with resistance. Our results suggest that deer damage has the potential to exert selection because browsing reduces plant fitness, but limited standing genetic variation in tolerance is expected to constrain adaptive evolution in O. biennis. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Contributions of DNA repair and damage response pathways to the non-linear genotoxic responses of alkylating agents

PubMed Central

Klapacz, Joanna; Pottenger, Lynn H.; Engelward, Bevin P.; Heinen, Christopher D.; Johnson, George E.; Clewell, Rebecca A.; Carmichael, Paul L.; Adeleye, Yeyejide; Andersen, Melvin E.

2016-01-01

From a risk assessment perspective, DNA-reactive agents are conventionally assumed to have genotoxic risks at all exposure levels, thus applying a linear extrapolation for low-dose responses. New approaches discussed here, including more diverse and sensitive methods for assessing DNA damage and DNA repair, strongly support the existence of measurable regions where genotoxic responses with increasing doses are insignificant relative to control. Model monofunctional alkylating agents have in vitro and in vivo datasets amenable to determination of points of departure (PoDs) for genotoxic effects. A session at the 2013 Society of Toxicology meeting provided an opportunity to survey the progress in understanding the biological basis of empirically-observed PoDs for DNA alkylating agents. Together with the literature published since, this review discusses cellular pathways activated by endogenous and exogenous alkylation DNA damage. Cells have evolved conserved processes that monitor and counteract a spontaneous steady-state level of DNA damage. The ubiquitous network of DNA repair pathways serves as the first line of defense for clearing of the DNA damage and preventing mutation. Other biological pathways discussed here that are activated by genotoxic stress include post-translational activation of cell cycle networks and transcriptional networks for apoptosis/cell death. The interactions of various DNA repair and DNA damage response pathways provide biological bases for the observed PoD behaviors seen with genotoxic compounds. Thus, after formation of DNA adducts, the activation of cellular pathways can lead to the avoidance a mutagenic outcome. The understanding of the cellular mechanisms acting within the low-dose region will serve to better characterize risks from exposures to DNA-reactive agents at environmentally-relevant concentrations. PMID:27036068

Contributions of DNA repair and damage response pathways to the non-linear genotoxic responses of alkylating agents.

PubMed

Klapacz, Joanna; Pottenger, Lynn H; Engelward, Bevin P; Heinen, Christopher D; Johnson, George E; Clewell, Rebecca A; Carmichael, Paul L; Adeleye, Yeyejide; Andersen, Melvin E

2016-01-01

From a risk assessment perspective, DNA-reactive agents are conventionally assumed to have genotoxic risks at all exposure levels, thus applying a linear extrapolation for low-dose responses. New approaches discussed here, including more diverse and sensitive methods for assessing DNA damage and DNA repair, strongly support the existence of measurable regions where genotoxic responses with increasing doses are insignificant relative to control. Model monofunctional alkylating agents have in vitro and in vivo datasets amenable to determination of points of departure (PoDs) for genotoxic effects. A session at the 2013 Society of Toxicology meeting provided an opportunity to survey the progress in understanding the biological basis of empirically-observed PoDs for DNA alkylating agents. Together with the literature published since, this review discusses cellular pathways activated by endogenous and exogenous alkylation DNA damage. Cells have evolved conserved processes that monitor and counteract a spontaneous steady-state level of DNA damage. The ubiquitous network of DNA repair pathways serves as the first line of defense for clearing of the DNA damage and preventing mutation. Other biological pathways discussed here that are activated by genotoxic stress include post-translational activation of cell cycle networks and transcriptional networks for apoptosis/cell death. The interactions of various DNA repair and DNA damage response pathways provide biological bases for the observed PoD behaviors seen with genotoxic compounds. Thus, after formation of DNA adducts, the activation of cellular pathways can lead to the avoidance of a mutagenic outcome. The understanding of the cellular mechanisms acting within the low-dose region will serve to better characterize risks from exposures to DNA-reactive agents at environmentally-relevant concentrations. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2013-01-01

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

Technical Operating Procedures for Providing Funding to Natural Resource Trustees to Conduct an Initiation of Assessment of Natural Resource Damages Under the Oil Pollution Act of 1990

DOT National Transportation Integrated Search

1996-06-01

Technical Operating Procedures (TOPS) for Providing Funding to Natural Resources : Trustees To Conduct An Initiation of Assessment of Natural Resource Damages : under the Oil Pollution Act of 1990 have been developed to provide guidance on : funding ...

Statistical damage constitutive model for rocks subjected to cyclic stress and cyclic temperature

NASA Astrophysics Data System (ADS)

Zhou, Shu-Wei; Xia, Cai-Chu; Zhao, Hai-Bin; Mei, Song-Hua; Zhou, Yu

2017-10-01

A constitutive model of rocks subjected to cyclic stress-temperature was proposed. Based on statistical damage theory, the damage constitutive model with Weibull distribution was extended. Influence of model parameters on the stress-strain curve for rock reloading after stress-temperature cycling was then discussed. The proposed model was initially validated by rock tests for cyclic stress-temperature and only cyclic stress. Finally, the total damage evolution induced by stress-temperature cycling and reloading after cycling was explored and discussed. The proposed constitutive model is reasonable and applicable, describing well the stress-strain relationship during stress-temperature cycles and providing a good fit to the test results. Elastic modulus in the reference state and the damage induced by cycling affect the shape of reloading stress-strain curve. Total damage induced by cycling and reloading after cycling exhibits three stages: initial slow increase, mid-term accelerated increase, and final slow increase.

An enhancement to the NA4 gear vibration diagnostic parameter

NASA Technical Reports Server (NTRS)

Decker, Harry J.; Handschuh, Robert F.; Zakrajsek, James J.

1994-01-01

A new vibration diagnostic parameter for health monitoring of gears, NA4*, is proposed and tested. A recently developed gear vibration diagnostic parameter NA4 outperformed other fault detection methods at indicating the start and initial progression of damage. However, in some cases, as the damage progressed, the sensitivity of the NA4 and FM4 parameters tended to decrease and no longer indicated damage. A new parameter, NA4* was developed by enhancing NA4 to improve the trending of the parameter. This allows for the indication of damage both at initiation and also as the damage progresses. The NA4* parameter was verified and compared to the NA4 and FM4 parameters using experimental data from single mesh spur and spiral bevel gear fatigue rigs. The primary failure mode for the test cases was naturally occurring tooth surface pitting. The NA4* parameter is shown to be a more robust indicator of damage.

Action spectra affect variability of the climatology of biologically effective ultraviolet radiation on cloud-free days.

PubMed

Grifoni, D; Zipoli, G; Sabatini, F; Messeri, G; Bacci, L

2013-12-01

Action spectrum (AS) describes the relative effectiveness of ultraviolet (UV) radiation in producing biological effects and allows spectral UV irradiance to be weighted in order to compute biologically effective UV radiation (UVBE). The aim of this research was to study the seasonal and latitudinal distribution over Europe of daily UVBE doses responsible for various biological effects on humans and plants. Clear sky UV radiation spectra were computed at 30-min time intervals for the first day of each month of the year for Rome, Potsdam and Trondheim using a radiative transfer model fed with climatological data. Spectral data were weighted using AS for erythema, vitamin D synthesis, cataract and photokeratitis for humans, while the generalised plant damage and the plant damage AS were used for plants. The daily UVBE doses for the above-mentioned biological processes were computed and are analysed in this study. The patterns of variation due to season (for each location) and latitude (for each date) resulted as being specific for each adopted AS. The biological implications of these results are briefly discussed highlighting the importance of a specific UVBE climatology for each biological process.

A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY TOXIC INDUSTRIAL CHEMICALS

EPA Science Inventory

Numerous natural and man-made agents are continuously released into the environment due to human activity. Many of these agents cause irreversible damage to the normal biological functions leading to morbidity and mortality in the exposed organisms. The possibility of deliberat...

AMBIENT PARTICULATE MATTER STIMULATES OXIDATIVE STRESS IN BRAIN MICROGLIA AND DAMAGES NEURONS IN CULTURE.

EPA Science Inventory

Ambient particulate matter (PM) damages biological targets through oxidative stress (OS) pathways. Several reports indicate that the brain is one of those targets. Since microglia (brain macrophage) are critical to OS-mediated neurodegeneration, their response to concentrated amb...

Influence of p53 status on the effects of boron neutron capture therapy in glioblastoma.

PubMed

Seki, Keiko; Kinashi, Yuko; Takahashi, Sentaro

2015-01-01

The tumor suppressor gene p53 is mutated in glioblastoma. We studied the relationship between the p53 gene and the biological effects of boron neutron capture therapy (BNCT). The human glioblastoma cells; A172, expressing wild-type p53, and T98G, with mutant p53, were irradiated by the Kyoto University Research Reactor (KUR). The biological effects after neutron irradiation were evaluated by the cell killing effect, 53BP1 foci assay and apoptosis induction. The survival-fraction data revealed that A172 was more radiosensitive than T98G, but the difference was reduced when boronophenylalanine (BPA) was present. Both cell lines exhibited similar numbers of foci, suggesting that the initial levels of DNA damage did not depend on p53 function. Detection of apoptosis revealed a lower rate of apoptosis in the T98G. BNCT causes cell death in glioblastoma cells, regardless of p53 mutation status. In T98G cells, cell killing and apoptosis occurred effectively following BNCT. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Solar irradiance changes and photobiological effects at earth's surface following astrophysical ionizing radiation events.

PubMed

Thomas, Brian C; Neale, Patrick J; Snyder, Brock R

2015-03-01

Astrophysical ionizing radiation events have been recognized as a potential threat to life on Earth, primarily through depletion of stratospheric ozone and subsequent increase in surface-level solar ultraviolet radiation. Simulations of the atmospheric effects of a variety of events (such as supernovae, gamma-ray bursts, and solar proton events) have been previously published, along with estimates of biological damage at Earth's surface. In this work, we employed the Tropospheric Ultraviolet and Visible (TUV) radiative transfer model to expand and improve calculations of surface-level irradiance and biological impacts following an ionizing radiation event. We considered changes in surface-level UVB, UVA, and photosynthetically active radiation (visible light) for clear-sky conditions and fixed aerosol parameter values. We also considered a wide range of biological effects on organisms ranging from humans to phytoplankton. We found that past work overestimated UVB irradiance but that relative estimates for increase in exposure to DNA-damaging radiation are still similar to our improved calculations. We also found that the intensity of biologically damaging radiation varies widely with organism and specific impact considered; these results have implications for biosphere-level damage following astrophysical ionizing radiation events. When considering changes in surface-level visible light irradiance, we found that, contrary to previous assumptions, a decrease in irradiance is only present for a short time in very limited geographical areas; instead we found a net increase for most of the modeled time-space region. This result has implications for proposed climate changes associated with ionizing radiation events.

Low-concentration BPAF- and BPF-induced cell biological effects are mediated by ROS in MCF-7 breast cancer cells.

PubMed

Lei, Bingli; Sun, Su; Xu, Jie; Feng, Chenglian; Yu, Yingxin; Xu, Gang; Wu, Minghong; Peng, Wei

2018-02-01

Reactive oxygen species (ROS) induced by bisphenol A (BPA) have been implicated in cellular oxidative damage and carcinogenesis. It is not known whether the potential alternatives of BPA, bisphenol AF (BPAF), and bisphenol F (BPF) can also induce ROS involved in mediating biological responses. This study evaluated the toxicity of BPAF and BPF on cell proliferation, DNA damage, intracellular calcium homeostasis, and ROS generation in MCF-7 human breast cancer cells. The results showed that BPAF at 0.001-1 μM and BPF at 0.01-1 μM significantly increased cell viability and at 25 and 50 μM, both compounds decreased cell viability. At 0.01-10 μM, both BPAF and BPF increased DNA damage and significantly elevated ROS and intracellular Ca 2+ levels in MCF-7 cells. These biological effects were attenuated by the ROS scavenger N-acetylcysteine (NAC), indicating that ROS played a key role in the observed biological effects of BPAF and BPF on MCF-7 cells. These findings can deepen our understanding on the toxicity of BPAF and BPF, and provide basis data to further evaluate the potential health harm and establish environmental standard of BPAF and BPF.

Track structure model of cell damage in space flight

NASA Technical Reports Server (NTRS)

Katz, Robert; Cucinotta, Francis A.; Wilson, John W.; Shinn, Judy L.; Ngo, Duc M.

1992-01-01

The phenomenological track-structure model of cell damage is discussed. A description of the application of the track-structure model with the NASA Langley transport code for laboratory and space radiation is given. Comparisons to experimental results for cell survival during exposure to monoenergetic, heavy-ion beams are made. The model is also applied to predict cell damage rates and relative biological effectiveness for deep-space exposures.

DNA DAMAGE QUANTITATION BY ALKALINE GEL ELECTROPHORESIS.

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

SUTHERLAND,B.M.; BENNETT,P.V.; SUTHERLAND, J.C.

2004-03-24

Physical and chemical agents in the environment, those used in clinical applications, or encountered during recreational exposures to sunlight, induce damages in DNA. Understanding the biological impact of these agents requires quantitation of the levels of such damages in laboratory test systems as well as in field or clinical samples. Alkaline gel electrophoresis provides a sensitive (down to {approx} a few lesions/5Mb), rapid method of direct quantitation of a wide variety of DNA damages in nanogram quantities of non-radioactive DNAs from laboratory, field, or clinical specimens, including higher plants and animals. This method stems from velocity sedimentation studies of DNAmore » populations, and from the simple methods of agarose gel electrophoresis. Our laboratories have developed quantitative agarose gel methods, analytical descriptions of DNA migration during electrophoresis on agarose gels (1-6), and electronic imaging for accurate determinations of DNA mass (7-9). Although all these components improve sensitivity and throughput of large numbers of samples (7,8,10), a simple version using only standard molecular biology equipment allows routine analysis of DNA damages at moderate frequencies. We present here a description of the methods, as well as a brief description of the underlying principles, required for a simplified approach to quantitation of DNA damages by alkaline gel electrophoresis.« less

Gold nanoparticles induce DNA damage in the blood and liver of rats

NASA Astrophysics Data System (ADS)

Cardoso, Eria; Londero, Eduardo; Ferreira, Gabriela Kozuchovski; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rohr, Paula; da Silva, Luciano; Andrade, Vanessa M.; da Silva Paula, Marcos Marques

2014-11-01

The potential of gold nanoparticles (GNPs) for use in different biological applications has led to a strong interest in the study of their possible deleterious effects in biological systems and how these effects may be mitigated. This study was undertaken to investigate the effects of the acute and chronic administration of GNPs with mean diameters of 10 and 30 nm on deoxyribonucleic acid (DNA) damage in the blood and liver of adult rats. For the acute administration, Wistar adult rats received a single intraperitoneal injection of either GNPs or a saline solution. For the chronic administration, Wistar adult rats received a daily single injection of the same GNPs or saline solution for 28 days. Twenty-four hours after either the single (acute) or final injection (chronic), the rats were euthanised by decapitation, and the blood and liver were isolated for the evaluation of DNA damage. In this study, we demonstrated that the acute and chronic administration of GNPs 10 and 30 nm in size increased the frequency of DNA damage and the damage index in the blood and liver of adult rats. These findings suggest that the DNA damage may be caused by oxidative stress, which occurred regardless of the type of administration and GNP size.

What Should Be in the Biology Curriculum?

ERIC Educational Resources Information Center

Leyser, Ottoline

2014-01-01

The ever-increasing amount of biological knowledge has resulted in compression of topics in the curriculum to a précis of current understanding. This gives the impression that biology is about a list of things we know. This misconception is extremely damaging, contributing to the idea that science is an impersonal process that generates facts,…

Nonlinear dynamics and damage induced properties of soft matter with application in oncology

NASA Astrophysics Data System (ADS)

Naimark, O.

2017-09-01

Molecular-morphological signs of oncogenesis could be linked to multiscale collective effects in molecular, cell and tissue related to defects (damage) dynamics. It was shown that nonlinear behavior of biological systems can be linked to the existence of characteristic collective open state modes providing the coherent expression dynamics. New type of criticality in nonequilibrium systems with defects—structural-scaling transition allows the definition of the `driving force' for a biological soft matter related to consolidated open states. The set of collective open states (breathers, autosolitons and blow-up modes) in the molecular ensembles provides the collective expression dynamics to attract the entire system (cell, tissue) toward a few preferred global states. The co-existence of three types of collective modes determines the multifractal scenario of biological soft matter dynamics. The appearance of `globally convergent' dynamics corresponding to the coherent behavior of multiscale blow-up open states (blow-up gene expression) leads to anomalous localized softening (blow-up localized damage) and the subjection of the cells (or tissue) to monofractal dynamics. This dynamics can be associated with cancer progression.

Repair of clustered DNA damage caused by high LET radiation in human fibroblasts

NASA Technical Reports Server (NTRS)

Rydberg, B.; Lobrich, M.; Cooper, P. K.; Chatterjee, A. (Principal Investigator)

1998-01-01

It has recently been demonstrated experimentally that DNA damage induced by high LET radiation in mammalian cells is non-randomly distributed along the DNA molecule in the form of clusters of various sizes. The sizes of such clusters range from a few base-pairs to at least 200 kilobase-pairs. The high biological efficiency of high LET radiation for induction of relevant biological endpoints is probably a consequence of this clustering, although the exact mechanisms by which the clustering affects the biological outcome is not known. We discuss here results for induction and repair of base damage, single-strand breaks and double-strand breaks for low and high LET radiations. These results are discussed in the context of clustering. Of particular interest is to determine how clustering at different scales affects overall rejoining and fidelity of rejoining of DNA double-strand breaks. However, existing methods for measuring repair of DNA strand breaks are unable to resolve breaks that are close together in a cluster. This causes problems in interpretation of current results from high LET radiation and will require new methods to be developed.

RNA/DNA Hybrid Interactome Identifies DXH9 as a Molecular Player in Transcriptional Termination and R-Loop-Associated DNA Damage.

PubMed

Cristini, Agnese; Groh, Matthias; Kristiansen, Maiken S; Gromak, Natalia

2018-05-08

R-loops comprise an RNA/DNA hybrid and displaced single-stranded DNA. They play important biological roles and are implicated in pathology. Even so, proteins recognizing these structures are largely undefined. Using affinity purification with the S9.6 antibody coupled to mass spectrometry, we defined the RNA/DNA hybrid interactome in HeLa cells. This consists of known R-loop-associated factors SRSF1, FACT, and Top1, and yet uncharacterized interactors, including helicases, RNA processing, DNA repair, and chromatin factors. We validate specific examples of these interactors and characterize their involvement in R-loop biology. A top candidate DHX9 helicase promotes R-loop suppression and transcriptional termination. DHX9 interacts with PARP1, and both proteins prevent R-loop-associated DNA damage. DHX9 and other interactome helicases are overexpressed in cancer, linking R-loop-mediated DNA damage and disease. Our RNA/DNA hybrid interactome provides a powerful resource to study R-loop biology in health and disease. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Induced defences alter the strength and direction of natural selection on reproductive traits in common milkweed.

PubMed

Thompson, K A; Cory, K A; Johnson, M T J

2017-06-01

Evolutionary biologists have long sought to understand the ecological processes that generate plant reproductive diversity. Recent evidence indicates that constitutive antiherbivore defences can alter natural selection on reproductive traits, but it is unclear whether induced defences will have the same effect and whether reduced foliar damage in defended plants is the cause of this pattern. In a factorial field experiment using common milkweed, Asclepias syriaca L., we induced plant defences using jasmonic acid (JA) and imposed foliar damage using scissors. We found that JA-induced plants experienced selection for more inflorescences that were smaller in size (fewer flowers), whereas control plants only experienced a trend towards selection for larger inflorescences (more flowers); all effects were independent of foliar damage. Our results demonstrate that induced defences can alter both the strength and direction of selection on reproductive traits, and suggest that antiherbivore defences may promote the evolution of plant reproductive diversity. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

The Biological Effectiveness of Silicon Ions is Significantly Higher than Iron Ions for the Induction of Chromosome Damage in Human Lymphocytes

NASA Technical Reports Server (NTRS)

George, Kerry; Hada, Megumi; Cucinotta, F. A.

2010-01-01

Chromosome aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to Si-28-ions with energies ranging from 90 to 600 MeV/u, or Fe-56-ions with energies ranging from 200 to 5,000 MeV/u. The LET of the various Fe beams in this study ranged from 145 to 440 keV/micron and the LET Si ions ranged from 48 to 158 keV/micron. Doses delivered were in the 10 to 200 cGy range. Dose response curves for chromosome exchanges in cells at first division after exposure, measured using fluorescence in situ hybridization (FISH) with whole chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose response curve for chromosome damage with respect to gamma-rays. The estimates of RBE(sub max) values for total chromosome exchanges ranged from 4.4+/-0.4 to 31.5+/-2.6 for Fe ions, and 11.8+/-1.0 to 42.2+/-3.3 for Si ions. The highest RBE(sub max) value for Fe ions was obtained with the 600 Mev/u beam and 170 MeV/u beam produced the highest RBE(sub max) value for Si ions. For both ions the RBE(sub max) values increased with LET, reaching a maximum at about 180 keV/micron for Fe and about 100 keV/micron for Si, and decreased with further increase in LET.

Material heterogeneity in cancellous bone promotes deformation recovery after mechanical failure

PubMed Central

Torres, Ashley M.; Matheny, Jonathan B.; Keaveny, Tony M.; Taylor, David; Rimnac, Clare M.; Hernandez, Christopher J.

2016-01-01

Many natural structures use a foam core and solid outer shell to achieve high strength and stiffness with relatively small amounts of mass. Biological foams, however, must also resist crack growth. The process of crack propagation within the struts of a foam is not well understood and is complicated by the foam microstructure. We demonstrate that in cancellous bone, the foam-like component of whole bones, damage propagation during cyclic loading is dictated not by local tissue stresses but by heterogeneity of material properties associated with increased ductility of strut surfaces. The increase in surface ductility is unexpected because it is the opposite pattern generated by surface treatments to increase fatigue life in man-made materials, which often result in reduced surface ductility. We show that the more ductile surfaces of cancellous bone are a result of reduced accumulation of advanced glycation end products compared with the strut interior. Damage is therefore likely to accumulate in strut centers making cancellous bone more tolerant of stress concentrations at strut surfaces. Hence, the structure is able to recover more deformation after failure and return to a closer approximation of its original shape. Increased recovery of deformation is a passive mechanism seen in biology for setting a broken bone that allows for a better approximation of initial shape during healing processes and is likely the most important mechanical function. Our findings suggest a previously unidentified biomimetic design strategy in which tissue level material heterogeneity in foams can be used to improve deformation recovery after failure. PMID:26929343

The Influence of Shielding on the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage

NASA Technical Reports Server (NTRS)

Goeorge, Kerry; Cucinotta, Francis A.

2007-01-01

Chromosome damage was assessed in human peripheral blood lymphocytes after in vitro exposure to the either Si-28 (490 or 600 MeV/n), Ti-48 (1000 MeV/n), or Fe-56 (600, 1000, or 5000 MeV/n). LET values for these ions ranged from 51 to 184 keV/micron and doses ranged from 10 to 200 cGy. The effect of either aluminum or polyethylene shielding on the induction of chromosome aberrations was investigated for each ion. Chromosome exchanges were measured using fluorescence in situ hybridization (FISH) with whole chromosome probes in cells collected at G2 and mitosis in first division post irradiation after chromosomes were prematurely condensed using calyculin-A. The yield of chromosomal aberrations increased linearly with dose and the relative biological effectiveness (RBE) for the primary beams, estimated from the initial slope of the dose response curve for total chromosomal exchanges with respect to gamma-rays, ranged from 9 to 35. The RBE values increased with LET, reaching a maximum for the 600 MeV/n Fe ions with LET of 184 keV/micron. When the LET of the primary beam was below approximately 100 keV/micron, the addition of shielding material increased the effectiveness per unit dose. Whereas shielding decreased the effectiveness per unit dose when the LET of primary beams was higher than 100 keV/micron. The yield of aberrations correlated with the dose-average LET of the beam after traversal through the shielding.

Protein oxidation and peroxidation

PubMed Central

Davies, Michael J.

2016-01-01

Proteins are major targets for radicals and two-electron oxidants in biological systems due to their abundance and high rate constants for reaction. With highly reactive radicals damage occurs at multiple side-chain and backbone sites. Less reactive species show greater selectivity with regard to the residues targeted and their spatial location. Modification can result in increased side-chain hydrophilicity, side-chain and backbone fragmentation, aggregation via covalent cross-linking or hydrophobic interactions, protein unfolding and altered conformation, altered interactions with biological partners and modified turnover. In the presence of O2, high yields of peroxyl radicals and peroxides (protein peroxidation) are formed; the latter account for up to 70% of the initial oxidant flux. Protein peroxides can oxidize both proteins and other targets. One-electron reduction results in additional radicals and chain reactions with alcohols and carbonyls as major products; the latter are commonly used markers of protein damage. Direct oxidation of cysteine (and less commonly) methionine residues is a major reaction; this is typically faster than with H2O2, and results in altered protein activity and function. Unlike H2O2, which is rapidly removed by protective enzymes, protein peroxides are only slowly removed, and catabolism is a major fate. Although turnover of modified proteins by proteasomal and lysosomal enzymes, and other proteases (e.g. mitochondrial Lon), can be efficient, protein hydroperoxides inhibit these pathways and this may contribute to the accumulation of modified proteins in cells. Available evidence supports an association between protein oxidation and multiple human pathologies, but whether this link is causal remains to be established. PMID:27026395

Toxicity of Biologically Active Peptides and Future Safety Aspects: An Update.

PubMed

Khan, Fazlullah; Niaz, Kamal; Abdollahi, Mohammad

2018-02-18

Peptides are fragments of proteins with significant biological activities. These peptides are encoded in the protein sequence. Initially, such peptides are inactive in their parental form, unless proteolytic enzymes are released. These peptides then exhibit various functions and play a therapeutic role in the body. Besides the therapeutic and physiological activities of peptides, the main purpose of this study was to highlight the safety aspects of peptides. We performed an organized search of available literature using PubMed, Google Scholar, Medline, EMBASE, Reaxys and Scopus databases. All the relevant citations including research and review articles about the toxicity of biologically active peptides were evaluated and gathered in this study. Biological peptides are widely used in the daily routine ranging from food production to the cosmetics industry and also they have a beneficial role in the treatment and prevention of different diseases. These peptides are manufactured by both chemical and biotechnological techniques, which show negligible toxicity, however, some naturally occurring peptides and enzymes may induce high toxicity. Depending upon the demand and expected use in the food or pharmaceutical industry, we need different approaches to acertain the safety of these peptides preferentially through in silico methods. Intestinal wall disruption, erythrocytes and lymphocytes toxicity, free radical production, enzymopathic and immunopathic tissue damage and cytotoxicity due to the consumption of peptides are the main problems in the biological system that lead to various complicated disorders. Therefore, before considering biologically active peptides for food production and for therapeutic purpose, it is first necessary to evaluate the immunogenicity and toxicities of peptides. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

DETECTION OF LOW DOSE RADIATION-AND CHEMICALLY-INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAYS

EPA Science Inventory

Rapid, sensitive and simple assays for radiation- and chemically-induced DNA damage can be of significant benefit to a number of fields including radiation biology, clinical research, and environmental monitoring. Although temperature-induced DNA strand separation has been use...

(WASHINGTON, DC) A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY TOXIC INDUSTRIAL CHEMICALS

EPA Science Inventory

Numerous natural and man-made agents are continuously released into the environment due to human activity. Many of these agents cause irreversible damage to the normal biological functions leading to morbidity and mortality in the exposed organisms. The possibility of deliberat...

EVALUATION OF GENETIC DAMAGE IN FISH EXPOSED TO PESTICIDES IN FIELD AQUATIC MICROCOSMS

EPA Science Inventory

Single cell gel electrophoresis (SCG) and micronucleus (MN) assays were used to measure DNA strand breaks and chromosomal damage in fish blood erythrocytes as biological indicators of exposure to alachlor and atrazine in a surrogate aquatic ecosystem. Caged common carp (Cyprinus...

ESR study of a biological assay on whole blood: antioxidant efficiency of various vitamins.

PubMed

Stocker, Pierre; Lesgards, Jean-François; Vidal, Nicolas; Chalier, Florence; Prost, Michel

2003-04-07

This study deals with the activity of various vitamins against the radical-mediated oxidative damage in human whole blood. We have used a biological method that allows both the evaluation of plasma and that of red blood cell resistance against the free radicals induced by 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH). Spin trapping measures using mainly 5-(diethoxyphosphoryl)-5-methyl-1-pyrolline N-oxide nitrone (DEPMPO) were carried out under several conditions to identify the free radicals implicated in this test. Only the oxygenated-centred radical generated from AAPH was found highly reactive to initiate red blood cell lysis. With DEPMPO only alkoxyl radicals were observed and no evidence was found for alkylperoxyl radicals. The antioxidant activity of several lipid- and water-soluble vitamins has been assessed by the biological assay and through two chemical methods. We have noticed high antioxidant activities for tocopherols (in the order delta>gamma>alpha) in the biological test but not through chemical methods. At 1 microM, the delta-tocopherol efficiency in inhibiting radical-induced red blood cell hemolysis was three times as high as the alpha-tocopherol efficiency. For beta-carotene no significant activity even in whole blood was shown. Highly surprising antioxidant activities were observed for acid folic and pyridoxine, compared to ascorbic acid. At 10 microM, the effectiveness of folic acid was almost three times as high as vitamin C. The biological test seems clinically more relevant than most other common assays because it can detect several classes of antioxidants.

[Abdominal traumatic evisceration: reconstruction abdominal wall with biologic mesh and negative pressure therapy].

PubMed

Jiménez Gómez, M; Betancor Rivera, N; Lima Sánchez, J; Hernández Hernández, J R

2016-04-10

Abdominal traumatic evisceration as a result of high energy trauma is uncommon. Once repaired the possible internal damage, an abdominal wall defect of high complexity may exist, whose reconstruction represents a surgical challenge. Politraumatized male with important abdominal muculocutaneous avulsion and evisceration. After initial repair, the patient developed a big eventration in which we use a porcine dermis-derived mesh (Permacol TM ), a safe and effective alternative in abdominal wall repair, thanks to its seamless integration with other tissues, even when exposed. Negative pressure therapy has been used for the management of wound complications after surgical implantation of PermacolTM mesh. We describe our experience with the use of PermacolTM mesh and negative pressure therapy to aid the wound closure after skin necrosis and exposed mesh.

Evolutionary Convergence and Divergence in NLR Function and Structure.

PubMed

Meunier, Etienne; Broz, Petr

2017-10-01

The recognition of cellular damage caused by either pathogens or abiotic stress is essential for host defense in all forms of life in the plant and animal kingdoms. The NOD-like receptors (NLRs) represent a large family of multidomain proteins that were initially discovered for their role in host defense in plants and vertebrates. Over recent years the wide distribution of NLRs among metazoans has become apparent and their origins have begun to emerge. Moreover, intense study of NLR function has shown that they play essential roles beyond pathogen recognition - in the regulation of antigen presentation, cell death, inflammation, and even in embryonic development. We summarize here the latest insights into NLR biology and discuss examples of converging and diverging evolution of NLR function and structure. Copyright © 2017 Elsevier Ltd. All rights reserved.

In situ study of live specimens in an environmental scanning electron microscope.

PubMed

Tihlaříková, Eva; Neděla, Vilém; Shiojiri, Makoto

2013-08-01

In this paper we introduce new methodology for the observation of living biological samples in an environmental scanning electron microscope (ESEM). The methodology is based on an unconventional initiation procedure for ESEM chamber pumping, free from purge-flood cycles, and on the ability to control thermodynamic processes close to the sample. The gradual and gentle change of the working environment from air to water vapor enables the study of not only living samples in dynamic in situ experiments and their manifestation of life (sample walking) but also its experimentally stimulated physiological reactions. Moreover, Monte Carlo simulations of primary electron beam energy losses in a water layer on the sample surface were studied; consequently, the influence of the water thickness on radiation, temperature, or chemical damage of the sample was considered.

Double Linear Damage Rule for Fatigue Analysis

NASA Technical Reports Server (NTRS)

Halford, G.; Manson, S.

1985-01-01

Double Linear Damage Rule (DLDR) method for use by structural designers to determine fatigue-crack-initiation life when structure subjected to unsteady, variable-amplitude cyclic loadings. Method calculates in advance of service how many loading cycles imposed on structural component before macroscopic crack initiates. Approach eventually used in design of high performance systems and incorporated into design handbooks and codes.

Flexural testing on carbon fibre laminates taking into account their different behaviour under tension and compression

NASA Astrophysics Data System (ADS)

Serna Moreno, M. C.; Romero Gutierrez, A.; Martínez Vicente, J. L.

