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Sample records for damage mechanics formulation

  1. Treatment of anisotropic damage development within a scalar damage formulation

    SciTech Connect

    Chan, K.S.; Bodner, S.R.; Munson, D.E.

    1996-11-01

    This paper is concerned with describing a damage mechanics formulation which provides for non-isotropic effects using a scalar damage variable. An investigation has been in progress for establishing the constitutive behavior of rock salt at long times and low to moderate confining pressures in relation to the possible use of excavated rooms in rock salt formations as repositories for nuclear waste. An important consideration is the effect of damage manifested principally by the formation of shear induced wing cracks which have a stress dependent orientation. The analytical formulation utilizes a scalar damage parameter, but is capable of indicating the non- isotropic dependence of inelastic straining on the stress state and the confining pressure. Also, the equations indicate the possibility of volumetric expansions leading to the onset of tertiary creep and eventually rupture if the damage variable reaches a critical value.

  2. Differential genotoxicity of Roundup(®) formulation and its constituents in blood cells of fish (Anguilla anguilla): considerations on chemical interactions and DNA damaging mechanisms.

    PubMed

    Guilherme, S; Santos, M A; Barroso, C; Gaivão, I; Pacheco, M

    2012-07-01

    It has been widely recognized that pesticides represent a potential threat in aquatic ecosystems. However, the knowledge on the genotoxicity of pesticides to fish is still limited. Moreover, genotoxic studies have been almost exclusively focused on the active ingredients, whereas the effect of adjuvants is frequently ignored. Hence, the present study addressed the herbicide Roundup®, evaluating the relative contribution of the active ingredient (glyphosate) and the surfactant (polyethoxylated amine; POEA) to the genotoxicity of the commercial formulation on Anguilla anguilla. Fish were exposed to equivalent concentrations of Roundup® (58, 116 μg L⁻¹), glyphosate (17.9, 35.7 μg L⁻¹) and POEA (9.3, 18.6 μg L⁻¹), during 1 and 3 days. The comet assay was applied to blood cells, either as the standard procedure, or with an extra step involving DNA lesion-specific repair enzymes in an attempt to clarify DNA damaging mechanisms. The results confirmed the genotoxicity of Roundup®, also demonstrating the genotoxic potential of glyphosate and POEA individually. Though both components contributed to the overall genotoxicity of the pesticide formulation, the sum of their individual effects was never observed, pointing out an antagonistic interaction. Although POEA is far from being considered biologically inert, it did not increase the risk associated to glyphosate when the two were combined. The analysis of oxidatively induced breaks suggested that oxidation of DNA bases was not a dominant mechanism of damage. The present findings highlighted the risk posed to fish populations by the assessed chemicals, jointly or individually, emphasizing the need to define regulatory thresholds for all the formulation components and recommending, in particular, the revision of the hazard classification of POEA.

  3. Operator Formulation of Classical Mechanics.

    ERIC Educational Resources Information Center

    Cohn, Jack

    1980-01-01

    Discusses the construction of an operator formulation of classical mechanics which is directly concerned with wave packets in configuration space and is more similar to that of convential quantum theory than other extant operator formulations of classical mechanics. (Author/HM)

  4. Mechanism of DNA damage tolerance.

    PubMed

    Bi, Xin

    2015-08-26

    DNA damage may compromise genome integrity and lead to cell death. Cells have evolved a variety of processes to respond to DNA damage including damage repair and tolerance mechanisms, as well as damage checkpoints. The DNA damage tolerance (DDT) pathway promotes the bypass of single-stranded DNA lesions encountered by DNA polymerases during DNA replication. This prevents the stalling of DNA replication. Two mechanistically distinct DDT branches have been characterized. One is translesion synthesis (TLS) in which a replicative DNA polymerase is temporarily replaced by a specialized TLS polymerase that has the ability to replicate across DNA lesions. TLS is mechanistically simple and straightforward, but it is intrinsically error-prone. The other is the error-free template switching (TS) mechanism in which the stalled nascent strand switches from the damaged template to the undamaged newly synthesized sister strand for extension past the lesion. Error-free TS is a complex but preferable process for bypassing DNA lesions. However, our current understanding of this pathway is sketchy. An increasing number of factors are being found to participate or regulate this important mechanism, which is the focus of this editorial. PMID:26322163

  5. Finite strain formulation of viscoelastic damage model for simulation of fabric reinforced polymers under dynamic loading

    NASA Astrophysics Data System (ADS)

    Treutenaere, S.; Lauro, F.; Bennani, B.; Matsumoto, T.; Mottola, E.

    2015-09-01

    The use of fabric reinforced polymers in the automotive industry is growing significantly. The high specific stiffness and strength, the ease of shaping as well as the great impact performance of these materials widely encourage their diffusion. The present model increases the predictability of explicit finite element analysis and push the boundaries of the ongoing phenomenological model. Carbon fibre composites made up various preforms were tested by applying different mechanical load up to dynamic loading. This experimental campaign highlighted the physical mechanisms affecting the initial mechanical properties, namely intra- and interlaminar matrix damage, viscoelasticty and fibre failure. The intralaminar behaviour model is based on the explicit formulation of the matrix damage model developed by the ONERA as the given damage formulation correlates with the experimental observation. Coupling with a Maxwell-Wiechert model, the viscoelasticity is included without losing the direct explicit formulation. Additionally, the model is formulated under a total Lagrangian scheme in order to maintain consistency for finite strain. Thus, the material frame-indifference as well as anisotropy are ensured. This allows reorientation of fibres to be taken into account particularly for in-plane shear loading. Moreover, fall within the framework of the total Lagrangian scheme greatly makes the parameter identification easier, as based on the initial configuration. This intralaminar model thus relies upon a physical description of the behaviour of fabric composites and the numerical simulations show a good correlation with the experimental results.

  6. Immunoglobulin: production, mechanisms of action and formulations

    PubMed Central

    Novaretti, Marcia Cristina Zago; Dinardo, Carla Luana

    2011-01-01

    Human immunoglobulin (Ig) began to be applied in the clinical practice with the treatment of primary immunodeficiencies. Quickly, applications of Ig increased, as its anti-inflammatory and immunomodulatory functions were elucidated. Currently, Ig is the most commonly used blood product. Ig is obtained by processing plasma; methods, in particular, techniques to reduce plasma viral loads have been evolving over the years and include: pasteurization, solvent/ detergent treatment, caprylic acid treatment and nanofiltration. These methods contribute to increased safety and quality of blood products. The mechanisms of action of Ig not only involve the blockade of Fc receptors of phagocytes, but also control complement pathways, idiotype-anti-idiotype dimer formation, blockage of superantigen binding to T cells, inhibition of dendritic cells and stimulation of regulatory T cells (Tregs). There are several formulations of Ig available, each one with its own peculiar characteristics. In Brazil, there is stringent legislation regulating the quality of Ig. Only Ig products that completely fulfill the quality control criteria are released for use. These standards involve different tests from visual inspection to determination of anti-complementary activity. This paper will further review the history and current status of Ig, including its production and mechanisms of action. The formulations available in Brazil and also the criteria of quality control currently applied will be presented. PMID:23049343

  7. On the formulation, parameter identification and numerical integration of the EMMI model :plasticity and isotropic damage.

    SciTech Connect

    Bammann, Douglas J.; Johnson, G. C. (University of California, Berkeley, CA); Marin, Esteban B.; Regueiro, Richard A.

    2006-01-01

    In this report we present the formulation of the physically-based Evolving Microstructural Model of Inelasticity (EMMI) . The specific version of the model treated here describes the plasticity and isotropic damage of metals as being currently applied to model the ductile failure process in structural components of the W80 program . The formulation of the EMMI constitutive equations is framed in the context of the large deformation kinematics of solids and the thermodynamics of internal state variables . This formulation is focused first on developing the plasticity equations in both the relaxed (unloaded) and current configurations. The equations in the current configuration, expressed in non-dimensional form, are used to devise the identification procedure for the plasticity parameters. The model is then extended to include a porosity-based isotropic damage state variable to describe the progressive deterioration of the strength and mechanical properties of metals induced by deformation . The numerical treatment of these coupled plasticity-damage constitutive equations is explained in detail. A number of examples are solved to validate the numerical implementation of the model.

  8. Recent Advances in Composite Damage Mechanics

    NASA Technical Reports Server (NTRS)

    Reifsnider, Ken; Case, Scott; Iyengar, Nirmal

    1996-01-01

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

  9. A comparative review of four formulations of noncommutative quantum mechanics

    NASA Astrophysics Data System (ADS)

    Gouba, Laure

    2016-07-01

    Four formulations of quantum mechanics on noncommutative Moyal phase spaces are reviewed. These are the canonical, path-integral, Weyl-Wigner and systematic formulations. Although all these formulations represent quantum mechanics on a phase space with the same deformed Heisenberg algebra, there are mathematical and conceptual differences which we discuss.

  10. An explicit finite element formulation for dynamic strain localization and damage evolution in metals

    SciTech Connect

    Mourad, Hashem M; Bronkhorst, Curt A; Addessio, Francis L

    2010-12-16

    An explicit finite element formulation, used to study the behavior and failure mechanisms of metallic materials under high strain rate loading, is presented. The formulation is based on the assumed-strain approach of Fish and Belytschko [1988], which allows localization bands to be embedded within an element, thereby alleviating mesh sensitivity and reducing the required computational effort. The behavior of the material outside localization bands (and of the virgin material prior to the onset of strain localization) is represented using a Gurson-type coupled plasticity-damage model based on the work of Johnson and Addessio [1988]. Assuming adiabatic conditions, the response of the localization band material is represented by a set of constitutive equations for large elasticviscoplastic deformations in metals at high strain rates and high homologous temperatures (see Brown et al. [1989]). Computational results are compared to experimental data for different metallic alloys to illustrate the advantages of the proposed modeling strategy.

  11. MATERIAL SHAPE OPTIMIZATION FOR FIBER REINFORCED COMPOSITES APPLYING A DAMAGE FORMULATION

    NASA Astrophysics Data System (ADS)

    Kato, Junji; Ramm, Ekkehard; Terada, Kenjiro; Kyoya, Takashi

    The present contribution deals with an optimization strategy of fiber reinforced composites. Although the methodical concept is very general we concentrate on Fiber Reinforced Concrete with a complex failure mechanism resulting from material brittleness of both constituents matrix and fibers. The purpose of the present paper is to improve the structural ductility of the fiber reinforced composites applying an optimization method with respect to the geometrical layout of continuous long textile fibers. The method proposed is achieved by applying a so-called embedded reinforcement formulation. This methodology is extended to a damage formulation in order to represent a realistic structural behavior. For the optimization problem a gradient-based optimization scheme is assumed. An optimality criteria method is applied because of its numerically high efficiency and robustness. The performance of the method is demonstrated by a series of numerical examples; it is verified that the ductility can be substantially improved.

  12. Damaging HMX/HTPB formulations: In-situ compression imaging using X-ray micro computed tomography

    SciTech Connect

    Patterson, Brian M.; Cordes, Nikolaus Lynn; Tappan, Bryce C.; Thompson, Darla Graff; Manner, Virginia Warren

    2015-04-17

    HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) is a powerful high explosive that is routinely used in formulations such as PBX 9501. Much remains to be learned about the performance and mechanical properties of HMX formulations such as these, particularly after dynamic damage has occurred. We have prepared formulations with HMX using hydroxyl terminated polybutadiene (HTPB) binder in order to form an explosive that is relatively insensitive to mild stimuli, analogous to PBXB-110 (different only is substitution of dioctyladipate (DO) for isodecyl pelargonate).

  13. Majorization formulation of uncertainty in quantum mechanics

    SciTech Connect

    Partovi, M. Hossein

    2011-11-15

    Heisenberg's uncertainty principle is formulated for a set of generalized measurements within the framework of majorization theory, resulting in a partial uncertainty order on probability vectors that is stronger than those based on quasientropic measures. The theorem that emerges from this formulation guarantees that the uncertainty of the results of a set of generalized measurements without a common eigenstate has an inviolable lower bound which depends on the measurement set but not the state. A corollary to this theorem yields a parallel formulation of the uncertainty principle for generalized measurements corresponding to the entire class of quasientropic measures. Optimal majorization bounds for two and three mutually unbiased bases in two dimensions are calculated. Similarly, the leading term of the majorization bound for position and momentum measurements is calculated which provides a strong statement of Heisenberg's uncertainty principle in direct operational terms. Another theorem provides a majorization condition for the least-uncertain generalized measurement of a given state with interesting physical implications.

  14. On the proper formulation of Maxwellian electrodynamics for continuum mechanics

    NASA Astrophysics Data System (ADS)

    Weile, Daniel S.; Hopkins, David A.; Gazonas, George A.; Powers, Brian M.

    2014-05-01

    Despite the importance of electromagnetomechanical physics to processes ranging from piezoelectricity to the dynamics of electron beams, confusion abounds in the continuum mechanics literature as to how Maxwell's equations of electrodynamics should be formulated in the material frame of continuum mechanics. Current formulations in the literature conflict as to the manner in which the authors define fields, derive constitutive relations, and interpret contradictory formulations. The difficulties persist even when the phenomena described are electrostatic. This paper will demonstrate that the perplexity arises from two sources: a misunderstanding of the limitations of material frame descriptions, and the failure to appreciate the centrality of relativity theory to the formulation of electrodynamic equations in the vicinity of mechanical motion. Two new formulations of Maxwell's equations are provided that avoid the paradoxes of earlier formulations and thus describe the physics clearly and without self-contradiction.

  15. [Mechanisms of electromagnetic radiation damaging male reproduction].

    PubMed

    Xue, Lei; Chen, Hao-Yu; Wang, Shui-Ming

    2012-08-01

    More and more evidence from over 50 years of researches on the effects of electromagnetic radiation on male reproduction show that a certain dose of electromagnetic radiation obviously damages male reproduction, particularly the structure and function of spermatogenic cells. The mechanisms of the injury may be associated with energy dysmetabolism, lipid peroxidation, abnormal expressions of apoptosis-related genes and proteins, and DNA damage.

  16. New Formulation of Statistical Mechanics Using Thermal Pure Quantum States

    NASA Astrophysics Data System (ADS)

    Sugiura, Sho; Shimizu, Akira

    2014-03-01

    We formulate statistical mechanics based on a pure quantum state, which we call a "thermal pure quantum (TPQ) state". A single TPQ state gives not only equilibrium values of mechanical variables, such as magnetization and correlation functions, but also those of genuine thermodynamic variables and thermodynamic functions, such as entropy and free energy. Among many possible TPQ states, we discuss the canonical TPQ state, the TPQ state whose temperature is specified. In the TPQ formulation of statistical mechanics, thermal fluctuations are completely included in quantum-mechanical fluctuations. As a consequence, TPQ states have much larger quantum entanglement than the equilibrium density operators of the ensemble formulation. We also show that the TPQ formulation is very useful in practical computations, by applying the formulation to a frustrated two-dimensional quantum spin system.

  17. Phototoxicity to the retina: mechanisms of damage.

    PubMed

    Glickman, Randolph D

    2002-01-01

    Light damage to the retina occurs through three general mechanisms involving thermal, mechanical, or photochemical effects. The particular mechanism activated depends on the wavelength and exposure duration of the injuring light. The transitions between the various light damage mechanism may overlap to some extent. Energy confinement is a key concept in understanding or predicting the type of damage mechanism produced by a given light exposure. As light energy (either from a laser or an incoherent source) is deposited in the retina, its penetration through, and its absorption in, various tissue compartments is determined by its wavelength. Strongly absorbing tissue components will tend to "concentrate" the light energy. The effect of absorbed light energy largely depends on the rate of energy deposition, which is correlated with the exposure duration. If the rate of energy deposition is too low to produce an appreciable temperature increase in the tissue, then any resulting tissue damage necessarily occurs because of chemical (oxidative) reactions induced by absorption of energetic photons (photochemical damage). If the rate of energy deposition is faster than the rate of thermal diffusion (thermal confinement), then the temperature of the exposed tissue rises. If a critical temperature is reached (typically about 10 degrees C above basal), then thermal damage occurs. If the light energy is deposited faster than mechanical relaxation can occur (stress confinement), then a thermoelastic pressure wave is produced, and tissue is disrupted by shear forces or by cavitation-nonlinear effects. Very recent evidence suggests that ultrashort laser pulses can produce tissue damage through nonlinear and photochemical mechanisms; the latter because of two-photon excitation of cellular chromophores. In addition to tissue damage caused directly by light absorption, light toxicity can be produced by the presence of photosensitizing agents. Drugs excited to reactive states by

  18. An axiomatic formulation of the Montevideo interpretation of quantum mechanics

    NASA Astrophysics Data System (ADS)

    Gambini, Rodolfo; García-Pintos, Luis Pedro; Pullin, Jorge

    We make a first attempt to axiomatically formulate the Montevideo interpretation of quantum mechanics. In this interpretation environmental decoherence is supplemented with loss of coherence due to the use of realistic clocks to measure time to solve the measurement problem. The resulting formulation is framed entirely in terms of quantum objects. Unlike in ordinary quantum mechanics, classical time only plays the role of an unobservable parameter. The formulation eliminates any privileged role of the measurement process giving an objective definition of when an event occurs in a system.

  19. Mechanisms of Diabetes-Induced Liver Damage

    PubMed Central

    Mohamed, Jamaludin; Nazratun Nafizah, A. H.; Zariyantey, A. H.; Budin, S. B.

    2016-01-01

    Diabetes mellitus is a non-communicable disease that occurs in both developed and developing countries. This metabolic disease affects all systems in the body, including the liver. Hyperglycaemia, mainly caused by insulin resistance, affects the metabolism of lipids, carbohydrates and proteins and can lead to non-alcoholic fatty liver disease, which can further progress to non-alcoholic steatohepatitis, cirrhosis and, finally, hepatocellular carcinomas. The underlying mechanism of diabetes that contributes to liver damage is the combination of increased oxidative stress and an aberrant inflammatory response; this activates the transcription of pro-apoptotic genes and damages hepatocytes. Significant involvement of pro-inflammatory cytokines—including interleukin (IL)-1β, IL-6 and tumour necrosis factor-α—exacerbates the accumulation of oxidative damage products in the liver, such as malondialdehyde, fluorescent pigments and conjugated dienes. This review summarises the biochemical, histological and macromolecular changes that contribute to oxidative liver damage among diabetic individuals. PMID:27226903

  20. Friction coefficients for mechanically damaged bovine articular cartilage.

    PubMed

    Shi, Liu; Brunski, Daniel B; Sikavitsas, Vassilios I; Johnson, Matthew B; Striolo, Alberto

    2012-07-01

    We used a pin-on-disc tribometer to measure the friction coefficient of both pristine and mechanically damaged cartilage samples in the presence of different lubricant solutions. The experimental set up maximizes the lubrication mechanism due to interstitial fluid pressurization. In phosphate buffer solution (PBS), the measured friction coefficient increases with the level of damage. The main result is that when poly(ethylene oxide) (PEO) or hyaluronic acid (HA) are dissolved in PBS, or when synovial fluid (SF) is used as lubricant, the friction coefficients measured for damaged cartilage samples are only slightly larger than those obtained for pristine cartilage samples, indicating that the surface damage is in part alleviated by the presence of the various lubricants. Among the lubricants considered, 100 mg/mL of 100,000 Da MW PEO in PBS appears to be as effective as SF. We attempted to discriminate the lubrication mechanism enhanced by the various compounds. The lubricants viscosity was measured at shear rates comparable to those employed in the friction experiments, and a quartz crystal microbalance with dissipation monitoring was used to study the adsorption of PEO, HA, and SF components on collagen type II adlayers pre-formed on hydroxyapatite. Under the shear rates considered the viscosity of SF is slightly larger than that of PBS, but lower than that of lubricant formulations containing HA or PEO. Neither PEO nor HA showed strong adsorption on collagen adlayers, while evidence of adsorption was found for SF. Combined, these results suggest that synovial fluid is likely to enhance boundary lubrication. It is possible that all three formulations enhance lubrication via the interstitial fluid pressurization mechanism, maximized by the experimental set up adopted in our friction tests.

  1. Non-Local Ductile Damage Formulations for Sheet Bulk Metal Forming

    NASA Astrophysics Data System (ADS)

    Beese, Steffen; Loehnert, Stefan; Wriggers, Peter

    2016-08-01

    A ductile damage model for sheet bulk metal forming processes and its efficient and accurate treatment in the context of the Finite Element Method is presented. The damage is introduced as a non-local field to overcome pathological mesh dependency. Since standard elements tend to show volumetric locking in the bulk forming process a mixed formulation is implemented in the commercial software simufact.forming to obtain better results.

  2. Significance of Strain in Formulation in Theory of Solid Mechanics

    NASA Technical Reports Server (NTRS)

    Patnaik, Surya N.; Coroneos, Rula M.; Hopkins, Dale A.

    2003-01-01

    The basic theory of solid mechanics was deemed complete circa 1860 when St. Venant provided the strain formulation or the field compatibility condition. The strain formulation was incomplete. The missing portion has been formulated and identified as the boundary compatibility condition (BCC). The BCC, derived through a variational formulation, has been verified through integral theorem and solution of problems. The BCC, unlike the field counterpart, do not trivialize when expressed in displacements. Navier s method and the stiffness formulation have to account for the extra conditions especially at the inter-element boundaries in a finite element model. Completion of the strain formulation has led to the revival of the direct force calculation methods: the Integrated Force Method (IFM) and its dual (IFMD) for finite element analysis, and the completed Beltrami-Michell formulation (CBMF) in elasticity. The benefits from the new methods in elasticity, in finite element analysis, and in design optimization are discussed. Existing solutions and computer codes may have to be adjusted for the compliance of the new conditions. Complacency because the discipline is over a century old and computer codes have been developed for half a century can lead to stagnation of the discipline.

  3. Scattering in the Euclidean formulation of relativistic quantum mechanics

    NASA Astrophysics Data System (ADS)

    Polyzou, Wayne

    2013-10-01

    Euclidean relativistic quantum mechanics is a formulation of relativistic quantum mechanics based on the Osterwalder-Schrader reconstruction theorem that exploits the logical independence of locality from the rest of the axioms of Euclidean field theory. I discuss the properties of Euclidean Green functions necessary for the existence of Møller wave operators and the construction of these wave operators in this formalism. Supported by the US Department of Energy, Grant - DE-AC02-81ER40038.

  4. DNA damage by bromate: mechanism and consequences.

    PubMed

    Ballmaier, Daniel; Epe, Bernd

    2006-04-17

    Exposure of mammalian cells to bromate (BrO3-) generates oxidative DNA modifications, in particular 7,8-dihydro-8-oxo-guanine (8-oxoG). The damaging mechanism is quite unique, since glutathione, which is protective against most oxidants and alkylating agents, mediates a metabolic activation, while bromate itself does not react directly with DNA. Neither enzymes nor transition metals are required as catalysts in the activation. The ultimate DNA damaging species has not yet been established, but experiments under cell-free conditions suggest that neither molecular bromine nor reactive oxygen species such as superoxide, hydrogen peroxide or singlet oxygen are involved. Rather bromine radicals (Br*) or oxides (BrO*, BrO2*) might be responsible. Compared to hypochlorite (ClO-), bromate is much less cytotoxic, probably because the former halite efficiently reacts with proteins and other vitally important cellular constituents. In consequence, oxidative DNA damage and the induction of mutations and micronuclei is easily detectable at non-cytotoxic concentrations of bromate, while DNA damage by hypochlorite is observed only at cytotoxic concentrations and follows a non-linear (hockey-stick-like) dose response. PMID:16490296

  5. Thermomechanical formulation of ductile damage coupled to nonlinear isotropic hardening and multiplicative viscoplasticity

    NASA Astrophysics Data System (ADS)

    Soyarslan, C.; Bargmann, S.

    2016-06-01

    In this paper, we present a thermomechanical framework which makes use of the internal variable theory of thermodynamics for damage-coupled finite viscoplasticity with nonlinear isotropic hardening. Damage evolution, being an irreversible process, generates heat. In addition to its direct effect on material's strength and stiffness, it causes deterioration of the heat conduction. The formulation, following the footsteps of Simó and Miehe (1992), introduces inelastic entropy as an additional state variable. Given a temperature dependent damage dissipation potential, we show that the evolution of inelastic entropy assumes a split form relating to plastic and damage parts, respectively. The solution of the thermomechanical problem is based on the so-called isothermal split. This allows the use of the model in 2D and 3D example problems involving geometrical imperfection triggered necking in an axisymmetric bar and thermally triggered necking of a 3D rectangular bar.

  6. Damage mechanics characterization on fatigue behavior of a solder joint material

    SciTech Connect

    Chow, C.L.; Yang, F.; Fang, H.E.

    1998-08-01

    This paper presents the first part of a comprehensive mechanics approach capable of predicting the integrity and reliability of solder joint material under fatigue loading without viscoplastic damage considerations. A separate report will be made to present a comprehensive damage model describing life prediction of the solder material under thermomechanical fatigue loading. The method is based on a theory of damage mechanics which makes possible a macroscopic description of the successive material deterioration caused by the presence of microcracks/voids in engineering materials. A damage mechanics model based on the thermodynamic theory of irreversible processes with internal state variables is proposed and used to provide a unified approach in characterizing the cyclic behavior of a typical solder material. With the introduction of a damage effect tensor, the constitutive equations are derived to enable the formulation of a fatigue damage dissipative potential function and a fatigue damage criterion. The fatigue evolution is subsequently developed based on the hypothesis that the overall damage is induced by the accumulation of fatigue and plastic damage. This damage mechanics approach offers a systematic and versatile means that is effective in modeling the entire process of material failure ranging from damage initiation and propagation leading eventually to macro-crack initiation and growth. As the model takes into account the load history effect and the interaction between plasticity damage and fatigue damage, with the aid of a modified general purpose finite element program, the method can readily be applied to estimate the fatigue life of solder joints under different loading conditions.

  7. Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering.

    PubMed

    Nims, Robert J; Durney, Krista M; Cigan, Alexander D; Dusséaux, Antoine; Hung, Clark T; Ateshian, Gerard A

    2016-02-01

    This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process. PMID:26855751

  8. Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering.

    PubMed

    Nims, Robert J; Durney, Krista M; Cigan, Alexander D; Dusséaux, Antoine; Hung, Clark T; Ateshian, Gerard A

    2016-02-01

    This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process.

  9. An Equilibrium Constitutive Model of Anisotropic Cartilage Damage to Elucidate Mechanisms of Damage Initiation and Progression.

    PubMed

    Stender, Michael E; Regueiro, Richard A; Klisch, Stephen M; Ferguson, Virginia L

    2015-08-01

    Traumatic injuries and gradual wear-and-tear of articular cartilage (AC) that can lead to osteoarthritis (OA) have been hypothesized to result from tissue damage to AC. In this study, a previous equilibrium constitutive model of AC was extended to a constitutive damage articular cartilage (CDAC) model. In particular, anisotropic collagen (COL) fibril damage and isotropic glycosaminoglycan (GAG) damage were considered in a 3D formulation. In the CDAC model, time-dependent effects, such as viscoelasticity and poroelasticity, were neglected, and thus all results represent the equilibrium response after all time-dependent effects have dissipated. The resulting CDAC model was implemented in two different finite-element models. The first simulated uniaxial tensile loading to failure, while the second simulated spherical indentation with a rigid indenter displaced into a bilayer AC sample. Uniaxial tension to failure simulations were performed for three COL fibril Lagrangian failure strain (i.e., the maximum elastic COL fibril strain) values of 15%, 30%, and 45%, while spherical indentation simulations were performed with a COL fibril Lagrangian failure strain of 15%. GAG damage parameters were held constant for all simulations. Our results indicated that the equilibrium postyield tensile response of AC and the macroscopic tissue failure strain are highly dependent on COL fibril Lagrangian failure strain. The uniaxial tensile response consisted of an initial nonlinear ramp region due to the recruitment of intact fibrils followed by a rapid decrease in tissue stress at initial COL fibril failure, as a result of COL fibril damage which continued until ultimate tissue failure. In the spherical indentation simulation, damage to both the COL fibril and GAG constituents was located only in the superficial zone (SZ) and near the articular surface with tissue thickening following unloading. Spherical indentation simulation results are in agreement with published experimental

  10. An Equilibrium Constitutive Model of Anisotropic Cartilage Damage to Elucidate Mechanisms of Damage Initiation and Progression.

    PubMed

    Stender, Michael E; Regueiro, Richard A; Klisch, Stephen M; Ferguson, Virginia L

    2015-08-01

    Traumatic injuries and gradual wear-and-tear of articular cartilage (AC) that can lead to osteoarthritis (OA) have been hypothesized to result from tissue damage to AC. In this study, a previous equilibrium constitutive model of AC was extended to a constitutive damage articular cartilage (CDAC) model. In particular, anisotropic collagen (COL) fibril damage and isotropic glycosaminoglycan (GAG) damage were considered in a 3D formulation. In the CDAC model, time-dependent effects, such as viscoelasticity and poroelasticity, were neglected, and thus all results represent the equilibrium response after all time-dependent effects have dissipated. The resulting CDAC model was implemented in two different finite-element models. The first simulated uniaxial tensile loading to failure, while the second simulated spherical indentation with a rigid indenter displaced into a bilayer AC sample. Uniaxial tension to failure simulations were performed for three COL fibril Lagrangian failure strain (i.e., the maximum elastic COL fibril strain) values of 15%, 30%, and 45%, while spherical indentation simulations were performed with a COL fibril Lagrangian failure strain of 15%. GAG damage parameters were held constant for all simulations. Our results indicated that the equilibrium postyield tensile response of AC and the macroscopic tissue failure strain are highly dependent on COL fibril Lagrangian failure strain. The uniaxial tensile response consisted of an initial nonlinear ramp region due to the recruitment of intact fibrils followed by a rapid decrease in tissue stress at initial COL fibril failure, as a result of COL fibril damage which continued until ultimate tissue failure. In the spherical indentation simulation, damage to both the COL fibril and GAG constituents was located only in the superficial zone (SZ) and near the articular surface with tissue thickening following unloading. Spherical indentation simulation results are in agreement with published experimental

  11. Damage mechanisms in shock wave lithotripsy (SWL)

    NASA Astrophysics Data System (ADS)

    Lokhandwalla, Murtuza

    Shock wave lithotripsy is a 'non-invasive' therapy for treating kidney stones. Focused shock waves fragment stones to a size that can be passed naturally. There is, however, considerable tissue injury, and the mechanisms of stone fragmentation and tissue injury are not well understood. This work investigates potential tissue damage mechanisms, with an aim towards enhancing stone fragmentation and minimizing tissue damage. Lysis of red blood cells (RBC's) due to in vitro exposure to shock waves was investigated. Fluid flow-fields induced by a non-uniform shock wave, as well as radial expansion/implosion of a bubble was hypothesized to cause cell lysis. Both the above flow-fields constitute an unsteady extensional flow, exerting inertial as well as viscous forces on the RBC membrane. The resultant membrane tension and the membrane areal strain due to the above flow-fields were estimated. Both were found to exert a significantly higher inertial force (50--100 mN/m) than the critical membrane tension (10 mN/m). Bubble-induced flow-field was estimated to last for a longer duration (˜1 microsec) compared to the shock-induced flow (˜1 ns) and hence, was predicted to be lytically more effective, in typical in vitro experimental conditions. However, in vivo conditions severely constrain bubble growth, and cell lysis due to shock-induced shear could be dominant. Hemolysis due to shock-induced shear, in absence of cavitation, was experimentally investigated. The lithotripter-generated shock wave was refocused by a parabolic reflector. This refocused wave-field had a tighter focus (smaller beam-width and a higher amplitude) than the lithotripter wave-field. Cavitation was eliminated by applying overpressure to the fluid. Acoustic emissions due to bubble activity were monitored by a novel passive cavitation detector (HP-PCD). Aluminum foils were also used to differentiate cavitational from non-cavitational mode of damage. RBC's were exposed to the reflected wave-field from

  12. Damage Mechanics Approach for Bearing Lifetime Prognostics

    NASA Astrophysics Data System (ADS)

    Qiu, Jing; Seth, Brij B.; Liang, Steven Y.; Zhang, Cheng

    2002-09-01

    The ability to achieve accurate bearing prognostics is critical to the optimal maintenance of rotating machinery in the interest of cost and productivity. However, techniques to real time predict the lifetime of a bearing under practical operating conditions have not been well developed. In this paper, a stiffness-based prognostic model for bearing systems based on vibration response analysis and damage mechanics is discussed. As the bearing system is considered as a single-degree-of-freedom vibratory system, its natural frequency and its acceleration amplitude at the natural frequency can be related to the system stiffness. On the other hand, the relationship between failure lifetime, running time and stiffness variation can be established from the damage mechanics. Combining the above two, the natural frequency and the acceleration amplitude of a bearing system can be related to its running time and failure lifetime. Thus, the failure lifetime of a bearing system can be predicted on-line based on vibration measurement. Experiments have been performed on a tapered roller bearing life testing stand under various operation conditions to calibrate and to validate the proposed model. The comparison between model-calculated data and experimental results indicates that this model can be used to effectively predict the failure lifetime and the remaining life of a bearing system.

  13. Protective effect of Xingnaojia formulation on rats with brain and liver damage caused by chronic alcoholism

    PubMed Central

    LI, SHUANG; WANG, SU; GUO, ZHI-GANG; HUANG, NING; ZHAO, FAN-RONG; ZHU, MO-LI; MA, LI-JUAN; LIANG, JIN-YING; ZHANG, YU-LIN; HUANG, ZHONG-LIN; WAN, GUANG-RUI

    2015-01-01

    The aim of this study was to observe the effect of a formulation of traditional Chinese medicine extracts known as Xingnaojia (XNJ) on the liver function, learning ability and memory of rats with chronic alcoholism and to verify the mechanism by which it protects the brain and liver. A rat model of chronic alcoholism was used in the study. The spatial learning ability and memory of the rats were tested. The rats were then sacrificed and their brains and hepatic tissues were isolated. The activity of superoxide dismutase (SOD) and levels of glutamate (Glu), N-methyl D-aspartate receptor subtype 2B (NR2B), cyclin-dependent kinase 5 (CDK5) and cannabinoid receptor 1 (CB1) in the hippocampus were analyzed. The ultrastructure of the hepatic tissue was observed by electron microscopy. In addition, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in serum were tested and the levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG) and total cholesterol (TCHOL) were analyzed. XNJ enhanced the learning and memory of rats with chronic alcoholism. Treatment with XNJ increased the activity of SOD, and decreased the expression levels of NR2B mRNA and NR2B, CB1 and CDK5 proteins in the brain tissues compared with those in the model rats. It also increased the activity of ALDH in the serum and liver, decreased the serum levels of LDL, TG and TCHOL and increased the serum level of HDL. These results indicate that XNJ exhibited a protective effect against brain and liver damage in rats with chronic alcoholism. PMID:26640531

  14. On certain fundamental issues in continuum damage mechanics

    NASA Astrophysics Data System (ADS)

    Voyiadjis, George Z.; Kattan, Peter I.

    2012-11-01

    In this article, we discuss three fundamental issues in continuum damage mechanics. First, we investigate the nature of the damage process. For this purpose, we dissect the expression of the effective stress into an infinite geometric series and introduce several stages of damage that we call primary damage, secondary damage, tertiary damage, etc. The second issue to be discussed is the problem of small damage. In this regard, we introduce a new definition of the damage variable that is suitable for small-damage cases. Finally, we discuss the new concept of undamageable materials. These are currently hypothetical materials that maintain a zero value of the damage variable throughout the deformation process. It is hoped that these proposed new types of materials will open the way to new areas of research in both damage mechanics and materials science.

  15. Mechanism of frost damage to concrete

    NASA Astrophysics Data System (ADS)

    Sun, Zhenhua

    We studied several topics that are important to explain the mechanisms of frost damage to concrete, including the volume change of concrete during freezing, the role of air voids in protecting concrete from frost damage, the pore structure of concrete, and the nucleation and propagation of ice in concrete. By combining calorimetric measurements with dilatometry, we were able to calculate the contributions of thermal expansion, pore pressure, and crystallization pressure of ice to the strain observed in a mortar during freezing/thawing cycles. Air-entrained mortars contract upon freezing due to the cryo-suction effect, while non-air-entrained mortars expand primarily due to hydraulic pressure. Based on the theory originally proposed by Powers and Helmuth, we show that the poromechanical calculations account quantitatively for the contraction of samples with air entrainment, which is shown to quantitatively account for a reduction of salt scaling damage based on the glue-spall theory. The method of thermoporometry (TPM) that we used to study the pore structure of concrete is also discussed. In a study of ice propagation inside concrete, we re-examined experiments by Helmuth [Proc. 4th Int. Cong. Chem. Cement, NBS Monog. 43, Vol. II (National Bureau of Standards, Washington, D.C., 1962) pp. 855--869] from which he concluded that ice grows in the pores of cement paste under heat-flow control, and that the internal temperature rises to the melting point given by the Gibbs-Thomson equation. Using experimental and computational methods, we find that his conclusions are correct, but the growth rates he reports are misleading. Our experiment reveals the true growth rate, which is about three times smaller than found by Helmuth. The dendritic morphology explains how fast constant growth rates can occur when the interior temperature of the sample is very near the melting point: the temperature at the tip of the dendrite is a few degrees below the melting point, but the liquid

  16. Formulation and Mechanical Properties of LLM-105 PBXs

    SciTech Connect

    Hoffman, D M; Lorenz, K T; Cunningham, B; Gagliardi, F

    2008-04-03

    Eight different polymer binders were formulated with bimodal distributions of 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) in 5/95 weight ratio of polymer to explosive at the 25 gram level. The polymers evaluated included: Kel-F 800, Viton A, Oxy 461, Cytop A, Hyflon AD 60, Hytemp 5545, Technoflon PFR 91 and Technoflon P 459. LLM-105 had an average particle size of 35.6 {+-} 0.6 {micro}m. This material was ground in a ball mill for 24 h to achieve a particle size of 0.72 {+-} 0.02 {micro}m. Small angle light scattering measurements were used to obtain particle size distributions on both ground and unground LLM-105. Optical microscopy was used to characterize the morphology of the crystals. Bimodal mixes of approximately 75/25% coarse to fine LLM-105 were used in all formulations. Cylinders 1.27 cm diameter by 2.54 cm long were compression molded using 3 three-minute cycles at 105 C, except in the case of Cytop and Hyflon formulations which were molded at {approx}130 C. Densities varied between 94-98% of theoretical maximum. Stress strain measurements were made in compression at -30, ambient and 74 C at a strain rate of 0.0001 sec{sup -1}. As expected, the mechanical strength scaled with temperature depending on the glass transition temperature of the polymer.

  17. Skin permeation mechanism of aceclofenac using novel nanoemulsion formulation.

    PubMed

    Shakeel, F; Baboota, S; Ahuja, A; All, J; Shafiq, S

    2008-08-01

    The aim of the present study was to investigate the skin permeation mechanism of aceclofenac using a novel nanoemulsion formulation. An optimized oil-in-water nanoemulsion of aceclofenac was prepared by the spontaneous emulsification method. The optimized nanoemulsion contained 2% w/w aceclofenac, 10% w/w Labrafil, 5% w/w Triacetin, 35.33% w/w Tween 80, 17.66% w/w Transcutol P and 32% w/w distilled water. The skin permeation mechanism was evaluated by FTIR spectroscopy, DSC thermography, activation energy measurement and histopathological examination. FTIR spectra of skin treated with the nanoemulsion formulation indicated breaking of the hydrogen bond network at the head of ceramides. DSC thermograms indicated that intracellular transport could be a possible mechanism of permeation enhancement and that permeation occurred due to the extraction of SC lipids by the nanoemulsion. The significant decrease in activation energy for aceclofenac permeation across rat skin indicated that the SC lipid bilayers were significantly disrupted (p < 0.05). Photomicrography of skin showed disruption and extraction of lipid bilayers as distinct voids and empty spaces visible in the epidermal region. Overall these findings indicated that nanoemulsions can be successfully used to enhance skin permeation of drugs.

  18. An homogenization-based hyperelastic damage model: formulation and application to an EPDM/PP composite

    NASA Astrophysics Data System (ADS)

    Bouchart, Vanessa; Brieu, Mathias; Kondo, Djimedo; Naït-Abdelaziz, Moussa

    2008-05-01

    The present Note concerns the formulation, implementation and a first application of a micromechanically based hyperelastic damage model. The approach is based on the second order homogenization method proposed by Lopez-Pamies and Ponte Castañeda (2000) for hyperelastic composites and recently developed by Lopez-Pamies and Ponte Castañeda (2007) in the case of porous elastomers. We first implement the method and proceed to its verification by comparison with Finite Element simulations on a unit cell. Taking advantage of this validation and by using standard thermodynamics arguments, we propose an hyperelastic damage model founded on voids growth phenomena. Finally, we provide an example of validation of the model by comparison with experimental data obtained on an EPDM/PP composite. To cite this article: V. Bouchart et al., C. R. Mecanique 336 (2008).

  19. Damage and fracture mechanics of composite materials

    NASA Astrophysics Data System (ADS)

    Abdussalam, Saleh Ramadan

    The design of structural systems in the aerospace industry has been characterized by a continuing search for strong, yet lightweight, materials to achieve maximum payload capability for minimum weight. In recent years, this search has led to a wide use of fiber reinforced composites, such as carbon, glass and kevelar based composites. Comparison of these new materials with the traditional ones (metals) according to the basic properties, such as density, elastic modulus and also long-time and short-time strength, shows their superiority over traditional materials, when weight is a major design factor, like in the aerospace industry. Most composite materials of interest to aerospace applications have been adequately characterized under static loading conditions. Related work to study their fracture behaviour has been limited. Since most failure mechanisms involve crack growth and/or delamination, design of such components requires knowledge and understanding of their fracture properties. This thesis includes an experimental and analytical investigation of fracture characteristics of composite materials. The post-peak response of notched specimens subjected to uniaxial cyclic loading is established to evaluate the fracture energy associated with progressive matrix damage and subsequent crack growth. A total of 75 uniaxial tension specimens were tested. The experimental work consisted of first testing several un-notched specimens with different thickness (number of layers) to determine the initial and secondary elastic modulus as well as the tensile strength. The investigation studied the effect of the various fracture parameters, including thickness, fiber orientation, and crack width ratio (a/w) on the behaviour of crack propagation, peak load, and post-peak response. The specimens used in this research were prepared using the vacuum bagging technique, with a chosen number of fiber glass cloth layers and fiber orientation. The experimental results provided

  20. Mechanical Properties of Shock-Damaged Rocks

    NASA Technical Reports Server (NTRS)

    He, Hongliang; Ahrens, T. J.

    1994-01-01

    Stress-strain tests were performed both on shock-damaged gabbro and limestone. The effective Young's modulus decreases with increasing initial damage parameter value, and an apparent work-softening process occurs prior to failure. To further characterize shock-induced microcracks, the longitudinal elastic wave velocity behavior of shock-damaged gabbro in the direction of compression up to failure was measured using an acoustic transmission technique under uniaxial loading. A dramatic increase in velocity was observed for the static compressive stress range of 0-50 MPa. Above that stress range, the velocity behavior of lightly damaged (D(sub 0) less than 0.1) gabbro is almost equal to unshocked gabbro. The failure strength of heavily-damaged (D(sub 0) greater than 0.1) gabbro is approx. 100-150 MPa, much lower than that of lightly damaged and unshocked gabbros (approx. 230-260 MPa). Following Nur's theory, the crack shape distribution was analyzed. The shock-induced cracks in gabbro appear to be largely thin penny-shaped cracks with c/a values below 5 x 10(exp -4). Moreover, the applicability of Ashby and Sammis's theory relating failure strength and damage parameter of shock-damaged rocks was examined and was found to yield a good estimate of the relation of shock-induced deficit in elastic modulus with the deficit in compressive strength.

  1. A signed particle formulation of non-relativistic quantum mechanics

    SciTech Connect

    Sellier, Jean Michel

    2015-09-15

    A formulation of non-relativistic quantum mechanics in terms of Newtonian particles is presented in the shape of a set of three postulates. In this new theory, quantum systems are described by ensembles of signed particles which behave as field-less classical objects which carry a negative or positive sign and interact with an external potential by means of creation and annihilation events only. This approach is shown to be a generalization of the signed particle Wigner Monte Carlo method which reconstructs the time-dependent Wigner quasi-distribution function of a system and, therefore, the corresponding Schrödinger time-dependent wave-function. Its classical limit is discussed and a physical interpretation, based on experimental evidences coming from quantum tomography, is suggested. Moreover, in order to show the advantages brought by this novel formulation, a straightforward extension to relativistic effects is discussed. To conclude, quantum tunnelling numerical experiments are performed to show the validity of the suggested approach.

  2. Penetration study of formulated nanosized titanium dioxide in models of damaged and sun-irradiated skins.

    PubMed

    Miquel-Jeanjean, Corinne; Crépel, Frédéric; Raufast, Véronique; Payre, Bruno; Datas, Lucien; Bessou-Touya, Sandrine; Duplan, Hélène

    2012-01-01

    Inorganic ultraviolet filters such as titanium dioxide (TiO(2)), safe to use on healthy skin, are often applied on compromised and irradiated skin. The aim of this study was to evaluate in vitro the cutaneous penetration of TiO(2) nanoparticles (≥20 nm primary size), included in a sunscreen, in intact, damaged, irradiated, and damaged/irradiated pigskin. Cutaneous penetration and localization of TiO(2) after a 24-h sunscreen application were investigated quantitatively using inductively coupled plasma-mass spectrometry, and qualitatively using transmission electron microscopy (TEM). Elemental identity of the nanoparticles was evaluated by TEM-coupled Energy Dispersive X-ray analysis (TEM-EDX). In intact and damaged/irradiated skins, 102.35±4.20% and 102.84±5.67% of the titanium deposited, respectively, were found at the surface and stratum corneum (SC), whereas only 0.19±0.15% and 0.39±0.39% were found in the viable epidermis and dermis and no titanium was detected in the receptor fluid. TEM-EDX analysis confirmed the presence of titanium in the aggregates formed by TiO(2) at the SC surface, as already characterized in the sunscreen formulation. TiO(2) nanoparticles included in a sunscreen thus remain in the uppermost layers of the SC, whether in intact skin or in compromised and/or skin exposed to simulated solar radiation.

  3. Noncommutative spaces and covariant formulation of statistical mechanics

    NASA Astrophysics Data System (ADS)

    Hosseinzadeh, V.; Gorji, M. A.; Nozari, K.; Vakili, B.

    2015-07-01

    We study the statistical mechanics of a general Hamiltonian system in the context of symplectic structure of the corresponding phase space. This covariant formalism reveals some interesting correspondences between properties of the phase space and the associated statistical physics. While topology, as a global property, turns out to be related to the total number of microstates, the invariant measure which assigns a priori probability distribution over the microstates is determined by the local form of the symplectic structure. As an example of a model for which the phase space has a nontrivial topology, we apply our formulation on the Snyder noncommutative space-time with de Sitter four-momentum space and analyze the results. Finally, in the framework of such a setup, we examine our formalism by studying the thermodynamical properties of a harmonic oscillator system.

  4. Induction of microtubule damage in Allium cepa meristematic cells by pharmaceutical formulations of thiabendazole and griseofulvin.

    PubMed

    Andrioli, Nancy B; Soloneski, Sonia; Larramendy, Marcelo L; Mudry, Marta D

    2014-09-15

    Microtubules (MT) are formed by the assembly of α- and β-tubulins and MT-associated proteins. We characterized the effects of pharmaceutical formulations containing the microtubule disruptors thiabendazole (TBZ) and griseofulvin (GF) on the mitotic machinery of plant (A. cepa) meristematic cells. GF concentrations between 10 and 250 μg/ml were tested. GF induced mitotic index inhibition and genotoxic effects, including chromosome fragments, bridges, lagged chromosomes, C-metaphases, tripolar cell division, disorganized anaphases and nuclear abnormalities in interphase cells. Efects on the mitotic machinery were studied by direct immunofluorescence with β-tubulin labeling and by DNA counterstaining with 4',6-diamidino-2-phenylindole (DAPI). Exposure of meristematic root cells to TBZ or GF, 100 μg/ml, caused microtubular damage which led to abnormal MT arrays. Our results suggest that GF induces abnormalities in spindle symmetry/polarity, while TBZ causes chromosome missegregation, polyploidy, and lack of cytokinesis.

  5. Non-Local Damage Modelling of Sheet Metal Forming Processes with ALE Formulation

    NASA Astrophysics Data System (ADS)

    Adetoro, O. B.; Cardoso, Rui P. R.

    2016-08-01

    The modelling of material degradation due to nucleation, growth and coalescence of micro-voids is vital in sheet metal forming process due to the large deformation typically experienced by the part. Nonlocal damage modelling or nonlocal continuum is gaining a lot of interest because it is an effective approach to modelling the strain-softening, whilst avoiding the spurious localization that gives rise to strong mesh sensitivity in numerical computations. However to accurately resolve the evolving narrow bands of highly localised strain, it is necessary to use sufficient computational grids. In this paper an ALE formulation is used for modelling the localization pattern. An approach for relocating the node points is presented and explored.

  6. 3D Progressive Damage Modeling for Laminated Composite Based on Crack Band Theory and Continuum Damage Mechanics

    NASA Technical Reports Server (NTRS)

    Wang, John T.; Pineda, Evan J.; Ranatunga, Vipul; Smeltzer, Stanley S.

    2015-01-01

    A simple continuum damage mechanics (CDM) based 3D progressive damage analysis (PDA) tool for laminated composites was developed and implemented as a user defined material subroutine to link with a commercially available explicit finite element code. This PDA tool uses linear lamina properties from standard tests, predicts damage initiation with an easy-to-implement Hashin-Rotem failure criteria, and in the damage evolution phase, evaluates the degradation of material properties based on the crack band theory and traction-separation cohesive laws. It follows Matzenmiller et al.'s formulation to incorporate the degrading material properties into the damaged stiffness matrix. Since nonlinear shear and matrix stress-strain relations are not implemented, correction factors are used for slowing the reduction of the damaged shear stiffness terms to reflect the effect of these nonlinearities on the laminate strength predictions. This CDM based PDA tool is implemented as a user defined material (VUMAT) to link with the Abaqus/Explicit code. Strength predictions obtained, using this VUMAT, are correlated with test data for a set of notched specimens under tension and compression loads.

  7. Phenomenological approach to mechanical damage growth analysis.

    PubMed

    Pugno, Nicola; Bosia, Federico; Gliozzi, Antonio S; Delsanto, Pier Paolo; Carpinteri, Alberto

    2008-10-01

    The problem of characterizing damage evolution in a generic material is addressed with the aim of tracing it back to existing growth models in other fields of research. Based on energetic considerations, a system evolution equation is derived for a generic damage indicator describing a material system subjected to an increasing external stress. The latter is found to fit into the framework of a recently developed phenomenological universality (PUN) approach and, more specifically, the so-called U2 class. Analytical results are confirmed by numerical simulations based on a fiber-bundle model and statistically assigned local strengths at the microscale. The fits with numerical data prove, with an excellent degree of reliability, that the typical evolution of the damage indicator belongs to the aforementioned PUN class. Applications of this result are briefly discussed and suggested. PMID:18999489

  8. Formulation and computational aspects of plasticity and damage models with application to quasi-brittle materials

    SciTech Connect

    Chen, Z.; Schreyer, H.L.

    1995-09-01

    The response of underground structures and transportation facilities under various external loadings and environments is critical for human safety as well as environmental protection. Since quasi-brittle materials such as concrete and rock are commonly used for underground construction, the constitutive modeling of these engineering materials, including post-limit behaviors, is one of the most important aspects in safety assessment. From experimental, theoretical, and computational points of view, this report considers the constitutive modeling of quasi-brittle materials in general and concentrates on concrete in particular. Based on the internal variable theory of thermodynamics, the general formulations of plasticity and damage models are given to simulate two distinct modes of microstructural changes, inelastic flow and degradation of material strength and stiffness, that identify the phenomenological nonlinear behaviors of quasi-brittle materials. The computational aspects of plasticity and damage models are explored with respect to their effects on structural analyses. Specific constitutive models are then developed in a systematic manner according to the degree of completeness. A comprehensive literature survey is made to provide the up-to-date information on prediction of structural failures, which can serve as a reference for future research.

  9. Bohmian mechanics with complex action: a new trajectory-based formulation of quantum mechanics.

    PubMed

    Goldfarb, Yair; Degani, Ilan; Tannor, David J

    2006-12-21

    In recent years there has been a resurgence of interest in Bohmian mechanics as a numerical tool because of its local dynamics, which suggest the possibility of significant computational advantages for the simulation of large quantum systems. However, closer inspection of the Bohmian formulation reveals that the nonlocality of quantum mechanics has not disappeared-it has simply been swept under the rug into the quantum force. In this paper we present a new formulation of Bohmian mechanics in which the quantum action, S, is taken to be complex. This leads to a single equation for complex S, and ultimately complex x and p but there is a reward for this complexification-a significantly higher degree of localization. The quantum force in the new approach vanishes for Gaussian wave packet dynamics, and its effect on barrier tunneling processes is orders of magnitude lower than that of the classical force. In fact, the current method is shown to be a rigorous extension of generalized Gaussian wave packet dynamics to give exact quantum mechanics. We demonstrate tunneling probabilities that are in virtually perfect agreement with the exact quantum mechanics down to 10(-7) calculated from strictly localized quantum trajectories that do not communicate with their neighbors. The new formulation may have significant implications for fundamental quantum mechanics, ranging from the interpretation of non-locality to measures of quantum complexity.

  10. Mechanism of lung damage in explosive decompression.

    PubMed

    Topliff, E D

    1976-05-01

    It is known that pressure equalization via the trachea may diminish or prevent lung damage in explosive decompression. In this report, evidence is presented which demonstrates that closure of the trachea does not affect lethality in mice exposed to maximally rapid decompression. This observation suggests that in maximally rapid decompression the lungs and thorax may be treated as a closed system to which Boyle's Law might be applicable. PMID:1275842

  11. Damage Evolution On Mechanical Parts Under Cyclic Loading

    NASA Astrophysics Data System (ADS)

    Lestriez, P.; Bogard, F.; Shan, J. L.; Guo, Y. Q.

    2007-05-01

    This paper presents a fatigue damage model, based on the continuum damage mechanics and general thermodynamic theory, proposed by Lemaitre and Chaboche, for rolling bearings under very numerous loading cycles. A flow surface of fatigue using the Sines criterion is adopted. The coupling between the hardening plasticity and damage effects is considered in the constitutive equations. An explicit algorithm of weak coupling leads to a calculation very fast. This fatigue damage model is implemented into Abaqus/Explicit using a Vumat user's subroutine. Moreover, the damage variable in function of time is transformed into a function of number of cycles. An algorithm of cycle jump, with a criterion for choosing the number increment of cycles, is proposed, which allows to largely reduce the CPU time. The present damage simulation allows to determine the lifetime of mechanical parts under cyclic loading.

  12. A coupled mechanical and chemical damage model for concrete affected by alkali–silica reaction

    SciTech Connect

    Pignatelli, Rossella; Comi, Claudia; Monteiro, Paulo J.M.

    2013-11-15

    To model the complex degradation phenomena occurring in concrete affected by alkali–silica reaction (ASR), we formulate a poro-mechanical model with two isotropic internal variables: the chemical and the mechanical damage. The chemical damage, related to the evolution of the reaction, is caused by the pressure generated by the expanding ASR gel on the solid concrete skeleton. The mechanical damage describes the strength and stiffness degradation induced by the external loads. As suggested by experimental results, degradation due to ASR is considered to be localized around reactive sites. The effect of the degree of saturation and of the temperature on the reaction development is also modeled. The chemical damage evolution is calibrated using the value of the gel pressure estimated by applying the electrical diffuse double-layer theory to experimental values of the surface charge density in ASR gel specimens reported in the literature. The chemo-damage model is first validated by simulating expansion tests on reactive specimens and beams; the coupled chemo-mechanical damage model is then employed to simulate compression and flexure tests results also taken from the literature. -- Highlights: •Concrete degradation due to ASR in variable environmental conditions is modeled. •Two isotropic internal variables – chemical and mechanical damage – are introduced. •The value of the swelling pressure is estimated by the diffuse double layer theory. •A simplified scheme is proposed to relate macro- and microscopic properties. •The chemo-mechanical damage model is validated by simulating tests in literature.

  13. Oxidative damage to RNA: mechanisms, consequences, and diseases

    PubMed Central

    Kong, Qiongman

    2010-01-01

    Overproduction of free radicals can damage cellular components resulting in progressive physiological dysfunction, which has been implicated in many human diseases. Oxidative damage to RNA received little attention until the past decade. Recent studies indicate that RNA, such as messenger RNA and ribosomal RNA, is very vulnerable to oxidative damage. RNA oxidation is not a consequence of dying cells but an early event involved in pathogenesis. Oxidative modification to RNA results in disturbance of the translational process and impairment of protein synthesis, which can cause cell deterioration or even cell death. In this review, we discuss the mechanisms of oxidative damage to RNA and the possible biological consequences of damaged RNA. Furthermore, we review recent evidence suggesting that oxidative damage to RNA may contribute to progression of many human diseases. PMID:20148281

  14. Laser damage mechanisms in conductive widegap semiconductor films.

    PubMed

    Yoo, Jae-Hyuck; Menor, Marlon G; Adams, John J; Raman, Rajesh N; Lee, Jonathan R I; Olson, Tammy Y; Shen, Nan; Suh, Joonki; Demos, Stavros G; Bude, Jeff; Elhadj, Selim

    2016-08-01

    Laser damage mechanisms of two conductive wide-bandgap semiconductor films - indium tin oxide (ITO) and silicon doped GaN (Si:GaN) were studied via microscopy, spectroscopy, photoluminescence (PL), and elemental analysis. Nanosecond laser pulse exposures with a laser photon energy (1.03 eV, 1064 nm) smaller than the conductive films bandgaps were applied and radically different film damage morphologies were produced. The laser damaged ITO film exhibited deterministic features of thermal degradation. In contrast, laser damage in the Si:GaN film resulted in highly localized eruptions originating at interfaces. For ITO, thermally driven damage was related to free carrier absorption and, for GaN, carbon complexes were proposed as potential damage precursors or markers. PMID:27505731

  15. A damage mechanics based approach to structural deterioration and reliability

    SciTech Connect

    Bhattcharya, B.; Ellingwood, B.

    1998-02-01

    Structural deterioration often occurs without perceptible manifestation. Continuum damage mechanics defines structural damage in terms of the material microstructure, and relates the damage variable to the macroscopic strength or stiffness of the structure. This enables one to predict the state of damage prior to the initiation of a macroscopic flaw, and allows one to estimate residual strength/service life of an existing structure. The accumulation of damage is a dissipative process that is governed by the laws of thermodynamics. Partial differential equations for damage growth in terms of the Helmholtz free energy are derived from fundamental thermodynamical conditions. Closed-form solutions to the equations are obtained under uniaxial loading for ductile deformation damage as a function of plastic strain, for creep damage as a function of time, and for fatigue damage as function of number of cycles. The proposed damage growth model is extended into the stochastic domain by considering fluctuations in the free energy, and closed-form solutions of the resulting stochastic differential equation are obtained in each of the three cases mentioned above. A reliability analysis of a ring-stiffened cylindrical steel shell subjected to corrosion, accidental pressure, and temperature is performed.

  16. Ontogenetic contingency of tolerance mechanisms in response to apical damage

    PubMed Central

    Gruntman, Michal; Novoplansky, Ariel

    2011-01-01

    Background and Aims Plants are able to tolerate tissue loss through vigorous branching which is often triggered by release from apical dominance and activation of lateral meristems. However, damage-induced branching might not be a mere physiological outcome of released apical dominance, but an adaptive response to environmental signals, such as damage timing and intensity. Here, branching responses to both factors were examined in the annual plant Medicago truncatula. Methods Branching patterns and allocation to reproductive traits were examined in response to variable clipping intensities and timings in M. truncatula plants from two populations that vary in the onset of reproduction. Phenotypic selection analysis was used to evaluate the strength and direction of selection on branching under the damage treatments. Key Results Plants of both populations exhibited an ontogenetic shift in tolerance mechanisms: while early damage induced greater meristem activation, late damage elicited investment in late-determined traits, including mean pod and seed biomass, and supported greater germination rates. Severe damage mostly elicited simultaneous development of multiple-order lateral branches, but this response was limited to early damage. Selection analyses revealed positive directional selection on branching in plants under early- compared with late- or no-damage treatments. Conclusions The results demonstrate that damage-induced meristem activation is an adaptive response that could be modified according to the plant's developmental stage, severity of tissue loss and their interaction, stressing the importance of considering these effects when studying plastic responses to apical damage. PMID:21873259

  17. Continuous damage parameter calculation under thermo-mechanical random loading

    PubMed Central

    Nagode, Marko

    2014-01-01

    The paper presents a method on how the mean stress effect on fatigue damage can be taken into account under an arbitrary low cycle thermo-mechanical loading. From known stress, elastoplastic strain and temperature histories the cycle amplitudes and cycle mean values are extracted and the damage parameter is computed. In contrast to the existing methods the proposed method enables continuous damage parameter computation without the need of waiting for the cycles to close. The limitations of the standardized damage parameters are thus surpassed. The damage parameters derived initially for closed and isothermal cycles assuming that the elastoplastic stress–strain response follows the Masing and memory rules can now be used to take the mean stress effect into account under an arbitrary low cycle thermo-mechanical loading. The method includes:•stress and elastoplastic strain history transformation into the corresponding amplitude and mean values;•stress and elastoplastic strain amplitude and mean value transformation into the damage parameter amplitude history;•damage parameter amplitude history transformation into the damage parameter history. PMID:26150939

  18. Micromechanical Modeling of Impact Damage Mechanisms in Unidirectional Composite Laminates

    NASA Astrophysics Data System (ADS)

    Meng, Qinghua; Wang, Zhenqing

    2016-05-01

    Composite laminates are susceptible to the transverse impact loads resulting in significant damage such as matrix cracking, fiber breakage and delamination. In this paper, a micromechanical model is developed to predict the impact damage of composite laminates based on microstructure and various failure models of laminates. The fiber and matrix are represented by the isotropic and elastic-plastic solid, and their impact failure behaviors are modeled based on shear damage model. The delaminaton failure is modeling by the interface element controlled by cohesive damage model. Impact damage mechanisms of laminate are analyzed by using the micromechanical model proposed. In addition, the effects of impact energy and laminated type on impact damage behavior of laminates are investigated. Due to the damage of the surrounding matrix near the impact point caused by the fiber deformation, the surface damage area of laminate is larger than the area of ​​impact projectile. The shape of the damage area is roughly rectangle or elliptical with the major axis extending parallel to the fiber direction in the surface layer of laminate. The alternating laminated type with two fiber directions is more propitious to improve the impact resistance of laminates.

  19. Numerical Modelling and Damage Assessment of Rotary Wing Aircraft Cabin Door Using Continuum Damage Mechanics Model

    NASA Astrophysics Data System (ADS)

    Boyina, Gangadhara Rao T.; Rayavarapu, Vijaya Kumar; Subba Rao, V. V.

    2016-08-01

    The prediction of ultimate strength remains the main challenge in the simulation of the mechanical response of composite structures. This paper examines continuum damage model to predict the strength and size effects for deformation and failure response of polymer composite laminates when subjected to complex state of stress. The paper also considers how the overall results of the exercise can be applied in design applications. The continuum damage model is described and the resulting prediction of size effects are compared against the standard benchmark solutions. The stress analysis for strength prediction of rotary wing aircraft cabin door is carried out. The goal of this study is to extend the proposed continuum damage model such that it can be accurately predict the failure around stress concentration regions. The finite element-based continuum damage mechanics model can be applied to the structures and components of arbitrary configurations where analytical solutions could not be developed.