2016-07-01

An analytical model has been derived for describing the results of three-point-bending tests in materials with different behaviour under tension and compression. The shift of the neutral plane and the damage initiation mode and its location have been defined. The validity of the equations has been reviewed by testing carbon fibre-reinforced polymers (CFRP), typically employed in different weight-critical applications. Both unidirectional and cross-ply laminates have been studied. The initial failure mode produced depends directly on the beam span- thickness relation. Therefore, specimens with different thicknesses have been analysed for examining the damage initiation due to either the bending moment or the out-of-plane shear load. The experimental description of the damage initiation and evolution has been shown by means of optical microscopy. The good agreement between the analytical estimations and the experimental results shows the validity of the analytical model exposed.

Tracking down the links between charged particles and biological response: A UK perspective

NASA Astrophysics Data System (ADS)

Hill, Mark A.

2013-07-01

The UK has a long history of radiobiology research into charged particles, with interest likely to expand in the coming years following the recent government announcement of £250 million to build two proton beam therapy facilities in the UK. A brief overview of research and facilities past and present with respect to radiation protection and oncology along with biological consequences and underlying mechanisms will be presented and discussed. Increased knowledge of the mechanisms underpinning the radiation action on biological systems is important in understanding, not only the risks associated with exposure, but also in optimising radiotherapy treatment of cancer. Ionizing radiation is always in the form of structure tracks which are a unique characteristic of ionizing radiation alone producing damage grossly different and far more biologically effective than endogenous damage. The track structure is the prime determinant of biological response to DNA, with charged particles of increasing LET leading to an increase in the frequency and complexity of clustered DNA damage. High-LET particles will also produce non-homogeneous dose distribution through a cell nucleus resulting in correlated DNA breaks along the path of the particle and an increase in the probability of complex chromosomal rearrangements. However it is now well established that there is variety of phenomena that do not conform to the conventional paradigm of targeted radiobiology, but there is insufficient evidence to assess the implications of these non-targeted effects for radiotherapy or relevance to risk for human health.

Using Autonomous Bio Nanosatellites for Deep Space Exploration

NASA Astrophysics Data System (ADS)

Santa Maria, S. R.; Liddell, L. C.; Tieze, S. M.; Ricco, A. J.; Hanel, R.; Bhattacharya, S.

2018-02-01

NASA's BioSentinel mission will conduct the first study of biological response to deep-space radiation in 45 years. It is an automated nanosatellite that will measure the DNA damage response to ambient space radiation in a model biological organism.

Damage Progression in Buckle-Resistant Notched Composite Plates Loaded in Uniaxial Compression

NASA Technical Reports Server (NTRS)

McGowan, David M.; Davila, Carlos G.; Ambur, Damodar R.

2001-01-01

Results of an experimental and analytical evaluation of damage progression in three stitched composite plates containing an angled central notch and subjected to compression loading are presented. Parametric studies were conducted systematically to identify the relative effects of the material strength parameters on damage initiation and growth. Comparisons with experiments were conducted to determine the appropriate in situ values of strengths for progressive failure analysis. These parametric studies indicated that the in situ value of the fiber buckling strength is the most important parameter in the prediction of damage initiation and growth in these notched composite plates. Analyses of the damage progression in the notched, compression-loaded plates were conducted using in situ material strengths. Comparisons of results obtained from these analyses with experimental results for displacements and axial strains show good agreement.

Current Status of Single Particle Imaging with X-ray Lasers

DOE PAGES

Sun, Zhibin; Fan, Jiadong; Li, Haoyuan; ...

2018-01-22

The advent of ultrafast X-ray free-electron lasers (XFELs) opens the tantalizing possibility of the atomic-resolution imaging of reproducible objects such as viruses, nanoparticles, single molecules, clusters, and perhaps biological cells, achieving a resolution for single particle imaging better than a few tens of nanometers. Improving upon this is a significant challenge which has been the focus of a global single particle imaging (SPI) initiative launched in December 2014 at the Linac Coherent Light Source (LCLS), SLAC National Accelerator Laboratory, USA. A roadmap was outlined, and significant multi-disciplinary effort has since been devoted to work on the technical challenges of SPImore » such as radiation damage, beam characterization, beamline instrumentation and optics, sample preparation and delivery and algorithm development at multiple institutions involved in the SPI initiative. Currently, the SPI initiative has achieved 3D imaging of rice dwarf virus (RDV) and coliphage PR772 viruses at ~10 nm resolution by using soft X-ray FEL pulses at the Atomic Molecular and Optical (AMO) instrument of LCLS. Meanwhile, diffraction patterns with signal above noise up to the corner of the detector with a resolution of ~6 Ångström (Å) were also recorded with hard X-rays at the Coherent X-ray Imaging (CXI) instrument, also at LCLS. Achieving atomic resolution is truly a grand challenge and there is still a long way to go in light of recent developments in electron microscopy. However, the potential for studying dynamics at physiological conditions and capturing ultrafast biological, chemical and physical processes represents a tremendous potential application, attracting continued interest in pursuing further method development. In this paper, we give a brief introduction of SPI developments and look ahead to further method development.« less

Current Status of Single Particle Imaging with X-ray Lasers

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

Sun, Zhibin; Fan, Jiadong; Li, Haoyuan

The advent of ultrafast X-ray free-electron lasers (XFELs) opens the tantalizing possibility of the atomic-resolution imaging of reproducible objects such as viruses, nanoparticles, single molecules, clusters, and perhaps biological cells, achieving a resolution for single particle imaging better than a few tens of nanometers. Improving upon this is a significant challenge which has been the focus of a global single particle imaging (SPI) initiative launched in December 2014 at the Linac Coherent Light Source (LCLS), SLAC National Accelerator Laboratory, USA. A roadmap was outlined, and significant multi-disciplinary effort has since been devoted to work on the technical challenges of SPImore » such as radiation damage, beam characterization, beamline instrumentation and optics, sample preparation and delivery and algorithm development at multiple institutions involved in the SPI initiative. Currently, the SPI initiative has achieved 3D imaging of rice dwarf virus (RDV) and coliphage PR772 viruses at ~10 nm resolution by using soft X-ray FEL pulses at the Atomic Molecular and Optical (AMO) instrument of LCLS. Meanwhile, diffraction patterns with signal above noise up to the corner of the detector with a resolution of ~6 Ångström (Å) were also recorded with hard X-rays at the Coherent X-ray Imaging (CXI) instrument, also at LCLS. Achieving atomic resolution is truly a grand challenge and there is still a long way to go in light of recent developments in electron microscopy. However, the potential for studying dynamics at physiological conditions and capturing ultrafast biological, chemical and physical processes represents a tremendous potential application, attracting continued interest in pursuing further method development. In this paper, we give a brief introduction of SPI developments and look ahead to further method development.« less

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.

Vision-guided micromanipulation system for biomedical application

NASA Astrophysics Data System (ADS)

Shim, Jae-Hong; Cho, Sung-Yong; Cha, Dong-Hyuk

2004-10-01

In these days, various researches for biomedical application of robots have been carried out. Particularly, robotic manipulation of the biological cells has been studied by many researchers. Usually, most of the biological cell's shape is sphere. Commercial biological manipulation systems have been utilized the 2-Dimensional images through the optical microscopes only. Moreover, manipulation of the biological cells mainly depends on the subjective viewpoint of an operator. Due to these reasons, there exist lots of problems such as slippery and destruction of the cell membrane and damage of the pipette tip etc. In order to overcome the problems, we have proposed a vision-guided biological cell manipulation system. The newly proposed manipulation system makes use of vision and graphic techniques. Through the proposed procedures, an operator can inject the biological cell scientifically and objectively. Also, the proposed manipulation system can measure the contact force occurred at injection of a biological cell. It can be transmitted a measured force to the operator by the proposed haptic device. Consequently, the proposed manipulation system could safely handle the biological cells without any damage. This paper presents the introduction of our vision-guided manipulation techniques and the concept of the contact force sensing. Through a series of experiments the proposed vision-guided manipulation system shows the possibility of application for precision manipulation of the biological cell such as DNA.

Catastrophic failure of contaminated fused silica optics at 355 nm

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

Genin, F. Y., LLNL

1996-12-03

For years, contamination has been known to degrade the performance of optics and to sometimes initiate laser-induced damage to initiate. This study has W to quantify these effects for fused silica windows used at 355 mm Contamination particles (Al, Cu, TiO{sub 2} and ZrO{sub 2}) were artificially deposited onto the surface and damage tests were conducted with a 3 ns NdYAG laser. The damage morphology was characterized by Nomarski optical microscopy. The results showed that the damage morphology for input and output surface contamination is different. For input surface contamination, both input and output surfaces can damage. In particular, themore » particle can induce pitting or drilling of the surface where the beam exits. Such damage usually grows catastrophically. Output surface contamination is usually ablated away on the shot but can also induce catastrophic damage. Plasmas are observed during illumination and seem to play an important role in the damage mechanism. The relationship between fluence and contamination size for which catastrophic damage occurred was plotted for different contamination materials. The results show that particles even as small as 10 {micro}m can substantially decrease the damage threshold of the window and that metallic particles on the input surface have a more negative effect than oxide particles.« less

GENETIC DAMAGE INDICATORS IN FISH EXPOSED TO VARYING STREAM CONDITIONS IN AN AGRICULTURAL WATERSHED

EPA Science Inventory

Micronucleus (MN) and single cell gel electrophoresis (SCG) measures of genetic damage in fish erythrocytes were included in an evaluation of a wide range of biological and physical stream condition parameters being developed for use in watershed and regional scale assessments. B...

Microsoft Biology Initiative: .NET Bioinformatics Platform and Tools

PubMed Central

Diaz Acosta, B.

2011-01-01

The Microsoft Biology Initiative (MBI) is an effort in Microsoft Research to bring new technology and tools to the area of bioinformatics and biology. This initiative is comprised of two primary components, the Microsoft Biology Foundation (MBF) and the Microsoft Biology Tools (MBT). MBF is a language-neutral bioinformatics toolkit built as an extension to the Microsoft .NET Framework—initially aimed at the area of Genomics research. Currently, it implements a range of parsers for common bioinformatics file formats; a range of algorithms for manipulating DNA, RNA, and protein sequences; and a set of connectors to biological web services such as NCBI BLAST. MBF is available under an open source license, and executables, source code, demo applications, documentation and training materials are freely downloadable from http://research.microsoft.com/bio. MBT is a collection of tools that enable biology and bioinformatics researchers to be more productive in making scientific discoveries.

A novel modeling and simulation technique of photo--thermal interactions between lasers and living biological tissues undergoing multiple changes in phase.

PubMed

Dua, Rajan; Chakraborty, Suman

2005-06-01

Knowledge of heat transfer in biological bodies has many therapeutic applications involving either raising or lowering of temperature, and often requires precise monitoring of the spatial distribution of thermal histories that are produced during a treatment protocol. Extremes of temperature into the freezing and burning ranges are useful in surgical procedures for selective killing and/or removal of target tissues. For example, the primary objective of hyperthermia is to raise the temperature of the diseased tissue to a therapeutic value, typically 41- 44 degrees C, and then thermally destroy it. The present paper therefore aims to develop a mathematical model for effective simulation of photo--thermal interactions between laser rays and biological tissues. In particular, damage of biological tissues when subjected to single point laser diathermy is numerically investigated using a unique enthalpy-based approach for modeling multiple phase change, (namely, melting of fat and vaporization of water content of the tissues) and the associated release/absorption of latent heat in conjunction with unsteady state heat conduction mechanisms. The governing equations of bio-heat transfer coupled with initial and boundary conditions are solved using a finite volume approach in conjunction with line by a line tri-diagonal matrix algorithm (TDMA) solver. Temperature responses of tissues subject to laser heating are quantitatively investigated in detail using the present model, and the resultant solutions are expected to be immensely useful in a variety of Bio-thermal practices in medicine and surgery.

Creativity, brain, and art: biological and neurological considerations.

PubMed

Zaidel, Dahlia W

2014-01-01

Creativity is commonly thought of as a positive advance for society that transcends the status quo knowledge. Humans display an inordinate capacity for it in a broad range of activities, with art being only one. Most work on creativity's neural substrates measures general creativity, and that is done with laboratory tasks, whereas specific creativity in art is gleaned from acquired brain damage, largely in observing established visual artists, and some in visual de novo artists (became artists after the damage). The verb "to create" has been erroneously equated with creativity; creativity, in the classic sense, does not appear to be enhanced following brain damage, regardless of etiology. The turning to communication through art in lieu of language deficits reflects a biological survival strategy. Creativity in art, and in other domains, is most likely dependent on intact and healthy knowledge and semantic conceptual systems, which are represented in several pathways in the cortex. It is adversely affected when these systems are dysfunctional, for congenital reasons (savant autism) or because of acquired brain damage (stroke, dementia, Parkinson's), whereas inherent artistic talent and skill appear less affected. Clues to the neural substrates of general creativity and specific art creativity can be gleaned from considering that art is produced spontaneously mainly by humans, that there are unique neuroanatomical and neurofunctional organizations in the human brain, and that there are biological antecedents of innovation in animals.

Creativity, brain, and art: biological and neurological considerations

PubMed Central

Zaidel, Dahlia W.

2014-01-01

Creativity is commonly thought of as a positive advance for society that transcends the status quo knowledge. Humans display an inordinate capacity for it in a broad range of activities, with art being only one. Most work on creativity’s neural substrates measures general creativity, and that is done with laboratory tasks, whereas specific creativity in art is gleaned from acquired brain damage, largely in observing established visual artists, and some in visual de novo artists (became artists after the damage). The verb “to create” has been erroneously equated with creativity; creativity, in the classic sense, does not appear to be enhanced following brain damage, regardless of etiology. The turning to communication through art in lieu of language deficits reflects a biological survival strategy. Creativity in art, and in other domains, is most likely dependent on intact and healthy knowledge and semantic conceptual systems, which are represented in several pathways in the cortex. It is adversely affected when these systems are dysfunctional, for congenital reasons (savant autism) or because of acquired brain damage (stroke, dementia, Parkinson’s), whereas inherent artistic talent and skill appear less affected. Clues to the neural substrates of general creativity and specific art creativity can be gleaned from considering that art is produced spontaneously mainly by humans, that there are unique neuroanatomical and neurofunctional organizations in the human brain, and that there are biological antecedents of innovation in animals. PMID:24917807

Comparison of helical scan and standard rotation methods in single-crystal X-ray data collection strategies.

PubMed

Polsinelli, Ivan; Savko, Martin; Rouanet-Mehouas, Cecile; Ciccone, Lidia; Nencetti, Susanna; Orlandini, Elisabetta; Stura, Enrico A; Shepard, William

2017-01-01

X-ray radiation in macromolecular crystallography can chemically alter the biological material and deteriorate the integrity of the crystal lattice with concomitant loss of resolution. Typical alterations include decarboxylation of glutamic and aspartic residues, breaking of disulfide bonds and the reduction of metal centres. Helical scans add a small translation to the crystal in the rotation method, so that for every image the crystal is shifted to expose a fresh part. On beamline PROXIMA 2A at Synchrotron SOLEIL, this procedure has been tested with various parameters in an attempt to understand how to mitigate the effects of radiation damage. Here, the strategies used and the crystallographic metrics for various scenarios are reported. Among these, the loss of bromine from bromophenyl moieties appears to be a useful monitor of radiation damage as the carbon-bromine bond is very sensitive to X-ray irradiation. Two cases are focused on where helical scans are shown to be superior in obtaining meaningful data compared with conventional methods. In one case the initial resolution of the crystal is extended over time, and in the second case the anomalous signal is preserved to provide greater effective multiplicity and easier phasing.

Ocular Involvement of Behçet's Syndrome: a Comprehensive Review.

PubMed

Ozyazgan, Yilmaz; Ucar, Didar; Hatemi, Gulen; Yazici, Yusuf

2015-12-01

Behçet's syndrome (BS) is a vasculitis involving several organ systems including the eyes. Ocular involvement is one of the most disabling complications of BS, causing loss of vision that may progress to blindness if left untreated. The typical form of ocular involvement is a relapsing and remitting panuveitis and retinal vasculitis. Initial attacks may spontaneously improve and subsequently disappear in a few weeks but tend to recur if left untreated. Destructive and recurrent attacks, especially with posterior segment and retina involvement, may cause irreversible ocular structural changes and permanent damage in sensory retina, resulting in loss of vision. The risk of irreversible damage to ocular tissue which may result in loss of vision warrants early and intensive treatment especially in patients at high risk such as young men who tend to follow an aggressive disease course. The management strategy involves rapid suppression of inflammation during the attacks and prevention of recurrent attacks. Local and systemic measures including immunosuppressives, corticosteroids, and biologic agents are used for this purpose. Surgery may be required in selected cases. The prognosis of eye involvement has greatly improved over the last decades with the effective use of immunosuppressives.

Oxidative Stress, Inflammation, and DNA Damage Responses Elicited by Silver, Titanium Dioxide, and Cerium Oxide Nanomaterials

EPA Science Inventory

Previous literature on the biological effects of engineered nanomaterials has focused largely on oxidative stress and inflammation endpoints without further investigating potential pathways. Here we examine time-sensitive biological response pathways affected by engineered nanoma...

Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells

PubMed Central

Sato, Hiromi

2017-01-01

Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways including endothelial barrier damage and inflammation, potentially leading to vascular hyperpermeability and severe illness in vivo. This work provides new insights into the pathophysiological mechanisms of Leptospira infection. PMID:28750011

Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells.

PubMed

Sato, Hiromi; Coburn, Jenifer

2017-07-01

Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways including endothelial barrier damage and inflammation, potentially leading to vascular hyperpermeability and severe illness in vivo. This work provides new insights into the pathophysiological mechanisms of Leptospira infection.

Programmable Hydrogel Ionic Circuits for Biologically Matched Electronic Interfaces.

PubMed

Zhao, Siwei; Tseng, Peter; Grasman, Jonathan; Wang, Yu; Li, Wenyi; Napier, Bradley; Yavuz, Burcin; Chen, Ying; Howell, Laurel; Rincon, Javier; Omenetto, Fiorenzo G; Kaplan, David L

2018-06-01

The increased need for wearable and implantable medical devices has driven the demand for electronics that interface with living systems. Current bioelectronic systems have not fully resolved mismatches between engineered circuits and biological systems, including the resulting pain and damage to biological tissues. Here, salt/poly(ethylene glycol) (PEG) aqueous two-phase systems are utilized to generate programmable hydrogel ionic circuits. High-conductivity salt-solution patterns are stably encapsulated within PEG hydrogel matrices using salt/PEG phase separation, which route ionic current with high resolution and enable localized delivery of electrical stimulation. This strategy allows designer electronics that match biological systems, including transparency, stretchability, complete aqueous-based connective interface, distribution of ionic electrical signals between engineered and biological systems, and avoidance of tissue damage from electrical stimulation. The potential of such systems is demonstrated by generating light-emitting diode (LED)-based displays, skin-mounted electronics, and stimulators that deliver localized current to in vitro neuron cultures and muscles in vivo with reduced adverse effects. Such electronic platforms may form the basis of future biointegrated electronic systems. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

United States Department of Agriculture-Agricultural Research Service research on biological control of arthropods.

PubMed

Hopper, Keith R

2003-01-01

During 1999-2001, ARS scientists published over 100 papers on more than 30 species of insect pest and 60 species of predator and parasitoid. These papers address issues crucial to the three strategies of biological control: conservation, augmentation and introduction. Conservation biological control includes both conserving extant populations of natural enemies by using relatively non-toxic pesticides and increasing the abundance of natural enemies in crops by providing or improving refuges for population growth and dispersal into crops. ARS scientists have been very active in determining the effects of pesticides on beneficial arthropods and in studying movement of natural enemies from refuges into crops. Augmentation involves repeated releases of natural enemies in the field, which can be inoculative or inundative. Inoculative releases are used to initiate self-propagating populations at times or in places where they would be slow to colonize. ARS scientists have studied augmentative biological control of a variety of pest insects. The targets are mostly pests in annual crops or other ephemeral habitats, where self-reproducing populations of natural enemies are not sufficiently abundant early enough to keep pest populations in check. ARS research in augmentative biological control centers on methods for rearing large numbers of healthy, effective natural enemies and for releasing them where and when they are needed at a cost less than the value of the reduction in damage to the crop. ARS scientists have researched various aspects of introductions of exotic biological control agents against a diversity of pest insects. The major issues in biological control introductions are accurate identification and adequate systematics of both natural enemies and target pests, exploration for natural enemies, predicting the success of candidates for introduction and the likelihood of non-target impacts, quarantine and rearing methods, and post-introduction evaluation of establishment, control and non-target impacts. ARS scientists have published research on several general issues in biological control. Among the most important are the mechanisms affecting mate- and host-finding and host specificity.

Comparison of Model Calculations of Biological Damage from Exposure to Heavy Ions with Measurements

NASA Astrophysics Data System (ADS)

Kim, Myung-Hee Y.; Wu, Honglu; Hada, Megumi; Cucinotta, Francis

The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET g or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. Dose delivered by the charged particle increases sharply at the Bragg peak. However, the Bragg curve does not necessarily represent the biological damage along the particle path since biological effects are influenced by the track structures of both primary and secondary particles. Therefore, the ‘‘biological Bragg curve’’ is dependent on the energy and the type of the primary particle and may vary for different biological end points. Measurements of the induction of micronuclei (MN) have made across the Bragg curve in human fibroblasts exposed to energetic silicon and iron ions in vitro at two different energies, 300 MeV/nucleon and 1 GeV/nucleon. Although the data did not reveal an increased yield of MN at the location of the Bragg peak, the increased inhibition of cell progression, which is related to cell death, was found at the Bragg peak location. These results are compared to the calculations of biological damage using a stochastic Monte-Carlo track structure model, Galactic Cosmic Ray Event-based Risk Model (GERM) code (Cucinotta et al., 2011). The GERM code estimates the basic physical properties along the passage of heavy ions in tissue and shielding materials, by which the experimental set-up can be interpreted. The code can also be used to describe the biophysical events of interest in radiobiology, cancer therapy, and space exploration. The calculation has shown that the severely damaged cells at the Bragg peak are more likely to go through reproductive death, the so called “overkill”. F. A. Cucinotta, I. Plante, A. L. Ponomarev, and M. Y. Kim, Nuclear Interactions in Heavy Ion Transport and Event-based Risk Models, Radiation Protection Dosimetry, 143 (2-4), 384-390, 2011, doi:10.1093/rpd/ncq512

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.

Fatigue In Continuous-Fiber/Metal-Matrix Composites

NASA Technical Reports Server (NTRS)

Johnson, William S.

1992-01-01

Report describes experimental approaches to quantification of fatigue damage in metal-matrix composites (MMC's). Discusses number of examples of development of damage and failure along with associated analytical models of behavior of MMC. Objectives of report are twofold. First, present experimental procedures and techniques for conducting meaningful fatigue tests to detect and quantify fatigue damage in MMC's. Second, present examples of how fatigue damage initiated and grows in various MMC's. Report furnishes some insight into what type of fatigue damage occurs and how damage quantified.

Biology and control of Varroa destructor.

PubMed

Rosenkranz, Peter; Aumeier, Pia; Ziegelmann, Bettina

2010-01-01

The ectoparasitic honey bee mite Varroa destructor was originally confined to the Eastern honey bee Apis cerana. After a shift to the new host Apis mellifera during the first half of the last century, the parasite dispersed world wide and is currently considered the major threat for apiculture. The damage caused by Varroosis is thought to be a crucial driver for the periodical colony losses in Europe and the USA and regular Varroa treatments are essential in these countries. Therefore, Varroa research not only deals with a fascinating host-parasite relationship but also has a responsibility to find sustainable solutions for the beekeeping. This review provides a survey of the current knowledge in the main fields of Varroa research including the biology of the mite, damage to the host, host tolerance, tolerance breeding and Varroa treatment. We first present a general view on the functional morphology and on the biology of the Varroa mite with special emphasis on host-parasite interactions during reproduction of the female mite. The pathology section describes host damage at the individual and colony level including the problem of transmission of secondary infections by the mite. Knowledge of both the biology and the pathology of Varroa mites is essential for understanding possible tolerance mechanisms in the honey bee host. We comment on the few examples of natural tolerance in A. mellifera and evaluate recent approaches to the selection of Varroa tolerant honey bees. Finally, an extensive listing and critical evaluation of chemical and biological methods of Varroa treatments is given. This compilation of present-day knowledge on Varroa honey bee interactions emphasizes that we are still far from a solution for Varroa infestation and that, therefore, further research on mite biology, tolerance breeding, and Varroa treatment is urgently needed. Copyright 2009 Elsevier Inc. All rights reserved.

Mathematical modeling of damage in unidirectional composites

NASA Technical Reports Server (NTRS)

Goree, J. G.; Dharani, L. R.; Jones, W. F.

1983-01-01

Extending the work of Goree and Gross (1979), solutions are given for a two-dimensional region of unidirectional fibers embedded in an elastic matrix whose initial flaw may take the form of a transverse notch, a rectangular cutout, or a circular hole. Subsequent flaw-induced damage is generated by remote stresses acting parallel to the fibers. For the case of such ductile matrix composites as boron/aluminum, present results indicate that both longitudinal matrix yielding and transverse notch extension must be included in order for the model to agree with experimental results. Little difference is found for the three types of initial damage considered. In all cases, the presence of additional damage changes the nature of stress distribution through the unbroken fibers.

Progressive Fracture of Fiber Composite Thin Shell Structures Under Internal Pressure and Axial Loads

NASA Technical Reports Server (NTRS)

Gotsis, Pascal K.; Chamis, Christos C.; Minnetyan, Levon

1996-01-01

Graphite/epoxy composite thin shell structures were simulated to investigate damage and fracture progression due to internal pressure and axial loading. Defective and defect-free structures (thin cylinders) were examined. The three different laminates examined had fiber orientations of (90/0/+/-0)(sub s), where 0 is 45, 60, and 75 deg. CODSTRAN, an integrated computer code that scales up constituent level properties to the structural level and accounts for all possible failure modes, was used to simulate composite degradation under loading. Damage initiation, growth, accumulation, and propagation to fracture were included in the simulation. Burst pressures for defective and defect-free shells were compared to evaluate damage tolerance. The results showed that damage initiation began with matrix failure whereas damage and/or fracture progression occurred as a result of additional matrix failure and fiber fracture. In both thin cylinder cases examined (defective and defect-free), the optimum layup configuration was (90/0/+/-60)(sub s) because it had the best damage tolerance with respect to the burst pressure.

Probabilistic Assessment of Fracture Progression in Composite Structures

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Minnetyan, Levon; Mauget, Bertrand; Huang, Dade; Addi, Frank

1999-01-01

This report describes methods and corresponding computer codes that are used to evaluate progressive damage and fracture and to perform probabilistic assessment in built-up composite structures. Structural response is assessed probabilistically, during progressive fracture. The effects of design variable uncertainties on structural fracture progression are quantified. The fast probability integrator (FPI) is used to assess the response scatter in the composite structure at damage initiation. The sensitivity of the damage response to design variables is computed. The methods are general purpose and are applicable to stitched and unstitched composites in all types of structures and fracture processes starting from damage initiation to unstable propagation and to global structure collapse. The methods are demonstrated for a polymer matrix composite stiffened panel subjected to pressure. The results indicated that composite constituent properties, fabrication parameters, and respective uncertainties have a significant effect on structural durability and reliability. Design implications with regard to damage progression, damage tolerance, and reliability of composite structures are examined.

Nonlinear damage analysis: Postulate and evaluation

NASA Technical Reports Server (NTRS)

Leis, B. N.; Forte, T. P.

1983-01-01

The objective of this program is to assess the viability of a damage postulate which asserts that the fatigue resistance curve of a metal is history dependent due to inelastic action. The study focusses on OFE copper because this simple model material accentuates the inelastic action central to the damage postulate. Data relevant to damage evolution and crack initiation are developed via a study of surface topography. The effects of surface layer residual stresses are explored via comparative testing as were the effects in initial prestraining. The results of the study very clearly show the deformation history dependence of the fatigue resistance of OFE copper. Furthermore the concept of deformation history dependence is shown to qualitatively explain the fatigue resistance of all histories considered. Likewise quantitative predictions for block cycle histories are found to accurately track the observed results. In this respect the assertion that damage per cycle for a given level of the damage parameter is deformation history dependent appears to be physically justified.

Effect of Curvature on the Impact Damage Characteristics and Residual Strength of Composite Plates

NASA Technical Reports Server (NTRS)

Ambur, Damodar R.; Starnes, James H., Jr.

1998-01-01

The results of a study of the response and failure characteristics of thin, cylindrically curved, composite plates subjected to low-speed impact damage are presented. The results indicate that the plate radius and the plate thickness are important structural parameters that influence the nonlinear response of a plate for a given amount of impact energy. Analytical and experimental contact-force results are compared for several plates and the results correlate well. The impact-energy levels required to cause damage initiation and barely visible impact damage are a function of the plate radius for a given plate thickness. The impact-energy levels required to initiate impact damage for plates with a certain range of radii are greater than plates with other radii. The contact-force results corresponding to these impact-energy levels follow a similar trend. Residual strength results for plates with barely visible impact damage suggest that the compression-after-impact residual strength is also a function of plate radius. The residual strength of impact-damaged flat plates appears to be lower than the residual strength of the corresponding cylindrically curved plates.

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

PubMed

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

2014-08-01

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

High speed imaging for assessment of impact damage in natural fibre biocomposites

NASA Astrophysics Data System (ADS)

Ramakrishnan, Karthik Ram; Corn, Stephane; Le Moigne, Nicolas; Ienny, Patrick; Leger, Romain; Slangen, Pierre R.

2017-06-01

The use of Digital Image Correlation has been generally limited to the estimation of mechanical properties and fracture behaviour at low to moderate strain rates. High speed cameras dedicated to ballistic testing are often used to measure the initial and residual velocities of the projectile but rarely for damage assessment. The evaluation of impact damage is frequently achieved post-impact using visual inspection, ultrasonic C-scan or other NDI methods. Ultra-high speed cameras and developments in image processing have made possible the measurement of surface deformations and stresses in real time during dynamic cracking. In this paper, a method is presented to correlate the force- displacement data from the sensors to the slow motion tracking of the transient failure cracks using real-time high speed imaging. Natural fibre reinforced composites made of flax fibres and polypropylene matrix was chosen for the study. The creation of macro-cracks during the impact results in the loss of stiffness and a corresponding drop in the force history. However, optical instrumentation shows that the initiation of damage is not always evident and so the assessment of damage requires the use of a local approach. Digital Image Correlation is used to study the strain history of the composite and to identify the initiation and progression of damage. The effect of fly-speckled texture on strain measurement by image correlation is also studied. The developed method can be used for the evaluation of impact damage for different composite materials.

A comparative study with biologically and chemically synthesized nZVI: applications in Cr (VI) removal and ecotoxicity assessment using indigenous microorganisms from chromium-contaminated site.

PubMed

Ravikumar, K V G; Kumar, Deepak; Rajeshwari, A; Madhu, G M; Mrudula, P; Chandrasekaran, Natarajan; Mukherjee, Amitava

2016-02-01

In the present communication, we report a comparative study of Cr (VI) removal using biologically synthesized nano zero valent iron (BS-nZVI) and chemically synthesized nZVI (CS-nZVI), both immobilized in calcium alginate beads. The parameters like initial Cr (VI) concentration, nZVI concentration, and the contact time for Cr (VI) removal were optimized based on Box-Behnken design (BBD) by response surface modeling at a constant pH 7. Under the optimized conditions (concentration of nZVI = 1000 mg L(-1), contact time = ∼ 80 min, and initial concentration of Cr (VI) = 10 mg L(-1)), the Cr (VI) removal by the immobilized BS-nZVI and CS-nZVI alginate beads was 80.04 and 81.08 %, respectively. The adsorption of Cr (VI) onto the surface of alginate beads was confirmed by scanning electron microscopy with energy-dispersive x-ray spectroscopy (SEM-EDX), Fourier transform infrared spectroscopy (FT-IR), and Brunauer-Emmett-Teller (BET) analysis. The applicability of the process using both the sorbents was successfully test medium Cr (VI) spiked environmental water samples. In order to assess the ecotoxic effects of nZVI, the decline in cell viability, generation of intracellular reactive oxygen species (ROS), cell membrane damage, and biouptake was studied at 1000 mg L(-1) concentration, with five indigenous bacterial isolates from chromium-contaminated lake sediments and their consortium.

Relative biological effectiveness (RBE) of 210Po alpha-particles versus X-rays on lethality in bovine endothelial cells.

PubMed

Thomas, P A; Tracy, B L; Ping, T; Wickstrom, M; Sidhu, N; Hiebert, L

2003-02-01

Alpha-radiation from polonium-210 ((210)Po) can elevate background radiation dose by an order of magnitude in people consuming large quantities of meat and seafood, particularly caribou and reindeer. Because up to 50% of the ingested (210)Po body burden is initially found in the blood, a primary target for the short range alpha-particles is the endothelial cells lining the blood vessels. This study examined the relative biological effectiveness (RBE) of (210)Po alpha-particles versus 250 kVp X-rays in producing injury to cultured bovine aortic endothelial cells. Radiation effects on cells were measured in four different ways: the percentage viable cells by trypan blue dye exclusion, the number of live cells, the lactate dehydrogenase (LDH) release to medium and the ability to form colonies (clonogenic survival). Comparison of dose-response curves yielded RBE values of 13.1+/-2.5 (SEM) for cell viability, 10.3+/-1.0 for live cell number and 11.1+/-3.0 for LDH activity. The RBE values for clonogenic survival were 14.0+/-1.0 based on the ratio of the initial slopes of the dose-response curves and 13.1, 9.9 and 7.7 for 50, 10 and 1% survival rate, respectively. At X-ray doses <0.25 Gy, a pronounced stimulatory effect on proliferation was noted. Exposure to (210)Po alpha-particles was seven to 14 times more effective than X-ray exposure in causing endothelial cell damage.