  20. Biconvex intraocular lenses and Nd:YAG capsulotomy: Experimental comparison of surface damage with different poly(methyl methacrylate) formulations

    SciTech Connect

    Downing, J.E.; Alberhasky, M.T. )

    1990-11-01

    Biconvex posterior chamber lenses have optical advantages and decrease the risk of capsular opacification, but they are more likely to be pitted during ND:YAG capsulotomy because of apposition of the lens to the capsule. This study reports the likelihood of surface damage to different formulations of poly(methyl methacrylate) at the energy levels required to open posterior capsules. Molded lenses are more easily damaged than higher molecular weight lathe-cut materials (P less than .01), as expected. However, by keeping energy output low, even injection-molded lenses showed minimal damage, with mean pit size 39 +/- 39 microns at 1 mJ. By using a converging contact lens, low power, and keeping the focus behind the capsule, damage to all materials tested should be clinically insignificant.

  1. Characterizing mechanical effects of aging damage

    SciTech Connect

    Sewell, T.D.; Chen, S.P.; Schoonover, J.R.; Trent, B.C.; Howe, P.M.; Hjelm, R.P.; Browning, R.V.

    1998-12-01

    This is the final report of a two-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The goal was to develop and apply several different experimental and theoretical/computational tools to better understand physical and chemical aging phenomena in plastic-bonded high explosives, and to develop a methodology for predicting the likely effects of aging on the mechanical properties of the composite based on input from these fundamental studies. Initial comparisons were done for spectra of fresh and aged Esane, as well as PBX-9501, and the authors found differences in the carbonyl region of the spectrum, which possibly reflect differences in hydrogen bonding due to aging phenomena. The micromechanical model of composites was extended to study various volume fractions of HMX with binders. The results showed that, as the binder fraction increases, there is a decrease in the maximum stress that can be supported but an increase in the percent strain at final fracture. A more realistic microstructural model was obtained through the use of a phase field model. Using this model, the authors have studied the microstructural evolution as a function of the grain boundary energy vs. misorientation relationship. The initial results indicate that there are some changes in the grain growth rate when the grain-boundary energy dependence on the angle is not constant. They also find that solute tends to segregate at the grain boundary and slows the grain growth kinetics.

  2. Are DNA-damaging effects induced by herbicide formulations (Roundup® and Garlon®) in fish transient and reversible upon cessation of exposure?

    PubMed

    Guilherme, S; Santos, M A; Gaivão, I; Pacheco, M

    2014-10-01

    Owing to the seasonality of crop cultivation and subsequent periodic/seasonal application of herbicides, their input to the aquatic systems is typically intermittent. Consequently, exposure of fish to this type of contaminants can be short and followed by a period of permanence in non-contaminated areas. Thus, the assessment of genotoxic endpoints in fish after removal of the contamination source appears as a crucial step to improve the knowledge on the dynamics of herbicide genotoxicity, as well as to determine the actual magnitude of risk posed by these agrochemicals. Therefore, the present study intended to shed light on the ability of fish to recover from the DNA damage induced by short-term exposures to the herbicide formulations Roundup(®) (glyphosate-based) and Garlon(®) (triclopyr-based) upon the exposure cessation. European eel (Anguilla anguilla) was exposed to the above commercial formulations for 3 days, and allowed to recover for 1, 7 and 14 days (post-exposure period). The comet assay was used to identify the DNA damage in blood cells during both exposure and post-exposure periods. As an attempt to clarify the DNA damaging mechanisms involved, an extra-step including the incubation of the nucleotides with DNA lesion-specific repair enzyme was added to the standard comet. The genotoxic potential of both herbicides was confirmed, concerning the exposure period. In addition, the involvement of oxidative DNA damage on the action of Roundup(®) (pointed out as pyrimidine bases oxidation) was demonstrated, while for Garlon(®) this damaging mechanism was less evident. Fish exposed to Garlon(®), though presenting some evidence towards a tendency of recovery, did not achieve a complete restoration of DNA integrity. In what concerns to Roundup(®), a recovery was evident when considering non-specific DNA damage on day 14 post-exposure. In addition, this herbicide was able to induce a late oxidative DNA damage (day 14). Blood cells of A. anguilla exposed to

  3. Mechanisms for radiation damage in DNA. Final report, June 1, 1986--August 31, 1996

    SciTech Connect

    Sevilla, M.D.

    1996-08-01

    Over the last 10 years significant advances have been made impacting the understanding of radiation damage to DNA. The principal objective of this work was the elucidation of the fundamental mechanisms of radiation damage to DNA through the direct and indirect effects. Recently the work concentrated on the direct effect of radiation damage on DNA. The objective was to elucidate the ultimate radiation chemical damage to DNA arising from the direct effect. In this effort the focus was on the application of three techniques. ESR spectroscopic measurement of initial radicals formed in DNA and its hydration layer at low temperatures. Ab initio molecular orbital calculations were employed to give highly accurate theoretical predictions of early events such as electron and hole localization sites which serve to test and to clarify the experimental observations. HPLC and GC-mass spectroscopic assays of DNA base products formation provide the ultimate chemical outcome of the initial radiation events. The bridge between the early ion radical species and the non-radical products is made in ESR studies which follow the chemistry of the early species as they react with water and or other DNA bases. The use of these techniques has resulted in a new and fundamental understanding of the radiation damage to DNA on a molecular scale. From this work, a working model for DNA damage from the initial ionization event to the eventual formation of molecular base damage products and strand breaks has been formulated. Results over the past several years which have led to the formulation of this model are described.

  4. High-Temperature Oxide Regrowth on Mechanically-Damaged Surfaces

    SciTech Connect

    Blau, Peter Julian; Lowe, Tracie M

    2008-01-01

    Here we report the effects of mechanical damage from a sharp stylus on the regrowth of oxide layers on a Ni-based superalloy known as Pyromet 80A . It was found that the oxide that reformed on the damaged portion of a pre-oxidized surface differed from that which formed on undamaged areas after the equal exposures to elevated temperature in air. These findings have broad implications for modeling the processes of material degradation in applications such as exhaust valves in internal combustion engines because they imply that static oxidation data for candidate materials may not adequately reflect their reaction to operating environments that involve both mechanical contact and oxidation.

  5. Mechanical Data for Use in Damage Tolerance Analyses

    NASA Technical Reports Server (NTRS)

    Forth, Scott C.; James, Mark A.; Newman, John A.; Everett, Richard A., Jr.; Johnston, William M., Jr.

    2004-01-01

    This report describes the results of a research program to determine the damage tolerance properties of metallic propeller materials. Three alloys were selected for investigation: 2025-T6 Aluminum, D6AC Steel and 4340 Steel. Mechanical response, fatigue (S-N) and fatigue crack growth rate data are presented for all of the alloys. The main conclusions that can be drawn from this study are as follows. The damage tolerant design of a propeller system will require a complete understanding of the fatigue crack growth threshold. There exists no experimental procedure to reliably develop the fatigue crack growth threshold data that is needed for damage tolerant design methods. Significant research will be required to fully understand the fatigue crack growth threshold. The development of alternative precracking methods, evaluating the effect of specimen configuration and attempting to identify micromechanical issues are simply the first steps to understanding the mechanics of the threshold.

  6. Damage mechanisms in uniaxial compression of single enamel rods.

    PubMed

    An, Bingbing; Wang, Raorao; Arola, Dwayne; Zhang, Dongsheng

    2015-02-01

    Enamel possesses a complex hierarchical structure, which bestows this tissue with unique mechanical properties. In this study, the mechanical behavior of single enamel rods was investigated under uniaxial compression. Numerical simulations were also performed using micromechanics models for individual enamel rods to identify the damage mechanisms contributing to the constitutive behavior. Experimental results showed that the single rods exhibited an elastic modulus ranging from 10~31 GPa, and that they undergo post-yield strain-hardening. The primary damage mode consisted of delamination within the assembly of mineral crystals. Results from numerical simulations suggest that strain localization within individual rods is responsible for the observed delamination, which is believed to arise from the non-uniform arrangement of mineral crystals. This mechanism was independent of mineral morphology and properties. The non-uniform crystal arrangement results in friction between crystals with different inclination angles and is believed to be responsible for the post-yield strain hardening behavior. PMID:25460920

  7. Development of an autonomous continuous monitoring system for mechanical damage detection.

    SciTech Connect

    Sohn, H.; Allen, D. W.; Farrar, C. R.; Worden, K.

    2002-01-01

    The primary objective of damage identification is to ascertain the existence of damage within a mechanical system. This study applies the Sequential Probability Ratio Test (SPRT) to examine if damage is present or not. In the original formulation of the SPRT, the distribution of data is assumed Gaussian and thresholds for monitoring are set focusing on the center mass properties of the distribution. Decision-making for damage identification is, however, often sensitive to the tails of the distribution and the tails may not necessarily be governed by Gaussian characteristics. By modeling the tails using the technique of Extreme Value Statistics (EVS), the thresholds for the SPRT may be set more accurately avoiding the unnecessary normality assumption. The proposed combination of the SPRT and the EVS is demonstrated using experimental data collected from a three-story frame structure with bolted connections. The primary goal of structural health monitoring is simply to identify from measured data if a structure has deviated from a normal operational condition. Particularly, vibration-based damage detection techniques assume that changes of the structure's integrity affect characteristics of the measured vibration signals enabling one to detect damage. Many current approaches to this problem involve methods that leave much to the interpretation of analysts. These methods may enable a trained eye to discern and locate damage but are not easily automated or objective. In an attempt to automate the damage identification procedure, the SPRT is employed for the decision-making procedure. The original SPRT assumes that the extracted features have a Gaussian distribution. This normality assumption, however, may place misleading constraints on the tails of the distribution. As the problem of damage detection specifically focuses attention on the tails, the assumption of normality is likely to lead the analysis astray. To overcome this difficulty, the performance of the SPRT

  8. Herbal Formulation C168 Attenuates Proliferation and Induces Apoptosis in HCT 116 Human Colorectal Carcinoma Cells: Role of Oxidative Stress and DNA Damage

    PubMed Central

    Leong, Lek Mun; Chan, Kok Meng; Hamid, Asmah; Latip, Jalifah; Rajab, Nor Fadilah

    2016-01-01

    The use of herbal formulations has gained scientific interest, particularly in cancer treatment. In this study, the herbal formulation of interest, denoted as C168, is a mixture of eight genera of plants. This study aims to investigate the antiproliferative effect of C168 methanol extract (CME) on various cancer cells and its underlying mechanism of action on the most responsive cell line, namely, HCT 116 cells. CME exerted antiproliferative activities on HCT 116 colorectal carcinoma cells and HepG2 hepatocellular carcinoma cells but not on CCD-841-CoN normal colon epithelial cells, Jurkat E6.1 lymphoblastic leukemic cells, and V79-4 Chinese hamster lung fibroblasts. Further investigation on HCT 116 cells showed that CME induced G2/M cell-cycle arrest and apoptosis. Treatment of CME induced oxidative stress in HCT 116 cells by increasing the superoxide anion level and decreasing the intracellular glutathione. CME also increased tail moment value and H2AX phosphorylation in HCT 116 cells, suggesting DNA damage as an early signal of CME induced apoptosis. Loss of mitochondrial membrane potential in CME-treated cells also indicated the involvement of mitochondria in CME induced apoptosis. This study indicated the selectivity of CME toward colon cancer cells with the involvement of oxidative damage as its possible mechanism of action. PMID:26884792

  9. Hepatoprotective and antioxidant activity of Karisalai Karpam, a polyherbal Siddha formulation against acetaminophen-induced hepatic damage in rats

    PubMed Central

    Sen, Saikat; Chakraborty, Raja; Thangavel, Ganesh; Logaiyan, Sivakumar

    2015-01-01

    Background: The usage of Siddha medicine in Tamil Nadu and several parts of Southern India has considerably increased over the past two decades and it is steadily crossing the various geographies owing to its inexpensiveness compared to conventional medicines and has fairly high acceptance rates because of its herbal origin and therefore its nontoxic nature. Aim: This study aims to investigate the anti-hepatotoxic and antioxidant potential of the Karisalai Karpam formulation. Materials and Methods: Karisalai Karpam tablet at 50, 100, and 200 mg/kg/day, p.o. doses were administered orally to rats for three consecutive days. Single dose of acetaminophen (3 g/kg, p.o.) was administered on the 3rd day. Animals were sacrificed 48 h after the administration of acetaminophen, and their serum bilirubin, different hepatic enzymes and in vivo antioxidant activity were estimated. Statistical Analysis: Data were evaluated using analysis of variance, followed by Tukey tests. A level of P < 0.05 was considered statistically significant. Results: Pretreatment with Karisalai Karpam tablet showed dose-dependent hepatoprotective activity. Karisalai Karpam tablet (200 mg/kg) reduces serum glutamic oxaloacetate transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase and total bilirubin, direct bilirubin by 67.8%, 72.3%, 47.6%, 61.3% and 62.9% respectively compared to disease control group. A significant increase (P < 0.001) in antioxidant enzyme level was observed in Karisalai Karpam treated animals. At higher doses, Karisalai Karpam prevented the depletion of glutathione in liver tissue. Conclusion: Results confirmed that Karisalai Karpam tablet could protect the liver against acetaminophen-induced oxidative damage possibly by increasing the antioxidant defence mechanism in rats. PMID:26283804

  10. Mechanisms for microvascular damage induced by ultrasound-activated microbubbles

    NASA Astrophysics Data System (ADS)

    Chen, Hong; Brayman, Andrew A.; Evan, Andrew P.; Matula, Thomas J.

    2012-10-01

    To provide insight into the mechanisms of microvascular damage induced by ultrasound-activated microbubbles, experimental studies were performed to correlate microvascular damage to the dynamics of bubble-vessel interactions. High-speed photomicrography was used to record single microbubbles interacting with microvessels in ex vivo tissue, under the exposure of short ultrasound pulses with a center frequency of 1 MHz and peak negative pressures (PNP) ranging from 0.8-4 MPa. Vascular damage associated with observed bubble-vessel interactions was either indicated directly by microbubble extravasation or examined by transmission electron microscopy (TEM) analyses. As observed previously, the high-speed images revealed that ultrasound-activated microbubbles could cause distention and invagination of adjacent vessel walls, and could form liquid jets in microvessels. Vessel distention, invagination, and liquid jets were associated with the damage of microvessels whose diameters were smaller than those of maximally expanded microbubbles. However, vessel invagination appeared to be the dominant mechanism for the damage of relative large microvessels.

  11. Mechanisms for microvascular damage induced by ultrasound-activated microbubbles

    SciTech Connect

    Chen Hong; Brayman, Andrew A.; Evan, Andrew P.; Matula, Thomas J.

    2012-10-03

    To provide insight into the mechanisms of microvascular damage induced by ultrasound-activated microbubbles, experimental studies were performed to correlate microvascular damage to the dynamics of bubble-vessel interactions. High-speed photomicrography was used to record single microbubbles interacting with microvessels in ex vivo tissue, under the exposure of short ultrasound pulses with a center frequency of 1 MHz and peak negative pressures (PNP) ranging from 0.8-4 MPa. Vascular damage associated with observed bubble-vessel interactions was either indicated directly by microbubble extravasation or examined by transmission electron microscopy (TEM) analyses. As observed previously, the high-speed images revealed that ultrasound-activated microbubbles could cause distention and invagination of adjacent vessel walls, and could form liquid jets in microvessels. Vessel distention, invagination, and liquid jets were associated with the damage of microvessels whose diameters were smaller than those of maximally expanded microbubbles. However, vessel invagination appeared to be the dominant mechanism for the damage of relative large microvessels.

  12. Lightning Strike Induced Damage Mechanisms of Carbon Fiber Composites

    NASA Astrophysics Data System (ADS)

    Kawakami, Hirohide

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

  13. Fatigue and Mechanical Damage Propagation in Automotive PEM Fuel Cells

    NASA Astrophysics Data System (ADS)

    Banan, Roshanak

    Polymer electrolyte membrane (PEM) fuel cells are generally exposed to high magnitude road-induced vibrations and impact loads, frequent humidity-temperature loading cycles, and freeze/thaw stresses when employed in automotive applications. The resultant mechanical stresses can play a significant role in the evolution of mechanical defects in the membrane electrode assembly (MEA). The focus of this research is to investigate fatigue challenges due to humidity-temperature (hygrothermal) cycles and vibrations and their effects on damage evolution in PEM fuel cells. To achieve this goal, this thesis is divided into three parts that provide insight into damage propagation in the MEA under i) hygrothermal cycles, ii) external applied vibrations, and iii) a combination of both to simulate realistic automotive conditions. A finite element damage model based on cohesive zone theory was developed to simulate the propagation of micro-scale defects (cracks and delaminations) in the MEA under fuel cell operating conditions. It was found that the micro-defects can propagate to critical states under start-up and shut-down cycles, prior to reaching the desired lifespan of the fuel cell. The simultaneous presence of hygrothermal cycles and vibrations severely intensified damage propagation and resulted in considerably large defects within 75% of the fuel cell life expectancy. However, the order of generated damage was found to be larger under hygrothermal cycles than vibrations. Under hygrothermal cycles, membrane crack propagation was more severe compared to delamination propagation. Conversely, the degrading influence of vibrations was more significant on delaminations. The presence of an anode/cathode channel offset under the combined loadings lead to a 2.5-fold increase in the delamination length compared to the aligned-channel case. The developed model can be used to investigate the damage behaviour of current materials employed in fuel cells as well as to evaluate the

  14. Differential continuum damage mechanics models for creep and fatigue of unidirectional metal matrix composites

    NASA Technical Reports Server (NTRS)

    Arnold, S. M.; Kruch, S.

    1991-01-01

    Three multiaxial isothermal continuum damage mechanics models for creep, fatigue, and creep/fatigue interaction of a unidirectional metal matrix composite volume element are presented, only one of which will be discussed in depth. Each model is phenomenological and stress based, with varying degrees of complexity to accurately predict the initiation and propagation of intergranular and transgranular defects over a wide range of loading conditions. The development of these models is founded on the definition of an initially transversely isotropic fatigue limit surface, static fracture surface, normalized stress amplitude function and isochronous creep damage failure surface, from which both fatigue and creep damage evolutionary laws can be obtained. The anisotropy of each model is defined through physically meaningful invariants reflecting the local stress and material orientation. All three transversely isotropic models have been shown, when taken to their isotropic limit, to directly simplify to previously developed and validated creep and fatigue continuum damage theories. Results of a nondimensional parametric study illustrate (1) the flexibility of the present formulation when attempting to characterize a large class of composite materials, and (2) its ability to predict anticipated qualitative trends in the fatigue behavior of unidirectional metal matrix composites. Additionally, the potential for the inclusion of various micromechanical effects (e.g., fiber/matrix bond strength, fiber volume fraction, etc.), into the phenomenological anisotropic parameters is noted, as well as a detailed discussion regarding the necessary exploratory and characterization experiments needed to utilize the featured damage theories.

  15. Metric space formulation of quantum mechanical conservation laws

    NASA Astrophysics Data System (ADS)

    Sharp, P. M.; D'Amico, I.

    2014-03-01

    We show that conservation laws in quantum mechanics naturally lead to metric spaces for the set of related physical quantities. All such metric spaces have an "onion-shell" geometry. We demonstrate the power of this approach by considering many-body systems immersed in a magnetic field, with a finite ground state current. In the associated metric spaces we find regions of allowed and forbidden distances, a "band structure" in metric space directly arising from the conservation of the z component of the angular momentum.

  16. A damage mechanics approach to high temperature fatigue crack growth

    SciTech Connect

    Qian, Z.; Takezono, S.; Tao, K.

    1995-12-31

    A nonlocal damage constitutive model is developed for elasto-visco-plastic materials and is used to analyze fatigue crack growth at high temperature. In this model, no kinematic hardening rule is needed to account for the subsequent yielding and strain hardening behavior of the materials. A calculation method for nonlocal damage is introduced. The fatigue crack growth tests and the cyclic strain controlled fatigue tests are carried out at 723 K (450 C) on pure titanium. By means of FEM, the stress distribution near the crack tip, and the relationships between the crack growth rate dl/dN and some mechanical parameters, such as the crack tip opening displacement (CTOD), and the range of viscoplastic strain {Delta}{var_epsilon}{sub y}{sup vp} at the crack tip, are investigated. The mesh size dependence of these mechanical parameters in finite element analysis is discussed. The numerical results are given and compared with the experimental ones.

  17. Coating formulation and method for refinishing the surface of surface-damaged graphite articles

    DOEpatents

    Ardary, Z.L.; Benton, S.T.

    1987-07-08

    The described development is directed to a coating formulation for filling surface irregularities in graphite articles such as molds, crucibles, and matched die sets used in high-temperature metallurgical operations. The coating formulation of the present invention is formed of carbon black flour, thermosetting resin and a solvent for the resin. In affixing the coating to the article, the solvent is evaporated, the resin cured to bond the coating to the surface of the article and then pyrolyzed to convert the resin to carbon. Upon completion of the pyrolysis step, the coating is shaped and polished to provide the article with a surface restoration that is essentially similar to the original or desired surface finish without the irregularity.

  18. Coating formulation and method for refinishing the surface of surface-damaged graphite articles

    DOEpatents

    Ardary, Zane L.; Benton, Samuel T.

    1988-01-01

    The described development is directed to a coating formulation for filling surface irregularities in graphite articles such as molds, crucibles, and matched die sets used in high-temperature metallurgical operations. The coating formulation of the present invention is formed of carbon black flour, thermosetting resin and a solvent for the resin. In affixing the coating to the article, the solvent is evaporated, the resin cured to bond the coating to the surface of the article and then pyrolyzed to convert the resin to carbon. Upon completion of the pyrolysis step, the coating is shaped and polished to provide the article with a surface restoration that is essentially similar to the original or desired surface finish without the irregularity.

  19. Coating formulation and method for refinishing the surface of surface-damaged graphite articles

    DOEpatents

    Ardary, Z.L.; Benton, S.T.

    1988-11-22

    The described development is directed to a coating formulation for filling surface irregularities in graphite articles such as molds, crucibles, and matched die sets used in high-temperature metallurgical operations. The coating formulation of the present invention is formed of carbon black flour, thermosetting resin and a solvent for the resin. In affixing the coating to the article, the solvent is evaporated, the resin cured to bond the coating to the surface of the article and then pyrolyzed to convert the resin to carbon. Upon completion of the pyrolysis step, the coating is shaped and polished to provide the article with a surface restoration that is essentially similar to the original or desired surface finish without the irregularity.

  20. Mechanical impedance measurement and damage detection using noncontact laser ultrasound.

    PubMed

    Lee, Hyeonseok; Lim, Hyeong Uk; Hong, Jung-Wuk; Sohn, Hoon

    2014-06-01

    This Letter proposes a mechanical impedance (MI) measurement technique using noncontact laser ultrasound. The ultrasound is generated by shooting a pulse laser beam onto a target structure, and its response is measured using a laser vibrometer. Once ultrasound propagation converges to structural vibration, MI is formed over the entire structure. Because noncontact lasers are utilized, this technique is applicable in harsh environments, free of electromagnetic interference, and able to perform wide-range scanning. The formation of MI and its feasibility for damage detection are verified through thermo-mechanical finite element analysis and lab-scale experiments.

  1. Mechanism study of goldenseal-associated DNA damage.

    PubMed

    Chen, Si; Wan, Liqing; Couch, Letha; Lin, Haixia; Li, Yan; Dobrovolsky, Vasily N; Mei, Nan; Guo, Lei

    2013-07-31

    Goldenseal has been used for the treatment of a wide variety of ailments including gastrointestinal disturbances, urinary tract disorders, and inflammation. The five major alkaloid constituents in goldenseal are berberine, palmatine, hydrastine, hydrastinine, and canadine. When goldenseal was evaluated by the National Toxicology Program (NTP) in the standard 2-year bioassay, goldenseal induced an increase in liver tumors in rats and mice; however, the mechanism of goldenseal-associated liver carcinogenicity remains unknown. In this study, the toxicity of the five goldenseal alkaloid constituents was characterized, and their toxic potencies were compared. As measured by the Comet assay and the expression of γ-H2A.X, berberine, followed by palmatine, appeared to be the most potent DNA damage inducer in human hepatoma HepG2 cells. Berberine and palmatine suppressed the activities of both topoisomerase (Topo) I and II. In berberine-treated cells, DNA damage was shown to be directly associated with the inhibitory effect of Topo II, but not Topo I by silencing gene of Topo I or Topo II. In addition, DNA damage was also observed when cells were treated with commercially available goldenseal extracts and the extent of DNA damage was positively correlated to the berberine content. Our findings suggest that the Topo II inhibitory effect may contribute to berberine- and goldenseal-induced genotoxicity and tumorigenicity.

  2. Visual indication of mechanical damage using core-shell microcapsules.

    PubMed

    Odom, Susan A; Jackson, Aaron C; Prokup, Alex M; Chayanupatkul, Sarut; Sottos, Nancy R; White, Scott R; Moore, Jeffrey S

    2011-12-01

    We report a new core-shell microcapsule system for the visual detection of mechanical damage. The core material, 1,3,5,7-cyclooctatetraene, is a conjugated cyclic olefin and a precursor to intensely colored polyacetylene. A combination of poly(urea-formaldehyde) and polyurethane is required to effectively encapsulate the volatile core material. Increasing the outer shell wall thickness and including a core-side prepolymer improves the thermal stability and free-flowing nature of these capsules, which tend to leach and rupture with thinner shell walls. Capsules ruptured in the presence of the Grubbs-Love ruthenium catalyst show immediate color change from nearly colorless to red-orange and dark purple over time, and color change in thin films resulted from scratch damage. PMID:22114767

  3. [Pathogenic mechanisms of neuronal damage in multiple sclerosis].

    PubMed

    Flores-Alvarado, Luis Javier; Gabriel-Ortiz, Genaro; Pacheco-Mois, Fermín P; Bitzer-Quintero, K

    2015-06-01

    Multiple sclerosis is the most common cause of progressive neurological disability in young adults. This disease involves damage to the myelin sheath that normally insulates the electrical activity of nerve fibers. This leads to a wide range of symptoms as specific nerves become injured and lose their function. Epidemiological and experimental studies show that genetic alterations, antioxidant enzyme abnormalities and autoimmunity are risk factors for developing the disease. Recent evidence suggests that inflammation and oxidative stress within the central nervous system are major causes of ongoing tissue damage. Resident central nervous system cells and invading inflammatory cells release several reactive oxygen and nitrogen species which cause the histopathological features of multiple sclerosis: demyelization and axonal damage. The interplay between inflammatory and neurodegenerative processes results in an intermittent neurological disturbance followed by progressive accumulation of disability. Reductions in inflammation and oxidative stress status are important therapeutic strategies to slow or halt the disease processes. Therefore, several drugs are currently in trial in clinical practice to target this mechanism; particularly the use of supplements such as antioxidants and omega-3 polyunsaturated fatty acids, in order to improve the survival and quality of patients' lives. PMID:26299060

  4. Positive-operator-valued measures in the Hamiltonian formulation of quantum mechanics

    NASA Astrophysics Data System (ADS)

    Arsenović, D.; Burić, N.; Popović, D. B.; Radonjić, M.; Prvanović, S.

    2015-06-01

    In the Hilbert space formulation of quantum mechanics, ideal measurements of physical variables are discussed using the spectral theory of Hermitian operators and the corresponding projector-valued measures (PVMs). However, more general types of measurements require the treatment in terms of positive-operator-valued measures (POVMs). In the Hamiltonian formulation of quantum mechanics, canonical coordinates are related to PVM. In this paper the results of an analysis of various aspects of applications of POVMs in the Hamiltonian formulation are reported. Several properties of state parameters and quantum observables given by POVMs or represented in an overcomplete basis, including the general Hamiltonian treatment of the Neumark extension, are presented. An analysis of the phase operator, given by the corresponding POVMs, in the Hilbert space and the Hamiltonian frameworks is also given.

  5. Hygrothermal damage mechanisms in graphite-epoxy composites

    NASA Technical Reports Server (NTRS)

    Crossman, F. W.; Mauri, R. E.; Warren, W. J.

    1979-01-01

    T300/5209 and T300/5208 graphite epoxy laminates were studied experimentally and analytically in order to: (1) determine the coupling between applied stress, internal residual stress, and moisture sorption kinetics; (2) examine the microscopic damage mechanisms due to hygrothermal cycling; (3) evaluate the effect of absorbed moisture and hygrothermal cycling on inplane shear response; (4) determine the permanent loss of interfacial bond strength after moisture absorption and drying; and (5) evaluate the three dimensional stress state in laminates under a combination of hygroscopic, thermal, and mechanical loads. Specimens were conditioned to equilibrium moisture content under steady exposure to 55% or 95% RH at 70 C or 93 C. Some specimens were tested subsequent to moisture conditioning and 100 cycles between -54 C and either 70 C or 93 C.

  6. Fisetin Protects DNA Against Oxidative Damage and Its Possible Mechanism

    PubMed Central

    Wang, Tingting; Lin, Huajuan; Tu, Qian; Liu, Jingjing; Li, Xican

    2016-01-01

    Purpose: The paper tries to assess the protective effect of fisetin against •OH-induced DNA damage, then to investigate the possible mechanism. Methods: The protective effect was evaluated based on the content of malondialdehyde (MDA). The possible mechanism was analyzed using various antioxidant methods in vitro, including •OH scavenging (deoxyribose degradation), •O2- scavenging (pyrogallol autoxidation), DPPH• scavenging, ABTS•+ scavenging, and Cu2+-reducing power assays. Results: Fisetin increased dose-dependently its protective percentages against •OH-induced DNA damage (IC50 value =1535.00±29.60 µM). It also increased its radical-scavenging percentages in a dose-dependent manner in various antioxidants assays. Its IC50 values in •OH scavenging, •O2- scavenging, DPPH• scavenging, ABTS•+ scavenging, and Cu2+-reducing power assays, were 47.41±4.50 µM, 34.05±0.87 µM, 9.69±0.53 µM, 2.43±0.14 µM, and 1.49±0.16 µM, respectively. Conclusion: Fisetin can effectively protect DNA against •OH-induced oxidative damage possibly via reactive oxygen species (ROS) scavenging approach, which is assumed to be hydrogen atom (H•) and/or single electron (e) donation (HAT/SET) pathways. In the HAT pathway, the 3’,4’-dihydroxyl moiety in B ring of fisetin is thought to play an important role, because it can be ultimately oxidized to a stable ortho-benzoquinone form. PMID:27478791

  7. Mechanisms of alcohol liver damage: aldehydes, scavenger receptors, and autoimmunity.

    PubMed

    Duryee, Michael J; Willis, Monte S; Freeman, Thomas L; Kuszynski, Charles A; Tuma, Dean J; Klassen, Lynell W; Thiele, Geoffrey M

    2004-09-01

    While most of the investigations into the causative events in the development of alcoholic liver disease (ALD) have been focused on multiple factors, increasing interest has centered around the possible role of immune mechanisms in the pathogenesis and perpetuation of ALD. This is because many of the clinical features of ALD suggest that immune effector mechanisms may be contributing to liver tissue damage, as evidenced by the detection of circulating autoantibodies, and the presence of CD4+ and CD8+ lymphoid cells in the livers of patients with ALD. One mechanism that has been associated with the development of autoimmune responses is the modification (haptenation or adduction) of liver proteins with aldehydes or other products of oxidative stress. This is because it has been shown that these adducted proteins can induce specific immune responses, to the adduct, the adduct plus protein (conformational antigens), as well as the unmodified parts of the protein. More importantly, it is possible to demonstrate that adducted self-proteins can induce reactivity to the normal self-protein and thereby induce autoimmune responses. Therefore, it is the purpose of this manuscript to outline the mechanism(s) by which these modified self proteins can induce autoimmune reactivity, and thus play a role in the development and/or progression of ALD.

  8. Damage detection technique by measuring laser-based mechanical impedance

    SciTech Connect

    Lee, Hyeonseok; Sohn, Hoon

    2014-02-18

    This study proposes a method for measurement of mechanical impedance using noncontact laser ultrasound. The measurement of mechanical impedance has been of great interest in nondestructive testing (NDT) or structural health monitoring (SHM) since mechanical impedance is sensitive even to small-sized structural defects. Conventional impedance measurements, however, have been based on electromechanical impedance (EMI) using contact-type piezoelectric transducers, which show deteriorated performances induced by the effects of a) Curie temperature limitations, b) electromagnetic interference (EMI), c) bonding layers and etc. This study aims to tackle the limitations of conventional EMI measurement by utilizing laser-based mechanical impedance (LMI) measurement. The LMI response, which is equivalent to a steady-state ultrasound response, is generated by shooting the pulse laser beam to the target structure, and is acquired by measuring the out-of-plane velocity using a laser vibrometer. The formation of the LMI response is observed through the thermo-mechanical finite element analysis. The feasibility of applying the LMI technique for damage detection is experimentally verified using a pipe specimen under high temperature environment.

  9. Characteristics and mechanisms of acrylate polymer damage to maize seedlings.

    PubMed

    Chen, Xian; Mao, Xiaoyun; Lu, Qin; Liao, Zongwen; He, Zhenli

    2016-07-01

    Superabsorbent acrylate polymers (SAPs) have been widely used to maintain soil moisture in agricultural management, but they may cause damage to plants, and the mechanisms are not well understood. In this study, seed germination, soil pot culture, hydroponic experiments, and SAPs degradation were conducted to investigate damage characteristics and mechanisms associated with SAPs application. The Results showed that SAPs inhibited maize growth and altered root morphology (irregular and loose arrangement of cells and breakage of cortex parenchyma), and the inhibitory effects were enhanced at higher SAPs rates. After 1h SAP hydrogels treatment, root malondialdehyde (MDA) content was significantly increased, while superoxide dismutase (SOD) and catalase (CAT) content were significantly decreased. Hydroponics experiment indicated that root and shoot growth was inhibited at 2.5mgL(-1) acrylic acid (AA), and the inhibition was enhanced with increasing AA rates. This effect was exacerbated by the presence of Na(+) at a high concentration in the hydrogels. Release and degradation of AA were enhanced at higher soil moisture levels. A complete degradation of AA occurred between 15 and 20 days after incubation (DAI), but it took longer for Na(+) concentration to decrease to a safe level. These results indicate that high concentration of both AA and Na(+) present in the SAPs inhibits plant growth. The finding of this study may provide a guideline for appropriate application of SAPs in agriculture. PMID:27057990

  10. A displacement-based finite element formulation for incompressible and nearly-incompressible cardiac mechanics.

    PubMed

    Hadjicharalambous, Myrianthi; Lee, Jack; Smith, Nicolas P; Nordsletten, David A

    2014-06-01

    The Lagrange Multiplier (LM) and penalty methods are commonly used to enforce incompressibility and compressibility in models of cardiac mechanics. In this paper we show how both formulations may be equivalently thought of as a weakly penalized system derived from the statically condensed Perturbed Lagrangian formulation, which may be directly discretized maintaining the simplicity of penalty formulations with the convergence characteristics of LM techniques. A modified Shamanskii-Newton-Raphson scheme is introduced to enhance the nonlinear convergence of the weakly penalized system and, exploiting its equivalence, modifications are developed for the penalty form. Focusing on accuracy, we proceed to study the convergence behavior of these approaches using different interpolation schemes for both a simple test problem and more complex models of cardiac mechanics. Our results illustrate the well-known influence of locking phenomena on the penalty approach (particularly for lower order schemes) and its effect on accuracy for whole-cycle mechanics. Additionally, we verify that direct discretization of the weakly penalized form produces similar convergence behavior to mixed formulations while avoiding the use of an additional variable. Combining a simple structure which allows the solution of computationally challenging problems with good convergence characteristics, the weakly penalized form provides an accurate and efficient alternative to incompressibility and compressibility in cardiac mechanics.

  11. A displacement-based finite element formulation for incompressible and nearly-incompressible cardiac mechanics

    PubMed Central

    Hadjicharalambous, Myrianthi; Lee, Jack; Smith, Nicolas P.; Nordsletten, David A.

    2014-01-01

    The Lagrange Multiplier (LM) and penalty methods are commonly used to enforce incompressibility and compressibility in models of cardiac mechanics. In this paper we show how both formulations may be equivalently thought of as a weakly penalized system derived from the statically condensed Perturbed Lagrangian formulation, which may be directly discretized maintaining the simplicity of penalty formulations with the convergence characteristics of LM techniques. A modified Shamanskii–Newton–Raphson scheme is introduced to enhance the nonlinear convergence of the weakly penalized system and, exploiting its equivalence, modifications are developed for the penalty form. Focusing on accuracy, we proceed to study the convergence behavior of these approaches using different interpolation schemes for both a simple test problem and more complex models of cardiac mechanics. Our results illustrate the well-known influence of locking phenomena on the penalty approach (particularly for lower order schemes) and its effect on accuracy for whole-cycle mechanics. Additionally, we verify that direct discretization of the weakly penalized form produces similar convergence behavior to mixed formulations while avoiding the use of an additional variable. Combining a simple structure which allows the solution of computationally challenging problems with good convergence characteristics, the weakly penalized form provides an accurate and efficient alternative to incompressibility and compressibility in cardiac mechanics. PMID:25187672

  12. Oxidant conditioning protects cartilage from mechanically induced damage.

    PubMed

    Ramakrishnan, Prem; Hecht, Benjamin A; Pedersen, Douglas R; Lavery, Matthew R; Maynard, Jerry; Buckwalter, Joseph A; Martin, James A

    2010-07-01

    Articular cartilage degeneration in osteoarthritis has been linked to abnormal mechanical stresses that are known to cause chondrocyte apoptosis and metabolic derangement in in vitro models. Evidence implicating oxidative damage as the immediate cause of these harmful effects suggests that the antioxidant defenses of chondrocytes might influence their tolerance for mechanical injury. Based on evidence that antioxidant defenses in many cell types are stimulated by moderate oxidant exposure, we hypothesized that oxidant preconditioning would reduce acute chondrocyte death and proteoglycan depletion in cartilage explants after exposure to abnormal mechanical stresses. Porcine cartilage explants were treated every 48 h with tert-butyl hydrogen peroxide (tBHP) at nonlethal concentrations (25, 100, 250, and 500 microM) for a varying number of times (one, two, or four) prior to a bout of unconfined axial compression (5 MPa, 1 Hz, 1800 cycles). When compared with untreated controls, tBHP had significant positive effects on post-compression viability, lactate production, and proteoglycan losses. Overall, the most effective regime was 100 microM tBHP applied four times. RNA analysis revealed significant effects of 100 microM tBHP on gene expression. Catalase, hypoxia-inducible factor-1alpha (HIF-1alpha), and glyceraldehyde 6-phosphate dehydrogenase (GAPDH) were significantly increased relative to untreated controls in explants treated four times with 100 microM tBHP, a regime that also resulted in a significant decrease in matrix metalloproteinase-3 (MMP-3) expression. These findings demonstrate that repeated exposure of cartilage to sublethal concentrations of peroxide can moderate the acute effects of mechanical stress, a conclusion supported by evidence of peroxide-induced changes in gene expression that could render chondrocytes more resistant to oxidative damage. PMID:20058262

  13. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    PubMed

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-01

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity.

  14. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    PubMed

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-01

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity. PMID:26485141

  15. Damage mechanisms in PBT-GF30 under thermo-mechanical cyclic loading

    SciTech Connect

    Schaaf, A. De Monte, M. Hoffmann, C.; Vormwald, M.; Quaresimin, M.

    2014-05-15

    The scope of this paper is the investigation of damage mechanisms at microscopic scale on a short glass fiber reinforced polybutylene terephthalate (PBT-GF30) under thermo-mechanical cyclic loading. In addition the principal mechanisms are verified through micro mechanical FE models. In order to investigate the fatigue behavior of the material both isothermal strain controlled fatigue (ISCF) tests at three different temperatures and thermo-mechanical fatigue (TMF) tests were conducted on plain and notched specimens, manufactured by injection molding. The goal of the work is to determine the damage mechanisms occurring under TMF conditions and to compare them with the mechanisms occurring under ISCF. For this reason fracture surfaces of TMF and ISCF samples loaded at different temperature levels were analyzed using scanning electron microscopy. Furthermore, specimens that failed under TMF were examined on microsections revealing insight into both crack initiation and crack propagation. The findings of this investigation give valuable information about the main damage mechanisms of PBT-GF30 under TMF loading and serve as basis for the development of a TMF life estimation methodology.

  16. A Micromechanical Damage Mechanics Model for the Seismic Coupling of Underground Nuclear Explosions

    NASA Astrophysics Data System (ADS)

    Rogers-Martinez, M. A.; Sammis, C. G.; Mihaly, J. M.; Bhat, H. S.

    2014-12-01

    Seismological discrimination between underground explosions and earthquakes is complicated by the observation that explosions generate significant S wave radiation. Whether these S waves are generated mainly in the non-linear source region, or by slip on nearby faults, or by mode conversion at boundaries along the propagation path remains controversial. In this study we explore the hypothesis that S wave radiation is generated during the ubiquitous generation of fractures observed in the non-linear source region. We model the nucleation, growth, and interaction of these fractures using a fully dynamic micromechanical damage mechanics recently formulated by Bhat et al. (J. Appl. Mech., 2012). Parameters in the model include the size, density, and orientation of initial fractures in the source rock, the coefficient of friction on their faces, and the dynamic critical stress intensity factor for nucleation and propagation. The damage mechanics is built into the ABAQUS dynamic finite element code as a user-defined rheology and is used to calculate the spatial extent and geometry of the fracture damage as well as resultant seismic radiation generated by an explosion with a specified pressure time-function. A fundamental result of these calculations is that any process that breaks the spherical symmetry of the explosion produces S waves. Sources of asymmetry include an anisotropic distribution of initial fracture (e.g. a rift in the granitic texture), an anisotropic regional pre-stress, or even heterogeneity that breaks the symmetry of the radial fractures. We compare our calculations with field experiments (by Weston Geophysical and New England Research) in a granite quarry and with laboratory experiments that use high-speed photography and laser velocimeters to record the evolution of the damage pattern and resultant seismic radiation.

  17. Molecular mechanisms involved in initiation of the DNA damage response

    PubMed Central

    Barnum, Kevin J; O’Connell, Matthew J

    2015-01-01

    DNA is subject to a wide variety of damage. In order to maintain genomic integrity, cells must respond to this damage by activating repair and cell cycle checkpoint pathways. The initiating events in the DNA damage response entail recognition of the lesion and the assembly of DNA damage response complexes at the DNA. Here, we review what is known about these processes for various DNA damage pathways. PMID:27308403

  18. Review: Wind impacts on plant growth, mechanics and damage.

    PubMed

    Gardiner, Barry; Berry, Peter; Moulia, Bruno

    2016-04-01

    Land plants have adapted to survive under a range of wind climates and this involve changes in chemical composition, physical structure and morphology at all scales from the cell to the whole plant. Under strong winds plants can re-orientate themselves, reconfigure their canopies, or shed needles, leaves and branches in order to reduce the drag. If the wind is too strong the plants oscillate until the roots or stem fail. The mechanisms of root and stem failure are very similar in different plants although the exact details of the failure may be different. Cereals and other herbaceous crops can often recover after wind damage and even woody plants can partially recovery if there is sufficient access to water and nutrients. Wind damage can have major economic impacts on crops, forests and urban trees. This can be reduced by management that is sensitive to the local site and climatic conditions and accounts for the ability of plants to acclimate to their local wind climate. Wind is also a major disturbance in many plant ecosystems and can play a crucial role in plant regeneration and the change of successional stage.

  19. Review: Wind impacts on plant growth, mechanics and damage.

    PubMed

    Gardiner, Barry; Berry, Peter; Moulia, Bruno

    2016-04-01

    Land plants have adapted to survive under a range of wind climates and this involve changes in chemical composition, physical structure and morphology at all scales from the cell to the whole plant. Under strong winds plants can re-orientate themselves, reconfigure their canopies, or shed needles, leaves and branches in order to reduce the drag. If the wind is too strong the plants oscillate until the roots or stem fail. The mechanisms of root and stem failure are very similar in different plants although the exact details of the failure may be different. Cereals and other herbaceous crops can often recover after wind damage and even woody plants can partially recovery if there is sufficient access to water and nutrients. Wind damage can have major economic impacts on crops, forests and urban trees. This can be reduced by management that is sensitive to the local site and climatic conditions and accounts for the ability of plants to acclimate to their local wind climate. Wind is also a major disturbance in many plant ecosystems and can play a crucial role in plant regeneration and the change of successional stage. PMID:26940495

  20. DEVELOPMENT OF NONLINEAR HARMONIC SENSORS FOR DETECTION OF MECHANICAL DAMAGE

    SciTech Connect

    Alfred E. Crouch; Alan Dean; Carl Torres; Jeff Aron

    2004-03-01

    In a joint effort with Tuboscope Pipeline Services of Houston, Texas, Southwest Research Institute (SwRI) adapted its nonlinear harmonic (NLH) sensing technology for use on a new in-line inspection system (smart pig). Nonlinear harmonics, an AC magnetic method for detecting local anomalies of stress and plastic deformation, shows promise of improved characterization of mechanical damage defects such as gouged dents, even though the dents may have re-rounded. The SwRI-Tuboscope project produced a sensor design, electronic design, and sensor suspension design that are directly adaptable to a multitechnology ILI system. This report describes the NLH method, the sensor, circuit, and suspension designs, and shows results from the supporting laboratory work.

  1. Mechanisms and prevention of secondary brain damage during intensive care.

    PubMed

    Dearden, N M

    1998-01-01

    The injured brain may be damaged by primary impact, secondary injury from secondary damage due to initiation of destructive inflammatory and biochemical cascades by the primary injury or secondary ischemic injury following secondary insults that initiate or augment these immunological and biochemical cascades. Cerebral ischemia will arise whenever delivery of oxygen and substrates to the brain fall below metabolic needs. Many factors lead to the development of secondary insults to the injured brain during initial resuscitation, transport, surgery, and subsequent intensive care. Continuous monitoring of cerebral oxygenation (jugular oximetry, brain tissue PO2) and cerebral blood flow velocity (transcranial Doppler ultrasonography) in patients with brain trauma reveals multiple episodes of transient hypoperfusion with an adverse relationship between incidence and outcome. Secondary brain insults arise through systemic or intracranial mechanisms that reduce cerebral blood flow from compromised CPP, vascular distortion or cerebrovascular narrowing or lower oxygen delivery from hypoxemia associated with airway obstruction, pulmonary pathology, or anemia. Secondary brain ischemia remains a common pathway to secondary brain damage in most critically ill neurosurgical patients. In the future prevention of secondary brain injury may well hinge on giving a cocktail of novel agents that modify destructive biochemical and inflammatory pathways, each having a potential therapeutic window possibly in a subgroup of patients. To date, phase 3 clinical trials of several agents including PEGSOD and tyrilizad mesylate have failed to show relevant efficacy after brain trauma or subarachnoid hemorrhage. The therapeutic role of calcium channel blockers in traumatic subarachnoid hemorrhage is currently under investigation following the results of subgroup metaanalysis. Several phase 3, NMDA receptor antagonist studies are underway in brain trauma with results expected soon. Although we

  2. Damage Pre-Cursors Based Assessment of Accrued Thermo-Mechanical Damage and Remaining Useful Life in Field Deployed Electronics

    NASA Astrophysics Data System (ADS)

    Lall, Pradeep; Harsha, Mahendra; Goebel, Kai; Jones, Jim

    Field deployed electronics may accrue damage due to environmental exposure and usage after finite period of service but may not often have any o-indicators of failure such as cracks or delamination. A method to interrogate the damage state of field deployed electronics in the pre-failure space may allow insight into the damage initiation, progression, and remaining useful life of the deployed system. Aging has been previously shown to effect the reliability and constitutive behavior of second-level leadfree interconnects. Prognostication of accrued damage and assessment of residual life can provide valuable insight into impending failure. In this paper, field deployed parts have been extracted and prognosticated for accrued damage and remaining useful life in an anticipated future deployment environment. A subset of the field deployed parts have been tested to failure in the anticipated field deployed environment to validate the assessment of remaining useful life. In addition, some parts have been subjected to additional known thermo-mechanical stresses and the incremental damage accrued validated with respect to the amount of additional damage imposed on the assemblies. The presented methodology uses leading indicators of failure based on micro-structural evolution of damage to identify accrued damage in electronic systems subjected to sequential stresses of thermal aging and thermal cycling. Damage equivalency methodologies have been developed to map damage accrued in thermal aging to the reduction in thermo-mechanical cyclic life based on damage proxies. The expected error with interrogation of system state and assessment of residual life has been quantified. Prognostic metrics including α-λmetric, sample standard deviation, mean square error, mean absolute percentage error, average bias, relative accuracy, and cumulative relative accuracy have been used to compare the performance of the damage proxies.

  3. Ballistic impact damage and penetration mechanics of fiber-reinforced composite laminates

    NASA Astrophysics Data System (ADS)

    Patts, Henry Michael

    2000-10-01

    Experimental and theoretical studies were performed to characterize and model the processes of damage evolution and resulting penetration failure of graphite fiber-reinforced epoxy resin composite laminates ("structural grade") under ballistic impact. In contrast to the local yielding demonstrated by ductile isotropic materials, the penetration failure of fiber-reinforced composites produced extensive fragmentation of material with multiple modes of damage propagation such as "delamination," "interfiber matrix splitting," "transverse fiber cuts," and "through-the-thickness plugging." Due to the formation of damage zones in three-dimensional scale, the increase in target thickness raised the amount of kinetic energy absorption for full penetration in a "non-linear" fashion in fiber composites unlike the linear correlation for isotropic material such as polycarbonate and aluminum. Interfiber matrix splitting and delamination were found to be the first sign of structural deterioration occurring far below V50 and precede transverse cutting of fibers and plugging. The development of interfiber splitting into delamination of composites is explained by relying on the contact mechanics of a spherical indentor. Matrix splits on adjacent plies formed one pair of geometrical "wedges" at the ply interface, resulting in a delamination zone connected through an "isthmus." Contained in this free ply region, stress concentration readily led to transverse cutting (approximately at 85 percent of the V50) of plies when longitudinal stress of the reinforcing fibers reaches a critical level for fracture. The observed distribution of the damage leading to transverse fiber cuts was modeled by idealizing a circular target panel of staircase laminate into three zones with different values of bending stiffness due to the progression of damage. In "three-zone" model, the energy absorbed by the panel were represented in three forms of potential energy; surface free energy due to delamination

  4. Mechanical damage to Escherichia coli cells in a model of amino-acid crystal fermentation.

    PubMed

    Okutani, Satoshi; Iwai, Takayoshi; Iwatani, Shintaro; Kondo, Kazuya; Osumi, Tsuyoshi; Tsujimoto, Nobuharu; Matsuno, Kiyoshi

    2012-04-01

    We investigated the mechanical damage to the Escherichia coli cell caused by polyvinyl chloride particles as a model of amino-acid crystal fermentation. Our results indicated that the glucose-consumption rate and the intracellular ATP concentration temporarily increased by the mechanical damage, and decreased after considerable damage had occurred on cell membrane. PMID:22153714

  5. Mechanisms of formation damage in matrix-permeability geothermal wells

    SciTech Connect

    Bergosh, J.L.; Wiggins, R.B.; Enniss, D.O.

    1982-04-01

    Tests were conducted to determine mechanisms of formation damage that can occur in matrix permeability geothermal wells. Two types of cores were used in the testing, actual cores from the East Mesa Well 78-30RD and cores from a fairly uniform generic sandstone formation. Three different types of tests were run. The East Mesa cores were used in the testing of the sensitivity of core to filtrate chemistry. The tests began with the cores exposed to simulated East Mesa brine and then different filtrates were introduced and the effects of the fluid contrast on core permeability were measured. The East Mesa cores were also used in the second series of tests which tested formation sandstone cores were used in the third test series which investigated the effects of different sizes of entrained particles in the fluid. Tests were run with both single-particle sizes and distributions of particle mixes. In addition to the testing, core preparation techniques for simulating fracture permeability were evaluated. Three different fracture formation mechanisms were identified and compared. Measurement techniques for measuring fracture size and permeability were also developed.

  6. A Look Behind the Salt Curve: An Examination of Thickening Mechanisms in Shampoo Formulations

    NASA Astrophysics Data System (ADS)

    Penfield, Kevin

    2008-07-01

    Dynamic oscillatory rheological measurements are used to examine two mechanisms for thickening simple shampoo formulations. The salt curve, in which viscosity of a surfactant solution is maximized at intermediate levels of salt, is shown to be due to the variation in relaxation time; this is found to correlate with variation in the degree of entanglement per micelle. This is contrasted with the effect of PEG-150 distearate, which alters viscosity through a change in modulus.

  7. DNA Damage Response and Immune Defense: Links and Mechanisms.

    PubMed

    Nakad, Rania; Schumacher, Björn

    2016-01-01

    DNA damage plays a causal role in numerous human pathologies including cancer, premature aging, and chronic inflammatory conditions. In response to genotoxic insults, the DNA damage response (DDR) orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. The activation of immune signaling is triggered by different components of the DDR including DNA damage sensors, transducer kinases, and effectors. In this review, we describe recent advances on the understanding of the role of DDR in activating immune signaling. We highlight evidence gained into (i) which molecular and cellular pathways of DDR activate immune signaling, (ii) how DNA damage drives chronic inflammation, and (iii) how chronic inflammation causes DNA damage and pathology in humans. PMID:27555866

  8. DNA Damage Response and Immune Defense: Links and Mechanisms

    PubMed Central

    Nakad, Rania; Schumacher, Björn

    2016-01-01

    DNA damage plays a causal role in numerous human pathologies including cancer, premature aging, and chronic inflammatory conditions. In response to genotoxic insults, the DNA damage response (DDR) orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. The activation of immune signaling is triggered by different components of the DDR including DNA damage sensors, transducer kinases, and effectors. In this review, we describe recent advances on the understanding of the role of DDR in activating immune signaling. We highlight evidence gained into (i) which molecular and cellular pathways of DDR activate immune signaling, (ii) how DNA damage drives chronic inflammation, and (iii) how chronic inflammation causes DNA damage and pathology in humans. PMID:27555866

  9. Vaccine instability in the cold chain: mechanisms, analysis and formulation strategies.

    PubMed

    Kumru, Ozan S; Joshi, Sangeeta B; Smith, Dawn E; Middaugh, C Russell; Prusik, Ted; Volkin, David B

    2014-09-01

    Instability of vaccines often emerges as a key challenge during clinical development (lab to clinic) as well as commercial distribution (factory to patient). To yield stable, efficacious vaccine dosage forms for human use, successful formulation strategies must address a combination of interrelated topics including stabilization of antigens, selection of appropriate adjuvants, and development of stability-indicating analytical methods. This review covers key concepts in understanding the causes and mechanisms of vaccine instability including (1) the complex and delicate nature of antigen structures (e.g., viruses, proteins, carbohydrates, protein-carbohydrate conjugates, etc.), (2) use of adjuvants to further enhance immune responses, (3) development of physicochemical and biological assays to assess vaccine integrity and potency, and (4) stabilization strategies to protect vaccine antigens and adjuvants (and their interactions) during storage. Despite these challenges, vaccines can usually be sufficiently stabilized for use as medicines through a combination of formulation approaches combined with maintenance of an efficient cold chain (manufacturing, distribution, storage and administration). Several illustrative case studies are described regarding mechanisms of vaccine instability along with formulation approaches for stabilization within the vaccine cold chain. These include live, attenuated (measles, polio) and inactivated (influenza, polio) viral vaccines as well as recombinant protein (hepatitis B) vaccines.

  10. The anisotropic mechanical behaviour of electro-spun biodegradable polymer scaffolds: Experimental characterisation and constitutive formulation.

    PubMed

    Limbert, Georges; Omar, Rodaina; Krynauw, Hugo; Bezuidenhout, Deon; Franz, Thomas

    2016-01-01

    Electro-spun biodegradable polymer fibrous structures exhibit anisotropic mechanical properties dependent on the degree of fibre alignment. Degradation and mechanical anisotropy need to be captured in a constitutive formulation when computational modelling is used in the development and design optimisation of such scaffolds. Biodegradable polyester-urethane scaffolds were electro-spun and underwent uniaxial tensile testing in and transverse to the direction of predominant fibre alignment before and after in vitro degradation of up to 28 days. A microstructurally-based transversely isotropic hyperelastic continuum constitutive formulation was developed and its parameters were identified from the experimental stress-strain data of the scaffolds at various stages of degradation. During scaffold degradation, maximum stress and strain in circumferential direction decreased from 1.02 ± 0.23 MPa to 0.38 ± 0.004 MPa and from 46 ± 11 % to 12 ± 2 %, respectively. In longitudinal direction, maximum stress and strain decreased from 0.071 ± 0.016 MPa to 0.010 ± 0.007 MPa and from 69 ± 24 % to 8 ± 2 %, respectively. The constitutive parameters were identified for both directions of the non-degraded and degraded scaffold for strain range varying between 0% and 16% with coefficients of determination r(2)>0.871. The six-parameter constitutive formulation proved versatile enough to capture the varying non-linear transversely isotropic behaviour of the fibrous scaffold throughout various stages of degradation.

  11. Why irreversibility? The formulation of classical and quantum mechanics for nonintegrable systems

    SciTech Connect

    Prigogine, I.

    1995-01-05

    Nonintegrable Poincare systems with a continuous spectrum lead to the appearance of diffusive terms in the frame of classical or quantum dynamics. These terms break time symmetry. They lead, therefore, to limitations to classical trajectory theory and of wave-function formalism. These diffusive terms correspond to well-defined classes of dynamical processes. The diffusive effects are amplified in situations corresponding to persistent interactions. As a result, we have to include, already, in the fundamental dynamical description the two basic aspects, probability and irreversibility, which are so conspicuous on the macroscopic level. We have to formulate both classical and quantum mechanics on the Liouville level of probability distributions. For integrable systems, we recover the usual formulation of classical or quantum mechanics. Instead of being primitive concepts, which cannot be further analyzed, trajectories and wave functions appear as special solutions of the Liouville-von Neumann equations. This extension of classical and quantum dynamics permits us to unify the two concepts of nature that we inherited from the nineteenth century, based, on the one hand, on dynamical time-reversible laws and, on the other, on an evolutionary view associated to entropy. It leads also to a unified formulation of quantum theory, avoiding the conventional dual structure based on Schroedinger`s equation, on the one hand, and on the {open_quotes}collapse{close_quotes} of the wave function, on the other. A dynamical interpretation is given to processes such as decoherence or approach to equilibrium without any appeal to extra dynamic considerations. There is a striking parallelism between classical and quantum theory. For large Poincare systems (LPS), we have, in general, both a {open_quotes}collapse{close_quotes} of trajectories and of wave functions. In both cases, we need a generalized formulation of dynamics in terms of probability distributions or density matrices.

  12. Damage detection in mechanical structures using extreme value statistic.

    SciTech Connect

    Worden, K.; Allen, D. W.; Sohn, H.; Farrar, C. R.

    2002-01-01

    The first and most important objective of any damage identification algorithms is to ascertain with confidence if damage is present or not. Many methods have been proposed for damage detection based on ideas of novelty detection founded in pattern recognition and multivariate statistics. The philosophy of novelty detection is simple. Features are first extracted from a baseline system to be monitored, and subsequent data are then compared to see if the new features are outliers, which significantly depart from the rest of population. In damage diagnosis problems, the assumption is that outliers are generated from a damaged condition of the monitored system. This damage classification necessitates the establishment of a decision boundary. Choosing this threshold value is often based on the assumption that the parent distribution of data is Gaussian in nature. While the problem of novelty detection focuses attention on the outlier or extreme values of the data i.e. those points in the tails of the distribution, the threshold selection using the normality assumption weighs the central population of data. Therefore, this normality assumption might impose potentially misleading behavior on damage classification, and is likely to lead the damage diagnosis astray. In this paper, extreme value statistics is integrated with the novelty detection to specifically model the tails of the distribution of interest. Finally, the proposed technique is demonstrated on simulated numerical data and time series data measured from an eight degree-of-freedom spring-mass system.

  13. Qualitative sensing of mechanical damage by a fluorogenic "click" reaction.

    PubMed

    Döhler, Diana; Rana, Sravendra; Rupp, Harald; Bergmann, Henrik; Behzadi, Shahed; Crespy, Daniel; Binder, Wolfgang H

    2016-09-25

    A simple and unique damage-sensing tool mediated by a Cu(i)-catalyzed [3+2] cycloaddition reaction is reported, where a fluorogenic "click"-reaction highlights physical damage by a strong fluorescence increase accompanied by in situ monitoring of localized self-healing. PMID:27538696

  14. Micro-mechanical modeling of perforating shock damage

    SciTech Connect

    Swift, R.P.; Krogh, K.E.; Behrmann, L.A.; Halleck, P.M.

    1997-11-17

    Shaped charge jet induced formation damage from perforation treatments hinders productivity. Manifestation of this damage is in the form of grain fragmentation resulting in fines that plug up pore throats along with the breakdown of inter-grain cementation. The authors use the Smooth Particle Hydrodynamic (SPH) computational method as a way to explicitly model, on a grain pore scale, the dynamic interactions of grains and grain/pores to calculate the damage resulting from perforation type stress wave loading. The SPH method is a continuum Lagrangian, meshless approach that features particles. Clusters of particles are used for each grain to provide representation of a grain pore structure that is similar to x-ray synchrotron microtomography images. Numerous damage models are available to portray fracture and fragmentation. In this paper the authors present the results of well defined impact loading on a grain pore structure that illustrate how the heterogeneity affects stress wave behavior and damage evolution. The SPH approach easily accommodates the coupling of multi-materials. Calculations for multi-material conditions with the pore space treated as a void, fluid filled, and/or clay filled show diverse effects on the stress wave propagation behavior and damage. SPH comparisons made with observed damage from recovered impacted sandstone samples in gas gun experiments show qualitatively the influence of stress intensity. The modeling approach presented here offers a unique way in concert with experiments to define a better understanding of formation damage resulting from perforation completion treatments.

  15. A damage mechanics approach for quantifying stress changes due to brittle failure of porous rocks

    NASA Astrophysics Data System (ADS)

    Jacquey, Antoine B.; Cacace, Mauro; Blöcher, Guido; Milsch, Harald; Scheck-Wenderoth, Magdalena

    2016-04-01

    Natural fault zones or man-made injection or production of fluid impact the regional stress distribution in Earth's crust and can be responsible for localized stress discontinuities. Understanding the processes controlling fracturing of the porous rocks and mechanical behaviour of fault zones is therefore of interest for several applications including geothermal energy production. In this contribution, we will present a thermodynamically consistent visco-poroelastic damage model which can deal with the multi-scale and multi-physics nature of the physical processes controlling the deformation of porous rocks during and after brittle failure. Deformation of a porous medium is crucially influenced by the changes in the effective stress. Considering a strain-formulated yield cap and the compaction-dilation transition, three different regimes can be identified: quasi-elastic deformation, cataclastic compaction with microcracking (damage accumulation) and macroscopic brittle failure with dilation. The governing equations for deformation, damage accumulation/healing and fluid flow have been implemented in a fully-coupled finite-element-method based framework (MOOSE). The MOOSE framework provides a powerful and flexible platform to solve multiphysics problems implicitly and in a tightly coupled manner on unstructured meshes which is of interest for such non-linear context. To illustrate the model, simulation of a compaction experiment of a sandstone leading to shear failure will be presented which allows to quantify the stress drop accompanying the failure. Finally, we will demonstrate that this approach can also be used at the field scale to simulate hydraulic fracturing and assess the resulting changes in the stress field.