Lectin I from Bauhinia variegata (BVL-I) expressed by Pichia pastoris inhibits initial adhesion of oral bacteria in vitro.

PubMed

Klafke, Gabriel Baracy; Moreira, Gustavo Marçal Schmidt Garcia; Pereira, Juliano Lacava; Oliveira, Patrícia Diaz; Conceição, Fabricio Rochedo; Lund, Rafael Guerra; Grassmann, André Alex; Dellagostin, Odir Antonio; da Silva Pinto, Luciano

2016-12-01

Lectins are non-immune proteins that reversibly bind to carbohydrates in a specific manner. Bauhinia variegata lectin I (BVL-I) is a Gal/GalNAc-specific, single-chain lectin isolated from Bauhinia variegata seeds that has been implicated in the inhibition of bacterial adhesion and the healing of damaged skin. Since the source of the native protein (nBVL) is limited, this study aimed to produce recombinant BVL-I in Pichia pastoris (rBVL-Ip). The coding sequence for BVL-I containing preferential codons for P. pastoris was cloned into the pPICZαB plasmid. A single expressing clone was selected and fermented, resulting in the secretion and glycosylation of the protein. Fed-batch fermentation in 7L-scale was performed, and the recombinant lectin was purified from culture supernatant, resulting in a yield of 1.5mg/L culture. Further, rBVL-Ip was compared to nBVL and its recombinant version expressed in Escherichia coli BL21 (DE3) (rBVL-Ie). Although it was expressed as a monomer, rBVL-Ip retained its biological activity since it was able to impair the initial adhesion of Streptococcus mutans and S. sanguinis in an in vitro model of biofilm formation and bacterial adhesion. In summary, rBVL-Ip produced in Pichia pastoris represents a viable alternative to large-scale production, encouraging further biological application studies with this lectin. Copyright © 2016 Elsevier B.V. All rights reserved.

Photoactivated methods for enabling cartilage-to-cartilage tissue fixation

NASA Astrophysics Data System (ADS)

Sitterle, Valerie B.; Roberts, David W.

2003-06-01

The present study investigates whether photoactivated attachment of cartilage can provide a viable method for more effective repair of damaged articular surfaces by providing an alternative to sutures, barbs, or fibrin glues for initial fixation. Unlike artificial materials, biological constructs do not possess the initial strength for press-fitting and are instead sutured or pinned in place, typically inducing even more tissue trauma. A possible alternative involves the application of a photosensitive material, which is then photoactivated with a laser source to attach the implant and host tissues together in either a photothermal or photochemical process. The photothermal version of this method shows potential, but has been almost entirely applied to vascularized tissues. Cartilage, however, exhibits several characteristics that produce appreciable differences between applying and refining these techniques when compared to previous efforts involving vascularized tissues. Preliminary investigations involving photochemical photosensitizers based on singlet oxygen and electron transfer mechanisms are discussed, and characterization of the photodynamic effects on bulk collagen gels as a simplified model system using FTIR is performed. Previous efforts using photothermal welding applied to cartilaginous tissues are reviewed.

Single-shot diffraction data from the Mimivirus particle using an X-ray free-electron laser.

PubMed

Ekeberg, Tomas; Svenda, Martin; Seibert, M Marvin; Abergel, Chantal; Maia, Filipe R N C; Seltzer, Virginie; DePonte, Daniel P; Aquila, Andrew; Andreasson, Jakob; Iwan, Bianca; Jönsson, Olof; Westphal, Daniel; Odić, Duško; Andersson, Inger; Barty, Anton; Liang, Meng; Martin, Andrew V; Gumprecht, Lars; Fleckenstein, Holger; Bajt, Saša; Barthelmess, Miriam; Coppola, Nicola; Claverie, Jean-Michel; Loh, N Duane; Bostedt, Christoph; Bozek, John D; Krzywinski, Jacek; Messerschmidt, Marc; Bogan, Michael J; Hampton, Christina Y; Sierra, Raymond G; Frank, Matthias; Shoeman, Robert L; Lomb, Lukas; Foucar, Lutz; Epp, Sascha W; Rolles, Daniel; Rudenko, Artem; Hartmann, Robert; Hartmann, Andreas; Kimmel, Nils; Holl, Peter; Weidenspointner, Georg; Rudek, Benedikt; Erk, Benjamin; Kassemeyer, Stephan; Schlichting, Ilme; Strüder, Lothar; Ullrich, Joachim; Schmidt, Carlo; Krasniqi, Faton; Hauser, Günter; Reich, Christian; Soltau, Heike; Schorb, Sebastian; Hirsemann, Helmut; Wunderer, Cornelia; Graafsma, Heinz; Chapman, Henry; Hajdu, Janos

2016-08-01

Free-electron lasers (FEL) hold the potential to revolutionize structural biology by producing X-ray pules short enough to outrun radiation damage, thus allowing imaging of biological samples without the limitation from radiation damage. Thus, a major part of the scientific case for the first FELs was three-dimensional (3D) reconstruction of non-crystalline biological objects. In a recent publication we demonstrated the first 3D reconstruction of a biological object from an X-ray FEL using this technique. The sample was the giant Mimivirus, which is one of the largest known viruses with a diameter of 450 nm. Here we present the dataset used for this successful reconstruction. Data-analysis methods for single-particle imaging at FELs are undergoing heavy development but data collection relies on very limited time available through a highly competitive proposal process. This dataset provides experimental data to the entire community and could boost algorithm development and provide a benchmark dataset for new algorithms.

Single-shot diffraction data from the Mimivirus particle using an X-ray free-electron laser

NASA Astrophysics Data System (ADS)

Ekeberg, Tomas; Svenda, Martin; Seibert, M. Marvin; Abergel, Chantal; Maia, Filipe R. N. C.; Seltzer, Virginie; Deponte, Daniel P.; Aquila, Andrew; Andreasson, Jakob; Iwan, Bianca; Jönsson, Olof; Westphal, Daniel; Odić, Duško; Andersson, Inger; Barty, Anton; Liang, Meng; Martin, Andrew V.; Gumprecht, Lars; Fleckenstein, Holger; Bajt, Saša; Barthelmess, Miriam; Coppola, Nicola; Claverie, Jean-Michel; Loh, N. Duane; Bostedt, Christoph; Bozek, John D.; Krzywinski, Jacek; Messerschmidt, Marc; Bogan, Michael J.; Hampton, Christina Y.; Sierra, Raymond G.; Frank, Matthias; Shoeman, Robert L.; Lomb, Lukas; Foucar, Lutz; Epp, Sascha W.; Rolles, Daniel; Rudenko, Artem; Hartmann, Robert; Hartmann, Andreas; Kimmel, Nils; Holl, Peter; Weidenspointner, Georg; Rudek, Benedikt; Erk, Benjamin; Kassemeyer, Stephan; Schlichting, Ilme; Strüder, Lothar; Ullrich, Joachim; Schmidt, Carlo; Krasniqi, Faton; Hauser, Günter; Reich, Christian; Soltau, Heike; Schorb, Sebastian; Hirsemann, Helmut; Wunderer, Cornelia; Graafsma, Heinz; Chapman, Henry; Hajdu, Janos

2016-08-01

Free-electron lasers (FEL) hold the potential to revolutionize structural biology by producing X-ray pules short enough to outrun radiation damage, thus allowing imaging of biological samples without the limitation from radiation damage. Thus, a major part of the scientific case for the first FELs was three-dimensional (3D) reconstruction of non-crystalline biological objects. In a recent publication we demonstrated the first 3D reconstruction of a biological object from an X-ray FEL using this technique. The sample was the giant Mimivirus, which is one of the largest known viruses with a diameter of 450 nm. Here we present the dataset used for this successful reconstruction. Data-analysis methods for single-particle imaging at FELs are undergoing heavy development but data collection relies on very limited time available through a highly competitive proposal process. This dataset provides experimental data to the entire community and could boost algorithm development and provide a benchmark dataset for new algorithms.

Adalimumab with Methotrexate in Treatment-Naïve Japanese Patients with Rheumatoid Arthritis at Risk of Progressive Structural Joint Damage: A Postmarketing Observational Study.

PubMed

Ito, Yukiko; Hozumi, Kaori; Okada, Yukiko; Kurimoto, Sarina

2017-06-01

The objective of this study was to evaluate the real-world safety and effectiveness of adalimumab with methotrexate (MTX) in disease-modifying antirheumatic drug (DMARD)- and biologic-naïve Japanese patients with rheumatoid arthritis (RA) at risk of progressive structural joint damage. This multicenter, prospective, observational, postmarketing surveillance study was conducted between February 2013 and April 2015 at 84 centers in Japan. Patients with RA at risk of progressive structural joint damage were enrolled and initiated treatment with adalimumab and MTX. Adverse events were recorded up to week 28. Effectiveness/disease activity was assessed using the Disease Activity Score based on a 28-joint count with erythrocyte sedimentation rate and C-reactive protein (DAS28-4ESR and DAS28-4CRP), Clinical Disease Activity Index, and Simplified Disease Activity Index at 0, 4, 12, and 24 weeks. DAS28-4CRP response was evaluated in the low-dose (<8 mg/week) and high-dose (≥8 mg to ≤16 mg/week) MTX groups at week 24. One hundred fifty-seven of 163 patients comprised the safety cohort: mean (SD) age, 56.5 (13.9) years; females, 65.6%; rheumatoid factor positive, 73.2%; anti-cyclic citrullinated peptide antibody positive, 66.9%; bone erosions, 51.6%; mean disease duration, 9.5 months. The majority of patients (≥80%) had moderate or high disease activity at baseline, and ≥50% with available data achieved remission or low disease activity at week 24 (DAS28-4CRP <3.2). Five serious adverse drug reactions occurred in four patients, including pyelonephritis, Pneumocystis jiroveci pneumonia, interstitial lung disease, pleurisy, and pericarditis; the outcomes were either recovered or recovering. Significant improvements/reductions in disease activity over 24 weeks were noted in all effectiveness measures (P < 0.0001). Most of the population achieved DAS28-4CRP remission (<2.6) at week 24 regardless of the MTX dose. Adalimumab in combination with MTX could be a beneficial treatment option for DMARD- and biologic-naïve Japanese patients with RA at risk of progressive structural joint damage. AbbVie GK and Eisai. ClinicalTrials.gov identifier, NCT01783730.

Cancer Risk Assessment for Space Radiation

NASA Technical Reports Server (NTRS)

Richmond, Robert C.; Cruz, Angela; Bors, Karen; Curreri, Peter A. (Technical Monitor)

2001-01-01

Predicting the occurrence of human cancer following exposure to any agent causing genetic damage is a difficult task. This is because the uncertainty of uniform exposure to the damaging agent, and the uncertainty of uniform processing of that damage within a complex set of biological variables, degrade the confidence of predicting the delayed expression of cancer as a relatively rare event within any given clinically normal individual. The radiation health research priorities for enabling long-duration human exploration of space were established in the 1996 NRC Report entitled 'Radiation Hazards to Crews of Interplanetary Missions: Biological Issues and Research Strategies'. This report emphasized that a 15-fold uncertainty in predicting radiation-induced cancer incidence must be reduced before NASA can commit humans to extended interplanetary missions. That report concluded that the great majority of this uncertainty is biologically based, while a minority is physically based due to uncertainties in radiation dosimetry and radiation transport codes. Since that report, the biologically based uncertainty has remained large, and the relatively small uncertainty associated with radiation dosimetry has increased due to the considerations raised by concepts of microdosimetry. In a practical sense, however, the additional uncertainties introduced by microdosimetry are encouraging since they are in a direction of lowered effective dose absorbed through infrequent interactions of any given cell with the high energy particle component of space radiation. Additional information is contained in the original extended abstract.

Effects of Ionizing Radiation on Biological Molecules—Mechanisms of Damage and Emerging Methods of Detection

PubMed Central

Reisz, Julie A.; Bansal, Nidhi; Qian, Jiang; Zhao, Weiling

2014-01-01

Abstract Significance: The detrimental effects of ionizing radiation (IR) involve a highly orchestrated series of events that are amplified by endogenous signaling and culminating in oxidative damage to DNA, lipids, proteins, and many metabolites. Despite the global impact of IR, the molecular mechanisms underlying tissue damage reveal that many biomolecules are chemoselectively modified by IR. Recent Advances: The development of high-throughput “omics” technologies for mapping DNA and protein modifications have revolutionized the study of IR effects on biological systems. Studies in cells, tissues, and biological fluids are used to identify molecular features or biomarkers of IR exposure and response and the molecular mechanisms that regulate their expression or synthesis. Critical Issues: In this review, chemical mechanisms are described for IR-induced modifications of biomolecules along with methods for their detection. Included with the detection methods are crucial experimental considerations and caveats for their use. Additional factors critical to the cellular response to radiation, including alterations in protein expression, metabolomics, and epigenetic factors, are also discussed. Future Directions: Throughout the review, the synergy of combined “omics” technologies such as genomics and epigenomics, proteomics, and metabolomics is highlighted. These are anticipated to lead to new hypotheses to understand IR effects on biological systems and improve IR-based therapies. Antioxid. Redox Signal. 21: 260–292. PMID:24382094

Relative biological effectiveness for photons: implication of complex DNA double-strand breaks as critical lesions

NASA Astrophysics Data System (ADS)

Liang, Ying; Fu, Qibin; Wang, Xudong; Liu, Feng; Yang, Gen; Luo, Chunxiong; Ouyang, Qi; Wang, Yugang

2017-03-01

Current knowledge in radiobiology ascribes the adverse biological effects of ionizing radiation primarily to the induction of DNA double-strand breaks (DSBs), which is supposed to be potentially lethal and may be converted to lethal damage due to misrepair. Soft and ultrasoft x-rays have been found to bear elevated biological effectiveness for cell killing compared with conventional x-rays or 60Co γ-rays. This phenomenon is qualitatively interpreted as the increased level of DSB induction for low energy photons, however, a thorough quantitative reasoning is lacking. Here, we systematically compared the relative biological effectiveness (RBE) with relative DSB induction for photons from several hundreds of eV up to MeV. Although there is an approximate two-fold increase in the yields of DSB for low energy photons found in our calculation and a large number of experimental measurements, it is far from enough to account for the three- to four-fold increase in RBE. Further theoretical investigations show that DSB complexity (additional single-strand breaks and base damage within 10 base pairs) increases notably for low energy photons, which largely reconciles the discrepancy between RBE and DSB induction. Our theoretical results are in line with accumulating experimental evidence that complex DSBs are refractory to repair machinery and may contribute predominantly to the formation of lethal damage.

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases

NASA Technical Reports Server (NTRS)

Schoenfeld, Michael P.; Ansari,Rafat R.; Nakao, Atsunori; Wink, David

2011-01-01

Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including, cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, parkinson s and alzheimer s disease, cataracts, and aging

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases as Medical Counter Measures

NASA Technical Reports Server (NTRS)

Schoenfeld, Michael P.; Ansari, Rafat R.; Nakao, Atsunori; Wink, David

2012-01-01

Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, Parkinson s and Alzheimer s disease, cataracts, and aging.

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases

NASA Technical Reports Server (NTRS)

Schoenfeld, Michael P.; Ansari, Rafat R.; Nakao, Atsunori; Wink, David

2011-01-01

Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, Parkinson s and Alzheimer s disease, cataracts, and aging.

Radiation effects on Brassica seeds and seedlings

NASA Astrophysics Data System (ADS)

Deoli, Naresh; Hasenstein, Karl H.

2016-07-01

Space radiation consists of high energy charged particles and affects biological systems, but because of its stochastic, non-directional nature is difficult to replicate on Earth. Radiation damages biological systems acutely at high doses or cumulatively at low doses through progressive changes in DNA organization. These damages lead to death or cause of mutations. While radiation biology typically focuses on mammalian or human systems, little is known as to how radiation affects plants. In addition, energetic ion beams are widely used to generate new mutants in plants considering their high-LET (Linear Energy Transfer) as compared to gamma rays and X-rays. Understanding the effect of ionizing radiation on plant provides a basis for studying effects of radiation on biological systems and will help mitigate (space) radiation damage in plants. We exposed dry and imbibed Brassica rapa seeds and seedling roots to proton beams of varying qualities and compared the theoretical penetration range of different energy levels with observable growth response. We used 1, 2 and 3 MeV protons in air at the varying fluences to investigate the effect of direct irradiation on the seeds (1012 - 1015 ions/cm2) and seedlings (1013 ions/cm2). The range of protons in the tissue was calculated using Monte-Carlo based SRIM (Stopping and Range of Ions in Matter) software. The simulation and biological results indicate that ions did not penetrate the tissue of dry or hydrated seeds at all used ion energies. Therefore the entire energy was transferred to the treated tissue. Irradiated seeds were germinated vertically under dim light and roots growth was observed for two days after imbibition. The LD50 of the germination was about 2×1014 ions/cm2 and about 5×1014 ions/cm2 for imbibed and dry seeds, respectively. Since seedlings are most sensitive to gravity, the change in gravitropic behavior is a convenient means to assess radiation damage on physiological responses other than direct tissue damage. We compared curvature in untreated with irradiated roots and measured the inhibition of curvature at 2×1013 - 8×1013 ions/cm2. Despite greater mass of imbibed seeds, the dose-response curve showed greater sensitivity of imbibed than for dry seeds. In addition, germination rate was found to be strongly dependent on ion beam current, at least for 3 MeV protons. Our data show that weak ionizing particles (low MeV protons) are suitable to study radiation effects and seedlings are a useful biological systems to study space radiation. Supported by NASA grant NNX13AN05A.

DNA damage and repair after high LET radiation

NASA Astrophysics Data System (ADS)

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

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

Physical and biological studies with protons and HZE particles in a NASA supported research center in radiation health.

PubMed

Chatterjee, A; Borak, T H

2001-01-01

NASA has established and supports a specialized center for research and training (NSCORT) to specifically address the potential deleterious effects of HZE particles on human health. The NSCORT in radiation health is a joint effort between Lawrence Berkeley National Laboratory (LBNL) and Colorado State University (CSU). The overall scope of research encompasses a broad range of subjects from microdosimetric studies to cellular and tissue responses to initial damage produced by highly energetic protons and heavy charged particles of the type found in galactic cosmic rays (GCR) spectrum. The objectives of the microdosimetry studies are to determine the response of Tissue Equivalent Proportional Counter (TEPC) to cosmic rays using ground based accelerators. This includes evaluation of energy loss due to the escape of high-energy delta rays and increased energy deposition due to the enhanced delta ray production in the wall of the detector. In this report major results are presented for 56Fe at 1000, 740, 600 and 400 MeV/nucleon. An assessment of DNA repair and early development of related chromosomal changes is extremely important to our overall understanding of enhanced biological effectiveness of high LET particle radiation. Results are presented with respect to the fidelity of the rejoining of double strand breaks and the implications of misrejoining. The relationship between molecular and cytogenetic measurements is presented by studying damage processing in highly heterochromatic supernumerary (correction of sypernumerary) X chromosomes and the active X-chromosome. One of the important consequences of cell's inability to handle DNA damage can be evaluated through mutation studies. Part of our goal is the assessment of potential radioprotectors to reduce the mutation yield following HZE exposures, and some promising results are presented on one compound. A second goal is the integration of DNA repair and mutation studies. Results are presented on a direct comparison of initial double strand breaks induction, the time course and fidelity of double strand break rejoining, cell killing and mutation induction in the same human model system. In order to understand the carcinogenic potential of protons and HZE particles, the role of damaged microenvironment in this process must be understood. In this project it has been postulated that radiation affects the microenvironment, which then modifies cell interactions in a manner conducive to neoplastic progression. Both TGF-beta and FGF-2 are important components of microenvironment. A recent result on the assessment of the role of FGF-2 and its cross-talk with TGF-beta as a function of radiation quality is presented. Theoretical modeling has so far played a central role in analyzing and integrating experimental data on repair and mutation studies and predicting new phenomena. The integrated NSCORT program also provides a broad training experience for students and postdoctoral fellows in space radiation health.

Physical and biological studies with protons and HZE particles in a NASA supported research center in radiation health

NASA Technical Reports Server (NTRS)

Chatterjee, A.; Borak, T. H.

2001-01-01

NASA has established and supports a specialized center for research and training (NSCORT) to specifically address the potential deleterious effects of HZE particles on human health. The NSCORT in radiation health is a joint effort between Lawrence Berkeley National Laboratory (LBNL) and Colorado State University (CSU). The overall scope of research encompasses a broad range of subjects from microdosimetric studies to cellular and tissue responses to initial damage produced by highly energetic protons and heavy charged particles of the type found in galactic cosmic rays (GCR) spectrum. The objectives of the microdosimetry studies are to determine the response of Tissue Equivalent Proportional Counter (TEPC) to cosmic rays using ground based accelerators. This includes evaluation of energy loss due to the escape of high-energy delta rays and increased energy deposition due to the enhanced delta ray production in the wall of the detector. In this report major results are presented for 56Fe at 1000, 740, 600 and 400 MeV/nucleon. An assessment of DNA repair and early development of related chromosomal changes is extremely important to our overall understanding of enhanced biological effectiveness of high LET particle radiation. Results are presented with respect to the fidelity of the rejoining of double strand breaks and the implications of misrejoining. The relationship between molecular and cytogenetic measurements is presented by studying damage processing in highly heterochromatic supernumerary (correction of sypernumerary) X chromosomes and the active X-chromosome. One of the important consequences of cell's inability to handle DNA damage can be evaluated through mutation studies. Part of our goal is the assessment of potential radioprotectors to reduce the mutation yield following HZE exposures, and some promising results are presented on one compound. A second goal is the integration of DNA repair and mutation studies. Results are presented on a direct comparison of initial double strand breaks induction, the time course and fidelity of double strand break rejoining, cell killing and mutation induction in the same human model system. In order to understand the carcinogenic potential of protons and HZE particles, the role of damaged microenvironment in this process must be understood. In this project it has been postulated that radiation affects the microenvironment, which then modifies cell interactions in a manner conducive to neoplastic progression. Both TGF-beta and FGF-2 are important components of microenvironment. A recent result on the assessment of the role of FGF-2 and its cross-talk with TGF-beta as a function of radiation quality is presented. Theoretical modeling has so far played a central role in analyzing and integrating experimental data on repair and mutation studies and predicting new phenomena. The integrated NSCORT program also provides a broad training experience for students and postdoctoral fellows in space radiation health.

Bridging from Cells to Cognition in Autism Pathophysiology: Biological Pathways to Defective Brain Function and Plasticity

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

Anderson, Matthew; Hooker, Brian S.; Herbert, Martha

We review evidence to support the model that autism may begin when a maternal environmental, infectious, or autoantibody insult causes inflammation which increases reactive oxygen species (ROS) production in the fetus, leading to fetal DNA damage (nuclear and mitochondrial), and that these inflammatory and oxidative stressors persist beyond early development (with potential further exacerbations), producing ongoing functional consequences. In organs with a high metabolic demand such as the central nervous system, the continued use of mitochondria with DNA damage may generate additional ROS which will activate the innate immune system leading to more ROS production. Such a mechanism would self-sustainmore » and possibly progressively worsen. The mitochondrial dysfunction and altered redox signal transduction pathways found in autism would conspire to activate both astroglia and microglia. These activated cells can then initiate a broad-spectrum proinflammatory gene response. Neurons may have acquired receptors for these inflammatory signals to inhibit neuronal signaling as a protection from excitotoxic damage during various pathologic insults (e.g., infection). In autism, over-zealous neuroinflammatory responses could not only influence neural developmental processes, but may more significantly impair neural signaling involved in cognition in an ongoing fashion. This model makes specific predictions in patients and experimental animal models and suggests a number of targets sites of intervention. Our model of potentially reversible pathophysiological mechanisms in autism motivates our hope that effective therapies may soon appear on the horizon.« less

Evaluation of external hazards to nuclear power plants in the United States

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

Kimura, C.Y.; Budnitz, R.J.

1987-12-01

The Lawrence Livermore National Laboratory (LLNL) has performed a study of the risk of core damage to nuclear power plants in the United States due to externally initiated events. The broad objective has been to gain an understanding of whether or not each external initiator is among the major potential accident initiators that may pose a threat of severe reactor core damage or of large radioactive release to the environment from the reactor. Four external hazards were investigated in this report. These external hazards are internal fires, high winds/tornadoes, external floods, and transportation accidents. Analysis was based on two figures-of-merit,more » one based on core damage frequency and the other based on the frequency of large radioactive releases. Using these two figures-of-merit as evaluation criteria, it has been feasible to ascertain whether the risk from externally initiated accidents is, or is not, an important contributor to overall risk for the US nuclear power plants studied. This has been accomplished for each initiator separately. 208 refs., 17 figs., 45 tabs.« less

Geospatial relationships of tree species damage caused by Hurricane Katrina in south Mississippi

Treesearch

Mark W. Garrigues; Zhaofei Fan; David L. Evans; Scott D. Roberts; William H. Cooke III

2012-01-01

Hurricane Katrina generated substantial impacts on the forests and biological resources of the affected area in Mississippi. This study seeks to use classification tree analysis (CTA) to determine which variables are significant in predicting hurricane damage (shear or windthrow) in the Southeast Mississippi Institute for Forest Inventory District. Logistic regressions...

Cold atmospheric-pressure plasma induces DNA-protein crosslinks through protein oxidation.

PubMed

Guo, Li; Zhao, Yiming; Liu, Dingxin; Liu, Zhichao; Chen, Chen; Xu, Ruobing; Tian, Miao; Wang, Xiaohua; Chen, Hailan; Kong, Michael G

2018-05-03

Reactive oxygen and nitrogen species (ROS and RNS) generated by cold atmospheric-pressure plasma could damage genomic DNA, although the precise type of these DNA damage induced by plasma are poorly characterized. Understanding plasma-induced DNA damage will help to elucidate the biological effect of plasma and guide the application of plasma in ROS-based therapy. In this study, it was shown that ROS and RNS generated by physical plasma could efficiently induce DNA-protein crosslinks (DPCs) in bacteria, yeast, and human cells. An in vitro assay showed that plasma treatment resulted in the formation of covalent DPCs by activating proteins to crosslink with DNA. Mass spectrometry and hydroperoxide analysis detected oxidation products induced by plasma. DPC formation were alleviated by singlet oxygen scavenger, demonstrating the importance of singlet oxygen in this process. These results suggested the roles of DPC formation in DNA damage induced by plasma, which could improve the understanding of the biological effect of plasma and help to develop a new strategy in plasma-based therapy including infection and cancer therapy.

Why do some intervertebral discs degenerate, when others (in the same spine) do not?

PubMed

Adams, Michael A; Lama, Polly; Zehra, Uruj; Dolan, Patricia

2015-03-01

This review suggests why some discs degenerate rather than age normally. Intervertebral discs are avascular pads of fibrocartilage that allow movement between vertebral bodies. Human discs have a low cell density and a limited ability to adapt to mechanical demands. With increasing age, the matrix becomes yellowed, fibrous, and brittle, but if disc structure remains intact, there is little impairment in function, and minimal ingrowth of blood vessels or nerves. Approximately half of old lumbar discs degenerate in the sense of becoming physically disrupted. The posterior annulus and lower lumbar discs are most affected, presumably because they are most heavily loaded. Age and genetic inheritance can weaken discs to such an extent that they are physically disrupted during everyday activities. Damage to the endplate or annulus typically decompresses the nucleus, concentrates stress within the annulus, and allows ingrowth of nerves and blood vessels. Matrix disruption progresses by mechanical and biological means. The site of initial damage leads to two disc degeneration "phenotypes": endplate-driven degeneration is common in the upper lumbar and thoracic spine, and annulus-driven degeneration is common at L4-S1. Discogenic back pain can be initiated by tissue disruption, and amplified by inflammation and infection. Healing is possible in the outer annulus only, where cell density is highest. We conclude that some discs degenerate because they are disrupted by excessive mechanical loading. This can occur without trauma if tissues are weakened by age and genetic inheritance. Moderate mechanical loading, in contrast, strengthens all spinal tissues, including discs. © 2014 Wiley Periodicals, Inc.

The Roles of Mitochondrial Damage-Associated Molecular Patterns in Diseases

PubMed Central

Nakahira, Kiichi; Hisata, Shu

2015-01-01

Abstract Significance: Mitochondria, vital cellular power plants to generate energy, are involved in immune responses. Mitochondrial damage-associated molecular patterns (DAMPs) are molecules that are released from mitochondria to extracellular space during cell death and include not only proteins but also DNA or lipids. Mitochondrial DAMPs induce inflammatory responses and are critically involved in the pathogenesis of various diseases. Recent Advances: Recent studies elucidate the molecular mechanisms by which mitochondrial DAMPs are released and initiate immune responses by use of genetically modulated cells or animals. Importantly, the levels of mitochondrial DAMPs in patients are often associated with severity and prognosis of human diseases, such as infection, asthma, ischemic heart disease, and cancer. Critical Issues: Although mitochondrial DAMPs can represent proinflammatory molecules in various experimental models, their roles in human diseases may be multifunctional and complex. It remains unclear where and how mitochondrial DAMPs are liberated into extracellular spaces and exert their biological functions particularly in vivo. In addition, while mitochondria can secrete several types of DAMPs during cell death, the interaction of each mitochondrial DAMP (e.g., synergistic effects) remains unclear. Future Directions: Regulation of mitochondrial DAMP-mediated immune responses may be important to alter the progression of human diseases. In addition, measuring mitochondrial DAMPs in patients may be clinically useful as biomarkers to predict prognosis or response to therapies. Further studies of the mechanisms by which mitochondrial DAMPs impact the initiation and progression of diseases may lead to the development of therapeutics specifically targeting this pathway. Antioxid. Redox Signal. 23, 1329–1350. PMID:26067258

Next generation control system for reflexive aerostructures

NASA Astrophysics Data System (ADS)

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

2010-04-01

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

WE-H-BRA-08: A Monte Carlo Cell Nucleus Model for Assessing Cell Survival Probability Based On Particle Track Structure Analysis

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

Lee, B; Georgia Institute of Technology, Atlanta, GA; Wang, C

Purpose: To correlate the damage produced by particles of different types and qualities to cell survival on the basis of nanodosimetric analysis and advanced DNA structures in the cell nucleus. Methods: A Monte Carlo code was developed to simulate subnuclear DNA chromatin fibers (CFs) of 30nm utilizing a mean-free-path approach common to radiation transport. The cell nucleus was modeled as a spherical region containing 6000 chromatin-dense domains (CDs) of 400nm diameter, with additional CFs modeled in a sparser interchromatin region. The Geant4-DNA code was utilized to produce a particle track database representing various particles at different energies and dose quantities.more » These tracks were used to stochastically position the DNA structures based on their mean free path to interaction with CFs. Excitation and ionization events intersecting CFs were analyzed using the DBSCAN clustering algorithm for assessment of the likelihood of producing DSBs. Simulated DSBs were then assessed based on their proximity to one another for a probability of inducing cell death. Results: Variations in energy deposition to chromatin fibers match expectations based on differences in particle track structure. The quality of damage to CFs based on different particle types indicate more severe damage by high-LET radiation than low-LET radiation of identical particles. In addition, the model indicates more severe damage by protons than of alpha particles of same LET, which is consistent with differences in their track structure. Cell survival curves have been produced showing the L-Q behavior of sparsely ionizing radiation. Conclusion: Initial results indicate the feasibility of producing cell survival curves based on the Monte Carlo cell nucleus method. Accurate correlation between simulated DNA damage to cell survival on the basis of nanodosimetric analysis can provide insight into the biological responses to various radiation types. Current efforts are directed at producing cell survival curves for high-LET radiation.« less

Quantifying conservation biological control for management of Bemisia tabaci (Hemiptera: Aleyrodidae) in cotton

USDA-ARS?s Scientific Manuscript database

Conservation biological control can be an effective tactic for minimizing insect-induced damage to agricultural production. The most effective manner of applying CBC is through an Integrated Pest Management (IPM) strategy, combining many tactics including cultural controls, pest sampling, the use of...