  16. Chemo-mechanics of salt damage in stone.

    PubMed

    Flatt, Robert J; Caruso, Francesco; Sanchez, Asel Maria Aguilar; Scherer, George W

    2014-01-01

    Many porous materials are damaged by pressure exerted by salt crystals growing in their pores. This is a serious issue in conservation science, geomorphology, geotechnical engineering and concrete materials science. In all cases, a central question is whether crystallization pressure will cause damage. Here we present an experiment in which the crystallization pressure and the pore saturation are varied in a controlled way. We demonstrate that a strain energy failure criterion can be used to predict when damage will occur. The experiment considered is the most widely used means to study the susceptibility to salt crystallization, so quantification of this test has far-reaching implications. PMID:25208600

  17. Fractal mechanism for characterizing singularity of mode shape for damage detection

    SciTech Connect

    Cao, M. S.; Ostachowicz, W.; Bai, R. B.; Radzieński, M.

    2013-11-25

    Damage is an ordinary physical phenomenon jeopardizing structural safety; damage detection is an ongoing interdisciplinary issue. Waveform fractal theory has provided a promising resource for detecting damage in plates while presenting a concomitant problem: susceptibility to false features of damage. This study proposes a fractal dimension method based on affine transformation to address this problem. Physical experiments using laser measurement demonstrate that this method can substantially eliminate false features of damage and accurately identify complex cracks in plates, providing a fundamental mechanism that brings the merits of waveform fractal theory into full play in structural damage detection applications.

  18. Fabrication and Mechanical Evaluation of Anatomically-Inspired Quasilaminate Hydrogel Structures with Layer-Specific Formulations

    PubMed Central

    Tseng, Hubert; Cuchiara, Maude L.; Durst, Christopher A.; Cuchiara, Michael P.; Lin, Chris J.; West, Jennifer L.; Grande-Allen, K. Jane

    2012-01-01

    A major tissue engineering challenge is the creation of multilaminate scaffolds with layer-specific mechanical properties representative of native tissues, such as heart valve leaflets, blood vessels, and cartilage. For this purpose, poly(ethylene glycol) diacrylate (PEGDA) hydrogels are attractive materials due to their tunable mechanical and biological properties. This study explored the fabrication of trilayer hydrogel quasilaminates. A novel sandwich method was devised to create quasilaminates with layers of varying stiffnesses. The trilayer structure was comprised of two “stiff” outer layers and one “soft” inner layer. Tensile testing of bilayer quasilaminates demonstrated that these scaffolds do not fail at the interface. Flexural testing showed that the bending modulus of acellular quasilaminates fell between the bending moduli of the “stiff” and “soft” hydrogel layers. The bending modulus and swelling of trilayer scaffolds with the same formulations were not significantly different than single layer gels of the same formulation. The encapsulation of cells and the addition of phenol red within the hydrogel layers decreased bending modulus of the trilayer scaffolds. The data presented demonstrates that this fabrication method can make quasilaminates with robust interfaces, integrating layers of different mechanical properties and biofunctionalization, and thus forming the foundation for a multilaminate scaffold that more accurately represents native tissue. PMID:23053300

  19. Mechanisms and impact of damage resulting from hydraulic fracturing. Topical report, May 1995-July 1996

    SciTech Connect

    Penny, G.S.; Conway, M.W.; Almond, S.W.; Himes, R.; Nick, K.E.

    1996-08-01

    This topical report documents the mechanisms of formation damage following hydraulic fracturing and their impact upon gas well productivity. The categories of damage reviewed include absolute or matrix permeability damage, relative permeability alterations, the damage of natural fracture permeability mechanisms and proppant conductivity impairment. Case studies are reviewed in which attempts are made to mitigate each of the damage types. Industry surveys have been conducted to determine the perceptions of the industry on the topic of formation damage following hydraulic fracturing and to identify key formations in which formation damage is a problem. From this information, technical hurdles and new technology needs are identified and estimates are made of the benefits of developing and applying minimum formation damage technology.

  20. Influence of binder type on interacting variables acting on mechanical properties of a sulfadimidine tablet formulation.

    PubMed

    Alebiowu, G; Ojeleye, O O

    2007-01-01

    A study of the quantitative effect of type of binder (N), applied pressure (P), and granular size (G) on two mechanical properties-tensile strength (TS) and brittle fracture index (BFI) - of a sulfadimidine tablet formulation has been carried out by using a 2(3) factorial experimental design. The results obtained from this work suggest that P exhibited the largest individual effect on TS and BFI. It is also seen from this work that the nature of binders in combination affects the influence that P and G had on the TS or BFI.

  1. Mechanical relaxation of localized residual stresses associatedwith foreign object damage

    SciTech Connect

    Boyce, B.L.; Chen, X.; Peters, J.O.; Hutchinson, J.H.; Ritchie,R.O.

    2002-05-01

    Foreign-object damage associated with the ingestion ofdebris into aircraft turbine engines can lead to a marked degradation inthe high-cycle fatigue life of turbine components. This degradation isgenerally considered to be associated with the premature initiation offatigue cracks at or near the damage sites; this is suspected to be dueto, at least in part, the impact-induced residual stress state, which canbe strongly tensile in these locations.

  2. Discrete fracture modeling of hydro-mechanical damage processes in geological systems

    NASA Astrophysics Data System (ADS)

    Kim, K.; Rutqvist, J.; Houseworth, J. E.; Birkholzer, J. T.

    2014-12-01

    This study presents a modeling approach for investigating coupled thermal-hydrological-mechanical (THM) behavior, including fracture development, within geomaterials and structures. In the model, the coupling procedure consists of an effective linkage between two codes: TOUGH2, a simulator of subsurface multiphase flow and mass transport based on the finite volume approach; and an implementation of the rigid-body-spring network (RBSN) method, a discrete (lattice) modeling approach to represent geomechanical behavior. One main advantage of linking these two codes is that they share the same geometrical mesh structure based on the Voronoi discretization, so that a straightforward representation of discrete fracture networks (DFN) is available for fluid flow processes. The capabilities of the TOUGH-RBSN model are demonstrated through simulations of hydraulic fracturing, where fluid pressure-induced fracturing and damage-assisted flow are well represented. The TOUGH-RBSN modeling methodology has been extended to enable treatment of geomaterials exhibiting anisotropic characteristics. In the RBSN approach, elastic spring coefficients and strength parameters are systematically formulated based on the principal bedding direction, which facilitate a straightforward representation of anisotropy. Uniaxial compression tests are simulated for a transversely isotropic material to validate the new modeling scheme. The model is also used to simulate excavation fracture damage for the HG-A microtunnel in the Opalinus Clay rock, located at the Mont Terri underground research laboratory (URL) near Saint-Ursanne, Switzerland. The Opalinus Clay has transversely isotropic material properties caused by natural features such as bedding, foliation, and flow structures. Preferential fracturing and tunnel breakouts were observed following excavation, which are believed to be strongly influenced by the mechanical anisotropy of the rock material. The simulation results are qualitatively

  3. 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.

  4. Fatigue damage-fracture mechanics interaction in cortical bone.

    PubMed

    Yeni, Y N; Fyhrie, D P

    2002-03-01

    Fatigue loading causes accumulation of damage that may lead to the initiation of a macrocrack and result in a catastrophic failure of bone. The objective of this study was to examine the influence of fatigue damage on crack growth parameters in bovine cortical bone. Nineteen rectangular beam specimens (4 x 4 x 48 mm) were machined from bovine tibiae. The long axis of the beams was aligned with the long axis of bones. Using a four-point bending fatigue setup, ten specimens were fatigue-damaged to different levels as indicated by stiffness loss. A through-thickness notch was machined at the center of each damaged and undamaged beam. The notched specimens were then monotonically loaded beyond failure using a three-point bending protocol. Critical stress intensity factor, K(I), and work to critical load, W(Q), were significantly lower in the damaged group than in the undamaged group (p < 0.03). When the undamaged specimens were assigned a percent stiffness loss of zero and pooled with the damaged group, significant negative correlations of percent stiffness loss with K(I) (R = 0.58, p < 0.01), W(Q) (R = 0.54, p < 0.02), maximum load, P(max) (R = 0.59, p < 0.008), deflection at maximum load, Delta(max) (R = 0.48, p < 0.04), structural stiffness, S(max) (R = 0.53, p < 0.02), W(max) (R = 0.55, p < 0.02), and load at 1.4 mm deflection (a value beyond failure but without complete fracture), P(1.4) (R = 0.47, p < 0.05), were found. Post hoc analysis revealed that the average load-deflection curve from the damaged group was transformable into that from the undamaged group through a special shift on the load-deflection plane. Fatigue damage reduces bone stiffness and resistance to crack initiation, maximum load-carrying capacity, and deflection before and after failure in cortical bone. The data suggest there is a single rule that governs the overall effect of fatigue damage on the fracture behavior of cortical bone. PMID:11882466

  5. Damage mechanisms avoided or managed for NIF large optics

    DOE PAGESBeta

    Manes, K. R.; Spaeth, M. L.; Adams, J. J.; Bowers, M. W.; Bude, J. D.; Carr, C. W.; Conder, A. D.; DiNicola, J. M. G.; Dixit, S. N.; Feigenbaum, E.; et al

    2016-02-09

    After every other failure mode has been considered, in the end, the high-performance limit of all lasers is set by optical damage. The demands of inertial confinement fusion (ICF) pushed lasers designed as ICF drivers into this limit from their very earliest days. The first ICF lasers were small, and their pulses were short. Their goal was to provide as much power to the target as possible. Typically, they faced damage due to high intensity on their optics. As requests for higher laser energy, longer pulse lengths, and better symmetry appeared, new kinds of damage also emerged, some of themmore » anticipated and others unexpected. This paper will discuss the various types of damage to large optics that had to be considered, avoided to the extent possible, or otherwise managed as the National Ignition Facility (NIF) laser was designed, fabricated, and brought into operation. Furthermore, it has been possible for NIF to meet its requirements because of the experience gained in previous ICF systems and because NIF designers have continued to be able to avoid or manage new damage situations as they have appeared.« less

  6. Mechanisms underlying spinal cord damage in decompression sickness.

    PubMed

    Hallenbeck, J M; Bove, A A; Elliott, D H

    1975-04-01

    Decompression sickness, which damaged the spinal cord, was produced in anesthetized dogs using a compression chamber. Cerebrospinal fluid pressure and several intravascular and intracardiac pressures were monitored during the course of the simulated dives. Manometric responses to forcible lung inflation and abdominal compression were measured both predive and postdive after signs of spinal cord damage were evident. Cinevenography of the epidural vertebral venous system was performed both predive and postdive. Histopathologic studies of the brains and cords of both predive and postdive. Histopathologic studies of the brains and cords of paretic animals were carried out. The results indicate that the epidural vertebral venous system becomes obstructed during spinal cord damaging decompression sickness and strongly suggests that spinal cord infarction in decompression sickness is caused by obstruction of cord venous drainage at the level of the epidural vertebral venous system. PMID:1168317

  7. Fatigue damage mechanisms in boron-aluminium composite laminates

    NASA Technical Reports Server (NTRS)

    Dvorak, G. J.; Johnson, W. S.

    1980-01-01

    The relationship between fatigue and shakedown in metal matrix composites is investigated theoretically and experimentally for unidirectional and laminated 6061 Al-B materials. It is shown that no fatigue damage takes place if the applied stress range is such that the material remains elastic, or shakes down, i.e., resumes elastic cyclic straining after a small number of plastic strain cycles. Fatigue damage occurs only in specimens subjected to stress ranges which cause sustained cyclic plastic straining in the aluminum matrix. If the applied stress range is smaller than that required for fatigue failure, after about 10 to the 6th cycles a saturation damage state is reached which remains essentially unchanged with increasing number of cycles.

  8. Conical intersections in solution: Formulation, algorithm, and implementation with combined quantum mechanics/molecular mechanics method

    NASA Astrophysics Data System (ADS)

    Cui, Ganglong; Yang, Weitao

    2011-05-01

    The significance of conical intersections in photophysics, photochemistry, and photodissociation of polyatomic molecules in gas phase has been demonstrated by numerous experimental and theoretical studies. Optimization of conical intersections of small- and medium-size molecules in gas phase has currently become a routine optimization process, as it has been implemented in many electronic structure packages. However, optimization of conical intersections of small- and medium-size molecules in solution or macromolecules remains inefficient, even poorly defined, due to large number of degrees of freedom and costly evaluations of gradient difference and nonadiabatic coupling vectors. In this work, based on the sequential quantum mechanics and molecular mechanics (QM/MM) and QM/MM-minimum free energy path methods, we have designed two conical intersection optimization methods for small- and medium-size molecules in solution or macromolecules. The first one is sequential QM conical intersection optimization and MM minimization for potential energy surfaces; the second one is sequential QM conical intersection optimization and MM sampling for potential of mean force surfaces, i.e., free energy surfaces. In such methods, the region where electronic structures change remarkably is placed into the QM subsystem, while the rest of the system is placed into the MM subsystem; thus, dimensionalities of gradient difference and nonadiabatic coupling vectors are decreased due to the relatively small QM subsystem. Furthermore, in comparison with the concurrent optimization scheme, sequential QM conical intersection optimization and MM minimization or sampling reduce the number of evaluations of gradient difference and nonadiabatic coupling vectors because these vectors need to be calculated only when the QM subsystem moves, independent of the MM minimization or sampling. Taken together, costly evaluations of gradient difference and nonadiabatic coupling vectors in solution or

  9. EFFECT OF FORMULATION AND PROCESS VARIABLES ON THE RELEASE, MECHANICAL AND MUCOADHESIVE PROPERTIES OF IBUPROFEN TABLET FORMULATIONS.

    PubMed

    Adetunji, Oladapo A; Odeniyi, Michael A; Itiola, Oludele A

    2015-01-01

    A 2(4) full factorial analysis was used to study the individual and interactive effects of binder type, X1; binder concentration, X2; relative density, X3 and tabletting technique, X4, on disintegration time (DT), brittle fracture index (BFI), tensile strength (TS) and mucoadhesion time (MT) of ibuprofen tablets formulated by direct compression (DC) and wet granulation (WG), and containing Entandophragnia angolense gum (ENTA) as binder, in comparison with hydroxypropylcellulose. The result of the FTIR and UV peaks suggests the absence of any interaction between ENTA and ibuprofen. Interactions between the polymers and ibuprofen were determined using FTIR and UV determinations. The ranking of the individual effects on DT and BFI was X2 > X3 > X1 > X4, on TS; X3 > X2> X1 > X4 and on MT; X2> X > X4 > X3. The effects of changing the binder from hydroxypropylcellulose to ENTA led to an increase in DT and decrease in TS, BFI and MT. Changing X2 and X3 to higher values increased the DT and TS. The interaction between X1 and X2 had the highest influence on BEI and MT, while interaction between "X3 and X4", and "X2 and X3" had the highest influence on DT and TS, respectively. Ibuprofen tablets prepared by wet granulation method and containing Entandophragma angolense gum showed lower capping/lamination tendencies and better mucoadhesive drug release profiles. PMID:26642687

  10. Mechanisms of cell damage in agitated microcarrier tissue culture reactors

    NASA Technical Reports Server (NTRS)

    Cherry, Robert S.; Papoutsakis, E. Terry

    1986-01-01

    Cells growing on microcarriers may be damaged by collisions of the microcarrier against another microcarrier or the reactor agitator. Bead-bead collisions are caused by small-scale turbulence, which can also cause high local shear stress on the cells. The cells are also exposed to 10-20 Hz cyclic shear stress by bead rotation.

  11. Formulation of thermo-hydro-mechanical coupling behavior of unsaturated soils based on hybrid mixture theory

    NASA Astrophysics Data System (ADS)

    Cai, Guo-Qing; Zhao, Cheng-Gang; Sheng, Dai-Chao; Zhou, An-Nan

    2014-08-01

    Thermo-Hydro-Mechanical (THM) coupling processes in unsaturated soils are very important in both theoretical researches and engineering applications. A coupled formulation based on hybrid mixture theory is derived to model the THM coupling behavior of unsaturated soils. The free-energy and dissipative functions for different phases are derived from Taylor's series expansions. Constitutive relations for THM coupled behaviors of unsaturated soils, which include deformation, entropy change, fluid flow, heat conduction, and dynamic compatibility conditions on the interfaces, are then established. The number of field equations is shown to be equal to the number of unknown variables; thus, a closure of this coupling problem is established. In addition to modifications of the physical conservation equations with coupling effect terms, the constitutive equations, which consider the coupling between elastoplastic deformation of the soil skeleton, fluid flow, and heat transfer, are also derived.

  12. a Geometric Formulation of the Higgs Mechanism via Internal Metric Fields.

    NASA Astrophysics Data System (ADS)

    Talmadge, Andrew Vansickle, Jr.

    1990-01-01

    This dissertation is divided into two parts. The first part (chapters 1-3) formulates the Higgs mechanism for the standard model of electroweak interactions in terms of sesquilinear forms that govern the interactions of the leptonic spinors of the theory. It is shown that a geometric choice of a sesquilinear form that links the left- and right-handed components of the spinors reproduces the results of the Higg's mechanism. The mass identifications (for the leptons and the bosons) in this model do not contain any terms arising from the sesquilinear form that is used to model the interactions. The second part (chapter 4) of this work is centered on the geometry of the internal fields in a general U(n) -type gauge theory. It is shown that the Higgs mechanism can be interpreted geometrically as the choice of a generalized metric field on the internal spaces of the theory. Existence and properties of such metric fields are discussed for Minkowski spacetime and a one point compactification of Minkowski spacetime which is diffeomorphic to S ^4.

  13. Hierarchical nanoreinforced composites: Computational analysis of damage mechanisms

    NASA Astrophysics Data System (ADS)

    Mishnaevsky, Leon, Jr.; Pontefisso, Alessandro; Dai, Gaoming

    2016-07-01

    The potential of hierarchical composites with secondary nanoreinforcement is discussed and analysed on the basis of the computational modelling. The concept of nanostructuring of interfaces as an important reserve of the improvement of the composite properties is discussed. The influence of distribution, shape, orientation of nanoparticles (carbon nanotube, graphene) in unidirectional polymer matrix composites on the strength and damage resistance of the composites is studied in computational studies. The possible directions of the improvement of nanoreinforced composites by controlling shapes, localization and other parameters of nanoreinforcements are reviewed.

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

    NASA Astrophysics Data System (ADS)

    Fan, Linfeng; Lehmann, Peter; Or, Dani

    2015-10-01

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

  15. [Continuous damage mechanics: Critical states: Technical progress report

    SciTech Connect

    Krajcinovic, D.

    1992-06-01

    Failure can occur in many distinctly different ways depending on the material, stress and strain fields, temperature field, environmental effects, strain rate, etc. The proposed research program will focus on a single well defined class of failure modes common to many structures and machine elements. This class of problems is characterized by a gradually evolving microscale process which at a certain point triggers a discontinuous or singular (qualitative) change of macroscale response. Consideration of critical states of cooperative processes requires radical departure from the well traveled paths. Recently developing methods of statistical physics seem to be applicable to the class of problems under consideration. These models are generally formulated as discrete enabling consideration of spatial-temporal complexities as they raise from the microstructural disorder. However, in many cases these models in the limit do not converge to the traditional continuum theories.

  16. (Continuous damage mechanics: Critical states: Technical progress report)

    SciTech Connect

    Krajcinovic, D.

    1992-01-01

    Failure can occur in many distinctly different ways depending on the material, stress and strain fields, temperature field, environmental effects, strain rate, etc. The proposed research program will focus on a single well defined class of failure modes common to many structures and machine elements. This class of problems is characterized by a gradually evolving microscale process which at a certain point triggers a discontinuous or singular (qualitative) change of macroscale response. Consideration of critical states of cooperative processes requires radical departure from the well traveled paths. Recently developing methods of statistical physics seem to be applicable to the class of problems under consideration. These models are generally formulated as discrete enabling consideration of spatial-temporal complexities as they raise from the microstructural disorder. However, in many cases these models in the limit do not converge to the traditional continuum theories.

  17. Derivation of the Schrodinger Equation from the Hamilton-Jacobi Equation in Feynman's Path Integral Formulation of Quantum Mechanics

    ERIC Educational Resources Information Center

    Field, J. H.

    2011-01-01

    It is shown how the time-dependent Schrodinger equation may be simply derived from the dynamical postulate of Feynman's path integral formulation of quantum mechanics and the Hamilton-Jacobi equation of classical mechanics. Schrodinger's own published derivations of quantum wave equations, the first of which was also based on the Hamilton-Jacobi…

  18. Initiation and progression of mechanical damage in the intervertebral disc under cyclic loading using continuum damage mechanics methodology: A finite element study

    PubMed Central

    Qasim, Muhammad; Natarajan, Raghu N.; An, Howard S.; Andersson, Gunnar B.J.

    2013-01-01

    It is difficult to study the breakdown of disc tissue over several years of exposure to bending and lifting by experimental methods. There is also no finite element model that elucidates the failure mechanism due to repetitive loading of the lumbar motion segment. The aim of this study was to refine an already validated poro-elastic finite element model of lumbar motion segment to investigate the initiation and progression of mechanical damage in the disc under simple and complex cyclic loading conditions. Continuum damage mechanics methodology was incorporated into the finite element model to track the damage accumulation in the annulus in response to the repetitive loading. The analyses showed that the damage initiated at the posterior inner annulus adjacent to the endplates and propagated outwards towards its periphery under all loading conditions simulated. The damage accumulated preferentially in the posterior region of the annulus. The analyses also showed that the disc failure is unlikely to happen with repetitive bending in the absence of compressive load. Compressive cyclic loading with low peak load magnitude also did not create the failure of the disc. The finite element model results were consistent with the experimental and clinical observations in terms of the region of failure, magnitude of applied loads and the number of load cycles survived. PMID:22682891

  19. Progress in research on laser damage mechanisms and contamination problem

    NASA Astrophysics Data System (ADS)

    Jitsuno, T.; Murakami, H.; Kato, K.; Sato, E.; Mikami, K.; Motokoshi, S.; Miyanaga, N.; Azechi, H.

    2014-09-01

    In high power laser systems, the laser-induced damage threshold (LIDT) in optical coating is very important parameters for obtaining high performances. Recently, LIDT was found to have strong temperature dependences in the bulk, surface of substrates, and in coatings. These temperature dependences of LIDT were carefully measured, and the damage formation model was constructed regarding to this temperature dependence. To explain this temperature dependence of LIDT, the temperature dependences of the initial electron generation and electron multiplication in the avalanche process were taken into account. On the other hand, LIDT in optical coating is very sensitive to organic contaminations accumulated in coating layers during storage and using condition. This paper also introduces the oil-contamination problem in LFEX laser system for First Ignition scheme in the laser fusion. We have analyzed contaminants and evaluated the effects of the contamination. We also developed new cleaning methods to remove contamination from the coating, and we have succeeded to prevent the degradation in LIDT for the duration of evacuation with Silica-gel in the chamber. The quantitative analysis of contamination on LIDT was made. We have investigated the characteristics of LIDT in dielectric coatings under the controlled contamination with several materials.

  20. Structural fluctuation of protein in water around its native state: a new statistical mechanics formulation.

    PubMed

    Kim, Bongsoo; Hirata, Fumio

    2013-02-01

    A new statistical mechanics formulation of characterizing the structural fluctuation of protein correlated with that of water is presented based on the generalized Langevin equation and the 3D-reference interaction site model (RISM)/RISM theory of molecular liquids. The displacement vector of atom positions, and their conjugated momentum, are chosen for the dynamic variables for protein, while the density fields of atoms and their momentum fields are chosen for water. Projection of other degrees of freedom onto those dynamic variables using the standard projection operator method produces essentially two equations, which describe the time evolution of fluctuation concerning the density field of solvent and the conformation of protein around an equilibrium state, which are coupled with each other. The equation concerning the protein dynamics is formally akin to that of the coupled Langevin oscillators, and is a generalization of the latter, to atomic level. The most intriguing feature of the new equation is that it contains the variance-covariance matrix as the "Hessian" term describing the "force" restoring an equilibrium conformation, which is the second moment of the fluctuation of atom positions. The "Hessian" matrix is naturally identified as the second derivative of the free energy surface around the equilibrium. A method to evaluate the Hessian matrix based on the 3D-RISM/RISM theory is proposed. Proposed also is an application of the present formulation to the molecular recognition, in which the conformational fluctuation of protein around its native state becomes an important factor as exemplified by so called "induced fitting."

  1. Structural fluctuation of protein in water around its native state: A new statistical mechanics formulation

    NASA Astrophysics Data System (ADS)

    Kim, Bongsoo; Hirata, Fumio

    2013-02-01

    A new statistical mechanics formulation of characterizing the structural fluctuation of protein correlated with that of water is presented based on the generalized Langevin equation and the 3D-reference interaction site model (RISM)/RISM theory of molecular liquids. The displacement vector of atom positions, and their conjugated momentum, are chosen for the dynamic variables for protein, while the density fields of atoms and their momentum fields are chosen for water. Projection of other degrees of freedom onto those dynamic variables using the standard projection operator method produces essentially two equations, which describe the time evolution of fluctuation concerning the density field of solvent and the conformation of protein around an equilibrium state, which are coupled with each other. The equation concerning the protein dynamics is formally akin to that of the coupled Langevin oscillators, and is a generalization of the latter, to atomic level. The most intriguing feature of the new equation is that it contains the variance-covariance matrix as the "Hessian" term describing the "force" restoring an equilibrium conformation, which is the second moment of the fluctuation of atom positions. The "Hessian" matrix is naturally identified as the second derivative of the free energy surface around the equilibrium. A method to evaluate the Hessian matrix based on the 3D-RISM/RISM theory is proposed. Proposed also is an application of the present formulation to the molecular recognition, in which the conformational fluctuation of protein around its native state becomes an important factor as exemplified by so called "induced fitting."

  2. True porosity measurement of hair: a new way to study hair damage mechanisms.

    PubMed

    Hessefort, Yin; Holland, Brian T; Cloud, Richard W

    2008-01-01

    This study employs a novel method, gas sorption (1), to quantify the porosity characteristics of hair by determining total pore volume, adsorption pore-size distribution, and the surface area of damaged hair. Damage mechanisms were studied by comparing the different pore volume and surface area resulting from two different types of damage: chemical and UV. Hair color measurement and tensile strength, both reflecting the changes in hair cortex, were also employed in this study. The results suggest that hair damage caused by oxidative bleach and UV oxidation follows different pathways. Chemical damage (oxidative bleach) nearly triples the hair surface area in the first minute of bleaching due to the increase in the number of pores, followed by a sudden drop after 10 min of bleaching from smaller pores breaking down into larger ones. In contrast, UV damage shows an immediate loss in surface area in the first 200 hr of exposure and a gradual increase as exposure time continues.

  3. True porosity measurement of hair: a new way to study hair damage mechanisms.

    PubMed

    Hessefort, Yin; Holland, Brian T; Cloud, Richard W

    2008-01-01

    This study employs a novel method, gas sorption (1), to quantify the porosity characteristics of hair by determining total pore volume, adsorption pore-size distribution, and the surface area of damaged hair. Damage mechanisms were studied by comparing the different pore volume and surface area resulting from two different types of damage: chemical and UV. Hair color measurement and tensile strength, both reflecting the changes in hair cortex, were also employed in this study. The results suggest that hair damage caused by oxidative bleach and UV oxidation follows different pathways. Chemical damage (oxidative bleach) nearly triples the hair surface area in the first minute of bleaching due to the increase in the number of pores, followed by a sudden drop after 10 min of bleaching from smaller pores breaking down into larger ones. In contrast, UV damage shows an immediate loss in surface area in the first 200 hr of exposure and a gradual increase as exposure time continues. PMID:18818850

  4. Heat transfer in damaged material

    NASA Astrophysics Data System (ADS)

    Kruis, J.

    2013-10-01

    Fully coupled thermo-mechanical analysis of civil engineering problems is studied. The mechanical analysis is based on damage mechanics which is useful for modeling of behaviour of quasi-brittle materials, especially in tension. The damage is assumed to be isotropic. The heat transfer is assumed in the form of heat conduction governed by the Fourier law and heat radiation governed by the Stefan-Boltzmann law. Fully coupled thermo-mechanical problem is formulated.

  5. Temporal Effects of Mechanical Loading on Deformation-Induced Damage in Skeletal Muscle Tissue

    PubMed Central

    Stekelenburg, A.; Strijkers, G. J.; Rijpkema, J. J. M.; Baaijens, F. P. T.; Bader, D. L.; Nicolay, K.; Oomens, C. W. J.

    2010-01-01

    Mechanical loading of soft tissues covering bony prominences can cause skeletal muscle damage, ultimately resulting in a severe pressure ulcer termed deep tissue injury. Recently, by means of an experimental-numerical approach, it was shown that local tissue deformations cause tissue damage once a deformation threshold is exceeded. In the present study, the effects of load exposure time and intermittent load relief on the development of deformation-induced muscle damage were investigated. The data showed that a 2 h loading period caused more damage than 10 min loading. Intermittent load reliefs of 2 min during a 2 h loading period had minimal effect on the evolution of skeletal muscle damage. In addition, a local deformation threshold for damage was found, which was similar for each of the loading regimes applied in this study. For short loading periods, these results imply that local tissue deformations determine whether muscle damage will develop and the exposure time influences the amount of tissue damage. Temporary load reliefs were inefficient in reducing deformation-induced damage, but may still influence the development of ischemia-induced damage during longer loading periods. PMID:20232152

  6. 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.

  7. Experimental Study on the Thermal Damage Characteristics of Limestone and Underlying Mechanism

    NASA Astrophysics Data System (ADS)

    Zhang, Weiqiang; Sun, Qiang; Hao, Shuqing; Wang, Bo

    2016-08-01

    This work discusses an experimental investigation on the thermal damage characteristics of limestone and underlying mechanism. Cylindrical rock samples were heated to a specific temperature level of 25, 100, 200, 300, 400, 500, 600, 700, 800, and 900 °C. Then the thermal damage evolution equation was established based on the experimental results and the characteristics of thermal damage were analyzed. Last, possible mechanisms for the observed thermo-physical and mechanical response are discussed. The results show that with the increase of temperature in the tested range of temperature, the P-wave velocity, peak compressive strength and elastic modulus decrease, but the peak strain increases; the damage factors increase faster in 200-600 °C; the development of high-temperature-induced cracks conforms to the dislocation theory; the decomposition of magnesium carbonate and dolomite is the main reaction in the tested temperature range.

  8. Vascular damage, fibrosis, and chronic inflammation in mechanical back pain problems.

    PubMed

    Jayson, M I

    1989-05-01

    Our current hypothesis is that mechanical damage in the spine such as a disc prolapse can lead directly to pain. However, pain arising for this reason is usually of short duration. In many subjects, however, the mechanical problems lead to vascular damage and, in particular, venous obstruction and dilatation with endothelial damage, fibrin deposition, and intravascular thromboses. In turn, this is associated with perineural and intraneural fibrosis. There is a defect in the fibrinolytic system in the peripheral blood that may be the result of vascular damage but in turn may contribute to the persistence of this problem. Therefore, it seems likely that in many patients with chronic mechanical back pain there are important vascular, fibrotic, and inflammatory components to the problem. Treatment in the future should be directed specifically at these aspects of the disorder and hopefully can lead to better control of symptoms.

  9. Pre- and post-annealing of mechanical damage in silicon wafers

    NASA Technical Reports Server (NTRS)

    Schwottke, G. H.

    1982-01-01

    Basic properties of mechanical damage in silicon consisting of cracks and abrasion were studied using transmission electron microscopy. The crystallographic structure of mechanical damage was determined before and after high temperature annealing. The main findings include that stresses in silicon around crack tips are not plastically relieved at room temperature and that abrasion at room temperature introduces shear loops into the silicon. It was also found that cracks of micron size can be annealed out, specifically, if cleavage occurs on 111 planes. The healing products of such cracks are 60 deg and 90 deg dislocations. Submicron cracks transform into stacking faults during annealing. Likewise high concentrations of shear loops due abrasion were found to anneal into stacking faults. A one to one correlation between surface areas containing small cracks and stacking faults was made. Measurements of damage removal on silicon surfaces through chemical-mechanical etching techniques are presented. It is shown that silicon dioxide repolishes damaged silicon surfaces most effectively.

  10. Saengshik, a formulated health food, prevents liver damage in CCl4-induced mice and increases antioxidant activity in elderly women.

    PubMed

    Kim, Hwa-young; Kim, Joong-Hark; Lee, Seong-Ae; Chang, Hey-eun; Park, Mi-hyoun; Hwang, Sung-joo; Lee, Ju-yeon; Mok, Chulkyoon; Hong, Seong-gil

    2008-06-01

    Saengshik is a Korean noncooked food made with of more than 30 different whole gains, vegetables, fruits, mushrooms, and seaweeds. All of these ingredients are frozen and dried to minimize the loss of nutrients. Saengshik has become popular among health-conscious people in the Republic of Korea. The study aims to investigate antioxidant effects of Saengshik by in vivo and human experiments. In in vivo tests, mice were fed Saengshik for 4 weeks, and oxidative damage was induced by CCl(4). Then the effects of Saengshik on oxidative damage were examined. It was found that plasma lipid hydroperoxide and protein oxidative damages were significantly suppressed and antioxidants, glutathione, and thiol groups were increased. The activity of the antioxidant enzyme superoxide dismutase was increased, and the level of glutamate pyruvate transaminase was decreased. In a human study, elderly people were given Saengshik for 24 weeks, and changes in antioxidant defense of the body were examined. Antioxidant activities in plasma were enhanced, although the difference was not significant. Therefore, it is expected that Saengshik is effective at removing oxidants from body tissues, preventing oxidative damage, and eventually boosting the antioxidant capacity of the body.

  11. Alphavirus Encephalomyelitis: Mechanisms and Approaches to Prevention of Neuronal Damage.

    PubMed

    Griffin, Diane E

    2016-07-01

    Mosquito-borne viruses are important causes of death and long-term neurologic disability due to encephalomyelitis. Studies of mice infected with the alphavirus Sindbis virus have shown that outcome is dependent on the age and genetic background of the mouse and virulence of the infecting virus. Age-dependent susceptibility reflects the acquisition by neurons of resistance to virus replication and virus-induced cell death with maturation. In mature mice, the populations of neurons most susceptible to infection are in the hippocampus and anterior horn of the spinal cord. Hippocampal infection leads to long-term memory deficits in mice that survive, while motor neuron infection can lead to paralysis and death. Neuronal death is immune-mediated, rather than a direct consequence of virus infection, and associated with entry and differentiation of pathogenic T helper 17 cells in the nervous system. To modulate glutamate excitotoxicity, mice were treated with an N-methyl-D-aspartate receptor antagonist, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonists or a glutamine antagonist. The N-methyl-D-aspartate receptor antagonist MK-801 protected hippocampal neurons but not motor neurons, and mice still became paralyzed and died. α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonists GYKI-52466 and talampanel protected both hippocampal and motor neurons and prevented paralysis and death. Glutamine antagonist 6-diazo-5-l-norleucine protected hippocampal neurons and improved memory generation in mice surviving infection with an avirulent virus. Surprisingly, in all cases protection was associated with inhibition of the antiviral immune response, reduced entry of inflammatory cells into the central nervous system, and delayed virus clearance, emphasizing the importance of treatment approaches that include prevention of immunopathologic damage. PMID:27114366

  12. Experimental investigation on mechanical damage characteristics of sandstone under triaxial cyclic loading

    NASA Astrophysics Data System (ADS)

    Yang, Sheng-Qi; Ranjith, P. G.; Huang, Yan-Hua; Yin, Peng-Fei; Jing, Hong-Wen; Gui, Yi-Lin; Yu, Qing-Lei

    2015-05-01

    The mechanical damage characteristics of sandstone subjected to cyclic loading is very significant to evaluate the stability and safety of deep excavation damage zones. However to date, there are very few triaxial experimental studies of sandstone under cyclic loading. Moreover, few X-ray micro-computed tomography (micro-CT) observations have been adopted to reveal the damage mechanism of sandstone under triaxial cyclic loading. Therefore, in this research, a series of triaxial cyclic loading tests and X-ray micro-CT observations were conducted to analyse the mechanical damage characteristics of sandstone with respect to different confining pressures. The results indicated that at lower confining pressures, the triaxial strength of sandstone specimens under cyclic loading is higher than that under monotonic loading; whereas at confining pressures above 20 MPa, the triaxial strength of sandstone under cyclic loading is approximately equal to that under monotonic loading. With the increase of cycle number, the crack damage threshold of sandstone first increases, and then significantly decreases and finally remains constant. Based on the damage evolution of irreversible deformation, it appears that the axial damage value of sandstone is all higher than the radial damage value before the peak strength; whereas the radial damage value is higher than the axial damage value after the peak strength. The evolution of Young's modulus and Poisson's ratio of sandstone can be characterized as having four stages: (i) Stage I: material strengthening; (ii) Stage II: material degradation; (iii) Stage III: material failure and (iv) Stage IV: structure slippage. X-ray micro-CT observations demonstrated that the CT scanning surface images of sandstone specimens are consistent with actual surface crack photographs. The analysis of the cross-sections of sandstone supports that the system of crack planes under triaxial cyclic loading is much more complicated than that under triaxial

  13. Suppression of nano-absorbing precursors and damage mechanism in optical coatings for 3ω mirrors.

    PubMed

    Wang, Hu; Qi, Hongji; Zhang, Weili; Sun, Jian; Chai, Yingjie; Tu, Feifei; Zhao, Jiaoling; Yu, Zhen; Wang, Bin; Zhu, Meiping; Yi, Kui; Shao, Jianda

    2016-03-15

    Damage precursors in the 3ω (351 nm) mirror for a high-power laser system are investigated as well as the relevant damage mechanisms. The precursors are classified into two ensembles according to the different laser resistance and damage features. The former is nano-absorbing precursors, which are sensitive to the standing wave electric field and vulnerable to the laser irradiation. The latter is submicrometer nodular defects, which have higher laser resistance and are sensitive to the adhesion strength between the fluoride coatings and oxide coatings. The damage due to nano-absorbing precursors is efficiently suppressed with the double stack design that screens the electric field in the oxides. Currently, the nodular seed is major originating from the Al2O3/SiO2 stack. Even for the same defect type and mirror, the final damage features are dependent on the local mechanical properties at the irradiation location. The investigations of the damage mechanisms provide a direction to further improve the laser-induced damage threshold of the 3ω mirror.

  14. Conditioning polymers in today's shampoo formulations - efficacy, mechanism and test methods.

    PubMed

    Hössel, P; Dieing, R; Nörenberg, R; Pfau, A; Sander, R

    2000-02-01

    Today's shampoo formulations are beyond the stage of pure cleansing of the hair. Additional benefits are expected, e.g. conditioning, smoothing of the hair surface, improvement of combability and lather creaminess. Cationic polymers play an important role in providing many of those features. Therefore, within the last few years their use in shampoos has increased greatly. In the only last two decades, shampoo designation has gradually changed from '2-in-1' to '3-in-1' and then to 'multifunctional', as at present. The consumer demands products which live up to their promises. Modern shampoos contain a wide variety of ingredients such as co-surfactants, vitamins and pro-vitamins, protein derivatives, silicones, natural-based plant extracts and other 'active ingredients', but there is still a need for conditioning polymers. The specific objective of this study is to assess the conditioning efficacy of cationic polymers and to investigate their mechanisms in a shampoo system. The investigations were carried out on formulations that contained sodium lauryl ether sulphate and different cationic polymers, e.g. Polyquaternium 7, 10, 11, cationic guar gum and Luviquat Care (Polyquaternium 44), a new branched copolymer of vinylpyrrolidone (VP) and quaternized vinylimidazolium salts (QVI). We used test methods relevant to the applications in question, such as combing force measurements, the feel of the hair and the creaminess of the lather, to assess the efficacy. Atomic force microscopy and electrokinetics (streaming potential) were used to detect polymer residues on treated hair. All the polymers under investigation improved the overall performance of the shampoo formulations. This was demonstrated by means of combing force measurements, sensorial tests and analytical methods, namely zeta potential measurement and atomic force microscopy. Polyquaternium 44 exhibited the best conditioning properties on wet hair without sacrificing removability or absence of build-up. The

  15. Conditioning polymers in today's shampoo formulations - efficacy, mechanism and test methods.

    PubMed

    Hössel, P; Dieing, R; Nörenberg, R; Pfau, A; Sander, R

    2000-02-01

    Today's shampoo formulations are beyond the stage of pure cleansing of the hair. Additional benefits are expected, e.g. conditioning, smoothing of the hair surface, improvement of combability and lather creaminess. Cationic polymers play an important role in providing many of those features. Therefore, within the last few years their use in shampoos has increased greatly. In the only last two decades, shampoo designation has gradually changed from '2-in-1' to '3-in-1' and then to 'multifunctional', as at present. The consumer demands products which live up to their promises. Modern shampoos contain a wide variety of ingredients such as co-surfactants, vitamins and pro-vitamins, protein derivatives, silicones, natural-based plant extracts and other 'active ingredients', but there is still a need for conditioning polymers. The specific objective of this study is to assess the conditioning efficacy of cationic polymers and to investigate their mechanisms in a shampoo system. The investigations were carried out on formulations that contained sodium lauryl ether sulphate and different cationic polymers, e.g. Polyquaternium 7, 10, 11, cationic guar gum and Luviquat Care (Polyquaternium 44), a new branched copolymer of vinylpyrrolidone (VP) and quaternized vinylimidazolium salts (QVI). We used test methods relevant to the applications in question, such as combing force measurements, the feel of the hair and the creaminess of the lather, to assess the efficacy. Atomic force microscopy and electrokinetics (streaming potential) were used to detect polymer residues on treated hair. All the polymers under investigation improved the overall performance of the shampoo formulations. This was demonstrated by means of combing force measurements, sensorial tests and analytical methods, namely zeta potential measurement and atomic force microscopy. Polyquaternium 44 exhibited the best conditioning properties on wet hair without sacrificing removability or absence of build-up. The

  16. Redox instability, mechanical deformation, and heterogeneous damage accumulation in solid oxide fuel cell anodes

    NASA Astrophysics Data System (ADS)

    Abdeljawad, F.; Nelson, G. J.; Chiu, W. K. S.; Haataja, M.

    2012-08-01

    Mechanical integrity and damage tolerance represent two key challenges in the design of solid oxide fuel cells (SOFCs). In particular, reduction and oxidation (redox) cycles, and the associated large transformation strains have a notable impact on the mechanical stability and failure mode of SOFC anodes. In this study, the deformation behavior under redox cycling is investigated computationally with an approach that provides a detailed, microstructurally based view of heterogeneous damage accumulation behavior within an experimentally obtained nickel/yttria stabilized zirconia SOFC anode microstructure. Simulation results underscore the critical role that the microstructure plays in the mechanical deformation behavior of and failure within such materials.

  17. Mechanical damage assessment by means of thermo-electrical lock-in thermography

    NASA Astrophysics Data System (ADS)

    Kordatos, E. Z.; Exarchos, D. A.; Matikas, T. E.

    2016-04-01

    The present work deals with the nondestructive assessment of the metallic materials' mechanical damage. An innovative Nondestructive Evaluation (NDE) methodology based on two thermographic approaches was developed in order the state of fatigue damage to be assessed. The first approach allows the detection of heat waves generated by the thermomechanical coupling during the fatigue loading (online method). Specifically, both the thermo-elastic and intrinsic dissipated energy was correlated with the mechanical degradation and the remaining fatigue life. The second approach involves the monitoring of the materials' thermal behavior using a Peltier device for accurate thermal excitation (offline method). The correlation of the thermal behavior and the state of damage was achieved by the determination of the material's thermal response. The combination of these two approaches enables the rapid and accurate assessment of the cumulative damage.

  18. Mechanisms of sensorineural cell damage, death and survival in the cochlea

    PubMed Central

    Wong, Ann C. Y.; Ryan, Allen F.

    2015-01-01

    The majority of acquired hearing loss, including presbycusis, is caused by irreversible damage to the sensorineural tissues of the cochlea. This article reviews the intracellular mechanisms that contribute to sensorineural damage in the cochlea, as well as the survival signaling pathways that can provide endogenous protection and tissue rescue. These data have primarily been generated in hearing loss not directly related to age. However, there is evidence that similar mechanisms operate in presbycusis. Moreover, accumulation of damage from other causes can contribute to age-related hearing loss (ARHL). Potential therapeutic interventions to balance opposing but interconnected cell damage and survival pathways, such as antioxidants, anti-apoptotics, and pro-inflammatory cytokine inhibitors, are also discussed. PMID:25954196

  19. Effects of Thermal Damage and Confining Pressure on the Mechanical Properties of Coarse Marble

    NASA Astrophysics Data System (ADS)

    Yao, Mengdi; Rong, Guan; Zhou, Chuangbing; Peng, Jun

    2016-06-01

    Heating treatment generally causes thermal damage inside rocks, and the influence of thermal damage on mechanical properties of rocks is an important topic in rock mechanics. The coarse marble specimens drilled out from a rock block were first heated to a specific temperature level of 200, 400 and 600 °C except the control group left at 20 °C. A series of triaxial compression tests subjected to the confining pressure of 0, 5, 10, 15, 20, 25, 30, 35 and 40 MPa were conducted. Coupling effects of thermal damage and confining pressure on the mechanical properties of marbles including post-peak behaviors and failure modes, strength and deformation parameters, characteristic stresses in the progressive failure process had been investigated. Meanwhile, accompanied tests of physical properties were carried out to study the effect of thermal damage on microstructure, porosity and P-wave velocity. Finally, the degradation parameter was defined and a strength-degradation model to describe the peak strength was proposed. Physical investigations show that porosity increases slowly and P-wave velocity reduces dramatically, which could be re-demonstrated by the microscopy results. As for the post-peak behaviors and the failure modes, there is a brittle to ductile transition trend with increasing confining pressure and thermal effect reinforces the ductility to some degree. The comparative study on strength and deformation parameters concludes that heating causes damage and confining pressure inhibits the damage to develop. Furthermore, crack damage stress and crack initiation stress increase, while the ratios of crack damage stress to peak strength and crack initiation stress to peak strength show a decreasing trend with the increase of confining pressure; the magnitude of crack damage stress or crack initiation stress shows a tendency of decrease with the increasing heating temperature and the tendency vanishes subjected to high confinement.

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

    PubMed

    Ma, Songyun; Scheider, Ingo; Bargmann, Swantje

    2016-09-01

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

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

    PubMed

    Ma, Songyun; Scheider, Ingo; Bargmann, Swantje

    2016-09-01

    An anisotropic constitutive model is proposed in the framework of finite deformation to capture several damage mechanisms occurring in the microstructure of dental enamel, a hierarchical bio-composite. It provides the basis for a homogenization approach for an efficient multiscale (in this case: multiple hierarchy levels) investigation of the deformation and damage behavior. The influence of tension-compression asymmetry and fiber-matrix interaction on the nonlinear deformation behavior of dental enamel is studied by 3D micromechanical simulations under different loading conditions and fiber lengths. The complex deformation behavior and the characteristics and interaction of three damage mechanisms in the damage process of enamel are well captured. The proposed constitutive model incorporating anisotropic damage is applied to the first hierarchical level of dental enamel and validated by experimental results. The effect of the fiber orientation on the damage behavior and compressive strength is studied by comparing micro-pillar experiments of dental enamel at the first hierarchical level in multiple directions of fiber orientation. A very good agreement between computational and experimental results is found for the damage evolution process of dental enamel. PMID:27294283

  2. Mechanisms of damage to corals exposed to sedimentation.

    PubMed

    Weber, Miriam; de Beer, Dirk; Lott, Christian; Polerecky, Lubos; Kohls, Katharina; Abed, Raeid M M; Ferdelman, Timothy G; Fabricius, Katharina E

    2012-06-12

    We investigated the mechanisms leading to rapid death of corals when exposed to runoff and resuspended sediments, postulating that the killing was microbially mediated. Microsensor measurements were conducted in mesocosm experiments and in naturally accumulated sediment on corals. In organic-rich, but not in organic-poor sediment, pH and oxygen started to decrease as soon as the sediment accumulated on the coral. Organic-rich sediments caused tissue degradation within 1 d, whereas organic-poor sediments had no effect after 6 d. In the harmful organic-rich sediment, hydrogen sulfide concentrations were low initially but increased progressively because of the degradation of coral mucus and dead tissue. Dark incubations of corals showed that separate exposures to darkness, anoxia, and low pH did not cause mortality within 4 d. However, the combination of anoxia and low pH led to colony death within 24 h. When hydrogen sulfide was added after 12 h of anoxia and low pH, colonies died after an additional 3 h. We suggest that sedimentation kills corals through microbial processes triggered by the organic matter in the sediments, namely respiration and presumably fermentation and desulfurylation of products from tissue degradation. First, increased microbial respiration results in reduced O(2) and pH, initiating tissue degradation. Subsequently, the hydrogen sulfide formed by bacterial decomposition of coral tissue and mucus diffuses to the neighboring tissues, accelerating the spread of colony mortality. Our data suggest that the organic enrichment of coastal sediments is a key process in the degradation of coral reefs exposed to terrestrial runoff.

  3. Fault damage zones in mechanically layered rocks: The effects of planar anisotropy

    NASA Astrophysics Data System (ADS)

    Misra, Santanu; Ellis, Susan; Mandal, Nibir

    2015-08-01

    This study shows how inherited strength anisotropy influences damage localization at both the tip and wall regions of a fault or fracture. We performed analogue and numerical compression experiments on transversely isotropic models with single and multiple cuts of finite length, simulating the propagation of preexisting faults and cracks in layered rock. The stress-strain curves from the analogue experiments show a change in bulk yield behavior with fault inclination and anisotropy orientation with respect to the stress direction. Earlier isotropic models demonstrated a brittle (wing fracturing) to ductile (shear-zone formation) transition as the fault angle (α) to the principal compression direction increased. The experiments with anisotropic models show patterns of damage localization change dramatically with the orientation of transversely isotropic planes (θ, measured with respect to principal extension direction). Under layer-normal (θ = 0°) and layer-parallel compression (θ = 90°), preexisting faults undergo significant reactivation when 0 < α < 90°, and fault slip eventually leads to mechanical instabilities within the anisotropic layering, causing damage zones in the tip regions. For layer-normal (θ = 0°) compression, the damage processes involve intense extensional shear localization, whereas for layer-parallel compression, contractional shear localization and tensile opening result in characteristic internal shear-band structures. In contrast, for 0 < θ < 90°, the faults undergo little or no reactivation, irrespective of α. In this case, bulk compression leads to an interlayer slip-mediated global deformation. Obliquely anisotropic models thus produce weak or no fault damage zones. We also show that the fault-parallel principal damage localized at the tips can be coupled with transversely oriented, antithetic secondary damage in the wall regions. However, secondary damage develops predominantly when θ = 90°. Field examples of fault damage

  4. Effects of formulation design on niacin therapeutics: mechanism of action, metabolism, and drug delivery.

    PubMed

    Cooper, Dustin L; Murrell, Derek E; Roane, David S; Harirforoosh, Sam

    2015-07-25

    Niacin is a highly effective, lipid regulating drug associated with a number of metabolically induced side effects such as prostaglandin (PG) mediated flushing and hepatic toxicity. In an attempt to reduce the development of these adverse effects, scientists have investigated differing methods of niacin delivery designed to control drug release and alter metabolism. However, despite successful formulation of various orally based capsule and tablet delivery systems, patient adherence to niacin therapy is still compromised by adverse events such as PG-induced flushing. While the primary advantage of orally dosed formulations is ease of use, alternative delivery options such as transdermal delivery or polymeric micro/nanoparticle encapsulation for oral administration have shown promise in niacin reformulation. However, the effectiveness of these alternative delivery options in reducing inimical effects of niacin and maintaining drug efficacy is still largely unknown and requires more in-depth investigation. In this paper, we present an overview of niacin applications, its metabolic pathways, and current drug delivery formulations. Focus is placed on oral immediate, sustained, and extended release niacin delivery as well as combined statin and/or prostaglandin antagonist niacin formulation. We also examine and discuss current findings involving transdermal niacin formulations and polymeric micro/nanoparticle encapsulated niacin delivery.

  5. Experimental verification of a progressive damage model for composite laminates based on continuum damage mechanics. M.S. Thesis Final Report

    NASA Technical Reports Server (NTRS)

    Coats, Timothy William

    1994-01-01

    Progressive failure is a crucial concern when using laminated composites in structural design. Therefore the ability to model damage and predict the life of laminated composites is vital. The purpose of this research was to experimentally verify the application of the continuum damage model, a progressive failure theory utilizing continuum damage mechanics, to a toughened material system. Damage due to tension-tension fatigue was documented for the IM7/5260 composite laminates. Crack density and delamination surface area were used to calculate matrix cracking and delamination internal state variables, respectively, to predict stiffness loss. A damage dependent finite element code qualitatively predicted trends in transverse matrix cracking, axial splits and local stress-strain distributions for notched quasi-isotropic laminates. The predictions were similar to the experimental data and it was concluded that the continuum damage model provided a good prediction of stiffness loss while qualitatively predicting damage growth in notched laminates.

  6. Multiscale Approach to the Physics of Ion-Beam Therapy:. Thermo-Mechanical Damage

    NASA Astrophysics Data System (ADS)

    Solov'yov, A. V.; Yakubovich, A. V.; Surdutovich, E.

    2012-01-01

    We present a brief overview of the multiscale approach towards the understanding of processes responsible for the radiation damage caused by energetic ions. This knowledge is important because it can be utilized in the ion-beam cancer therapy, which is one of the most advanced modern techniques to cure certain types of cancer. The central element of the multiscale approach is the theoretical evaluation and quantification of DNA damage within cell environment. We consider different pathways of DNA damage and focus on the the illustration of the thermo-mechanical effects caused by the propagation of ions through the biological environment and in particular on the possibility of the creation of the shock waves in the vicinity of the ion tracks. We demonstrate that at the initial stages after ion's passage the shock wave is so strong that it can contribute to the DNA damage due to large pressure gradients developed at the distances of a few nanometers from the ionic tracks. This novel mechanism of the DNA damage provides an important contribution to the cumulative bio-damage caused by low-energy secondary electrons, holes and free radicals.

  7. Earthquake Induced Damage Mechanism of Long Period Structures Using Energy Response

    SciTech Connect

    Du Yongfeng; Li Hui

    2008-07-08

    This paper presents a method of expounding the damage of RC long period frame structure using energy analysis method. Since the damage of structures usually occurs under major earthquakes, the structure is assumed to be in elasto-plastic state, and degraded Bouc-Wen model is used to describe the hysteretic component of the restoring force. A double index damage criterion defined by the maximum drift and energy absorption is used as the damage criterion. The energy transferring relation in a structure is derived, and both momentary and cumulative energy response is used to reflect the delay of the collapse of a long period structure. The mechanism of collapse delay of the long period structure is suggested through a numerical example combing the energy response and time history response.

  8. Prediction of Size Effects in Notched Laminates Using Continuum Damage Mechanics

    NASA Technical Reports Server (NTRS)

    Camanho, D. P.; Maimi, P.; Davila, C. G.

    2007-01-01

    This paper examines the use of a continuum damage model to predict strength and size effects in notched carbon-epoxy laminates. The effects of size and the development of a fracture process zone before final failure are identified in an experimental program. The continuum damage model is described and the resulting predictions of size effects are compared with alternative approaches: the point stress and the inherent flaw models, the Linear-Elastic Fracture Mechanics approach, and the strength of materials approach. The results indicate that the continuum damage model is the most accurate technique to predict size effects in composites. Furthermore, the continuum damage model does not require any calibration and it is applicable to general geometries and boundary conditions.

  9. Mechanisms of Diabetes-Induced Liver Damage: The role of oxidative stress and inflammation.

    PubMed

    Mohamed, Jamaludin; Nazratun Nafizah, A H; Zariyantey, A H; Budin, S B

    2016-05-01

    Diabetes mellitus is a non-communicable disease that occurs in both developed and developing countries. This metabolic disease affects all systems in the body, including the liver. Hyperglycaemia, mainly caused by insulin resistance, affects the metabolism of lipids, carbohydrates and proteins and can lead to non-alcoholic fatty liver disease, which can further progress to non-alcoholic steatohepatitis, cirrhosis and, finally, hepatocellular carcinomas. The underlying mechanism of diabetes that contributes to liver damage is the combination of increased oxidative stress and an aberrant inflammatory response; this activates the transcription of pro-apoptotic genes and damages hepatocytes. Significant involvement of pro-inflammatory cytokines-including interleukin (IL)-1β, IL-6 and tumour necrosis factor-α-exacerbates the accumulation of oxidative damage products in the liver, such as malondialdehyde, fluorescent pigments and conjugated dienes. This review summarises the biochemical, histological and macromolecular changes that contribute to oxidative liver damage among diabetic individuals. PMID:27226903

  10. A fracture mechanics analysis of impact damage in a thick composite laminate

    NASA Technical Reports Server (NTRS)

    Poe, C. C., Jr.

    1985-01-01

    Graphite/epoxy filament-wound cases (FWC) for the solid rocket motors of the space shuttle are being made by NASA. The FWC cases are wound with AS4W graphite fiber impregnated with an epoxy resin and are about 1.4 inches or more thick. Graphite-epoxy composite laminates, unlike metals, can be damaged easily by low velocity impacts of objects like dropped tools. The residual tension strength of the FWC laminate, after impact, is being studied at Langley Research Center. The conditions that give minimum visual evidence of damage are being emphasized. A fracture mechanics analysis was developed to predict the residual strength, after impact, using radiographs to measure the size of the damage and an equivalent surface crack to represent the damage.

  11. Model-Based Fatigue Prognosis of Fiber-Reinforced Laminates Exhibiting Concurrent Damage Mechanisms

    NASA Technical Reports Server (NTRS)

    Corbetta, M.; Sbarufatti, C.; Saxena, A.; Giglio, M.; Goebel, K.

    2016-01-01

    Prognostics of large composite structures is a topic of increasing interest in the field of structural health monitoring for aerospace, civil, and mechanical systems. Along with recent advancements in real-time structural health data acquisition and processing for damage detection and characterization, model-based stochastic methods for life prediction are showing promising results in the literature. Among various model-based approaches, particle-filtering algorithms are particularly capable in coping with uncertainties associated with the process. These include uncertainties about information on the damage extent and the inherent uncertainties of the damage propagation process. Some efforts have shown successful applications of particle filtering-based frameworks for predicting the matrix crack evolution and structural stiffness degradation caused by repetitive fatigue loads. Effects of other damage modes such as delamination, however, are not incorporated in these works. It is well established that delamination and matrix cracks not only co-exist in most laminate structures during the fatigue degradation process but also affect each other's progression. Furthermore, delamination significantly alters the stress-state in the laminates and accelerates the material degradation leading to catastrophic failure. Therefore, the work presented herein proposes a particle filtering-based framework for predicting a structure's remaining useful life with consideration of multiple co-existing damage-mechanisms. The framework uses an energy-based model from the composite modeling literature. The multiple damage-mode model has been shown to suitably estimate the energy release rate of cross-ply laminates as affected by matrix cracks and delamination modes. The model is also able to estimate the reduction in stiffness of the damaged laminate. This information is then used in the algorithms for life prediction capabilities. First, a brief summary of the energy-based damage model

  12. Prediction of anisotropic behavior of nano/micro composite based on damage mechanics with cell modeling.

    PubMed

    Lee, Dock-Jin; Kim, Young-Jin; Kim, Moon-Ki; Choi, Jae-Boong; Chang, Yoon-Suk; Liu, Wing Kam

    2011-01-01

    New advanced composite materials have recently been of great interest. Especially, many researchers have studied on nano/micro composites based on matrix filled with nano-particles, nano-tubes, nano-wires and so forth, which have outstanding characteristics on thermal, electrical, optical, chemical and mechanical properties. Therefore, the need of numerical approach for design and development of the advanced materials has been recognized. In this paper, finite element analysis based on multi-resolution continuum theory is carried out to predict the anisotropic behavior of nano/micro composites based on damage mechanics with a cell modeling. The cell modeling systematically evaluates constitutive relationships from microstructure of the composite material. Effects of plastic anisotropy on deformation behavior and damage evolution of nano/micro composite are investigated by using Hill's 48 yield function and also compared with those obtained from Gurson-Tvergaard-Needleman isotropic damage model based on von Mises yield function.

  13. Cationic liposomes formulated with DMPC and a gemini surfactant traverse the cell membrane without causing a significant bio-damage.

    PubMed

    Stefanutti, E; Papacci, F; Sennato, S; Bombelli, C; Viola, I; Bonincontro, A; Bordi, F; Mancini, G; Gigli, G; Risuleo, G

    2014-10-01

    Cationic liposomes have been intensively studied both in basic and applied research because of their promising potential as non-viral molecular vehicles. This work was aimed to gain more information on the interactions between the plasmamembrane and liposomes formed by a natural phospholipid and a cationic surfactant of the gemini family. The present work was conducted with the synergistic use of diverse experimental approaches: electro-rotation measurements, atomic force microscopy, ζ-potential measurements, laser scanning confocal microscopy and biomolecular/cellular techniques. Electro-rotation measurements pointed out that the interaction of cationic liposomes with the cell membrane alters significantly its dielectric and geometric parameters. This alteration, being accompanied by significant changes of the membrane surface roughness as measured by atomic force microscopy, suggests that the interaction with the liposomes causes locally substantial modifications to the structure and morphology of the cell membrane. However, the results of electrophoretic mobility (ζ-potential) experiments show that upon the interaction the electric charge exposed on the cell surface does not vary significantly, pointing out that the simple adhesion on the cell surface of the cationic liposomes or their fusion with the membrane is to be ruled out. As a matter of fact, confocal microscopy images directly demonstrated the penetration of the liposomes inside the cell and their diffusion within the cytoplasm. Electro-rotation experiments performed in the presence of endocytosis inhibitors suggest that the internalization is mediated by, at least, one specific pathway. Noteworthy, the liposome uptake by the cell does not cause a significant biological damage.

  14. Cationic liposomes formulated with DMPC and a gemini surfactant traverse the cell membrane without causing a significant bio-damage.

    PubMed

    Stefanutti, E; Papacci, F; Sennato, S; Bombelli, C; Viola, I; Bonincontro, A; Bordi, F; Mancini, G; Gigli, G; Risuleo, G

    2014-10-01

    Cationic liposomes have been intensively studied both in basic and applied research because of their promising potential as non-viral molecular vehicles. This work was aimed to gain more information on the interactions between the plasmamembrane and liposomes formed by a natural phospholipid and a cationic surfactant of the gemini family. The present work was conducted with the synergistic use of diverse experimental approaches: electro-rotation measurements, atomic force microscopy, ζ-potential measurements, laser scanning confocal microscopy and biomolecular/cellular techniques. Electro-rotation measurements pointed out that the interaction of cationic liposomes with the cell membrane alters significantly its dielectric and geometric parameters. This alteration, being accompanied by significant changes of the membrane surface roughness as measured by atomic force microscopy, suggests that the interaction with the liposomes causes locally substantial modifications to the structure and morphology of the cell membrane. However, the results of electrophoretic mobility (ζ-potential) experiments show that upon the interaction the electric charge exposed on the cell surface does not vary significantly, pointing out that the simple adhesion on the cell surface of the cationic liposomes or their fusion with the membrane is to be ruled out. As a matter of fact, confocal microscopy images directly demonstrated the penetration of the liposomes inside the cell and their diffusion within the cytoplasm. Electro-rotation experiments performed in the presence of endocytosis inhibitors suggest that the internalization is mediated by, at least, one specific pathway. Noteworthy, the liposome uptake by the cell does not cause a significant biological damage. PMID:25017801

  15. Changes of color coordinates of biological tissue with superficial skin damage due to mechanical trauma

    NASA Astrophysics Data System (ADS)

    Pteruk, Vail; Mokanyuk, Olexander; Kvaternuk, Olena; Yakenina, Lesya; Kotyra, Andrzej; Romaniuk, Ryszard S.; Dussembayeva, Shynar

    2015-12-01

    Change of color coordinates of normal and pathological biological tissues is based on calculated spectral diffuse reflection. The proposed color coordinates of normal and pathological biological tissues of skin provided using standard light sources, allowing accurately diagnose skin damage due to mechanical trauma with a blunt object for forensic problems.

  16. Fluorescent protein senses and reports mechanical damage in glass-fiber-reinforced polymer composites.

    PubMed

    Makyła, Katarzyna; Müller, Christoph; Lörcher, Samuel; Winkler, Thomas; Nussbaumer, Martin G; Eder, Michaela; Bruns, Nico

    2013-05-21

    Yellow fluorescent protein (YFP) is used as a mechanoresponsive layer at the fiber/resin interface in glass-fiber-reinforced composites. The protein loses its fluorescence when subjected to mechanical stress. Within the material, it reports interfacial shear debonding and barely visible impact damage by a transition from a fluorescent to a non-fluorescent state. PMID:23423911

  17. DNA DAMAGE REPAIR AND CELL CYCLE CONTROL: A NATURAL BIO-DEFENSE MECHANISM

    EPA Science Inventory

    DNA DAMAGE REPAIR AND CELL CYCLE CONTROL: A natural bio-defense mechanism
    Anuradha Mudipalli.

    Maintenance of genetic information, including the correct sequence of nucleotides in DNA, is essential for replication, gene expression, and protein synthesis. DNA lesions onto...

  18. Coordination of DNA damage tolerance mechanisms with cell cycle progression in fission yeast

    PubMed Central

    Callegari, A. John; Kelly, Thomas J.

    2016-01-01

    ABSTRACT DNA damage tolerance (DDT) mechanisms allow cells to synthesize a new DNA strand when the template is damaged. Many mutations resulting from DNA damage in eukaryotes are generated during DDT when cells use the mutagenic translesion polymerases, Rev1 and Polζ, rather than mechanisms with higher fidelity. The coordination among DDT mechanisms is not well understood. We used live-cell imaging to study the function of DDT mechanisms throughout the cell cycle of the fission yeast Schizosaccharomyces pombe. We report that checkpoint-dependent mitotic delay provides a cellular mechanism to ensure the completion of high fidelity DDT, largely by homology-directed repair (HDR). DDT by mutagenic polymerases is suppressed during the checkpoint delay by a mechanism dependent on Rad51 recombinase. When cells pass the G2/M checkpoint and can no longer delay mitosis, they completely lose the capacity for HDR and simultaneously exhibit a requirement for Rev1 and Polζ. Thus, DDT is coordinated with the checkpoint response so that the activity of mutagenic polymerases is confined to a vulnerable period of the cell cycle when checkpoint delay and HDR are not possible. PMID:26652183

  19. Coordination of DNA damage tolerance mechanisms with cell cycle progression in fission yeast.

    PubMed

    Callegari, A John; Kelly, Thomas J

    2016-01-01

    DNA damage tolerance (DDT) mechanisms allow cells to synthesize a new DNA strand when the template is damaged. Many mutations resulting from DNA damage in eukaryotes are generated during DDT when cells use the mutagenic translesion polymerases, Rev1 and Polζ, rather than mechanisms with higher fidelity. The coordination among DDT mechanisms is not well understood. We used live-cell imaging to study the function of DDT mechanisms throughout the cell cycle of the fission yeast Schizosaccharomyces pombe. We report that checkpoint-dependent mitotic delay provides a cellular mechanism to ensure the completion of high fidelity DDT, largely by homology-directed repair (HDR). DDT by mutagenic polymerases is suppressed during the checkpoint delay by a mechanism dependent on Rad51 recombinase. When cells pass the G2/M checkpoint and can no longer delay mitosis, they completely lose the capacity for HDR and simultaneously exhibit a requirement for Rev1 and Polζ. Thus, DDT is coordinated with the checkpoint response so that the activity of mutagenic polymerases is confined to a vulnerable period of the cell cycle when checkpoint delay and HDR are not possible. PMID:26652183

  20. Phagocytosis-dependent and independent mechanisms underlie the microglial cell damage caused by carbon nanotube agglomerates.

    PubMed

    Shigemoto-Mogami, Yukari; Hoshikawa, Kazue; Hirose, Akihiko; Sato, Kaoru

    2016-01-01

    Although carbon nanotubes (CNTs) are used in many fields, including energy, healthcare, environmental technology, materials, and electronics, the adverse effects of CNTs in the brain are poorly understood. In this study, we investigated the effects of CNTs on cultured microglia, as microglia are the first responders to foreign materials. We compared the effects of sonicated suspensions of 5 kinds of CNTs and their flow-through filtered with a 0.22 µm membrane filter on microglial viability. We found that sonicated suspensions caused microglial cell damage, but their flow-through did not. The number of microglial aggregates was well correlated with the extent of the damage. We also determined that the CNT agglomerates consisted of two groups: one was phagocytosed by microglia and caused microglial cell damage, and the other caused cell damage without phagocytosis. These results suggest that phagocytosis-dependent and independent mechanisms underlie the microglial cell damage caused by CNT agglomerates and it is important to conduct studies about the relationships between physical properties of nanomaterial-agglomerates and cell damage. PMID:27432236

  1. Imperfect asymmetry: The mechanism governing asymmetric partitioning of damaged cellular components during mitosis

    PubMed Central

    Pattabiraman, Sundararaghavan; Kaganovich, Daniel

    2014-01-01

    Aging is universally associated with organism-wide dysfunction and a decline in cellular fitness. From early development onwards, the efficiency of self-repair, energy production, and homeostasis all decrease. Due to the multiplicity of systems that undergo agingrelated decline, the mechanistic basis of organismal aging has been difficult to pinpoint. At the cellular level, however, recent work has provided important insight. Cellular aging is associated with the accumulation of several types of damage, in particular damage to the proteome and organelles. Groundbreaking studies have shown that replicative aging is the result of a rejuvenation mechanism that prevents the inheritance of damaged components during division, thereby confining the effects of aging to specific cells, while removing damage from others. Asymmetric inheritance of misfolded and aggregated proteins, as well as reduced mitochondria, has been shown in yeast. Until recently, however, it was not clear whether a similar mechanism operates in mammalian cells, which were thought to mostly divide symmetrically. Our group has recently shown that vimentin establishes mitotic polarity in immortalized mammalian cells, and mediates asymmetric partitioning of multiple factors through direct interaction. These findings prompt a provocative hypothesis: that intermediate filaments serve as asymmetric partitioning modules or “sponges” that, when expressed prior to mitosis, can “clean” emerging cells of the damage they have accumulated. PMID:25941938

  2. Dissecting the molecular mechanism of ionizing radiation-induced tissue damage in the feather follicle.

    PubMed

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

    2014-01-01

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

  3. Conservation of clay-bearing stones: Understanding the swelling and damage mechanisms

    NASA Astrophysics Data System (ADS)

    Wangler, Timothy

    Certain sandstones used in historic monuments and decorative building facades may contain clays that swell upon wetting, producing differential strains during wetting and drying cycles and leading to the development of stresses that are on the order of the strength of the stone. This leads to damage observed in the field as buckling and surface delamination, damage expected to occur during a wetting cycle as a thin wet layer of stone goes into compression relative to the bulk of the dry stone. Clays swell due to hydration of counterbalancing cations that exist between the negatively charged aluminosilicate layers that make up a clay particle. This swelling has been observed to occur over two distinct ranges: short-range, discrete intracrystalline swelling, and long-range, continuous, osmotic swelling. Additionally, it has been shown that swelling can be reduced, but not eliminated, by exchanging the counterbalancing cations in the interlayer with alpha,o diaminoalkanes. In order to mitigate damage due to swelling, it is important to understand the mechanism by which clays swell, the mechanism by which alpha,o diaminoalkanes inhibit swelling, and the mechanism by which damage occurs on a macroscopic level. In this work, it is shown that for the sandstones studied, clays swell almost entirely via intracrystalline swelling and that alpha,o diaminoalkanes inhibit swelling via ion exchange and subsequently reduced rehydration. A buckling damage mechanism is verified experimentally and a flaw propagation mechanism in which flaws can grow to a critical buckling size is explored. An understanding of the development of stresses during wetting is explored via a novel warping experiment and swelling pressure experiments.

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  5. Mechanism of DNA damage by cadmium and interplay of antioxidant enzymes and agents.

    PubMed

    Badisa, Veera L D; Latinwo, Lekan M; Odewumi, Caroline O; Ikediobi, Christopher O; Badisa, Ramesh B; Ayuk-Takem, Lambert T; Nwoga, Jude; West, John

    2007-04-01

    Cadmium is an environmental toxicant, which causes cancer in different organs. It was found that it damages DNA in the various tissues and cultured cell lines. To investigate the mechanism of DNA damage, we have studied the effect of cadmium-induced DNA damage in plasmid pBR322 DNA, and the possible ameliorative effects of antioxidative agents under in vitro conditions. It was observed that cadmium alone did not cause DNA damage. However, it caused DNA damage in the presence of hydrogen peroxide, in a dose dependent manner, because of production of hydroxyl radicals. Findings from this study show the conversion of covalently closed circular double-stranded pBR 322 DNA to the open circular and linear forms of DNA when treated with 10 muM cadmium and various concentrations of H(2)O(2). The conversion was due to nicking in DNA strands. The observed rate of DNA strand breakage was dependent on H(2)O(2) concentration, temperature, and time. Metallothionein I failed to prevent cadmium-induced DNA nicking in the presence of H(2)O(2). Of the two antioxidant enzymes (catalase and superoxide dismutase) studied, only catalase conferred significant (50-60%) protection. EDTA and DMSO exhibited protection similar to catalase, while mannitol showed only about 20% protection against DNA damage. Ethyl alcohol failed to ameliorate cadmium-induced DNA strands break. From this study, it is plausible to infer that cadmium in the presence of hydrogen peroxide causes DNA damage probably by the formation of hydroxyl ions. These results may indicate that cadmium in vivo could play a major role in the DNA damage induced by oxidative stress. PMID:17366568

  6. Identification of Fracture Toughness for Discrete Damage Mechanics Analysis of Glass-Epoxy Laminates

    NASA Astrophysics Data System (ADS)

    Barbero, E. J.; Cosso, F. A.; Martinez, X.

    2014-08-01

    A methodology for determination of the intralaminar fracture toughness is presented, based on fitting discrete damage mechanics (DDM) model predictions to available experimental data. DDM is constitutive model that, when incorporated into commercial finite element software via user material subroutines, is able to predict intralaminar transverse and shear damage initiation and evolution in terms of the fracture toughness of the composite. The applicability of the DDM model is studied by comparison to available experimental data for Glass-Epoxy laminates. Sensitivity of the DDM model to h- and p-refinement is studied. Also, the effect of in-situ correction of strength is highlighted.

  7. Inelastic Deformation of Metal Matrix Composites. Part 1; Plasticity and Damage Mechanisms

    NASA Technical Reports Server (NTRS)

    Majumdar, B. S.; Newaz, G. M.

    1992-01-01

    The deformation mechanisms of a Ti 15-3/SCS6 (SiC fiber) metal matrix composite (MMC) were investigated using a combination of mechanical measurements and microstructural analysis. The objectives were to evaluate the contributions of plasticity and damage to the overall inelastic response, and to confirm the mechanisms by rigorous microstructural evaluations. The results of room temperature experiments performed on 0 degree and 90 degree systems primarily are reported in this report. Results of experiments performed on other laminate systems and at high temperatures will be provided in a forthcoming report. Inelastic deformation of the 0 degree MMC (fibers parallel to load direction) was dominated by the plasticity of the matrix. In contrast, inelastic deformations of the 90 degree composite (fibers perpendicular to loading direction) occurred by both damage and plasticity. The predictions of a continuum elastic plastic model were compared with experimental data. The model was adequate for predicting the 0 degree response; however, it was inadequate for predicting the 90 degree response largely because it neglected damage. The importance of validating constitutive models using a combination of mechanical measurements and microstructural analysis is pointed out. The deformation mechanisms, and the likely sequence of events associated with the inelastic deformation of MMCs, are indicated in this paper.

  8. Deterministic and Probabilistic Creep and Creep Rupture Enhancement to CARES/Creep: Multiaxial Creep Life Prediction of Ceramic Structures Using Continuum Damage Mechanics and the Finite Element Method

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

    High temperature and long duration applications of monolithic ceramics can place their failure mode in the creep rupture regime. A previous model advanced by the authors described a methodology by which the creep rupture life of a loaded component can be predicted. That model was based on the life fraction damage accumulation rule in association with the modified Monkman-Grant creep ripture criterion However, that model did not take into account the deteriorating state of the material due to creep damage (e.g., cavitation) as time elapsed. In addition, the material creep parameters used in that life prediction methodology, were based on uniaxial creep curves displaying primary and secondary creep behavior, with no tertiary regime. The objective of this paper is to present a creep life prediction methodology based on a modified form of the Kachanov-Rabotnov continuum damage mechanics (CDM) theory. In this theory, the uniaxial creep rate is described in terms of stress, temperature, time, and the current state of material damage. This scalar damage state parameter is basically an abstract measure of the current state of material damage due to creep deformation. The damage rate is assumed to vary with stress, temperature, time, and the current state of damage itself. Multiaxial creep and creep rupture formulations of the CDM approach are presented in this paper. Parameter estimation methodologies based on nonlinear regression analysis are also described for both, isothermal constant stress states and anisothermal variable stress conditions This creep life prediction methodology was preliminarily added to the integrated design code CARES/Creep (Ceramics Analysis and Reliability Evaluation of Structures/Creep), which is a postprocessor program to commercially available finite element analysis (FEA) packages. Two examples, showing comparisons between experimental and predicted creep lives of ceramic specimens, are used to demonstrate the viability of this methodology and

  9. Oxidative Damage and Cellular Defense Mechanisms in Sea Urchin Models of Aging

    PubMed Central

    Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

    2013-01-01

    The free radical or oxidative stress theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging due to the existence of species with tremendously different natural life spans including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus and Strongylocentrotus purpuratus which has an intermediate lifespan. Levels of protein carbonyls and 4-hydroxynonenal (HNE) measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age-pigment lipofuscin measured in muscle, nerve and esophagus, increased with age however it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species, however further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. PMID:23707327

  10. Damage Mechanisms of Filled Siloxanes for Predictive Multiscale Modeling of Aging Behavior

    SciTech Connect

    Balazs, B; Maxwell, R; de Teresa, S; Dinh, L; Gee, R

    2002-04-02

    Predictions of component performance versus lifetime are often risky for complex materials in which there may be many underlying aging or degradation mechanisms. In order to develop more accurate predictive models for silica-filled siloxane components, we are studying damage mechanisms over a broad range of size domains, linked together through several modeling efforts. Atomistic and molecular dynamic modeling has elucidated the chemistry of the silica filler to polymer interaction, as this interaction plays a key role in this material's aging behavior. This modeling work has been supported by experimental data on the removal of water from the silica surface, the effect of the surrounding polymer on this desiccation, and on the subsequent change in the mechanical properties of the system. Solid State NMR efforts have characterized the evolution of the polymer and filler dynamics as the material is damaged through irradiation or desiccation. These damage signatures have been confirmed by direct measurements of changes in polymer crosslink density and filler interaction as measured by solvent swelling, and by mechanical property tests. Data from the changes at these molecular levels are simultaneously feeding the development of age-aware constitutive models for polymer behavior. In addition, the microstructure of the foam, including under load, has been determined by Computed Tomography, and this data is being introduced into Finite Element Analysis codes to allow component level models. All of these techniques are directed towards the incorporation of molecular and microstructural aging signatures into predictive models for overall component performance.

  11. Application of the damage mechanics to the description of multiple cracks development in shales

    NASA Astrophysics Data System (ADS)

    Izvekov, Oleg

    2014-05-01

    Oil and gas shales are one of the most perspective sources of hydrocarbons. Damage processes are in the focus of any technology of oil shales development because of their extremely low permeability. As a rule the aim of stimulation treatments is to make a system of multiple cracks. Real rock masses are almost heterogeneous. Strength of layered rocks like shales has anisotropic properties. Damage mechanics gives one of the natural ways of description of multiple cracks development. The phenomenological model of multiple cracks evolution in porous media based on general principles of thermodynamics [Kondaurov V.I., Izvekov O.Y., 2009] was generalized to the case of layered rocks. This model takes into account elastic domain existence, dependency of elastic domain on orientation of axis of anisotropy, reduction of elasticity modulus in active process, permeability and porosity change. The model involves latent energy of damage and elastic energy release due to damage evolution. In the report some coupled problems of damage and filtration are discussed. This work was supported by Russian President Grant for Young Scientists MK-7249.2013.5. Kondaurov V.I., Izvekov O.Y. A Model of Saturated Porous Media with an Elastic Brittle Skeleton // Proc. of the 4-th Biot Conference on Poromechanics, POROMECHANICS IV. - EStech Publications, Inc., PA,USA, 2009.

  12. Endogenous recovery after brain damage: molecular mechanisms that balance neuronal life/death fate.

    PubMed

    Tovar-y-Romo, Luis B; Penagos-Puig, Andrés; Ramírez-Jarquín, Josué O

    2016-01-01

    Neuronal survival depends on multiple factors that comprise a well-fueled energy metabolism, trophic input, clearance of toxic substances, appropriate redox environment, integrity of blood-brain barrier, suppression of programmed cell death pathways and cell cycle arrest. Disturbances of brain homeostasis lead to acute or chronic alterations that might ultimately cause neuronal death with consequent impairment of neurological function. Although we understand most of these processes well when they occur independently from one another, we still lack a clear grasp of the concerted cellular and molecular mechanisms activated upon neuronal damage that intervene in protecting damaged neurons from death. In this review, we summarize a handful of endogenously activated mechanisms that balance molecular cues so as to determine whether neurons recover from injury or die. We center our discussion on mechanisms that have been identified to participate in stroke, although we consider different scenarios of chronic neurodegeneration as well. We discuss two central processes that are involved in endogenous repair and that, when not regulated, could lead to tissue damage, namely, trophic support and neuroinflammation. We emphasize the need to construct integrated models of neuronal degeneration and survival that, in the end, converge in neuronal fate after injury. Under neurodegenerative conditions, endogenously activated mechanisms balance out molecular cues that determine whether neurons contend toxicity or die. Many processes involved in endogenous repair may as well lead to tissue damage depending on the strength of stimuli. Signaling mediated by trophic factors and neuroinflammation are examples of these processes as they regulate different mechanisms that mediate neuronal demise including necrosis, apoptosis, necroptosis, pyroptosis and autophagy. In this review, we discuss recent findings on balanced regulation and their involvement in neuronal death.

  13. Mechanisms for radiation damage in DNA. Progress report, June 1, 1994--May 31, 1995

    SciTech Connect

    Sevilla, M.D.

    1994-11-01

    In this project we have proposed several mechanisms for radiation damage to DNA and its constituents, and have detailed a series of experiments utilizing electron spin resonance spectroscopy, HPLC, GC-mass spectroscopy and ab initio molecular orbital calculations to test the proposed mechanisms. The results from these various techniques have resulted in an understanding of consequences of radiation damage to DNA from the early ionization event to the production of non-radical lesions (discussed in detail in Comprehensive Report). In this year`s work we have found the hydroxyl radical in DNA`s hydration layer. This is an important result which impacts the hole transfer hypothesis and the understanding of the direct vs. indirect effect in DNA. Further we have found the first ESR evidence for sugar radicals as a result of direct radiation damage to DNA nucleotides in an aqueous environment. This is significant as it impacts the biological endpoint of radiation damage to DNA and suggests future work in DNA. Work with DNA-polypeptides show clear evidence for electron transfer to DNA from the polypeptide which we believe is a radioprotective mechanism. Our work with ab initio molecular orbital theory has gain insight into the initial events of radiation damage to DNA. Ab initio calculations have provided an understanding of the energetics involved in anion and cation formation, ion radical transfer in DNA as well as proton transfer with DNA base pair radical ions. This has been extended in this year`s work to new, more accurate values for the electron affinities of the DNA bases, understanding of the relative stability of all possible sugar radicals formed by hydrogen abstraction on the deoxyribose group, hydration effects on, thiol radioprotectors, and an ongoing study of radical intermediates formed from initial DNA ion radicals. During this fiscal year five articles have been published, three are in press, two are submitted and several more are in preparation.

  14. Mechanical blood trauma in assisted circulation: sublethal RBC damage preceding hemolysis.

    PubMed

    Olia, Salim E; Maul, Timothy M; Antaki, James F; Kameneva, Marina V

    2016-06-15

    After many decades of improvements in mechanical circulatory assist devices (CADs), blood damage remains a serious problem during support contributing to variety of adverse events, and consequently affecting patient survival and quality of life. The mechanisms of cumulative cell damage in continuous-flow blood pumps are still not fully understood despite numerous in vitro, in vivo, and in silico studies of blood trauma. Previous investigations have almost exclusively focused on lethal blood damage, namely hemolysis, which is typically negligible during normal operation of current generation CADs. The measurement of plasma free hemoglobin (plfHb) concentration to characterize hemolysis is straightforward, however sublethal trauma is more difficult to detect and quantify since no simple direct test exists. Similarly, while multiple studies have focused on thrombosis within blood pumps and accessories, sublethal blood trauma and its sequelae have yet to be adequately documented or characterized. This review summarizes the current understanding of sublethal trauma to red blood cells (RBCs) produced by exposure of blood to flow parameters and conditions similar to those within CADs. It also suggests potential strategies to reduce and/or prevent RBC sublethal damage in a clinically-relevant context, and encourages new research into this relatively uncharted territory.

  15. Mechanisms for radiation damage in DNA. Progress report, June 1, 1993--May 31, 1994

    SciTech Connect

    Sevilla, M.D.

    1993-12-01

    In this project the author has proposed several mechanisms for radiation damage to DNA and its constituents, and has detailed a series of experiments utilizing electron spin resonance spectroscopy, HPLC, GC-mass spectroscopy and ab initio molecular orbital calculations to test the proposed mechanisms. In this years work he has completed several experiments on the role of hydration water on DNA radiation damage, continued the investigation of the localization of the initial charges and their reactions on DNA, investigated protonation reactions in DNA base anions, and employed ab initio molecular orbital theory to gain insight into the initial events of radiation damage to DNA. Ab initio calculations have provided an understanding of the energetics evolved in anion and cation formation, ion radical transfer in DNA as well as proton transfer with DNA base pair radical ions. This has been extended in this years work to a consideration of ionization energies of various components of the DNA deoxyribose backbone and resulting neutral sugar radicals. This information has aided the formation of new radiation models for the effect of radiation on DNA. During this fiscal year four articles have been published, four are in press, one is submitted and several more are in preparation. Four papers have been presented at scientific meetings. This years effort will include another review article on the {open_quotes}Electron Spin Resonance of Radiation Damage to DNA{close_quotes}.

  16. Damage evolution and mechanical response of cross-ply ceramic composite laminates

    SciTech Connect

    Weitsman, Y.; Yu, N.; Zhu, H.

    1995-12-31

    A mechanistic model for the damage evolution and mechanical response of cross-ply ceramic composite laminates under monotonically increasing uniaxial tension is presented. The model accounts for a variety of damage mechanisms evolving in cross-ply ceramic composite laminates, such as fiber-bridged matrix cracks in 0{degrees}-plies, transversely oriented matrix cracks in 90{degrees}-plies, and slips at 0{degrees}/90{degrees} ply interfaces as well as at the fiber/matrix interfaces. Energy criteria are developed to determine the creation and progression of matrix cracks and slip zones. The model predicts that the crack density in 0{degrees}-plies becomes higher than that within the 90{degrees}-plies as the applied load is incrementally increased, which agrees with the experimental observation. It is also shown that the model provides a reasonable prediction for the nonlinear stress-strain behavior of crossply SiC/CAS ceramic composites.

  17. Molecular mechanism of photosensitization. XI. Membrane damage and DNA cleavage photoinduced by enoxacin.

    PubMed

    Sortino, S; Condorelli, G; De Guidi, G; Giuffrida, S

    1998-11-01

    The photosensitizing activity of enoxacin, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)- 1,8-naphthyridine-3-carboxilic acid (ENX), toward membranes and DNA has been studied, taking into account human erythrocyte photohemolysis, unilamellar liposome alterations and plasmid pBR322 DNA photocleavage. Hydroxyl radicals and an aromatic carbene generated from ENX photodefluorination seem to be the active intermediates involved in the photosensitization process. The steady-state photolysis products do not participate in the process. The mechanism of photosensitization responsible for the membrane damage depends on the oxygen concentration and follows a different path with respect to that operative for DNA cleavage. Between oxygenated radicals, the hydroxyl seems the species mainly responsible for membrane damage, whereas DNA cleavage is mainly produced by the carbene intermediate. A molecular mechanism of the photosensitization induced by ENX is proposed.

  18. A control system formulation of the mechanism that controls the secretions of serum group hormone in humans during sleep

    NASA Technical Reports Server (NTRS)

    Howard, J. C.; Young, D. R.

    1975-01-01

    Plasma growth hormone concentrations during sleep were determined experimentally. An elevated level of plasma growth hormone was observed during the initial phase of sleep and remained elevated for approximately 3 hr before returning to the steady-state level. Moreover, subsequent to a prolonged interruption of sleep, of the order of 2-3 hr, an elevated level of plasma growth hormone was again observed during the initial phase of resumed sleep. A control system formulation of the mechanism that controls the secretions of serum growth hormone in humans was used to account for the growth hormone responses observed.

  19. Continuum Damage Mechanics Models for the Analysis of Progressive Failure in Open-Hole Tension Laminates

    NASA Technical Reports Server (NTRS)

    Song, Kyonchan; Li, Yingyong; Rose, Cheryl A.

    2011-01-01

    The performance of a state-of-the-art continuum damage mechanics model for interlaminar damage, coupled with a cohesive zone model for delamination is examined for failure prediction of quasi-isotropic open-hole tension laminates. Limitations of continuum representations of intra-ply damage and the effect of mesh orientation on the analysis predictions are discussed. It is shown that accurate prediction of matrix crack paths and stress redistribution after cracking requires a mesh aligned with the fiber orientation. Based on these results, an aligned mesh is proposed for analysis of the open-hole tension specimens consisting of different meshes within the individual plies, such that the element edges are aligned with the ply fiber direction. The modeling approach is assessed by comparison of analysis predictions to experimental data for specimen configurations in which failure is dominated by complex interactions between matrix cracks and delaminations. It is shown that the different failure mechanisms observed in the tests are well predicted. In addition, the modeling approach is demonstrated to predict proper trends in the effect of scaling on strength and failure mechanisms of quasi-isotropic open-hole tension laminates.

  20. Tertiary mechanisms of brain damage: a new hope for treatment of cerebral palsy?

    PubMed

    Fleiss, Bobbi; Gressens, Pierre

    2012-06-01

    Cerebral palsy is caused by injury or developmental disturbances to the immature brain and leads to substantial motor, cognitive, and learning deficits. In addition to developmental disruption associated with the initial insult to the immature brain, injury processes can persist for many months or years. We suggest that these tertiary mechanisms of damage might include persistent inflammation and epigenetic changes. We propose that these processes are implicit in prevention of endogenous repair and regeneration and predispose patients to development of future cognitive dysfunction and sensitisation to further injury. We suggest that treatment of tertiary mechanisms of damage might be possible by various means, including preventing the repressive effects of microglia and astrocyte over-activation, recapitulating developmentally permissive epigenetic conditions, and using cell therapies to stimulate repair and regeneration Recognition of tertiary mechanisms of damage might be the first step in a complex translational task to tailor safe and effective therapies that can be used to treat the already developmentally disrupted brain long after an insult.

  1. Antiasthmatic Role of "Pentapala -04" a Herbal Formulation Against Ova Albumin and Aluminium HydroxideInduced LungDamage in Rats.

    PubMed

    Rao, D Srinivasa; Jayaraaj, Indira A; Jayaraaj, R

    2005-01-01

    Bronchial asthma is a clinical syndrome characterized by proximal dysphasia and wheeze due to increased resistance to the flow of air through the narrowed bronchi. Asthma has become the most common chronic disease in the world and epidemiological studies suggest that its prevalence, severity and mortality are rising at a time when mortality from other common treatable conditions is falling. The reasons for the above statistics are environmental factors such as increased exposure to allergens and atmospheric pollutants. Antiasthmatic treatment includes corticosteroids, which are very effective in the treatment of asthma. But corticosteroids are costly and if given systemically, have many severe adverse effects. Hence, the present research work involves the use of a herbal compound formulation Pentapala -04 prepared from five medicinal plants namely, Adhatoda vasica Need, Ocimum sanctum Linn, Coleus aromaticus Benth, Glycyrrhiza glabra Linn and Alpiania galangal Sw.The effect of "Pentapala-04" on ova albumin and aluminium hydroxide induced lung damage in albino wistar rats was investigated. The rats were divided into three groups of four animals each. Group I, II and III serves as control, toxic and post treatment group respectively. Our results showed that their was increased level of lipid peroxidation and secreased level of antioxidants in toxic group animals. But the levels of antioxidant enzymes were restored in post-treated groups of animals, which might be due to the ability of "ability of "Pentapala-04 to scavenge the reactive oxygen species. PMID:22557168

  2. The Role of Logic and Mathematics in the Heisenberg Formulation of Quantum Mechanics

    NASA Astrophysics Data System (ADS)

    Venezia, Antonio

    2006-06-01

    In this paper, by means of a logical and linguistic analysis of Heisenberg's work, the properties of a logical model suitable for quantum mechanics are obtained. This model is an alternative to traditional quantum logic, because it uses an intuitionist negation. It is able to justify the passage from the problem of conjugate variables measurement to the mathematical formalization (commutation rules) of matrix mechanics.

  3. The evaluation of damage mechanism of unreinforced masonry buildings after Van (2011) and Elazig (2010) Earthquakes

    NASA Astrophysics Data System (ADS)

    Güney, D.; Aydin, E.; Öztürk, B.

    2015-07-01

    On March 8th, 2010 Karakocan-Elazig earthquake of magnitude 6.0 occurred at a region where masonry and adobe construction is very common. Karakocan-Elazig is located in a high seismicity region on Eastern Anatolian Fault System (EAFS). Due to the earthquake, 42 people were killed and 14’113 buildings were damaged. Another city, Van located at South east of Turkey is hit by earthquakes with M = 7.2 occurred on October 23rd, 2011 at 13:41 (local time), whose epicenter was about 16 km north of Van (Tabanli village) and M = 5.6 on November 9th, 2011 with an epicenter near the town of Edremit, south of Van and caused the loss of life and heavy damages. Both earthquakes killed 644 people and 2608 people were injured. Approximately 10’000 buildings were seriously damaged. There are many traditional types of structures existing in the region hit by earthquakes (both Van and Elazig). These buildings were built as adobe, unreinforced masonry or mixed type. These types of buildings are very common in rural areas (especially south and east) of Turkey because of easy workmanship and cheap construction cost. Many of those traditional type structures experienced serious damages. The use of masonry is very common in some of the world's most hazard-prone regions, such as in Latin America, Africa, the Indian subcontinent and other parts of Asia, the Middle East, and southern Europe. Based on damage and failure mechanism of those buildings, the parameters affecting the seismic performance of those traditional buildings are analyzed in this paper. The foundation type, soil conditions, production method of the masonry blocks, construction method, the geometry of the masonry walls, workmanship quality, existence of wooden beams, type of roof, mortar between adobe blocks are studied in order to understand the reason of damage for these types of buildings.

  4. Theoretical research on damage mechanism of ultrafast laser ablation crystal silicon

    NASA Astrophysics Data System (ADS)

    Shao, Junfeng; Guo, Jin; Wang, Tingfeng

    2013-09-01

    High peak power picosecond laser ablation of silicon draws great attention in solar cell manufacture,laser optoelectric countermeasure applications, eta. This paper reports the damage process of ultrafast lasers interaction with silicon,which is based on Two-Temperature Model(TTM) and 1-on-1 damage threshold test method. Pulsed laser caused damage manifests in several ways, such as heat damage, mechanical effect and even eletrical effect. In this paper, a modified Two Temperature Model is applied in ultrashort laser interaction with silicon.The traditional Two-Temperature Model methods is proposed by Anismov in 1970s to calculate the interaction between ultrafast laser with metals, which is composed of free electrons and lattice. Beyond the carrier and lattice temperture model, an additional excited term and Auger recombination term of carriers is taken into account in this modified Two-Temperature Model model to reflect the characteristics in semicondutors. Under the same pulse-duration condition, the damage threshold is found to be 161 mJ/cm2 and a characteritic double-peak shape shows up. As the pulse energy density rises from 50mJ/cm2 to 161 mJ/cm2, the difference between carrier and lattice temperature steps down proportionally.Also,a detailed interaction process between photon-electron and electron-phonon is discussed. Electron and lattice temperature evolutes distinctly different, while the former is much higher than the latter until heat tranfer finished at 200 picoseconds. Two-peak feature of electron temperature is also identified. As the pulse duration increases from 20 picosecond to 60 picosecond, the he difference between carrier and lattice temperature steps down significantly. The calculated damage threshold does not change fundamentally, remaining approximately 0.16J/cm2. Also, the damage mechanism is found to be thermal heating with the pulse width between 20 and 60 picoseconds at threshold fluences which is identical to experiment test result

  5. Insight into mechanism of lanthanum (III) induced damage to plant photosynthesis.

    PubMed

    Hu, Huiqing; Wang, Lihong; Li, Yueli; Sun, Jingwen; Zhou, Qing; Huang, Xiaohua

    2016-05-01

    A great deal of literature is available regarding the environmental and ecological effects of rare earth element pollution on plants. These studies have shown that excess lanthanum (La) (III) in the environment can inhibit plant growth and even cause plant death. Moreover, inhibition of plant photosynthesis is known to be one of the physiological bases of these damages. However, the mechanism responsible for these effects is still unclear. In this study, the mechanism of La(III)-induced damage to plant photosynthesis was clarified from the viewpoint of the chloroplast ultrastructure, the contents of chloroplast mineral elements and chlorophyll, the transcription of chloroplast ATPase subunits and chloroplast Mg(2+)-ATPase activity, in which rice was selected as a study object. Following treatment with low level of La(III), the chloroplast ultrastructure of rice was not changed, and the contents of chloroplast mineral elements (Mg, P, K, Ca, Mn, Fe, Ni, Cu, and Zn) increased, but the chlorophyll content did not change significantly. Moreover, the transcription of chloroplast ATPase subunits, chloroplast Mg(2+)-ATPase activity, the net photosynthetic rate and growth indices increased. Following treatment with high levels of La(III), the chloroplast ultrastructure was damaged, chloroplast mineral elements (except Cu and Zn) and chlorophyll contents decreased, and the transcription of chloroplast ATPase subunits, chloroplast Mg(2+)-ATPase activity, the net photosynthetic rate and growth indices decreased. Based on these results, a possible mechanism of La(III)-induced damage to plant photosynthesis was proposed to provide a reference for scientific evaluation of the potential ecological risk of rare earth elements in the environment.

  6. Mechanisms of DNA damage response to targeted irradiation in organotypic 3D skin cultures.

    PubMed

    Acheva, Anna; Ghita, Mihaela; Patel, Gaurang; Prise, Kevin M; Schettino, Giuseppe

    2014-01-01

    DNA damage (caused by direct cellular exposure and bystander signaling) and the complex pathways involved in its repair are critical events underpinning cellular and tissue response following radiation exposures. There are limited data addressing the dynamics of DNA damage induction and repair in the skin particularly in areas not directly exposed. Here we investigate the mechanisms regulating DNA damage, repair, intracellular signalling and their impact on premature differentiation and development of inflammatory-like response in the irradiated and surrounding areas of a 3D organotypic skin model. Following localized low-LET irradiation (225 kVp X-rays), low levels of 53BP1 foci were observed in the 3D model (3.8±0.28 foci/Gy/cell) with foci persisting and increasing in size up to 48 h post irradiation. In contrast, in cell monolayers 14.2±0.6 foci/Gy/cell and biphasic repair kinetics with repair completed before 24 h was observed. These differences are linked to differences in cellular status with variable level of p21 driving apoptotic signalling in 2D and accelerated differentiation in both the directly irradiated and bystander areas of the 3D model. The signalling pathways utilized by irradiated keratinocytes to induce DNA damage in non-exposed areas of the skin involved the NF-κB transcription factor and its downstream target COX-2. PMID:24505255

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

    PubMed

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

    2016-10-01

    The main components of sunlight reaching the eye lens are UVA and visible light exerting their photo-damaging effects indirectly by the aid of endogenous photosensitizer molecules such as riboflavin (RF). In this study, lens proteins solutions were incubated with RF and exposed to the sunlight. Then, gel mobility shift analysis and different spectroscopic assessments were applied to examine the structural damaging effects of solar radiation on these proteins. Exposure of lens proteins to direct sunlight, in the presence of RF, leads to marked structural crosslinking, oligomerization and proteolytic instability. These structural damages were also accompanied with reduction in the emission fluorescence of Trp and Tyr and appearance of a new absorption peak between 300 and 400nm which can be related to formation of new chromophores. Also, photo-oxidation of lens crystallins increases their oligomeric size distribution as examined by dynamic light scattering analysis. The above mentioned structural insults, as potential sources of sunlight-induced senile cataract and blindness, were significantly attenuated in the presence of ascorbic acid and glutathione which are two important components of lens antioxidant defense system. Therefore, the powerful antioxidant defense mechanism of eye lens is an important barrier against molecular photo-damaging effects of solar radiations during the life span. PMID:27316765

  8. An investigation of the influence of process and formulation variables on mechanical properties of high shear granules using design of experiment.

    PubMed

    Mangwandi, Chirangano; Adams, Michael J; Hounslow, Michael J; Salman, Agba D

    2012-05-10

    Being able to predict the properties of granules from the knowledge of the process and formulation variables is what most industries are striving for. This research uses experimental design to investigate the effect of process variables and formulation variables on mechanical properties of pharmaceutical granules manufactured from a classical blend of lactose and starch using hydroxypropyl cellulose (HPC) as the binder. The process parameters investigated were granulation time and impeller speed whilst the formulation variables were starch-to-lactose ratio and HPC concentration. The granule properties investigated include granule packing coefficient and granule strength. The effect of some components of the formulation on mechanical properties would also depend on the process variables used in granulation process. This implies that by subjecting the same formulation to different process conditions results in products with different properties.

  9. Damage Development in High Purity Copper Under Varying Dynamic Conditions and Microstructural States Using Continuum Damage Mechanics

    NASA Astrophysics Data System (ADS)

    Bonora, N.; Ruggiero, A.; Esposito, L.; Iannitti, G.

    2009-12-01

    In the framework of CDM, the evolution of the plastic strain, at which damage processes initiates, as a function of stress triaxiality, making the assumption of constant damage dissipated work is derived. Based on this, the CDM model proposed by Bonora (Eng. Frac. Mech., 58, 1-2, 1997) has been used to predict the occurrence of ductile failure at different stress triaxiality conditions, under both quasi-static and dynamic loading conditions. This solution allows the possibility to correctly predict the conditions for which ductile damage can initiate under uniaxial strain (such as that for the flyer plate impact test) and mixed conditions such as those in the Taylor impact test. The solution offers the possibility to correlate continuum damage model parameters to micro structural features such as grain size and purity grade.

  10. Enamel Insulated Copper Wire in Electric Motors: Sliding Behavior and Possible Damage Mechanisms During Die Bending

    NASA Astrophysics Data System (ADS)

    Demiri, Albion

    This study investigates the sliding friction and the forming behaviour of enamel insulated copper wire during the die-forming process. It also aims to determine potential damage mechanisms to the wire during bending process for electric motor coils. In this investigation a wire-bending machine was designed and built in order to simulate the wire forming process in a laboratory scale. Bending angle of the wire and the bending radii were used to control the strain on the wire surface. The effect of speed on COF was investigated for different speeds of of 1, 5, 10, 15, and 20mm/s. A positive correlation was observed between the COF and the testing speed. Additionally, the effect of strain on COF was studied for 2% and 23% to determine its influence on the COF. A general trend was observed of decreased COF with increased strain in wires. Finally, the ability of the enamel coating to resist external damage and wire strain was investigated by tensile testing of pre-scratched magnet wire. The results showed that wire enamel can withstand significant surface damage prior to breach and failure. The insulating polymer coating failed under the scratch tests at 20N load using a Rockwell indenter and at 5N load using a 90° conical steel indenter. Additional tests, such as tensile testing, scratch testing and reciprocating friction testing, were used to characterize the mechanical and tribological properties of the enamel insulated copper wire.

  11. Microcavitation as a Neuronal Damage Mechanism in Blast Traumatic Brain Injury

    NASA Astrophysics Data System (ADS)

    Franck, Christian; Estrada, Jonathan

    2015-11-01

    Blast traumatic brain injury (bTBI) is a leading cause of injury in the armed forces. Diffuse axonal injury, the hallmark feature of blunt TBI, has been investigated in direct mechanical loading conditions. However, recent evidence suggests inertial cavitation as a possible bTBI mechanism, particularly in the case of exposure to blasts. Cavitation damage to free surfaces has been well-studied, but bubble interactions within confined 3D environments, in particular their stress and strain signatures are not well understood. The structural damage due to cavitation in living tissues - particularly at the cellular level - are incompletely understood, in part due to the rapid bubble formation and deformation strain rates of up to ~ 105-106 s-1. This project aims to characterize material damage in 2D and 3D cell culture environments by utilizing a novel high-speed red-blue diffraction assisted image correlation method at speeds of up to 106 frames per second. We gratefully acknowledge funding from the Office of Naval Research (POC: Dr. Tim Bentley).

  12. Duration of emission of volatile organic compounds from mechanically damaged plant leaves.

    PubMed

    Smith, Lincoln; Beck, John J

    2015-09-01

    Classical biological control of invasive alien weeds depends on the use of arthropod herbivores that are sufficiently host specific to avoid risk of injuring nontarget plants. Host plant specificity is usually evaluated by using a combination of behavioral and developmental experiments under choice, no-choice and field conditions. Secondary plant compounds are likely to have an important influence on host plant specificity. However, relatively little is known about the volatile organic compounds (VOCs) that are emitted by target and nontarget plants, and how environmental conditions may affect their emission. Previous studies have shown that mechanical damage of leaves increases the composition and content of VOCs emitted. In this study we measured the VOC emissions of five species of plants in the subtribe Centaureinae (Asteraceae)--Carthamus tinctorius, Centaurea cineraria, Centaurea melitensis, Centaurea rothrockii, and Centaurea solstitialis--that have previously been used in host specificity experiments for a prospective biological control agent of yellow starthistle (C. solstitialis). Leaves of each plant were punctured with a needle and the VOCs were collected by solid-phase microextraction (SPME) periodically over 48 h and analyzed by GC-MS. A total of 49 compounds were detected. Damage caused an immediate increase of 200-600% in the composition of VOCs emitted from each plant species, and the amounts generally remained high for at least 48 h. The results indicate that a very unspecific mechanical damage can cause a prolonged change in the VOC profile of plants. PMID:26398629

  13. Tension Strength, Failure Prediction and Damage Mechanisms in 2D Triaxial Braided Composites with Notch

    NASA Technical Reports Server (NTRS)

    Norman, Timothy L.; Anglin, Colin

    1995-01-01

    The unnotched and notched (open hole) tensile strength and failure mechanisms of two-dimensional (2D) triaxial braided composites were examined. The effect of notch size and notch position were investigated. Damage initiation and propagation in notched and unnotched coupons were also examined. Theory developed to predict the normal stress distribution near an open hole and failure for tape laminated composites was evaluated for its applicability to 2D triaxial braided textile composite materials. Four different fiber architectures were considered; braid angle, yarn and braider size, percentage of longitudinal yarns and braider angle varied. Tape laminates equivalent to textile composites were also constructed for comparison. Unnotched tape equivalents were stronger than braided textiles but exhibited greater notch sensitivity. Notched textiles and tape equivalents have roughly the same strength at large notch sizes. Two common damage mechanisms were found: braider yarn cracking and near notch longitudinal yarn splitting. Cracking was found to initiate in braider yarns in unnotched and notched coupons, and propagate in the direction of the braider yarns until failure. Damage initiation stress decreased with increasing braid angle. No significant differences in prediction of near notch strain between textile and tape equivalents could be detected for small braid angle, but the correlations were weak for textiles with large braid angle. Notch strength could not be predicted using existing anisotropic theory for braided textiles due to their insensitivity to notch.

  14. Duration of emission of volatile organic compounds from mechanically damaged plant leaves.

    PubMed

    Smith, Lincoln; Beck, John J

    2015-09-01

    Classical biological control of invasive alien weeds depends on the use of arthropod herbivores that are sufficiently host specific to avoid risk of injuring nontarget plants. Host plant specificity is usually evaluated by using a combination of behavioral and developmental experiments under choice, no-choice and field conditions. Secondary plant compounds are likely to have an important influence on host plant specificity. However, relatively little is known about the volatile organic compounds (VOCs) that are emitted by target and nontarget plants, and how environmental conditions may affect their emission. Previous studies have shown that mechanical damage of leaves increases the composition and content of VOCs emitted. In this study we measured the VOC emissions of five species of plants in the subtribe Centaureinae (Asteraceae)--Carthamus tinctorius, Centaurea cineraria, Centaurea melitensis, Centaurea rothrockii, and Centaurea solstitialis--that have previously been used in host specificity experiments for a prospective biological control agent of yellow starthistle (C. solstitialis). Leaves of each plant were punctured with a needle and the VOCs were collected by solid-phase microextraction (SPME) periodically over 48 h and analyzed by GC-MS. A total of 49 compounds were detected. Damage caused an immediate increase of 200-600% in the composition of VOCs emitted from each plant species, and the amounts generally remained high for at least 48 h. The results indicate that a very unspecific mechanical damage can cause a prolonged change in the VOC profile of plants.

  15. MECHANISMS FOR COUNTERING OXIDATIVE STRESS AND DAMAGE IN RETINAL PIGMENT EPITHELIUM

    PubMed Central

    Plafker, Scott M.; O’Mealey, Gary B.; Szweda, Luke I.

    2013-01-01

    Clinical and experimental evidence supports that chronic oxidative stress is a primary contributing factor to numerous retinal degenerative diseases, such as age-related macular degeneration (AMD). Eyes obtained postmortem from AMD patients have extensive free radical damage to the proteins, lipids, DNA, and mitochondria of their retinal pigment epithelial (RPE) cells. In addition, several mouse models of chronic oxidative stress develop many of the pathological hallmarks of AMD. However, the extent to which oxidative stress is an etiologic component versus its involvement in disease progression remains a major unanswered question. Further, whether the primary target of oxidative stress and damage is photoreceptors or RPE cells, or both, is still unclear. In this review, we discuss the major functions of RPE cells with an emphasis on the oxidative challenges these cells encounter and the endogenous antioxidant mechanisms employed to neutralize the deleterious effects that such stresses can elicit if left unchecked. PMID:22878106

  16. Molecular Mechanism of Aggravation of Hypertensive Organ Damages by Short-Term Blood Pressure Variability

    PubMed Central

    Kai, Hisashi; Kudo, Hiroshi; Takayama, Narimasa; Yasuoka, Suguru; Aoki, Yuji; Imaizumi, Tsutomu

    2015-01-01

    There is increasing evidence that not only the elevation of systolic and diastolic blood pressure (BP) but also the increase in BP variability (or fluctuation) are associated with hypertensive organ damages and the morbidity and mortality of cerebrovascular and cardiovascular events. However, the molecular mechanism whereby the increase in BP variability aggravates hypertensive organ damages remains unknown. Thus, we created a rat chronic model of a combination of hypertension and large BP variability by performing bilateral sino-aortic denervation in spontaneously hypertensive rat. A series of our studies using this model revealed that large BP variability induces chronic myocardial inflammation by activating local angiotensin II and mineralocorticoid receptor systems and thereby aggravates cardiac hypertrophy and myocardial fibrosis, leading to systolic dysfunction, in hypertensive hearts. In addition, large BP variability induces the aggravation of arteriolosclerotic changes and ischemic cortical fibrosis in hypertensive kidney via local angiotensin II system. PMID:25544288

  17. A Novel Mechanism of Spine Damages in Stroke via DAPK1 and Tau

    PubMed Central

    Pei, Lei; Wang, Shan; Jin, Huijuan; Bi, Linlin; Wei, Na; Yan, Honglin; Yang, Xin; Yao, Chengye; Xu, Mengmeng; Shu, Shu; Guo, Yu; Yan, Huanhuan; Wu, Jianhua; Li, Hao; Pang, Pei; Tian, Tian; Tian, Qing; Zhu, Ling-Qiang; Shang, You; Lu, Youming

    2015-01-01

    Synaptic spine loss is one of the major preceding consequences of stroke damages, but its underlying molecular mechanisms remain unknown. Here, we report that a direct interaction of DAPK1 with Tau causes spine loss and subsequently neuronal death in a mouse model with stroke. We found that DAPK1 phosphorylates Tau protein at Ser262 (pS262) in cortical neurons of stroke mice. Either genetic deletion of DAPK1 kinase domain (KD) in mice (DAPK1-KD−/−) or blocking DAPK1-Tau interaction by systematic application of a membrane permeable peptide protects spine damages and improves neurological functions against stroke insults. Thus, disruption of DAPK1-Tau interaction is a promising strategy in clinical management of stroke. PMID:25995053

  18. The Double-Well Potential in Quantum Mechanics: A Simple, Numerically Exact Formulation

    ERIC Educational Resources Information Center

    Jelic, V.; Marsiglio, F.

    2012-01-01

    The double-well potential is arguably one of the most important potentials in quantum mechanics, because the solution contains the notion of a state as a linear superposition of "classical" states, a concept which has become very important in quantum information theory. It is therefore desirable to have solutions to simple double-well potentials…

  19. Plasticity and ductility in graphene oxide through a mechanochemically induced damage tolerance mechanism

    PubMed Central

    Wei, Xiaoding; Mao, Lily; Soler-Crespo, Rafael A.; Paci, Jeffrey T.; Espinosa, Horacio D.

    2015-01-01

    The ability to bias chemical reaction pathways is a fundamental goal for chemists and material scientists to produce innovative materials. Recently, two-dimensional materials have emerged as potential platforms for exploring novel mechanically activated chemical reactions. Here we report a mechanochemical phenomenon in graphene oxide membranes, covalent epoxide-to-ether functional group transformations that deviate from epoxide ring-opening reactions, discovered through nanomechanical experiments and density functional-based tight binding calculations. These mechanochemical transformations in a two-dimensional system are directionally dependent, and confer pronounced plasticity and damage tolerance to graphene oxide monolayers. Additional experiments on chemically modified graphene oxide membranes, with ring-opened epoxide groups, verify this unique deformation mechanism. These studies establish graphene oxide as a two-dimensional building block with highly tuneable mechanical properties for the design of high-performance nanocomposites, and stimulate the discovery of new bond-selective chemical transformations in two-dimensional materials. PMID:26289729

  20. Plasticity and ductility in graphene oxide through a mechanochemically induced damage tolerance mechanism

    NASA Astrophysics Data System (ADS)

    Wei, Xiaoding; Mao, Lily; Soler-Crespo, Rafael A.; Paci, Jeffrey T.; Huang, Jiaxing; Nguyen, Sonbinh T.; Espinosa, Horacio D.

    2015-08-01

    The ability to bias chemical reaction pathways is a fundamental goal for chemists and material scientists to produce innovative materials. Recently, two-dimensional materials have emerged as potential platforms for exploring novel mechanically activated chemical reactions. Here we report a mechanochemical phenomenon in graphene oxide membranes, covalent epoxide-to-ether functional group transformations that deviate from epoxide ring-opening reactions, discovered through nanomechanical experiments and density functional-based tight binding calculations. These mechanochemical transformations in a two-dimensional system are directionally dependent, and confer pronounced plasticity and damage tolerance to graphene oxide monolayers. Additional experiments on chemically modified graphene oxide membranes, with ring-opened epoxide groups, verify this unique deformation mechanism. These studies establish graphene oxide as a two-dimensional building block with highly tuneable mechanical properties for the design of high-performance nanocomposites, and stimulate the discovery of new bond-selective chemical transformations in two-dimensional materials.

  1. Chromatin Modifications during Repair of Environmental Exposure-Induced DNA Damage: A Potential Mechanism for Stable Epigenetic Alterations

    PubMed Central

    O’Hagan, Heather M.

    2014-01-01

    Exposures to environmental toxicants and toxins cause epigenetic changes that likely play a role in the development of diseases associated with exposure. The mechanism behind these exposure-induced epigenetic changes is currently unknown. One commonality between most environmental exposures is that they cause DNA damage either directly or through causing an increase in reactive oxygen species, which can damage DNA. Like transcription, DNA damage repair must occur in the context of chromatin requiring both histone modifications and ATP-dependent chromatin remodeling. These chromatin changes aid in DNA damage accessibility and signaling. Several proteins and complexes involved in epigenetic silencing during both development and cancer have been found to be localized to sites of DNA damage. The chromatin-based response to DNA damage is considered a transient event, with chromatin being restored to normal as DNA damage repair is completed. However, in individuals chronically exposed to environmental toxicants or with chronic inflammatory disease, repeated DNA damage-induced chromatin rearrangement may ultimately lead to permanent epigenetic alterations. Understanding the mechanism behind exposure-induced epigenetic changes will allow us to develop strategies to prevent or reverse these changes. This review focuses on epigenetic changes and DNA damage induced by environmental exposures, the chromatin changes that occur around sites of DNA damage, and how these transient chromatin changes may lead to heritable epigenetic alterations at sites of chronic exposure. PMID:24259318

  2. Switch telomerase to ALT mechanism by inducing telomeric DNA damages and dysfunction of ATRX and DAXX.

    PubMed

    Hu, Yang; Shi, Guang; Zhang, Laichen; Li, Feng; Jiang, Yuanling; Jiang, Shuai; Ma, Wenbin; Zhao, Yong; Songyang, Zhou; Huang, Junjiu

    2016-01-01

    Activation of telomerase or alternative lengthening of telomeres (ALT) is necessary for tumours to escape from dysfunctional telomere-mediated senescence. Anti-telomerase drugs might be effective in suppressing tumour growth in approximately 85-90% of telomerase-positive cancer cells. However, there are still chances for these cells to bypass drug treatment after switching to the ALT mechanism to maintain their telomere integrity. But the mechanism underlying this switch is unknown. In this study, we used telomerase-positive cancer cells (HTC75) to discover the mechanism of the telomerase-ALT switch by inducing telomere-specific DNA damage, alpha-thalassemia X-linked syndrome protein (ATRX) knockdown and deletion of death associated protein (DAXX). Surprisingly, two important ALT hallmarks in the ALT-like HTC75 cells were observed after treatments: ALT-associated promyelocytic leukaemia bodies (APBs) and extrachromosomal circular DNA of telomeric repeats. Moreover, knocking out hTERT by utilizing the CRISPR/Cas9 technique led to telomere elongation in a telomerase-independent manner in ALT-like HTC75 cells. In summary, this is the first report to show that inducing telomeric DNA damage, disrupting the ATRX/DAXX complex and inhibiting telomerase activity in telomerase-positive cancer cells lead to the ALT switch. PMID:27578458

  3. Switch telomerase to ALT mechanism by inducing telomeric DNA damages and dysfunction of ATRX and DAXX

    PubMed Central

    Hu, Yang; Shi, Guang; Zhang, Laichen; Li, Feng; Jiang, Yuanling; Jiang, Shuai; Ma, Wenbin; Zhao, Yong; Songyang, Zhou; Huang, Junjiu

    2016-01-01

    Activation of telomerase or alternative lengthening of telomeres (ALT) is necessary for tumours to escape from dysfunctional telomere-mediated senescence. Anti-telomerase drugs might be effective in suppressing tumour growth in approximately 85–90% of telomerase-positive cancer cells. However, there are still chances for these cells to bypass drug treatment after switching to the ALT mechanism to maintain their telomere integrity. But the mechanism underlying this switch is unknown. In this study, we used telomerase-positive cancer cells (HTC75) to discover the mechanism of the telomerase-ALT switch by inducing telomere-specific DNA damage, alpha-thalassemia X-linked syndrome protein (ATRX) knockdown and deletion of death associated protein (DAXX). Surprisingly, two important ALT hallmarks in the ALT-like HTC75 cells were observed after treatments: ALT-associated promyelocytic leukaemia bodies (APBs) and extrachromosomal circular DNA of telomeric repeats. Moreover, knocking out hTERT by utilizing the CRISPR/Cas9 technique led to telomere elongation in a telomerase-independent manner in ALT-like HTC75 cells. In summary, this is the first report to show that inducing telomeric DNA damage, disrupting the ATRX/DAXX complex and inhibiting telomerase activity in telomerase-positive cancer cells lead to the ALT switch. PMID:27578458

  4. Failure Predictions for VHTR Core Components using a Probabilistic Contiuum Damage Mechanics Model

    SciTech Connect

    Fok, Alex

    2013-10-30

    The proposed work addresses the key research need for the development of constitutive models and overall failure models for graphite and high temperature structural materials, with the long-term goal being to maximize the design life of the Next Generation Nuclear Plant (NGNP). To this end, the capability of a Continuum Damage Mechanics (CDM) model, which has been used successfully for modeling fracture of virgin graphite, will be extended as a predictive and design tool for the core components of the very high- temperature reactor (VHTR). Specifically, irradiation and environmental effects pertinent to the VHTR will be incorporated into the model to allow fracture of graphite and ceramic components under in-reactor conditions to be modeled explicitly using the finite element method. The model uses a combined stress-based and fracture mechanics-based failure criterion, so it can simulate both the initiation and propagation of cracks. Modern imaging techniques, such as x-ray computed tomography and digital image correlation, will be used during material testing to help define the baseline material damage parameters. Monte Carlo analysis will be performed to address inherent variations in material properties, the aim being to reduce the arbitrariness and uncertainties associated with the current statistical approach. The results can potentially contribute to the current development of American Society of Mechanical Engineers (ASME) codes for the design and construction of VHTR core components.

  5. Effects of tissue mechanical properties on susceptibility to histotripsy-induced tissue damage

    NASA Astrophysics Data System (ADS)

    Vlaisavljevich, Eli; Kim, Yohan; Owens, Gabe; Roberts, William; Cain, Charles; Xu, Zhen

    2014-01-01

    Histotripsy is a non-invasive tissue ablation method capable of fractionating tissue by controlling acoustic cavitation. To determine the fractionation susceptibility of various tissues, we investigated histotripsy-induced damage on tissue phantoms and ex vivo tissues with different mechanical strengths. A histotripsy bubble cloud was formed at tissue phantom surfaces using 5-cycle long ultrasound pulses with peak negative pressure of 18 MPa and PRFs of 10, 100, and 1000 Hz. Results showed significantly smaller lesions were generated in tissue phantoms of higher mechanical strength. Histotripsy was also applied to 43 different ex vivo porcine tissues with a wide range of mechanical properties. Gross morphology demonstrated stronger tissues with higher ultimate stress, higher density, and lower water content were more resistant to histotripsy damage in comparison to weaker tissues. Based on these results, a self-limiting vessel-sparing treatment strategy was developed in an attempt to preserve major vessels while fractionating the surrounding target tissue. This strategy was tested in porcine liver in vivo. After treatment, major hepatic blood vessels and bile ducts remained intact within a completely fractionated liver volume. These results identify varying susceptibilities of tissues to histotripsy therapy and provide a rational basis to optimize histotripsy parameters for treatment of specific tissues.

  6. Inelastic deformation of metal matrix composites: Plasticity and damage mechanisms, part 2

    NASA Technical Reports Server (NTRS)

    Majumdar, B. S.; Newaz, G. M.

    1992-01-01

    The inelastic deformation mechanisms for the SiC (SCS-6)/Ti-15-3 system were studied at 538 C (1000 F) using a combination of mechanical measurements and detailed microstructural examinations. The objectives were to evaluate the contributions of plasticity and damage to the overall MMC response, and to compare the room temperature and elevated temperature deformation behaviors. Four different laminates were studied: (0)8, (90)8,(+ or -45)2s, and (0/90)2s, with the primary emphasis on the unidirectional (0)8, and (90)8 systems. The elevated temperature responses were similar to those at room temperature, involving a two-stage elastic-plastic type of response for the (0)8 system, and a characteristic three-stage deformation response for the (90)8 and (+ or -45)2s systems. The primary effects of elevated temperatures included: (1) reduction in the 'yield' and failure strengths; (2) plasticity through diffused slip rather than concentrated planar slip (which occurred at room temperature); and (3) time-dependent deformation. The inelastic deformation mechanism for the (0)8 MMC was dominated by plasticity at both temperatures. For the (90)8 and (+ or -45)2s MMCs, a combination of damage and plasticity contributed to the deformation at both temperatures.

  7. 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

  8. Molecular and sensory mechanisms to mitigate sunlight-induced DNA damage in treefrog tadpoles.

    PubMed

    Schuch, André P; Lipinski, Victor M; Santos, Mauricio B; Santos, Caroline P; Jardim, Sinara S; Cechin, Sonia Z; Loreto, Elgion L S

    2015-10-01

    The increased incidence of solar ultraviolet B (UVB) radiation has been proposed as an environmental stressor, which may help to explain the enigmatic decline of amphibian populations worldwide. Despite growing knowledge regarding the UV-induced biological effects in several amphibian models, little is known about the efficacy of DNA repair pathways. In addition, little attention has been given to the interplay between these molecular mechanisms with other physiological strategies that avoid the damage induced by sunlight. Here, DNA lesions induced by environmental doses of solar UVB and UVA radiation were detected in genomic DNA samples of treefrog tadpoles (Hypsiboas pulchellus) and their DNA repair activity was evaluated. These data were complemented by monitoring the induction of apoptosis in blood cells and tadpole survival. Furthermore, the tadpoles' ability to perceive and escape from UV wavelengths was evaluated as an additional strategy of photoprotection. The results show that tadpoles are very sensitive to UVB light, which could be explained by the slow DNA repair rates for both cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6,4) pyrimidone photoproducts (6,4PPs). However, they were resistant to UVA, probably as a result of the activation of photolyases during UVA irradiation. Surprisingly, a sensory mechanism that triggers their escape from UVB and UVA light avoids the generation of DNA damage and helps to maintain the genomic integrity. This work demonstrates the genotoxic impact of both UVB and UVA radiation on tadpoles and emphasizes the importance of the interplay between molecular and sensory mechanisms to minimize the damage caused by sunlight.

  9. Synthesis of a novel photopolymerized nanocomposite hydrogel for the treatment of acute mechanical damage to cartilage

    NASA Astrophysics Data System (ADS)

    Schlichting, Kathryn; Copeland-Johnson, Trishelle; Goodman, Matthew; Lipert, Robert; McKinley, Todd; Martin, James; Mallapragada, Surya; Lin, Zhiqun

    2011-03-01

    Posttraumatic osteoarthritis is caused by a cascade of pathobiologic and pathomechanical events starting with intraarticular fractures in the cartilage. Currently, treatment of fractures is completely focused on restoration of the macroanatomy of the joint. The premise is that restoring the macroanatomy will prevent ongoing stresses and in turn prevent cartilage degeneration. However, current treatment ignores acute mechanical damage sustained by cartilage at the time of injury. This study describes the initial development of a novel nanocomposite photopolymerizing copolymer that has potential to restore local structural integrity to acutely injured cartilage, and subsequently act as a carrier for chondrocyte-enhancing bioactive agents.