A bio-inspired structural health monitoring system based on ambient vibration

NASA Astrophysics Data System (ADS)

Lin, Tzu-Kang; Kiremidjian, Anne; Lei, Chi-Yang

2010-11-01

A structural health monitoring (SHM) system based on naïve Bayesian (NB) damage classification and DNA-like expression data was developed in this research. Adapted from the deoxyribonucleic acid (DNA) array concept in molecular biology, the proposed structural health monitoring system is constructed utilizing a double-tier regression process to extract the expression array from the structural time history recorded during external excitations. The extracted array is symbolized as the various genes of the structure from the viewpoint of molecular biology and reflects the possible damage conditions prevalent in the structure. A scaled down, six-story steel building mounted on the shaking table of the National Center for Research on Earthquake Engineering (NCREE) was used as the benchmark. The structural response at different damage levels and locations under ambient vibration was collected to support the database for the proposed SHM system. To improve the precision of detection in practical applications, the system was enhanced by an optimization process using the likelihood selection method. The obtained array representing the DNA array of the health condition of the structure was first evaluated and ranked. A total of 12 groups of expression arrays were regenerated from a combination of four damage conditions. To keep the length of the array unchanged, the best 16 coefficients from every expression array were selected to form the optimized SHM system. Test results from the ambient vibrations showed that the detection accuracy of the structural damage could be greatly enhanced by the optimized expression array, when compared to the original system. Practical verification also demonstrated that a rapid and reliable result could be given by the final system within 1 min. The proposed system implements the idea of transplanting the DNA array concept from molecular biology into the field of SHM.

Severe impingement of lumbar disc replacements increases the functional biological activity of polyethylene wear debris.

PubMed

Baxter, Ryan M; Macdonald, Daniel W; Kurtz, Steven M; Steinbeck, Marla J

2013-06-05

Wear, oxidation, and particularly rim impingement damage of ultra-high molecular weight polyethylene total disc replacement components have been observed following surgical revision. However, neither in vitro testing nor retrieval-based evidence has shown the effect(s) of impingement on the characteristics of polyethylene wear debris. Thus, we sought to determine (1) differences in polyethylene particle size, shape, number, or biological activity that correspond to mild or severe rim impingement and (2) in an analysis of all total disc replacements, regardless of impingement classification, whether there are correlations between the extent of regional damage and the characteristics of polyethylene wear debris. The extent of dome and rim damage was characterized for eleven retrieved polyethylene cores obtained at revision surgery after an average duration of implantation of 9.7 years (range, 4.6 to 16.1 years). Polyethylene wear debris was isolated from periprosthetic tissues with use of nitric acid and was imaged with use of environmental scanning electron microscopy. Subsequently, particle size, shape, number, biological activity, and chronic inflammation scores were determined. Grouping of particles by size ranges that represented high biological relevance (<0.1 to 1-μm particles), intermediate biological relevance (1 to 10-μm particles), and low biological relevance (>10-μm particles) revealed an increased volume fraction of particles in the <0.1 to 1-μm and 1 to 10-μm size ranges in the mild-impingement cohort as compared with the severe-impingement cohort. The increased volume fractions resulted in a higher specific biological activity per unit particle volume in the mild-impingement cohort than in the severe-impingement cohort. However, functional biological activity, which is normalized by particle volume (mm3/g of tissue), was significantly higher in the severe-impingement cohort. This increase was due to a larger volume of particles in all three size ranges. In both cohorts, the functional biological activity correlated with the chronic inflammatory response, and the extent of rim penetration positively correlated with increasing particle size, number, and functional biological activity. The results of this study suggest that severe rim impingement increases the production of biologically relevant particles from motion-preserving lumbar total disc replacement components. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Severe Impingement of Lumbar Disc Replacements Increases the Functional Biological Activity of Polyethylene Wear Debris

PubMed Central

Baxter, Ryan M.; MacDonald, Daniel W.; Kurtz, Steven M.; Steinbeck, Marla J.

2013-01-01

Background: Wear, oxidation, and particularly rim impingement damage of ultra-high molecular weight polyethylene total disc replacement components have been observed following surgical revision. However, neither in vitro testing nor retrieval-based evidence has shown the effect(s) of impingement on the characteristics of polyethylene wear debris. Thus, we sought to determine (1) differences in polyethylene particle size, shape, number, or biological activity that correspond to mild or severe rim impingement and (2) in an analysis of all total disc replacements, regardless of impingement classification, whether there are correlations between the extent of regional damage and the characteristics of polyethylene wear debris. Methods: The extent of dome and rim damage was characterized for eleven retrieved polyethylene cores obtained at revision surgery after an average duration of implantation of 9.7 years (range, 4.6 to 16.1 years). Polyethylene wear debris was isolated from periprosthetic tissues with use of nitric acid and was imaged with use of environmental scanning electron microscopy. Subsequently, particle size, shape, number, biological activity, and chronic inflammation scores were determined. Results: Grouping of particles by size ranges that represented high biological relevance (<0.1 to 1-μm particles), intermediate biological relevance (1 to 10-μm particles), and low biological relevance (>10-μm particles) revealed an increased volume fraction of particles in the <0.1 to 1-μm and 1 to 10-μm size ranges in the mild-impingement cohort as compared with the severe-impingement cohort. The increased volume fractions resulted in a higher specific biological activity per unit particle volume in the mild-impingement cohort than in the severe-impingement cohort. However, functional biological activity, which is normalized by particle volume (mm3/g of tissue), was significantly higher in the severe-impingement cohort. This increase was due to a larger volume of particles in all three size ranges. In both cohorts, the functional biological activity correlated with the chronic inflammatory response, and the extent of rim penetration positively correlated with increasing particle size, number, and functional biological activity. Conclusions: The results of this study suggest that severe rim impingement increases the production of biologically relevant particles from motion-preserving lumbar total disc replacement components. Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID:23780545

On the monitoring and implications of growing damages caused by manufacturing defects in composite structures

NASA Astrophysics Data System (ADS)

Schagerl, M.; Viechtbauer, C.; Hörrmann, S.

2015-07-01

Damage tolerance is a classical safety concept for the design of aircraft structures. Basically, this approach considers possible damages in the structure, predicts the damage growth under applied loading conditions and predicts the following decrease of the structural strength. As a fundamental result the damage tolerance approach yields the maximum inspection interval, which is the time a damage grows from a detectable to a critical level. The above formulation of the damage tolerance safety concept targets on metallic structures where the damage is typically a simple fatigue crack. Fiber-reinforced polymers show a much more complex damage behavior, such as delaminationsin laminated composites. Moreover, progressive damage in composites is often initiated by manufacturing defects. The complex manufacturing processes for composite structures almost certainly yield parts with defects, e.g. pores in the matrix or undulations of fibers. From such defects growing damages may start after a certain time of operation. The demand to simplify or even avoid the inspection of composite structures has therefore led to a comeback of the traditional safe-life safety concept. The aim of the so-called safe-life flaw tolerance concept is a structure that is capable of carrying the static loads during operation, despite significant damages and after a representative fatigue load spectrum. A structure with this property does not need to be inspected, respectively monitored at all during its service life. However, its load carrying capability is thereby not fully utilized. This article presents the possible refinement of the state-of-the-art safe-life flaw tolerance concept for composite structures towards a damage tolerance approach considering also the influence of manufacturing defects on damage initiation and growth. Based on fundamental physical relations and experimental observations the challenges when developing damage growth and residual strength curves are discussed.

Damage spreading and opinion dynamics on scale-free networks

NASA Astrophysics Data System (ADS)

Fortunato, Santo

2005-03-01

We study damage spreading among the opinions of a system of agents, subjected to the dynamics of the Krause-Hegselmann consensus model. The damage consists in a sharp change of the opinion of one or more agents in the initial random opinion configuration, supposedly due to some external factors and/or events. This may help to understand for instance under which conditions special shocking events or targeted propaganda are able to influence the results of elections. For agents lying on the nodes of a Barabási-Albert network, there is a damage spreading transition at a low value εd of the confidence bound parameter. Interestingly, we find as well that there is some critical value εs above which the initial perturbation manages to propagate to all other agents.

Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit 1. Volume 5: Analysis of core damage frequency from seismic events during mid-loop operations

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

Budnitz, R.J.; Davis, P.R.; Ravindra, M.K.

1994-08-01

In 1989 the US Nuclear Regulatory Commission (NRC) initiated an extensive program to examine carefully the potential risks during low-power and shutdown operations. The program included two parallel projects, one at Brookhaven National Laboratory studying a pressurized water reactor (Surry Unit 1) and the other at Sandia National Laboratories studying a boiling water reactor (Grand Gulf). Both the Brookhaven and Sandia projects have examined only accidents initiated by internal plant faults--so-called ``internal initiators.`` This project, which has explored the likelihood of seismic-initiated core damage accidents during refueling shutdown conditions, is complementary to the internal-initiator analyses at Brookhaven and Sandia. Thismore » report covers the seismic analysis at Surry Unit 1. All of the many systems modeling assumptions, component non-seismic failure rates, and human error rates that were used in the internal-initiator study at Surry have been adopted here, so that the results of the two studies can be as comparable as possible. Both the Brookhaven study and this study examine only two shutdown plant operating states (POSs) during refueling outages at Surry, called POS 6 and POS 10, which represent mid-loop operation before and after refueling, respectively. This analysis has been limited to work analogous to a level-1 seismic PRA, in which estimates have been developed for the core-damage frequency from seismic events during POSs 6 and 10. The results of the analysis are that the core-damage frequency of earthquake-initiated accidents during refueling outages in POS 6 and POS 10 is found to be low in absolute terms, less than 10{sup {minus}6}/year.« less

Evaluation of potential severe accidents during low power and shutdown operations at Grand Gulf, Unit 1. Volume 5: Analysis of core damage frequency from seismic events for plant operational state 5 during a refueling outage

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

Budnitz, R.J.; Davis, P.R.; Ravindra, M.K.

In 1989 the US Nuclear Regulatory Commission (NRC) initiated an extensive program to examine carefully the potential risks during low-power and shutdown operations. The program included two parallel projects, one at Sandia National Laboratories studying a boiling water reactor (Grand Gulf), and the other at Brookhaven National Laboratory studying a pressurized water reactor (Surry Unit 1). Both the Sandia and Brookhaven projects have examined only accidents initiated by internal plant faults---so-called ``internal initiators.`` This project, which has explored the likelihood of seismic-initiated core damage accidents during refueling outage conditions, is complementary to the internal-initiator analyses at Brookhaven and Sandia. Thismore » report covers the seismic analysis at Grand Gulf. All of the many systems modeling assumptions, component non-seismic failure rates, and human effort rates that were used in the internal-initiator study at Grand Gulf have been adopted here, so that the results of the study can be as comparable as possible. Both the Sandia study and this study examine only one shutdown plant operating state (POS) at Grand Gulf, namely POS 5 representing cold shutdown during a refueling outage. This analysis has been limited to work analogous to a level-1 seismic PRA, in which estimates have been developed for the core-damage frequency from seismic events during POS 5. The results of the analysis are that the core-damage frequency for earthquake-initiated accidents during refueling outages in POS 5 is found to be quite low in absolute terms, less than 10{sup {minus}7}/year.« less

Update on the Treatment of Uveitis in Patients with Juvenile Idiopathic Arthritis: A Review.

PubMed

Asproudis, Ioannis; Katsanos, Andreas; Kozeis, Nikolaos; Tantou, Alexandra; Konstas, Anastasios G

2017-12-01

Chronic uveitis is a common extra-articular manifestation of juvenile idiopathic arthritis. The classic clinical picture is one of chronic anterior uveitis, which usually remains asymptomatic until ocular complications arise. The risk of uveitis is increased in girls with an early onset of oligoarthritis and positive antinuclear antibodies. Even though the inflammation in patients with juvenile idiopathic arthritis is initially limited in the anterior part of the eye, chronic active inflammation may eventually cause significant damage to the posterior pole. Complications may include band keratopathy, cataract, secondary glaucoma, posterior synechiae, cystoid macular edema, and hypotony. The cooperation of ophthalmologists with rheumatologists may help define the best treatment plan. The ophthalmic therapeutic regimen includes topical corticosteroids and mydriatics, while in severe cases immunosuppressive and biological agents are introduced. Surgical management of complications might be needed.

Correlating measured transient temperature rises with damage rate processes in cultured cells

NASA Astrophysics Data System (ADS)

Denton, Michael L.; Tijerina, Amanda J.; Gonzalez, Cherry C.; Gamboa, B. Giovana; Noojin, Gary D.; Ahmed, Elharith M.; Rickman, John M.; Dyer, Phillip H.; Rockwell, Benjamin A.

2017-02-01

Thermal 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. Here, two disparate approaches were used to study thermal damage rate processes in cultured retinal pigment epithelial cells. Laser exposure (photothermal) parameters included 2-μm laser exposure of non-pigmented cells and 532-nm exposures of cells possessing a variety of melanosome particle densities. Photothermal experiments used a mid-IR camera to record temperature histories with spatial resolution of about 8 μm, while fluorescence microscopy of the cell monolayers identified threshold damage at the boundary between live and dead cells. Photothermal exposure durations ranged from 0.05-20 s, and the effects of varying ambient temperature were investigated. Temperature during heat transfer using a water-jacketed cuvette was recorded with a fast microthermister, while damage and viability of the suspended cells were determined as percentages. Exposure durations for the heat transfer experiments ranged from 50- 60 s. Empirically-determined kinetic parameters for the two heating methods were compared with each other, and with values found in the literature.

Evaluation of DNA damage induced by Auger electrons from 137Cs.

PubMed

Watanabe, Ritsuko; Hattori, Yuya; Kai, Takeshi

2016-11-01

To understand the biological effect of external and internal exposure from 137 Cs, DNA damage spectrum induced by directly emitted electrons (γ-rays, internal conversion electrons, Auger electrons) from 137 Cs was compared with that induced by 137 Cs γ-rays. Monte Carlo track simulation method was used to calculate the microscopic energy deposition pattern in liquid water. Simulation was performed for the two simple target systems in microscale. Radiation sources were placed inside for one system and outside for another system. To simulate the energy deposition by directly emitted electrons from 137 Cs placed inside the system, the multiple ejections of electrons after internal conversion were considered. In the target systems, induction process of DNA damage was modeled and simulated for both direct energy deposition and the water radical reaction on the DNA. The yield and spatial distribution of simple and complex DNA damage including strand breaks and base lesions were calculated for irradiation by electrons and γ-rays from 137 Cs. The simulation showed that the significant difference in DNA damage spectrum was not caused by directly ejected electrons and γ-rays from 137 Cs. The result supports the existing perception that the biological effects by internal and external exposure by 137 Cs are equivalent.

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.

Regulation of ATM-Dependent DNA Damage Responses in Breast Cancer by the RhoGEF Net1

DTIC Science & Technology

2013-04-01

Science 279: 509-514. 5. Jaffe AB. et al., (2010) RhoGTPases: Biochemistry and Biology. Annu. Rev. Cell Dev. Biol. 21:247-269. 6. Rossman KL, et al...exchange factor Net1 is regulated by nuclear sequestration. J. Biol. Chem. 277:17, 14581-14588. 17. Harper JW, et al., (2007) The DNA Damage Response: Ten...Research (AACR) Annual Meeting and 2013 Annual Cancer Research Biochemistry Retreat Regulation of ATM-dependent DNA damage signaling in human breast

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

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

Photo-damage protective effect of two facial products, containing a unique complex of Dead Sea minerals and Himalayan actives.

PubMed

Wineman, Eitan; Portugal-Cohen, Meital; Soroka, Yoram; Cohen, Dror; Schlippe, Gerrit; Voss, Werner; Brenner, Sarah; Milner, Yoram; Hai, Noam; Ma'or, Zeevi

2012-09-01

Skin appearance is badly affected when exposed to solar UV rays, which encourage physiological and structural cutaneous alterations that eventually lead to skin photo-damage. To test the capability of two facial preparations, extreme day cream (EXD) and extreme night treatment (EXN), containing a unique complex of Dead Sea water and three Himalayan extracts, to antagonize biological effects induced by photo-damage. Pieces of organ cultures of human skin were used as a model to assess the biological effects of UVB irradiation and the protective effect of topical application of two Extreme preparations. Skin pieces were analyzed for mitochondrial activity by MTT assay, for apoptosis by caspase 3 assay, and for cytokine secretion by solid phase ELISA. Human subjects were tested to evaluate the effect of Extreme preparations on skin wrinkle depth using PRIMOS and skin hydration by a corneometer. UVB irradiation induced cell apoptosis in the epidermis of skin organ cultures and increased their pro-inflammatory cytokine, tumor necrosis α (TNFα) secretion. Topical applications of both preparations significantly attenuated all these effects. Furthermore, in human subjects, a reduction in wrinkle depth and an elevation in the intense skin moisture were observed. The observations clearly show that EXD and EXN preparations have protective anti-apoptotic and anti-inflammatory properties that can attenuate biological effects of skin photo-damage. Topical application of the preparations improves skin appearance by reducing its wrinkles depth and increasing its moisturizing impact. © 2012 Wiley Periodicals, Inc.

COMPUTATIONAL MODELING OF SIGNALING PATHWAYS MEDIATING CELL CYCLE AND APOPTOTIC RESPONSES TO IONIZING RADIATION MEDIATED DNA DAMAGE

EPA Science Inventory

Demonstrated of the use of a computational systems biology approach to model dose response relationships. Also discussed how the biologically motivated dose response models have only limited reference to the underlying molecular level. Discussed the integration of Computational S...

Economic Analysis of Biological Invasions in Forests

Treesearch

Tomas P. Holmes; Julian Aukema; Jeffrey Englin; Robert G. Haight; Kent Kovacs; Brian Leung

2014-01-01

Biological invasions of native forests by nonnative pests result from complex stochastic processes that are difficult to predict. Although economic optimization models describe efficient controls across the stages of an invasion, the ability to calibrate such models is constrained by lack of information on pest population dynamics and consequent economic damages. Here...

Biological control of tropical soda apple (Solanaceae) in Florida: Post-release evaluation

USDA-ARS?s Scientific Manuscript database

The leaf feeding beetle Gratiana boliviana Spaeth (Coleoptera: Chrysomelidae) was released as a biological control agent against tropical soda apple (TSA) (Solanum viarum Dunal (Solanaceae)) in Sumter County, FL in 2006. Evaluation of beetle feeding damage to TSA plants and changes in the beetle po...

Integration of biological control and transgenic insect protection for mitigation of mycotoxins in corn

USDA-ARS?s Scientific Manuscript database

Biological control is known to be effective in reducing aflatoxin contamination of corn and some transgenic corn hybrids incur greatly reduced damage from corn earworm (Helicoverpa zea). We conducted seven field trials over two years to test the hypothesis that transgenic insect protection and biol...

Recent progress in a classical biological control program for olive fruit fly in California

USDA-ARS?s Scientific Manuscript database

The olive fruit fly, Bactrocera oleae (Diptera: Tephritidae), causes severe damage to olive production worldwide. Control of olive fruit fly typically relies on pesticides, and under such conditions the impact of natural enemies is relatively low. About 15 years ago, the USDA-ARS European Biologic...

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

NASA Technical Reports Server (NTRS)

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

2011-01-01

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

Roles of oxidative stress in synchrotron radiation X-ray-induced testicular damage of rodents

PubMed Central

Ma, Yingxin; Nie, Hui; Sheng, Caibin; Chen, Heyu; Wang, Ban; Liu, Tengyuan; Shao, Jiaxiang; He, Xin; Zhang, Tingting; Zheng, Chaobo; Xia, Weiliang; Ying, Weihai

2012-01-01

Synchrotron radiation (SR) X-ray has characteristic properties such as coherence and high photon flux, which has excellent potential for its applications in medical imaging and cancer treatment. However, there is little information regarding the mechanisms underlying the damaging effects of SR X-ray on biological tissues. Oxidative stress plays an important role in the tissue damage induced by conventional X-ray, while the role of oxidative stress in the tissue injury induced by SR X-ray remains unknown. In this study we used the male gonads of rats as a model to study the roles of oxidative stress in SR X-ray-induced tissue damage. Exposures of the testes to SR X-ray at various radiation doses did not significantly increase the lipid peroxidation of the tissues, assessed at one day after the irradiation. No significant decreases in the levels of GSH or total antioxidation capacity were found in the SR X-ray-irradiated testes. However, the SR X-ray at 40 Gy induced a marked increase in phosphorylated H2AX – a marker of double-strand DNA damage, which was significantly decreased by the antioxidant N-acetyl cysteine (NAC). NAC also attenuated the SR X-ray-induced decreases in the cell layer number of seminiferous tubules. Collectively, our observations have provided the first characterization of SR X-ray-induced oxidative damage of biological tissues: SR X-ray at high doses can induce DNA damage and certain tissue damage during the acute phase of the irradiation, at least partially by generating oxidative stress. However, SR X-ray of various radiation doses did not increase lipid peroxidation. PMID:22837810

Thermoelectric needle probe for temperature measurements in biological materials.

PubMed

Korn, U; Rav-Noy, Z; Shtrikman, S; Zafrir, M

1980-04-01

In certain biological and medical applications it is important to measure and follow temperature changes inside a body or tissue. Any probe inserted into a tissue causes damage to tissue and distortion to the initial temperature distribution. To minimize this interference, a fine probe is needed. Thus, thin film technology is advantageous and was utilized by us to produce sensitive probes for these applications. The resulting probe is a small thermocouple at the tip of a thin needle (acupuncture stainless steel needle, approximately 0.26 mm in diameter and length in the range 5-10 cm was used). The junction was produced at the needle's tip by coating the needle with thin layers of insulating and thermoelectric materials. The first layer is an insulating one and is composed of polyacrylonitrile (PAN) and polymide produced by plasma polymerization and dip-coating respectively. This layer covers all the needle except the tip. The second layer is a vacuum deposited thermoelectric thin layer of Bi-5% Sb alloy coating also the tip. The third layer is for insulation and protection and is composed of PAN and polyimide. In this arrangement the junction is at the needle's tip, the needle is one conductor, the thermoelectric layer is the other and they are isolated by the plastic layer. The probe is handy and mechanically sturdy. The sensitivity is typically 77 microV/degrees C at room temperature and is constant to within 2% up to 90 degrees C. The response is fast (less than 1 sec) the noise is small, (less than 0.05 degrees C) and because of the small dimension, damage to tissue and disturbance to the measured temperature field are minimal.

The Biological Effectiveness of Different Radiation Qualities for the Induction of Chromosome Damage in Human Lymphocytes

NASA Technical Reports Server (NTRS)

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

2010-01-01

Chromosome aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to 28Si- ions with energies ranging from 90 to 600 MeV/u, or to 56Fe-ions with energies ranging from 200 to 5,000 MeV/u. The LET of the various Fe beams in this study ranged from 145 to 440 keV/micron and the LET of the Si ions ranged from 48 to 158 keV/ m. Doses delivered were in the 10- to 200-cGy range. Dose-response curves for chromosome exchanges in cells at first division after exposure, measured using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosome damage with respect to -rays. The estimates of RBE(sub max) values for total chromosome exchanges ranged from 4.4+/-0.4 to 31.5+/-2.6 for Fe ions, and 11.8+/-1.0 to 42.2+/-3.3 for Si ions. The highest RBE(sub max) value for Fe ions was obtained with the 600-Mev/u beam, and the highest RBE(sub max) value for Si ions was obtained with the 170 MeV/u beam. For both ions the RBEmax values increased with LET, reaching a maximum at about 180 keV/micron for Fe and about 100 keV/ m for Si, and decreasing with further increase in LET. Additional studies for low doses 28Si-ions down to 0.02 Gy will be discussed.

Gene expression of corals in response to macroalgal competitors.

PubMed

Shearer, Tonya L; Snell, Terry W; Hay, Mark E

2014-01-01

As corals decline and macroalgae proliferate on coral reefs, coral-macroalgal competition becomes more frequent and ecologically important. Whether corals are damaged by these interactions depends on susceptibility of the coral and traits of macroalgal competitors. Investigating changes in gene expression of corals and their intracellular symbiotic algae, Symbiodinium, in response to contact with different macroalgae provides insight into the biological processes and cellular pathways affected by competition with macroalgae. We evaluated the gene expression profiles of coral and Symbiodinium genes from two confamilial corals, Acropora millepora and Montipora digitata, after 6 h and 48 h of contact with four common macroalgae that differ in their allelopathic potency to corals. Contacts with macroalgae affected different biological pathways in the more susceptible (A. millepora) versus the more resistant (M. digitata) coral. Genes of coral hosts and of their associated Symbiodinium also responded in species-specific and time-specific ways to each macroalga. Changes in number and expression intensity of affected genes were greater after 6 h compared to 48 h of contact and were greater following contact with Chlorodesmis fastigiata and Amphiroa crassa than following contact with Galaxaura filamentosa or Turbinaria conoides. We documented a divergence in transcriptional responses between two confamilial corals and their associated Symbiodinium, as well as a diversity of dynamic responses within each coral species with respect to the species of macroalgal competitor and the duration of exposure to that competitor. These responses included early initiation of immune processes by Montipora, which is more resistant to damage after long-term macroalgal contact. Activation of the immune response by corals that better resist algal competition is consistent with the hypothesis that some macroalgal effects on corals may be mediated by microbial pathogens.

Modern Initial Management of Severe Limbs Trauma in War Surgery: Orthopaedic Damage Control

DTIC Science & Technology

2010-04-01

avoid fat embolism , allow an optimal nursing and medical evacuation without any secondary functional consequences [3]. 2.2.1 Indications: The...decrease the risk of fat embolism . Modern Initial Management of Severe Limbs Trauma in War Surgery: “Orthopaedic Damage Control” RTO-MP-HFM-182 17...injuries. Orthopaedic Imperious: Multiple open shaft fractures with blood loss, complex epiphysal fractures requiring a long difficult surgical bloody

Hot-Spot Fatigue and Impact Damage Detection on a Helicopter Tailboom

DTIC Science & Technology

2011-09-01

other 14 PZT disks were used as sensors. Among the 28 PZT disks, 16 PZT disks were placed in the two fatigue hot-spot areas to detect cracks initiated...more efficient and effective airframe maintenance, fatigue cracking and impact damage detection technologies were developed and demonstrated on a...SHM system in successfully monitoring fatigue cracks initiated from cyclical loading conditions; detecting, locating and quantifying ballistic

Damage threshold dependence of optical coatings on substrate materials

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

Zhouling, W.; Zhenxiu, F.

1996-04-01

Damage threshold dependence on substrate materials was investigated for TiO2, ZrO2, SiO2, MgF2, ZnS, and single and TiO2/SiO2 multilayers. The results show that the damage threshold increases with increasing substrate thermal conductivity for single layers and AR coatings and remains the same for HR coatings. With the help of localized absorption measurement and in-situ damage process analysis, these phenomena were well correlated with local absorption-initiated thermal damage mechanism.

Developing Navy Capability to Recover Forces in Chemical, Biological, and Radiological Hazard Environments

DTIC Science & Technology

2013-01-01

damage control; LHD flight deck and well deck operations; fleet surgical team; Afloat Training Group; Assault Craft Unit; Naval Surface Warfare Center ...Biological, Radiological and Nuclear School, and U.S. Army Edgewood Chemical Biological Center , Guidelines for Mass Casualty Decontamination During a HAZMAT...Policy Center of the RAND National Defense Research Institute, a federally funded research and development center sponsored by OSD, the Joint Staff

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

Harvest operations for density management: planning requirements, production, costs, stand damage, and recommendations

Treesearch

Loren D. Kellogg; Stephen J. Pilkerton

2013-01-01

Since the early 1990s, several studies have been undertaken to determine the planning requirements, productivity, costs, and residual stand damage of harvest operations in thinning treatments designed to promote development of complex forest structure in order to enhance ecological functioning and biological diversity. Th ese studies include the Oregon State...

Managing Sirex noctilio populations in Patagonia (Argentina): silviculture and biological control

Treesearch

José Villacide; Deborah Fischbein; Nélida Jofré; Juan Corley

2010-01-01

Sirex noctilio is a primitive wood boring solitary wasp with a univoltine life cycle. Characteristic of this species is the occurrence of severely damaging, pulse-like eruptive population outbreaks. During outbreaks, the damage to pine plantations can be severe; tree mortality may reach levels close to 80 percent. Outbreak behavior is thus important...

Biology and impact of Thrips calcaratus Uzel in the Great Lakes Region

Treesearch

Kenneth F. Raffa

1991-01-01

Basswood (Tilia americana L.) stands in the Lake States have been experiencing defoliation since around 1979. These symptoms were originally attributed to frost damage because they occur in early spring. However, the pattern of damaged trees was atypical of frost injury. Only basswood trees were affected, and there was no relationship to sites known...

Sam68 Is Required for DNA Damage Responses via Regulating Poly(ADP-ribosyl)ation

PubMed Central

Hodgson, Andrea; Wier, Eric M.; Wen, Matthew G.; Kamenyeva, Olena; Xia, Xue; Koo, Lily Y.

2016-01-01

The rapid and robust synthesis of polymers of adenosine diphosphate (ADP)-ribose (PAR) chains, primarily catalyzed by poly(ADP-ribose) polymerase 1 (PARP1), is crucial for cellular responses to DNA damage. However, the precise mechanisms through which PARP1 is activated and PAR is robustly synthesized are not fully understood. Here, we identified Src-associated substrate during mitosis of 68 kDa (Sam68) as a novel signaling molecule in DNA damage responses (DDRs). In the absence of Sam68, DNA damage-triggered PAR production and PAR-dependent DNA repair signaling were dramatically diminished. With serial cellular and biochemical assays, we demonstrated that Sam68 is recruited to and significantly overlaps with PARP1 at DNA lesions and that the interaction between Sam68 and PARP1 is crucial for DNA damage-initiated and PARP1-conferred PAR production. Utilizing cell lines and knockout mice, we illustrated that Sam68-deleted cells and animals are hypersensitive to genotoxicity caused by DNA-damaging agents. Together, our findings suggest that Sam68 plays a crucial role in DDR via regulating DNA damage-initiated PAR production. PMID:27635653

Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1

PubMed Central

Calvo, Jennifer A.; Moroski-Erkul, Catherine A.; Lake, Annabelle; Eichinger, Lindsey W.; Shah, Dharini; Jhun, Iny; Limsirichai, Prajit; Bronson, Roderick T.; Christiani, David C.; Meira, Lisiane B.; Samson, Leona D.

2013-01-01

Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag −/− mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage. PMID:23593019

Effects of Biologic Agents in Patients with Rheumatoid Arthritis and Amyloidosis Treated with Hemodialysis.

PubMed

Kuroda, Takeshi; Tanabe, Naohito; Nozawa, Yukiko; Sato, Hiroe; Nakatsue, Takeshi; Kobayashi, Daisuke; Wada, Yoko; Saeki, Takako; Nakano, Masaaki; Narita, Ichiei

Objective Our objective was to examine the safety and effects of therapy with biologics on the prognosis of rheumatoid arthritis (RA) patients with reactive amyloid A (AA) amyloidosis on hemodialysis (HD). Methods Twenty-eight patients with an established diagnosis of reactive AA amyloidosis participated in the study. The survival was calculated from the date of HD initiation until the time of death, or up to end of June 2015 for the patients who were still alive. HD initiation was according to the program of HD initiation for systemic amyloidosis patients associated with RA. Results Ten patients had been treated with biologics before HD initiation for a mean of 28.2 months (biologic group), while 18 had not (non-biologic group). HD was initiated in patients with similar characteristics except for the tender joint count, swollen joint count, and disease activity score (DAS)28-C-reactive protein (CRP). History of biologics showed that etanercept was frequently used for 8 patients as the first biologic. There was no significant difference in the mortality rate according to a Kaplan-Meier analysis (p=0.939) and or associated risk of death in an age-adjusted Cox proportional hazards model (p=0.758) between both groups. Infections were significantly more frequent causes of death in the biologic group than in the non-biologic group (p=0.021). However, treatment with biologics improved the DAS28-CRP score (p=0.004). Conclusion Under the limited conditions of AA amyloidosis treated with HD, the use of biologics might affect infection and thus may not improve the prognosis. Strict infection control is necessary for the use of biologics with HD to improve the prognosis.

Effects of Biologic Agents in Patients with Rheumatoid Arthritis and Amyloidosis Treated with Hemodialysis

PubMed Central

Kuroda, Takeshi; Tanabe, Naohito; Nozawa, Yukiko; Sato, Hiroe; Nakatsue, Takeshi; Kobayashi, Daisuke; Wada, Yoko; Saeki, Takako; Nakano, Masaaki; Narita, Ichiei

2016-01-01

Objective Our objective was to examine the safety and effects of therapy with biologics on the prognosis of rheumatoid arthritis (RA) patients with reactive amyloid A (AA) amyloidosis on hemodialysis (HD). Methods Twenty-eight patients with an established diagnosis of reactive AA amyloidosis participated in the study. The survival was calculated from the date of HD initiation until the time of death, or up to end of June 2015 for the patients who were still alive. HD initiation was according to the program of HD initiation for systemic amyloidosis patients associated with RA. Results Ten patients had been treated with biologics before HD initiation for a mean of 28.2 months (biologic group), while 18 had not (non-biologic group). HD was initiated in patients with similar characteristics except for the tender joint count, swollen joint count, and disease activity score (DAS)28-C-reactive protein (CRP). History of biologics showed that etanercept was frequently used for 8 patients as the first biologic. There was no significant difference in the mortality rate according to a Kaplan-Meier analysis (p=0.939) and or associated risk of death in an age-adjusted Cox proportional hazards model (p=0.758) between both groups. Infections were significantly more frequent causes of death in the biologic group than in the non-biologic group (p=0.021). However, treatment with biologics improved the DAS28-CRP score (p=0.004). Conclusion Under the limited conditions of AA amyloidosis treated with HD, the use of biologics might affect infection and thus may not improve the prognosis. Strict infection control is necessary for the use of biologics with HD to improve the prognosis. PMID:27725536

Emerging opportunities in structural biology with X-ray free-electron lasers

PubMed Central

Schlichting, Ilme; Miao, Jianwei

2012-01-01

X-ray free-electron lasers (X-FELs) produce X-ray pulses with extremely brilliant peak intensity and ultrashort pulse duration. It has been proposed that radiation damage can be “outrun” by using an ultra intense and short X-FEL pulse that passes a biological sample before the onset of significant radiation damage. The concept of “diffraction-before-destruction” has been demonstrated recently at the Linac Coherent Light Source, the first operational hard X-ray FEL, for protein nanocrystals and giant virus particles. The continuous diffraction patterns from single particles allow solving the classical “phase problem” by the oversampling method with iterative algorithms. If enough data are collected from many identical copies of a (biological) particle, its three-dimensional structure can be reconstructed. We review the current status and future prospects of serial femtosecond crystallography (SFX) and single-particle coherent diffraction imaging (CDI) with X-FELs. PMID:22922042

Assessment of genotoxic exposure in Swedish coke-oven work by different methods of biological monitoring.

PubMed

Reuterwall, C; Aringer, L; Elinder, C G; Rannug, A; Levin, J O; Juringe, L; Onfelt, A

1991-04-01

This study evaluated the results of several biological methods used simultaneously to monitor coke-oven work. Blood samples from 44 male coke-oven workers and 48 male referents, matched for age and smoking/snuff consumption, were examined for cytogenetic damage in lymphocytes. Urinary thioether excretion was determined for 62, and urine mutagenicity for 31, of the subjects, who followed a standardized diet during the urine sampling. Exposure to polycyclic aromatic hydrocarbons varied with work task, the ambient air levels of benzo[a]pyrene sometimes exceeding 5 micrograms/m3. Cytogenetic damage, urine mutagenicity, and thioether excretion did not differ between the groups. The smokers, however, had significantly higher sister chromatid exchange frequencies, urine mutagenicity, and thioether excretion than the nonsmokers. The absence of biological indications of genotoxic exposure was unexpected and indicates that the studied methods are not adequate to assess the carcinogenic risks of Swedish coke-oven workers.

Radiation biology of HZE particles

NASA Technical Reports Server (NTRS)

Nelson, Gregory A.

1990-01-01

The biological effects of heavy charged particle (HZE) radiation are of particular interest to travellers and planners for long duration space flights where exposure levels represent a potential health hazard. The unique feature of HZE radiation is the structured pattern of its energy deposition in targets which may be related to charge, velocity, or rate of energy loss. There are many consequences of this feature to biological endpoints when compared to effects of ionizing photons. Dose vs response and dose rate kinetics are modified, DNA and cellular repair systems are altered in their abilities to cope with damage and, the qualitative features of damage are unique for different ions. These features must be incorporated into any risk assessment system for radiation health management. HZE induced mutation, cell inactivation and altered organogenesis will be discussed emphasizing studies with the nematode Caenorhabditis elegans and cultured cells. Observations from radiobiology experiments in space will also be reviewed along with plans for future space-based studies.

Continuum damage modeling and simulation of hierarchical dental enamel

NASA Astrophysics Data System (ADS)

Ma, Songyun; Scheider, Ingo; Bargmann, Swantje

2016-05-01

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

Engineering long term clinical success of advanced ceramic prostheses.

PubMed

Rekow, Dianne; Thompson, Van P

2007-01-01

Biocompatability and, in some applications, esthetics make all-ceramic prostheses compelling choices but despite significant improvements in materials properties and toughening mechanisms, these still have significant failure rates. Factors that contribute to the degradation in strength and survival include material selection and prosthesis design which set the upper limit for performance. However, fabrication operations introduce damage that can be exacerbated by environmental conditions and clinical function. Using all-ceramic dental crowns as an example, experimentally derived models provide insight into the relationships between materials properties and initial critical loads to failure. Analysis of fabrication operations suggests strategies to minimize damage. Environmental conditions can create viscoplastic flow of supporting components which can contribute additional stress within the prosthesis. Fatigue is a particularly challenging problem, not only providing the energy to propagate existing damage but, when combined with the wet environment, can create new damage modes. While much is known, the influence of these new damage modes has not been completely elucidated. The role of complex prosthesis geometry and its interaction with other factors on damage initiation and propagation has yet to be well characterized.

Fatigue testing and damage development in continuous fiber reinforced metal matrix composites

NASA Technical Reports Server (NTRS)

Johnson, W. S.

1988-01-01

A general overview of the fatigue behavior of metal matrix composites (MMC) is presented. The first objective is to present experimental procedures and techniques for conducting a meaningful fatigue test to detect and quantify fatigue damage in MMC. These techniques include interpretation of stress-strain responses, acid etching of the matrix, edge replicas of the specimen under load, radiography, and micrographs of the failure surfaces. In addition, the paper will show how stiffness loss in continuous fiber reinforced metal matrix composites can be a useful parameter for detecting fatigue damage initiation and accumulation. Second, numerous examples of how fatigue damage can initiate and grow in various MMC are given. Depending on the relative fatigue behavior of the fiber and matrix, and the interface properties, the failure modes of MMC can be grouped into four categories: (1) matrix dominated, (2) fiber dominated, (3) self-similar damage growth, and (4) fiber/matrix interfacial failures. These four types of damage will be discussed and illustrated by examples with the emphasis on the fatigue of unnotched laminates.

Fatigue testing and damage development in continuous fiber reinforced metal matrix composites

NASA Technical Reports Server (NTRS)

Johnson, W. S.

1989-01-01

A general overview of the fatigue behavior of metal matrix composites (MMC) is presented. The first objective is to present experimental procedures and techniques for conducting a meaningful fatigue test to detect and quantify fatigue damage in MMC. These techniques include interpretation of stress-strain responses, acid etching of the matrix, edge replicas of the specimen under load, radiography, and micrographs of the failure surfaces. In addition, the paper will show how stiffness loss in continuous fiber reinforced metal matrix composites can be a useful parameter for detecting fatigue damage initiation and accumulation. Second, numerous examples of how fatigue damage can initiate and grow in various MMC are given. Depending on the relative fatigue behavior of the fiber and matrix, and the interface properties, the failure modes of MMC can be grouped into four categories: (1) matrix dominated, (2) fiber dominated, (3) self-similar damage growth, and (4) fiber/matrix interfacial failures. These four types of damage will be discussed and illustrated by examples with the emphasis on the fatigue of unnotched laminates.

Depletion of ribosomal protein L37 occurs in response to DNA damage and activates p53 through the L11/MDM2 pathway.

PubMed

Llanos, Susana; Serrano, Manuel

2010-10-01

Perturbation of ribosomal biogenesis has recently emerged as a relevant p53-activating pathway. This pathway can be initiated by depletion of certain ribosomal proteins, which is followed by the binding and inhibition of MDM2 by a different subset of ribosomal proteins that includes L11. Here, we report that depletion of L37 leads to cell cycle arrest in a L11- and p53-dependent manner. DNA damage can initiate ribosomal stress, although little is known about the mechanisms involved. We have found that some genotoxic insults, namely, UV light and cisplatin, lead to proteasomal degradation of L37 in the nucleoplasm and to the ensuing L11-dependent stabilization of p53. Moreover, ectopic L37 overexpression can attenuate the DNA damage response mediated by p53. These results support the concept that DNA damage-induced proteasomal degradation of L37 constitutes a mechanistic link between DNA damage and the ribosomal stress pathway, and is a relevant contributing signaling pathway for the activation of p53 in response to DNA damage.

Systems biology approaches to understand the effects of nutrition and promote health.

PubMed

Badimon, Lina; Vilahur, Gemma; Padro, Teresa

2017-01-01

Within the last years the implementation of systems biology in nutritional research has emerged as a powerful tool to understand the mechanisms by which dietary components promote health and prevent disease as well as to identify the biologically active molecules involved in such effects. Systems biology, by combining several '-omics' disciplines (mainly genomics/transcriptomics, proteomics and metabolomics), creates large data sets that upon computational integration provide in silico predictive networks that allow a more extensive analysis of the individual response to a nutritional intervention and provide a more global comprehensive understanding of how diet may influence health and disease. Numerous studies have demonstrated that diet and particularly bioactive food components play a pivotal role in helping to counteract environmental-related oxidative damage. Oxidative stress is considered to be strongly implicated in ageing and the pathophysiology of numerous diseases including neurodegenerative disease, cancers, metabolic disorders and cardiovascular diseases. In the following review we will provide insights into the role of systems biology in nutritional research and focus on transcriptomic, proteomic and metabolomics studies that have demonstrated the ability of functional foods and their bioactive components to fight against oxidative damage and contribute to health benefits. © 2016 The British Pharmacological Society.

Unusual plastic deformation and damage features in titanium: Experimental tests and constitutive modeling

NASA Astrophysics Data System (ADS)

Revil-Baudard, Benoit; Cazacu, Oana; Flater, Philip; Chandola, Nitin; Alves, J. L.

2016-03-01

In this paper, we present an experimental study on plastic deformation and damage of polycrystalline pure HCP Ti, as well as modeling of the observed behavior. Mechanical characterization data were conducted, which indicate that the material is orthotropic and displays tension-compression asymmetry. The ex-situ and in-situ X-ray tomography measurements conducted reveal that damage distribution and evolution in this HCP Ti material is markedly different than in a typical FCC material such as copper. Stewart and Cazacu (2011) anisotropic elastic/plastic damage model is used to describe the behavior. All the parameters involved in this model have a clear physical significance, being related to plastic properties, and are determined from very few simple mechanical tests. It is shown that this model predicts correctly the anisotropy in plastic deformation, and its strong influence on damage distribution and damage accumulation. Specifically, for a smooth axisymmetric specimen subject to uniaxial tension, damage initiates at the center of the specimen, and is diffuse; the level of damage close to failure being very low. On the other hand, for a notched specimen subject to the same loading the model predicts that damage initiates at the outer surface of the specimen, and further grows from the outer surface to the center of the specimen, which corroborates with the in-situ tomography data.

Light-driven enzymatic catalysis of DNA repair: a review of recent biophysical studies on photolyase.

PubMed

Weber, Stefan

2005-02-25

More than 50 years ago, initial experiments on enzymatic photorepair of ultraviolet (UV)-damaged DNA were reported [Proc. Natl. Acad. Sci. U. S. A. 35 (1949) 73]. Soon after this discovery, it was recognized that one enzyme, photolyase, is able to repair UV-induced DNA lesions by effectively reversing their formation using blue light. The enzymatic process named DNA photoreactivation depends on a non-covalently bound cofactor, flavin adenine dinucleotide (FAD). Flavins are ubiquitous redox-active catalysts in one- and two-electron transfer reactions of numerous biological processes. However, in the case of photolyase, not only the ground-state redox properties of the FAD cofactor are exploited but also, and perhaps more importantly, its excited-state properties. In the catalytically active, fully reduced redox form, the FAD absorbs in the blue and near-UV ranges of visible light. Although there is no direct experimental evidence, it appears generally accepted that starting from the excited singlet state, the chromophore initiates a reductive cleavage of the two major DNA photodamages, cyclobutane pyrimidine dimers and (6-4) photoproducts, by short-distance electron transfer to the DNA lesion. Back electron transfer from the repaired DNA segment is believed to eventually restore the initial redox states of the cofactor and the DNA nucleobases, resulting in an overall reaction with net-zero exchanged electrons. Thus, the entire process represents a true catalytic cycle. Many biochemical and biophysical studies have been carried out to unravel the fundamentals of this unique mode of action. The work has culminated in the elucidation of the three-dimensional structure of the enzyme in 1995 that revealed remarkable details, such as the FAD-cofactor arrangement in an unusual U-shaped configuration. With the crystal structure of the enzyme at hand, research on photolyases did not come to an end but, for good reason, intensified: the geometrical structure of the enzyme alone is not sufficient to fully understand the enzyme's action on UV-damaged DNA. Much effort has therefore been invested to learn more about, for example, the geometry of the enzyme-substrate complex, and the mechanism and pathways of intra-enzyme and enzyme <-->DNA electron transfer. Many of the key results from biochemical and molecular biology characterizations of the enzyme or the enzyme-substrate complex have been summarized in a number of reviews. Complementary to these articles, this review focuses on recent biophysical studies of photoreactivation comprising work performed from the early 1990s until the present.

Space Biophysics: Accomplishments, Trends, Challenges

NASA Technical Reports Server (NTRS)

Smith, Jeffrey D.

2015-01-01

Physics and biology are inextricably linked. All the chemical and biological processes of life are dutifully bound to follow the rules and laws of physics. In space, these physical laws seem to turn on their head and biological systems, from microbes to humans, adapt and evolve in myriad ways to cope with the changed physical influences of the space environment. Gravity is the most prominent change in space that influences biology. In microgravity, the physical processes of sedimentation, density-driven convective flow, influence of surface tension and fluid pressure profoundly influence biology at the molecular and cellular level as well as at the whole-body level. Gravity sensing mechanisms are altered, structural and functional components of biology (such as bone and muscle) are reduced and changes in the way fluids and gasses behave also drive the way microbial systems and biofilms grow as well as the way plants and animals adapt. The radiation environment also effects life in space. Solar particle events and high energy cosmic radiation can cause serious damage to DNA and other biomolecules. The results can cause mutation, cellular damage or death, leading to health consequences of acute radiation damage or long-term health consequences such as increased cancer risk. Space Biophysics is the study and utilization of physical changes in space that cause changes in biological systems. The unique physical environment in space has been used successfully to grow high-quality protein crystals and 3D tissue cultures that could not be grown in the presence of unidirectional gravitational acceleration here on Earth. All biological processes that change in space have their root in a biophysical alteration due to microgravity and/or the radiation environment of space. In order to fully-understand the risks to human health in space and to fully-understand how humans, plants, animals and microbes can safely and effectively travel and eventually live for long periods beyond the protective environment of Earth, the biophysical properties underlying these changes must be studied, characterized and understood. This lecture reviews the current state of NASA biophysics research accomplishments and identifies future trends and challenges for biophysics research on the International Space Station and beyond.

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

NASA Technical Reports Server (NTRS)

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

2003-01-01

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

Induction and repair of DNA strand breaks in bovine lens epithelial cells after high LET irradiation

NASA Astrophysics Data System (ADS)

Baumstark-Khan, C.; Heilmann, J.; Rink, H.

The lens epithelium is the initiation site for the development of radiation induced cataracts. While in the cortex and nucleus radiation interacts with proteins, experimental results from cultured lenses and lens epithelial cells demonstrate mutagenic and cytotoxic effects in the epithelium. It is suggested that incorrectly repaired DNA damage may be lethal in terms of cellular reproduction and also may initiate the development of mutations or transformations in surviving cells. The occurrence of such genetically modified cells may lead to lens opacification. For a quantitative risk estimation for astronauts and space travelers it is necessary to know the radiation's relative biological effectiveness (RBE), because cosmic rays differ significantly from X-rays. RBEs for the induction of DNA strand breaks and the efficiency of repair of these breaks were measured in cultured diploid bovine lens epithelial cells exposed to different LET irradiations. Irradiations were performed either with 300 kV X-rays or at the UNILAC accelerator at GSI. Accelerated ions from Z=8 (O) to Z=92 (U) were used. For strand break measurements hydroxyapatite chromatography of alka-line unwound DNA (overall strand breaks) and non-denaturing filter elution technique (double strand breaks) were applied. Experiments showed that DNA damage occurs as a function of dose, of kinetic energy and of LET. For particles having the same LET the severity of the DNA damage increases with dose. For a given particle dose, as the LET rises, the numbers of DNA strand breaks increase to a maximum and then reach a plateau or decrease. Repair kinetics depend on the fluence (irradiation dose). At any LET value, repair is much slower after heavy ion exposure than after X-irradiation. For ions with an LET of less than 10,000 keV/μm more than 90 percent of the strand breaks induced are repaired within 24 hours. At higher particle fluences, especially for low energetic particles with a very high local density of energy deposition within the particle track, a higher proportion of non-rejoined breaks is found, even after prolonged periods of incubation. At the highest LET value (16,300 keV/μm) no significant repair is observed. These observations are consistent with the current theory of the mechanism of radiation induced cataractogenesis which posts that genomic damage to the epithelial cells surviving the exposure is responsible for lens opacification.

Biomarkers of oxidative stress and cataract. Novel drug delivery therapeutic strategies targeting telomere reduction and the expression of telomerase activity in the lens epithelial cells with N-acetylcarnosine lubricant eye drops: anti-cataract which helps to prevent and treat cataracts in the eyes of dogs and other animals.

PubMed

Babizhayev, Mark A; Yegorov, Yegor E

2014-01-01

Cataracts in small animals are shown to be at least partially caused by oxidative damage to lens epithelial cells (LECs) and the internal lens; biomarkers of oxidative stress in the lens are considered as general biomarkers for life expectancy in the canine and other animals. Telomeres lengths and expressed telomerase activity in canine LECs may serve as important monitors of oxidative damage in normal LECs with documented higher levels of telomerase activity in cataractous LECs during cells' lifespan. Loss of functional telomere length below a critical threshold in LECs of canines during the effect of UV and chronic oxidative stress or metabolic failure, can activate programs leading to LEC senescence or death. Telomerase is induced in LECs of canines at critical stages of cataractogenesis initiation and exposure to oxidative stress through the involvement of catalytically active prooxidant transition metal (iron) ions. This work documents that transition metal ions (such as, ferrous ions- catalytic oxidants) might induce premature senescence in LECs of canines, telomere shortening with increased telomerase activity as adaptive response to UV light, oxidative and metabolic stresses. The therapeutic treatment with 1% N-acetylcarnosine (NAC) prodrug delivery is beneficial for prevention and dissolution of ripe cataracts in canines. This biological activity is based on the findings of ferroxidase activity pertinent to the dipeptide carnosine released ophthalmically from NAC prodrug of L-carnosine, stabilizing properties of carnosine on biological membranes based on the ability of the imidazole-containing dipeptides to interact with lipid peroxidation products and reactive oxygen species (ROS), to prevent membrane damage and delute the associated with membrane fragements protein aggregates. The advent of therapeutic treatment of cataracts in canines with N-acetylcarnosine lubricant eye drops through targeting the prevention of loss of functional telomere length below a critical threshold and "flirting" with an indirect effect with telomerase expression in LECs of canines during the effects of UV, chronic oxidative stress increases the successful rate of cataract management challenges in home veterinary care.

Mechanism of action for anti-radiation vaccine in reducing the biological impact of high-dose gamma irradiation

NASA Astrophysics Data System (ADS)

Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after high-dose gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naïve animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which they mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

Mechanism of Action for Anti-radiation Vaccine in Reducing the Biological Impact of High-dose Gamma Irradiation

NASA Technical Reports Server (NTRS)

Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

2007-01-01

Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then collected and circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naive animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which the mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

An Interface Damage Model for the Simulation of Delamination Under Variable-Mode Ratio in Composite Materials

NASA Technical Reports Server (NTRS)

Turon, Albert; Camanho, Pedro P.; Costa, Josep; Davila, Carlos G.

2004-01-01

A thermodynamically consistent damage model for the simulation of progressive delamination under variable mode ratio is presented. The model is formulated in the context of the Damage Mechanics (DM). The constitutive equations that result from the variation of the free energy with damage are used to model the initiation and propagation of delamination. A new delamination initiation criterion is developed to assure that the formulation can account for changes in the loading mode in a thermodynamically consistent way. Interfacial penetration of two adjacent layers after complete decohesion is prevented by the formulation of the free energy. The model is implemented into the commercial finite element code ABAQUS by means of a user-written decohesion element. Finally, the numerical predictions given by the model are compared with experimental results.

Dissociating basal forebrain and medial temporal amnesic syndromes: insights from classical conditioning.

PubMed

Myer, Catherine E; Bryant, Deborah; DeLuca, John; Gluck, Mark A

2002-01-01

In humans, anterograde amnesia can result from damage to the medial temporal (MT) lobes (including hippocampus), as well as to other brain areas such as basal forebrain. Results from animal classical conditioning studies suggest that there may be qualitative differences in the memory impairment following MT vs. basal forebrain damage. Specifically, delay eyeblink conditioning is spared after MT damage in animals and humans, but impaired in animals with basal forebrain damage. Recently, we have likewise shown delay eyeblink conditioning impairment in humans with amnesia following anterior communicating artery (ACoA) aneurysm rupture, which damages the basal forebrain. Another associative learning task, a computer-based concurrent visual discrimination, also appears to be spared in MT amnesia while ACoA amnesics are slower to learn the discriminations. Conversely, animal and computational models suggest that, even though MT amnesics may learn quickly, they may learn qualitatively differently from controls, and these differences may result in impaired transfer when familiar information is presented in novel combinations. Our initial data suggests such a two-phase learning and transfer task may provide a double dissociation between MT amnesics (spared initial learning but impaired transfer) and ACoA amnesics (slow initial learning but spared transfer). Together, these emerging data suggest that there are subtle but dissociable differences in the amnesic syndrome following damage to the MT lobes vs. basal forebrain, and that these differences may be most visible in non-declarative tasks such as eyeblink classical conditioning and simple associative learning.

FEM investigation of concrete silos damaged and reinforced externally with CFRP

NASA Astrophysics Data System (ADS)

Kermiche, Sihem; Boussaid, Ouzine; Redjel, Bachir; Amirat, Abdelaziz

2018-03-01

The present work investigates the reinforcement of concrete wheat-grain silos under initial damage. The reinforcement is achieved by mounting bands of carbon fiber reinforced polymer (CFRP) on the external walls of the silo. 4 modes of reinforcement are adapted according to the width of the band, the gap between two bands, the height of reinforcement and the number of layers achieved through banding. Analytical analyses were conducted using the Reimbert method and the Eurocode 1 Part 4 method, as well as numerically through the finite element software Abaqus. Results show that the normal pressure reaches a peak value when approaching the silo hopper. Initial damage in a concrete silo was first determined using a 3D geometrical model, while the damage analyses were conducted to optimize the CFRP reinforcement by mounting 2 CFRP bands close together above and below the cylinder-hopper joint. Increasing the number of banding layers could produce better performance as the damage was slightly decreased from 0.161 to 0.152 for 1 and 4 layers respectively.

Seasonal and diurnal variations in Martian surface ultraviolet irradiation: biological and chemical implications for the Martian regolith

NASA Astrophysics Data System (ADS)

Patel, M. R.; Bérces, A.; Kolb, C.; Lammer, H.; Rettberg, P.; Zarnecki, J. C.; Selsis, F.

2003-01-01

The issue of the variation of the surface ultraviolet (UV) environment on Mars was investigated with particular emphasis being placed on the interpretation of data in a biological context. A UV model has been developed to yield the surface UV irradiance at any time and place over the Martian year. Seasonal and diurnal variations were calculated and dose rates evaluated. Biological interpretation of UV doses is performed through the calculation of DNA damage effects upon phage T7 and Uracil, used as examples for biological dosimeters. A solar UV "hotspot" was revealed towards perihelion in the southern hemisphere, with a significant damaging effect upon these species. Diurnal profiles of UV irradiance are also seen to vary markedly between aphelion and perihelion. The effect of UV dose is also discussed in terms of the chemical environment of the Martian regolith, since UV irradiance can reach high enough levels so as to have a significant effect upon the soil chemistry. We show, by assuming that H2O is the main source of hydrogen in the Martian atmosphere, that the stoichiometrically desirable ratio of 2:1 for atmospheric H and O loss rates to space are not maintained and at present the ratio is about 20:1. A large planetary oxygen surface sink is therefore necessary, in contrast with escape to space. This surface oxygen sink has important implications for the oxidation potential and the toxicology of the Martian soil. UV-induced adsorption of O_{2}^{-} super-radicals plays an important role in the oxidative environment of the Martian surface, and the biologically damaging areas found in this study are also shown to be regions of high subsurface oxidation. Furthermore, we briefly cover the astrobiological implications for landing sites that are planned for future Mars missions

First radiobiological results of LDEF-1 experiment A0015 with Arabidopsis seed embryos and Sordaria fungus spores

NASA Astrophysics Data System (ADS)

Zimmermann, M. W.; Gartenbach, K. E.; Kranz, A. R.

1994-10-01

This article highlights the first results of investigations on the general vitality and damage endpoints caused by cosmic ionizing radiation in dry, dormant plant seeds of the crucifer plant Arabidopsis thaliana (L.) Hennh. and the ascomycete Sordaria fimicola after 69 month stay in space. Wild-type and mutant gene marker lines were included in Free Flyer Biostack containers and exposed on earth and side tray of the LDEF-1 satellite. The damage in biological endpoints observed in the seeds increased in the side tray sample compared to the earth tray sample. For the ascospores we found different effects depending on the biological endpoints investigated for both expositions.

First radiobiological results of LDEF-1 experiment A0015 with Arabidopsis seed embryos and Sordaria fungus spores.

PubMed

Zimmermann, M W; Gartenbach, K E; Kranz, A R

1994-10-01

This article highlights the first results of investigations on the general vitality and damage endpoints caused by cosmic ionizing radiation in dry, dormant plant seeds of the crucifer plant Arabidopsis thaliana (L.) Heynh. and the ascomycete Sordaria fimicola after 69 month stay in space. Wild-type and mutant gene marker lines were included in Free Flyer Biostack containers and exposed on earth and side tray of the LDEF-1 satellite. The damage in biological endpoints observed in the seeds increased in the side tray sample compared to the earth tray sample. For the ascospores we found different effects depending on the biological endpoints investigated for both expositions.

Fatigue Life of Postbuckled Structures with Indentation Damage

NASA Technical Reports Server (NTRS)

Davila, Carlos G.; Bisagni, Chiara

2016-01-01

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

Potential for biological control of native North American Dendroctonus beetles (Coleoptera: Scolytidae)

Treesearch

M.C. Miller; John C. Moser; M. McGregor; J.C. Gregoire; M. Baisier; D.L. Dahlsten; R.A. Werner

1987-01-01

Bark beetles of the genus Dendroctonus inflict serious damage in North American coniferous forests. Biological control, which has never been seriously attempted with bark beetles in the United States, should be reconsidered in light of results disclosed here. Impact of indigenous associates is discussed, as well as previous, unsuccessful attempts to...

Host range of the inadvertent biological control agent Caloptilia triadicae: an invasive herbivore of Chinese tallowtree

USDA-ARS?s Scientific Manuscript database

An inadvertent biological control agent of the invasive weed Chinese tallowtree (Triadica sebifera) first appeared in North America in 2004. Identified as a Caloptilia triadicae, this leaf miner was found damaging T. sebifera saplings. In Gainesville, FL we exposed naturalized populations of C. tria...

Classifying transcription factor targets and discovering relevant biological features

PubMed Central

Holloway, Dustin T; Kon, Mark; DeLisi, Charles

2008-01-01

Background An important goal in post-genomic research is discovering the network of interactions between transcription factors (TFs) and the genes they regulate. We have previously reported the development of a supervised-learning approach to TF target identification, and used it to predict targets of 104 transcription factors in yeast. We now include a new sequence conservation measure, expand our predictions to include 59 new TFs, introduce a web-server, and implement an improved ranking method to reveal the biological features contributing to regulation. The classifiers combine 8 genomic datasets covering a broad range of measurements including sequence conservation, sequence overrepresentation, gene expression, and DNA structural properties. Principal Findings (1) Application of the method yields an amplification of information about yeast regulators. The ratio of total targets to previously known targets is greater than 2 for 11 TFs, with several having larger gains: Ash1(4), Ino2(2.6), Yaf1(2.4), and Yap6(2.4). (2) Many predicted targets for TFs match well with the known biology of their regulators. As a case study we discuss the regulator Swi6, presenting evidence that it may be important in the DNA damage response, and that the previously uncharacterized gene YMR279C plays a role in DNA damage response and perhaps in cell-cycle progression. (3) A procedure based on recursive-feature-elimination is able to uncover from the large initial data sets those features that best distinguish targets for any TF, providing clues relevant to its biology. An analysis of Swi6 suggests a possible role in lipid metabolism, and more specifically in metabolism of ceramide, a bioactive lipid currently being investigated for anti-cancer properties. (4) An analysis of global network properties highlights the transcriptional network hubs; the factors which control the most genes and the genes which are bound by the largest set of regulators. Cell-cycle and growth related regulators dominate the former; genes involved in carbon metabolism and energy generation dominate the latter. Conclusion Postprocessing of regulatory-classifier results can provide high quality predictions, and feature ranking strategies can deliver insight into the regulatory functions of TFs. Predictions are available at an online web-server, including the full transcriptional network, which can be analyzed using VisAnt network analysis suite. Reviewers This article was reviewed by Igor Jouline, Todd Mockler(nominated by Valerian Dolja), and Sandor Pongor. PMID:18513408

Regulation of ATM-Dependent DNA Damage Responses in Breast Cancer by the RhoGEF Net1

DTIC Science & Technology

2014-04-01

1998) Science 279: 509-514. 12. Harper JW, et al., (2007) The DNA Damage Response: Ten years after. Mol. Cell 28; 739-745. 13. Hill R, et al., (2010...RhoGTPases: Biochemistry and Biology. Annu. Rev. Cell Dev. Biol. 21:247-269. 17. Khanna KK, et al., (2001) ATM, a central controller of cellular

PRESENTED AT TRIANGLE CONSORTIUM OF REPRODUCTIVE BIOLOGY, CHAPEL HILL, NC: GST M1 GENOTYPE INFLUENCES SPERM DNA DAMAGE ASSOCIATED WITH EXPOSURE TO AIR POLLUTION

EPA Science Inventory

Exposure to episodic air pollution in the Czech Republic has been associated with abnormal semen quality and sperm DNA damage (EHP 108:887;2000). A subsequentlongitudinal study evaluated semenfrom 36 men sampled up to 7 times over a period of two years to capture exposures durin...

P66Shc signals to age

PubMed Central

Trinei, Mirella; Berniakovich, Ina; Beltrami, Elena; Migliaccio, Enrica; Fassina, Ambrogio; Pelicci, PierGiuseppe; Giorgio, Marco

2009-01-01

Oxygen metabolism is thought to impact on aging through the formation of reactive oxygen species (ROS) that are supposed to damage biological molecules. The study of p66Shc, a crucial regulator of ROS level involved in aging dysfunction, suggests that the incidence of degenerative disease and longevity are determined by a specific signaling function of ROS other than their unspecific damaging property. PMID:20157533

Solar ultraviolet radiation induces biological alterations in human skin in vitro: relevance of a well-balanced UVA/UVB protection.

PubMed

Bernerd, Francoise; Marionnet, Claire; Duval, Christine

2012-06-01

Cutaneous damages such as sunburn, pigmentation, and photoaging are known to be induced by acute as well as repetitive sun exposure. Not only for basic research, but also for the design of the most efficient photoprotection, it is crucial to understand and identify the early biological events occurring after ultraviolet (UV) exposure. Reconstructed human skin models provide excellent and reliable in vitro tools to study the UV-induced alterations of the different skin cell types, keratinocytes, fibroblasts, and melanocytes in a dose- and time-dependent manner. Using different in vitro human skin models, the effects of UV light (UVB and UVA) were investigated. UVB-induced damages are essentially epidermal, with the typical sunburn cells and DNA lesions, whereas UVA radiation-induced damages are mostly located within the dermal compartment. Pigmentation can also be obtained after solar simulated radiation exposure of pigmented reconstructed skin model. Those models are also highly adequate to assess the potential of sunscreens to protect the skin from UV-associated damage, sunburn reaction, photoaging, and pigmentation. The results showed that an effective photoprotection is provided by broad-spectrum sunscreens with a potent absorption in both UVB and UVA ranges.

Entropy in DNA Double-Strand Break, Detection and Signaling

NASA Astrophysics Data System (ADS)

Zhang, Yang; Schindler, Christina; Heermann, Dieter

2014-03-01

In biology, the term entropy is often understood as a measure of disorder - a restrictive interpretation that can even be misleading. Recently it has become clearer and clearer that entropy, contrary to conventional wisdom, can help to order and guide biological processes in living cells. DNA double-strand breaks (DSBs) are among the most dangerous lesions and efficient damage detection and repair is essential for organism viability. However, what remains unknown is the precise mechanism of targeting the site of damage within billions of intact nucleotides and a crowded nuclear environment, a process which is often referred to as recruitment or signaling. Here we show that the change in entropy associated with inflicting a DSB facilitates the recruitment of damage sensor proteins. By means of computational modeling we found that higher mobility and local chromatin structure accelerate protein association at DSB ends. We compared the effect of different chromatin architectures on protein dynamics and concentrations in the vicinity of DSBs, and related these results to experiments on repair in heterochromatin. Our results demonstrate how entropy contributes to a more efficient damage detection. We identify entropy as the physical basis for DNA double-strand break signaling.