  10. Finite Element Modeling of Magnetic Flux Leakage Signals from Mechanical Damage Containing Corrosion Pits

    NASA Astrophysics Data System (ADS)

    Babbar, Vijay; Clapham, Lynann

    2009-03-01

    Steel pipeline defects such as mechanical damage (dents) and corrosion pits have been studied using the magnetic flux leakage (MFL) technique and finite element modeling (FEM). The nature of MFL signals from these defects is generally known. However, since a dented region is more susceptible to corrosion, a dent-pit defect combination may be formed, which adds complexity to signal interpretation. The present work employs FEM to investigate the change in dent signal in the presence of a pit of varying dimensions. It helps to infer if a pit located inside a dent is detectable.

  11. [DIFFERENTIATED APPROACH TO CLOSING OF WOUND SURFACES TRUNK AND EXTREMITIES AFTER ITS MECHANICAL DAMAGE].

    PubMed

    Ponomarenko, O V

    2015-07-01

    The results of examination and treatment of 231 patients on defects covering tissues of the trunk and limbs were presented. The severity of the injury determined by classification A. V. Kaplan, O. M. Markova. In 10 patients wound treatment method used, developed in the clinic, using the combined preparation of hyaluronic acid with sodium succinate (Latsert), ensuring efficiency of treatment. Differentiated approach to the selection of closing wound surfaces method caused by mechanical damage, allowed to achieve satisfactory results in 97.84% of cases. PMID:26591223

  12. Polycaprolactone/maltodextrin nanocarrier for intracellular drug delivery: formulation, uptake mechanism, internalization kinetics, and subcellular localization

    PubMed Central

    Korang-Yeboah, Maxwell; Gorantla, Yamini; Paulos, Simon A; Sharma, Pankaj; Chaudhary, Jaideep; Palaniappan, Ravi

    2015-01-01

    Prostate cancer (PCa) disease progression is associated with significant changes in intracellular and extracellular proteins, intracellular signaling mechanism, and cancer cell phenotype. These changes may have direct impact on the cellular interactions with nanocarriers; hence, there is the need for a much-detailed understanding, as nanocarrier cellular internalization and intracellular sorting mechanism correlate directly with bioavailability and clinical efficacy. In this study, we report the differences in the rate and mechanism of cellular internalization of a biocompatible polycaprolactone (PCL)/maltodextrin (MD) nanocarrier system for intracellular drug delivery in LNCaP, PC3, and DU145 PCa cell lines. PCL/MD nanocarriers were designed and characterized. PCL/MD nanocarriers significantly increased the intracellular concentration of coumarin-6 and fluorescein isothiocyanate-labeled bovine serum albumin, a model hydrophobic and large molecule, respectively. Fluorescence microscopy and flow cytometry analysis revealed rapid internalization of the nanocarrier. The extent of nanocarrier cellular internalization correlated directly with cell line aggressiveness. PCL/MD internalization was highest in PC3 followed by DU145 and LNCaP, respectively. Uptake in all PCa cell lines was metabolically dependent. Extraction of endogenous cholesterol by methyl-β-cyclodextrin reduced uptake by 75%±4.53% in PC3, 64%±6.01% in LNCaP, and 50%±4.50% in DU145, indicating the involvement of endogenous cholesterol in cellular internalization. Internalization of the nanocarrier in LNCaP was mediated mainly by macropinocytosis and clathrin-independent pathways, while internalization in PC3 and DU145 involved clathrin-mediated endocytosis, clathrin-independent pathways, and macropinocytosis. Fluorescence microscopy showed a very diffused and non-compartmentalized subcellular localization of the PCL/MD nanocarriers with possible intranuclear localization and minor colocalization in

  13. Polycaprolactone/maltodextrin nanocarrier for intracellular drug delivery: formulation, uptake mechanism, internalization kinetics, and subcellular localization.

    PubMed

    Korang-Yeboah, Maxwell; Gorantla, Yamini; Paulos, Simon A; Sharma, Pankaj; Chaudhary, Jaideep; Palaniappan, Ravi

    2015-01-01

    Prostate cancer (PCa) disease progression is associated with significant changes in intracellular and extracellular proteins, intracellular signaling mechanism, and cancer cell phenotype. These changes may have direct impact on the cellular interactions with nanocarriers; hence, there is the need for a much-detailed understanding, as nanocarrier cellular internalization and intracellular sorting mechanism correlate directly with bioavailability and clinical efficacy. In this study, we report the differences in the rate and mechanism of cellular internalization of a biocompatible polycaprolactone (PCL)/maltodextrin (MD) nanocarrier system for intracellular drug delivery in LNCaP, PC3, and DU145 PCa cell lines. PCL/MD nanocarriers were designed and characterized. PCL/MD nanocarriers significantly increased the intracellular concentration of coumarin-6 and fluorescein isothiocyanate-labeled bovine serum albumin, a model hydrophobic and large molecule, respectively. Fluorescence microscopy and flow cytometry analysis revealed rapid internalization of the nanocarrier. The extent of nanocarrier cellular internalization correlated directly with cell line aggressiveness. PCL/MD internalization was highest in PC3 followed by DU145 and LNCaP, respectively. Uptake in all PCa cell lines was metabolically dependent. Extraction of endogenous cholesterol by methyl-β-cyclodextrin reduced uptake by 75%±4.53% in PC3, 64%±6.01% in LNCaP, and 50%±4.50% in DU145, indicating the involvement of endogenous cholesterol in cellular internalization. Internalization of the nanocarrier in LNCaP was mediated mainly by macropinocytosis and clathrin-independent pathways, while internalization in PC3 and DU145 involved clathrin-mediated endocytosis, clathrin-independent pathways, and macropinocytosis. Fluorescence microscopy showed a very diffused and non-compartmentalized subcellular localization of the PCL/MD nanocarriers with possible intranuclear localization and minor colocalization in

  14. Surface damage of metallic implants due to mechanical loading and chemical reactions

    NASA Astrophysics Data System (ADS)

    Ryu, Jaejoong

    The present study investigates interfacial damage mechanism of modular implants due to synergetic action of mechanical contact loading and corrosion. Modular implants are manufactured such that surfaces have a characteristic degree of roughness determined by tool tip size and motion of tool path or feeding speed. The central hypothesis for this work is that during contact loading of metallic implants, mechanisms of damage and dissolution are determined by contact loads, plastic deformation, residual stresses and environmental conditions at the nanoscale surface asperities; while during subsequent rest periods, mechanism of metallic dissolution is determined by the environmental conditions and residual stress field induced due to long range elastic interactions of the plastically deformed asperities. First part of the thesis is focused on investigating the mechanisms underlying surface roughness evolution due to stress-assisted dissolution during the rest period. The latter part is focused on investigating material removal mechanisms during single asperity contact of implant surfaces. Experimental study was performed to elucidate the roughness evolution mechanism by combined effect of multi-asperity contact and environmental corrosion. Cobalt-chromium-molybdenum specimen was subjected to either contact loading alone or alternating contact loading and exposure to reactive environment. Roughness of the specimen surface was monitored by optical profilometry and Fast Fourier Transform (FFT) calculation was used to characterize the evolving behavior of roughness modes. Finite element analysis (FEA) was employed to identify influences of surface morphological configurations and contact pressures on the residual stress development. Analytical model of multi-asperity contact has been developed for prediction of residual stress field for different roughness configurations during varying magnitude of contact loads based on elastic inclusion theory. Experimental results

  15. Ion-induced electron production in tissue-like media and DNA damage mechanisms

    NASA Astrophysics Data System (ADS)

    Surdutovich, E.; Obolensky, O. I.; Scifoni, E.; Pshenichnov, I.; Mishustin, I.; Solov'yov, A. V.; Greiner, W.

    2009-01-01

    This work is the first stage in the development of an inclusive approach to calculation of the DNA damage caused by irradiation of biological tissue by ion/proton beams. The project starts with an analysis of ionization caused by the projectiles and the characteristics of secondary electrons produced in tissue-like media. We consider interactions with the medium on a microscopic level and this allows us to obtain the energy spectrum and abundance of secondary electrons as functions of the projectile’s kinetic energy. The physical information obtained in this analysis is related to biological processes responsible for the DNA damage induced by the projectile. In particular, we consider double strand breaks of DNA caused by secondary electrons and free radicals, and local heating in the ion’s track. The heating may enhance the biological effectiveness of electron/free radical nteractions with the DNA and may even be considered as an independent mechanism of DNA damage. Numerical estimates are performed for the case of carbon-ion beams. The obtained dose-depth curves are compared with results of the MCHIT model based on the GEANT4 toolkit.

  16. Assessing the mechanism of DNA damage induced by lead through direct and indirect interactions.

    PubMed

    Zhang, Hao; Wei, Kai; Zhang, Mengyu; Liu, Rutao; Chen, Yadong

    2014-07-01

    Lead still possesses great threats to human health owing to its widespread distribution in the environment caused by human activities, although various actions have been taken to cut down the use and distribution of lead. In this work, mechanisms of DNA damage caused by lead through indirect and direct interactions were investigated. Results from comet assay showed lead at 1-10 μM induced DNA strand breaks in mice liver cells according to olive tail moment analysis. Signals of DNA-protein crosslinks (DPC) were not significantly detected until exposed at 100 μM Pb(2+). Further more, direct interactions between Pb(2+) and DNA were explored to determine the binding mode between them using spectra analysis, isothermal titration calorimetry studies and molecular docking investigations, which indicated that Pb(2+) could bind to DNA with four binding sites to form Pb(2)(+)-DNA complex by minor groove binding effects and electrostatic forces, resulting in damage to the structure of DNA double helix. Combined studies of lead genotoxicity in indirect (comet assay and DPC assay) and direct (binding mode investigations) interactions can be applied to study the potential damages to DNA induced by heavy metal pollutants.

  17. ANALYSES OF VARIOUS DAMAGE MECHANISMS IN TRANSPARENT ARMOR SUBJECT TO PROJECTILE IMPACT

    SciTech Connect

    Lai, Canhai; Sun, Xin; Templeton, Douglas W.

    2009-01-23

    Design and manufacturing of transparent armor have been historically carried out using experimental approaches. In this study, we use advanced computational modeling tools to study the various stress components during the impact event and to identify the different crack/damage driving mechanisms for the different cracking patterns. Experimentally observed damage patterns for a thick glass laminate under fragmentation simulation projectile (FSP) impact are used to compare with the modeling results. AHPCRC developed modeling software EPIC’06 [1] is used in predicting the penetration resistance of transparent armor systems. It is found that a 1-parameter single state model can be used to predict the impact penetration depth with relatively good accuracy. In addition, hoop stress and circumferential stresses are found to produce ripple cracks, needle cracks and radial cracks. It is also found that a region of high hoop stress and circumferential stress is produced by the impact at the back side of the target plate, causing the floret damage region possibly leading to higher penetration depth for thinner laminates or higher velocity impact.

  18. Damage morphology and mechanism in ablation cutting of thin glass sheets with picosecond pulsed lasers

    NASA Astrophysics Data System (ADS)

    Sun, Mingying; Eppelt, Urs; Hartmann, Claudia; Schulz, Wolfgang; Zhu, Jianqiang; Lin, Zunqi

    2016-06-01

    We experimentally investigated the morphology and mechanism of laser-induced damage in the ablation cutting of thin glass sheets with picosecond pulsed lasers and we compared the experimental results to our models. After several passes of laser ablation, we observed two different kinds of damage morphologies on the cross-section of the cut channel. They are distinguished to be the damage region caused by high-density free-electrons and the heat-affected zone due to the heat accumulation, respectively. Furthermore, micro-cracks can be observed on the top surface of the workpiece near the cut edge. The nano-cracks could be generated by high energy free-electrons but opened and developed to be visible micro-cracks by thermal stress generated in the heat-affected zone. The crack length was proportional to the volume of heat-affected zone. Heat-affected-zone and visible-cracks free conditions of glass cutting were achieved by controlling the repetition rate and spatial overlap of laser pulses.

  19. Mechanism of cross-sectoral coordination between nature protection and forestry in the Natura 2000 formulation process in Slovakia.

    PubMed

    Sarvašová, Zuzana; Sálka, Jaroslav; Dobšinská, Zuzana

    2013-09-01

    Nature protection as a policy sector is not isolated and is directly or indirectly influenced by many other sectors (e.g. forestry, water management, rural development, energy, etc.). These policy sectors are neither completely segmented nor unaffected by the decisions taken in other policy sectors. Policy formulation in nature protection is therefore also influenced by different sectors. For that reason it is inevitable to stress the need for inter-sectoral coordination to assure their policy coherence. The aim of this article is to describe the mechanism and modes of cross-sectoral coordination and to analyze the relevant actors and their interaction, using the case of the Natura 2000 formulation process in Slovakia. The European Union (EU) set up an ecological network of special protected areas, known as Natura 2000 to ensure biodiversity by conserving natural habitats and wild fauna and flora in the territory of the Member States. An optimized nature protection must therefore carefully consider existing limits and crossdisciplinary relationships at the EU, national and regional levels. The relations between forestry and biodiversity protection are analyzed using the advocacy coalition framework (ACF). The ACF is used for analyzing how two coalitions, in this case ecological and forest owners' coalitions, advocate or pursue their beliefs from the nature protection and forestry policy field. The whole process is illustrated at the regional scale on the case study of Natura 2000 sites formulation in the Slovak Republic. For better reliability and validity of research, a combination of various empiric research methods was used, supported by existing theories. So called triangulation of sociological research or triangulation of methods consists of mutual results testing of individual methodological steps through identifying corresponding political-science theories, assessing their formal points using primary and secondary document analysis and assessing their

  20. Mechanism of cross-sectoral coordination between nature protection and forestry in the Natura 2000 formulation process in Slovakia.

    PubMed

    Sarvašová, Zuzana; Sálka, Jaroslav; Dobšinská, Zuzana

    2013-09-01

    Nature protection as a policy sector is not isolated and is directly or indirectly influenced by many other sectors (e.g. forestry, water management, rural development, energy, etc.). These policy sectors are neither completely segmented nor unaffected by the decisions taken in other policy sectors. Policy formulation in nature protection is therefore also influenced by different sectors. For that reason it is inevitable to stress the need for inter-sectoral coordination to assure their policy coherence. The aim of this article is to describe the mechanism and modes of cross-sectoral coordination and to analyze the relevant actors and their interaction, using the case of the Natura 2000 formulation process in Slovakia. The European Union (EU) set up an ecological network of special protected areas, known as Natura 2000 to ensure biodiversity by conserving natural habitats and wild fauna and flora in the territory of the Member States. An optimized nature protection must therefore carefully consider existing limits and crossdisciplinary relationships at the EU, national and regional levels. The relations between forestry and biodiversity protection are analyzed using the advocacy coalition framework (ACF). The ACF is used for analyzing how two coalitions, in this case ecological and forest owners' coalitions, advocate or pursue their beliefs from the nature protection and forestry policy field. The whole process is illustrated at the regional scale on the case study of Natura 2000 sites formulation in the Slovak Republic. For better reliability and validity of research, a combination of various empiric research methods was used, supported by existing theories. So called triangulation of sociological research or triangulation of methods consists of mutual results testing of individual methodological steps through identifying corresponding political-science theories, assessing their formal points using primary and secondary document analysis and assessing their

  1. Anisotropic mechanical properties of zircon and the effect of radiation damage

    NASA Astrophysics Data System (ADS)

    Beirau, Tobias; Nix, William D.; Bismayer, Ulrich; Boatner, Lynn A.; Isaacson, Scott G.; Ewing, Rodney C.

    2016-10-01

    This study provides new insights into the relationship between radiation-dose-dependent structural damage due to natural U and Th impurities and the anisotropic mechanical properties (Poisson's ratio, elastic modulus and hardness) of zircon. Natural zircon samples from Sri Lanka (see Muarakami et al. in Am Mineral 76:1510-1532, 1991) and synthetic samples, covering a dose range of zero up to 6.8 × 1018 α-decays/g, have been studied by nanoindentation. Measurements along the [100] crystallographic direction and calculations, based on elastic stiffness constants determined by Özkan (J Appl Phys 47:4772-4779, 1976), revealed a general radiation-induced decrease in stiffness (~54 %) and hardness (~48 %) and an increase in the Poisson's ratio (~54 %) with increasing dose. Additional indentations on selected samples along the [001] allowed one to follow the amorphization process to the point that the mechanical properties are isotropic. This work shows that the radiation-dose-dependent changes of the mechanical properties of zircon can be directly correlated with the amorphous fraction as determined by previous investigations with local and global probes (Ríos et al. in J Phys Condens Matter 12:2401-2412, 2000a; Farnan and Salje in J Appl Phys 89:2084-2090, 2001; Zhang and Salje in J Phys Condens Matter 13:3057-3071, 2001). The excellent agreement, revealed by the different methods, indicates a large influence of structural and even local phenomena on the macroscopic mechanical properties. Therefore, this study indicates the importance of acquiring better knowledge about the mechanical long-term stability of radiation-damaged materials.

  2. Characterization of damage mechanisms associated with reference point indentation in human bone.

    PubMed

    Beutel, Bryan G; Kennedy, Oran D

    2015-06-01

    Measurement of bone mineral density (BMD) is the clinical gold standard in cases of compromised skeletal integrity, such as with osteoporosis. While BMD is a useful measurement to index skeletal health, it is also limited since it cannot directly assess any mechanical properties. The ability to directly assess mechanical properties of bone tissue would be clinically important. Reference point indentation (RPI) is a technology that has been designed to try and achieve this goal. While RPI has been shown to detect altered bone tissue properties, the underlying physical mechanism of these measurements has not been characterized. Thus, we designed a study whereby the contribution of (1) test cycle number and (2) test load level to RPI test-induced sub-surface damage was characterized and quantified. Standardized specimens were prepared from cadaveric human tibiae (n=6), such that 12 replicates of each testing condition could be carried out. A custom rig was fabricated to accurately position and map indentation sites. One set of tests was carried out with 1, 5, 10, 15 and 20 cycles (Max Load: 8 N, Freq: 2 Hz), and a second set of tests was carried out with Load levels of 2, 4, 6, 8 or 10 N (Cycle number: 20, Freq: 2 Hz). The RPI parameter Loading Slope (LS) was cycle dependent at 5, 10, 15 and 20 cycles (p<0.05). First Cycle Indentation Distance (ID 1st), Total Indentation Distance (TID), Mean Energy Dissipation (ED), First Cycle Unloading Slope (US 1st), Mean Unloading Slope (US) and LS were significantly different at 6, 8 and 10 N compared to 2 N (p<0.05). From the histomorphometric measurements, damage zone span was significantly different after 5, 10, 15 and 20 cycles compared with 1 cycle while indent profile width and indent profile depth were significantly different at 10, 15 and 20 cycles (p<0.05). With the load varying protocol, each of these parameters differed significantly at each increased load level (4, 6, 8, 10 N) compared with the basal level of 2 N (p<0

  3. New thermo-mechanical fluid flow modeling of multiscale deformations in the Levant basin: formulation, verification, and preliminary analysis

    NASA Astrophysics Data System (ADS)

    Belferman, Mariana; Katsman, Regina; Agnon, Amotz

    2015-04-01

    The Levant has been repeatedly devastated by numerous earthquakes since prehistorical time, as recorded in historical documents, archaeological ruins, and sedimentary archives. In order to understand the role of the dynamics of the water bodies in triggering the deformations in the Levant basin, a new theoretical thermo-mechanical model is constructed and extended by including a fluid flow component. The latter is modeled on a basis of two-way poroelastic coupling with momentum equation. This coupling is essential to capture the fluid flow evolution induced by dynamic water loading and to resolve porosity changes. All the components of the model, namely elasticity, creep, plasticity, fluid flow, etc., have been extensively verified and presented. Results of the initial sensitivity analysis addressing the relative importance of each process in earthquakes triggering are discussed. The rich archives of pre-instrumental destructive earthquakes will set constraints for future modeling under the present formulation.

  4. Coupled hydro-mechanical properties of Cobourg limestone with special reference to excavation damage zones

    NASA Astrophysics Data System (ADS)

    Nasseri, Mohammad H.; Sehizadeh, Mahdi; Ye, Sheng; Su, Grant; Nguyen, Son; Young, R. Paul

    2016-04-01

    Argillaceous rock formations being considered as potential host or cap rocks for the geological disposal of radioactive wastes are usually characterized by the presence of bedding planes, resulting in anisotropy of their strength and deformation properties. A laboratory experimental program was performed at the Rock Fracture Dynamics Facility at the University of Toronto to determine the coupled hydro-mechanical properties of the Cobourg limestone with special reference to its potential for damage. The program consists of triaxial tests with measurement of permeability using the pulse decay method and measurement of the seismic wave velocity at different stress levels. The tests were carried out on specimens parallel and perpendicular to the foliation planes within a geophysical imaging cell under different stress levels up to and beyond their peak strength. The specimens are characterized by random and irregular clay pockets and discontinuous argillaceous weak layers. Permeability of the specimens was measured with the pulse decay method under different pre - and post- failure deviatoric stresses. The specimens tested parallel to foliation planes show higher triaxial compressive strengths and higher axial strains at failure in comparison to the specimens tested perpendicular to the foliation planes. The permeability (k) values measured under different stress levels for all specimens show a consistent trend. The k value decreases with the stress increase at the beginning due to the closure of pre-existing fissures and beddings. The k value then increases continuously with the increase in the stress level with highest k values obtained at the post-failure stage. The evolution of the compressional and shear-wave velocities and shear wave splitting as a function of the axial stress is compatible with preferably oriented weak planes and with the evolution of the hydro-mechanical properties of the Cobourg limestone. From the test results, it can be interpreted that at

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

    PubMed

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

    2016-05-11

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

  6. The protective mechanisms of paracetamol against ethanol-induced gastric mucosal damage in rats.

    PubMed

    Poon, Y K; Cho, C H; Ogle, C W

    1989-08-01

    The protective mechanisms of paracetamol against ethanol-induced gastric mucosal damage have been examined. The antiulcer action of subcutaneously (s.c.)-injected paracetamol, 250 mg kg-1, was attenuated by either subdiaphragmatic vagotomy or s.c. injection of N-ethylmaleimide, 10 mg kg-1. This attenuation was not seen in rats given paracetamol by the oral route (p.o.). Indomethacin pretreatment, 5 mg kg-1, did not influence the lesion-preventing action of paracetamol given s.c. or p.o. The findings suggest that the antiulcer effect of s.c.-administered paracetamol results from an action involving the vagal nerve and tissue sulfhydryls, but not prostaglandins. On the other hand, the protective mechanism of paracetamol p.o. is independent of the vagal system or tissue sulfhydryls and prostaglandins. It seems that paracetamol given p.o. exerts its antiulcer effect by acting directly on the mucosal cell to strengthen mucosal integrity.

  7. Calcitriol-induced DNA damage: toward a molecular mechanism of selective cell death.

    PubMed

    Hasan, S Saif; Rizvi, Asim; Naseem, Imrana

    2013-09-01

    Calcitriol, the biologically active form of vitamin D, is known to function as an important anticancer agent. The exact mechanism by which calcitriol exerts its effects remains unknown. Recent evidence suggests a link between calcitriol-induced, free-radical-mediated DNA damage and cell death, in the presence of elevated levels of copper, such as those observed in malignant cells. As calcitriol is a lipid-soluble molecule, its interaction with DNA and copper would require a "chaperone"-like molecule, which binds the relatively hydrophobic calcitriol and polar DNA. A candidate protein is the vitamin D receptor (VDR), which binds both molecules. Using the recently elucidated full-length structure of the VDR molecule, we present and discuss three possible mechanisms to explain the interaction between calcitriol and DNA, as mediated by VDR.

  8. γ-Ray irradiation stability and damage mechanism of glycidyl amine epoxy resin

    NASA Astrophysics Data System (ADS)

    Diao, Feiyu; Zhang, Yan; Liu, Yujian; Fang, Jun; Luan, Weilin

    2016-09-01

    Irradiation stability of triglycidyl-p-aminophenol (TGPAP) epoxy resins was evaluated according to the changes of physico-chemical and mechanical properties under 60Co γ-ray irradiation with a dose rate of 10 kGy/h. The result shows that with the increase of radiation dose, bending strength, thermal stability, free radical concentration and storage modulus of epoxy resin decrease first, then increase slightly, and decline sharply at the end with a dose of 960 kGy, due to competition effects between radiation-induced degradation and cross-linking reaction. The damage mechanism was derived by analyzing structure and composition change of AFG-90 resins after irradiation via IR and XPS. Irradiation will result in weak bond breaking such as Csbnd C and Csbnd N bond, and new bond forming like Cdbnd C and Cdbnd O.

  9. Mechanisms for radiation damage in DNA. Progress report, January 1, 1980-December 31, 1980

    SciTech Connect

    Sevilla, M D

    1980-09-01

    In this project several mechanisms are proposed for radiation damage to DNA constituents and DNA, and a series of experiments detailed utilizing electron spin resonance spectrometry to test the proposed mechanisms. Under current investigation are irradiated systems of DNA constituents which may shed light on indirect effects. In addition, studies of radiation effects on lipids have been undertaken which will shed light on the only other proposed site for cell kill, the membrane. Studies completed during the past year are: (1) ..pi.. cations produced in DNA bases by attack of oxidizing radicals; (2) INDO studies of radicals produced in peptides and carboxylic acid model compounds; (3) electron reactions with carboxylic acids, ketones and aldehydes; and (4) ..gamma..-irradiation of esters and triglycerides. Progress has been made this year in a study of radicals generated in model compounds for the sugar-phosphate backbone.

  10. The 2015 Nobel Prize in Chemistry The Discovery of Essential Mechanisms that Repair DNA Damage.

    PubMed

    Lindahl, Tomas; Modrich, Paul; Sancar, Aziz

    2016-01-01

    The Royal Swedish Academy awarded the Nobel Prize in Chemistry for 2015 to Tomas Lindahl, Paul Modrich and Aziz Sancar for their discoveries in fundamental mechanisms of DNA repair. This pioneering research described three different essential pathways that correct DNA damage, safeguard the integrity of the genetic code to ensure its accurate replication through generations, and allow proper cell division. Working independently of each other, Tomas Lindahl, Paul Modrich and Aziz Sancar delineated the mechanisms of base excision repair, mismatch repair and nucleotide excision repair, respectively. These breakthroughs challenged and dismissed the early view that the DNA molecule was very stable, paving the way for the discovery of human hereditary diseases associated with distinct DNA repair deficiencies and a susceptibility to cancer. It also brought a deeper understanding of cancer as well as neurodegenerative or neurological diseases, and let to novel strategies to treat cancer.

  11. The 2015 Nobel Prize in Chemistry The Discovery of Essential Mechanisms that Repair DNA Damage.

    PubMed

    Lindahl, Tomas; Modrich, Paul; Sancar, Aziz

    2016-01-01

    The Royal Swedish Academy awarded the Nobel Prize in Chemistry for 2015 to Tomas Lindahl, Paul Modrich and Aziz Sancar for their discoveries in fundamental mechanisms of DNA repair. This pioneering research described three different essential pathways that correct DNA damage, safeguard the integrity of the genetic code to ensure its accurate replication through generations, and allow proper cell division. Working independently of each other, Tomas Lindahl, Paul Modrich and Aziz Sancar delineated the mechanisms of base excision repair, mismatch repair and nucleotide excision repair, respectively. These breakthroughs challenged and dismissed the early view that the DNA molecule was very stable, paving the way for the discovery of human hereditary diseases associated with distinct DNA repair deficiencies and a susceptibility to cancer. It also brought a deeper understanding of cancer as well as neurodegenerative or neurological diseases, and let to novel strategies to treat cancer. PMID:27183258

  12. Metabolic fingerprinting to understand therapeutic effects and mechanisms of silybin on acute liver damage in rat

    PubMed Central

    Liang, Qun; Wang, Cong; Li, Binbing; Zhang, Ai-hua

    2015-01-01

    Background: Metabolic fingerprinting is a rapid and noninvasive analysis, representing a powerful approach for the characterization of phenotypes and the distinction of specific metabolic states due to environmental alterations. It has become a valuable analytical approach for the characterization of phenotypes and is the rapidly evolving field of the comprehensive measurement of ideally all endogenous metabolites in bio-samples. Silybin has displayed bright prospects in the prevention and therapy of liver injury, and we had conducted a preliminary exploration on the molecular mechanism of the hepatoprotective effects of silybin. Because the knowledge on the metabolic responses of an acute liver damage rat to the silybin is still scarce, metabolic fingerprinting can provide relevant information on the intrinsic metabolic adjustments. Materials and Methods: Here, the physiological and metabolic changes in the acute liver damage rat were investigated by performing a metabolic analysis. The phenotypic response was assessed by liquid chromatography/mass spectrometry (LC/MS) combined with pattern recognition approaches such as principal components analysis and partial least squares projection to supervised latent structures and discriminant analysis. Multivariate analysis of the data showed trends in scores plots that were related to the concentration of the silybin. Results: Results indicate 10 ions (7 upregulated and 3 downregulated) as differentiating metabolites. Key observations include perturbations of metabolic pathways linked to glutathione metabolism, tryptophan metabolism, cysteine and methionine metabolism, etc., Overall, this investigation illustrates the power of the LC/MS combined with the pattern recognition methods that can engender new insights into silybin affecting on metabolism pathways of an acute liver damage rat. Conclusion: The present study demonstrates that the combination of metabolic fingerprinting with appropriate chemometric analysis is a

  13. Mechanisms of isoproterenol-induced cardiac mitochondrial damage: protective actions of melatonin.

    PubMed

    Mukherjee, Debasri; Ghosh, Arnab K; Dutta, Mousumi; Mitra, Elina; Mallick, Sanjaya; Saha, Bhaskar; Reiter, Russel J; Bandyopadhyay, Debasish

    2015-04-01

    Mitochondrial dysfunction due to oxidative damage is the key feature of several diseases. We have earlier reported mitochondrial damage resulting from the generation of oxidative stress as a major pathophysiological effect of isoproterenol (ISO)-induced myocardial ischemia in rats. That melatonin is an antioxidant that ameliorates oxidative stress in experimental animals as well as in humans is well established. We previously demonstrated that melatonin provides cardioprotection against ISO-induced myocardial injury as a result of its antioxidant properties. The mechanism of ISO-induced cardiac mitochondrial damage and protection by melatonin, however, remains to be elucidated in vitro. In this study, we provide evidence that ISO causes dysfunction of isolated goat heart mitochondria. Incubation of cardiac mitochondria with increasing concentrations of ISO decreased mitochondrial succinate dehydrogenase (SDH) activity, which plays a pivotal role in mitochondrial bioenergetics, as well as altered the activities of other key enzymes of the Kreb's cycle and the respiratory chain. Co-incubation of ISO-challenged mitochondria with melatonin prevented the alterations in enzyme activity. That these changes in mitochondrial energy metabolism were due to the perpetration of oxidative stress by ISO was evident from the increased levels of lipid peroxidation and decreased reduced glutathione/oxidized glutathione ratio. ISO-induced oxidative stress also altered mitochondrial redox potential and brought about changes in the activity of the antioxidant enzymes manganese superoxide dismutase and glutathione peroxidase, eventually leading to alterations in total ATPase activity and membrane potential. Melatonin ameliorated these changes likely through its antioxidant abilities suggesting a possible mechanism of cardioprotection by this indole against ISO-induced myocardial injury. PMID:25652673

  14. Membrane vesiculation of Naegleria fowleri amoebae as a mechanism for resisting complement damage.

    PubMed

    Toney, D M; Marciano-Cabral, F

    1994-03-15

    Pathogenic and nonpathogenic Naegleria amoebae activate the alternative C pathway; however, only pathogenic amoebae are resistant to C-mediated damage. The present study was undertaken to determine the mechanism by which highly pathogenic N. fowleri amoebae resist C-mediated damage. Nomarski optics microscopy and electron microscopy of Naegleria amoebae revealed membrane blebbing on the surface of C-resistant N. fowleri, but not on C-sensitive N. gruberi, in response to incubation in normal human serum diluted 1:4 to 1:16. Immunofluorescent staining of pathogenic amoebae, by using antiserum to human C proteins comprising the membrane attack complex, C5b through C9, and FITC-labeled goat anti-rabbit IgG, confirmed that the membrane attack complex was concentrated on the membrane blebs. Binding studies with the use of radioiodinated C9 demonstrated a decrease in the 125I-labeled C9 cpm associated with N. fowleri amoebae and an increase in the 125I-labeled C9 cpm associated with the released membrane vesicles after increasing incubation periods in normal human serum. Treatment of pathogenic, C-resistant N. fowleri with cytochalasin D or cytochalasin B to inhibit actin-dependent exocytic processes increased the susceptibility of the amoebae to C damage. In contrast, incubation of nonpathogenic, C-sensitive amoebae with cytochalasins did not alter their susceptibility to C lysis. These data indicate that pathogenic N. fowleri use membrane vesiculation to remove membrane-deposited C proteins, specifically the membrane attack complex (C5b-C9). The ability to remove surface-associated membrane attack complexes serves as one mechanism by which pathogenic N. fowleri resist C lysis.

  15. Adaptive coupling between damage mechanics and peridynamics: A route for objective simulation of material degradation up to complete failure

    NASA Astrophysics Data System (ADS)

    Han, Fei; Lubineau, Gilles; Azdoud, Yan

    2016-09-01

    The objective (mesh-independent) simulation of evolving discontinuities, such as cracks, remains a challenge. Current techniques are highly complex or involve intractable computational costs, making simulations up to complete failure difficult. We propose a framework as a new route toward solving this problem that adaptively couples local-continuum damage mechanics with peridynamics to objectively simulate all the steps that lead to material failure: damage nucleation, crack formation and propagation. Local-continuum damage mechanics successfully describes the degradation related to dispersed microdefects before the formation of a macrocrack. However, when damage localizes, it suffers spurious mesh dependency, making the simulation of macrocracks challenging. On the other hand, the peridynamic theory is promising for the simulation of fractures, as it naturally allows discontinuities in the displacement field. Here, we present a hybrid local-continuum damage/peridynamic model. Local-continuum damage mechanics is used to describe "volume" damage before localization. Once localization is detected at a point, the remaining part of the energy is dissipated through an adaptive peridynamic model capable of the transition to a "surface" degradation, typically a crack. We believe that this framework, which actually mimics the real physical process of crack formation, is the first bridge between continuum damage theories and peridynamics. Two-dimensional numerical examples are used to illustrate that an objective simulation of material failure can be achieved by this method.

  16. Plasma damage mechanisms in low k organosilicate glass and their inhibition by Ar ion bombardment

    SciTech Connect

    Kazi, Haseeb; Kelber, Jeffry A.

    2014-03-15

    In-situ x-ray photoelectron spectroscopy and ex-situ Fourier transform infrared spectroscopy studies of vacuum ultraviolet (VUV) photons with or without O{sub 2}, and O radicals point to distinct mechanisms of carbon abstraction in nanoporous organosilicate glass (OSG) films. VUV alone in the absence of O{sub 2} results in Si-CH{sub 3} bond scission and recombination preferentially at silicon monomethyl sites, obeying diffusion kinetics. In contrast, the presence of O{sub 2} interferes with recombination, resulting in diffusion-dominated carbon loss kinetics, enhanced Si oxidation, and greatly accelerating the rate of carbon loss in both the near surface and bulk regions of the OSG, at both monomethyl and dimethyl sites. Carbon abstraction due to exposure to (O({sup 3}P)) does not follow diffusion kinetics, and such interactions yield a SiO{sub 2}-like surface layer inhibiting further O diffusion. Results indicate that diffusion-dominated carbon abstraction kinetics previously observed for OSG exposure to O{sub 2} plasma damage is primarily attributable to the diffusion of O{sub 2} down OSG nanopores, reacting at photoactivated sites, rather than the diffusion of O radicals. OSG pretreatment by 900 eV Ar{sup +} bombardment effectively inhibits both VUV + O{sub 2} and O damage mechanisms by formation of ∼1 nm thick SiO{sub 2}-like surface region that inhibits both O and O{sub 2} diffusion.

  17. A PDE Formulation of Non-Equilibrium Statistical Mechanics for Ionic Permeation

    NASA Astrophysics Data System (ADS)

    Schuss, Zeev; Nadler, Boaz; Singer, Amit; Eisenberg, Robert S.

    2003-05-01

    When there is a steady net flux in a system of interacting particles, the microscopic structure of the system can no longer be determined from the Boltzmann equilibrium distribution (partition function). Nonetheless, the microscopic structure of a finite system of diffusing interacting particles can be described by Poisson-Nernst-Planck-type partial differential equations. These equations, defined in a finite domain, are the non-equilibrium generalization of the BBGKY hierarchy of equilibrium statistical mechanics. Indeed, when no-flux conditions are imposed on the domain boundaries, equilibrium results are recovered. When non-homogeneous boundary conditions are given for these equations, the solutions describe densities and electrostatic potentials of particle systems not in equilibrium. The construction of a pair correlation function under these conditions will be a new result in statistical physics. As in the equilibrium case, a closure relation between a higher and a lower order correlation function has to be assumed. However, since we are considering a finite system, boundary conditions for the higher order correlation functions must also be derived. In applications to the permeation of ions through protein channels of biological membranes the computation of the pair correlation function will lead to a prediction of current through an open channel, given the spatial structure and fixed charge distribution. The pair correlation function contains finite size effects that lead to blocking in a narrow channel and possibly to selectivity.

  18. The Split Second Effect: The Mechanism of How Equinus Can Damage the Human Foot and Ankle

    PubMed Central

    Amis, James

    2016-01-01

    We are currently in the process of discovering that many, if not the majority, of the non-traumatic acquired adult foot and ankle problems are caused by a singular etiology: non-neuromuscular equinus or the isolated gastrocnemius contracture. There is no question that this biomechanical association exists and in time much more will be uncovered. There are three basic questions that must be answered: why would our calves tighten as we normally age, how does a tight calf, or equinus, actually cause problems remotely in the foot and ankle, and how do the forces produced by equinus cause so many seemingly unrelated pathologies in the foot and ankle? The purpose of this paper is to address the second question: how does a tight calf mechanically cause problems remotely in the foot and ankle? There has been little evidence in the literature addressing the biomechanical mechanisms by which equinus creates damaging forces upon the foot and ankle, and as a result, a precise, convincing mechanism is still lacking. Thus, the mere concept that equinus has anything to do with foot pathology is generally unknown or disregarded. The split second effect, described here, defines exactly how the silent equinus contracture creates incremental and significant damage and injury to the human foot and ankle resulting in a wide variety of pathological conditions. The split second effect is a dissenting theory based on 30 years of clinical and academic orthopedic foot and ankle experience, keen clinical observation along the way, and review of the developing literature, culminating in examination of many hours of slow motion video of normal and abnormal human gait. To my knowledge, no one has ever described the mechanism in detail this precise. PMID:27512692

  19. The Split Second Effect: The Mechanism of How Equinus Can Damage the Human Foot and Ankle.

    PubMed

    Amis, James

    2016-01-01

    We are currently in the process of discovering that many, if not the majority, of the non-traumatic acquired adult foot and ankle problems are caused by a singular etiology: non-neuromuscular equinus or the isolated gastrocnemius contracture. There is no question that this biomechanical association exists and in time much more will be uncovered. There are three basic questions that must be answered: why would our calves tighten as we normally age, how does a tight calf, or equinus, actually cause problems remotely in the foot and ankle, and how do the forces produced by equinus cause so many seemingly unrelated pathologies in the foot and ankle? The purpose of this paper is to address the second question: how does a tight calf mechanically cause problems remotely in the foot and ankle? There has been little evidence in the literature addressing the biomechanical mechanisms by which equinus creates damaging forces upon the foot and ankle, and as a result, a precise, convincing mechanism is still lacking. Thus, the mere concept that equinus has anything to do with foot pathology is generally unknown or disregarded. The split second effect, described here, defines exactly how the silent equinus contracture creates incremental and significant damage and injury to the human foot and ankle resulting in a wide variety of pathological conditions. The split second effect is a dissenting theory based on 30 years of clinical and academic orthopedic foot and ankle experience, keen clinical observation along the way, and review of the developing literature, culminating in examination of many hours of slow motion video of normal and abnormal human gait. To my knowledge, no one has ever described the mechanism in detail this precise. PMID:27512692

  20. Collagen insulated from tensile damage by domains that unfold reversibly: in situ X-ray investigation of mechanical yield and damage repair in the mussel byssus

    PubMed Central

    Harrington, Matthew J.; Gupta, Himadri S.; Fratzl, Peter; Waite, J. Herbert

    2009-01-01

    The byssal threads of the California mussel, Mytilus californianus, are highly hysteretic, elastomeric fibers that collectively perform a holdfast function in wave-swept rocky seashore habitats. Following cyclic loading past the mechanical yield point, threads exhibit a damage-dependent reduction in mechanical performance. However, the distal portion of the byssal thread is capable of recovering initial material properties through a time-dependent healing process in the absence of active cellular metabolism. Byssal threads are composed almost exclusively of multi-domain hybrid collagens known as preCols, which largely determine the mechanical properties of the thread. Here, the structure-property relationships that govern thread mechanical performance are further probed. The molecular rearrangements that occur during yield and damage repair were investigated using time-resolved in situ wide angle X-ray diffraction (WAXD) coupled with cyclic tensile loading of threads and through thermally enhanced damage-repair studies. Results indicate that the collagen domains in byssal preCols are mechanically protected by the unfolding of sacrificial non-collagenous domains that refold on a slower time-scale. Time-dependent healing is primarily attributed to stochastic recoupling of broken histidine-metal coordination complexes. PMID:19275941

  1. Multiscale Modeling of Damage Processes in Aluminum Alloys: Grain-Scale Mechanisms

    NASA Technical Reports Server (NTRS)

    Hochhalter, J. D.; Veilleux, M. G.; Bozek, J. E.; Glaessgen, E. H.; Ingraffea, A. R.

    2008-01-01

    This paper has two goals related to the development of a physically-grounded methodology for modeling the initial stages of fatigue crack growth in an aluminum alloy. The aluminum alloy, AA 7075-T651, is susceptible to fatigue cracking that nucleates from cracked second phase iron-bearing particles. Thus, the first goal of the paper is to validate an existing framework for the prediction of the conditions under which the particles crack. The observed statistics of particle cracking (defined as incubation for this alloy) must be accurately predicted to simulate the stochastic nature of microstructurally small fatigue crack (MSFC) formation. Also, only by simulating incubation of damage in a statistically accurate manner can subsequent stages of crack growth be accurately predicted. To maintain fidelity and computational efficiency, a filtering procedure was developed to eliminate particles that were unlikely to crack. The particle filter considers the distributions of particle sizes and shapes, grain texture, and the configuration of the surrounding grains. This filter helps substantially reduce the number of particles that need to be included in the microstructural models and forms the basis of the future work on the subsequent stages of MSFC, crack nucleation and microstructurally small crack propagation. A physics-based approach to simulating fracture should ultimately begin at nanometer length scale, in which atomistic simulation is used to predict the fundamental damage mechanisms of MSFC. These mechanisms include dislocation formation and interaction, interstitial void formation, and atomic diffusion. However, atomistic simulations quickly become computationally intractable as the system size increases, especially when directly linking to the already large microstructural models. Therefore, the second goal of this paper is to propose a method that will incorporate atomistic simulation and small-scale experimental characterization into the existing multiscale

  2. a Study of Biophysical Mechanisms of Damage by Ionizing Radiation to Mammalian Cells in Vitro.

    NASA Astrophysics Data System (ADS)

    Chen, Chun-Zhang

    Available from UMI in association with The British Library. An extensive survey made of published survival data of damage by ionizing radiation to mammalian cells in vitro has led to the new conclusion that the damage is determined by the specific ionization or the mean free path between ionizing events along the charged particle tracks. The optimum damage is observed when the mean free path is equivalent to the DNA double strand spacing of 1.8 nm. Therefore, the biological mechanism of ionizing radiation to mammalian cells in vitro is intra track dominant. A 100 keV electron accelerator has been constructed and commissioned to produce a broad beam irradiation field of greater than 1 cm diameter. The fluence rate may be adjusted from 10^8cm^ {-2}sec^{-1} downwards to enable further development as a chronic irradiation facility. Another new feature of the accelerator is that it incorporates a differential vacuum system which permits irradiation of the monolayer cell cultures to be carried out in normal pressure. Experiments of irradiation to Chinese hamster cells, by ^{241}Am alpha particles at low fluence rate, have supplied satisfactory data for testing a new DNA-rupture model which is under development. For V79 cells irradiated at a low fluence rate of 10^5cm^{ -2}min^{-1}, when survival data were fitted into the model, new biophysical parameters were extracted and a proposal was made that the repair phenomenon of cellular survival at very low doses is determined by three time factors: the irradiation time, the damage fixation time and the repair time. The values obtained were 3-4 hours for the mean repair time, and more than 10 hours for the damage to be considered permanent. Details of the monolayer cell culture technique developed and used in the present experiments are described. Consideration has been given to the significance of the results obtained from the study in radiation protection and in radiotherapy. In future studies it is recommended that more

  3. Mechanism for enhanced absorption of a solid dispersion formulation of LY2300559 using the artificial stomach duodenum model.

    PubMed

    Polster, Christopher S; Wu, Sy-Juen; Gueorguieva, Ivelina; Sperry, David C

    2015-04-01

    An artificial stomach duodenum (ASD) model has been used to demonstrate the performance difference between two formulations of LY2300559, a low-solubility acidic developmental drug. The two formulations investigated were a conventional high-shear wet granulation (HSWG) formulation and a solid dispersion formulation. A pharmacokinetic study in humans demonstrated the enhanced performance of the solid dispersion formulation relative to the HSWG formulation. The Cmax and AUC of the solid dispersion was 2.6 and 1.9 times greater, respectively, compared to the HSWG formulation. In the ASD, the solid dispersion formulation performance was characterized by three main phases: (1) rapid release in the stomach, creating a supersaturated concentration of drug, (2) precipitation in the stomach, and (3) rapid redissolution of the precipitate in the duodenum to concentration levels that are supersaturated relative to crystalline drug. A series of complementary experiments were employed to describe this performance behavior mechanistically. Imaging experiments with a pH indicating dye showed that local pH gradients from meglumine in the solid dispersion formulation were responsible for creating a high initial supersaturation concentration in the stomach. Upon dissipation of meglumine, the drug precipitated in the stomach as an amorphous solid. Because the precipitated drug is in an amorphous form, it can then rapidly redissolve as it transits to the more neutral environment of the duodenum. This unexpected sequence of physical state changes gives a mechanistic explanation for the enhanced in vivo performance of the solid dispersion formulation relative to the HSWG formulation. PMID:25723790

  4. Mechanism for enhanced absorption of a solid dispersion formulation of LY2300559 using the artificial stomach duodenum model.

    PubMed

    Polster, Christopher S; Wu, Sy-Juen; Gueorguieva, Ivelina; Sperry, David C

    2015-04-01

    An artificial stomach duodenum (ASD) model has been used to demonstrate the performance difference between two formulations of LY2300559, a low-solubility acidic developmental drug. The two formulations investigated were a conventional high-shear wet granulation (HSWG) formulation and a solid dispersion formulation. A pharmacokinetic study in humans demonstrated the enhanced performance of the solid dispersion formulation relative to the HSWG formulation. The Cmax and AUC of the solid dispersion was 2.6 and 1.9 times greater, respectively, compared to the HSWG formulation. In the ASD, the solid dispersion formulation performance was characterized by three main phases: (1) rapid release in the stomach, creating a supersaturated concentration of drug, (2) precipitation in the stomach, and (3) rapid redissolution of the precipitate in the duodenum to concentration levels that are supersaturated relative to crystalline drug. A series of complementary experiments were employed to describe this performance behavior mechanistically. Imaging experiments with a pH indicating dye showed that local pH gradients from meglumine in the solid dispersion formulation were responsible for creating a high initial supersaturation concentration in the stomach. Upon dissipation of meglumine, the drug precipitated in the stomach as an amorphous solid. Because the precipitated drug is in an amorphous form, it can then rapidly redissolve as it transits to the more neutral environment of the duodenum. This unexpected sequence of physical state changes gives a mechanistic explanation for the enhanced in vivo performance of the solid dispersion formulation relative to the HSWG formulation.

  5. Anisotropic mechanical properties of zircon and the effect of radiation damage

    DOE PAGESBeta

    Beirau, Tobias; Nix, William D.; Bismayer, Ulrich; Boatner, Lynn A.; Isaacson, Scott G.; Ewing, Rodney C.

    2016-06-02

    Our study provides new insights into the relationship between radiation-dose-dependent structural damage, due to natural U and Th impurities, and the anisotropic mechanical properties (Poisson s ratio, elastic modulus and hardness) of zircon. Natural zircon samples from Sri Lanka (see Muarakami et al. 1991) and synthetic samples, covering a dose range of zero up to 6.8 x 1018 -decays/g, have been studied by nanoindentation. Measurements along the [100] crystallographic direction and calculations, based on elastic stiffness constants determined by zkan (1976), revealed a general radiation-induced decrease in stiffness (~ 54 %) and hardness (~ 48 %) and an increase ofmore » the Poisson s ratio (~ 54 %) with increasing dose. Additional indentations on selected samples along the [001] allowed one to follow the amorphization process to the point that the mechanical properties are isotropic. This work shows that the radiation-dose-dependent changes of the mechanical properties of zircon can be directly correlated with the amorphous fraction as determined by previous investigations with local and global probes (Rios et al. 2000a; Farnan and Salje 2001; Zhang and Salje 2001). This agreement, revealed by the different methods, indicates a huge influence of structural and even local phenomena on the macroscopic mechanical properties.« less

  6. Relations between a micro-mechanical model and a damage model for ductile failure in shear

    NASA Astrophysics Data System (ADS)

    Tvergaard, Viggo; Nielsen, Kim Lau

    2010-09-01

    Gurson type constitutive models that account for void growth to coalescence are not able to describe ductile fracture in simple shear, where there is no hydrostatic tension in the material. But recent micro-mechanical studies have shown that in shear the voids are flattened out to micro-cracks, which rotate and elongate until interaction with neighbouring micro-cracks gives coalescence. Thus, the failure mechanism is very different from that under tensile loading. Also, the Gurson model has recently been extended to describe failure in shear, by adding a damage term to the expression for the growth of the void volume fraction, and it has been shown that this extended model can represent experimental observations. Here, numerical studies are carried out to compare predictions of the shear-extended Gurson model with the shear failures predicted by the micro-mechanical cell model. Both models show a strong dependence on the level of hydrostatic tension. Even though the reason for this pressure dependence is different in the two models, as the shear-extended Gurson model does not describe voids flattening out and the associated failure mechanism by micro-cracks interacting with neighbouring micro-cracks, it is shown that the trends of the predictions are in good agreement.

  7. Mechanism of plasma-induced damage to low-k SiOCH films during plasma ashing of organic resists

    NASA Astrophysics Data System (ADS)

    Takeda, Keigo; Miyawaki, Yudai; Takashima, Seigo; Fukasawa, Masanaga; Oshima, Keiji; Nagahata, Kazunori; Tatsumi, Tetsuya; Hori, Masaru

    2011-02-01

    Plasma-induced damage to porous SiOCH (p-SiOCH) films during organic resist film ashing using dual-frequency capacitively coupled O2 plasmas was investigated using the pallet for plasma evaluation method developed by our group. The damage was characterized by ellipsometry and Fourier-transform infrared spectroscopy. Individual and synergetic damage associated with vacuum ultraviolet (VUV) and UV radiation, radicals, and ions in the O2 plasma were clarified. It was found that the damage was caused not only by radicals but also by synergetic reactions of radicals with VUV and UV radiation emitted by the plasmas. It is noteworthy that the damage induced by plasma exposure without ion bombardment was larger than the damage with ion bombardment. These results differed from those obtained using an H2/N2 plasma for resist ashing. Finally, the mechanism of damage to p-SiOCH caused by O2 and H2/N2 plasma ashing of organic resist films is discussed. These results are very important in understanding the mechanism of plasma-induced damage to p-SiOCH films.

  8. Mechanism of plasma-induced damage to low-k SiOCH films during plasma ashing of organic resists

    SciTech Connect

    Takeda, Keigo; Miyawaki, Yudai; Takashima, Seigo; Fukasawa, Masanaga; Oshima, Keiji; Nagahata, Kazunori; Tatsumi, Tetsuya; Hori, Masaru

    2011-02-01

    Plasma-induced damage to porous SiOCH (p-SiOCH) films during organic resist film ashing using dual-frequency capacitively coupled O{sub 2} plasmas was investigated using the pallet for plasma evaluation method developed by our group. The damage was characterized by ellipsometry and Fourier-transform infrared spectroscopy. Individual and synergetic damage associated with vacuum ultraviolet (VUV) and UV radiation, radicals, and ions in the O{sub 2} plasma were clarified. It was found that the damage was caused not only by radicals but also by synergetic reactions of radicals with VUV and UV radiation emitted by the plasmas. It is noteworthy that the damage induced by plasma exposure without ion bombardment was larger than the damage with ion bombardment. These results differed from those obtained using an H{sub 2}/N{sub 2} plasma for resist ashing. Finally, the mechanism of damage to p-SiOCH caused by O{sub 2} and H{sub 2}/N{sub 2} plasma ashing of organic resist films is discussed. These results are very important in understanding the mechanism of plasma-induced damage to p-SiOCH films.

  9. Self-sealing of thermal fatigue and mechanical damage in fiber-reinforced composite materials

    NASA Astrophysics Data System (ADS)

    Moll, Jericho L.

    Fiber reinforced composite tanks provide a promising method of storage for liquid oxygen and hydrogen for aerospace applications. The inherent thermal fatigue of these vessels leads to the formation of microcracks, which allow gas phase leakage across the tank walls. In this dissertation, self-healing functionality is imparted to a structural composite to effectively seal microcracks induced by both mechanical and thermal loading cycles. Two different microencapsulated healing chemistries are investigated in woven glass fiber/epoxy and uni-weave carbon fiber/epoxy composites. Self-healing of mechanically induced damage was first studied in a room temperature cured plain weave E-glass/epoxy composite with encapsulated dicyclopentadiene (DCPD) monomer and wax protected Grubbs' catalyst healing components. A controlled amount of microcracking was introduced through cyclic indentation of opposing surfaces of the composite. The resulting damage zone was proportional to the indentation load. Healing was assessed through the use of a pressure cell apparatus to detect nitrogen flow through the thickness direction of the damaged composite. Successful healing resulted in a perfect seal, with no measurable gas flow. The effect of DCPD microcapsule size (51 microm and 18 microm) and concentration (0--12.2 wt%) on the self-sealing ability was investigated. Composite specimens with 6.5 wt% 51 microm capsules sealed 67% of the time, compared to 13% for the control panels without healing components. A thermally stable, dual microcapsule healing chemistry comprised of silanol terminated poly(dimethyl siloxane) plus a crosslinking agent and a tin catalyst was employed to allow higher composite processing temperatures. The microcapsules were incorporated into a satin weave E-glass fiber/epoxy composite processed at 120°C to yield a glass transition temperature of 127°C. Self-sealing ability after mechanical damage was assessed for different microcapsule sizees (25 microm and 42

  10. Microscopic mechanism of DNA damage searching by hOGG1.

    PubMed

    Rowland, Meng M; Schonhoft, Joseph D; McKibbin, Paige L; David, Sheila S; Stivers, James T

    2014-08-01

    The DNA backbone is often considered a track that allows long-range sliding of DNA repair enzymes in their search for rare damage sites in DNA. A proposed exemplar of DNA sliding is human 8-oxoguanine ((o)G) DNA glycosylase 1 (hOGG1), which repairs mutagenic (o)G lesions in DNA. Here we use our high-resolution molecular clock method to show that macroscopic 1D DNA sliding of hOGG1 occurs by microscopic 2D and 3D steps that masquerade as sliding in resolution-limited single-molecule images. Strand sliding was limited to distances shorter than seven phosphate linkages because attaching a covalent chemical road block to a single DNA phosphate located between two closely spaced damage sites had little effect on transfers. The microscopic parameters describing the DNA search of hOGG1 were derived from numerical simulations constrained by the experimental data. These findings support a general mechanism where DNA glycosylases use highly dynamic multidimensional diffusion paths to scan DNA.

  11. Representing Matrix Cracks Through Decomposition of the Deformation Gradient Tensor in Continuum Damage Mechanics Methods

    NASA Technical Reports Server (NTRS)

    Leone, Frank A., Jr.

    2015-01-01

    A method is presented to represent the large-deformation kinematics of intraply matrix cracks and delaminations in continuum damage mechanics (CDM) constitutive material models. The method involves the additive decomposition of the deformation gradient tensor into 'crack' and 'bulk material' components. The response of the intact bulk material is represented by a reduced deformation gradient tensor, and the opening of an embedded cohesive interface is represented by a normalized cohesive displacement-jump vector. The rotation of the embedded interface is tracked as the material deforms and as the crack opens. The distribution of the total local deformation between the bulk material and the cohesive interface components is determined by minimizing the difference between the cohesive stress and the bulk material stress projected onto the cohesive interface. The improvements to the accuracy of CDM models that incorporate the presented method over existing approaches are demonstrated for a single element subjected to simple shear deformation and for a finite element model of a unidirectional open-hole tension specimen. The material model is implemented as a VUMAT user subroutine for the Abaqus/Explicit finite element software. The presented deformation gradient decomposition method reduces the artificial load transfer across matrix cracks subjected to large shearing deformations, and avoids the spurious secondary failure modes that often occur in analyses based on conventional progressive damage models.

  12. A numerical investigation of blood damage in the hinge area of bileaflet mechanical heart valves

    NASA Astrophysics Data System (ADS)

    Yun, Min; Wu, Jingshu; Simon, Helene; Sotiropoulos, Fotis; Aidun, Cyrus; Yoganathan, Ajit

    2010-11-01

    Studies have shown that high shear stress and large recirculation regions have a strong impact on thromboembolic complications in Bileaflet mechanical heart valves (BMHV). This study quantitatively compares the hinge flow field and blood damage of the 23mm St. Jude Medical (SJM) regent with different hinge gap widths and the 23mm CarboMedics (CM) valves. The lattice-Boltzmann method with external boundary force (LBM-EBF) [Wu and Aidun, Int. J Num. Methods Fluids, 62, 7, 2009] was implemented to simulate the flow and capture the dynamics and the surface shear stress of the platelets with realistic geometry. The velocity boundary conditions for the small-scale hinge flow are obtained from previous 3D large-scale computational fluid dynamics (CFD) simulations [Simon et al, Annals of Biomedical Engineering, 38, 3, 2009]. The flow patterns of three hinges that were studied were similar during diastole. However, velocity magnitudes and shear stresses at the hinge gap were different, which may explain the higher blood damage index (BDI) value for the CM valve and lower BDI value for the SJM valve with a larger gap width. The multiscale computational method used to quantitatively measure the BDI during a full cardiac cycle will be discussed.

  13. Free radical-mediated oxidative DNA damage in the mechanism of thalidomide teratogenicity.

    PubMed

    Parman, T; Wiley, M J; Wells, P G

    1999-05-01

    The sedative drug thalidomide ([+]-alpha-phthalimidoglutarimide), once abandoned for causing birth defects in humans, has found new therapeutic license in leprosy and other diseases, with renewed teratological consequences. Although the mechanism of teratogenesis and determinants of risk remain unclear, related teratogenic xenobiotics are bioactivated by embryonic prostaglandin H synthase (PHS) to a free-radical intermediates that produce reactive oxygen species (ROS), which cause oxidative damage to DNA and other cellular macromolecules. Similarly, thalidomide is bioactivated by horseradish peroxidase, and oxidizes DNA and glutathione, indicating free radical-mediated oxidative stress. Furthermore, thalidomide teratogenicity in rabbits is reduced by the PHS inhibitor acetylsalicylic acid, indicating PHS-catalyzed bioactivation. Here, we show in rabbits that thalidomide initiates embryonic DNA oxidation and teratogenicity, both of which are abolished by pre-treatment with the free radical spin trapping agent alpha-phenyl-N-t-butylnitrone (PBN). In contrast, in mice, a species resistant to thalidomide teratogenicity, thalidomide does not enhance DNA oxidation, even at a dose 300% higher than that used in rabbits, providing insight into an embryonic determinant of species-dependent susceptibility. In addition to their therapeutic implications, these results constitute direct evidence that the teratogenicity of thalidomide may involve free radical-mediated oxidative damage to embryonic cellular macromolecules.

  14. Vibration damage mechanism analysis on rotor of diesel generating set with rigid coupling

    NASA Astrophysics Data System (ADS)

    Yan, Bing; Shi, Weizhen; Hua, Chunrong; Liu, Jingming; Dong, Dawei; Chen, Jun

    2015-07-01

    The crankshaft output end is generally connected with generator rotor through the coupling in diesel generating set. When using rigid coupling, the attachments and connecting parts of generator rotor (especially at larger gyration radius) are vulnerable to fatigue damage even if the vibration level of the generating set does not exceed the acceptable “usual value”. In order to investigate the reasons, the torsional vibration of the rotor in the diesel generating set was calculated and measured in this paper, which shows that using high rigidity coupling would result in large torsional vibration on the generator rotor, and that the linear vibration (the tangential vibration) value induced by torsional vibration at larger gyration radius of generator motor is almost the same as the vibration level of the generating set. Then, the vibration level of generating set was obtained, and the maximum vibration velocities of the generator are below the permissible value regulated by ISO 8528-9. But the velocities of synthetic vibration of the generating set vibration and the linear vibration induced by torsional vibration at larger gyration radius are much higher than permissible value 2(28mm/s) regulated by ISO 8528-9, which may be the reason of the mechanical damage of the attachments and connecting parts at larger gyration radius of generator motor caused by exceeded vibration.

  15. AFM investigation on surface damage caused by mechanical probing with small ruby spheres

    NASA Astrophysics Data System (ADS)

    Meli, Felix; Küng, Alain

    2007-02-01

    One challenge for today's coordinate metrology is fast and accurate 3D measurements on small objects. Mechanical probing is considered to be simple and accurate but limitations may arise from elastic and plastic deformations at the contact point. Understanding these limits quantitatively will help to avoid surface damage and measurement errors. Static and dynamic forces for single point probings and for scanning measurements were investigated in the present work using a metrology AFM and a micro-CMM. The obtained results were compared with theoretical predictions made by Hertz's theory. We found that the standard forces used by the METAS micro-CMM can be kept below the macroscopic damage threshold. On the other hand, plastic deformation of microscopic contact points which forms at the interface due to the surface roughness of the probe and sample is always present. Additionally, probe contamination by build-up of ductile metal on the probe surface was observed and probe wear on a hard sample was measured.

  16. S1P lyase regulates DNA damage responses through a novel sphingolipid feedback mechanism.

    PubMed

    Kumar, A; Oskouian, B; Fyrst, H; Zhang, M; Paris, F; Saba, J D

    2011-01-01

    The injurious consequences of ionizing radiation (IR) to normal human cells and the acquired radioresistance of cancer cells represent limitations to cancer radiotherapy. IR induces DNA damage response pathways that orchestrate cell cycle arrest, DNA repair or apoptosis such that irradiated cells are either repaired or eliminated. Concomitantly and independent of DNA damage, IR activates acid sphingomyelinase (ASMase), which generates ceramide, thereby promoting radiation-induced apoptosis. However, ceramide can also be metabolized to sphingosine-1-phosphate (S1P), which acts paradoxically as a radioprotectant. Thus, sphingolipid metabolism represents a radiosensitivity pivot point, a notion supported by genetic evidence in IR-resistant cancer cells. S1P lyase (SPL) catalyzes the irreversible degradation of S1P in the final step of sphingolipid metabolism. We show that SPL modulates the kinetics of DNA repair, speed of recovery from G2 cell cycle arrest and the extent of apoptosis after IR. SPL acts through a novel feedback mechanism that amplifies stress-induced ceramide accumulation, and downregulation/inhibition of either SPL or ASMase prevents premature cell cycle progression and mitotic death. Further, oral administration of an SPL inhibitor to mice prolonged their survival after exposure to a lethal dose of total body IR. Our findings reveal SPL to be a regulator of ASMase, the G2 checkpoint and DNA repair and a novel target for radioprotection.

  17. CHARACTERIZATION OF CONDITIONS OF NATURAL GAS STORAGE RESERVOIRS AND DESIGN AND DEMONSTRATION OF REMEDIAL TECHNIQUES FOR DAMAGE MECHANISMS FOUND THEREIN

    SciTech Connect

    J.H. Frantz Jr; K.G. Brown; W.K. Sawyer; P.A. Zyglowicz; P.M. Halleck; J.P. Spivey

    2004-12-01

    The underground gas storage (UGS) industry uses over 400 reservoirs and 17,000 wells to store and withdrawal gas. As such, it is a significant contributor to gas supply in the United States. It has been demonstrated that many UGS wells show a loss of deliverability each year due to numerous damage mechanisms. Previous studies estimate that up to one hundred million dollars are spent each year to recover or replace a deliverability loss of approximately 3.2 Bscf/D per year in the storage industry. Clearly, there is a great potential for developing technology to prevent, mitigate, or eliminate the damage causing deliverability losses in UGS wells. Prior studies have also identified the presence of several potential damage mechanisms in storage wells, developed damage diagnostic procedures, and discussed, in general terms, the possible reactions that need to occur to create the damage. However, few studies address how to prevent or mitigate specific damage types, and/or how to eliminate the damage from occurring in the future. This study seeks to increase our understanding of two specific damage mechanisms, inorganic precipitates (specifically siderite), and non-darcy damage, and thus serves to expand prior efforts as well as complement ongoing gas storage projects. Specifically, this study has resulted in: (1) An effective lab protocol designed to assess the extent of damage due to inorganic precipitates; (2) An increased understanding of how inorganic precipitates (specifically siderite) develop; (3) Identification of potential sources of chemical components necessary for siderite formation; (4) A remediation technique that has successfully restored deliverability to storage wells damaged by the inorganic precipitate siderite (one well had nearly a tenfold increase in deliverability); (5) Identification of the types of treatments that have historically been successful at reducing the amount of non-darcy pressure drop in a well, and (6) Development of a tool that can

  18. Laser-Induced Thermal-Mechanical Damage Characteristics of Cleartran Multispectral Zinc Sulfide with Temperature-Dependent Properties

    NASA Astrophysics Data System (ADS)

    Peng, Yajing; Jiang, Yanxue; Yang, Yanqiang

    2015-01-01

    Laser-induced thermal-mechanical damage characteristics of window materials are the focus problems in laser weapon and anti-radiation reinforcement technology. Thermal-mechanical effects and damage characteristics are investigated for cleartran multispectral zinc sulfide (ZnS) thin film window materials irradiated by continuous laser using three-dimensional (3D) thermal-mechanical model. Some temperature-dependent parameters are introduced into the model. The temporal-spatial distributions of temperature and thermal stress are exhibited. The damage mechanism is analyzed. The influences of temperature effect of material parameters and laser intensity on the development of thermal stress and the damage characteristics are examined. The results show, the von Mises equivalent stress along the thickness direction is fluctuant, which originates from the transformation of principal stresses from compressive stress to tensile stress with the increase of depth from irradiated surface. The damage originates from the thermal stress but not the melting. The thermal stress is increased and the damage is accelerated by introducing the temperature effect of parameters or the increasing laser intensity.

  19. The axon-glia unit in white matter stroke: mechanisms of damage and recovery

    PubMed Central

    Shira, Rosenzweig; Thomas, Carmichael S.

    2015-01-01

    Approximately one quarter of all strokes in humans occur in white matter, and the progressive nature of white matter lesions often results in severe physical and mental disability. Unlike cortical grey matter stroke, the pathology of white matter stroke revolves around disrupted connectivity and injured axons and glial cells, rather than neuronal cell bodies. Consequently, the mechanisms behind ischemic damage to white matter elements, the regenerative responses of glial cells and their signaling pathways, all differ significantly from those in grey matter. Development of effective therapies for white matter stroke would require an enhanced understanding of the complex cellular and molecular interactions within the white matter, leading to the identification of new therapeutic targets. This review will address the unique properties of the axon-glia unit during white matter stroke, describe the challenging process of promoting effective white matter repair, and discuss recently-identified signaling pathways which may hold potential targets for repair in this disease. PMID:25704204

  20. The Response to Oxidative DNA Damage in Neurons: Mechanisms and Disease

    PubMed Central

    Narciso, Laura; Parlanti, Eleonora; Racaniello, Mauro; Simonelli, Valeria; Cardinale, Alessio; Merlo, Daniela; Dogliotti, Eugenia

    2016-01-01

    There is a growing body of evidence indicating that the mechanisms that control genome stability are of key importance in the development and function of the nervous system. The major threat for neurons is oxidative DNA damage, which is repaired by the base excision repair (BER) pathway. Functional mutations of enzymes that are involved in the processing of single-strand breaks (SSB) that are generated during BER have been causally associated with syndromes that present important neurological alterations and cognitive decline. In this review, the plasticity of BER during neurogenesis and the importance of an efficient BER for correct brain function will be specifically addressed paying particular attention to the brain region and neuron-selectivity in SSB repair-associated neurological syndromes and age-related neurodegenerative diseases. PMID:26942017

  1. In situ damage monitoring in vibration mechanics: diagnostics and predictive maintenance

    NASA Astrophysics Data System (ADS)

    Basseville, M.; Benveniste, A.; Gach-Devauchelle, B.; Goursat, M.; Bonnecase, D.; Dorey, P.; Prevosto, M.; Olagnon, M.

    1993-09-01

    A system identification approach is presented for damage monitoring in vibration mechanics. Identification, detection, and diagnostics are performed using accelerometer measurements from the system at work so that the excitation is not controlled, usually not observed and may involve turbulent phenomena. Targeted applications include power engineering (rotating machines, core and pipes of nuclear power plants), civil engineering (large buildings subject to hurricanes or earthquakes, bridges, dams, offshore structures), aeronautics (wings and other structures subject to strength), automobile, rail transportation etc. The method is illustrated by a laboratory example, and the results of 3 years industrial usage. This paper is a progress report on a 10 year project involving three people almost permanently. We describe here the whole approach but omit the technical details which are available in previous papers.

  2. A Continuum Damage Mechanics Model to Predict Kink-Band Propagation Using Deformation Gradient Tensor Decomposition

    NASA Technical Reports Server (NTRS)

    Bergan, Andrew C.; Leone, Frank A., Jr.

    2016-01-01

    A new model is proposed that represents the kinematics of kink-band formation and propagation within the framework of a mesoscale continuum damage mechanics (CDM) model. The model uses the recently proposed deformation gradient decomposition approach to represent a kink band as a displacement jump via a cohesive interface that is embedded in an elastic bulk material. The model is capable of representing the combination of matrix failure in the frame of a misaligned fiber and instability due to shear nonlinearity. In contrast to conventional linear or bilinear strain softening laws used in most mesoscale CDM models for longitudinal compression, the constitutive response of the proposed model includes features predicted by detailed micromechanical models. These features include: 1) the rotational kinematics of the kink band, 2) an instability when the peak load is reached, and 3) a nonzero plateau stress under large strains.

  3. Mitigation of Shear-Induced Blood Damage by Mechanical Bileaflet Heart Valves

    NASA Astrophysics Data System (ADS)

    Zakharin, Boris; Arjunon, Sivakkumar; Saikrishnan, Neelakantan; Yoganathan, Ajit; Glezer, Ari

    2010-11-01

    The strong transitory shear stress generated during the time-periodic closing of bileaflet mechanical heart valves that is associated with the formation of counter-rotating vortices near the leaflet edges may be damaging to blood elements and may result in platelet activation and therefore thrombosis and thromboembolism complications. These flow transients are investigated using fluorescent PIV in a new, low-volume test setup that reproduces the pulsatile physiological conditions associated with a 25 mm St. Jude Medical valve. The flow transients are partially suppressed and the platelet activation is minimized using miniature vortex generator arrays that are embedded on the surface of the leaflets. Measurements of the ensuing flow taken phase-locked to the leaflet motion demonstrate substantial modification of the transient vertical structures and concomitant reduction of Reynolds shear stresses. Human blood experiments validated the effectiveness of miniature vortex generators in reducing thrombus formation by over 42 percent.

  4. Radiation Damage Mechanisms for Luminescence in Eu-doped GaN

    SciTech Connect

    Tringe, J W; Castelaz, J M; Felter, T E; Wetzel, C; Talley, C E; Morse, J D; Stevens, C G

    2005-11-01

    Thin films of Eu-doped GaN are irradiated with 500 keV He{sup +} ions to understand radiation damage mechanisms and to quantify luminescence efficiency. Ion beam induced luminescence was monitored spectroscopically as function of fluence. Behavior observed is consistent with simultaneous creation of non-radiative defects and destruction of luminescent centers associated with the 4f-4f core-level transition in Eu{sup 3+}. This model contrasts with a previous description which takes into account only non-radiative defect generation in GaN:Eu. Based on light from a BaF{sub 2} scintillator standard, the luminescent energy generation efficiency of GaN:Eu films doped to {approx}3 x 10{sup 18} cm{sup -3} Eu is estimated to be {approx}0.1%.

  5. Time dependent reliability model incorporating continuum damage mechanics for high-temperature ceramics

    NASA Technical Reports Server (NTRS)

    Duffy, Stephen F.; Gyekenyesi, John P.

    1989-01-01

    Presently there are many opportunities for the application of ceramic materials at elevated temperatures. In the near future ceramic materials are expected to supplant high temperature metal alloys in a number of applications. It thus becomes essential to develop a capability to predict the time-dependent response of these materials. The creep rupture phenomenon is discussed, and a time-dependent reliability model is outlined that integrates continuum damage mechanics principles and Weibull analysis. Several features of the model are presented in a qualitative fashion, including predictions of both reliability and hazard rate. In addition, a comparison of the continuum and the microstructural kinetic equations highlights a strong resemblance in the two approaches.

  6. Damage mechanism at different transpassive potentials of solution-annealed 316 and 316l stainless steels

    NASA Astrophysics Data System (ADS)

    Morshed Behbahani, K.; Pakshir, M.; Abbasi, Z.; Najafisayar, P.

    2015-01-01

    Electrochemical impedance spectroscopy (EIS), anodic polarization and scanning electron microscopy techniques were used to investigate the damage mechanism in the transpassive potential region of AISI 316 and AISI 316L solution-annealed stainless steels (SS) with different degrees of sensitization. Depending on the DC potential applied during EIS tests, the AC responses in the transpassive region included three different regions: the first one associated with anodic dissolution of the passive layer, the second one contributed to the dissolution at the area near grain boundaries, and the last one attributed to pitting corrosion. In addition, the fitting results to experimental data showed that as the DC bias during the EIS test increases the charge transfer resistance ( R ct) decreases. Moreover, the R ct values decreased as the sensitization temperature increases but the AISI 316L SS samples exhibited a higher resistance to intergranular corrosion than 316 SS samples.

  7. Pathological display of affect in patients with depression and right frontal brain damage. An alternative mechanism.

    PubMed

    Ross, E D; Stewart, R S

    1987-03-01

    Two patients are reported with the acute onset of pathological crying following right inferior frontal brain damage. Both had severe endogenous depression and neither had pseudobulbar palsy. These and other cases argue that two organic brain diseases--one structural and the other "physiopharmacological"--may interact to produce pathological display of affect that cannot be accounted for by traditional neurological explanations. A pharmacological mechanism for the rapid amelioration of pathological affect by tricyclic medications and its possible relationship to the newly discovered descending motor systems of the brain that use norepinephrine and serotonin as neurotransmitters is offered. These cases also suggest that pathological affect is a valuable clinical indicator of an underlying major depression in some brain-injured patients. PMID:3819712

  8. Optical detection of mechanically damaged areas on manufactured metal parts by spatial frequency filtering

    NASA Astrophysics Data System (ADS)

    Uno, Katsuhiro; Kihou, Takemune

    2014-05-01

    An inspection of mechanically damaged areas on manufactured metal parts is necessary to produce high-quality products. A scanning probe on a sample is necessary for a conventional surface inspection system, which is time-consuming. We propose a novel high-speed detection method for defects on metal surfaces with rolling indentations. To obtain a large field of view in a measurement, we used a laser sheet that was expanded with a laser line generator and also used an expanded collimated beam, rather than a small laser spot as used in conventional techniques. Furthermore, we used an obliquely incident laser beam to suppress the effect of the rolling indentations surrounding defects, and also applied spatial frequency filtering to extract only defects. The spatial frequency filtering under oblique incidence is theoretically explained and defect extraction was investigated in experiments.

  9. Towards mechanism-based simulation of impact damage using Exascale computing

    NASA Astrophysics Data System (ADS)

    Shterenlikht, Anton; Margetts, Lee; McDonald, Samuel; Bourne, Neil

    2015-06-01

    Over the past 60 years, the finite element method has been very successful in modelling deformation in engineering structures. However the method requires the definition of constitutive models that represent the response of the material to applied loads. There are two issues. Firstly, the models are often difficult to define. Secondly, there is often no physical connection between the models and the mechanisms that accommodate deformation. In this paper, we present a potentially disruptive two-level strategy which couples the finite element method in the macroscale with cellular automata in the mesoscale. The cellular automata are used to simulate mechanisms, such as crack propagation. The stress-strain relationship emerges as a continuum mechanics scale interpretation of changes at the micro- and meso-scales. Iterative two-way updating between the cellular automata and finite elements drives the simulation forward as the material undergoes progressive damage at high strain rates. The strategy is particularly attractive on large-scale computing platforms as both methods scale well on tens of thousands of CPUs. Supported by the ARCHER Service (e347) and the Hartree Centre (HCP010).

  10. Kinetic gating mechanism of DNA damage recognition by Rad4/XPC

    DOE PAGESBeta

    Chen, Xuejing; Velmurugu, Yogambigai; Zheng, Guanqun; Park, Beomseok; Shim, Yoonjung; Kim, Youngchang; Liu, Lili; Van Houten, Bennett; He, Chuan; Ansari, Anjum; et al

    2015-01-06

    The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformations similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivitymore » arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump pertubation spectroscopy. Kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.« less

  11. Kinetic gating mechanism of DNA damage recognition by Rad4/XPC

    SciTech Connect

    Chen, Xuejing; Velmurugu, Yogambigai; Zheng, Guanqun; Park, Beomseok; Shim, Yoonjung; Kim, Youngchang; Liu, Lili; Van Houten, Bennett; He, Chuan; Ansari, Anjum; Min, Jung -Hyun

    2015-01-06

    The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformations similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivity arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump pertubation spectroscopy. Kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.

  12. Kinetic gating mechanism of DNA damage recognition by Rad4/XPC

    NASA Astrophysics Data System (ADS)

    Chen, Xuejing; Velmurugu, Yogambigai; Zheng, Guanqun; Park, Beomseok; Shim, Yoonjung; Kim, Youngchang; Liu, Lili; van Houten, Bennett; He, Chuan; Ansari, Anjum; Min, Jung-Hyun

    2015-01-01

    The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformation similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivity arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump perturbation spectroscopy. Kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.

  13. Effects of edge grinding and sealing on mechanical properties of machine damaged laminate composites

    NASA Astrophysics Data System (ADS)

    Asmatulu, Ramazan; Yeoh, Jason; Alarifi, Ibrahim M.; Alharbi, Abdulaziz

    2016-04-01

    Fiber reinforced composites have been utilized for a number of different applications, including aircraft, wind turbine, automobile, construction, manufacturing, and many other industries. During the fabrication, machining (waterjet, diamond and band saws) and assembly of these laminate composites, various edge and hole delamination, fiber pullout and other micro and nanocracks can be formed on the composite panels. The present study mainly focuses on the edge grinding and sealing of the machine damaged fiber reinforced composites, such as fiberglass, plain weave carbon fiber and unidirectional carbon fiber. The MTS tensile test results confirmed that the composite coupons from the grinding process usually produced better and consistent mechanical properties compared to the waterjet cut samples only. In addition to these studies, different types of high strength adhesives, such as EPON 828 and Loctite were applied on the edges of the prepared composite coupons and cured under vacuum. The mechanical tests conducted on these coupons indicated that the overall mechanical properties of the composite coupons were further improved. These processes can lower the labor costs on the edge treatment of the composites and useful for different industrial applications of fiber reinforced composites.

  14. Kinetic gating mechanism of DNA damage recognition by Rad4/XPC

    PubMed Central

    Chen, Xuejing; Velmurugu, Yogambigai; Zheng, Guanqun; Park, Beomseok; Shim, Yoonjung; Kim, Youngchang; Liu, Lili; Van Houten, Bennett; He, Chuan; Ansari, Anjum; Min, Jung-Hyun

    2015-01-01

    The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformation similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivity arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump perturbation spectroscopy. Kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites. PMID:25562780

  15. Investigations of the damage mechanisms during ultrashort pulse laser ablation of dental tissue

    NASA Astrophysics Data System (ADS)

    Domke, Matthias; Wick, Sebastian; Laible, Maike; Rapp, Stephan; Kuznetsova, Julia; Homann, Christian; Huber, Heinz P.; Sroka, Ronald

    2015-07-01

    Several investigations of dental tissue ablation with ultrashort pulsed lasers suggest that these lasers enable precise and selective material removal and reduce the formation of micro cracks and thermal effects, when compared to ns-pulses. In this study, two damage mechanisms are presented occurring during ablation of dentin using a laser emitting pulses of a duration of 380 fs at a wavelength of 1040 nm. First, it was found that nano cracks appear around the craters after single fs-pulse ablation. These cracks are directed to the crater and cross the dentinal tubules. Transient investigation of the single fs-pulse ablation process by pump-probe microscopy suggest that the driving mechanism could be a pressure wave that is released after stress confinement. Second, squared ablation holes were created by moving the laser focus at scan speeds between 0.5 mm/s and 2.0 m/s and fluences up to 14 J/cm2. It was found that deep cracks appear at the edges of the squared holes, if the scan speed is about 0.5 m/s. The fluence has only a minor impact on the crack formation. The crack propagation was investigated in the depth using x-ray micro tomography and optical coherence tomography. It was found that these cracks appear in the depth down to the dental pulp. These findings suggest that fast scanning of the laser beam is the key for damage free processing using ultrashort pulse lasers. Then, ablation rates of about 2.5 - 3.5 mm3/min/W can be achieved in dentine with pulse durations of 380 fs.

  16. Investigation of cavitation as a possible damage mechanism in blast-induced traumatic brain injury.

    PubMed

    Goeller, Jacques; Wardlaw, Andrew; Treichler, Derrick; O'Bruba, Joseph; Weiss, Greg

    2012-07-01

    Cavitation was investigated as a possible damage mechanism for war-related traumatic brain injury (TBI) due to an improvised explosive device (IED) blast. When a frontal blast wave encounters the head, a shock wave is transmitted through the skull, cerebrospinal fluid (CSF), and tissue, causing negative pressure at the contrecoup that may result in cavitation. Numerical simulations and shock tube experiments were conducted to determine the possibility of cranial cavitation from realistic IED non-impact blast loading. Simplified surrogate models of the head consisted of a transparent polycarbonate ellipsoid. The first series of tests in the 18-inch-diameter shock tube were conducted on an ellipsoid filled with degassed water to simulate CSF and tissue. In the second series, Sylgard gel, surrounded by a layer of degassed water, was used to represent the tissue and CSF, respectively. Simulated blast overpressure in the shock tube tests ranged from a nominal 10-25 pounds per square inch gauge (psig; 69-170 kPa). Pressure in the simulated CSF was determined by Kulite thin line pressure sensors at the coup, center, and contrecoup positions. Using video taken at 10,000 frames/sec, we verified the presence of cavitation bubbles at the contrecoup in both ellipsoid models. In all tests, cavitation at the contrecoup was observed to coincide temporally with periods of negative pressure. Collapse of the cavitation bubbles caused by the surrounding pressure and elastic rebound of the skull resulted in significant pressure spikes in the simulated CSF. Numerical simulations using the DYSMAS hydrocode to predict onset of cavitation and pressure spikes during cavity collapse were in good agreement with the tests. The numerical simulations and experiments indicate that skull deformation is a significant factor causing cavitation. These results suggest that cavitation may be a damage mechanism contributing to TBI that requires future study.

  17. Fundamental Processes of Coupled Radiation Damage and Mechanical Behavior in Nuclear Fuel Materials for High Temperature Reactors

    SciTech Connect

    Phillpot, Simon; Tulenko, James

    2011-09-08

    The objective of this work has been to elucidate the relationship among microstructure, radiation damage and mechanical properties for nuclear fuel materials. As representative nuclear materials, we have taken an hcp metal (Mg as a generic metal, and Ti alloys for fast reactors) and UO2 (representing fuel). The degradation of the thermo-mechanical behavior of nuclear fuels under irradiation, both the fissionable material itself and its cladding, is a longstanding issue of critical importance to the nuclear industry. There are experimental indications that nanocrystalline metals and ceramics may be more resistant to radiation damage than their coarse-grained counterparts. The objective of this project look at the effect of microstructure on radiation damage and mechanical behavior in these materials. The approach to be taken was state-of-the-art, large-scale atomic-level simulation. This systematic simulation program of the effects of irradiation on the structure and mechanical properties of polycrystalline Ti and UO2 identified radiation damage mechanisms. Moreover, it will provided important insights into behavior that can be expected in nanocrystalline microstructures and, by extension, nanocomposites. The fundamental insights from this work can be expected to help in the design microstructures that are less susceptible to radiation damage and thermomechanical degradation.

  18. Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans

    PubMed Central

    Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley; Lee, Kristy; Robinson, Rosann; Campbell, Michael S.; Kiso, Wendy K.; Schmitt, Dennis L.; Waddell, Peter J; Bhaskara, Srividya; Jensen, Shane T.; Maley, Carlo C.; Schiffman, Joshua D.

    2016-01-01

    IMPORTANCE Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. OBJECTIVE To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). DESIGN, SETTING, AND PARTICIPANTS A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015. EXPOSURES Ionizing radiation and doxorubicin. MAIN OUTCOMES AND MEASURES Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. RESULTS Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95%CI, 0%–5%]; African wild dog, 8%[95%CI, 0%–16%]; lion, 2%[95%CI, 0% –7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95%CI, 3.14%–6.49%), compared with humans, who have 11% to 25%cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain

  19. Molecular mechanisms of silk gland damage caused by phoxim exposure and protection of phoxim-induced damage by cerium chloride in Bombyx mori.

    PubMed

    Li, Bing; Sun, Qingqing; Yu, Xiaohong; Xie, Yi; Hong, Jie; Zhao, Xiaoyang; Sang, Xuezi; Shen, Weide; Hong, Fashui

    2015-09-01

    It is known that exposure to organophosphorus pesticides (OP) including phoxim can produce oxidative stress, neurotoxicity, and greatly attenuate cocooning rate in the silkworm, Bombyx mori. Cerium treatment has been demonstrated to relieve phoxim-induced toxicity in B. mori; however, very little is known about the molecular mechanisms of silk gland injury due to OP exposure and protection of gland damage due to cerium pretreatment. The aim of this study was to evaluate silk gland damage and its molecular mechanisms in phoxim-induced silkworm toxicity and the protective mechanisms of cerium following exposure to phoxim. The results showed that phoxim exposure resulted in severe gland damage, reductions in protein synthesis and the cocooning rate of silkworms. Cerium (Ce) attenuated gland damage caused by phoxim, promoted protein synthesis, increased the antioxidant capacity of the gland and increased the cocooning rate of B. mori. Furthermore, digital gene expression data suggested that phoxim exposure led to significant up-regulation of 714 genes and down-regulation of 120 genes. Of these genes, 122 were related to protein metabolism, specifically, the down-regulated Ser2, Ser3, Fib-L, P25, and CYP450. Ce pretreatment resulted in up-regulation of 162 genes, and down-regulation of 141 genes, importantly, Ser2, Ser3, Fib-L, P25, and CYP333B8 were up-regulated. Treatment with CeCl3 + phoxim resulted in higher levels of Fib-L, P25, Ser2, Ser3, CAT, TPx, and CYP333B8 expression in the silk gland of silkworms. These findings indicated that Ce increased cocooning rate via the promotion of silk protein synthesis-related gene expression in the gland under phoxim-induced toxicity. These findings may expand the application of rare earths in sericulture.

  20. Epicutaneous Allergic Sensitization by Cooperation between Allergen Protease Activity and Mechanical Skin Barrier Damage in Mice.

    PubMed

    Shimura, Sakiko; Takai, Toshiro; Iida, Hideo; Maruyama, Natsuko; Ochi, Hirono; Kamijo, Seiji; Nishioka, Izumi; Hara, Mutsuko; Matsuda, Akira; Saito, Hirohisa; Nakae, Susumu; Ogawa, Hideoki; Okumura, Ko; Ikeda, Shigaku

    2016-07-01

    Allergen sources such as mites, insects, fungi, and pollen contain proteases. Airway exposure to proteases induces allergic airway inflammation and IgE/IgG1 responses via IL-33-dependent mechanisms in mice. We examined the epicutaneous sensitization of mice to a model protease allergen, papain; the effects of tape stripping, which induces epidermal barrier dysfunction; and the atopic march upon a subsequent airway challenge. Papain painting on ear skin and tape stripping cooperatively promoted dermatitis, the skin gene expression of proinflammatory cytokines and growth factors, up-regulation of serum total IgE, and papain-specific IgE/IgG1 induction. Epicutaneous sensitization induced T helper (Th) 2 cells and Th17 differentiation in draining lymph nodes. Ovalbumin and protease inhibitor-treated papain induced no or weak responses, whereas the co-administration of ovalbumin and papain promoted ovalbumin-specific IgE/IgG1 induction. Wild-type and IL-33-deficient mice showed similar responses in the epicutaneous sensitization phase. The subsequent airway papain challenge induced airway eosinophilia and maintained high papain-specific IgE levels in an IL-33-dependent manner. These results suggest that allergen source-derived protease activity and mechanical barrier damage such as that caused by scratching cooperatively promote epicutaneous sensitization and skin inflammation and that IL-33 is dispensable for epicutaneous sensitization but is crucial in the atopic march upon a subsequent airway low-dose encounter with protease allergens. PMID:26987428

  1. Characterization of mechanical damage mechanisms in ceramic composite materials. Technical report, 23 May 1987-24 May 1988

    SciTech Connect

    Lankford, J.

    1988-09-01

    High-strain-rate compressive failure mechanisms in fiber-reinforced ceramic-matrix composite materials were characterized. These are contrasted with composite damage development at low-strain rates, and with the dynamic failure of monolithic ceramics. It is shown that it is possible to derive major strain-rate strengthening benefits if a major fraction of the fiber reinforcement is aligned with the load axis. This effect considerably exceeds the inertial microfracture strengthening observed in monolithic ceramics, and non-aligned composites. Its basis is shown to be the trans-specimen propagation time period for heterogeneously-nucleated, high-strain kink bands. A brief study on zirconia focused on the remarkable inverse strength-strain rate result previously observed for both fully and partially-stabilized zirconia single crystals, whereby the strength decreased with increasing strain rate. Based on the hypothesis that the suppression of microplastic flow, hence, local stress relaxation, might be responsible for this behavior, fully stabilized (i.e., non-transformable) specimens were strain-gaged and subjected to compressive microstrain. The rather stunning observation was that the crystals are highly microplastic, exhibiting plastic yield on loading and anelasticity and reverse plasticity upon unloading. These results clearly support the hypothesis that with increasing strain rate, microcracking is favored at the expense of microplasticity.

  2. Sub-surface mechanical damage distributions during grinding of fused silica

    SciTech Connect

    Suratwala, T I; Wong, L L; Miller, P E; Feit, M D; Menapace, J A; Steele, R A; Davis, P A; Walmer, D

    2005-11-28

    The distribution and characteristics of surface cracking (i.e. sub-surface damage or SSD) formed during standard grinding processes has been investigated on fused silica glass. The SSD distributions of the ground surfaces were determined by: (1) creating a shallow (18-108 {micro}m) wedge/taper on the surface by magneto-rheological finishing; (2) exposing the SSD by HF acid etching; and (3) performing image analysis of the observed cracks from optical micrographs taken along the surface taper. The observed surface cracks are characterized as near-surface lateral and deeper trailing indent type fractures (i.e., chatter marks). The SSD depth distributions are typically described by a single exponential distribution followed by an asymptotic cutoff in depth (c{sub max}). The length of the trailing indent is strongly correlated with a given process. Using established fracture indentation relationships, it is shown that only a small fraction of the abrasive particles are being mechanically loaded and causing fracture, and it is likely the larger particles in the abrasive particle size distribution that bear the higher loads. The SSD depth was observed to increase with load and with a small amount of larger contaminant particles. Using a simple brittle fracture model for grinding, the SSD depth distribution has been related to the SSD length distribution to gain insight into ''effective'' size distribution of particles participating in the fracture. Both the average crack length and the surface roughness were found to scale linearly with the maximum SSD depth (c{sub max}). These relationships can serve as useful rules-of-thumb for nondestructively estimating SSD depth and to identify the process that caused the SSD. In certain applications such as high intensity lasers, SSD on the glass optics can serve as a reservoir for minute amounts of impurities that absorb the high intensity laser light and lead to subsequent laser-induced surface damage. Hence a more scientific

  3. Influence of dioctyl phthalate (DOP) on the mechanical, optical and thermal properties of formulations for the industrial manufacture of radiation sterilizable medical disposables

    NASA Astrophysics Data System (ADS)

    Ahmed, Shamshad; Mehmood, Mazhar; Iqbal, Rashid

    2010-03-01

    Shelf life of the formulations designed for the industrial manufacture of radiation sterilizable syringes and other medical disposables is a very important issue world over. Radiation compatible formulations were developed earlier in the laboratory by the incorporation of primary and secondary antioxidants along with processing stabilizers in a random polypropylene copolymer. It has been reported in literature that the mobilizing agents namely hydrocarbons, greases, wax and the plasticizer, dioctyl phthalate (DOP) impart radiation resistance to the polypropylene by providing free volume. It was envisaged that the addition of DOP to the afore-mentioned formulation might favorably influence the mechanical, optical and thermal properties of our formulation. To study the influence of addition of DOP on the afore-mentioned properties, the addition of 1%, 2% and 3% of the mobilizer was made, followed by the irradiation of resulting heat pressed sheets to the industrial standard dose of 25 kGy. Two important characteristic mechanical properties to determine the suitability of the radiation sterilized materials comprise angle of breakage and the haze percent. After irradiation and even on accelerated ageing of the irradiated material, the angle of breakage of heat press sheets of formulations containing 1%, 2% and 3% of DOP was found to be 180°, demonstrating the role of DOP, in imparting additional radiation stability. In case of the irradiated control sample, the angle of breakage was much lower. In the heat pressed sheets containing the DOP, a remarkable retention in the tensile strength, percentage elongation at break, along with improved thermal stability was observed. The formulation devoid of DOP demonstrated poor retention of the afore-mentioned characteristic properties .The observed improvement in thermal stability of the formulations containing DOP hints at the likely possibility of reuse of these materials by autoclaving which is considered an additional

  4. Mechanism of Action of Lung Damage Caused by a Nanofilm Spray Product

    PubMed Central

    Larsen, Søren T.; Dallot, Constantin; Larsen, Susan W.; Rose, Fabrice; Poulsen, Steen S.; Nørgaard, Asger W.; Hansen, Jitka S.; Sørli, Jorid B.; Nielsen, Gunnar D.; Foged, Camilla

    2014-01-01

    Inhalation of waterproofing spray products has on several occasions caused lung damage, which in some cases was fatal. The present study aims to elucidate the mechanism of action of a nanofilm spray product, which has been shown to possess unusual toxic effects, including an extremely steep concentration-effect curve. The nanofilm product is intended for application on non-absorbing flooring materials and contains perfluorosiloxane as the active film-forming component. The toxicological effects and their underlying mechanisms of this product were studied using a mouse inhalation model, by in vitro techniques and by identification of the binding interaction. Inhalation of the aerosolized product gave rise to increased airway resistance in the mice, as evident from the decreased expiratory flow rate. The toxic effect of the waterproofing spray product included interaction with the pulmonary surfactants. More specifically, the active film-forming components in the spray product, perfluorinated siloxanes, inhibited the function of the lung surfactant due to non-covalent interaction with surfactant protein B, a component which is crucial for the stability and persistence of the lung surfactant film during respiration. The active film-forming component used in the present spray product is also found in several other products on the market. Hence, it may be expected that these products may have a toxicity similar to the waterproofing product studied here. Elucidation of the toxicological mechanism and identification of toxicological targets are important to perform rational and cost-effective toxicological studies. Thus, because the pulmonary surfactant system appears to be an important toxicological target for waterproofing spray products, study of surfactant inhibition could be included in toxicological assessment of this group of consumer products. PMID:24863969

  5. Mechanisms of islet damage mediated by pancreas cold ischemia/rewarming.

    PubMed

    Omori, Keiko; Kobayashi, Eiji; Rawson, Jeffrey; Takahashi, Masafumi; Mullen, Yoko

    2016-10-01

    Prolonged pancreas cold ischemia is known to negatively correlate with islet isolation outcomes, hindering successful islet transplantation to treat Type-1 Diabetes. Due to poor islet isolation outcome, pancreata with over 16 h cold ischemia are currently not considered for islet transplantation. Mechanisms involved in pancreas cold ischemia/rewarming mediated islet damage during islet isolation and culture are not well understood. Using an en bloc cold preserved rat pancreas preparation, we attempted to clarify possible mechanisms of islet death associated with prolonged pancreas cold ischemia and subsequent rewarming. Cold ischemia lasting 16 h decreased post-isolation islet yield and increased islet death during the initial 6 h of culture. Electron micrographs revealed swelling and severe disruption of cellular and mitochondrial membranes, as well as an enlarged endoplasmic reticulum (ER) in β-cells isolated from cold preserved pancreata. Prolonged cold ischemia of the pancreas transiently activated mitogen-activated protein kinases (MAPKs) in isolated islets and increased lipid peroxidation products 4-hydroxynonenal (HNE) and heat shock protein (Hsp) 70 after culture, indicating the activation of oxidative stress signaling pathways. The islet isolation process, irrespective of pancreas cold ischemia, activated unfolded protein response (UPR), while the ER protective chaperon BiP was further upregulated by pancreas cold ischemia/rewarming. During the first 6 h of culture following islet isolation, p53 upregulated modulator of apoptosis (Puma) and caspase-3 activation were also upregulated. Our study indicates the involvement of both apoptosis and necrosis in islet death, and suggests oxidative stress and disruption of membranes are critical mechanisms mediated by pancreas cold ischemia/rewarming. PMID:27587006

  6. Mechanism of Radiation Damage Reduction in Equiatomic Multicomponent Single Phase Alloys.

    PubMed

    Granberg, F; Nordlund, K; Ullah, Mohammad W; Jin, K; Lu, C; Bei, H; Wang, L M; Djurabekova, F; Weber, W J; Zhang, Y

    2016-04-01

    Recently a new class of metal alloys, of single-phase multicomponent composition at roughly equal atomic concentrations ("equiatomic"), have been shown to exhibit promising mechanical, magnetic, and corrosion resistance properties, in particular, at high temperatures. These features make them potential candidates for components of next-generation nuclear reactors and other high-radiation environments that will involve high temperatures combined with corrosive environments and extreme radiation exposure. In spite of a wide range of recent studies of many important properties of these alloys, their radiation tolerance at high doses remains unexplored. In this work, a combination of experimental and modeling efforts reveals a substantial reduction of damage accumulation under prolonged irradiation in single-phase NiFe and NiCoCr alloys compared to elemental Ni. This effect is explained by reduced dislocation mobility, which leads to slower growth of large dislocation structures. Moreover, there is no observable phase separation, ordering, or amorphization, pointing to a high phase stability of this class of alloys. PMID:27081990

  7. Susceptibility to DNA Damage as a Molecular Mechanism for Non-Syndromic Cleft Lip and Palate

    PubMed Central

    Sunaga, Daniele Yumi; Francis-West, Philippa; Kuta, Anna; Almada, Bruno Vinícius Pimenta; Ferreira, Simone Gomes; de Andrade-Lima, Leonardo Carmo; Bueno, Daniela Franco; Raposo-Amaral, Cássio Eduardo; Menck, Carlos Frederico; Passos-Bueno, Maria Rita

    2013-01-01

    Non-syndromic cleft lip/palate (NSCL/P) is a complex, frequent congenital malformation, determined by the interplay between genetic and environmental factors during embryonic development. Previous findings have appointed an aetiological overlap between NSCL/P and cancer, and alterations in similar biological pathways may underpin both conditions. Here, using a combination of transcriptomic profiling and functional approaches, we report that NSCL/P dental pulp stem cells exhibit dysregulation of a co-expressed gene network mainly associated with DNA double-strand break repair and cell cycle control (p = 2.88×10−2–5.02×10−9). This network included important genes for these cellular processes, such as BRCA1, RAD51, and MSH2, which are predicted to be regulated by transcription factor E2F1. Functional assays support these findings, revealing that NSCL/P cells accumulate DNA double-strand breaks upon exposure to H2O2. Furthermore, we show that E2f1, Brca1 and Rad51 are co-expressed in the developing embryonic orofacial primordia, and may act as a molecular hub playing a role in lip and palate morphogenesis. In conclusion, we show for the first time that cellular defences against DNA damage may take part in determining the susceptibility to NSCL/P. These results are in accordance with the hypothesis of aetiological overlap between this malformation and cancer, and suggest a new pathogenic mechanism for the disease. PMID:23776525

  8. The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes.

    PubMed

    Markovic, Zoran; Todorovic-Markovic, Biljana; Kleut, Duska; Nikolic, Nadezda; Vranjes-Djuric, Sanja; Misirkic, Maja; Vucicevic, Ljubica; Janjetovic, Kristina; Isakovic, Aleksandra; Harhaji, Ljubica; Babic-Stojic, Branka; Dramicanin, Miroslav; Trajkovic, Vladimir

    2007-12-01

    Because of the ability to induce cell death in certain conditions, the fullerenes (C(60)) are potential anticancer and toxic agents. The colloidal suspension of crystalline C(60) (nano-C(60), nC(60)) is extremely toxic, but the mechanisms of its cytotoxicity are not completely understood. By combining experimental analysis and mathematical modelling, we investigate the requirements for the reactive oxygen species (ROS)-mediated cytotoxicity of different nC(60) suspensions, prepared by solvent exchange method in tetrahydrofuran (THF/nC(60)) and ethanol (EtOH/nC(60)), or by extended mixing in water (aqu/nC(60)). With regard to their capacity to generate ROS and cause mitochondrial depolarization followed by necrotic cell death, the nC(60) suspensions are ranked in the following order: THF/nC(60)>EtOH/nC(60)>aqu/nC(60). Mathematical modelling of singlet oxygen ((1)O(2)) generation indicates that the (1)O(2)-quenching power (THF/nC(60)damage. These data could have important implications for toxicology and biomedical application of colloidal fullerenes.

  9. A study of the mechanism of hydralazine enhancement of thermal damage in the KHT tumour.

    PubMed

    Honess, D J; Hu, D E; Bleehen, N M

    1991-01-01

    The mechanism of the potentiation of thermal damage by hydralazine (HDZ) has been investigated. Using the KHT sarcoma in the leg of C3H mice, it was shown that 5 mg/kg of HDZ given i.v. 15-20 min before irradiation or heat exposure: (i) increased the radiobiological hypoxic fraction from 1 to 32%; (ii) produced a greater than additive growth delay when combined with heating for 30 min at either 43 or 43.5 degrees C, or 60 min at 43 degrees C; (iii) produced only additive cell killing when combined with 30 min heating at 43, 43.5, or 44 degrees C, assayed by clonogenic cell survival immediately or 24 h after treatment; and (iv) produced a prolonged (greater than 72 h) reduction in relative tissue perfusion (RTP) in the tumour when combined with heating for 30 min at 43.5 degrees C. The effects of HDZ or heat alone lasted for less than 24 and 48 h, respectively. The RTP in skin was unaffected by either agent or combination of agents at the times assayed. The results show that this 30-fold increase in hypoxia does not increase the intrinsic thermosensitivity of KHT tumour cells, and that the prolonged reduction in RTP caused by the combined treatment is probably responsible, at least in part, for the greater than additive component of the measured growth delay in this system. The data suggest that non-perfused tumour vessels are more heat sensitive than perfused vessels.

  10. The axon-glia unit in white matter stroke: mechanisms of damage and recovery.

    PubMed

    Rosenzweig, Shira; Carmichael, S Thomas

    2015-10-14

    Approximately one quarter of all strokes in humans occur in white matter, and the progressive nature of white matter lesions often results in severe physical and mental disability. Unlike cortical grey matter stroke, the pathology of white matter stroke revolves around disrupted connectivity and injured axons and glial cells, rather than neuronal cell bodies. Consequently, the mechanisms behind ischemic damage to white matter elements, the regenerative responses of glial cells and their signaling pathways, all differ significantly from those in grey matter. Development of effective therapies for white matter stroke would require an enhanced understanding of the complex cellular and molecular interactions within the white matter, leading to the identification of new therapeutic targets. This review will address the unique properties of the axon-glia unit during white matter stroke, describe the challenging process of promoting effective white matter repair, and discuss recently-identified signaling pathways which may hold potential targets for repair in this disease. This article is part of a Special Issue entitled SI: Cell Interactions In Stroke.

  11. Mechanism of Radiation Damage Reduction in Equiatomic Multicomponent Single Phase Alloys.

    PubMed

    Granberg, F; Nordlund, K; Ullah, Mohammad W; Jin, K; Lu, C; Bei, H; Wang, L M; Djurabekova, F; Weber, W J; Zhang, Y

    2016-04-01

    Recently a new class of metal alloys, of single-phase multicomponent composition at roughly equal atomic concentrations ("equiatomic"), have been shown to exhibit promising mechanical, magnetic, and corrosion resistance properties, in particular, at high temperatures. These features make them potential candidates for components of next-generation nuclear reactors and other high-radiation environments that will involve high temperatures combined with corrosive environments and extreme radiation exposure. In spite of a wide range of recent studies of many important properties of these alloys, their radiation tolerance at high doses remains unexplored. In this work, a combination of experimental and modeling efforts reveals a substantial reduction of damage accumulation under prolonged irradiation in single-phase NiFe and NiCoCr alloys compared to elemental Ni. This effect is explained by reduced dislocation mobility, which leads to slower growth of large dislocation structures. Moreover, there is no observable phase separation, ordering, or amorphization, pointing to a high phase stability of this class of alloys.

  12. Mechanism of Radiation Damage Reduction in Equiatomic Multicomponent Single Phase Alloys

    NASA Astrophysics Data System (ADS)

    Granberg, F.; Nordlund, K.; Ullah, Mohammad W.; Jin, K.; Lu, C.; Bei, H.; Wang, L. M.; Djurabekova, F.; Weber, W. J.; Zhang, Y.

    2016-04-01

    Recently a new class of metal alloys, of single-phase multicomponent composition at roughly equal atomic concentrations ("equiatomic"), have been shown to exhibit promising mechanical, magnetic, and corrosion resistance properties, in particular, at high temperatures. These features make them potential candidates for components of next-generation nuclear reactors and other high-radiation environments that will involve high temperatures combined with corrosive environments and extreme radiation exposure. In spite of a wide range of recent studies of many important properties of these alloys, their radiation tolerance at high doses remains unexplored. In this work, a combination of experimental and modeling efforts reveals a substantial reduction of damage accumulation under prolonged irradiation in single-phase NiFe and NiCoCr alloys compared to elemental Ni. This effect is explained by reduced dislocation mobility, which leads to slower growth of large dislocation structures. Moreover, there is no observable phase separation, ordering, or amorphization, pointing to a high phase stability of this class of alloys.

  13. Having a direct look: Analysis of DNA damage and repair mechanisms by next generation sequencing

    PubMed Central

    Meier, Bettina; Gartner, Anton

    2014-01-01

    Genetic information is under constant attack from endogenous and exogenous sources, and the use of model organisms has provided important frameworks to understand how genome stability is maintained and how various DNA lesions are repaired. The advance of high throughput next generation sequencing (NGS) provides new inroads for investigating mechanisms needed for genome maintenance. These emerging studies, which aim to link genetic toxicology and mechanistic analyses of DNA repair processes in vivo, rely on defining mutational signatures caused by faulty replication, endogenous DNA damaging metabolites, or exogenously applied genotoxins; the analysis of their nature, their frequency and distribution. In contrast to classical studies, where DNA repair deficiency is assessed by reduced cellular survival, the localization of DNA repair factors and their interdependence as well as limited analysis of single locus reporter assays, NGS based approaches reveal the direct, quantal imprint of mutagenesis genome-wide, at the DNA sequence level. As we will show, such investigations require the analysis of DNA derived from single genotoxin treated cells, or DNA from cell populations regularly passaged through single cell bottlenecks when naturally occurring mutation accumulation is investigated. We will argue that the life cycle of the nematode Caenorhabditis elegans, its genetic malleability combined with whole genome sequencing provides an exciting model system to conduct such analysis. PMID:25131498

  14. A new characterization approach for studying relationships between microstructure and creep damage mechanisms of uranium dioxide

    NASA Astrophysics Data System (ADS)

    Iltis, X.; Ben Saada, M.; Mansour, H.; Gey, N.; Hazotte, A.; Maloufi, N.

    2016-06-01

    Four batches of UO2 pellets were studied comparatively, before and after creep tests, to evaluate a characterization methodology aimed to determine the links between microstructure and damage mechanisms induced by compressive creep of uranium dioxide at 1500 °C. They were observed by means of scanning electron microscopy (SEM) coupled with image analysis, to quantify their fabrication porosity and the occurrence of inter-granular cavities after creep, and electron back scattered diffraction (EBSD), especially to characterize sub-structures development associated with plastic deformation. Electron channeling contrast imaging (ECCI) was also applied to evidence dislocations, at an exploratory stage, on one of the deformed pellets. This approach helped to identify and quantify microstructural differences between batches. Their as-fabricated microstructures differed in terms of grain size and fabrication porosity distribution. The pellets which had the lowest strain rates were those with the largest number of intra-granular pores, regardless of their grain size. They also exhibited less numerous sub-boundaries within the grains. These first results clearly illustrate the benefit of systematic examinations of crept UO2 pellets at a mesoscopic scale, by SEM and EBSD, to study their deformation process. In addition, ECCI appears as a powerful tool to evidence local dislocations arrangements, in bulk samples. Even if the sampling was limited, the results of this study also tend to indicate that the intra-granular pores population, resulting from the manufacturing of the samples by powder metallurgy, could have a significant influence on the UO2 viscoplastic deformation mechanisms.

  15. HIPK2 restricts SIRT1 activity upon severe DNA damage by a phosphorylation-controlled mechanism

    PubMed Central

    Conrad, E; Polonio-Vallon, T; Meister, M; Matt, S; Bitomsky, N; Herbel, C; Liebl, M; Greiner, V; Kriznik, B; Schumacher, S; Krieghoff-Henning, E; Hofmann, T G

    2016-01-01

    Upon severe DNA damage a cellular signalling network initiates a cell death response through activating tumour suppressor p53 in association with promyelocytic leukaemia (PML) nuclear bodies. The deacetylase Sirtuin 1 (SIRT1) suppresses cell death after DNA damage by antagonizing p53 acetylation. To facilitate efficient p53 acetylation, SIRT1 function needs to be restricted. How SIRT1 activity is regulated under these conditions remains largely unclear. Here we provide evidence that SIRT1 activity is limited upon severe DNA damage through phosphorylation by the DNA damage-responsive kinase HIPK2. We found that DNA damage provokes interaction of SIRT1 and HIPK2, which phosphorylates SIRT1 at Serine 682 upon lethal damage. Furthermore, upon DNA damage SIRT1 and HIPK2 colocalize at PML nuclear bodies, and PML depletion abrogates DNA damage-induced SIRT1 Ser682 phosphorylation. We show that Ser682 phosphorylation inhibits SIRT1 activity and impacts on p53 acetylation, apoptotic p53 target gene expression and cell death. Mechanistically, we found that DNA damage-induced SIRT1 Ser682 phosphorylation provokes disruption of the complex between SIRT1 and its activator AROS. Our findings indicate that phosphorylation-dependent restriction of SIRT1 activity by HIPK2 shapes the p53 response. PMID:26113041

  16. Sensing of damage and substrate stress in concrete using electro-mechanical impedance measurements of bonded PZT patches

    NASA Astrophysics Data System (ADS)

    Narayanan, Arun; Subramaniam, Kolluru V. L.

    2016-09-01

    The influence of stress and induced damage in concrete on the electro-mechanical (EM) impedance response of bonded PZT patches is evaluated for applied compressive loading. Full field displacements obtained from digital image correlation are used to evaluate the level of stress-induced damage in concrete. Stress in the substrate produces an imposed strain on the PZT. A change in the imposed strain produces a rightward frequency shift and an increase in the amplitude of the resonant peak in the EM conductance spectrum of the PZT. An increase in the substrate compliance produces a decrease in the resonant frequency and an increase in the amplitude of the resonant peak. Changes in the resonant peak in the conductance spectrum induced by increasing substrate stress are of a significant magnitude when compared with the changes induced by damage. In the early stages of damage associated with distributed microcracking, the counteracting influences of increasing level of damage and increasing stress on the resonant peak result in no shift in frequency for measurements under applied load. There is however an increase in the amplitude of the resonance peak. When the applied stress is removed, there is a net decrease in frequency resulting from damage in the form of distributed microcracks. Measures of changes in the resonant peak based on root mean square deviation (RMSD), do not show any observable change when measurements are performed under applied loading. There is a consistent increase in RMSD values and frequency shift with increasing damage when the applied stress is removed. The centroidal measure of the normalized frequency spectrum reflects changes in substrate stress. At higher applied stress levels, there is a nonlinear increase in damage, leading to localization and cracking. The influence of damage is dominant in this region and significant changes are obtained in the RMSD values in both loaded and unloaded conditions.

  17. Development of 66kV XLPE submarine cable using optical fiber as a mechanical-damage-detection-sensor

    SciTech Connect

    Nishimoto, Toshio; Miyahara, Tsutomu; Takehana, Hajime; Tateno, Fuminori

    1995-10-01

    Submarine cables are exposed to great risk of serious mechanical damage by ship anchors or equipment used for fishing. Detection of such damage in a submarine cable is a very useful technology for improving the reliability of a submarine cable transmission line. A mechanical-damage-detection-sensor using optical fiber was developed. A prototype 66kV XLPE submarine cable incorporating the sensor was manufactured for trial, and the ability of a sensor was confirmed by compression test. Actual 66kV XLPE submarine cable incorporating the sensor was manufactured for trial, and the ability of a sensor was confirmed by compression test. Actual 66kV XLPE submarine cable with the sensor was manufactured and installed as an operating transmission line in Japan.

  18. Investigation of Ductile Damage in DP980 Steel Sheets Using Mechanical Tests and X-ray Micro-Tomography

    NASA Astrophysics Data System (ADS)

    Mishra, A.; Leguen, C.; Thuillier, S.; Maire, E.

    2011-05-01

    This study is part of a broader research project on the prediction of formability limits in bending on radius of the order of the sheet thickness, based on ductile damage. As a first step, ductile damage in DP980 steel sheet was investigated by means of micro-tomography and mechanical testing, including tensile and simple shear tests. The local strain in tension was measured with a digital image correlation device up to rupture, on macroscopic samples of standard dimensions. Moreover, interrupted tensile tests on smaller specimen were also performed, in order to analyze the void distribution by X-ray micro-tomography. The final aim is to perform numerical simulation of the tests, with Gurson-Tvergaard-Needleman model, to take into account the influence of ductile damage on the mechanical behavior. A fair description of the void volume fraction was obtained as well as the stress level, in the case of small-size specimen.

  19. Molecular mechanisms of phoxim-induced silk gland damage and TiO2 nanoparticle-attenuated damage in Bombyx mori.

    PubMed

    Li, Bing; Yu, Xiaohong; Gui, Suxin; Xie, Yi; Zhao, Xiaoyang; Hong, Jie; Sun, Qingqing; Sang, Xuezi; Sheng, Lei; Cheng, Zhe; Cheng, Jie; Hu, Rengping; Wang, Ling; Shen, Weide; Hong, Fashui

    2014-06-01

    Phoxim is a useful organophosphate (OP) pesticide used in agriculture in China, however, exposure to this pesticide can result in a significant reduction in cocooning in Bombyx mori (B. mori). Titanium dioxide nanoparticles (TiO2 NPs) have been shown to decrease phoxim-induced toxicity in B. mori; however, very little is known about the molecular mechanisms of silk gland damage due to OP exposure and repair of gland damage by TiO2 NP pretreatment. In the present study, exposure to phoxim resulted in a significant reduction in cocooning rate in addition to silk gland damage, whereas TiO2 NP attenuated phoxim-induced gland damage, increased the antioxidant capacity of the gland, and increased cocooning rate in B. mori. Furthermore, digital gene expression data suggested that phoxim exposure led to significant alterations in the expression of 833 genes. In particular, phoxim exposure caused significant down-regulation of Fib-L, Ser2, Ser3, and P25 genes involved in silk protein synthesis, and up-regulation of SFGH, UCH3, and Salhh genes involved in silk protein hydrolysis. A combination of both phoxim and TiO2 NP treatment resulted in marked changes in the expression of 754 genes, while treatment with TiO2 NPs led to significant alterations in the expression of 308 genes. Importantly, pretreatment with TiO2 NPs increased Fib-L, Ser2, Ser3, and P25 expression, and decreased SFGH, UCH3, and Salhh expression in silk protein in the silk gland under phoxim stress. Therefore, Fib-L, Ser2, Ser3, P25, SFGH, UCH3, and Salhh may be potential biomarkers of silk gland toxicity in B. mori caused by phoxim exposure.

  20. DIRECT-ACTING, DNA-DAMAGING AS (III)-METHYLATED SPECIES: IMPLICATIONS FOR A CARCINOGENIC MECHANISM OF ACTION OF ARSENICALS

    EPA Science Inventory

    Direct-acting, DNA-damaging As (III)-methylated species: implications for a carcinogenic . mechanism of action of arsenicals

    Inorganic arsenic (iAs, arsenite and arsenate) has been thought to act as a carcinogen without reacting directly with DNA; neither iAs nor the As(...

  1. Independent mechanisms for macrophage binding and macrophage phagocytosis of damaged erythrocytes. Evidence of receptor cooperativity.

    PubMed

    Sambrano, G R; Terpstra, V; Steinberg, D

    1997-12-01

    The binding and phagocytosis of oxidatively damaged red blood cells (OxRBCs) by mouse peritoneal macrophages can be inhibited by oxidatively modified LDL (OxLDL), implying some commonality at their receptor-binding domains. Studies from many different laboratories support the view that OxRBC binding is due to the disruption of plasma membrane phospholipid asymmetry and the subsequent exposure of phosphatidylserine (PS) on the outer membrane leaflet. Presumably, oxidation of LDL creates a surface structure on it in some way homologous to the PS-rich domain on OxRBCs. Apoptotic cells in some instances are also recognized because of PS exposure on the outer leaflet of the membrane, and apoptotic cells are a common feature of atherosclerotic lesions. In the present studies, the mechanisms of binding and internalization of cells recognized by virtue of their membrane PS were studied using OxRBCs or vanadate-treated erythrocytes (VaRBCs) as models. Disruption of phospholipid asymmetry with vanadate produced cells that were bound by macrophages in the same divalent cation-dependent manner as OxRBCs. However, whereas OxRBCs were rapidly phagocytosed, VaRBCs were not. Stimulation of mouse macrophages with phorbol myristate acetate resulted in a concentration-dependent induction of phagocytosis of bound VaRBCs, an effect that could be prevented by the protein kinase C inhibitor staurosporine. Because phagocytosis of OxRBCs occurred unassisted, we speculated that there must be additional membrane changes induced by oxidation (over and above the disruption of phospholipid asymmetry) that contribute to phagocytosis of OxRBCs, possibly resulting in the ligation of a distinct receptor that does not necessarily contribute to adherence. This proposal is supported by the finding that ligation of macrophage Fc gamma receptors by the anti-Fc gamma RII/RIII antibody 2.4G2 triggers the phagocytosis of bound VaRBCs. Phagocytosis is also triggered by subthreshold opsonization of VaRBC, i

  2. Ion implantation in Al{sub x}Ga{sub 1-x}As : damage structures and amorphization mechanisms.

    SciTech Connect

    Lagow, B. W.; Turkot, B. A.; Robertson, I. M.; Coleman, J. J.; Roh, S. D.; Forbes, D. V.; Rehn, L. E.; Baldo, P. M.; Materials Science Division; Univ. of Illinois

    1998-07-01

    We review previous research on ion implantation in Al{sub x}Ga{sub 1-x}As-GaAs heterostructures, and include observations from our current work in order to assess the various mechanisms that have been proposed to account for damage accumulation and amorphization in this system. In considering all of the experimental observations, the most consistent description is one where amorphization occurs by a combination of point-defect buildup and direct impact amorphization mechanisms.

  3. Comparison of ex-situ volatile emissions from intact and mechanically damaged walnuts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The codling moth (Cydia pomonella) and navel orangeworm (Amyelois transitella) are insect pests that inflict serious economic damage to California walnuts. Feeding by these larvae causes physical damage, resulting in lower kernel quality, and can lead to fungal contamination by the aflatoxigenic fun...

  4. In Vitro Comparative Assessment of Mechanical Blood Damage Induced by Different Hemodialysis Treatments.

    PubMed

    Sakota, Ranko; Lodi, Carlo Alberto; Sconziano, Sara Antonia; Beck, Werner; Bosch, Juan P

    2015-12-01

    routinely used dialysis treatments, bloodlines and machines. Although the in vitro measurement of the fHb increase in bovine blood does not allow a prediction of the absolute level of blood mechanical damage or the possible effects in humans, such measurements are valuable for assessing hemolytic harm by performing tests comparing the proposed treatment with existing devices.

  5. In Vitro Comparative Assessment of Mechanical Blood Damage Induced by Different Hemodialysis Treatments

    PubMed Central

    Lodi, Carlo Alberto; Sconziano, Sara Antonia; Beck, Werner; Bosch, Juan P.

    2015-01-01

    to RBCs compared with that observed for routinely used dialysis treatments, bloodlines and machines. Although the in vitro measurement of the fHb increase in bovine blood does not allow a prediction of the absolute level of blood mechanical damage or the possible effects in humans, such measurements are valuable for assessing hemolytic harm by performing tests comparing the proposed treatment with existing devices. PMID:25981394

  6. Common Practice Lightning Strike Protection Characterization Technique to Quantify Damage Mechanisms on Composite Substrates

    NASA Technical Reports Server (NTRS)

    Szatkowski, George N.; Dudley, Kenneth L.; Koppen, Sandra V.; Ely, Jay J.; Nguyen, Truong X.; Ticatch, Larry A.; Mielnik, John J.; Mcneill, Patrick A.

    2013-01-01

    To support FAA certification airworthiness standards, composite substrates are subjected to lightning direct-effect electrical waveforms to determine performance characteristics of the lightning strike protection (LSP) conductive layers used to protect composite substrates. Test results collected from independent LSP studies are often incomparable due to variability in test procedures & applied practices at different organizations, which impairs performance correlations between different LSP data sets. Under a NASA supported contract, The Boeing Company developed technical procedures and documentation as guidance in order to facilitate a test method for conducting universal common practice lightning strike protection test procedures. The procedures obtain conformity in future lightning strike protection evaluations to allow meaningful performance correlations across data sets. This universal common practice guidance provides the manufacturing specifications to fabricate carbon fiber reinforced plastic (CFRP) test panels, including finish, grounding configuration, and acceptable methods for pretest nondestructive inspection (NDI) and posttest destructive inspection. The test operations guidance elaborates on the provisions contained in SAE ARP5416 to address inconsistencies in the generation of damage protection performance data, so as to provide for maximum achievable correlation across capable lab facilities. In addition, the guidance details a direct effects test bed design to aid in quantification of the multi-physical phenomena surrounding a lightning direct attachment supporting validation data requirements for the development of predictive computational modeling. The lightning test bed is designed to accommodate a repeatable installation procedure to secure the test panel and eliminate test installation uncertainty. It also facilitates a means to capture the electrical waveform parameters in 2 dimensions, along with the mechanical displacement and thermal

  7. Effect of CO2 deastringency treatment on flesh disorders induced by mechanical damage in persimmon. Biochemical and microstructural studies.

    PubMed

    Novillo, Pedro; Salvador, Alejandra; Llorca, Empar; Hernando, Isabel; Besada, Cristina

    2014-02-15

    Manifestation of flesh browning while commercialising 'Rojo Brillante' persimmon is one of the main causes of postharvest loss. It is known that mechanical damage is a decisive factor for browning development and that astringent fruit is less sensitive to this disorder than fruit submitted to a CO2 deastringency treatment under standard conditions (24h, 95% CO2, 20 °C). However, there is no information available about the mechanism behind this alteration. In the present study, we evaluated the effect of treatment with high CO2 concentrations applied for 0-40 h on the incidence of mechanical impact-induced flesh disorders using biochemical, chromatographic and microstructural techniques. Our results show that the longer the CO2 exposure, the higher the incidence and the greater the severity browning. A deastringency treatment with CO2 results in O2(-) accumulation in fruit, which is greater the longer treatment is. However, mechanical damage triggers the browning manifestation, resulting in the accumulation of both O2(-) and H2O2. In this oxidative stress state, which must be greater as higher the level of O2(-) previously accumulated in the deastringency treatment, insoluble tannins initially uncolour, undergo an oxidation process and turn red-brown, observed as flesh browning. Moreover, we identified a new disorder, "pinkish-bruising", which is manifested in astringent fruit. The mechanism of this alteration, also associated with mechanical damage, seems similar to that of browning, but the oxidation process would affect soluble tannins.

  8. Modeling of damage generation mechanisms in silicon at energies below the displacement threshold

    SciTech Connect

    Santos, Ivan; Marques, Luis A.; Pelaz, Lourdes

    2006-11-01

    We have used molecular dynamics simulation techniques to study the generation of damage in Si within the low-energy deposition regime. We have demonstrated that energy transfers below the displacement threshold can produce a significant amount of damage, usually neglected in traditional radiation damage calculations. The formation of amorphous pockets agrees with the thermal spike concept of local melting. However, we have found that the order-disorder transition is not instantaneous, but it requires some time to reach the appropriate kinetic-potential energy redistribution for melting. The competition between the rate of this energy redistribution and the energy diffusion to the surrounding atoms determines the amount of damage generated by a given deposited energy. Our findings explain the diverse damage morphology produced by ions of different masses.

  9. Blood damage through a bileaflet mechanical heart valve: a quantitative computational study using a multiscale suspension flow solver.