Impact resistance of oil-immersed lignum vitae

NASA Astrophysics Data System (ADS)

Yin, Wei; Shan, Lei; Lu, Hongyu; Zheng, Yelong; Han, Zhiwu; Tian, Yu

2016-07-01

Biological materials immersed in vegetable and mineral oil, such as rattan armor and wooden sleepers, have been extensively used since ancient times because of their excellent mechanical properties. This study quantitatively investigated the viscoelasticity and tribological performance of lignum vitae immersed in poly-alpha-olefin (PAO) and tung oils (Aleuritesfordii Hemsl.) to reveal the mechanism of impact resistance. The acceleration of samples immersed in tung oil was higher than that of dry and PAO-immersed samples in the first impact. The elastic modulus of the samples immersed in tung oil increased slightly. The impact damage on the samples immersed in tung oil was reduced because of the low friction coefficient (0.07) resulted in a low wear rate. The extent of impact damage on the samples immersed in tung oil was approximately 34% and 58% lower than that on the dry and PAO oil-immersed samples, respectively, under an angle of 20° and a height of 10 cm. The impact damage on the PAO-immersed samples was reduced because of low friction coefficient. However, impact damage increased because of large elastic modulus. The findings of this study can serve as a reference for the application of modified biological materials with high strength and wear resistance.

Impact resistance of oil-immersed lignum vitae.

PubMed

Yin, Wei; Shan, Lei; Lu, Hongyu; Zheng, Yelong; Han, Zhiwu; Tian, Yu

2016-07-18

Biological materials immersed in vegetable and mineral oil, such as rattan armor and wooden sleepers, have been extensively used since ancient times because of their excellent mechanical properties. This study quantitatively investigated the viscoelasticity and tribological performance of lignum vitae immersed in poly-alpha-olefin (PAO) and tung oils (Aleuritesfordii Hemsl.) to reveal the mechanism of impact resistance. The acceleration of samples immersed in tung oil was higher than that of dry and PAO-immersed samples in the first impact. The elastic modulus of the samples immersed in tung oil increased slightly. The impact damage on the samples immersed in tung oil was reduced because of the low friction coefficient (0.07) resulted in a low wear rate. The extent of impact damage on the samples immersed in tung oil was approximately 34% and 58% lower than that on the dry and PAO oil-immersed samples, respectively, under an angle of 20° and a height of 10 cm. The impact damage on the PAO-immersed samples was reduced because of low friction coefficient. However, impact damage increased because of large elastic modulus. The findings of this study can serve as a reference for the application of modified biological materials with high strength and wear resistance.

Thermomechanical Fatigue Damage/Failure Mechanisms in SCS-6/Timetal 21S [0/90](Sub S) Composite

NASA Technical Reports Server (NTRS)

Castelli, Michael G.

1994-01-01

The thermomechanical fatigue (TMF) deformation, damage, and life behaviors of SCS6/Timetal 21S (0/90)s were investigated under zero-tension conditions. In-phase (IP) and out-of-phase (OP) loadings were investigated with a temperature cycle from 150 to 650 deg C. An advanced TMF test technique was used to quantify mechanically damage progression. The technique incorporated explicit measurements of the macroscopic (1) isothermal static moduli at the temperature extremes of the TMF cycle and (2) coefficient of thermal expansion (CTE) as functions of the TMF cycles. The importance of thermal property degradation and its relevance to accurate post-test data analysis and interpretation is briefly addressed. Extensive fractography and metallography were conducted on specimens from failed and interrupted tests to characterize the extent of damage at the microstructure level. Fatigue life results indicated trends analogous to those established for similar unidirectional(0) reinforced titanium matrix composite systems. High stress IP and mid to low stress OP loading conditions were life-limiting in comparison to maximum temperature isothermal conditions. Dominant damage mechanisms changed with cycle type. Damage resulting from IP TMF conditions produced measurable decreases in static moduli but only minimal changes in the CTE. Metallography on interrupted and failed specimens revealed extensive (0) fiber cracking with sparse matrix damage. No surface initiated matrix cracks were present. Comparable OP TMF conditions initiated environment enhanced surface cracking and matrix cracking initiated at (90) fiber/matrix (F/M) interfaces. Notable static moduli and CTE degradations were measured. Fractography and metallography revealed that the transverse cracks originating from the surface and (90) F/M interfaces tended to converge and coalesce at the (0) fibers.

Does Surface Topography Play a Role in Taper Damage in Head-neck Modular Junctions?

PubMed

Pourzal, Robin; Hall, Deborah J; Ha, Nguyen Q; Urban, Robert M; Levine, Brett R; Jacobs, Joshua J; Lundberg, Hannah J

2016-10-01

There are increasing reports of total hip arthroplasty failure subsequent to modular taper junction corrosion. The surfaces of tapers are machined to have circumferential machining marks, resulting in a surface topography of alternating peaks and valleys on the scale of micrometers. It is unclear if the geometry of this machined surface topography influences the degree of fretting and corrosion damage present on modular taper junctions or if there are differences between modular taper junction material couples. (1) What are the differences in damage score and surface topography between CoCr/CoCr and CoCr/Ti modular junctions? (2) How are initial surface topography, flexural rigidity, taper angle mismatch, and time in situ related to visual taper damage scores for CoCr/CoCr couples? (3) How are initial surface topography, flexural rigidity, taper angle mismatch, and time in situ related to visual taper damage scores for CoCr/Ti couples? Damage on stem and head tapers was evaluated with a modified Goldberg score. Differences in damage scores were determined between a group of 140 CoCr/CoCr couples and 129 CoCr/Ti couples using a chi-square test. For a subgroup of 70 retrievals, selected at random, we measured five variables, including initial stem taper machining mark height and spacing, initial head taper roughness, flexural rigidity, and taper angle mismatch. All retrievals were obtained at revision surgeries. None were retrieved as a result of metal-on-metal failures or were recalled implants. Components were chosen so there was a comparable number of each material couple and damage score. Machining marks around the circumference of the tapers were measured using white light interferometry to characterize the initial stem taper surface topography in terms of the height of and spacing between machining mark peaks as well as initial head taper roughness. The taper angle mismatch was assessed with a coordinate measuring machine. Flexural rigidity was determined based on measurements of gross taper dimensions and material properties. Differences of median or mean values of all variables between material couples were determined (Wilcoxon rank-sum tests and t-tests). The effect of all five variables along with time in situ on stem and head taper damage scores was tested with a multiple regression model. With 70 retrievals, a statistical power of 0.8 could be achieved for the model. Damage scores were different between CoCr/CoCr and CoCr/Ti modular taper junction material couples. CoCr/CoCr stem tapers were less likely to be mildly damaged (11%, p = 0.006) but more likely to be severely damaged (4%, p = 0.02) than CoCr/Ti stem tapers (28% and 1%, respectively). CoCr/CoCr couples were less likely to have moderately worn head tapers (7% versus 17%, p = 0.003). Stem taper machining mark height and spacing and head taper roughness were 11 (SD 3), 185 (SD 46), and 0.57 (SD 0.5) for CoCr/CoCr couples and 10 (SD 3), 170 (SD 56), and 0.64 (SD 0.4) for CoCr/Ti couples, respectively. There was no difference (p = 0.09, p = 0.1, p = 0.16, respectively) for either factor between material couples. Larger stem taper machining mark heights (p = 0.001) were associated with lower stem taper damage scores, and time in situ (p = 0.006) was associated with higher stem taper damage scores for CoCr/CoCr material couples. Stem taper machining marks that had higher peaks resulted in slower damage progression over time. For CoCr/Ti material couples, head taper roughness was associated with higher stem (p = 0.001) and head taper (p = 0.003) damage scores, and stem taper machining mark height, but not time in situ, was associated with lower stem taper damage scores (p = 0.007). Stem taper surface topography was related to damage scores on retrieved head-neck modular junctions; however, it affected CoCr/CoCr and CoCr/Ti couples differently. A taper topography of circumferential machining marks with higher peaks appears to enable slower damage progression and, subsequently, a reduction of the reported release of corrosion products. This may be of interest to implant designers and manufacturers in an effort to reduce the effects of metal release from modular femoral components.

Returning to Overuse Activity Following a Supraspinatus and Infraspinatus Tear Leads to Joint Damage in a Rat Model

PubMed Central

Reuther, Katherine E.; Thomas, Stephen J.; Evans, Elisabeth F.; Tucker, Jennica J.; Sarver, Joseph J.; Ilkhani-Pour, Sarah; Gray, Chancellor F.; Voleti, Pramod; Glaser, David L.; Soslowsky, Louis J.

2013-01-01

Large rotator cuff tears (supraspinatus and infraspinatus) are common in patients that perform overhead activities (laborers, athletes). In addition, following large cuff tears, these patients commonly attempt to return to pre-injury activity levels. However, there is a limited understanding of the damaging effects on the uninjured joint tissues when doing so. Therefore, the objective of this study was to investigate the effect of returning to overuse activity following a supraspinatus and infraspinatus tear on shoulder function and the structural and biological properties of the intact tendons and glenoid cartilage. Forty rats underwent four weeks of overuse followed by detachment of the supraspinatus and infraspinatus tendons and were then randomized into two groups: return to overuse or cage activity. Ambulatory measurements were performed over time and structural and biologic properties of the adjacent tendons and cartilage were evaluated. Results demonstrated that animals returning to overuse activity did not have altered shoulder function but despite this, did have altered cartilage and tendon properties. These mechanical changes corresponded to altered transcriptional regulation of chondrogenic genes within cartilage and tendon. This study helps define the mechanical and biologic mechanisms leading to joint damage and provides a framework for treating active cuff tear patients. PMID:23764174

Occurrence, Biological Consequences, and Human Health Relevance of Oxidative Stress-Induced DNA Damage.

PubMed

Yu, Yang; Cui, Yuxiang; Niedernhofer, Laura J; Wang, Yinsheng

2016-12-19

A variety of endogenous and exogenous agents can induce DNA damage and lead to genomic instability. Reactive oxygen species (ROS), an important class of DNA damaging agents, are constantly generated in cells as a consequence of endogenous metabolism, infection/inflammation, and/or exposure to environmental toxicants. A wide array of DNA lesions can be induced by ROS directly, including single-nucleobase lesions, tandem lesions, and hypochlorous acid (HOCl)/hypobromous acid (HOBr)-derived DNA adducts. ROS can also lead to lipid peroxidation, whose byproducts can also react with DNA to produce exocyclic DNA lesions. A combination of bioanalytical chemistry, synthetic organic chemistry, and molecular biology approaches have provided significant insights into the occurrence, repair, and biological consequences of oxidatively induced DNA lesions. The involvement of these lesions in the etiology of human diseases and aging was also investigated in the past several decades, suggesting that the oxidatively induced DNA adducts, especially bulky DNA lesions, may serve as biomarkers for exploring the role of oxidative stress in human diseases. The continuing development and improvement of LC-MS/MS coupled with the stable isotope-dilution method for DNA adduct quantification will further promote research about the clinical implications and diagnostic applications of oxidatively induced DNA adducts.

Progressive Fracture and Damage Tolerance of Composite Pressure Vessels

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Gotsis, Pascal K.; Minnetyan, Levon

1997-01-01

Structural performance (integrity, durability and damage tolerance) of fiber reinforced composite pressure vessels, designed for pressured shelters for planetary exploration, is investigated via computational simulation. An integrated computer code is utilized for the simulation of damage initiation, growth, and propagation under pressure. Aramid fibers are considered in a rubbery polymer matrix for the composite system. Effects of fiber orientation and fabrication defect/accidental damages are investigated with regard to the safety and durability of the shelter. Results show the viability of fiber reinforced pressure vessels as damage tolerant shelters for planetary colonization.

Quantifying white matter structural integrity with high-definition fiber tracking in traumatic brain injury.

PubMed

Presson, Nora; Krishnaswamy, Deepa; Wagener, Lauren; Bird, William; Jarbo, Kevin; Pathak, Sudhir; Puccio, Ava M; Borasso, Allison; Benso, Steven; Okonkwo, David O; Schneider, Walter

2015-03-01

There is an urgent, unmet demand for definitive biological diagnosis of traumatic brain injury (TBI) to pinpoint the location and extent of damage. We have developed High-Definition Fiber Tracking, a 3 T magnetic resonance imaging-based diffusion spectrum imaging and tractography analysis protocol, to quantify axonal injury in military and civilian TBI patients. A novel analytical methodology quantified white matter integrity in patients with TBI and healthy controls. Forty-one subjects (23 TBI, 18 controls) were scanned with the High-Definition Fiber Tracking diffusion spectrum imaging protocol. After reconstruction, segmentation was used to isolate bilateral hemisphere homologues of eight major tracts. Integrity of segmented tracts was estimated by calculating homologue correlation and tract coverage. Both groups showed high correlations for all tracts. TBI patients showed reduced homologue correlation and tract spread and increased outlier count (correlations>2.32 SD below control mean). On average, 6.5% of tracts in the TBI group were outliers with substantial variability among patients. Number and summed deviation of outlying tracts correlated with initial Glasgow Coma Scale score and 6-month Glasgow Outcome Scale-Extended score. The correlation metric used here can detect heterogeneous damage affecting a low proportion of tracts, presenting a potential mechanism for advancing TBI diagnosis. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Repair-Resistant DNA Lesions

PubMed Central

2017-01-01

The eukaryotic global genomic nucleotide excision repair (GG-NER) pathway is the major mechanism that removes most bulky and some nonbulky lesions from cellular DNA. There is growing evidence that certain DNA lesions are repaired slowly or are entirely resistant to repair in cells, tissues, and in cell extract model assay systems. It is well established that the eukaryotic DNA lesion-sensing proteins do not detect the damaged nucleotide, but recognize the distortions/destabilizations in the native DNA structure caused by the damaged nucleotides. In this article, the nature of the structural features of certain bulky DNA lesions that render them resistant to NER, or cause them to be repaired slowly, is compared to that of those that are good-to-excellent NER substrates. Understanding the structural features that distinguish NER-resistant DNA lesions from good NER substrates may be useful for interpreting the biological significance of biomarkers of exposure of human populations to genotoxic environmental chemicals. NER-resistant lesions can survive to replication and cause mutations that can initiate cancer and other diseases. Furthermore, NER diminishes the efficacy of certain chemotherapeutic drugs, and the design of more potent pharmaceuticals that resist repair can be advanced through a better understanding of the structural properties of DNA lesions that engender repair-resistance. PMID:28750166

Ocular neuropathic pain

PubMed Central

Rosenthal, Perry; Borsook, David

2016-01-01

As the biological alarm of impending or actual tissue damage, pain is essential for our survival. However, when it is initiated and/or sustained by dysfunctional elements in the nociceptive system, it is itself a disease known as neuropathic pain. While the critical nociceptive system provides a number of protective functions, it is unique in its central role of monitoring, preserving and restoring the optical tear film in the face of evaporative attrition without which our vision would be non-functional. Meeting this existential need resulted in the evolution of the highly complex, powerful and sensitive dry eye alarm system integrated in the peripheral and central trigeminal sensory network. The clinical consequences of corneal damage to these nociceptive pathways are determined by the type and location of its pathological elements and can range from the spectrum known as dry eye disease to the centalised oculofacial neuropathic pain syndrome characterised by a striking disparity between the high intensity of symptoms and paucity of external signs. These changes parallel those observed in somatic neuropathic pain. When seen through the neuroscience lens, diseases responsible for inadequately explained chronic eye pain (including those described as dry eye) can take on new meanings that may clarify long-standing enigmas and point to new approaches for developing preventive, symptomatic and disease-modifying interventions for these currently refractory disorders. PMID:25943558

Aflatoxin B1 and M1: Biological Properties and Their Involvement in Cancer Development.

PubMed

Marchese, Silvia; Polo, Andrea; Ariano, Andrea; Velotto, Salvatore; Costantini, Susan; Severino, Lorella

2018-05-24

Aflatoxins are fungal metabolites found in feeds and foods. When the ruminants eat feedstuffs containing Aflatoxin B1 (AFB1), this toxin is metabolized and Aflatoxin M1 (AFM1) is excreted in milk. International Agency for Research on Cancer (IARC) classified AFB1 and AFM1 as human carcinogens belonging to Group 1 and Group 2B, respectively, with the formation of DNA adducts. In the last years, some epidemiological studies were conducted on cancer patients aimed to evaluate the effects of AFB1 and AFM1 exposure on cancer cells in order to verify the correlation between toxin exposure and cancer cell proliferation and invasion. In this review, we summarize the activation pathways of AFB1 and AFM1 and the data already reported in literature about their correlation with cancer development and progression. Moreover, considering that few data are still reported about what genes/proteins/miRNAs can be used as damage markers due to AFB1 and AFM1 exposure, we performed a bioinformatic analysis based on interaction network and miRNA predictions to identify a panel of genes/proteins/miRNAs that can be used as targets in further studies for evaluating the effects of the damages induced by AFB1 and AFM1 and their capacity to induce cancer initiation.

DNA Dosimetry Assessment for Sunscreen Genotoxic Photoprotection

PubMed Central

Schuch, André Passaglia; Lago, Juliana Carvalhães; Yagura, Teiti; Menck, Carlos Frederico Martins

2012-01-01

Background Due to the increase of solar ultraviolet radiation (UV) incidence over the last few decades, the use of sunscreen has been widely adopted for skin protection. However, considering the high efficiency of sunlight-induced DNA lesions, it is critical to improve upon the current approaches that are used to evaluate protection factors. An alternative approach to evaluate the photoprotection provided by sunscreens against daily UV radiation-induced DNA damage is provided by the systematic use of a DNA dosimeter. Methodology/Principal Findings The Sun Protection Factor for DNA (DNA-SPF) is calculated by using specific DNA repair enzymes, and it is defined as the capacity for inhibiting the generation of cyclobutane pyrimidine dimers (CPD) and oxidised DNA bases compared with unprotected control samples. Five different commercial brands of sunscreen were initially evaluated, and further studies extended the analysis to include 17 other products representing various formulations and Sun Protection Factors (SPF). Overall, all of the commercial brands of SPF 30 sunscreens provided sufficient protection against simulated sunlight genotoxicity. In addition, this DNA biosensor was useful for rapidly screening the biological protection properties of the various sunscreen formulations. Conclusions/Significance The application of the DNA dosimeter is demonstrated as an alternative, complementary, and reliable method for the quantification of sunscreen photoprotection at the level of DNA damage. PMID:22768281

Distinct biological effects of low-dose radiation on normal and cancerous human lung cells are mediated by ATM signaling

PubMed Central

Li, Wei; Zhao, Yuguang; Wen, Xue; Liang, Xinyue; Zhang, Xiaoying; Zhou, Lei; Hu, Jifan; Niu, Chao; Tian, Huimin; Han, Fujun; Chen, Xiao; Dong, Lihua; Cai, Lu; Cui, Jiuwei

2016-01-01

Low-dose radiation (LDR) induces hormesis and adaptive response in normal cells but not in cancer cells, suggesting its potential protection of normal tissue against damage induced by conventional radiotherapy. However, the underlying mechanisms are not well established. We addressed this in the present study by examining the role of the ataxia telangiectasia mutated (ATM) signaling pathway in response to LDR using A549 human lung adenocarcinoma cells and HBE135-E6E7 (HBE) normal lung epithelial cells. We found that LDR-activated ATM was the initiating event in hormesis and adaptive response to LDR in HBE cells. ATM activation increased the expression of CDK4/CDK6/cyclin D1 by activating the AKT/glycogen synthase kinase (GSK)-3β signaling pathway, which stimulated HBE cell proliferation. Activation of ATM/AKT/GSK-3β signaling also increased nuclear accumulation of nuclear factor erythroid 2-related factor 2, leading to increased expression of antioxidants, which mitigated cellular damage from excessive reactive oxygen species production induced by high-dose radiation. However, these effects were not observed in A549 cells. Thus, the failure to activate these pathways in A549 cells likely explains the difference between normal and cancer cells in terms of hormesis and adaptive response to LDR. PMID:27708248

Suppression of E. multilocularis Hydatid Cysts after Ionizing Radiation Exposure

PubMed Central

Zhou, Rong; Zhang, Hong

2013-01-01

Background Heavy-ion therapy has an advantage over conventional radiotherapy due to its superb biological effectiveness and dose conformity in cancer therapy. It could be a potential alternate approach for hydatid cyst treatment. However, there is no information currently available on the cellular and molecular basis for heavy-ion irradiation induced cell death in cystic echinococcosis. Methododology/Principal Findings LD50 was scored by protoscolex death. Cellular and ultrastructural changes within the parasite were studied by light and electron microscopy, mitochondrial DNA (mtDNA) damage and copy number were measured by QPCR, and apoptosis was determined by caspase 3 expression and caspase 3 activity. Ionizing radiation induced sparse cytoplasm, disorganized and clumped organelles, large vacuoles and devoid of villi. The initial mtDNA damage caused by ionizing radiation increased in a dose-dependent manner. The kinetic of DNA repair was slower after carbon-ion radiation than that after X-rays radiation. High dose carbon-ion radiation caused irreversible mtDNA degradation. Cysts apoptosis was pronounced after radiation. Carbon-ion radiation was more effective to suppress hydatid cysts than X-rays. Conclusions These studies provide a framework to the evaluation of attenuation effect of heavy-ion radiation on cystic echinococcosis in vitro. Carbon-ion radiation is more effective to suppress E. multilocularis than X-rays. PMID:24205427

eIF4E Threshold Levels Differ in Governing Normal and Neoplastic Expansion of Mammary Stem and Luminal Progenitor cells

PubMed Central

Avdulov, Svetlana; Herrera, Jeremy; Smith, Karen; Peterson, Mark; Gomez-Garcia, Jose R.; Beadnell, Thomas C.; Schwertfeger, Kathryn L.; Benyumov, Alexey O.; Manivel, J. Carlos; Li, Shunan; Bielinsky, Anja-Katrin; Yee, Douglas; Bitterman, Peter B.; Polunovsky, Vitaly A.

2015-01-01

Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when overexpressed. The mechanisms by which eIF4E directs such distinct biological outputs remains unknown. We found that mouse mammary morphogenesis during pregnancy and lactation is accompanied by increased cap-binding capability of eIF4E and activation of the eIF4E-dependent translational apparatus, but only subtle oscillations in eIF4E abundance. Using a transgenic mouse model engineered so that lactogenic hormones stimulate a sustained increase in eIF4E abundance in stem/progenitor cells of lactogenic mammary epithelium during successive pregnancy/lactation cycles, eIF4E overexpression increased cell self-renewal, triggered DNA replication stress, and induced formation of pre-malignant and malignant lesions. Using complementary in vivo and ex vivo approaches, we found that increasing eIF4E levels rescued cells harboring oncogenic c-Myc or H-RasV12 from DNA replication stress and oncogene-induced replication catastrophe. Our findings indicate that distinct threshold levels of eIF4E govern its biological output in lactating mammary glands, and that eIF4E overexpression in the context of stem/progenitor cell population expansion can initiate malignant transformation by enabling cells to evade DNA damage checkpoints activated by oncogenic stimuli. Maintaining eIF4E levels below its pro-neoplastic threshold is an important anticancer defense in normal cells, with important implications for understanding pregnancy-associated breast cancer. PMID:25524901

Bradykinin mediates myogenic differentiation in murine myoblasts through the involvement of SK1/Spns2/S1P2 axis.

PubMed

Bruno, Gennaro; Cencetti, Francesca; Bernacchioni, Caterina; Donati, Chiara; Blankenbach, Kira Vanessa; Thomas, Dominique; Meyer Zu Heringdorf, Dagmar; Bruni, Paola

2018-05-01

Skeletal muscle tissue retains a remarkable regenerative capacity due to the activation of resident stem cells that in pathological conditions or after tissue damage proliferate and commit themselves into myoblasts. These immature myogenic cells undergo differentiation to generate new myofibers or repair the injured ones, giving a strong contribution to muscle regeneration. Cytokines and growth factors, potently released after tissue injury by leukocytes and macrophages, are not only responsible of the induction of the initial inflammatory response, but can also affect skeletal muscle regeneration. Growth factors exploit sphingosine kinase (SK), the enzyme that catalyzes the production of sphingosine 1-phosphate (S1P), to exert their biological effects in skeletal muscle. In this paper we show for the first time that bradykinin (BK), the leading member of kinin/kallikrein system, is able to induce myogenic differentiation in C2C12 myoblasts. Moreover, evidence is provided that SK1, the specific S1P-transporter spinster homolog 2 (Spns2) and S1P 2 receptor are involved in the action exerted by BK, since pharmacological inhibition/antagonism or specific down-regulation significantly alter BK-induced myogenic differentiation. Moreover, the molecular mechanism initiated by BK involves a rapid translocation of SK1 to plasma membrane, analyzed by time-lapse immunofluorescence analysis. The present study highlights the role of SK1/Spns2/S1P receptor 2 signaling axis in BK-induced myogenic differentiation, thus confirming the crucial involvement of this pathway in skeletal muscle cell biology. Copyright © 2018 Elsevier Inc. All rights reserved.

Tailoring non-equilibrium atmospheric pressure plasmas for healthcare technologies

NASA Astrophysics Data System (ADS)

Gans, Timo

2012-10-01

Non-equilibrium plasmas operated at ambient atmospheric pressure are very efficient sources for energy transport through reactive neutral particles (radicals and metastables), charged particles (ions and electrons), UV radiation, and electro-magnetic fields. This includes the unique opportunity to deliver short-lived highly reactive species such as atomic oxygen and atomic nitrogen. Reactive oxygen and nitrogen species can initiate a wide range of reactions in biochemical systems, both therapeutic and toxic. The toxicological implications are not clear, e.g. potential risks through DNA damage. It is anticipated that interactions with biological systems will be governed through synergies between two or more species. Suitable optimized plasma sources are improbable through empirical investigations. Quantifying the power dissipation and energy transport mechanisms through the different interfaces from the plasma regime to ambient air, towards the liquid interface and associated impact on the biological system through a new regime of liquid chemistry initiated by the synergy of delivering multiple energy carrying species, is crucial. The major challenge to overcome the obstacles of quantifying energy transport and controlling power dissipation has been the severe lack of suitable plasma sources and diagnostic techniques. Diagnostics and simulations of this plasma regime are very challenging; the highly pronounced collision dominated plasma dynamics at very small dimensions requires extraordinary high resolution - simultaneously in space (microns) and time (picoseconds). Numerical simulations are equally challenging due to the inherent multi-scale character with very rapid electron collisions on the one extreme and the transport of chemically stable species characterizing completely different domains. This presentation will discuss our recent progress actively combining both advance optical diagnostics and multi-scale computer simulations.

eIF4E threshold levels differ in governing normal and neoplastic expansion of mammary stem and luminal progenitor cells.

PubMed

Avdulov, Svetlana; Herrera, Jeremy; Smith, Karen; Peterson, Mark; Gomez-Garcia, Jose R; Beadnell, Thomas C; Schwertfeger, Kathryn L; Benyumov, Alexey O; Manivel, J Carlos; Li, Shunan; Bielinsky, Anja-Katrin; Yee, Douglas; Bitterman, Peter B; Polunovsky, Vitaly A

2015-02-15

Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when overexpressed. The mechanisms by which eIF4E directs such distinct biologic outputs remain unknown. We found that mouse mammary morphogenesis during pregnancy and lactation is accompanied by increased cap-binding capability of eIF4E and activation of the eIF4E-dependent translational apparatus, but only subtle oscillations in eIF4E abundance. Using a transgenic mouse model engineered so that lactogenic hormones stimulate a sustained increase in eIF4E abundance in stem/progenitor cells of lactogenic mammary epithelium during successive pregnancy/lactation cycles, eIF4E overexpression increased self-renewal, triggered DNA replication stress, and induced formation of premalignant and malignant lesions. Using complementary in vivo and ex vivo approaches, we found that increasing eIF4E levels rescued cells harboring oncogenic c-Myc or H-RasV12 from DNA replication stress and oncogene-induced replication catastrophe. Our findings indicate that distinct threshold levels of eIF4E govern its biologic output in lactating mammary glands and that eIF4E overexpression in the context of stem/progenitor cell population expansion can initiate malignant transformation by enabling cells to evade DNA damage checkpoints activated by oncogenic stimuli. Maintaining eIF4E levels below its proneoplastic threshold is an important anticancer defense in normal cells, with important implications for understanding pregnancy-associated breast cancer. ©2014 American Association for Cancer Research.

Multiscale approach to the physics of radiation damage with ions

NASA Astrophysics Data System (ADS)

Surdutovich, Eugene; Solov'yov, Andrey V.

2013-04-01

We review a multiscale approach to the physics of ion-beam cancer therapy, an approach suggested in order to understand the interplay of a large number of phenomena involved in radiation damage scenario occurring on a range of temporal, spatial, and energy scales. We briefly overview its history and present the current stage of its development. The differences of the multiscale approach from other methods of understanding and assessment of radiation damage are discussed as well as its relationship to other branches of physics, chemistry and biology.

Cellular characterization of compression-induceddamage in live biological samples

NASA Astrophysics Data System (ADS)

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

2012-03-01

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

Cloud cover and horizontal plane eye damaging solar UV exposures.

PubMed

Parisi, A V; Downs, N

2004-11-01

The spectral UV and the cloud cover were measured at intervals of 5 min with an integrated cloud and spectral UV measurement system at a sub-tropical Southern Hemisphere site for a 6-month period and solar zenith angle (SZA) range of 4.7 degrees to approximately 80 degrees . The solar UV spectra were recorded between 280 nm and 400 nm in 0.5 nm increments and weighted with the action spectra for photokeratitis and cataracts in order to investigate the effect of cloud cover on the horizontal plane biologically damaging UV irradiances for cataracts (UVBE(cat)) and photokeratitis (UVBE(pker)). Eighty five percent of the recorded spectra produced a measured irradiance to a cloud free irradiance ratio of 0.6 and higher while 76% produced a ratio of 0.8 and higher. Empirical non-linear expressions as a function of SZA have been developed for all sky conditions to allow the evaluation of the biologically damaging UV irradiances for photokeratitis and cataracts from a knowledge of the unweighted UV irradiances.

Carbon Ion Radiotherapy: A Review of Clinical Experiences and Preclinical Research, with an Emphasis on DNA Damage/Repair.

PubMed

Mohamad, Osama; Sishc, Brock J; Saha, Janapriya; Pompos, Arnold; Rahimi, Asal; Story, Michael D; Davis, Anthony J; Kim, D W Nathan

2017-06-09

Compared to conventional photon-based external beam radiation (PhXRT), carbon ion radiotherapy (CIRT) has superior dose distribution, higher linear energy transfer (LET), and a higher relative biological effectiveness (RBE). This enhanced RBE is driven by a unique DNA damage signature characterized by clustered lesions that overwhelm the DNA repair capacity of malignant cells. These physical and radiobiological characteristics imbue heavy ions with potent tumoricidal capacity, while having the potential for simultaneously maximally sparing normal tissues. Thus, CIRT could potentially be used to treat some of the most difficult to treat tumors, including those that are hypoxic, radio-resistant, or deep-seated. Clinical data, mostly from Japan and Germany, are promising, with favorable oncologic outcomes and acceptable toxicity. In this manuscript, we review the physical and biological rationales for CIRT, with an emphasis on DNA damage and repair, as well as providing a comprehensive overview of the translational and clinical data using CIRT.

Carbon Ion Radiotherapy: A Review of Clinical Experiences and Preclinical Research, with an Emphasis on DNA Damage/Repair

PubMed Central

Mohamad, Osama; Sishc, Brock J.; Saha, Janapriya; Pompos, Arnold; Rahimi, Asal; Story, Michael D.; Davis, Anthony J.; Kim, D.W. Nathan

2017-01-01

Compared to conventional photon-based external beam radiation (PhXRT), carbon ion radiotherapy (CIRT) has superior dose distribution, higher linear energy transfer (LET), and a higher relative biological effectiveness (RBE). This enhanced RBE is driven by a unique DNA damage signature characterized by clustered lesions that overwhelm the DNA repair capacity of malignant cells. These physical and radiobiological characteristics imbue heavy ions with potent tumoricidal capacity, while having the potential for simultaneously maximally sparing normal tissues. Thus, CIRT could potentially be used to treat some of the most difficult to treat tumors, including those that are hypoxic, radio-resistant, or deep-seated. Clinical data, mostly from Japan and Germany, are promising, with favorable oncologic outcomes and acceptable toxicity. In this manuscript, we review the physical and biological rationales for CIRT, with an emphasis on DNA damage and repair, as well as providing a comprehensive overview of the translational and clinical data using CIRT. PMID:28598362

Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder.

PubMed

Takata, Atsushi; Miyake, Noriko; Tsurusaki, Yoshinori; Fukai, Ryoko; Miyatake, Satoko; Koshimizu, Eriko; Kushima, Itaru; Okada, Takashi; Morikawa, Mako; Uno, Yota; Ishizuka, Kanako; Nakamura, Kazuhiko; Tsujii, Masatsugu; Yoshikawa, Takeo; Toyota, Tomoko; Okamoto, Nobuhiko; Hiraki, Yoko; Hashimoto, Ryota; Yasuda, Yuka; Saitoh, Shinji; Ohashi, Kei; Sakai, Yasunari; Ohga, Shouichi; Hara, Toshiro; Kato, Mitsuhiro; Nakamura, Kazuyuki; Ito, Aiko; Seiwa, Chizuru; Shirahata, Emi; Osaka, Hitoshi; Matsumoto, Ayumi; Takeshita, Saoko; Tohyama, Jun; Saikusa, Tomoko; Matsuishi, Toyojiro; Nakamura, Takumi; Tsuboi, Takashi; Kato, Tadafumi; Suzuki, Toshifumi; Saitsu, Hirotomo; Nakashima, Mitsuko; Mizuguchi, Takeshi; Tanaka, Fumiaki; Mori, Norio; Ozaki, Norio; Matsumoto, Naomichi

2018-01-16

Recent studies have established important roles of de novo mutations (DNMs) in autism spectrum disorders (ASDs). Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the "de novo paradigm" of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244) and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits. Analysis of individual genes identified 61 genes enriched for damaging DNMs, including ten genes for which our dataset now contributes to statistical significance. Screening of compounds altering the expression of genes hit by damaging DNMs reveals a global downregulating effect of valproic acid, a known risk factor for ASDs, whereas cardiac glycosides upregulate these genes. Collectively, our integrative approach provides deeper biological and potential medical insights into ASDs. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Healable thermoset polymer composite embedded with stimuli-responsive fibres

PubMed Central

Li, Guoqiang; Meng, Harper; Hu, Jinlian

2012-01-01

Severe wounds in biological systems such as human skin cannot heal themselves, unless they are first stitched together. Healing of macroscopic damage in thermoset polymer composites faces a similar challenge. Stimuli-responsive shape-changing polymeric fibres with outstanding mechanical properties embedded in polymers may be able to close macro-cracks automatically upon stimulation such as heating. Here, a stimuli-responsive fibre (SRF) with outstanding mechanical properties and supercontraction capability was fabricated for the purpose of healing macroscopic damage. The SRFs and thermoplastic particles (TPs) were incorporated into regular thermosetting epoxy for repeatedly healing macroscopic damages. The system works by mimicking self-healing of biological systems such as human skin, close (stitch) then heal, i.e. close the macroscopic crack through the thermal-induced supercontraction of the SRFs, and bond the closed crack through melting and diffusing of TPs at the crack interface. The healing efficiency determined using tapered double-cantilever beam specimens was 94 per cent. The self-healing process was reasonably repeatable. PMID:22896563

An overview of plant volatile metabolomics, sample treatment and reporting considerations with emphasis on mechanical damage and biological control of weeds.

PubMed

Beck, John J; Smith, Lincoln; Baig, Nausheena

2014-01-01

The technology for the collection and analysis of plant-emitted volatiles for understanding chemical cues of plant-plant, plant-insect or plant-microbe interactions has increased over the years. Consequently, the in situ collection, analysis and identification of volatiles are considered integral to elucidation of complex plant communications. Due to the complexity and range of emissions the conditions for consistent emission of volatiles are difficult to standardise. To discuss: evaluation of emitted volatile metabolites as a means of screening potential target- and non-target weeds/plants for insect biological control agents; plant volatile metabolomics to analyse resultant data; importance of considering volatiles from damaged plants; and use of a database for reporting experimental conditions and results. Recent literature relating to plant volatiles and plant volatile metabolomics are summarised to provide a basic understanding of how metabolomics can be applied to the study of plant volatiles. An overview of plant secondary metabolites, plant volatile metabolomics, analysis of plant volatile metabolomics data and the subsequent input into a database, the roles of plant volatiles, volatile emission as a function of treatment, and the application of plant volatile metabolomics to biological control of invasive weeds. It is recommended that in addition to a non-damaged treatment, plants be damaged prior to collecting volatiles to provide the greatest diversity of odours. For the model system provided, optimal volatile emission occurred when the leaf was punctured with a needle. Results stored in a database should include basic environmental conditions or treatments. Copyright © 2013 John Wiley & Sons, Ltd.

[Atmospheric pollution. Biological aspects and role of meteorologic factors in the distribution of respiratory hazards in the environment and relative prognostic and preventive measures].

PubMed

Rotondo, G

1983-08-25

The biometeorological factors underlying atmospheric pollution are discussed, together with its biological effects and its direct and indirect damage to human health. Damage is particularly likely when particularly adverse ambient and climatological conditions result in a massive and persistent concentration of contaminants in the ambient air. In this case, since the highly biologically interesting phenomenon of physicochemical reaction between pollutants and atmospheric components prevails over that of the dilution and dispersion of such contaminants, nature's major processes of removal and self-purification may be rendered nugatory and insufficiently prompt. The effects of atmospheric pollution, primarily with respect to urban background pollution, on human health make their appearance in the respiratory system, where there is a continuous relation between man and his environment throughout his life, in the form of immediate or short, medium and long-term damage. The desirability of preparing a meteorological map showing the distribution of the risk of atmospheric pollution is discussed. For this purpose, use could be made of meteorological data, and the hi-tech observations now made possible, inter alia, by the employment of satellites and aerospace data. A map of this kind would give more precise information concerning the part played by the weather in distributing the risk of respiratory damage caused by environmental pollution. It would also provide the knowledge required for the purpose of prediction and prevention in an organised struggle against such pollution. This would be of great social significance and value. Its practical applications could be enormous consequence to humanity.

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

PubMed

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

2016-10-15

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

Enzymatic recognition of DNA damage induced by UVB-photosensitized titanium dioxide and biological consequences in Saccharomyces cerevisiae: evidence for oxidatively DNA damage generation.

PubMed

Pinto, A Viviana; Deodato, Elder L; Cardoso, Janine S; Oliveira, Eliza F; Machado, Sérgio L; Toma, Helena K; Leitão, Alvaro C; de Pádula, Marcelo

2010-06-01

Although titanium dioxide (TiO(2)) has been considered to be biologically inert, finding use in cosmetics, paints and food colorants, recent reports have demonstrated that when TiO(2) is attained by UVA radiation oxidative genotoxic and cytotoxic effects are observed in living cells. However, data concerning TiO(2)-UVB association is poor, even if UVB radiation represents a major environmental carcinogen. Herein, we investigated DNA damage, repair and mutagenesis induced by TiO(2) associated with UVB irradiation in vitro and in vivo using Saccharomyces cerevisiae model. It was found that TiO(2) plus UVB treatment in plasmid pUC18 generated, in addition to cyclobutane pyrimidine dimers (CPDs), specific damage to guanine residues, such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG), which are characteristic oxidatively generated lesions. In vivo experiments showed that, although the presence of TiO(2) protects yeast cells from UVB cytotoxicity, high mutation frequencies are observed in the wild-type (WT) and in an ogg1 strain (deficient in 8-oxoG and FapyG repair). Indeed, after TiO(2) plus UVB treatment, induced mutagenesis was drastically enhanced in ogg1 cells, indicating that mutagenic DNA lesions are repaired by the Ogg1 protein. This effect could be attenuated by the presence of metallic ion chelators: neocuproine or dipyridyl, which partially block oxidatively generated damage occurring via Fenton reactions. Altogether, the results indicate that TiO(2) plus UVB potentates UVB oxidatively generated damage to DNA, possibly via Fenton reactions involving the production of DNA base damage, such as 8-oxo-7,8-dihydroguanine. Copyright 2010 Elsevier B.V. All rights reserved.

Puerarin ameliorates heat stress-induced oxidative damage and apoptosis in bovine Sertoli cells by suppressing ROS production and upregulating Hsp72 expression.

PubMed

Cong, Xia; Zhang, Qian; Li, Huatao; Jiang, Zhongling; Cao, Rongfeng; Gao, Shansong; Tian, Wenru

2017-01-15

Puerarin, a bioactive isoflavone glucoside extracted from radix Puerariae, has been proven to possess many biological activities. However, the role of puerarin in protecting bovine Sertoli cells (bSCs) under heat stress conditions remains to be clarified. The present study aimed to explore the possible protective mechanism of puerarin for primary cultured bSCs subjected to heat stress. Bovine Sertoli cells were treated with 15 μM of puerarin before they were exposed to 42 °C for 1 hour. The dose of puerarin (15 μM) was determined on the basis of cell viability. The results showed that puerarin treatment suppressed the production of reactive oxygen species and decreased the oxidative damage of the bSCs subjected to heat stress, as indicated by changes in superoxide dismutase, catalase, and glutathione peroxidase activities and malondialdehyde content. Moreover, puerarin treatment also suppressed the initiation of mitochondria-dependent apoptotic pathway, as revealed by changes in Bax to Bcl-2 ratio, mitochondrial membrane potential, cytochrome C release, caspase-3 activation, and apoptotic rate compared with the heat stress group. In addition, puerarin treatment increased Hsp72 expression in the bSCs with no apparent cellular cytotoxicity compared with the control group. Furthermore, increased Hsp72 was detected in the heat stress plus puerarin group compared with the heat stress group. In conclusion, puerarin attenuates heat stress-induced oxidative damage and apoptosis of bSCs by suppressing reactive oxygen species production and upregulating Hsp72 expression. Copyright © 2016 Elsevier Inc. All rights reserved.

Physiological Concentrations of Ascorbate Cannot Prevent the Potentially Damaging Reactions of Protein Radicals in Humans.

PubMed

Nauser, Thomas; Gebicki, Janusz M

2017-09-18

The principal initial biological targets of free radicals formed under conditions of oxidative stress are the proteins. The most common products of the interaction are carbon-centered alkyl radicals which react rapidly with oxygen to form peroxyl radicals and hydroperoxides. All these species are reactive, capable of propagating the free radical damage to enzymes, nucleic acids, lipids, and endogenous antioxidants, leading finally to the pathologies associated with oxidative stress. The best chance of preventing this chain of damage is in early repair of the protein radicals by antioxidants. Estimate of the effectiveness of the physiologically significant antioxidants requires knowledge of the antioxidant tissue concentrations and rate constants of their reaction with protein radicals. Previous studies by pulse radiolysis have shown that only ascorbate can repair the Trp and Tyr protein radicals before they form peroxyl radicals under physiological concentrations of oxygen. We have now extended this work to other protein C-centered radicals generated by hydroxyl radicals because these and many other free radicals formed under oxidative stress can produce secondary radicals on virtually any amino acid residue. Pulse radiolysis identified two classes of rate constants for reactions of protein radicals with ascorbate, a faster one in the range (9-60) × 10 7 M -1 s -1 and a slow one with a range of (0.5-2) × 10 7 M -1 s -1 . These results show that ascorbate can prevent further reactions of protein radicals only in the few human tissues where its concentration exceeds about 2.5 mM.

Remodeling in bone without osteocytes: Billfish challenge bone structure–function paradigms

PubMed Central

Atkins, Ayelet; Dean, Mason N.; Habegger, Maria Laura; Motta, Phillip J.; Ofer, Lior; Repp, Felix; Shipov, Anna; Weiner, Steve; Currey, John D.; Shahar, Ron

2014-01-01

A remarkable property of tetrapod bone is its ability to detect and remodel areas where damage has accumulated through prolonged use. This process, believed vital to the long-term health of bone, is considered to be initiated and orchestrated by osteocytes, cells within the bone matrix. It is therefore surprising that most extant fishes (neoteleosts) lack osteocytes, suggesting their bones are not constantly repaired, although many species exhibit long lives and high activity levels, factors that should induce considerable fatigue damage with time. Here, we show evidence for active and intense remodeling occurring in the anosteocytic, elongated rostral bones of billfishes (e.g., swordfish, marlins). Despite lacking osteocytes, this tissue exhibits a striking resemblance to the mature bone of large mammals, bearing structural features (overlapping secondary osteons) indicating intensive tissue repair, particularly in areas where high loads are expected. Billfish osteons are an order of magnitude smaller in diameter than mammalian osteons, however, implying that the nature of damage in this bone may be different. Whereas billfish bone material is as stiff as mammalian bone (unlike the bone of other fishes), it is able to withstand much greater strains (relative deformations) before failing. Our data show that fish bone can exhibit far more complex structure and physiology than previously known, and is apparently capable of localized repair even without the osteocytes believed essential for this process. These findings challenge the unique and primary role of osteocytes in bone remodeling, a basic tenet of bone biology, raising the possibility of an alternative mechanism driving this process. PMID:25331870

Human ISWI complexes are targeted by SMARCA5 ATPase and SLIDE domains to help resolve lesion-stalled transcription

PubMed Central

Aydin, Özge Z.; Marteijn, Jurgen A.; Ribeiro-Silva, Cristina; Rodríguez López, Aida; Wijgers, Nils; Smeenk, Godelieve; van Attikum, Haico; Poot, Raymond A.; Vermeulen, Wim; Lans, Hannes

2014-01-01

Chromatin compaction of deoxyribonucleic acid (DNA) presents a major challenge to the detection and removal of DNA damage. Helix-distorting DNA lesions that block transcription are specifically repaired by transcription-coupled nucleotide excision repair, which is initiated by binding of the CSB protein to lesion-stalled RNA polymerase II. Using live cell imaging, we identify a novel function for two distinct mammalian ISWI adenosine triphosphate (ATP)-dependent chromatin remodeling complexes in resolving lesion-stalled transcription. Human ISWI isoform SMARCA5/SNF2H and its binding partners ACF1 and WSTF are rapidly recruited to UV-C induced DNA damage to specifically facilitate CSB binding and to promote transcription recovery. SMARCA5 targeting to UV-C damage depends on transcription and histone modifications and requires functional SWI2/SNF2-ATPase and SLIDE domains. After initial recruitment to UV damage, SMARCA5 re-localizes away from the center of DNA damage, requiring its HAND domain. Our studies support a model in which SMARCA5 targeting to DNA damage-stalled transcription sites is controlled by an ATP-hydrolysis-dependent scanning and proofreading mechanism, highlighting how SWI2/SNF2 chromatin remodelers identify and bind nucleosomes containing damaged DNA. PMID:24990377

Towards the damage evaluation using Gurson-Tvergaard-Needleman (GTN) model for hot forming processes

NASA Astrophysics Data System (ADS)

Imran, Muhammad; Bambach, Markus

2018-05-01

In the production of semi-finished metal products, hot forming is used to eliminate the pores and voids from the casting process under compressive stresses and to modify the microstructure for further processing. In the case of caliber and flat rolling processes, tensile stresses occur at certain roll gap ratios which promote pore formation on nonmetallic inclusion. The formation of new pores contributes to ductile damage and reduces the load carrying capacity of the material. In the literature, the damage nucleation and growth during the hot forming process are not comprehensively described. The aim of this study is to understand the damage initiation and growth mechanism during hot forming processes. Hot tensile tests are performed at different temperatures and strain rates for 16MnCrS5 steel. To investigate the influence of geometrical variations on the damage mechanism, specimens with different stress triaxiality ratios are used. Finite element simulations using the Gurson-Tvergaard-Needleman (GTN) damage model are performed to estimate the critical void fraction for the damage initiation and the evolution of the void volume fraction. The results showed that the GTN model underestimates the softening of the material due to the independence of the temperature and the strain rate.

Optical damage observed in the LHMEL II output coupler

NASA Astrophysics Data System (ADS)

Eric, John J.; Bagford, John O.; Devlin, Christie L. H.; Hull, Robert J.; Seibert, Daniel B.

2008-01-01

During the annual NIST calibration testing done at the LHMEL facility in FY06 on its high energy Carbon-Dioxide lasers, the LHMEL II device suffered severe damage to the internal surface of its ZnSe output coupler optics. The damage occurred during a high power, short duration run and it was believed to have been the result of a significant amount of surface contaminants interacting with the LHMEL cavity beam. Initial theories as to the source of the contamination led to the inspection of the vacuum grease that seals the piping that supplies the source gases to the laser cavity. Other contamination sources were considered, and analysis was conducted in an effort to identify the material found at the damage sites on the optic, but the tests were mainly inconclusive. Some procedure changes were initiated to identify possible contamination before high energy laser operation in an attempt to mitigate and possibly prevent the continued occurrence of damage to the output coupler window. This paper is to illustrate the type and extent of the damage encountered, highlight some of the theories as to the contamination source, and serve as a notice as to the severity and consequences of damage that is possible even due to small amounts of foreign material in a high energy laser environment.

A Three-Parameter Model for Predicting Fatigue Life of Ductile Metals Under Constant Amplitude Multiaxial Loading

NASA Astrophysics Data System (ADS)

Liu, Jia; Li, Jing; Zhang, Zhong-ping

2013-04-01

In this article, a fatigue damage parameter is proposed to assess the multiaxial fatigue lives of ductile metals based on the critical plane concept: Fatigue crack initiation is controlled by the maximum shear strain, and the other important effect in the fatigue damage process is the normal strain and stress. This fatigue damage parameter introduces a stress-correlated factor, which describes the degree of the non-proportional cyclic hardening. Besides, a three-parameter multiaxial fatigue criterion is used to correlate the fatigue lifetime of metallic materials with the proposed damage parameter. Under the uniaxial loading, this three-parameter model reduces to the recently developed Zhang's model for predicting the uniaxial fatigue crack initiation life. The accuracy and reliability of this three-parameter model are checked against the experimental data found in literature through testing six different ductile metals under various strain paths with zero/non-zero mean stress.

Investigation of Sideband Index Response to Prototype Gear Tooth Damage

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.

2013-01-01

The objective of this analysis was to evaluate the ability of gear condition indicators (CI) to detect contact fatigue damage on spiral bevel gear teeth. Tests were performed in the NASA Glenn Spiral Bevel Gear Fatigue Rig on eight prototype gear sets (pinion/gear). Damage was initiated and progressed on the gear and pinion teeth. Vibration data was measured during damage progression at varying torque values while varying damage modes to the gear teeth were observed and documented with inspection photos. Sideband indexes (SI) and root mean square (RMS) CIs were calculated from the time synchronous averaged vibration data. Results found that both CIs respond differently to varying torque levels, damage levels and damage modes

Modelling low velocity impact induced damage in composite laminates

NASA Astrophysics Data System (ADS)

Shi, Yu; Soutis, Constantinos

2017-12-01

The paper presents recent progress on modelling low velocity impact induced damage in fibre reinforced composite laminates. It is important to understand the mechanisms of barely visible impact damage (BVID) and how it affects structural performance. To reduce labour intensive testing, the development of finite element (FE) techniques for simulating impact damage becomes essential and recent effort by the composites research community is reviewed in this work. The FE predicted damage initiation and propagation can be validated by Non Destructive Techniques (NDT) that gives confidence to the developed numerical damage models. A reliable damage simulation can assist the design process to optimise laminate configurations, reduce weight and improve performance of components and structures used in aircraft construction.

Assessment of compressive failure process of cortical bone materials using damage-based model.

PubMed

Ng, Theng Pin; R Koloor, S S; Djuansjah, J R P; Abdul Kadir, M R

2017-02-01

The main failure factors of cortical bone are aging or osteoporosis, accident and high energy trauma or physiological activities. However, the mechanism of damage evolution coupled with yield criterion is considered as one of the unclear subjects in failure analysis of cortical bone materials. Therefore, this study attempts to assess the structural response and progressive failure process of cortical bone using a brittle damaged plasticity model. For this reason, several compressive tests are performed on cortical bone specimens made of bovine femur, in order to obtain the structural response and mechanical properties of the material. Complementary finite element (FE) model of the sample and test is prepared to simulate the elastic-to-damage behavior of the cortical bone using the brittle damaged plasticity model. The FE model is validated in a comparative method using the predicted and measured structural response as load-compressive displacement through simulation and experiment. FE results indicated that the compressive damage initiated and propagated at central region where maximum equivalent plastic strain is computed, which coincided with the degradation of structural compressive stiffness followed by a vast amount of strain energy dissipation. The parameter of compressive damage rate, which is a function dependent on damage parameter and the plastic strain is examined for different rates. Results show that considering a similar rate to the initial slope of the damage parameter in the experiment would give a better sense for prediction of compressive failure. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Defining the human deubiquitinating enzyme interaction landscape.

PubMed

Sowa, Mathew E; Bennett, Eric J; Gygi, Steven P; Harper, J Wade

2009-07-23

Deubiquitinating enzymes (Dubs) function to remove covalently attached ubiquitin from proteins, thereby controlling substrate activity and/or abundance. For most Dubs, their functions, targets, and regulation are poorly understood. To systematically investigate Dub function, we initiated a global proteomic analysis of Dubs and their associated protein complexes. This was accomplished through the development of a software platform called CompPASS, which uses unbiased metrics to assign confidence measurements to interactions from parallel nonreciprocal proteomic data sets. We identified 774 candidate interacting proteins associated with 75 Dubs. Using Gene Ontology, interactome topology classification, subcellular localization, and functional studies, we link Dubs to diverse processes, including protein turnover, transcription, RNA processing, DNA damage, and endoplasmic reticulum-associated degradation. This work provides the first glimpse into the Dub interaction landscape, places previously unstudied Dubs within putative biological pathways, and identifies previously unknown interactions and protein complexes involved in this increasingly important arm of the ubiquitin-proteasome pathway.

Defining the Human Deubiquitinating Enzyme Interaction Landscape

PubMed Central

Sowa, Mathew E.; Bennett, Eric J.; Gygi, Steven P.; Harper, J. Wade

2009-01-01

Summary Deubiquitinating enzymes (Dubs) function to remove covalently attached ubiquitin from proteins, thereby controlling substrate activity and/or abundance. For most Dubs, their functions, targets, and regulation are poorly understood. To systematically investigate Dub function, we initiated a global proteomic analysis of Dubs and their associated protein complexes. This was accomplished through the development of a software platform, called CompPASS, which uses unbiased metrics to assign confidence measurements to interactions from parallel non-reciprocal proteomic datasets. We identified 774 candidate interacting proteins associated with 75 Dubs. Using Gene Ontology, interactome topology classification, sub-cellular localization and functional studies, we link Dubs to diverse processes, including protein turnover, transcription, RNA processing, DNA damage, and endoplasmic reticulum-associated degradation. This work provides the first glimpse into the Dub interaction landscape, places previously unstudied Dubs within putative biological pathways, and identifies previously unknown interactions and protein complexes involved in this increasingly important arm of the ubiquitin-proteasome pathway. PMID:19615732

Connecting the plant vasculature to friend or foe.

PubMed

Melnyk, Charles W

2017-03-01

Contents 1611 I. 1611 II. 1612 III. 1612 IV. 1614 V. 1614 VI. 1614 VII. 1615 VIII. 1616 1616 References 1616 SUMMARY: The plant vasculature transports water, sugars, hormones, RNAs and proteins. Such critical functions need to be protected from attack by pests and pathogens or from damage by wounding. Plants have developed mechanisms to repair vasculature when such protections fail and to even initiate new vascular connections to tissues supporting symbionts. The developmental phenomena underlying vascular repair and rewiring are therefore critical for horticultural grafting, for plant infection and for mutualist associations with rhizosphere microbes. Despite the biological and economic interest, we are only beginning to understand how plants connect and reconnect their vasculature to a wide variety of organisms. Here, I discuss recent work and future prospects for this emerging field. © 2016 The Author. New Phytologist © 2016 New Phytologist Trust.

The BioSentinel Bioanalytical Microsystem: Characterizing DNA Radiation Damage in Living Organisms Beyond Earth Orbit

NASA Technical Reports Server (NTRS)

Ricco, A. J.; Hanel, R.; Bhattacharya, S.; Boone, T.; Tan, M.; Mousavi, A.; Rademacher, A.; Schooley, A.; Klamm, B.; Benton, J.;

Investigation of Al Coated Mg for Biomedical Applications

NASA Astrophysics Data System (ADS)

Elmrabet, Nabila; Roe, Martin; Neate, Nigel; Grant, David M.; Brown, Paul D.

The corrosion resistant properties of 1-2 μm thick Al coatings deposited by radio frequency magnetron sputtering on polished Mg surfaces, within Ar and Ar/H2 environments, have been appraised. The coatings were heat-treated at 300°C for 5 h to induce the formation of bioinert Al2O3, and samples were corroded within phosphate buffered saline solution at 37°C to mimic the biological environment. Both the as-deposited and heat-treated coatings were found to delay the onset of corrosion, but showed higher initial corrosion rates, once established, as compared with polished Mg surfaces. Slightly improved performance of the coatings was achieved through the addition of H2 to the system which acted to inhibit Al-Mg alloying and MgO formation. However, localized accelerated corrosion associated with substrate polishing damage emphasized the need for improved process control and coating uniformity.

Mechanisms of DNA damage, repair and mutagenesis

PubMed Central

Chatterjee, Nimrat; Walker, Graham C.

2017-01-01

Living organisms are continuously exposed to a myriad of DNA damaging agents that can impact health and modulate disease-states. However, robust DNA repair and damage-bypass mechanisms faithfully protect the DNA by either removing or tolerating the damage to ensure an overall survival. Deviations in this fine-tuning are known to destabilize cellular metabolic homeostasis, as exemplified in diverse cancers where disruption or deregulation of DNA repair pathways results in genome instability. Because routinely used biological, physical and chemical agents impact human health, testing their genotoxicity and regulating their use have become important. In this introductory review, we will delineate mechanisms of DNA damage and the counteracting repair/tolerance pathways to provide insights into the molecular basis of genotoxicity in cells that lays the foundation for subsequent articles in this issue. PMID:28485537

Progressive damage and rupture in polymers

NASA Astrophysics Data System (ADS)

Talamini, Brandon; Mao, Yunwei; Anand, Lallit

2018-02-01

Progressive damage, which eventually leads to failure, is ubiquitous in biological and synthetic polymers. The simplest case to consider is that of elastomeric materials which can undergo large reversible deformations with negligible rate dependence. In this paper we develop a theory for modeling progressive damage and rupture of such materials. We extend the phase-field method, which is widely used to describe the damage and fracture of brittle materials, to elastomeric materials undergoing large deformations. A central feature of our theory is the recognition that the free energy of elastomers is not entirely entropic in nature - there is also an energetic contribution from the deformation of the bonds in the chains. It is the energetic part in the free energy which is the driving force for progressive damage and fracture.

Biopolymers for sample collection, protection, and preservation.

PubMed

Sorokulova, Iryna; Olsen, Eric; Vodyanoy, Vitaly

2015-07-01

One of the principal challenges in the collection of biological samples from air, water, and soil matrices is that the target agents are not stable enough to be transferred from the collection point to the laboratory of choice without experiencing significant degradation and loss of viability. At present, there is no method to transport biological samples over considerable distances safely, efficiently, and cost-effectively without the use of ice or refrigeration. Current techniques of protection and preservation of biological materials have serious drawbacks. Many known techniques of preservation cause structural damages, so that biological materials lose their structural integrity and viability. We review applications of a novel bacterial preservation process, which is nontoxic and water soluble and allows for the storage of samples without refrigeration. The method is capable of protecting the biological sample from the effects of environment for extended periods of time and then allows for the easy release of these collected biological materials from the protective medium without structural or DNA damage. Strategies for sample collection, preservation, and shipment of bacterial, viral samples are described. The water-soluble polymer is used to immobilize the biological material by replacing the water molecules within the sample with molecules of the biopolymer. The cured polymer results in a solid protective film that is stable to many organic solvents, but quickly removed by the application of the water-based solution. The process of immobilization does not require the use of any additives, accelerators, or plastifiers and does not involve high temperature or radiation to promote polymerization.

Relationships between common forest metrics and realized impacts of Hurricane Katrina on forest resources in Mississippi

Treesearch

Sonja N. Oswalt; Christopher M. Oswalt

2008-01-01

This paper compares and contrasts hurricane-related damage recorded across the Mississippi landscape in the 2 years following Katrina with initial damage assessments based on modeled parameters by the USDA Forest Service. Logistic and multiple regressions are used to evaluate the influence of stand characteristics on tree damage probability. Specifically, this paper...

Rapid assessment of wildfire damage using Forest Inventory data: A case in Georgia

Treesearch

Richard A. Harper; John W. Coulsten; Jeffery A. Turner

2009-01-01

The rapid assessment of damage caused by natural disasters is essential for planning the appropriate amount of disaster relief funds and public communication. Annual Forest Inventory and Analysis (FIA) data provided initial estimates of damage to timberland in a timely manner to State leaders during the 2007 Georgia Bay Complex Wildfire in southeast Georgia. FIA plots...

DNA double strand break (DSB) induction and cell survival in iodine-enhanced computed tomography (CT)

NASA Astrophysics Data System (ADS)

Streitmatter, Seth W.; Stewart, Robert D.; Jenkins, Peter A.; Jevremovic, Tatjana

2017-08-01

A multi-scale Monte Carlo model is proposed to assess the dosimetric and biological impact of iodine-based contrast agents commonly used in computed tomography. As presented, the model integrates the general purpose MCNP6 code system for larger-scale radiation transport and dose assessment with the Monte Carlo damage simulation to determine the sub-cellular characteristics and spatial distribution of initial DNA damage. The repair-misrepair-fixation model is then used to relate DNA double strand break (DSB) induction to reproductive cell death. Comparisons of measured and modeled changes in reproductive cell survival for ultrasoft characteristic k-shell x-rays (0.25-4.55 keV) up to orthovoltage (200-500 kVp) x-rays indicate that the relative biological effectiveness (RBE) for DSB induction is within a few percent of the RBE for cell survival. Because of the very short range of secondary electrons produced by low energy x-ray interactions with contrast agents, the concentration and subcellular distribution of iodine within and near cellular targets have a significant impact on the estimated absorbed dose and number of DSB produced in the cell nucleus. For some plausible models of the cell-level distribution of contrast agent, the model predicts an increase in RBE-weighted dose (RWD) for the endpoint of DSB induction of 1.22-1.40 for a 5-10 mg ml-1 iodine concentration in blood compared to an RWD increase of 1.07  ±  0.19 from a recent clinical trial. The modeled RWD of 2.58  ±  0.03 is also in good agreement with the measured RWD of 2.3  ±  0.5 for an iodine concentration of 50 mg ml-1 relative to no iodine. The good agreement between modeled and measured DSB and cell survival estimates provides some confidence that the presented model can be used to accurately assess biological dose for other concentrations of the same or different contrast agents.

Biaxial deformation in high purity aluminum

DOE PAGES

Livescu, V.; Bingert, J. F.; Liu, C.; ...

2015-09-25

The convergence of multiple characterization tools has been applied to investigate the relationship of microstructure on damage evolution in high purity aluminum. The extremely coarse grain size of the disc-shaped sample provided a quasi-two dimensional structure from which the location of surface-measured features could be inferred. In particular, the role of pre-existing defects on damage growth was accessible due to the presence of casting porosity in the aluminum. Micro tomography, electron backscatter diffraction, and digital image correlation were applied to interrogate the sample in three dimensions. Recently micro-bulge testing apparatus was used to deform the pre-characterized disc of aluminum inmore » biaxial tension, and related analysis techniques were applied to map local strain fields. Subsequent post-mortem characterization of the failed sample was performed to correlate structure to damaged regions. We determined that strain localization and associated damage was most strongly correlated with grain boundary intersections and plastic anisotropy gradients between grains. Pre-existing voids played less of an apparent role than was perhaps initially expected. Finally, these combined techniques provide insight to the mechanism of damage initiation, propagation, and failure, along with a test bed for predictive damage models incorporating anisotropic microstructural effects.« less

Fabrication of spherical mitigation pit on KH2PO4 crystal by micro-milling and modeling of its induced light intensification.

PubMed

Cheng, Jian; Chen, Mingjun; Liao, Wei; Wang, Haijun; Xiao, Yong; Li, Mingquan

2013-07-15

Micro-machining is the most promising method for KH(2)PO(4) crystal to mitigate the surface damage growth in high power laser system. In this work, spherical mitigation pit is fabricated by micro-milling with an efficient machining procedure. The light intensification caused by rear surface features before and after mitigation is numerically modeled based on the finite-difference time-domain method. The results indicate that the occurrence of total internal reflections should be responsible for the largest light intensification inside the crystal. For spherical pits after mitigation, the light intensification can be greatly alleviated by preventing the occurrence of total internal reflections. The light intensification caused by spherical mitigation pit is strongly dependent on the width-depth ratio and it is suggested that the width-depth ratio of spherical mitigation pit must be devised to be larger than 5.0 to achieve the minimal light intensification for the mitigation of surface damage growth. Laser damage tests for KH(2)PO(4) crystal validate that the laser damage resistance of initially damaged surface can be retrieved to near the level of ideal surface by replacing initial damage site with predesigned mitigation pit.

Detailed Post-Soft Impact Progressive Damage Assessment for Hybrid Structure Jet Engines

NASA Technical Reports Server (NTRS)

Siddens, Aaron; Bayandor, Javid; Celestina, Mark L.