    PubMed

    Min Yun, B; Aidun, Cyrus K; Yoganathan, Ajit P

    2014-10-01

    Bileaflet mechanical heart valves (BMHVs) are among the most popular prostheses to replace defective native valves. However, complex flow phenomena caused by the prosthesis are thought to induce serious thromboembolic complications. This study aims at employing a novel multiscale numerical method that models realistic sized suspended platelets for assessing blood damage potential in flow through BMHVs. A previously validated lattice-Boltzmann method (LBM) is used to simulate pulsatile flow through a 23 mm St. Jude Medical (SJM) Regent™ valve in the aortic position at very high spatiotemporal resolution with the presence of thousands of suspended platelets. Platelet damage is modeled for both the systolic and diastolic phases of the cardiac cycle. No platelets exceed activation thresholds for any of the simulations. Platelet damage is determined to be particularly high for suspended elements trapped in recirculation zones, which suggests a shift of focus in blood damage studies away from instantaneous flow fields and toward high flow mixing regions. In the diastolic phase, leakage flow through the b-datum gap is shown to cause highest damage to platelets. This multiscale numerical method may be used as a generic solver for evaluating blood damage in other cardiovascular flows and devices. PMID:25070372

  10. Assessing the Impact of Mechanical Damage on Full-Thickness Porcine and Human Skin Using an In Vitro Approach

    PubMed Central

    Dabboue, Hinda; Builles, Nicolas; Frouin, Éric; Scott, Dan; Ramos, Jeanne; Marti-Mestres, Gilberte

    2015-01-01

    For most xenobiotics, the rates of percutaneous absorption are limited by diffusion through the horny layer of skin. However, percutaneous absorption of chemicals may seriously increase when the skin is damaged. The aim of this work was to develop an in vitro representative model of mechanically damaged skins. The epidermal barrier was examined following exposure to a razor, a rotating brush, and a microneedle system in comparison to tape-stripping which acted as a reference. Excised full-thickness skins were mounted on a diffusion chamber in order to evaluate the effect of injuries and to mimic physiological conditions. The transepidermal water loss (TEWL) was greatly increased when the barrier function was compromised. Measurements were made for all the damaged biopsies and observed histologically by microscopy. On human and porcine skins, the tape-stripping application (0 to 40 times) showed a proportional increase in TEWL which highlights the destruction of the stratum corneum. Similar results were obtained for all cosmetic instruments. This is reflected in our study by the nonsignificant difference of the mean TEWL scores between 30 strips and mechanical damage. For a specific appreciation, damaged skins were then selected to qualitatively evaluate the absorption of a chlorogenic acid solution using fluorescence microscopy. PMID:26247021

  11. Prevention Effects and Possible Molecular Mechanism of Mulberry Leaf Extract and its Formulation on Rats with Insulin-Insensitivity.

    PubMed

    Liu, Yan; Li, Xuemei; Xie, Chen; Luo, Xiuzhen; Bao, Yonggang; Wu, Bin; Hu, Yuchi; Zhong, Zhong; Liu, Chang; Li, MinJie

    2016-01-01

    For centuries, mulberry leaf has been used in traditional Chinese medicine for the treatment of diabetes. This study aims to test the prevention effects of a proprietary mulberry leaf extract (MLE) and a formula consisting of MLE, fenugreek seed extract, and cinnamon cassia extract (MLEF) on insulin resistance development in animals. MLE was refined to contain 5% 1-deoxynojirimycin by weight. MLEF was formulated by mixing MLE with cinnamon cassia extract and fenugreek seed extract at a 6:5:3 ratio (by weight). First, the acute toxicity effects of MLE on ICR mice were examined at 5 g/kg BW dose. Second, two groups of normal rats were administrated with water or 150 mg/kg BW MLE per day for 29 days to evaluate MLE's effect on normal animals. Third, to examine the effects of MLE and MLEF on model animals, sixty SD rats were divided into five groups, namely, (1) normal, (2) model, (3) high-dose MLE (75 mg/kg BW) treatment; (4) low-dose MLE (15 mg/kg BW) treatment; and (5) MLEF (35 mg/kg BW) treatment. On the second week, rats in groups (2)-(5) were switched to high-energy diet for three weeks. Afterward, the rats were injected (ip) with a single dose of 105 mg/kg BW alloxan. After four more days, fasting blood glucose, post-prandial blood glucose, serum insulin, cholesterol, and triglyceride levels were measured. Last, liver lysates from animals were screened with 650 antibodies for changes in the expression or phosphorylation levels of signaling proteins. The results were further validated by Western blot analysis. We found that the maximum tolerance dose of MLE was greater than 5 g/kg in mice. The MLE at a 150 mg/kg BW dose showed no effect on fast blood glucose levels in normal rats. The MLE at a 75 mg/kg BW dose and MLEF at a 35 mg/kg BW dose, significantly (p < 0.05) reduced fast blood glucose levels in rats with impaired glucose and lipid metabolism. In total, 34 proteins with significant changes in expression and phosphorylation levels were identified. The

  12. Prevention Effects and Possible Molecular Mechanism of Mulberry Leaf Extract and its Formulation on Rats with Insulin-Insensitivity

    PubMed Central

    Xie, Chen; Luo, Xiuzhen; Bao, Yonggang; Wu, Bin; Hu, Yuchi; Zhong, Zhong; Liu, Chang; Li, MinJie

    2016-01-01

    For centuries, mulberry leaf has been used in traditional Chinese medicine for the treatment of diabetes. This study aims to test the prevention effects of a proprietary mulberry leaf extract (MLE) and a formula consisting of MLE, fenugreek seed extract, and cinnamon cassia extract (MLEF) on insulin resistance development in animals. MLE was refined to contain 5% 1-deoxynojirimycin by weight. MLEF was formulated by mixing MLE with cinnamon cassia extract and fenugreek seed extract at a 6:5:3 ratio (by weight). First, the acute toxicity effects of MLE on ICR mice were examined at 5 g/kg BW dose. Second, two groups of normal rats were administrated with water or 150 mg/kg BW MLE per day for 29 days to evaluate MLE’s effect on normal animals. Third, to examine the effects of MLE and MLEF on model animals, sixty SD rats were divided into five groups, namely, (1) normal, (2) model, (3) high-dose MLE (75 mg/kg BW) treatment; (4) low-dose MLE (15 mg/kg BW) treatment; and (5) MLEF (35 mg/kg BW) treatment. On the second week, rats in groups (2)-(5) were switched to high-energy diet for three weeks. Afterward, the rats were injected (ip) with a single dose of 105 mg/kg BW alloxan. After four more days, fasting blood glucose, post-prandial blood glucose, serum insulin, cholesterol, and triglyceride levels were measured. Last, liver lysates from animals were screened with 650 antibodies for changes in the expression or phosphorylation levels of signaling proteins. The results were further validated by Western blot analysis. We found that the maximum tolerance dose of MLE was greater than 5 g/kg in mice. The MLE at a 150 mg/kg BW dose showed no effect on fast blood glucose levels in normal rats. The MLE at a 75 mg/kg BW dose and MLEF at a 35 mg/kg BW dose, significantly (p < 0.05) reduced fast blood glucose levels in rats with impaired glucose and lipid metabolism. In total, 34 proteins with significant changes in expression and phosphorylation levels were identified. The

  13. Prevention Effects and Possible Molecular Mechanism of Mulberry Leaf Extract and its Formulation on Rats with Insulin-Insensitivity.

    PubMed

    Liu, Yan; Li, Xuemei; Xie, Chen; Luo, Xiuzhen; Bao, Yonggang; Wu, Bin; Hu, Yuchi; Zhong, Zhong; Liu, Chang; Li, MinJie

    2016-01-01

    For centuries, mulberry leaf has been used in traditional Chinese medicine for the treatment of diabetes. This study aims to test the prevention effects of a proprietary mulberry leaf extract (MLE) and a formula consisting of MLE, fenugreek seed extract, and cinnamon cassia extract (MLEF) on insulin resistance development in animals. MLE was refined to contain 5% 1-deoxynojirimycin by weight. MLEF was formulated by mixing MLE with cinnamon cassia extract and fenugreek seed extract at a 6:5:3 ratio (by weight). First, the acute toxicity effects of MLE on ICR mice were examined at 5 g/kg BW dose. Second, two groups of normal rats were administrated with water or 150 mg/kg BW MLE per day for 29 days to evaluate MLE's effect on normal animals. Third, to examine the effects of MLE and MLEF on model animals, sixty SD rats were divided into five groups, namely, (1) normal, (2) model, (3) high-dose MLE (75 mg/kg BW) treatment; (4) low-dose MLE (15 mg/kg BW) treatment; and (5) MLEF (35 mg/kg BW) treatment. On the second week, rats in groups (2)-(5) were switched to high-energy diet for three weeks. Afterward, the rats were injected (ip) with a single dose of 105 mg/kg BW alloxan. After four more days, fasting blood glucose, post-prandial blood glucose, serum insulin, cholesterol, and triglyceride levels were measured. Last, liver lysates from animals were screened with 650 antibodies for changes in the expression or phosphorylation levels of signaling proteins. The results were further validated by Western blot analysis. We found that the maximum tolerance dose of MLE was greater than 5 g/kg in mice. The MLE at a 150 mg/kg BW dose showed no effect on fast blood glucose levels in normal rats. The MLE at a 75 mg/kg BW dose and MLEF at a 35 mg/kg BW dose, significantly (p < 0.05) reduced fast blood glucose levels in rats with impaired glucose and lipid metabolism. In total, 34 proteins with significant changes in expression and phosphorylation levels were identified. The

  14. Organophosphate-induced brain damage: mechanisms, neuropsychiatric and neurological consequences, and potential therapeutic strategies.

    PubMed

    Chen, Yun

    2012-06-01

    Organophosphate (OP)-induced brain damage is defined as progressive damage to the brain, resulting from the cholinergic neuronal excitotoxicity and dysfunction induced by OP-induced irreversible AChE inhibition. This delayed secondary neuronal damage that occurs mainly in the cholinergic regions of the brain that contain dense accumulations of cholinergic neurons and the majority of cholinergic projection, might be largely responsible for persistent profound neuropsychiatric and neurological impairments (memory, cognitive, mental, emotional, motor and sensory deficits) in the victims of OP poisoning. Neuroprotective strategies for attenuating OP-induced brain damage should target different development stages of OP-induced brain damage, and may include but not limited to: (1) Antidote therapies with atropine and related efficient anticholinergic drugs; (2) Anti-excitotoxic therapies targeting attenuation of cerebral edema and inflammatory reaction, blockage of calcium influx, inhibition of apoptosis program, and the control of seizures; (3) Neuroprotective strategies using cytokines, antioxidants and NMDAR antagonists (a single drug or a combination of drugs) to slow down the process of secondary neuronal damage; and (4) Therapies targeting individual symptoms or clusters of chronic neuropsychiatric and neurological symptoms. These neuroprotective strategies may help limit or prevent secondary neuronal damage at the early stage of OP poisoning and attenuate the subsequent neuropsychiatric and neurological impairments, thus reducing the long-term disability caused by exposure to OPs. PMID:22498093

  15. Mutational analysis of the damage-recognition and catalytic mechanism of human SMUG1 DNA glycosylase.

    PubMed

    Matsubara, Mayumi; Tanaka, Tamon; Terato, Hiroaki; Ohmae, Eiji; Izumi, Shunsuke; Katayanagi, Katsuo; Ide, Hiroshi

    2004-01-01

    Single-strand selective monofunctional uracil-DNA glycosylase (SMUG1), previously thought to be a backup enzyme for uracil-DNA glycosylase, has recently been shown to excise 5-hydroxyuracil (hoU), 5-hydroxymethyluracil (hmU) and 5-formyluracil (fU) bearing an oxidized group at ring C5 as well as an uracil. In the present study, we used site-directed mutagenesis to construct a series of mutants of human SMUG1 (hSMUG1), and tested their activity for uracil, hoU, hmU, fU and other bases to elucidate the catalytic and damage-recognition mechanism of hSMUG1. The functional analysis of the mutants, together with the homology modeling of the hSMUG1 structure based on that determined recently for Xenopus laevis SMUG1, revealed the crucial residues for the rupture of the N-glycosidic bond (Asn85 and His239), discrimination of pyrimidine rings through pi-pi stacking to the base (Phe98) and specific hydrogen bonds to the Watson-Crick face of the base (Asn163) and exquisite recognition of the C5 substituent through water-bridged (uracil) or direct (hoU, hmU and fU) hydrogen bonds (Gly87-Met91). Integration of the present results and the structural data elucidates how hSMUG1 accepts uracil, hoU, hmU and fU as substrates, but not other oxidized pyrimidines such as 5-hydroxycytosine, 5-formylcytosine and thymine glycol, and intact pyrimidines such as thymine and cytosine.

  16. Modelling and simulations of the chemo-mechanical behaviour of leached cement-based materials: Interactions between damage and leaching

    SciTech Connect

    Stora, E.; Bary, B.; Deville, E.; Montarnal, P.

    2010-08-15

    The assessment of the durability of cement-based materials, which could be employed in underground structures for nuclear waste disposal, requires accounting for deterioration factors, such as chemical attacks and damage, and for the interactions between these phenomena. The objective of the present paper consists in investigating the long-term behaviour of cementitious materials by simulating their response to chemical and mechanical solicitations. In a companion paper (Stora et al., submitted to Cem. Concr. Res. 2008), the implementation of a multi-scale homogenization model into an integration platform has allowed for evaluating the evolution of the mineral composition, diffusive and elastic properties inside a concrete material subjected to leaching. To complete this previous work, an orthotropic micromechanical damage model is presently developed and incorporated in this numerical platform to estimate the mechanical and diffusive properties of damaged cement-based materials. Simulations of the chemo-mechanical behaviour of leached cementitious materials are performed with the tool thus obtained and compared with available experiments. The numerical results are insightful about the interactions between damage and chemical deteriorations.

  17. Effect of mechanical tissue properties on thermal damage in skin after IR-laser ablation

    NASA Astrophysics Data System (ADS)

    Frenz, M.; Mischler, Ch.; Romano, V.; Forrer, M.; Müller, O. M.; Weber, H. P.

    1991-04-01

    The damage created instantaneously in dorsal skin and in the subjacent skeletal muscle layer after CO2 and Er3+ laser incisions is histologically and ultrastructurally investigated. Light microscopical examinations show an up to three times larger damage zone in the subcutaneous layer of skeletal muscle than in the connective tissue above. The extent of thermally altered muscle tissue is classified by different zones and characterized by comparison to long time heating injuries. The unexpectedly large damage is a result of the change of elastic properties occurring abruptly at the transition between different materials. This leads to a discontinuity of the cutting dynamics that reduces the ejection of tissue material. We show that the degree of thermal damage originates from the amount of hot material that is not ejected out of the crater acting as a secondary heat source.

  18. Damage and fracture mechanisms in cross-woven C/SiC composite subjected to tensile loading

    SciTech Connect

    Wang, M.; Laird, C.

    1994-12-31

    In order to investigate the structure sensitivity of composite behavior, tensile tests were conducted on CVI processed cross-woven C/SiC composites. Tensile damage mechanisms were observed using SEM on loaded and then unloaded samples. The damage modes identified include bundle matrix cracking, fiber/matrix debonding, fiber breaking delamination and bundle splitting. Because of the inhomogeneous SiC distribution in the fiber bundles, matrix cracking was observed to develop three dimensionally, including the following processes: lateral growth in matrix dominated regions such as bundle coatings, and crack arrest due to the decrease in matrix volume fraction, followed by formation of new matrix cracks inside the bundle, producing a damage zone characterized by a high density of small inter-fiber cracks. Final failure of the composite resulted from fiber breaks at different locations across the fiber bundles, producing in a rugged fracture surface.

  19. Mechanical damage to pollen aids nutrient acquisition in Heliconius butterflies (Nymphalidae).

    PubMed

    Krenn, Harald W; Eberhard, Monika J B; Eberhard, Stefan H; Hikl, Anna-Laetitia; Huber, Werner; Gilbert, Lawrence E

    2009-12-01

    Neotropical Heliconius and Laparus butterflies actively collect pollen onto the proboscis and extract nutrients from it. This study investigates the impact of the processing behaviour on the condition of the pollen grains. Pollen samples (n = 72) were collected from proboscides of various Heliconius species and Laparus doris in surrounding habitats of the Tropical Research Station La Gamba (Costa Rica). Examination using a light microscope revealed that pollen loads contained 74.88 ± 53.67% of damaged Psychotria pollen, 72.04 ± 23.4% of damaged Psiguria/Gurania pollen, and 21.35 ± 14.5% of damaged Lantana pollen (numbers represent median ± first quartile). Damaged pollen grains showed deformed contours, inhomogeneous and/or leaking contents, or they were empty. Experiments with Heliconius and Laparus doris from a natural population in Costa Rica demonstrated that 200 min of pollen processing behaviour significantly increased the percentage of damaged pollen of Psychotria compared to pollen from anthers (P = 0.015, Z = -2.44, Mann-Whitney U-test). Examination of pollen loads from green house reared Heliconius butterflies resulted in significantly greater amounts of damaged Psiguria pollen after 200 min of processing behaviour compared to pollen from flowers (P < 0.001, Z = -4.583, Mann-Whitney U-test). These results indicate that pollen processing functions as extra oral digestion whereby pollen grains are ruptured to make the content available for ingestion.

  20. Scaling Between Fault Length, Damaged Zone Thickness and Width of Secondary Fault Fans Derived from Fracture Mechanics

    NASA Astrophysics Data System (ADS)

    Ampuero, Jean Paul; Mao, Xiaolin

    2016-04-01

    The interaction between earthquakes, fault network geometry and fault zone structure is a key question motivating the integration of dynamic rupture and long-term crustal deformation modeling. Here, we address the scaling between fault structural properties from the perspective of dynamic and quasi-static processes involved in fault system evolution. Faults are surrounded by materials damaged through quasi-static and dynamic processes, forming damaged zones whose thickness and damage intensity may vary as a function of fault maturity and length. In the vicinity (typically less than a few hundred meters) of their principal slip surface, faults develop an "inner damage zone", usually characterized by micro-fracture observations. At a larger scale, faults develop an "outer damage zone" of secondary macroscopic fault branches at their tips, which organize into fans of splay faults. Inner damage zones can significantly affect earthquake ruptures, enhance near-field ground motions and facilitate fluid transport in the crust. Fault zone trapped waves can generate pulse-like rupture and oscillatory rupture speed, facilitate supershear rupture transition and allow for steady rupture propagation at speeds that are unstable or inadmissible in homogeneous media. The effects of a fault damage zone crucially depend on its thickness. Field observations of inner damage zone thickness as a function of cumulated slip show linear scaling at small slip but saturation at large slip, with maximum damage zone thickness of a few hundred meters. We previously developed fracture mechanics theoretical arguments and dynamic rupture simulations with off-fault inelastic deformation that predict saturation of the thickness of co-seismic damage zone controlled by the depth extent of the seismogenic zone. In essence, the stress intensity factor at the front of a rupture, which controls the distance reached by the large off-fault stresses that cause damage, scales with the shortest characteristic

  1. 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.

  2. The Adenovirus E4orf4 Protein Provides a Novel Mechanism for Inhibition of the DNA Damage Response

    PubMed Central

    Kechker, Peter; Sharf, Rakefet; Kleinberger, Tamar

    2016-01-01

    The DNA damage response (DDR) is a conglomerate of pathways designed to detect DNA damage and signal its presence to cell cycle checkpoints and to the repair machinery, allowing the cell to pause and mend the damage, or if the damage is too severe, to trigger apoptosis or senescence. Various DDR branches are regulated by kinases of the phosphatidylinositol 3-kinase-like protein kinase family, including ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR). Replication intermediates and linear double-stranded genomes of DNA viruses are perceived by the cell as DNA damage and activate the DDR. If allowed to operate, the DDR will stimulate ligation of viral genomes and will inhibit virus replication. To prevent this outcome, many DNA viruses evolved ways to limit the DDR. As part of its attack on the DDR, adenovirus utilizes various viral proteins to cause degradation of DDR proteins and to sequester the MRN damage sensor outside virus replication centers. Here we show that adenovirus evolved yet another novel mechanism to inhibit the DDR. The E4orf4 protein, together with its cellular partner PP2A, reduces phosphorylation of ATM and ATR substrates in virus-infected cells and in cells treated with DNA damaging drugs, and causes accumulation of damaged DNA in the drug-treated cells. ATM and ATR are not mutually required for inhibition of their signaling pathways by E4orf4. ATM and ATR deficiency as well as E4orf4 expression enhance infection efficiency. Furthermore, E4orf4, previously reported to induce cancer-specific cell death when expressed alone, sensitizes cells to killing by sub-lethal concentrations of DNA damaging drugs, likely because it inhibits DNA damage repair. These findings provide one explanation for the cancer-specificity of E4orf4-induced cell death as many cancers have DDR deficiencies leading to increased reliance on the remaining intact DDR pathways and to enhanced susceptibility to DDR inhibitors such as E4orf4. Thus DDR inhibition

  3. The Adenovirus E4orf4 Protein Provides a Novel Mechanism for Inhibition of the DNA Damage Response.

    PubMed

    Brestovitsky, Anna; Nebenzahl-Sharon, Keren; Kechker, Peter; Sharf, Rakefet; Kleinberger, Tamar

    2016-02-01

    The DNA damage response (DDR) is a conglomerate of pathways designed to detect DNA damage and signal its presence to cell cycle checkpoints and to the repair machinery, allowing the cell to pause and mend the damage, or if the damage is too severe, to trigger apoptosis or senescence. Various DDR branches are regulated by kinases of the phosphatidylinositol 3-kinase-like protein kinase family, including ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR). Replication intermediates and linear double-stranded genomes of DNA viruses are perceived by the cell as DNA damage and activate the DDR. If allowed to operate, the DDR will stimulate ligation of viral genomes and will inhibit virus replication. To prevent this outcome, many DNA viruses evolved ways to limit the DDR. As part of its attack on the DDR, adenovirus utilizes various viral proteins to cause degradation of DDR proteins and to sequester the MRN damage sensor outside virus replication centers. Here we show that adenovirus evolved yet another novel mechanism to inhibit the DDR. The E4orf4 protein, together with its cellular partner PP2A, reduces phosphorylation of ATM and ATR substrates in virus-infected cells and in cells treated with DNA damaging drugs, and causes accumulation of damaged DNA in the drug-treated cells. ATM and ATR are not mutually required for inhibition of their signaling pathways by E4orf4. ATM and ATR deficiency as well as E4orf4 expression enhance infection efficiency. Furthermore, E4orf4, previously reported to induce cancer-specific cell death when expressed alone, sensitizes cells to killing by sub-lethal concentrations of DNA damaging drugs, likely because it inhibits DNA damage repair. These findings provide one explanation for the cancer-specificity of E4orf4-induced cell death as many cancers have DDR deficiencies leading to increased reliance on the remaining intact DDR pathways and to enhanced susceptibility to DDR inhibitors such as E4orf4. Thus DDR inhibition

  4. Bond breaks of nucleotides by dissociative electron transfer of nonequilibrium prehydrated electrons: a new molecular mechanism for reductive DNA damage.

    PubMed

    Wang, Chun-Rong; Nguyen, Jenny; Lu, Qing-Bin

    2009-08-19

    DNA damage is a central mechanism in the pathogenesis and treatment of human diseases, notably cancer. Little is known about reductive DNA damage in causing genetic mutations during oncogenesis and killing cancer cells during radiotherapy. The prehydrated electron (e(-)(pre)) has the highest yield among all the radicals generated in cells during ionizing radiation and has subpicosecond lifetimes (10(-13) s) and energies below 0 eV, but its role in DNA damage is unknown. In this work, our real-time measurements by femtosecond time-resolved laser spectroscopy have revealed that while adenine and cytosine can effectively trap an e(-)(pre) to form stable anions, thymidine and especially guanine are highly susceptible to dissociative electron transfer of e(-)(pre), leading to bond dissociation in DNA. Our finding demonstrates a dissociative electron transfer pathway for reductive DNA damage that might be related to various diseases such as cancer and stroke. Moreover, this finding challenges the conventional notion that damage to the genome is mainly induced by the oxidizing OH* radical and might eventually lead to improved radiotherapy of cancer and radioprotection of humans.

  5. Solid-extracellular fluid interaction and damage in the mechanical response of rat brain tissue under confined compression.

    PubMed

    Haslach, Henry W; Leahy, Lauren N; Riley, Peter; Gullapalli, Rao; Xu, Su; Hsieh, Adam H

    2014-01-01

    The mechanical processes that underlie mild traumatic brain injury from physical insults are not well understood. One aspect in particular that has not been examined is the tissue fluid, which is known to be critical in the mechanical function of other organs. To investigate the contributions of solid-fluid interactions to brain tissue mechanics, we performed confined compression tests, that force the extracellular fluid (ECF) to flow in the direction of the deformation, on 6.35mm diameter, 3mm long cylindrical samples excised from various regions of rat brains. Two types of tests in deformation control, (1) quasi-static, slow and moderate constant strain rate tests at 0.64×10(-5)/s, 0.001/s and 1/s to large strains and (2) several applications of slow linear deformation to 5% strain each followed by stress relaxation are employed to explore the solid-fluid interaction. At slow and moderate compressive strain rates, we observed stress peaks in the applied strain range at about 11%, whose magnitudes exhibited statistically significant dependence on strain rate. These data suggest that the ECF carries load until the tissue is sufficiently damaged to permit pathological fluid flow. Under the slow ramp rate in the ramp-relaxation cycles protocol, commonly used to estimate permeability, the stress relaxes to zero after the first cycle, rather than to a non-zero equilibrium stress corresponding to the applied strain, which further implicates mechanical damage. Magnetic resonance imaging (MRI) of changes in tissue microstructure during confined compression, before and after compression, provides further evidence of tissue damage. The solid-fluid interactions, reflected in the morphology of the stress-stretch curves and supported by the MRI data, suggest that increases in hydrostatic pressure in the ECF may contribute to mechanical damage of brain tissue.

  6. Histological aspects of retinal damage following exposure to pulsed Nd:YAG laser radiation in rabbits: indication for mechanism

    NASA Astrophysics Data System (ADS)

    Kadar, T.; Peri, D.; Turetz, J.; Fishbine, E.; Sahar, R.; Egoz, I.; Sapiens, N.; Brandeis, R.

    2007-02-01

    The severity and characteristics of retinal injury following laser radiation derived from laser and tissue related factors. We have previously shown that retinal damage following Nd:YAG Q-switched laser radiation in rabbits was related to physical parameters, i.e. energy levels and number of pulses. Yet, an extremely large variability in the severity of the damage was found under similar exposure paradigms, even within the same retina. This emphasizes the role of the biological variables in the pathological mechanism of laser-induced retinal damage. The aim of the present study was to further study histological parameters of the injury in relation to retinal site and to elucidate their role in the initiation and characteristics of the damage, following various energy levels (10-50 μJ) and number of pulses (1-4). Pigmented rabbits were exposed to Nd:YAG laser radiation (532nm, pulse duration: 20ns). Exposures were conducted in retina tissue, adjacent to the optic nerve, with a total of 20 exposures per retina. Animals were sacrificed 15 min or 24 hours post exposure, eyes enucleated and processed for paraffin embedding. 4μm thick serial sections, stained with hematoxylin and eosin, were examined under light microscopy. Two major types of retinal damage were observed: focal edema confined to the pigmented epithelium and the photoreceptor cells, and hemorrhages, associated with destruction of retinal tissue. While focal edema associated with slight elevation of the photoreceptor layer seems to depend on the pigmented epithelium, hemorrhages were related also to the choroid vasculature at the site of radiation. It is suggested that a thermo-mechanical mechanism is involved in laser induced retinal hemorrhages at energies above 10-30μJ (2-1 pulses, respectively).

  7. A space-time tensor formulation for continuum mechanics in general curvilinear, moving, and deforming coordinate systems

    NASA Technical Reports Server (NTRS)

    Avis, L. M.

    1976-01-01

    Tensor methods are used to express the continuum equations of motion in general curvilinear, moving, and deforming coordinate systems. The space-time tensor formulation is applicable to situations in which, for example, the boundaries move and deform. Placing a coordinate surface on such a boundary simplifies the boundary condition treatment. The space-time tensor formulation is also applicable to coordinate systems with coordinate surfaces defined as surfaces of constant pressure, density, temperature, or any other scalar continuum field function. The vanishing of the function gradient components along the coordinate surfaces may simplify the set of governing equations. In numerical integration of the equations of motion, the freedom of motion of the coordinate surfaces provides a potential for enhanced resolution of the continuum field function. An example problem of an incompressible, inviscid fluid with a top free surface is considered, where the surfaces of constant pressure (including the top free surface) are coordinate surfaces.

  8. A review of formulation techniques that impact the disintegration and mechanical properties of oradispersible drug delivery technologies.

    PubMed

    Manyikana, Martina; Choonara, Yahya E; Tomar, Lomas K; Tyagi, Charu; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

    2016-01-01

    The drug treatment of acute disorders such as neuropathic pain, migraines, insomnia, vomiting, allergic rhinitis or erectile dysfunction requires an immediate pharmacological effect that may be achieved through parenteral drug administration. However, the parenteral route is not always convenient for reasons that are well known. Therefore, in the recent past there has been a barrage of interest in formulating new, non-invasive, reliable and convenient oradispersible drug delivery technologies (ODDTs). Research in this area has focused extensively on developing ODDTs that are capable of releasing drugs immediately when they come into contact with saliva. This disregards the necessity of water during administration and several other advantages that is an attribute that makes this technology lucrative for groups such as pediatrics, geriatrics, psychiatrics and unconscious patients. Many reviews have been compiled on the salient features of ODDTs. However, none to date has focused on the actual formulation techniques used to produce these technologies and how this may impact their disintegration and physical stability for fulfilling their purpose. Therefore this review provides a concise incursion on the recent formulation techniques, excipients used as well as methods of testing the performance of ODDTs and critically assesses these in terms of improving their performance.

  9. Mechanism initiated by nanoabsorber for UV nanosecond-pulse-driven damage of dielectric coatings.

    PubMed

    Wei, Chaoyang; Shao, Jianda; He, Hongbo; Yi, Kui; Fan, Zhengxiu

    2008-03-01

    A model of plasma formation for UV nanosecond pulse-laser interaction with SiO(2) thin film based on nanoabsorber is proposed. The formalism considered the temperature dependence of band gap. The numerical results show that during the process of nanosecond pulsed-laser interaction with SiO(2) films, foreign inclusion absorbing a fraction of incident radiation heats the surrounding host material through heat conduction causing the decrease of the band gap and making the initial transparent matrix into an absorptive medium around the inclusion. During the remainder pulse, the abosorbing volume of the host material is effectively growed and lead to the formation of the damage craters. We investigated the experimental damage craters and compared with theoretical prediction. The pulselength dependence of damage threshold was also investigated. PMID:18542429

  10. Monodisperse Sn nanocrystals as a platform for the study of mechanical damage during electrochemical reactions with Li.

    PubMed

    Xu, Linping; Kim, Chunjoong; Shukla, Alpesh K; Dong, Angang; Mattox, Tracy M; Milliron, Delia J; Cabana, Jordi

    2013-04-10

    Monodisperse Sn spherical nanocrystals of 10.0 ± 0.2 nm were prepared in dispersible colloidal form. They were used as a model platform to study the impact of size on the accommodation of colossal volume changes during electrochemical lithiation using ex situ transmission electron microscopy (TEM). Significant mechanical damage was observed after full lithiation, indicating that even crystals at these very small dimensions are not sufficient to prevent particle pulverization that compromises electrode durability.

  11. Subsurface mechanical damage during bound abrasive grinding of fused silica glass

    NASA Astrophysics Data System (ADS)

    Blaineau, P.; André, D.; Laheurte, R.; Darnis, P.; Darbois, N.; Cahuc, O.; Neauport, J.

    2015-10-01

    The subsurface damage (SSD) introduced during bound abrasive grinding of fused silica glass was measured using a wet etch technique. Various process parameters and grinding configurations were studied. The relation between the SSD depth, the process parameters and forces applied by the grinding wheel on the sample was investigated and compared to a simulation using a discrete element method to model the grinding interface. The results reveal a relation between the SSD depth and the grinding forces normalized by the abrasive concentration. Regarding the creation of the SSD, numerical simulations indicate that only a small fraction of the largest particles in the diamond wheel are responsible for the depth of the damaged layer.

  12. Microemulsion formulation for enhanced absorption of poorly soluble drugs. II. In vivo study.

    PubMed

    Kawakami, Kohsaku; Yoshikawa, Takayoshi; Hayashi, Takashi; Nishihara, Yoshitaka; Masuda, Kazuyoshi

    2002-05-17

    Oral administration study of microemulsion formulations, which are known to improve the bioavailability of poorly soluble drugs, was performed using rats. Nitrendipine was used as a poorly soluble model drug, and its absorption was enhanced significantly by employing the microemulsion formulations compared to a suspension or an oil solution. The effect of the fed state on the oral absorption of nitrendipine became insignificant with the microemulsion formulations, although it affected the absorption from the suspension formulation significantly. The absorption behavior also varied with the type of surfactant. The absorption from Tween 80-based formulation was very rapid, while HCO-60-based formulation showed prolonged plasma concentration profile. However, the absorption from BL-9EX (polyoxyethylene alkyl ether)-based formulation was hardly observed. Damage to the gastrointestinal mucosa, which seems to be a serious problem of surfactant-based formulations, also differed with the type of surfactant employed. HCO-60 and Tween 80-based formulations were mild to the organs, while BL-9EX-based formulation caused serious damage. The behavior and absorption mechanism of the microemulsion formulations are discussed.

  13. Measure of mechanical impacts in commercial blueberry packing lines and potential damage to blueberry fruit

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Modern blueberry packing lines create impact damage to blueberries which will result in fruit bruising. In this study, impacts created by commercial blueberry packing lines were measured quantitatively using a miniature instrumented sphere. Impacts were recorded at transfer points. Average peakG ...

  14. Application of ARMAV models to the identification and damage detection of mechanical and civil engineering structures

    NASA Astrophysics Data System (ADS)

    Bodeux, J. B.; Golinval, J. C.

    2001-06-01

    In this paper, the application of auto-regressive moving average vector models to system identification and damage detection is investigated. These parametric models have already been applied for the analysis of multiple input-output systems under ambient excitation. Their main advantage consists in the capability of extracting modal parameters from the recorded time signals, without the requirement of excitation measurement. The excitation is supposed to be a stationary Gaussian white noise. The method also allows the estimation of modal parameter uncertainties. On the basis of these uncertainties, a statistically based damage detection scheme is performed and it becomes possible to assess whether changes of modal parameters are caused by, e.g. some damage or simply by estimation inaccuracies. The paper reports first an example of identification and damage detection applied to a simulated system under random excitation. The `Steel-Quake' benchmark proposed in the framework of COST Action F3 `Structural Dynamics' is also analysed. This structure was defined by the Joint Research Centre in Ispra (Italy) to test steel building performance during earthquakes. The proposed method gives an excellent identification of frequencies and mode shapes, while damping ratios are estimated with less accuracy.

  15. Task order #24 update: exploration of damage mechanisms in cylindrical geometry

    SciTech Connect

    Kaul, Ann M

    2011-01-14

    A typical method of failure for ductile materials is spallation damage, which is caused by the nucleation, growth and coalescence of voids due to the presence of high tensile stress in the material. Spallation damage models, such as TEPLA, are currently implemented in hydrodynamic computer codes used at Los Alamos National Laboratory (LANL). Parameters for such constitutive models are derived from data sets obtained primarily from gas gun and shock-driven experiments, which are designed to allow one-dimensional analysis of the evolution of the failure characteristics. However, in a non-planar geometry, advanced failure models predict failure to be a multi-dimensional process. Additionally, a limited amount of data exists for the process of void nucleation, growth and coalescence. Another lightly researched area is the state of the material in the event that the spallation layer is recollected and voids are closed. The experiments described here are being conducted as part of a Campaign-l effort to provide data addressing these issues. The Russian Damage Experimental Series is designed to provide fundamental non-planar (cylindrical) spallation damage data, including early time processes (void nucleation, growth and coalescence) and late time processes (recollection of the spallation layer). Previous experiments produced data addressing some of the early time processes. This presentation will be provided to LANL and VNIIEF colleagues as a means of assessing the status of Task Order No.24 at the current time.

  16. The formulation of dynamical contact problems with friction in the case of systems of rigid bodies and general discrete mechanical systems—Painlevé and Kane paradoxes revisited

    NASA Astrophysics Data System (ADS)

    Charles, Alexandre; Ballard, Patrick

    2016-08-01

    The dynamics of mechanical systems with a finite number of degrees of freedom (discrete mechanical systems) is governed by the Lagrange equation which is a second-order differential equation on a Riemannian manifold (the configuration manifold). The handling of perfect (frictionless) unilateral constraints in this framework (that of Lagrange's analytical dynamics) was undertaken by Schatzman and Moreau at the beginning of the 1980s. A mathematically sound and consistent evolution problem was obtained, paving the road for many subsequent theoretical investigations. In this general evolution problem, the only reaction force which is involved is a generalized reaction force, consistently with the virtual power philosophy of Lagrange. Surprisingly, such a general formulation was never derived in the case of frictional unilateral multibody dynamics. Instead, the paradigm of the Coulomb law applying to reaction forces in the real world is generally invoked. So far, this paradigm has only enabled to obtain a consistent evolution problem in only some very few specific examples and to suggest numerical algorithms to produce computational examples (numerical modeling). In particular, it is not clear what is the evolution problem underlying the computational examples. Moreover, some of the few specific cases in which this paradigm enables to write down a precise evolution problem are known to show paradoxes: the Painlevé paradox (indeterminacy) and the Kane paradox (increase in kinetic energy due to friction). In this paper, we follow Lagrange's philosophy and formulate the frictional unilateral multibody dynamics in terms of the generalized reaction force and not in terms of the real-world reaction force. A general evolution problem that governs the dynamics is obtained for the first time. We prove that all the solutions are dissipative; that is, this new formulation is free of Kane paradox. We also prove that some indeterminacy of the Painlevé paradox is fixed in this

  17. A novel perspective on neuron study: damaging and promoting effects in different neurons induced by mechanical stress.

    PubMed

    Wang, Yazhou; Wang, Wei; Li, Zong; Hao, Shilei; Wang, Bochu

    2016-10-01

    A growing volume of experimental evidence demonstrates that mechanical stress plays a significant role in growth, proliferation, apoptosis, gene expression, electrophysiological properties and many other aspects of neurons. In this review, first, the mechanical microenvironment and properties of neurons under in vivo conditions are introduced and analyzed. Second, research works in recent decades on the effects of different mechanical forces, especially compression and tension, on various neurons, including dorsal root ganglion neurons, retinal ganglion cells, cerebral cortex neurons, hippocampus neurons, neural stem cells, and other neurons, are summarized. Previous research results demonstrate that mechanical stress can not only injure neurons by damaging their morphology, impacting their electrophysiological characteristics and gene expression, but also promote neuron self-repair. Finally, some future perspectives in neuron research are discussed.

  18. Damage effect and mechanism of the GaAs pseudomorphic high electron mobility transistor induced by the electromagnetic pulse

    NASA Astrophysics Data System (ADS)

    Xiao-Wen, Xi; Chang-Chun, Chai; Gang, Zhao; Yin-Tang, Yang; Xin-Hai, Yu; Yang, Liu

    2016-04-01

    The damage effect and mechanism of the electromagnetic pulse (EMP) on the GaAs pseudomorphic high electron mobility transistor (PHEMT) are investigated in this paper. By using the device simulation software, the distributions and variations of the electric field, the current density and the temperature are analyzed. The simulation results show that there are three physical effects, i.e., the forward-biased effect of the gate Schottky junction, the avalanche breakdown, and the thermal breakdown of the barrier layer, which influence the device current in the damage process. It is found that the damage position of the device changes with the amplitude of the step voltage pulse. The damage appears under the gate near the drain when the amplitude of the pulse is low, and it also occurs under the gate near the source when the amplitude is sufficiently high, which is consistent with the experimental results. Project supported by the National Basic Research Program of China (Grant No. 2014CB339900), and the Open Fund of Key Laboratory of Complex Electromagnetic Environment Science and Technology, China Academy of Engineering Physics (CAEP) (Grant No. 2015-0214.XY.K).

  19. Polysorbate 20 Degradation in Biopharmaceutical Formulations: Quantification of Free Fatty Acids, Characterization of Particulates, and Insights into the Degradation Mechanism.

    PubMed

    Tomlinson, Anthony; Demeule, Barthélemy; Lin, Baiwei; Yadav, Sandeep

    2015-11-01

    Polysorbate 20 (PS20), a commonly used surfactant in biopharmaceuticals, showed degradation upon long-term (∼18-36 months) storage of two monoclonal antibody (mAb, mAb-A, and mAb-B) drug products at 2-8 °C. The PS20 degradation resulted in the accumulation of free fatty acids (FFA), which ultimately precipitated to form particles upon long-term storage. This study documents the development, qualification, and application of a method for FFA quantification in soluble and insoluble fraction of protein formulation. The method was applied to the quantification of capric acid, lauric acid, myristic acid, palmitic/oleic acid, and stearic acid in placebo as well as active protein formulations on stability. Quantification of FFA in both the soluble and insoluble fraction of mAb-A and mAb-B provided a better mechanistic understanding of PS20 degradation and the dynamics of subsequent fatty acid particle formation. Additionally, the use of this method for monitoring and quantitation of the FFA on real time storage stability appears to aid in identifying batches with higher probability for particulate formation upon extended storage at 5 °C. PMID:26419339

  20. Arsenic Biotransformation as a Cancer Promoting Factor by Inducing DNA Damage and Disruption of Repair Mechanisms

    PubMed Central

    Martinez, Victor D.; Vucic, Emily A.; Adonis, Marta; Gil, Lionel; Lam, Wan L.

    2011-01-01

    Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM). Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells, arsenic is also postulated to affect maintenance of normal DNA methylation patterns, chromatin structure, and genomic stability. The biological processes underlying the cancer promoting factors of arsenic metabolism, related to DNA damage and repair, will be discussed here. PMID:22091411

  1. Damage Mechanisms of a TiB2-Reinforced Steel Matrix Composite for Lightweight Automotive Application

    NASA Astrophysics Data System (ADS)

    Li, Y. Z.; Luo, Z. C.; Yi, H. L.; Huang, M. X.

    2016-09-01

    The microscopic strain-and-stress fields related to primary and eutectic particles in a lightweight steel matrix composite (SMC) produced by in situ precipitation of TiB2 particles during solidification were investigated by means of microscale digital image correlation and finite element method. The damage process in this SMC is a sequential process of primary particles cracking, the fracture of the surrounding eutectic particles, and finally the growth and coalescence of voids in the ferrite matrix.

  2. Damage Mechanisms of a TiB2-Reinforced Steel Matrix Composite for Lightweight Automotive Application

    NASA Astrophysics Data System (ADS)

    Li, Y. Z.; Luo, Z. C.; Yi, H. L.; Huang, M. X.

    2016-05-01

    The microscopic strain-and-stress fields related to primary and eutectic particles in a lightweight steel matrix composite (SMC) produced by in situ precipitation of TiB2 particles during solidification were investigated by means of microscale digital image correlation and finite element method. The damage process in this SMC is a sequential process of primary particles cracking, the fracture of the surrounding eutectic particles, and finally the growth and coalescence of voids in the ferrite matrix.

  3. Continuum Damage Mechanics Used to Predict the Creep Life of Monolithic Ceramics

    NASA Technical Reports Server (NTRS)

    Powers, Lynn M.; Jadaan, Osama M.

    1998-01-01

    Significant improvements in propulsion and power generation for the next century will require revolutionary advances in high-temperature materials and structural design. Advanced ceramics are candidate materials for these elevated temperature applications. High-temperature and long-duration applications of monolithic ceramics can place their failure mode in the creep rupture regime. An analytical methodology in the form of the integrated design program-Ceramics Analysis and Reliability Evaluation of Structures/Creep (CARES/Creep) has been developed by the NASA Lewis Research Center to predict the life of ceramic structural components subjected to creep rupture conditions. This program utilizes commercially available finite element packages and takes into account the transient state of stress and creep strain distributions (stress relaxation as well as the asymmetric response to tension and compression). The creep life of a component is discretized into short time steps, during which the stress distribution is assumed constant. Then, the damage is calculated for each time step on the basis of a modified Monkman-Grant (MMG) creep rupture criterion. The cumulative damage is subsequently calculated as time elapses in a manner similar to Miner's rule for cyclic fatigue loading. Failure is assumed to occur when the normalized cumulative damage at any point in the component reaches unity. The corresponding time is the creep rupture life for that component.

  4. Damage Prediction and Estimation in Structural Mechanics Based on Data Mining

    SciTech Connect

    Sandhu, S S; Kanapady, R; Tamma, K K; Kamath, C; Kumar, V

    2001-07-23

    Damage in a material includes localized softening or cracks in a structural component due to high operational loads, or the presence of flaws in a structure due to various manufacturing processes. Methods that identify the presence, the location and the severity of damage in the structure are useful for non-destructive evaluation procedures that are typically employed in agile manufacturing and rapid prototyping systems. The current state-of-the art techniques for these inverse problems are computationally intensive or ill conditioned when insufficient data exists. Early work by a number of researchers has shown that data mining techniques can provide a potential solution to this problem. In this paper, they investigate the use of data mining techniques for predicting failure in a variety of 2D and 3D structures using artificial neural networks (ANNs) and decision trees. This work shows that if the correct features are chosen to build the model, and the model is trained on an adequate amount of data, the model can then correctly classify the failure event as well as predict location and severity of the damage in these structures.

  5. The micro-mechanics of strength, durability and damage tolerance in composites: new insights from high resolution computed tomography

    NASA Astrophysics Data System (ADS)

    Spearing, S. Mark; Sinclair, Ian

    2016-07-01

    Recent work, led by the authors, on impact damage resistance, particle toughening and tensile fibre failure is reviewed in order to illustrate the use of high-resolution X-ray tomography to observe and quantify damage mechanisms in carbon fibre composite laminates. Using synchrotron and micro-focus X-ray sources resolutions of less than 1 μm have been routinely achieved. This enables individual broken fibres and the micromechanisms of particle toughening to be observed and quantified. The data for fibre failure, cluster formation and overall tensile strength are compared with model predictions. This allows strategies for future model development to be identified. The overall implications for using such high-resolution 3-D measurements to inform a “data-rich mechanics” approach to materials evaluation and modeling is discussed.

  6. 3,6-O-[N-(2-Aminoethyl)-acetamide-yl]-chitosan exerts antibacterial activity by a membrane damage mechanism.

    PubMed

    Yan, Feilong; Dang, Qifeng; Liu, Chengsheng; Yan, Jingquan; Wang, Teng; Fan, Bing; Cha, Dongsu; Li, Xiaoli; Liang, Shengnan; Zhang, Zhenzhen

    2016-09-20

    A novel chitosan derivative, 3,6-O-[N-(2-aminoethyl)-acetamide-yl]-chitosan (AACS), was successfully prepared to improve water solubility and antibacterial activity of chitosan. AACS had good antibacterial activity, with minimum inhibitory concentrations of 0.25mg/mL, against Escherichia coli and Staphylococcus aureus. Cell membrane integrity, electric conductivity and NPN uptake tests showed that AACS caused quickly increasing the release of intracellular nucleic acids, the uptake of NPN, and the electric conductivity by damaging membrane integrity. On the other hand, hydrophobicity, cell viability and SDS-PAGE experiments indicated that AACS was able to reduce the surface hydrophobicity, the cell viability and the intracellular proteins through increasing membrane permeability. SEM observation further confirmed that AACS could kill bacteria via disrupting their membranes. All results above verified that AACS mainly exerted antibacterial activity by a membrane damage mechanism, and it was expected to be a new food preservative. PMID:27261735

  7. Characterization and mechanisms of photoageing-related changes in skin. Damages of basement membrane and dermal structures.

    PubMed

    Amano, Satoshi

    2016-08-01

    Sun-exposed skin is characterized by superficial changes such as wrinkles, sagging and pigmentary changes, and also many internal changes in the structure and function of epidermis, basement membrane (BM) and dermis. These changes (so-called photoageing) are predominantly induced by the ultraviolet (UV) component of sunlight. Epidermis of UV-irradiated skin produced several enzymes such as matrix metalloproteinases (MMPs), urinary plasminogen activator (uPA)/plasmin and heparanase, which degrade dermal collagen fibres and elastic fibres in the dermis, and components of epidermal BM. The BM at the dermal-epidermal junction (DEJ) controls dermal-epidermal signalling and plays an important role in the maintenance of a healthy epidermis and dermis. BM is repetitively damaged in sun-exposed skin compared with unexposed skin, leading to epidermal and dermal deterioration and accelerated skin ageing. UV exposure also induces an increase in vascular endothelial growth factor (VEGF), an angiogenic factor, while thrombospondin-1 (TSP-1), an anti-angiogenic factor, is decreased; these changes induce angiogenesis in papillary dermis with increased migration of elastase-positive leucocytes, leading to dermal elastic fibre damage. Elastic fibres, such as oxytalan fibres in papillary dermis, are associated with not only skin resilience, but also skin surface texture, and elastic fibre formation by fibroblasts is facilitated by increased expression of fibulin-5. Thus, induction of fibulin-5 expression is a damage-repair mechanism, and fibulin-5 is an early marker of photoaged skin. UV-induced skin damage is cumulative and leads to premature ageing of skin. However, appropriate daily skincare may ameliorate photoageing by inhibiting processes causing damage and enhancing repair processes. PMID:27539897

  8. A mixed damage model for unsaturated porous media

    NASA Astrophysics Data System (ADS)

    Arson, Chloé; Gatmiri, Behrouz

    2009-02-01

    The aim of this study is to present a framework for the modeling of damage in continuous unsaturated porous geomaterials. The damage variable is a second-order tensor. The model is formulated in net stress and suction independent state variables. Correspondingly, the strain tensor is split into two independent thermodynamic strain components. The proposed framework mixes micro-mechanical and phenomenological approaches. On the one hand, the effective stress concept of Continuum Damage Mechanics is used in order to compute the damaged rigidities. On the other hand, the concept of equivalent mechanical state is introduced in order to get a simple phenomenological formulation of the behavior laws. Cracking effects are also taken into account in the fluid transfer laws. To cite this article: C. Arson, B. Gatmiri, C. R. Mecanique 337 (2009).

  9. Protective Effect of Sinapine against Hydroxyl Radical-Induced Damage to Mesenchymal Stem Cells and Possible Mechanisms.

    PubMed

    Li, Xican; Han, Lu; Li, Yunrong; Zhang, Jing; Chen, Jiemin; Lu, Wenbiao; Zhao, Xiaojun; Lai, Yingtao; Chen, Dongfeng; Wei, Gang

    2016-01-01

    As a phenolic alkaloid occurring in Cruciferous plants, sinapine was observed to protect mesenchymal stem cells (MSCs) against ·OH-induced damage in this study. It was also found to prevent DNA from damage, to scavenge various free radicals (·OH, ·O2(-), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt) (ABTS)(+·), and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·)), and to reduce Cu(2+) to Cu(+). To further explore the mechanism, the end-product of sinapine reaction with DPPH· was determined using HPLC-electrospray ionization (ESI)-MS/MS and HPLC-diode array detector (DAD). Four molecular ion peaks (m/z 701, 702, 703, and 351) in HPLC-ESI-MS/MS analysis indicated a radical adduct formation (RAF) pathway; while a bathochromic shift (λ(max) 334→475 nm) in HPLC-DAD indicated the formation of quinone as the oxidized product of the phenolic -OH group. Based on these results, it may be concluded that, (i) sinapine can effectively protect against ·OH-induced damage to DNA and MSCs; such protective effect may provide evidence for a potential role for sinapine in MSC transplantation therapy, and be responsible for the beneficial effects of Cruciferous plants. (ii) The possible mechanism for sinapine to protect against ·OH-induced oxidative damage is radical-scavenging, which is thought to be via hydrogen atom (H·) transfer (HAT) (or sequential electron (e) proton transfer (SEPT))→RAF pathways.

  10. Computer simulation of initial events in the biochemical mechanisms of DNA damage

    NASA Technical Reports Server (NTRS)

    Chatterjee, A.; Holley, W. R.

    1993-01-01

    Understanding the systematic and quantitative correlation between the physical events of energy deposition by ionizing radiation and the ensuing chemical and biochemical processes leading to DNA damage is one of the goals in radiation research. Significant progress has been made toward achieving the stated goal by using theoretical modeling techniques. These techniques are strongly dependent on computer simulation procedures. A review of such techniques with details of various stages of simulation development, including a comparison with available experimental data, is presented in this article.

  11. Computer simulation of initial events in the biochemical mechanisms of DNA damage.

    PubMed

    Chatterjee, A; Holley, W R

    1993-01-01

    Understanding the systematic and quantitative correlation between the physical events of energy deposition by ionizing radiation and the ensuing chemical and biochemical processes leading to DNA damage is one of the goals in radiation research. Significant progress has been made toward achieving the stated goal by using theoretical modeling techniques. These techniques are strongly dependent on computer simulation procedures. A review of such techniques with details of various stages of simulation development, including a comparison with available experimental data, is presented in this article. PMID:11537895

  12. Real internal microstructure based key mechanism analysis on the micro-damage process of short fibre-reinforced composites

    NASA Astrophysics Data System (ADS)

    Hu, Xiaofang; Fang, Jian; Xu, Feng; Dong, Bo; Xiao, Yu; Wang, Luobin

    2016-10-01

    In this work, the underlying micro-damage mechanisms of randomly oriented short fibre-reinforced composites were revealed based on real internal microstructural characteristics obtained by high-resolution (0.7 μm/pixel) synchrotron radiation X-ray computed tomography (SR-CT). The special ‘pore dominant micro-damage processes’ were directly observed through SR-CT three-dimensional reconstructed images, which were different from the well-known ‘fibre breakage dominant failure mode’. The mechanisms of pore formation and pore evolution were further investigated on the basis of the microstructural parameters extracted from the SR-CT results. On one hand, the pore formation mechanism caused by shear stress concentration was proposed by combining the shear-lag model with the microstructural parameters obtained from the experiment, including the fibre length and orientation angle. On the other hand, the ‘fibre-end aggregation-induced pore connection’ mode of crack initiation was proposed through a composites model, which considered the parameters of real internal microstructure, including the critical value of the distance between neighbouring fibre ends and the number of neighbouring fibre ends. The study indicated that the shear stress concentration was significant in the region with a large number of neighbouring fibre ends, thus causing pore connection and crack initiation.

  13. Real internal microstructure based key mechanism analysis on the micro-damage process of short fibre-reinforced composites

    PubMed Central

    Hu, Xiaofang; Fang, Jian; Xu, Feng; Dong, Bo; Xiao, Yu; Wang, Luobin

    2016-01-01

    In this work, the underlying micro-damage mechanisms of randomly oriented short fibre-reinforced composites were revealed based on real internal microstructural characteristics obtained by high-resolution (0.7 μm/pixel) synchrotron radiation X-ray computed tomography (SR-CT). The special ‘pore dominant micro-damage processes’ were directly observed through SR-CT three-dimensional reconstructed images, which were different from the well-known ‘fibre breakage dominant failure mode’. The mechanisms of pore formation and pore evolution were further investigated on the basis of the microstructural parameters extracted from the SR-CT results. On one hand, the pore formation mechanism caused by shear stress concentration was proposed by combining the shear-lag model with the microstructural parameters obtained from the experiment, including the fibre length and orientation angle. On the other hand, the ‘fibre-end aggregation-induced pore connection’ mode of crack initiation was proposed through a composites model, which considered the parameters of real internal microstructure, including the critical value of the distance between neighbouring fibre ends and the number of neighbouring fibre ends. The study indicated that the shear stress concentration was significant in the region with a large number of neighbouring fibre ends, thus causing pore connection and crack initiation. PMID:27713472

  14. Structure and mechanism of the UvrA-UvrB DNA damage sensor.

    PubMed

    Pakotiprapha, Danaya; Samuels, Martin; Shen, Koning; Hu, Johnny H; Jeruzalmi, David

    2012-03-01

    Nucleotide excision repair (NER) is used by all organisms to eliminate DNA lesions. We determined the structure of the Geobacillus stearothermophilus UvrA-UvrB complex, the damage-sensor in bacterial NER and a new structure of UvrA. We observe that the DNA binding surface of UvrA, previously found in an open shape that binds damaged DNA, also exists in a closed groove shape compatible with native DNA only. The sensor contains two UvrB molecules that flank the UvrA dimer along the predicted path for DNA, ~80 Å from the lesion. We show that the conserved signature domain II of UvrA mediates a nexus of contacts among UvrA, UvrB and DNA. Further, in our new structure of UvrA, this domain adopts an altered conformation while an adjacent nucleotide binding site is vacant. Our findings raise unanticipated questions about NER and also suggest a revised picture of its early stages. PMID:22307053

  15. Structure and mechanism of the UvrA-UvrB DNA damage sensor

    SciTech Connect

    Pakotiprapha, Danaya; Samuels, Martin; Shen, Koning; Hu, Johnny H; Jeruzalmi, David

    2012-04-17

    Nucleotide excision repair (NER) is used by all organisms to eliminate DNA lesions. We determined the structure of the Geobacillus stearothermophilus UvrA-UvrB complex, the damage-sensor in bacterial NER and a new structure of UvrA. We observe that the DNA binding surface of UvrA, previously found in an open shape that binds damaged DNA, also exists in a closed groove shape compatible with native DNA only. The sensor contains two UvrB molecules that flank the UvrA dimer along the predicted path for DNA, ~80 Å from the lesion. We show that the conserved signature domain II of UvrA mediates a nexus of contacts among UvrA, UvrB and DNA. Further, in our new structure of UvrA, this domain adopts an altered conformation while an adjacent nucleotide binding site is vacant. Our findings raise unanticipated questions about NER and also suggest a revised picture of its early stages.

  16. Fundamental mechanisms of DNA radiosensitization: damage induced by low-energy electrons in brominated oligonucleotide trimers.

    PubMed

    Park, Yeunsoo; Polska, Katarzyna; Rak, Janusz; Wagner, J Richard; Sanche, Léon

    2012-08-16

    The replacement of nucleobases with brominated analogs enhances DNA radiosensitivity. We examine the chemistry of low-energy electrons (LEEs) in this sensitization process by experiments with thin films of the oligonucleotide trimers TBrXT, where BrX = 5-BrU (5-bromouracil), 5-BrC (5-bromocytosine), 8-BrA (8-bromoadenine), or 8-BrG (8-bromoguanine). The products induced from irradiation of thin (∼ 2.5 nm) oligonucleotide films, with 10 eV electrons, under ultrahigh vacuum (UHV) are analyzed by HPLC-UV. The number of damaged brominated trimers ranges from about 12 to 15 × 10(-3) molecules per incident electron, whereas under the identical conditions, these numbers drop to 4-7 × 10(-3) for the same, but nonbrominated oligonucleotides. The results of HPLC analysis show that the main degradation pathway of trinucleotides containing brominated bases involve debromination (i.e., loss of the bromine atom and its replacement with a hydrogen atom). The electron-induced sum of products upon bromination increases by factors of 2.1 for the pyrimidines and 3.2 for the purines. Thus, substitution of any native nucleobase with a brominated one in simple models of DNA increases LEE-induced damage to DNA and hence its radiosensitivity. Furthermore, besides the brominated pyrimidines that have already been tested in clinical trials, brominated purines not only appear to be promising sensitizers for radiotherapy, but could provide a higher degree of radiosensitization.

  17. Membrane damage by hemolytic viruses, toxins, complement, and other cytotoxic agents. A common mechanism blocked by divalent cations.

    PubMed

    Bashford, C L; Alder, G M; Menestrina, G; Micklem, K J; Murphy, J J; Pasternak, C A

    1986-07-15

    Hemolytic viruses, bacterial and animal toxins, the components of activated complement, cationic proteins, and detergents induce a sequence of permeability changes at the plasma membrane that are in every case sensitive to changes in ionic strength and to divalent cations. Individually, each agent exhibits positive cooperativity; when two agents are present together, they show synergy. It is concluded that such cytotoxic agents damage membranes by a common mechanism. Hence permeability changes are unlikely to depend on the formation of specific, protein-lined channels, as previously envisaged in the case of activated complement or certain bacterial toxins.

  18. Damage mechanisms characterization of carbon fiber/epoxy composite laminates by both electrical resistance measurements and acoustic emission analysis

    SciTech Connect

    Ceysson, O.; Salvia, M.; Vincent, L.

    1996-04-15

    Carbon fiber reinforced plastics (CFRP) offer high specific mechanical properties (performance vs weight ratio). Since carbon fibers are electrical conductors ({rho} = 2.10{sup {minus}5} {Omega}.m), the measurement of the variations of electrical resistance appears to be a valuable technique for damage detection. In the case of CFRP samples, conductivity is not isotropic but depends on the orientation of the carbon fibers. The electrical conduction of (0{degree}) unidirectional (UD) CFRP parallel to the fibers is due to the current flow along the fibers. This can be modeled using the parallel resistance approach. In this present work, the variation of the electrical conductivity can be taken as an indicator of the evolution of various types of damage in classical longitudinal UD but also in ({+-} 45{degree}) CFRP laminates. By comparison with a more classical non-destructive technique such as Acoustic Emission, it has been shown that it is possible that the electrical resistance measurement allows one to monitor in-situ the evolution of various internal damage nucleation and growth in CFRP such as fiber fractures, intraply matrix cracks and interply delaminations.

  19. Square-wave adsorptive voltammetry of dexamethasone: redox mechanism, kinetic properties, and electroanalytical determinations in multicomponent formulations.

    PubMed

    Oliveira, Thiago Mielle B F; Ribeiro, Francisco Wirley P; Soares, Janete E S; de Lima-Neto, Pedro; Correia, Adriana N

    2011-06-15

    The electrochemical reduction behavior of dexamethasone at a hanging mercury drop electrode was investigated by cyclic and square-wave adsorptive voltammetries in a Britton-Robinson buffer at pH 2.0. The optimized experimental conditions consisted of a pulse potential frequency of 100 s(-1), a pulse amplitude of 15 mV, and a potential step height of 2 mV, with E(acc)=-0.60V and t(acc)=15s. From these parameters, it was also possible to develop a detailed study about the kinetic and mechanistic events involved in the reduction process. Two well-defined peaks were observed in the cathodic scan, and peak 2 was used to obtain analytical curves. A linear range between 4.98×10(-8) and 6.10×10(-7)mol L(-1), with a detection limit of 2.54×10(-9)mol L(-1) and a quantification limit of 8.47×10(-9)mol L(-1), was observed. Moreover, it was possible to achieve a simple, selective, and versatile methodology adaptable to the quantification of dexamethasone because common excipients used in multicomponent commercial formulations caused no interference. The satisfactory recoveries and the low relative standard deviation data reflected the high accuracy and precision of the proposed method for the determination of dexamethasone in injectable eye drops and elixir samples.