2014-01-01

Currently, certification of engine designs for resistance to bird strike is reliant on physical tests. Predictive modeling of engine structural damage has mostly been limited to evaluation of individual forward section components, such as fan blades within a fixed frame of reference, to direct impact with a bird. Such models must be extended to include interactions among engine components under operating conditions to evaluate the full extent of engine damage. This paper presents the results of a study aim to develop a methodology for evaluating bird strike damage in advanced propulsion systems incorporating hybrid composite/metal structures. The initial degradation and failure of individual fan blades struck by a bird were investigated. Subsequent damage to other fan blades and engine components due to resultant violent fan assembly vibrations and fragmentation was further evaluated. Various modeling parameters for the bird and engine components were investigated to determine guidelines for accurately capturing initial damage and progressive failure of engine components. Then, a novel hybrid structure modeling approach was investigated and incorporated into the crashworthiness methodology. Such a tool is invaluable to the process of design, development, and certification of future advanced propulsion systems.

The Effects of Fracture Anisotropy on the Damage Pattern and Seismic Radiation from a Chemical Explosion in a Granite Quarry

NASA Astrophysics Data System (ADS)

Rogers-Martinez, M. A.; Sammis, C. G.; Ezzedine, S. M.

2017-12-01

As part of the New England Damage Experiment (NEDE) a 122.7 kg Heavy ANFO charge was detonated at a depth of 13 m in a granite quarry in Barre Vt. Subsequent drill cores from the source region revealed that most of the resultant fracturing was concentrated in the rift plane of the highly anisotropic Barre granite. We simulated this explosion using a dynamic damage mechanics model embedded in the ABAQUS 3D finite element code. The damage mechanics was made anisotropic by taking the critical stress intensity factor to be a function of azimuth in concert with the physics of interacting parallel fractures and laboratory studies of anisotropic granite. In order to identify the effects of anisotropy, the explosion was also simulated assuming 1) no initial damage (pure elasticity) and 2) isotropic initial damage. For the anisotropic case, the calculated fracture pattern simulated that observed in NEDE. The simulated seismic radiation looked very much like that from a tensile fracture oriented in the rift plane, and similar to the crack-like moment tensor observed in the far field of many nuclear explosions.

Depletion of ribosomal protein L37 occurs in response to DNA damage and activates p53 through the L11/MDM2 pathway

PubMed Central

Llanos, Susana; Serrano, Manuel

2013-01-01

Perturbation of ribosomal biogenesis has recently emerged as a relevant p53-activating pathway. This pathway can be initiated by depletion of certain ribosomal proteins, which is followed by the binding and inhibition of MDM2 by a different subset of ribosomal proteins that includes L11. Here, we report that depletion of L37 leads to cell cycle arrest in a L11- and p53-dependent manner. DNA damage can initiate ribosomal stress, although little is known about the mechanisms involved. We have found that some genotoxic insults, namely UV light and cisplatin, lead to proteasomal degradation of L37 in the nucleoplasm and to the ensuing L11-dependent stabilization of p53. Moreover, ectopic L37 overexpression can attenuate the DNA damage response mediated by p53. These results support the concept that DNA damage-induced proteasomal degradation of L37 constitutes a mechanistic link between DNA damage and the ribosomal stress pathway, and is a relevant contributing signaling pathway for the activation of p53 in response to DNA damage. PMID:20935493

Fatigue Life of Postbuckled Structures with Indentation Damages

NASA Technical Reports Server (NTRS)

Davila, Carlos G.; Bisagni, Chiara

2016-01-01

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

Chromosome damage evolution after low and high LET irradiation

NASA Astrophysics Data System (ADS)

Andreev, Sergey; Eidelman, Yuri

Ionizing radiation induces DNA and chromatin lesions which are converted to chromosome lesions detected in the first post-irradiation mitosis by classic cytogenetic techniques as chromosomal aberrations (CAs). These techniques allow to monitor also delayed aberrations observed after many cell generations post-irradiation - the manifestation of chromosomal instability phenotype (CIN). The problem discussed is how to predict time evolution from initial to delayed DNA/chromosome damage. To address this question, in the present work a mechanistic model of CIN is elaborated which integrates pathways of (*) DNA damage induction and its conversion to chromosome lesions (aberrations), (**) lesion transmission and generation through cell cycles. Delayed aberrations in subsequent cycles are formed in the model owing to two pathways, DNA damage generation de novo as well as CA transmission from previous cycles. DNA damage generation rate is assumed to consist of bystander and non-bystander components. Bystander signals impact all cells roughly equally, whereas non-bystander DSB generation rate differs for the descendants of unirradiated and irradiated cells. Monte Carlo simulation of processes underlying CIN allows to predict the time evolution of initial radiation-induced damage - kinetics curve for delayed unstable aberrations (dicentrics) together with dose response and RBE as a function of time after high vs low LET irradiation. The experimental data for radiation-induced CIN in TK6 lymphoblastoid cells and human lymphocytes irradiated with low (gamma) and high (Fe, C) LET radiation are analyzed on the basis of the proposed model. One of the conclusions is that without bystander signaling, just taking into account the initial DNA damage and non-bystander DSB generation, it is impossible to describe the available experimental data for high-LET-induced CIN. The exact contribution of bystander effects for high vs low LET remains unknown, but the relative contribution may be assessed at large times after initial acute irradiation. RBE for delayed aberrations depends on LET, time and cell line, which probably reflects a genetic background for bystander component. The proposed modeling approach creates a basis for integration of complex network of bystander/inflammatory signaling in systems-level platform for quantification of radiation induced CIN.

Fast Biological Modeling for Voxel-based Heavy Ion Treatment Planning Using the Mechanistic Repair-Misrepair-Fixation Model and Nuclear Fragment Spectra

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

Kamp, Florian; Department of Radiation Oncology, Technische Universität München, Klinikum Rechts der Isar, München; Physik-Department, Technische Universität München, Garching

2015-11-01

Purpose: The physical and biological differences between heavy ions and photons have not been fully exploited and could improve treatment outcomes. In carbon ion therapy, treatment planning must account for physical properties, such as the absorbed dose and nuclear fragmentation, and for differences in the relative biological effectiveness (RBE) of ions compared with photons. We combined the mechanistic repair-misrepair-fixation (RMF) model with Monte Carlo-generated fragmentation spectra for biological optimization of carbon ion treatment plans. Methods and Materials: Relative changes in double-strand break yields and radiosensitivity parameters with particle type and energy were determined using the independently benchmarked Monte Carlo damagemore » simulation and the RMF model to estimate the RBE values for primary carbon ions and secondary fragments. Depth-dependent energy spectra were generated with the Monte Carlo code FLUKA for clinically relevant initial carbon ion energies. The predicted trends in RBE were compared with the published experimental data. Biological optimization for carbon ions was implemented in a 3-dimensional research treatment planning tool. Results: We compared the RBE and RBE-weighted dose (RWD) distributions of different carbon ion treatment scenarios with and without nuclear fragments. The inclusion of fragments in the simulations led to smaller RBE predictions. A validation of RMF against measured cell survival data reported in published studies showed reasonable agreement. We calculated and optimized the RWD distributions on patient data and compared the RMF predictions with those from other biological models. The RBE values in an astrocytoma tumor ranged from 2.2 to 4.9 (mean 2.8) for a RWD of 3 Gy(RBE) assuming (α/β){sub X} = 2 Gy. Conclusions: These studies provide new information to quantify and assess uncertainties in the clinically relevant RBE values for carbon ion therapy based on biophysical mechanisms. We present results from the first biological optimization of carbon ion radiation therapy beams on patient data using a combined RMF and Monte Carlo damage simulation modeling approach. The presented method is advantageous for fast biological optimization.« less

Confronting challenges to economic analysis of biological invasions in forests

Treesearch

Thomas P Holmes

2010-01-01

Biological invasions of forests by non-indigenous organisms present a complex, persistent, and largely irreversible threat to forest ecosystems around the globe. Rigorous assessments of the economic impacts of introduced species, at a national scale, are needed to provide credible information to policy makers. It is proposed here that microeconomic models of damage due...

Improvement of mass-rearing procedures for an olive fruit fly parasitoid – duration of exposure to hosts affects production of Psyttalia lounsburyi

USDA-ARS?s Scientific Manuscript database

The olive fruit fly, Bactrocera oleae (Diptera: Tephritidae), causes severe economic damage in California. Control of this fly is currently limited to pesticides. The USDA-ARS European Biological Control Laboratory in Montpellier, France established a classical biological control program nearly 15 y...

On crack initiation in notched, cross-plied polymer matrix composites

NASA Astrophysics Data System (ADS)

Yang, Q. D.; Schesser, D.; Niess, M.; Wright, P.; Mavrogordato, M. N.; Sinclair, I.; Spearing, S. M.; Cox, B. N.

2015-05-01

The physics of crack initiation in a polymer matrix composite are investigated by varying the modeling choices made in simulations and comparing the resulting predictions with high-resolution in situ images of cracks. Experimental data were acquired using synchrotron-radiation computed tomography (SRCT) at a resolution on the order of 1 μm, which provides detailed measurement of the location, shape, and size of small cracks, as well as the crack opening and shear displacements. These data prove sufficient to discriminate among competing physical descriptions of crack initiation. Simulations are executed with a high-fidelity formulation, the augmented finite element method (A-FEM), which permits consideration of coupled damage mechanisms, including both discrete cracks and fine-scale continuum damage. The discrete cracks are assumed to be nonlinear fracture events, governed by reasonably general mixed-mode cohesive laws. Crack initiation is described in terms of strength parameters within the cohesive laws, so that the cohesive law provides a unified model for crack initiation and growth. Whereas the cracks investigated are typically 1 mm or less in length, the fine-scale continuum damage refers to irreversible matrix deformation occurring over gauge lengths extending down to the fiber diameter (0.007 mm). We find that the location and far-field stress for crack initiation are predicted accurately only if the variations of local stress within plies and in the presence of stress concentrators (notches, etc.) are explicitly computed and used in initiation criteria; stress redistribution due to matrix nonlinearity that occurs prior to crack initiation is accounted for; and a mixed-mode criterion is used for crack initiation. If these factors are not all considered, which is the case for commonly used failure criteria, predictions of the location and far-field stress for initiation are not accurate.

Transcription factor Nrf2 hyperactivation in early-phase renal ischemia-reperfusion injury prevents tubular damage progression.

PubMed

Nezu, Masahiro; Souma, Tomokazu; Yu, Lei; Suzuki, Takafumi; Saigusa, Daisuke; Ito, Sadayoshi; Suzuki, Norio; Yamamoto, Masayuki

2017-02-01

Acute kidney injury is a devastating disease with high morbidity in hospitalized patients and contributes to the pathogenesis of chronic kidney disease. An underlying mechanism of acute kidney injury involves ischemia-reperfusion injury which, in turn, induces oxidative stress and provokes organ damage. Nrf2 is a master transcription factor that regulates the cellular response to oxidative stress. Here, we examined the role of Nrf2 in the progression of ischemia-reperfusion injury-induced kidney damage in mice using genetic and pharmacological approaches. Both global and tubular-specific Nrf2 activation enhanced gene expression of antioxidant and NADPH synthesis enzymes, including glucose-6-phosphate dehydrogenase, and ameliorated both the initiation of injury in the outer medulla and the progression of tubular damage in the cortex. Myeloid-specific Nrf2 activation was ineffective. Short-term administration of the Nrf2 inducer CDDO during the initial phase of injury ameliorated the late phase of tubular damage. This inducer effectively protected the human proximal tubular cell line HK-2 from oxidative stress-mediated cell death while glucose-6-phosphate dehydrogenase knockdown increased intracellular reactive oxygen species. These findings demonstrate that tubular hyperactivation of Nrf2 in the initial phase of injury prevents the progression of reactive oxygen species-mediated tubular damage by inducing antioxidant enzymes and NADPH synthesis. Thus, Nrf2 may be a promising therapeutic target for preventing acute kidney injury to chronic kidney disease transition. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Fatigue analysis of multiple site damage at a row of holes in a wide panel

NASA Technical Reports Server (NTRS)

Buhler, Kimberley; Grandt, Alten F., Jr.; Moukawsher, E. J.

1994-01-01

This paper is concerned with predicting the fatigue life of unstiffened panels which contain multiple site damage (MSD). The initial damage consists of through-the-thickness cracks emanating from a row of holes in the center of a finite width panel. A fracture mechanics analysis has been developed to predict the growth, interaction, and coalescence of the various cracks which propagate in the panel. A strain-life analysis incorporating Neuber's rule for notches, and Miner's rule for cumulative damage, is also employed to predict crack initiation for holes without initial cracking. This analysis is compared with the results of a series of fatigue tests on 2024-T3 aluminum panels, and is shown to do an excellent job of predicting the influence of MSD on the fatigue life of nine inch wide specimens. Having established confidence in the ability to analyze the influence of MSD on fatigue life, a parametric study is conducted to examine the influence of various MSD scenarios in an unstiffened panel. The numerical study considered 135 cases in all, with the parametric variables being the applied cyclic stress level, the lead crack geometry, and the number and location of MSD cracks. The numerical analysis provides details for the manner in which lead cracks and MSD cracks grow and coalesce leading to final failure. The results indicate that MSD located adjacent to lead cracks is the most damaging configuration, while for cases without lead cracks, MSD clusters which are not separated by uncracked holes are most damaging.

Biological Effects of Protracted Exposure to Ionizing Radiation: Review, Analysis, and Model Development

DTIC Science & Technology

1991-11-01

dynamics, physiological changes, morphologi- cal changes, cell/tissue damage and recovery mechanisms, and existing radiobiological injury and recovery...humans and the ferret. The gut injury model (GIM) is a three-compartment hierarchial- type tissue model to simulate radiation-induced changes in the...Prodromal Symptoms Diarrhea Gastrointestinal Symptoms Dose Rate Cell Survival Intestinal Injury Fatigability Cell Damage Cell Repair Cell Proliferation

Comparative impact of Scymnus ningshanensis and Pseudoscymnus tsugae (Coleoptera: Coccinellidae) on the hemlock woolly adelgid

Treesearch

Elizabeth Butin; Joseph Elkinton; Nathan Havill; Michael Montgomery

2003-01-01

The hemlock woolly adelgid (Adelges tsugae Annand) is an introduced pest thought to be native to Asia. Damage to eastern hemlock and Carolina hemlock can be serious (Salom et al. 1996), but western and Asian hemlocks are seldom damaged. Potential biological control agents have been observed in Japan and China (Sasaji and McClure 1997, Yu et al. 2000...

A Hypothesis on Biological Protection from Space Radiation Through the Use of Therapeutic Gases

NASA Technical Reports Server (NTRS)

Schoenfeld, Michael

2011-01-01

This slide presentation proposes a hypothesis to use therapeutic gases in space to enhance the biological protection for astronauts from space radiation. The fundamental role in how radiation causes biological damage appears to be radiolysis, the dissociation of water by radiation. A chain of events appears to cause molecular and biological transformations that ultimately manifest into medical diseases. The hypothesis of this work is that applying medical gases may increase resistance to radiation, by possessing the chemical properties that effectively improve the radical scavenging and enhance bond repair and to induce biological processes which enhance and support natural resistance and repair mechanisms.

Climate mitigation: sustainable preferences and cumulative carbon

NASA Astrophysics Data System (ADS)

Buckle, Simon

2010-05-01

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

Oligostilbenoids from Vatica Species and Bioactivities

NASA Astrophysics Data System (ADS)

Kamarozaman, A. S.; Rajab, N. F.; Latip, J.

Reactive species (RS) which are generated from the pollution, deep fried and spicy foods, leakage of electrons from mitochondrial electron transport chains etc. may result in an oxidative damage in the body. The oxidative damage may lead to various diseases such as Alzheimer, atherosclerosis and cancer. In order to prevent such diseases, antioxidants play important roles in reducing the powerful oxidizing agents. Vatica species that belongs to the family of Dipterocarpaceae has been widely known to contain abundant source of oligostilbenoids which demonstrated interesting result in biological activities such as anticancer and antioxidant. This may lead to a development of drugs as well as natural antioxidants. In this chapter, we are highlighting the oligostilbenoids isolated from Vatica species from various researcher as well as the biological activities.

A new record of longicorn beetle, Acanthophorus rugiceps, from India as a root borer on physic nut, Jatropha curcas, with a description of life stages, biology, and seasonal dynamics.

PubMed

Prabhakar, Mathyam; Prasad, Y G; Rao, G R; Venkateswarlu, B

2012-01-01

Longicorn beetle, Acanthophorus rugiceps Gahan (Coleoptera: Cerambycidae), is reported for the first time as a confirmed host on physic nut, Jatropha curcas L. (Malpighiales: Euphorbiaceae), from India, causing extensive damage to roots. Plants of three years age and above were prone to attack by this pest. In a six year study beginning in 2005, about 11.3 percent of plants in a 16.25 acre physic nut plantation were severely damaged by A. rugiceps. Life stages of A. rugiceps, including egg, larvae, pupae, and adult, are described with a note on their habitat, biology, and behavior. Strategies to manage this pest on physic nut are discussed.

Synthesis and biological evaluation of sulfur-containing cinnamate and salicylate derivatives.

PubMed

Chiang, Chih-Chia; Chang, Tsu-Chung; Tsai, Hou-Jen; Hsu, Ling-Yih

2008-03-01

UV irradiation induced formation of reactive oxygen radical species and matrix metalloproteinases (MMPs) are thought to be involved in photo-damage to the skin. MMP-1 is the major collagenolytic enzyme responsible for collagen destruction in skin tissue. To develop new anti-photoaging agents, a series of 2,2'-dithiocinnamate derivatives and 2,2'-dithio or 2-thiobenzoate derivatives were designed and synthesized. The biological activities of the synthesized compounds were assayed for ABTS [2,2'-azinobis-(3-ethyl-benzo-thiazoline-6-sulfonic acid)] radical scavenging activity, MMP-1 inhibitory activity, and cytotoxicity to human dermal fibroblast cells. Compounds with potential of resistance to UV irradiation were identified. These compounds are expected to be useful for preventing photo-damage to the skin.

Model-Based Structural Health Monitoring of Fatigue Damage Test-Bed Specimens

DTIC Science & Technology

2011-11-15

the hull welds or notches along component edges are good initial candidates for the hypothetical damage initiation areas. The branching process adds...to it off-center. The base plate and the stiffener plate are rigidly welded by a tungsten inert gas ( TIG ) weld . Three different crack paths...shown in Figure 9(a), an 18 in long stiffener plate has been welded to each of the tested plates with 0.625 in long discrete TIG welds at 5 locations

A combined field and numerical approach to understanding dilute pyroclastic density current dynamics and hazard potential: Auckland Volcanic Field, New Zealand

NASA Astrophysics Data System (ADS)

Brand, Brittany D.; Gravley, Darren M.; Clarke, Amanda B.; Lindsay, Jan M.; Bloomberg, Simon H.; Agustin-Flores, Javier; Németh, Károly

2014-04-01

The most dangerous and deadly hazards associated with phreatomagmatic eruptions in the Auckland Volcanic Field (AVF; Auckland, New Zealand) are those related to volcanic base surges - dilute, ground-hugging, particle laden currents with dynamic pressures capable of severe to complete structural damage. We use the well-exposed base surge deposits of the Maungataketake tuff ring (Manukau coast, Auckland), to reconstruct flow dynamics and destructive potential of base surges produced during the eruption. The initial base surge(s) snapped trees up to 0.5 m in diameter near their base as far as 0.7-0.9 km from the vent. Beyond this distance the trees were encapsulated and buried by the surge in growth position. Using the tree diameter and yield strength of the wood we calculate that dynamic pressures (Pdyn) in excess of 12-35 kPa are necessary to cause the observed damage. Next we develop a quantitative model for flow of and sedimentation from a radially-spreading, dilute pyroclastic density currents (PDCs) to determine the damage potential of the base surges produced during the early phases of the eruption and explore the implications of this potential on future eruptions in the region. We find that initial conditions with velocities on the order of 65 m s- 1, bulk density of 38 kg m- 3 and initial, near-vent current thicknesses of 60 m reproduce the field-based Pdyn estimates and runout distances. A sensitivity analysis revealed that lower initial bulk densities result in shorter run-out distances, more rapid deceleration of the current and lower dynamic pressures. Initial velocity does not have a strong influence on run-out distance, although higher initial velocity and slope slightly decrease runout distance due to higher rates of atmospheric entrainment. Using this model we determine that for base surges with runout distances of up to 4 km, complete destruction can be expected within 0.5 km from the vent, moderate destruction can be expected up to 2 km, but much less damage is expected up to the final runout distance of 4 km. For larger eruptions (base surge runout distance 4-6 km), Pdyn of > 35 kPa can be expected up to 2.5 km from source, ensuring complete destruction within this area. Moderate damage to reinforced structures and damage to weaker structures can be expected up to 6 km from source. In both cases hot ash may still cause damage due to igniting flammable materials in the distal-most regions of a base surge. This work illustrates our ability to combine field observations and numerical models to explore the depositional mechanisms, macroscale current dynamics, and potential impact of dilute PDCs. Thus, this approach may serve as a tool to understand the damage potential and extent of previous and potential future eruptions in the AVF.

Cost Sharing, Family Health Care Burden, and the Use of Specialty Drugs for Rheumatoid Arthritis

PubMed Central

Karaca-Mandic, Pinar; Joyce, Geoffrey F; Goldman, Dana P; Laouri, Marianne

2010-01-01

Objectives To examine the impact of benefit generosity and household health care financial burden on the demand for specialty drugs in the treatment of rheumatoid arthritis (RA). Data Sources/Study Setting Enrollment, claims, and benefit design information for 35 large private employers during 2000–2005. Study Design We estimated multivariate models of the effects of benefit generosity and household financial burden on initiation and continuation of biologic therapies. Data Extraction Methods We defined initiation of biologic therapy as first-time use of etanercept, adalimumab, or infliximab, and we constructed an index of plan generosity based on coverage of biologic therapies in each plan. We estimated the household's burden by summing up the annual out-of-pocket (OOP) expenses of other family members. Principal Findings Benefit generosity affected both the likelihood of initiating a biologic and continuing drug therapy, although the effects were stronger for initiation. Initiation of a biologic was lower in households where other family members incurred high OOP expenses. Conclusions The use of biologic therapy for RA is sensitive to benefit generosity and household financial burden. The increasing use of coinsurance rates for specialty drugs (as under Medicare Part D) raises concern about adverse health consequences. PMID:20831715

Proteomic Analysis of the Downstream Signaling Network of PARP1.

PubMed

Zhen, Yuanli; Yu, Yonghao

2018-01-30

Poly-ADP-ribosylation (PARylation) is a protein posttranslational modification (PTM) that is critically involved in many biological processes that are linked to cell stress responses. It is catalyzed by a class of enzymes known as poly-ADP-ribose polymerases (PARPs). In particular, PARP1 is a nuclear protein that is activated upon sensing nicked DNA. Once activated, PARP1 is responsible for the synthesis of a large number of PARylated proteins and initiation of the DNA damage response mechanisms. This observation provided the rationale for developing PARP1 inhibitors for the treatment of human malignancies. Indeed, three PARP1 inhibitors (Olaparib, Rucaparib, and Niraparib) have recently been approved by the Food and Drug Administration for the treatment of ovarian cancer. Moreover, in 2017, both Olaparib and Niraparib have also been approved for the treatment of fallopian tube cancer and primary peritoneal cancer. Despite this very exciting progress in the clinic, the basic signaling mechanism that connects PARP1 to a diverse array of biological processes is still poorly understood. This is, in large part, due to the inherent technical difficulty associated with the analysis of protein PARylation, which is a low-abundance, labile, and heterogeneous PTM. The study of PARylation has been greatly facilitated by the recent advances in mass spectrometry-based proteomic technologies tailored to the analysis of this modification. In this Perspective, we discuss these breakthroughs, including their technical development, and applications that provide a global view of the many biological processes regulated by this important protein modification.

Detection of DNA damage by using hairpin molecular beacon probes and graphene oxide.

PubMed

Zhou, Jie; Lu, Qian; Tong, Ying; Wei, Wei; Liu, Songqin

2012-09-15

A hairpin molecular beacon tagged with carboxyfluorescein in combination with graphene oxide as a quencher reagent was used to detect the DNA damage by chemical reagents. The fluorescence of molecular beacon was quenched sharply by graphene oxide; while in the presence of its complementary DNA the quenching efficiency decreased because their hybridization prevented the strong adsorbability of molecular beacon on graphene oxide. If the complementary DNA was damaged by a chemical reagent and could not form intact duplex structure with molecular beacon, more molecular beacon would adsorb on graphene oxide increasing the quenching efficiency. Thus, damaged DNA could be detected based on different quenching efficiencies afforded by damaged and intact complementary DNA. The damage effects of chlorpyrifos-methyl and three metabolites of styrene such as mandelieaeids, phenylglyoxylieaeids and epoxystyrene on DNA were studied as models. The method for detection of DNA damage was reliable, rapid and simple compared to the biological methods. Copyright © 2012 Elsevier B.V. All rights reserved.

A Novel Approach to Rotorcraft Damage Tolerance

NASA Technical Reports Server (NTRS)

Forth, Scott C.; Everett, Richard A.; Newman, John A.

2002-01-01

Damage-tolerance methodology is positioned to replace safe-life methodologies for designing rotorcraft structures. The argument for implementing a damage-tolerance method comes from the fundamental fact that rotorcraft structures typically fail by fatigue cracking. Therefore, if technology permits prediction of fatigue-crack growth in structures, a damage-tolerance method should deliver the most accurate prediction of component life. Implementing damage-tolerance (DT) into high-cycle-fatigue (HCF) components will require a shift from traditional DT methods that rely on detecting an initial flaw with nondestructive inspection (NDI) methods. The rapid accumulation of cycles in a HCF component will result in a design based on a traditional DT method that is either impractical because of frequent inspections, or because the design will be too heavy to operate efficiently. Furthermore, once a HCF component develops a detectable propagating crack, the remaining fatigue life is short, sometimes less than one flight hour, which does not leave sufficient time for inspection. Therefore, designing a HCF component will require basing the life analysis on an initial flaw that is undetectable with current NDI technology.

A Damage Model for the Simulation of Delamination in Advanced Composites under Variable-Mode Loading

NASA Technical Reports Server (NTRS)

Turon, A.; Camanho, P. P.; Costa, J.; Davila, C. G.

2006-01-01

A thermodynamically consistent damage model is proposed for the simulation of progressive delamination in composite materials under variable-mode ratio. The model is formulated in the context of Damage Mechanics. A novel constitutive equation is developed to model the initiation and propagation of delamination. A delamination initiation criterion is proposed to assure that the formulation can account for changes in the loading mode in a thermodynamically consistent way. The formulation accounts for crack closure effects to avoid interfacial penetration of two adjacent layers after complete decohesion. The model is implemented in a finite element formulation, and the numerical predictions are compared with experimental results obtained in both composite test specimens and structural components.

Live cell imaging at the Munich ion microbeam SNAKE - a status report.

PubMed

Drexler, Guido A; Siebenwirth, Christian; Drexler, Sophie E; Girst, Stefanie; Greubel, Christoph; Dollinger, Günther; Friedl, Anna A

2015-02-18

Ion microbeams are important tools in radiobiological research. Still, the worldwide number of ion microbeam facilities where biological experiments can be performed is limited. Even fewer facilities combine ion microirradiation with live-cell imaging to allow microscopic observation of cellular response reactions starting very fast after irradiation and continuing for many hours. At SNAKE, the ion microbeam facility at the Munich 14 MV tandem accelerator, a large variety of biological experiments are performed on a regular basis. Here, recent developments and ongoing research projects at the ion microbeam SNAKE are presented with specific emphasis on live-cell imaging experiments. An overview of the technical details of the setup is given, including examples of suitable biological samples. By ion beam focusing to submicrometer beam spot size and single ion detection it is possible to target subcellular structures with defined numbers of ions. Focusing of high numbers of ions to single spots allows studying the influence of high local damage density on recruitment of damage response proteins.

Climate warming increases biological control agent impact on a non-target species

PubMed Central

Lu, Xinmin; Siemann, Evan; He, Minyan; Wei, Hui; Shao, Xu; Ding, Jianqing

2015-01-01

Climate change may shift interactions of invasive plants, herbivorous insects and native plants, potentially affecting biological control efficacy and non-target effects on native species. Here, we show how climate warming affects impacts of a multivoltine introduced biocontrol beetle on the non-target native plant Alternanthera sessilis in China. In field surveys across a latitudinal gradient covering their full distributions, we found beetle damage on A. sessilis increased with rising temperature and plant life history changed from perennial to annual. Experiments showed that elevated temperature changed plant life history and increased insect overwintering, damage and impacts on seedling recruitment. These results suggest that warming can shift phenologies, increase non-target effect magnitude and increase non-target effect occurrence by beetle range expansion to additional areas where A. sessilis occurs. This study highlights the importance of understanding how climate change affects species interactions for future biological control of invasive species and conservation of native species. PMID:25376303

Experimental determination of cloud influence on the spectral UV irradiance and implications for biological effects

NASA Astrophysics Data System (ADS)

Mateos, David; di Sarra, Alcide; Meloni, Daniela; di Biagio, Claudia; Sferlazzo, Damiano M.

2011-08-01

Measurements of UV spectra, total ozone, cloud cover, and cloud optical thickness, obtained at Lampedusa (central Mediterranean), are used to investigate the influence of clouds on the spectral UV irradiance, through the cloud modification factor (CMF), and on five biological processes. The CMF decreases with cloud optical thickness (COT), from about 0.5 for COT˜15 to 0.25 for COT˜45, and decreases with increasing wavelength above 315-320-nm. Observations display an increase in the CMF from 295 to 320-nm, which is related to enhanced absorption by tropospheric ozone due to the long photon path lengths under cloudy conditions. The use of a wavelength independent CMF instead of the experimentally determined spectral curves produces an overestimation of the biological effects of UV irradiance. The overestimation may be as large as 30% for the DNA damage, 20% for vitamin D synthesis, 12% for plant damage, and 8-10% for phytoplankton inhibition and erythema.

Climate warming increases biological control agent impact on a non-target species.

PubMed

Lu, Xinmin; Siemann, Evan; He, Minyan; Wei, Hui; Shao, Xu; Ding, Jianqing

2015-01-01

Climate change may shift interactions of invasive plants, herbivorous insects and native plants, potentially affecting biological control efficacy and non-target effects on native species. Here, we show how climate warming affects impacts of a multivoltine introduced biocontrol beetle on the non-target native plant Alternanthera sessilis in China. In field surveys across a latitudinal gradient covering their full distributions, we found beetle damage on A. sessilis increased with rising temperature and plant life history changed from perennial to annual. Experiments showed that elevated temperature changed plant life history and increased insect overwintering, damage and impacts on seedling recruitment. These results suggest that warming can shift phenologies, increase non-target effect magnitude and increase non-target effect occurrence by beetle range expansion to additional areas where A. sessilis occurs. This study highlights the importance of understanding how climate change affects species interactions for future biological control of invasive species and conservation of native species. © 2014 The Authors. Ecology Letters published by John Wiley & Sons Ltd and CNRS.

On the relationship between indentation hardness and modulus, and the damage resistance of biological materials.

PubMed

Labonte, David; Lenz, Anne-Kristin; Oyen, Michelle L

2017-07-15

The remarkable mechanical performance of biological materials is based on intricate structure-function relationships. Nanoindentation has become the primary tool for characterising biological materials, as it allows to relate structural changes to variations in mechanical properties on small scales. However, the respective theoretical background and associated interpretation of the parameters measured via indentation derives largely from research on 'traditional' engineering materials such as metals or ceramics. Here, we discuss the functional relevance of indentation hardness in biological materials by presenting a meta-analysis of its relationship with indentation modulus. Across seven orders of magnitude, indentation hardness was directly proportional to indentation modulus. Using a lumped parameter model to deconvolute indentation hardness into components arising from reversible and irreversible deformation, we establish criteria which allow to interpret differences in indentation hardness across or within biological materials. The ratio between hardness and modulus arises as a key parameter, which is related to the ratio between irreversible and reversible deformation during indentation, the material's yield strength, and the resistance to irreversible deformation, a material property which represents the energy required to create a unit volume of purely irreversible deformation. Indentation hardness generally increases upon material dehydration, however to a larger extent than expected from accompanying changes in indentation modulus, indicating that water acts as a 'plasticiser'. A detailed discussion of the role of indentation hardness, modulus and toughness in damage control during sharp or blunt indentation yields comprehensive guidelines for a performance-based ranking of biological materials, and suggests that quasi-plastic deformation is a frequent yet poorly understood damage mode, highlighting an important area of future research. Instrumented indentation is a widespread tool for characterising the mechanical properties of biological materials. Here, we show that the ratio between indentation hardness and modulus is approximately constant in biological materials. A simple elastic-plastic series deformation model is employed to rationalise part of this correlation, and criteria for a meaningful comparison of indentation hardness across biological materials are proposed. The ratio between indentation hardness and modulus emerges as the key parameter characterising the relative amount of irreversible deformation during indentation. Despite their comparatively high hardness to modulus ratio, biological materials are susceptible to quasiplastic deformation, due to their high toughness: quasi-plastic deformation is hence hypothesised to be a frequent yet poorly understood phenomenon, highlighting an important area of future research. Copyright © 2017 Acta Materialia Inc. All rights reserved.