  20. How much can disaster and climate science contribute to loss and damage mechanisms in international climate policy?

    NASA Astrophysics Data System (ADS)

    Huggel, Christian; Allen, Simon; Eicken, Hajo; Hansen, Gerrit; Stone, Dáithí

    2015-04-01

    As the 5th Assessment Report of the Intergovernmental Panel on Climate Change (IPCC) recently has shown, there is increasing evidence of observed impacts of climate change on natural and human systems. Some of these impacts are negative and result in damage and loss of lives and assets. In international climate policy negotiations under the UNFCCC the discussions on loss and damage have gained significant traction during the past negotiation rounds. At COP 19 the Warsaw International Mechanism for Loss and Damage (WIM) was created as an institutional arrangement to address this issue. Thereby, loss and damage (L&D) are typically defined as the residual damage and loss that occur beyond mitigation and adaptation efforts. This implies that effective mitigation and adaptation policy can substantially reduce L&D. While there is wide agreement that knowledge and understanding needs to be strengthened on how L&D due to climate change affects countries, in particular highly vulnerable countries and populations, there is still substantial disagreement on several aspects. In fact, after COP20 in Lima a number of options are on the table, including whether L&D should be located under the adaptation framework or form a separate institutional arrangement, or whether a compensation regime should be established to support developing countries. Similarly, the scientific framework for a clear L&D concept, its application in real-world cases, and implications for international climate policy, in particular with respect to questions of responsibility, liability, compensation and financing, is still evolving. Earlier proposals, for instance, have included a threshold concept, with payments released upon crossing of certain thresholds of climate (related) parameters, similar to insurance procedures. The threshold would be defined as a departure of the parameter from baseline conditions, for instance a rainfall event that is more intense than a certain baseline based threshold. Further

  1. An automated dynamic fracture procedure and a continuum damage mechanics based model for finite element simulations of delamination failure in laminated composites

    NASA Astrophysics Data System (ADS)

    Aminjikarai Vedagiri, Srinivasa Babu

    explicitly in the model induces spurious high-frequency oscillations in the finite element results after crack initiation, a "gradual nodal release" procedure is implemented as part of the model to overcome this problem. Also, an in-built contact algorithm of DYNA3D is modified to adapt it to the remeshing strategy to maintain proper contact conditions at newly added elements. Finally, the model is suitably modified for simulating delamination failure in laminated composites and used to predict delamination resistance characteristics which are important considerations for effective use of composite structures. Continuum damage mechanics is a popular approach for modeling the in-plane failure modes in composites. However, its applicability to modeling delamination has not been sufficiently analyzed yet. Hence, as the second part of this dissertation work, a new material model is developed for unidirectional polymer matrix composites in which this approach is used to predict delamination failure and used to perform a qualitative study of the damage mechanics approach to modeling delamination. The new material model is developed using micro-mechanics and accounts for the strain-rate dependent behavior of polymer matrix composites. It is implemented for three different element formulations with different transverse shear strain assumptions and the effect of these assumptions on the delamination prediction using this approach is analyzed.

  2. Ichthyophonus-induced cardiac damage: a mechanism for reduced swimming stamina in salmonids

    USGS Publications Warehouse

    Kocan, R.; LaPatra, S.; Gregg, J.; Winton, J.; Hershberger, P.

    2006-01-01

    Swimming stamina, measured as time-to-fatigue, was reduced by approximately two-thirds in rainbow trout experimentally infected with Ichthyophonus. Intensity of Ichthyophonus infection was most severe in cardiac muscle but multiple organs were infected to a lesser extent. The mean heart weight of infected fish was 40% greater than that of uninfected fish, the result of parasite biomass, infiltration of immune cells and fibrotic (granuloma) tissue surrounding the parasite. Diminished swimming stamina is hypothesized to be due to cardiac failure resulting from the combination of parasite-damaged heart muscle and low myocardial oxygen supply during sustained aerobic exercise. Loss of stamina in Ichthyophonus-infected salmonids could explain the poor performance previously reported for wild Chinook and sockeye salmon stocks during their spawning migration. ?? 2006 Blackwell Publishing Ltd.

  3. Mechanism for radiation damage resistance in yttrium oxide dispersion strengthened steels

    NASA Astrophysics Data System (ADS)

    Brodrick, J.; Hepburn, D. J.; Ackland, G. J.

    2014-02-01

    ODS steels based on yttrium oxide have been suggested as potential fusion reactor wall materials due to their observed radiation resistance properties. Presumably this radiation resistance can be related to the interaction of the particle with vacancies, self-interstitial atoms (SIAs) and other radiation damage debris. Density functional theory has been used to investigate this at the atomic scale. Four distinct interfaces, some based on HRTEM observations, between iron and yttrium oxide were investigated. It is been shown that the Y2O3-Fe interface acts as a strong trap with long-range attraction for both interstitial and vacancy defects, allowing recombination without altering the interface structure. The catalytic elimination of defects without change to the microstructure explains the improved behaviour of ODS steels with respect to radiation creep and swelling.

  4. Twist-open mechanism of DNA damage recognition by the Rad4/XPC nucleotide excision repair complex.

    PubMed

    Velmurugu, Yogambigai; Chen, Xuejing; Slogoff Sevilla, Phillip; Min, Jung-Hyun; Ansari, Anjum

    2016-04-19

    DNA damage repair starts with the recognition of damaged sites from predominantly normal DNA. In eukaryotes, diverse DNA lesions from environmental sources are recognized by the xeroderma pigmentosum C (XPC) nucleotide excision repair complex. Studies of Rad4 (radiation-sensitive 4; yeast XPC ortholog) showed that Rad4 "opens" up damaged DNA by inserting a β-hairpin into the duplex and flipping out two damage-containing nucleotide pairs. However, this DNA lesion "opening" is slow (˜5-10 ms) compared with typical submillisecond residence times per base pair site reported for various DNA-binding proteins during 1D diffusion on DNA. To address the mystery as to how Rad4 pauses to recognize lesions during diffusional search, we examine conformational dynamics along the lesion recognition trajectory using temperature-jump spectroscopy. Besides identifying the ˜10-ms step as the rate-limiting bottleneck towards opening specific DNA site, we uncover an earlier ˜100- to 500-μs step that we assign to nonspecific deformation (unwinding/"twisting") of DNA by Rad4. The β-hairpin is not required to unwind or to overcome the bottleneck but is essential for full nucleotide-flipping. We propose that Rad4 recognizes lesions in a step-wise "twist-open" mechanism, in which preliminary twisting represents Rad4 interconverting between search and interrogation modes. Through such conformational switches compatible with rapid diffusion on DNA, Rad4 may stall preferentially at a lesion site, offering time to open DNA. This study represents the first direct observation, to our knowledge, of dynamical DNA distortions during search/interrogation beyond base pair breathing. Submillisecond interrogation with preferential stalling at cognate sites may be common to various DNA-binding proteins. PMID:27035942

  5. Computational simulations of flow dynamics and blood damage through a bileaflet mechanical heart valve scaled to pediatric size and flow.

    PubMed

    Yun, B Min; McElhinney, Doff B; Arjunon, Shiva; Mirabella, Lucia; Aidun, Cyrus K; Yoganathan, Ajit P

    2014-09-22

    Despite pressing needs, there are currently no FDA approved prosthetic valves available for use in the pediatric population. This study is performed for predictive assessment of blood damage in bileaflet mechanical heart valves (BMHVs) with pediatric sizing and flow conditions. A model of an adult-sized 23 mm St. Jude Medical (SJM) Regent(™) valve is selected for use in simulations, which is scaled in size for a 5-year old child and 6-month old infant. A previously validated lattice-Boltzmann method (LBM) is used to simulate pulsatile flow with thousands of suspended platelets for cases of adult, child, and infant BMHV flows. Adult BMHV flows demonstrate more disorganized small-scale flow features, but pediatric flows are associated with higher fluid shear stresses. Platelet damage in the pediatric cases is higher than in adult flow, highlighting thrombus complication dangers of pediatric BMHV flows. This does not necessarily suggest clinically important differences in thromboembolic potential. Highly damaged platelets in pediatric flows are primarily found far downstream of the valve, as there is less flow recirculation in pediatric flows. In addition, damage levels are well below expected thresholds for platelet activation. The extent of differences here documented between the pediatric and adult cases is of concern, demanding particular attention when pediatric valves are designed and manufactured. However, the differences between the pediatric and adult cases are not such that development of pediatric sized valves is untenable. This study may push for eventual approval of prosthetic valves resized for the pediatric population. Further studies will be necessary to determine the validity and potential thrombotic and clinical implications of these findings. PMID:25011622

  6. Twist-open mechanism of DNA damage recognition by the Rad4/XPC nucleotide excision repair complex

    PubMed Central

    Velmurugu, Yogambigai; Chen, Xuejing; Slogoff Sevilla, Phillip; Min, Jung-Hyun; Ansari, Anjum

    2016-01-01

    DNA damage repair starts with the recognition of damaged sites from predominantly normal DNA. In eukaryotes, diverse DNA lesions from environmental sources are recognized by the xeroderma pigmentosum C (XPC) nucleotide excision repair complex. Studies of Rad4 (radiation-sensitive 4; yeast XPC ortholog) showed that Rad4 “opens” up damaged DNA by inserting a β-hairpin into the duplex and flipping out two damage-containing nucleotide pairs. However, this DNA lesion “opening” is slow (˜5–10 ms) compared with typical submillisecond residence times per base pair site reported for various DNA-binding proteins during 1D diffusion on DNA. To address the mystery as to how Rad4 pauses to recognize lesions during diffusional search, we examine conformational dynamics along the lesion recognition trajectory using temperature-jump spectroscopy. Besides identifying the ˜10-ms step as the rate-limiting bottleneck towards opening specific DNA site, we uncover an earlier ˜100- to 500-μs step that we assign to nonspecific deformation (unwinding/“twisting”) of DNA by Rad4. The β-hairpin is not required to unwind or to overcome the bottleneck but is essential for full nucleotide-flipping. We propose that Rad4 recognizes lesions in a step-wise “twist-open” mechanism, in which preliminary twisting represents Rad4 interconverting between search and interrogation modes. Through such conformational switches compatible with rapid diffusion on DNA, Rad4 may stall preferentially at a lesion site, offering time to open DNA. This study represents the first direct observation, to our knowledge, of dynamical DNA distortions during search/interrogation beyond base pair breathing. Submillisecond interrogation with preferential stalling at cognate sites may be common to various DNA-binding proteins. PMID:27035942

  7. Antagonizing Effects and Mechanisms of Afzelin against UVB-Induced Cell Damage

    PubMed Central

    Shin, Seoung Woo; Jung, Eunsun; Kim, Seungbeom; Kim, Jang-Hyun; Kim, Eui-Gyun; Lee, Jongsung; Park, Deokhoon

    2013-01-01

    Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in human keratinocytes, resulting in skin inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effects of UV irradiation is essential. Therefore, in this study, we investigated the protective effects of afzelin, one of the flavonoids, against UV irradiation in human keratinocytes and epidermal equivalent models. Spectrophotometric measurements revealed that the afzelin extinction maxima were in the UVB and UVA range, and UV transmission below 376 nm was <10%, indicating UV-absorbing activity of afzelin. In the phototoxicity assay using the 3T3 NRU phototoxicity test (3T3-NRU-PT), afzelin presented a tendency to no phototoxic potential. In addition, in order to investigate cellular functions of afzelin itself, cells were treated with afzelin after UVB irradiation. In human keratinocyte, afzelin effectively inhibited the UVB-mediated increase in lipid peroxidation and the formation of cyclobutane pyrimidine dimers. Afzelin also inhibited UVB-induced cell death in human keratinocytes by inhibiting intrinsic apoptotic signaling. Furthermore, afzelin showed inhibitory effects on UVB-induced release of pro-inflammatory mediators such as interleukin-6, tumor necrosis factor-α, and prostaglandin-E2 in human keratinocytes by interfering with the p38 kinase pathway. Using an epidermal equivalent model exposed to UVB radiation, anti-apoptotic activity of afzelin was also confirmed together with a photoprotective effect at the morphological level. Taken together, our results suggest that afzelin has several cellular activities such as DNA-protective, antioxidant, and anti-inflammatory as well as UV-absorbing activity and may protect human skin from UVB-induced damage by a combination of UV-absorbing and cellular activities. PMID:23626759

  8. Casein films: effects of formulation, environmental conditions, and addition of citric pectin on the structure and mechanical properties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Thin casein films for food packaging applications reportedly possess good strength and low oxygen permeability, but low water-resistance and elasticity. Modifying and customizing the mechanical properties of the films to target specific behaviors depending on environmental conditions would enable a...

  9. Mechanical Response of Stitched T300 Mat/Urethane 420 IMR Composite Laminates: Property/Orientation Dependence and Damage Evolution

    SciTech Connect

    Deng, S.; Weitsman, Y.J.

    2000-03-01

    This report presents experimental and analytical results of investigations on the mechanical response of stitched T300 mat/urethane 420 IMR composite laminates with three different lay-up configurations. Tensile tests and short-term creep and recovery tests were conducted on the laminate coupons at various orientations. The X-ray photographic technique was adopted to detect the internal damage due to external loading history. The tensile data of laminates with antisymmetric and symmetric lay-ups indicated that lay- up sequences of cross-ply laminates do not have much influence on their tensile properties. However, misalignments within the stitch-bonded plies disturb the symmetry of intended quasi-isotropic laminates and thereby cause the mechanical properties to exhibit a certain amount of angular dependence. Classic lamination theory was found to be able to provide a very good prediction of tensile properties for the stitched laminates within linear range. Creep and recovery response of laminate coupons is greatly dependent on loading angles and load levels. The internal damage of laminate coupons is also directly related to loading angles and load levels as well as loading history.

  10. TREATMENT OF HYDROCARBON, ORGANIC RESIDUE AND PRODUCTION CHEMICAL DAMAGE MECHANISMS THROUGH THE APPLICATION OF CARBON DIOXIDE IN NATURAL GAS STORAGE WELLS

    SciTech Connect

    Lawrence J. Pekot; Ron Himes

    2004-05-31

    Core specimens and several material samples were collected from two natural gas storage reservoirs. Laboratory studies were performed to characterize the samples that were believed to be representative of a reservoir damage mechanism previously identified as arising from the presence of hydrocarbons, organic residues or production chemicals. A series of laboratory experiments were performed to identify the sample materials, use these materials to damage the flow capacity of the core specimens and then attempt to remove or reduce the induced damage using either carbon dioxide or a mixture of carbon dioxide and other chemicals. Results of the experiments showed that pure carbon dioxide was effective in restoring flow capacity to the core specimens in several different settings. However, in settings involving asphaltines as the damage mechanism, both pure carbon dioxide and mixtures of carbon dioxide and other chemicals provided little effectiveness in damage removal.

  11. The effect of thermal damage on the mechanical properties of polymer regrinds

    NASA Technical Reports Server (NTRS)

    Kundu, Nikhil K.

    1990-01-01

    Reprocessed polymers are subjected to high processing temperatures that result in the breakdown of molecular chains and changes in the molecular structures. These phenomena are reflected in the mechanical properties of materials. Practically every regrind is seen as a new material. These experiments deal with the molding, regrinding, and reprocessing of test specimens for the study of their mechanical properties. The comparative test data from each recycled material would give students an insight of the molecular structures and property degradation. Three important rheological and mechanical properties such as melt flow, impact strength, and flexural strength are to be determined. These properties play key roles in the selection of engineering materials. The material selected for demonstration was Makrolon 3000L, a polycarbonate thermoplastic from Bayer AG. The thermal degradation due to repeated processing is reflected in the decrease in molecular weight and breakdown of molecular chains causing increase in melt flow. The Izod-impact resistance and the flexural strength deteriorate gradually.

  12. Investigation of surface damage precursor evolutions and laser-induced damage threshold improvement mechanism during Ion beam etching of fused silica.

    PubMed

    Shi, Feng; Zhong, Yaoyu; Dai, Yifan; Peng, Xiaoqiang; Xu, Mingjin; Sui, Tingting

    2016-09-01

    Surface damage precursor evolution has great influence on laser-induced damage threshold improvement of fused silica surface during Ion beam etching. In this work, a series of ion sputtering experiment are carried out to obtain the evolutions of damage precursors (dot-form microstructures, Polishing-Induced Contamination, Hertz scratches, and roughness). Based on ion sputtering theory, surface damage precursor evolutions are analyzed. The results show that the dot-form microstructures will appear during ion beam etching. But as the ion beam etching depth goes up, the dot-form microstructures can be mitigated. And ion-beam etching can broaden and passivate the Hertz scratches without increasing roughness value. A super-smooth surface (0.238nm RMS) can be obtained finally. The relative content of Fe and Ce impurities both significantly reduce after ion beam etching. The laser-induced damage threshold of fused silica is improved by 34% after ion beam etching for 800nm. Research results can be a reference on using ion beam etching process technology to improve laser-induced damage threshold of fused silica optics. PMID:27607688

  13. Numerical investigation of the hydro-mechanical contribution to seismic attenuation in damaged rocks

    NASA Astrophysics Data System (ADS)

    Pollmann, Nele; Jänicke, Ralf; Renner, Jörg; Steeb, Holger

    2016-04-01

    The investigation of hydro-mechanical processes, in particular the modeling of seismic waves in fractured porous media, is essential for the physical interpretation of data obtained from seismic exploration. Here, we specifically investigate attenuation processes in fluid-saturated porous rock containing fracture networks to identify effective hydro-mechanical properties by numerical simulation. The main purpose of this work is the characterization of the overall hydro-mechanical properties by computational homogenization. We determine an effective Skempton coefficient by investigating the fluid pressure and the solid displacement of the skeleton saturated by compressible fluids. Fracture networks are stochastically generated to mimic geological in-situ situations. The fractures are approximated as ellipses with aspect ratios up to 1/100, i.e. they constitute thin and long hydraulic conduits with high permeabilities. Simulations are designed on the material scale with and without conservation of fluid mass in the control volume. Using computational homogenization approaches, we define an effective Skempton coefficient. A range of fracture networks with different characteristic properties is studied for different varieties of fractures. On the material scale we find strongly heterogeneous pressure propagation in the fracture network and the surrounding rock, respectively. The pressure diffusion is much faster in the fracture network than in the matrix, rendering the macroscopic hydro-mechanical behavior strongly time dependent. The effective Skempton coefficient converges to an ensemble-specific instantaneous value and to 1 for long-time studies. The ultimate objective of our study is to evaluate whether constraints on the structure of fracture networks can be deduced from observations of attenuation and its frequency dependence.

  14. Exposure damage mechanisms for KCl windows in high power laser systems

    NASA Technical Reports Server (NTRS)

    Blaszuk, P. R.; Woody, B. A.; Hulse, C. O.; Davis, J. W.; Waters, J. P.

    1976-01-01

    An experimental study of the 10.6 micrometer and 0.6328 micrometer optical properties of single crystal and europium doped polycrystal is described. Significant variations in the optical properties are observed over periods of exposure up to 100 hours. Models are proposed to predict the 10.6 micrometer absorptivity for long exposure periods. Mechanical creep has been detected in both materials at high temperature.

  15. DNA-damaging disinfection byproducts: alkylation mechanism of mutagenic mucohalic acids.

    PubMed

    Gómez-Bombarelli, Rafael; González-Pérez, Marina; Arenas-Valgañón, Jorge; Céspedes-Camacho, Isaac Fabián; Calle, Emilio; Casado, Julio

    2011-10-15

    Hydroxyhalofuranones form a group of genotoxic disinfection byproduct (DBP) of increasing interest. Among them, mucohalic acids (3,4-dihalo-5-hydroxyfuran-2(5H)-one, MXA) are known mutagens that react with nucleotides, affording etheno, oxaloetheno, and halopropenal derivatives. Mucohalic acids have also found use in organic synthesis due to their high functionalization. In this work, the alkylation kinetics of mucochloric and mucobromic acids with model nucleophiles aniline and NBP has been studied experimentally. Also, the alkylation mechanism of nucleosides by MXA has been studied in silico. The results described allow us to reach the following conclusions: (i) based on the kinetic and computational evidence obtained, a reaction mechanism was proposed, in which MXA react directly with amino groups in nucleotides, preferentially attacking the exocyclic amino groups over the endocyclic aromatic nitrogen atoms; (ii) the suggested mechanism is in agreement with both the product distribution observed experimentally and the mutational pattern of MXA; (iii) the limiting step in the alkylation reaction is addition to the carbonyl group, subsequent steps occurring rapidly; and (iv) mucoxyhalic acids, the hydrolysis products of MXA, play no role in the alkylation reaction by MXA.

  16. Attenuation of rat ischemic brain damage by aged garlic extracts: a possible protecting mechanism as antioxidants.

    PubMed

    Numagami, Y; Sato, S; Ohnishi, S T

    1996-08-01

    Effects of an aged garlic extract and its thioallyl components on rat brain ischemia were examined using a middle cerebral artery occlusion model and a transient global ischemia model. In focal ischemia, an aged garlic extract, S-allyl cysteine (SAC), Allyl sulfide (AS) or Allyl disulfide (ADS) was administered 30 min prior to ischemic insult. Three days after ischemic insult, water contents of both ischemic and contralateral hemispheres were measured to assess the degree of ischemic damage. The water content of the ischemic control (no drug treatment) group was 81.50 +/- 0.07% (mean +/- SEM). It was significantly reduced with the administration of 300 mg/kg of SAC; the water content was 80.66 +/- 0.11% (P < 0.001). The histological observation using 2,3,5-triphenyltetrazolium chloride staining demonstrated that the administration of SAC reduced infarct volume. Neither AS nor ADS was effective. In global ischemia, the production of reactive oxygen species (ROS) was measured ex vivo using a spin-trapping agent, alpha-phenyl-N-tert-butylnitrone, and electron paramagnetic resonance spectroscopy. The production of ROS had two peaks; first at 5 min and second at 20 min after reperfusion. Both SAC and 7-nitro indazole, a nitric oxide synthase inhibitor, did not attenuate the amount of ROS produced at the first peak, but did the amount of the second peak. A possible involvement of peroxinitrite, which may be formed from superoxide and nitric oxide and is known to be highly toxic in ischemia/reperfusion injury of the brain, was suggested.

  17. Rapid increase in training load affects markers of skeletal muscle damage and mechanical performance.

    PubMed

    Kamandulis, Sigitas; Snieckus, Audrius; Venckunas, Tomas; Aagaard, Per; Masiulis, Nerijus; Skurvydas, Albertas

    2012-11-01

    The aim of this study was to monitor the changes in indirect markers of muscle damage during 3 weeks (9 training sessions) of stretch-shortening (drop jump) exercise with constant load alternated with steep increases in load. Physically active men (n = 9, mean age 19.1 years) performed a program involving a rapid stepwise increase in the number of jumps, drop height, and squat depth, and the addition of weight. Concentric, isometric maximal voluntary contraction (MVC), and stimulated knee extension torque were measured before and 10 minutes after each session. Muscle soreness and plasma creatine kinase activity were assessed after each session. Steep increments in stretch-shortening exercise load in sessions 4 and 7 amplified the postexercise decrease in stimulated muscle torque and slightly increased muscle soreness but had a minimal effect on the recovery of MVC and stimulated torque. Maximal jump height increased by 7.8 ± 6.3% (p < 0.05), 11.4 ± 3.3% (p < 0.05), and 12.8 ± 3.6% (p < 0.05) at 3, 10, and 17 days after the final training session, respectively. Gains in isometric knee extension MVC (7.9 ± 8.2%) and 100-Hz-evoked torque (9.9 ± 9.6%) (both p < 0.05) were observed within 17 days after the end of the training. The magnitude of improvement was greater after this protocol than that induced by a continuous constant progression loading pattern with small gradual load increments in each training session. These findings suggest that plyometric training using infrequent but steep increases in loading intensity and volume may be beneficial to athletic performance. PMID:22158097

  18. Mechanism resulting in chemical imbalance due to cellular damage associated with mechanoporation: A molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Sliozberg, Yelena R.; Chantawansri, Tanya L.

    2016-05-01

    To elucidate the mechanism of ion transport through a transmembrane pore, all-atom molecular dynamics simulations were employed. A model membrane where a pore connects the intra- and extra-cellular compartment was considered. Pores with radii of 1.5 nm or less exhibited resealing over the course of 135 ns simulations, and ionic disturbance is minimal. Ion transport through a larger pore (2 nm radius) leads to a substantial change in the intra- and extra-cellular ionic concentrations. The influx of Na+ and Cl- ions down their concentration gradients is greater than the efflux of K+ leading to an osmotic influx of water.

  19. Molecular Mechanisms of Ultraviolet Radiation-Induced DNA Damage and Repair

    PubMed Central

    Rastogi, Rajesh P.; Richa; Kumar, Ashok; Tyagi, Madhu B.; Sinha, Rajeshwar P.

    2010-01-01

    DNA is one of the prime molecules, and its stability is of utmost importance for proper functioning and existence of all living systems. Genotoxic chemicals and radiations exert adverse effects on genome stability. Ultraviolet radiation (UVR) (mainly UV-B: 280–315 nm) is one of the powerful agents that can alter the normal state of life by inducing a variety of mutagenic and cytotoxic DNA lesions such as cyclobutane-pyrimidine dimers (CPDs), 6-4 photoproducts (6-4PPs), and their Dewar valence isomers as well as DNA strand breaks by interfering the genome integrity. To counteract these lesions, organisms have developed a number of highly conserved repair mechanisms such as photoreactivation, base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR). Additionally, double-strand break repair (by homologous recombination and nonhomologous end joining), SOS response, cell-cycle checkpoints, and programmed cell death (apoptosis) are also operative in various organisms with the expense of specific gene products. This review deals with UV-induced alterations in DNA and its maintenance by various repair mechanisms. PMID:21209706

  20. Damage mechanism involved in the solid particle erosion of CVD diamond

    NASA Astrophysics Data System (ADS)

    Davies, Alun R.; Field, John E.

    2001-09-01

    Sophisticated electro-optic sensors are employed on aircraft and missiles, and it is essential to protect them from relatively high-speed impacts with airborne dust particles. A loss in transmission caused by such an event can impair guidance, and catastrophic failure may occur. Protection is afforded by the installation of a hard cover that is transparent in the relevant regime. Diamond is potentially by far the most attractive window material due to excellent optical and mechanical properties, but it is difficult to shape. Chemical vapor deposited (CVD) diamond is a polycrystalline synthetic with properties that approach those of single crystal diamond, and it can be more easily shaped. The aims of the present research were to quantify the erosion and transmission losses, and to understand the material removal mechanisms involved. Steady-state erosion rates were obtained for CVD diamond of different grain sizes, using 300-600 micrometers quartz erodent at velocities between 60 and 140 m/s. Images of CVD diamond at various stages of erosion, obtained using an optical microscope and an environmental scanning electron microscope (ESEM), reveal that erosion initially occurs at grain boundaries and that so-called micro-features also have some influence on erosion.

  1. Thermal/Mechanical Response and Damage Growth in Polymeric Composites at Cryogenic Temperatures

    NASA Technical Reports Server (NTRS)

    Whitley, Karen S.; Gates, Thomas S.

    2002-01-01

    In order to increase the reliability of the next generation of space transportation systems, the mechanical behavior of polymeric matrix composite (PMC) materials at cryogenic temperatures must be investigated. This paper presents experimental data on the residual mechanical properties of a carbon fiber polymeric composite, IM7/PETI-5 both before and after aging at cryogenic temperatures. Tension modulus and strength were measured at room temperature, -196 C, and -269 C on five different specimen ply lay-ups, [0](sub 12), [90](sub 12), [+/-45](sub 3S), [+/-25](sub 3s) and [45,90(sub 3),-45,0(sub 3),-45,90(sub 3),45]. Specimens were preconditioned with one set of coupons being isothermally aged for 555 hours at -184 C in an unloaded state. Another set of corresponding coupons were mounted in constant displacement fixtures such that a constant uniaxial strain was applied to the specimens for 555 hours at -184 C. The measured lamina level properties indicated that cryogenic temperatures have an appreciable influence on behavior, and residual stress calculations based on lamination theory showed that the transverse tensile ply stresses could be quite high for cryogenic test temperatures. Microscopic examination of the surface morphology showed evidence of degradation along the exposed edges of the material due to aging at cryogenic temperatures.

  2. Energetic laser cleaning of metallic particles and surface damage on silica optics: investigation of the underlying mechanisms

    NASA Astrophysics Data System (ADS)

    Shen, Nan; Demos, Stavros G.; Negres, Raluca A.; Rubenchik, Alexander M.; Harris, Candace D.; Matthews, Manyalibo J.

    2015-11-01

    Surface particulate contamination on optics can lead to laser-induced damage hence limit the performance of high power laser system. In this work we focus on understanding the fundamental mechanisms that lead to damage initiation by metal contaminants. Using time resolved microscopy and plasma spectroscopy, we studied the dynamic process of ejecting ~30 μm stainless steel particles from the exit surface of fused silica substrate irradiated with 1064 nm, 10 ns and 355 nm, 8 ns laser pulses. Time-resolved plasma emission spectroscopy was used to characterize the energy coupling and temperature rise associated with single, 10-ns pulsed laser ablation of metallic particles bound to transparent substrates. Plasma associated with Fe(I) emission lines originating from steel microspheres was observe to cool from <24,000 K to ~15,000 K over ~220 ns as τ-0.22, consistent with radiative losses and adiabatic gas expansion of a relatively free plasma. Simultaneous emission lines from Si(II) associated with the plasma etching of the SiO2 substrate were observed yielding higher plasma temperatures, ~35,000 K, relative to the Fe(I) plasma. The difference in species temperatures is consistent with plasma confinement at the microsphere-substrate interface as the particle is ejected, and is directly visualized using pump-probe shadowgraphy as a function of pulsed laser energy.

  3. An investigation of the effects of history dependent damage in time dependent fracture mechanics: nano-scale studies of damage evolution

    SciTech Connect

    Brust, F.W. Jr; Mohan, R.; Yang, Y.P.; Oh, J.; Katsube, N.

    2002-12-01

    High-temperature operation of technical engineering systems is critical for system efficiency, and will be a key driver in the future US DOE energy policy. Developing an understanding of high-temperature creep and creep-fatigue failure processes is a key driver for the research work described here. The focus is on understanding the high-temperature deformation and damage development on the nano-scale (50 to 500 nm) level. The high-temperature damage development process, especially with regard to low and high cyclic loading, which has received little attention to date, is studied. Damage development under cyclic loading develops in a fashion quite different from the constant load situation. The development of analytical methodologies so that high-temperature management of new systems can be realized is the key goal of this work.

  4. Formulating a Sulfonated Anti-Viral Dendrimer in a Vaginal Microbicidal Gel having Dual Mechanisms of Action

    PubMed Central

    Mumper, Russell J.; Bell, Michael A.; Worthen, David R.; Cone, Richard A.; Lewis, Gareth R.; Moench, Thomas R.

    2009-01-01

    SPL7013 is the sodium salt of a sulfonated dendrimer that has potent antiviral properties. VivaGel®, a topical gel containing 3% w/w SPL7013, has been shown to be safe and well-tolerated in human clinical studies. BufferGel® is a Carbopol®-based acidic buffering gel that enhances the natural protective action of the vagina to produce a broad-spectrum microbicidal environment. The positive attributes of both gels were combined into a combination vaginal microbicidal gel having dual mechanisms of action. A 3% w/w SPL7013 combination gel, pH 3.7, was developed and fully characterized, and was shown to have more than 2-fold greater acidic buffering capacity than BufferGel. Ultracentrifugation experiments demonstrated that SPL7013 was not sequestered or entropically trapped in the viscous gel, thereby confirming, along with viral challenge studies, that SPL7013 has sufficient mobility in the viscous gel to exert antiviral properties. PMID:19040181

  5. Evaluation of the Influence of Formulation and Process Variables on Mechanical Properties of Oral Mucoadhesive Films Using Multivariate Data Analysis

    PubMed Central

    Landová, Hana; Gajdziok, Jan; Doležel, Petr; Muselík, Jan; Dvořáčková, Kateřina; Jekl, Vladimír; Hauptman, Karel

    2014-01-01

    Oral mucosa is an attractive region for the local and systemic application of many drugs. Oral mucoadhesive films are preferred for their prolonged time of residence, the improved bioavailability of the drug they contain, their painless application, their protection against lesions, and their nonirritating properties. This work was focused on preparation of nonmedicated carmellose-based films using both solvent casting and impregnation methods, respectively. Moreover, a modern approach to evaluation of mucoadhesive films applying analysis of texture and subsequent multivariate data analysis was used. In this experiment, puncture strength strongly correlated with tensile strength and could be used to obtain necessary information about the mechanical film characteristics in films prepared using both methods. Puncture work and tensile work were not correlated in films prepared using the solvent casting method, as increasing the amount of glycerol led to an increase in the puncture work in thinner films. All measured texture parameters in films prepared by impregnation were significantly smaller compared to films prepared by solvent casting. Moreover, a relationship between the amount of glycerol and film thickness was observed, and a greater recalculated tensile/puncture strength was needed for an increased thickness in films prepared by impregnation. PMID:25136560

  6. Numerical simulation of damage evolution for ductile materials and mechanical properties study

    NASA Astrophysics Data System (ADS)

    El Amri, A.; Hanafi, I.; Haddou, M. E. Y.; Khamlichi, A.

    2015-12-01

    This paper presents results of a numerical modelling of ductile fracture and failure of elements made of 5182H111 aluminium alloys subjected to dynamic traction. The analysis was performed using Johnson-Cook model based on ABAQUS software. The modelling difficulty related to prediction of ductile fracture mainly arises because there is a tremendous span of length scales from the structural problem to the micro-mechanics problem governing the material separation process. This study has been used the experimental results to calibrate a simple crack propagation criteria for shell elements of which one has often been used in practical analyses. The performance of the proposed model is in general good and it is believed that the presented results and experimental-numerical calibration procedure can be of use in practical finite-element simulations.

  7. Unveiling Ultra-High Temperature Wear and Indentation Damage Mechanisms of Thermal Barrier Coatings

    NASA Astrophysics Data System (ADS)

    Bumgardner, Clifton; Li, Xiaodong

    2015-12-01

    Thermal barrier coatings are necessary to protect turbine blades within jet engines from extreme environments that the substrate material may not be capable of withstanding. Therefore, failure of the coating due to wear during its operational lifecycle is a critical event. In order to understand the failure mechanisms of the coating layers, a zirconia-based coating on a nickel alloy substrate was subjected to wear testing to simulate pressure and temperature conditions within a jet engine. Using a Hertzian contact model, the maximum shear and its depth were determined and analyzed in conjunction with the coating material properties and scanning electron microscopy and energy dispersive x-ray spectrometry images. The coupled imaging and contact model analyses made possible the identification of the location and time of delamination and its underlying causes. Our findings provide key insights for the development of more resilient thermal barrier coatings.

  8. Mechanisms of Vascular Damage by Hemorrhagic Snake Venom Metalloproteinases: Tissue Distribution and In Situ Hydrolysis

    PubMed Central

    Baldo, Cristiani; Jamora, Colin; Yamanouye, Norma; Zorn, Telma M.; Moura-da-Silva, Ana M.

    2010-01-01

    Background Envenoming by viper snakes constitutes an important public health problem in Brazil and other developing countries. Local hemorrhage is an important symptom of these accidents and is correlated with the action of snake venom metalloproteinases (SVMPs). The degradation of vascular basement membrane has been proposed as a key event for the capillary vessel disruption. However, SVMPs that present similar catalytic activity towards extracellular matrix proteins differ in their hemorrhagic activity, suggesting that other mechanisms might be contributing to the accumulation of SVMPs at the snakebite area allowing capillary disruption. Methodology/Principal Findings In this work, we compared the tissue distribution and degradation of extracellular matrix proteins induced by jararhagin (highly hemorrhagic SVMP) and BnP1 (weakly hemorrhagic SVMP) using the mouse skin as experimental model. Jararhagin induced strong hemorrhage accompanied by hydrolysis of collagen fibers in the hypodermis and a marked degradation of type IV collagen at the vascular basement membrane. In contrast, BnP1 induced only a mild hemorrhage and did not disrupt collagen fibers or type IV collagen. Injection of Alexa488-labeled jararhagin revealed fluorescent staining around capillary vessels and co-localization with basement membrane type IV collagen. The same distribution pattern was detected with jararhagin-C (disintegrin-like/cysteine-rich domains of jararhagin). In opposition, BnP1 did not accumulate in the tissues. Conclusions/Significance These results show a particular tissue distribution of hemorrhagic toxins accumulating at the basement membrane. This probably occurs through binding to collagens, which are drastically hydrolyzed at the sites of hemorrhagic lesions. Toxin accumulation near blood vessels explains enhanced catalysis of basement membrane components, resulting in the strong hemorrhagic activity of SVMPs. This is a novel mechanism that underlies the difference between

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

    PubMed

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

    2014-02-01

    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.

  10. Platelet Apoptosis in Adult Immune Thrombocytopenia: Insights into the Mechanism of Damage Triggered by Auto-Antibodies

    PubMed Central

    Goette, Nora P.; Glembotsky, Ana C.; Lev, Paola R.; Grodzielski, Matías; Contrufo, Geraldine; Pierdominici, Marta S.; Espasandin, Yesica R.; Riveros, Dardo; García, Alejandro J.; Molinas, Felisa C.; Heller, Paula G.

    2016-01-01

    Mechanisms leading to decreased platelet count in immune thrombocytopenia (ITP) are heterogeneous. This study describes increased platelet apoptosis involving loss of mitochondrial membrane potential (ΔΨm), caspase 3 activation (aCasp3) and phosphatidylserine (PS) externalization in a cohort of adult ITP patients. Apoptosis was not related to platelet activation, as PAC-1 binding, P-selectin exposure and GPIb-IX internalization were not increased. Besides, ITP platelets were more sensitive to apoptotic stimulus in terms of aCasp3. Incubation of normal platelets with ITP plasma induced loss of ΔΨm, while PS exposure and aCasp3 remained unaltered. The increase in PS exposure observed in ITP platelets could be reproduced in normal platelets incubated with ITP plasma by adding normal CD3+ lymphocytes to the system as effector cells. Addition of leupeptin -a cathepsin B inhibitor- to this system protected platelets from apoptosis. Increased PS exposure was also observed when normal platelets and CD3+ lymphocytes were incubated with purified IgG from ITP patients and was absent when ITP plasma was depleted of auto-antibodies, pointing to the latter as responsible for platelet damage. Apoptosis was present in platelets from all patients carrying anti-GPIIb-IIIa and anti-GPIb auto-antibodies but was absent in the patient with anti-GPIa-IIa auto-antibodies. Platelet damage inversely correlated with platelet count and decreased during treatment with a thrombopoietin receptor agonist. These results point to a key role for auto-antibodies in platelet apoptosis and suggest that antibody-dependent cell cytotoxicity is the mechanism underlying this phenomenon. PMID:27494140

  11. Platelet Apoptosis in Adult Immune Thrombocytopenia: Insights into the Mechanism of Damage Triggered by Auto-Antibodies.

    PubMed

    Goette, Nora P; Glembotsky, Ana C; Lev, Paola R; Grodzielski, Matías; Contrufo, Geraldine; Pierdominici, Marta S; Espasandin, Yesica R; Riveros, Dardo; García, Alejandro J; Molinas, Felisa C; Heller, Paula G; Marta, Rosana F

    2016-01-01

    Mechanisms leading to decreased platelet count in immune thrombocytopenia (ITP) are heterogeneous. This study describes increased platelet apoptosis involving loss of mitochondrial membrane potential (ΔΨm), caspase 3 activation (aCasp3) and phosphatidylserine (PS) externalization in a cohort of adult ITP patients. Apoptosis was not related to platelet activation, as PAC-1 binding, P-selectin exposure and GPIb-IX internalization were not increased. Besides, ITP platelets were more sensitive to apoptotic stimulus in terms of aCasp3. Incubation of normal platelets with ITP plasma induced loss of ΔΨm, while PS exposure and aCasp3 remained unaltered. The increase in PS exposure observed in ITP platelets could be reproduced in normal platelets incubated with ITP plasma by adding normal CD3+ lymphocytes to the system as effector cells. Addition of leupeptin -a cathepsin B inhibitor- to this system protected platelets from apoptosis. Increased PS exposure was also observed when normal platelets and CD3+ lymphocytes were incubated with purified IgG from ITP patients and was absent when ITP plasma was depleted of auto-antibodies, pointing to the latter as responsible for platelet damage. Apoptosis was present in platelets from all patients carrying anti-GPIIb-IIIa and anti-GPIb auto-antibodies but was absent in the patient with anti-GPIa-IIa auto-antibodies. Platelet damage inversely correlated with platelet count and decreased during treatment with a thrombopoietin receptor agonist. These results point to a key role for auto-antibodies in platelet apoptosis and suggest that antibody-dependent cell cytotoxicity is the mechanism underlying this phenomenon. PMID:27494140

  12. Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion

    PubMed Central

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-feng; Kong, Liang; Yao, Ying-Jia; Jiao, Ya-Nan; Yan, Yu-Hui; Li, Shao-Heng; Tao, Zhen-Yu; Lian, Guan; Yang, Jing-Xian; Kang, Ting-Guo

    2016-01-01

    Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary brain injury and the determination of the underlying mechanism of action in a mouse model of SWI that mimics the process of CED. After CED, mice received a gavage of ARC from 30 min to 14 days. Neurological severity scores (NSS) and wound closure degree were assessed after the injury. Histological analysis and immunocytochemistry were used to evaluated the extent of brain damage and neuroinflammation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect universal apoptosis. Enzyme-linked immunosorbent assays (ELISA) was used to test the inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10) and lactate dehydrogenase (LDH) content. Gene levels of inflammation (TNF-α, IL-6, and IL-10) and apoptosis (Caspase-3, Bax and Bcl-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Using these, we analyzed ARC’s efficacy and mechanism of action. Results: ARC treatment improved neurological function by reducing brain water content and hematoma and accelerating wound closure relative to untreated mice. ARC treatment reduced the levels of TNF-α and IL-6 and the number of allograft inflammatory factor (IBA)- and myeloperoxidase (MPO)-positive cells and increased the levels of IL-10. ARC-treated mice had fewer TUNEL+ apoptotic neurons and activated caspase-3-positive neurons surrounding the lesion than controls, indicating increased neuronal survival. Conclusions: ARC treatment confers

  13. Translesion synthesis mechanisms depend on the nature of DNA damage in UV-irradiated human cells

    PubMed Central

    Quinet, Annabel; Martins, Davi Jardim; Vessoni, Alexandre Teixeira; Biard, Denis; Sarasin, Alain; Stary, Anne; Menck, Carlos Frederico Martins

    2016-01-01

    Ultraviolet-induced 6-4 photoproducts (6-4PP) and cyclobutane pyrimidine dimers (CPD) can be tolerated by translesion DNA polymerases (TLS Pols) at stalled replication forks or by gap-filling. Here, we investigated the involvement of Polη, Rev1 and Rev3L (Polζ catalytic subunit) in the specific bypass of 6-4PP and CPD in repair-deficient XP-C human cells. We combined DNA fiber assay and novel methodologies for detection and quantification of single-stranded DNA (ssDNA) gaps on ongoing replication forks and postreplication repair (PRR) tracts in the human genome. We demonstrated that Rev3L, but not Rev1, is required for postreplicative gap-filling, while Polη and Rev1 are responsible for TLS at stalled replication forks. Moreover, specific photolyases were employed to show that in XP-C cells, CPD arrest replication forks, while 6-4PP are responsible for the generation of ssDNA gaps and PRR tracts. On the other hand, in the absence of Polη or Rev1, both types of lesion block replication forks progression. Altogether, the data directly show that, in the human genome, Polη and Rev1 bypass CPD and 6-4PP at replication forks, while only 6-4PP are also tolerated by a Polζ-dependent gap-filling mechanism, independent of S phase. PMID:27095204

  14. Probing irradiation induced DNA damage mechanisms using excited state Car-Parrinello molecular dynamics

    NASA Astrophysics Data System (ADS)

    Markwick, Phineus R. L.; Doltsinis, Nikos L.; Schlitter, Jürgen

    2007-01-01

    Photoinduced proton transfer in the Watson-Crick guanine (G)-cytosine (C) base pair has been studied using Car-Parrinello molecular dynamics (CP-MD). A flexible mechanical constraint acting on all three hydrogen bonds in an unbiased fashion has been devised to explore the free energy profile along the proton transfer coordinate. The lowest barrier has been found for proton transfer from G to C along the central hydrogen bond. The resulting charge transfer excited state lies energetically close to the electronic ground state suggesting the possibility of efficient radiationless decay. It is found that dynamic, finite temperature fluctuations significantly reduce the energy gap between the ground and excited states for this charge transfer product, promoting the internal conversion process. A detailed analysis of the internal degrees of freedom reveals that the energy gap is considerably reduced by out-of-plane molecular vibrations, in particular. Consequently, it appears that considering only the minimum energy path provides an upper-bound estimate of the associated energy gap compared to the full-dimension dynamical reaction coordinate. Furthermore, the first CP-MD simulations of the G-C base pair in liquid water are presented, and the effects of solvation on its electronic structure are analyzed.

  15. Mitigation of Shear-Induced Blood Damage of Mechanical Bileaflet Heart Valves using Embedded Vortex Generators

    NASA Astrophysics Data System (ADS)

    Hidalgo, Pablo; Arjunon, Sivakkumar; Saikrishnan, Neelakantan; Yoganathan, Ajit; Glezer, Ari

    2012-11-01

    The strong transitory shear stress generated during the time-periodic closing of the mechanical prosthetic bileaflet aortic heart valve, is considered to be one of the main factors responsible for complications, associated with thrombosis and thromboembolism. These flow transients are investigated using phase and time-averaged PIV in a low-volume (about 150 ml) test setup that simulates the pulsatile physiological conditions associated with a 23 mm St. Jude Medical valve. The PIV measurements are accompanied by continuous monitoring of the ventricular and aortic pressures and valve flow rate. Following the valve closure, the leakage flow between the valve leaflets is caused by the pressure buildup across the leaflets, leading to the formation of a regurgitation jet starting from the BMHV B-datum line. As in a typical starting jet, a counter-rotating vortex pair is formed along each leaflet edge and the vorticity sheet is associated with high shear stress that may be result in blood platelet activation. The present investigation demonstrates that the placement of arrays of mm-scale vortex generators near the edges of the leaflets diffuses the vortex sheet and suppresses the formation of these vortices, weakening the local velocity gradients and small-scale vortical structures. Supported by NIH and NSF.

  16. Global DNA hypomethylation: a potential mechanism in King pigeon nerve tissue damage induced by avermectin.

    PubMed

    Cao, Ye; Chen, Li-Jie; Zhang, Zi-wei; Yao, Hai-dong; Liu, Ci; Li, Shu; Xu, Shi-wen

    2014-08-01

    As an effective insecticidal and nematicidal agent, avermectin (AVM) has been widely used in agricultural production and stock farming areas. Subsequently, the residues of AVM or its active metabolites in animal manure pose a toxic threat to non-target organisms in the environment. As the most characteristic epigenetic phenomena, DNA methylation status is a useful biological signal for the toxicity assessment of environmental chemical toxicants. In this study, analyses of the overall level of genomic DNA methylation were performed, and the expression levels of DNA methyltransferases (DNMTs), as well as demethylase methyl-CpG-binding domain protein 2 (MBD2), in pigeon brain tissues after subchronic exposure (with a AVM concentration of 20 mg/kg, 40 mg/kg and 60 mg/kg, respectively) to AVM for 30, 60 and 90 days were investigated. Global DNA hypomethylation and down-regulation of DNMT mRNA expression occurred in a dose-time-dependent manner in pigeon brains. The expression level of MBD2, which functions as a demethylase, was significantly enhanced in a dose-dependent but not time-dependent manner. In addition, the elevated expression level of MBD2 had a more robust effect on genomic DNA hypomethylation compared to changes in DNMT expression. Taken together, these results suggested that subchronic dose exposures of AVM could affect the global DNA methylation status, and this mechanism is closely related to changes in the expression levels of DNMTs and MBD2.

  17. Combined meso-scale modeling and experimental investigation of the effect of mechanical damage on the transport properties of cementitious composites

    NASA Astrophysics Data System (ADS)

    Raghavan, Balaji; Niknezhad, Davood; Bernard, Fabrice; Kamali-Bernard, Siham

    2016-09-01

    The transport properties of cementitious composites such as concrete are important indicators of their durability, and are known to be heavily influenced by mechanical loading. In the current work, we use meso-scale hygro-mechanical modeling with a morphological 3D two phase mortar-aggregate model, in conjunction with experimentally obtained properties, to investigate the coupling between mechanical loading and damage and the permeability of the composite. The increase in permeability of a cylindrical test specimen at 28% aggregate fraction during a uniaxial displacement-controlled compression test at 85% of the peak load was measured using a gas permeameter. The mortar's mechanical behavior is assumed to follow the well-known compression damaged plasticity (CDP) model with isotropic damage, at varying thresholds, and obtained from different envelope curves. The damaged intrinsic permeability of the mortar evolves according to a logarithmic matching law with progressive loading. We fit the matching law parameters to the experimental result for the test specimen by inverse identification using our meso-scale model. We then subject a series of virtual composite specimens to quasi-static uniaxial compressive loading with varying boundary conditions to obtain the simulated damage and strain evolutions, and use the damage data and the previously identified parameters to determine the evolution of the macroscopic permeability tensor for the specimens, using a network model. We conduct a full parameter study by varying aggregate volume fraction, granulometric distribution, loading/boundary conditions and "matching law" parameters, as well as for different strain-damage thresholds and uniaxial loading envelope curves. Based on this study, we propose Avrami equation-based upper and lower bounds for the evolution of the damaged permeability of the composite.

  18. Saltcrete formulation

    SciTech Connect

    Semones, G.B.; Connell, J.M.; Jorgensen, S.C.

    1994-09-28

    The information gathered since the first report shows that the currently generated waste and most of the waste in inventory has low concentrations of hazardous chemicals and is certifiable for disposable. This is based on preliminary analyses. Sampling and analysis for the purpose of gathering the legally defensible data required for certification and permanent disposal is in progress. The main technical issue is the expansion of the waste form. Some of the cemented waste expands and damages the containers. According to a petrology study, the expansion is caused by the formation of darapskite, a nitrate-sulfate salt. Darapskite occurs when there is high porosity causing microfractures and waste form expansion.

  19. Brittle dynamic damage due to earthquake rupture

    NASA Astrophysics Data System (ADS)

    Bhat, Harsha; Thomas, Marion

    2016-04-01

    The micromechanical damage mechanics formulated by Ashby and Sammis, 1990, and generalized by Deshpande and Evans 2008 has been extended to allow for a more generalized stress state and to incorporate an experimentally motivated new crack growth (damage evolution) law that is valid over a wide range of loading rates. This law is sensitive to both the crack tip stress field and its time derivative. Incorporating this feature produces additional strain-rate sensitivity in the constitutive response. The model is also experimentally verified by predicting the failure strength of Dionysus-Pentelicon marble over wide range of strain rates. We then implement this constitutive response to understand the role of dynamic brittle off-fault damage on earthquake ruptures. We show that off-fault damage plays an important role in asymmetry of rupture propagation and is a source of high-frequency ground motion in the near source region.

  20. Mechanism of Inhibition of Human Islet Amyloid Polypeptide-Induced Membrane Damage by a Small Organic Fluorogen

    NASA Astrophysics Data System (ADS)

    Li, Xiaoxu; Wan, Mingwei; Gao, Lianghui; Fang, Weihai

    2016-02-01

    Human islet amyloid polypeptide (hIAPP) is believed to be responsible for the death of insulin-producing β-cells. However, the mechanism of membrane damage at the molecular level has not been fully elucidated. In this article, we employ coarse- grained dissipative particle dynamics simulations to study the interactions between a lipid bilayer membrane composed of 70% zwitterionic lipids and 30% anionic lipids and hIAPPs with α-helical structures. We demonstrated that the key factor controlling pore formation is the combination of peptide charge-induced electroporation and peptide hydrophobicity-induced lipid disordering and membrane thinning. According to these mechanisms, we suggest that a water-miscible tetraphenylethene BSPOTPE is a potent inhibitor to rescue hIAPP-induced cytotoxicity. Our simulations predict that BSPOTPE molecules can bind directly to the helical regions of hIAPP and form oligomers with separated hydrophobic cores and hydrophilic shells. The micelle-like hIAPP-BSPOTPE clusters tend to be retained in the water/membrane interface and aggregate therein rather than penetrate into the membrane. Electrostatic attraction between BSPOTPE and hIAPP also reduces the extent of hIAPP binding to the anionic lipid bilayer. These two modes work together and efficiently prevent membrane poration.

  1. Mechanism of Inhibition of Human Islet Amyloid Polypeptide-Induced Membrane Damage by a Small Organic Fluorogen.

    PubMed

    Li, Xiaoxu; Wan, Mingwei; Gao, Lianghui; Fang, Weihai

    2016-01-01

    Human islet amyloid polypeptide (hIAPP) is believed to be responsible for the death of insulin-producing β-cells. However, the mechanism of membrane damage at the molecular level has not been fully elucidated. In this article, we employ coarse- grained dissipative particle dynamics simulations to study the interactions between a lipid bilayer membrane composed of 70% zwitterionic lipids and 30% anionic lipids and hIAPPs with α-helical structures. We demonstrated that the key factor controlling pore formation is the combination of peptide charge-induced electroporation and peptide hydrophobicity-induced lipid disordering and membrane thinning. According to these mechanisms, we suggest that a water-miscible tetraphenylethene BSPOTPE is a potent inhibitor to rescue hIAPP-induced cytotoxicity. Our simulations predict that BSPOTPE molecules can bind directly to the helical regions of hIAPP and form oligomers with separated hydrophobic cores and hydrophilic shells. The micelle-like hIAPP-BSPOTPE clusters tend to be retained in the water/membrane interface and aggregate therein rather than penetrate into the membrane. Electrostatic attraction between BSPOTPE and hIAPP also reduces the extent of hIAPP binding to the anionic lipid bilayer. These two modes work together and efficiently prevent membrane poration. PMID:26887358

  2. Mechanism of Inhibition of Human Islet Amyloid Polypeptide-Induced Membrane Damage by a Small Organic Fluorogen

    PubMed Central

    Li, Xiaoxu; Wan, Mingwei; Gao, Lianghui; Fang, Weihai

    2016-01-01

    Human islet amyloid polypeptide (hIAPP) is believed to be responsible for the death of insulin-producing β-cells. However, the mechanism of membrane damage at the molecular level has not been fully elucidated. In this article, we employ coarse- grained dissipative particle dynamics simulations to study the interactions between a lipid bilayer membrane composed of 70% zwitterionic lipids and 30% anionic lipids and hIAPPs with α-helical structures. We demonstrated that the key factor controlling pore formation is the combination of peptide charge-induced electroporation and peptide hydrophobicity-induced lipid disordering and membrane thinning. According to these mechanisms, we suggest that a water-miscible tetraphenylethene BSPOTPE is a potent inhibitor to rescue hIAPP-induced cytotoxicity. Our simulations predict that BSPOTPE molecules can bind directly to the helical regions of hIAPP and form oligomers with separated hydrophobic cores and hydrophilic shells. The micelle-like hIAPP-BSPOTPE clusters tend to be retained in the water/membrane interface and aggregate therein rather than penetrate into the membrane. Electrostatic attraction between BSPOTPE and hIAPP also reduces the extent of hIAPP binding to the anionic lipid bilayer. These two modes work together and efficiently prevent membrane poration. PMID:26887358

  3. Mechanisms of recovery from sublethal damage and potentially lethal damage induced by BrdUrd/313 nm light treatment: alkali-labile lesions.

    PubMed Central

    Hagan, M. P.; Han, A.; Smith, V. N.

    1984-01-01

    BrdUrd pulse labelling of synchronous Chinese hamster cell cultures was used to correlate repair of sublethal damage with removal of alkali-labile lesions. Both processes were modified in a quantitatively similar manner by cysteamine. In addition, the age responses for repair of sublethal damage and for cysteamine reduction of repair agreed. Through the use of thymidine as an S-phase-blocking agent it was further demonstrated that progression past the S-phase of the cell cycle was required for the loss of resistance to UVB light in BrdUrd-substituted cells. Similarly, a thymidine block administered before synthesis upon the BrdUrd-substituted template prevented the cell from acquiring the sensitivity to UVB light normally associated with synthesis on a lesioned template. The UVB-light-sensitive mutant V79-UC was shown to have reduced capacities both for the accumulation of sublethal injury and for the removal of alkali-labile lesions. These data support the notion that alkali-labile lesions are responsible for sublethal damage in BrdUrd pulse-labelled Chinese hamster cells. PMID:6582920

  4. Prediction of Damage in Randomly Oriented Short-Fibre Composites by means of A Mechanistic Approach

    SciTech Connect

    Nguyen, Ba Nghiep; Khaleel, Mohammad A.

    2004-05-01

    A micro-macro mechanistic approach to damage in short-fiber composites is developed in this paper. At the micro-scale, the damage mechanisms such as matrix cracking, fiber/matrix debonding are analyzed to define the associated damage variables. The stiffness reduction law dependent on these variables is then established using micromechanical models and average orientation distributions of fibers and microcracks. The macroscopic response is obtained by means of thermodynamics of continuous media, continuum damage mechanics and a finite element formulation.

  5. TREATMENT OF HYDROCARBON, ORGANIC RESIDUE AND PRODUCTION CHEMICAL DAMAGE MECHANISMS THROUGH THE APPLICATION OF CARBON DIOXIDE IN NATURAL GAS STORAGE WELLS

    SciTech Connect

    Lawrence J. Pekot

    2004-06-30

    Two gas storage fields were studied for this project. Overisel field, operated by Consumer's Energy, is located near the town of Holland, Michigan. Huntsman Storage Unit, operated by Kinder Morgan, is located in Cheyenne County, Nebraska near the town of Sidney. Wells in both fields experienced declining performance over several years of their annual injection/production cycle. In both fields, the presence of hydrocarbons, organic materials or production chemicals was suspected as the cause of progressive formation damage leading to the performance decline. Core specimens and several material samples were collected from these two natural gas storage reservoirs. Laboratory studies were performed to characterize the samples that were believed to be representative of a reservoir damage mechanism previously identified as arising from the presence of hydrocarbons, organic residues or production chemicals. A series of laboratory experiments were performed to identify the sample materials, use these materials to damage the flow capacity of the core specimens and then attempt to remove or reduce the induced damage using either carbon dioxide or a mixture of carbon dioxide and other chemicals. Results of the experiments showed that pure carbon dioxide was effective in restoring flow capacity to the core specimens in several different settings. However, in settings involving asphaltines as the damage mechanism, both pure carbon dioxide and mixtures of carbon dioxide and other chemicals provided little effectiveness in damage removal.

  6. Plasma damage mechanisms for low-k porous SiOCH films due to radiation, radicals, and ions in the plasma etching process

    SciTech Connect

    Uchida, Saburo; Takashima, Seigo; Hori, Masaru; Fukasawa, Masanaga; Ohshima, Keiji; Nagahata, Kazunori; Tatsumi, Tetsuya

    2008-04-01

    Low dielectric constant (low-k) films have been widely used as insulating materials in ultra-large-scale integrated circuits. Low-k films receive heavy damage during the plasma processes of etching or ashing, resulting in an increase in their dielectric constant. In order to realize damage-free plasma processes for low-k films, it is essential to determine the influence of radiation, radicals, and ions emitted in the plasma process on the characteristics of low-k films. We have developed a technique to evaluate the influence of radiation, radicals, ions, and their synergies on films in real plasma processes and have named it pallet for plasma evaluation (PAPE). Using the PAPE, plasma-induced damage on porous SiOCH films were investigated in dual-frequency capacitively coupled H{sub 2}/N{sub 2} plasmas. The damage was characterized by ellipsometry, Fourier-transform infrared spectroscopy, and thermal desorption spectroscopy. On the basis of the results, the damage mechanisms associated with vacuum ultraviolet (VUV) and UV radiation, radicals, and ions were clarified. The damage was caused not only by ions and radicals but also by VUV and UV radiation emitted by the plasmas. Moreover, it was found that the synergy between the radiation and the radicals enhanced the damage.

  7. Antidiabetic activity of a polyherbal formulation (DRF/AY/5001).

    PubMed

    Mandlik, Rahul V; Desai, Sandya K; Naik, Suresh R; Sharma, Gaurav; Kohli, R K

    2008-08-01

    The herbal formulation, DRF/AY/5001, elicits hypoglycemic/antidiabetic effects in both normal and experimentally induced hyperglycemic (epinephrine and alloxan) rats. Further, herbal formulation treatment can significantly alter the pattern of glucose tolerance in normal and diabetic rats. It is possible that the herbal formulation may act through both, pancreatic and extra-pancreatic mechanism(s). The DRF/AY/5001 also elicited a significant antioxidant effect in alloxan diabetic rats as reflected by its ability to inhibit lipid peroxidation and to elevate the enzymatic antioxidants in pancreatic tissue. The histopathological studies during the long-term treatment have shown to ameliorate the alloxan induced histological damage of islets of Langerhans. The inhibitory effects on biochemical and histological parameters induced by herbal formulation at a dose of 600 mg/kg were almost comparable to that of standard drug, glibenclamide (4 mg/kg). The present study demonstrates that herbal formulation exhibits promisisng antidiabetic activity and helps to maintain good glycemic and metabolic control.

  8. Damage mechanics - failure modes

    SciTech Connect

    Krajcinovic, D.; Vujosevic, M.

    1996-12-31

    The present study summarizes the results of the DOE sponsored research program focused on the brittle failure of solids with disordered microstructure. The failure is related to the stochastic processes on the microstructural scale; namely, the nucleation and growth of microcracks. The intrinsic failure modes, such as the percolation, localization and creep rupture, are studied by emphasizing the effect of the micro-structural disorder. A rich spectrum of physical phenomena and new concepts that emerges from this research demonstrates the reasons behind the limitations of traditional, deterministic, and local continuum models.

  9. Molecular Mechanisms of Lipoic Acid Protection against Aflatoxin B1-Induced Liver Oxidative Damage and Inflammatory Responses in Broilers

    PubMed Central

    Ma, Qiugang; Li, Yan; Fan, Yu; Zhao, Lihong; Wei, Hua; Ji, Cheng; Zhang, Jianyun

    2015-01-01

    Alpha-lipoic acid (α-LA) was evaluated in this study for its molecular mechanisms against liver oxidative damage and inflammatory responses induced by aflatoxin B1 (AFB1). Birds were randomly allocated into four groups with different diets for three weeks: a basal diet, a 300 mg/kg α-LA supplementation in a basal diet, a diet containing 74 μg/kg AFB1, and 300 mg/kg α-LA supplementation in a diet containing 74 μg/kg AFB1. In the AFB1 group, the expression of GSH-PX mRNA was down-regulated (p < 0.05), and the levels of lipid peroxide and nitric oxide were increased (p < 0.05) in the chicken livers compared to those of the control group. Additionally, the mRNA level of the pro-inflammatory factor interleukin-6 was up-regulated significantly (p < 0.05), the protein expressions of both the nuclear factor kappa B (NF-κB) p65 and the inducible nitric oxide synthase were enhanced significantly (p < 0.05) in the AFB1 group. All of these negative effects were inhibited by α-LA. These results indicate that α-LA may be effective in preventing hepatic oxidative stress, down-regulating the expression of hepatic pro-inflammatory cytokines, as well as inhibiting NF-κB expression. PMID:26694462

  10. YAP and TAZ in epithelial stem cells: A sensor for cell polarity, mechanical forces and tissue damage

    PubMed Central

    Elbediwy, Ahmed; Vincent‐Mistiaen, Zoé I.

    2016-01-01

    The YAP/TAZ family of transcriptional co‐activators drives cell proliferation in epithelial tissues and cancers. Yet, how YAP and TAZ are physiologically regulated remains unclear. Here we review recent reports that YAP and TAZ act primarily as sensors of epithelial cell polarity, being inhibited when cells differentiate an apical membrane domain, and being activated when cells contact the extracellular matrix via their basal membrane domain. Apical signalling occurs via the canonical Crumbs/CRB‐Hippo/MST‐Warts/LATS kinase cascade to phosphorylate and inhibit YAP/TAZ. Basal signalling occurs via Integrins and Src family kinases to phosphorylate and activate YAP/TAZ. Thus, YAP/TAZ is localised to the nucleus in basal stem/progenitor cells and cytoplasm in differentiated squamous cells or columnar cells. In addition, other signals such as mechanical forces, tissue damage and possibly receptor tyrosine kinases (RTKs) can influence MST‐LATS or Src family kinase activity to modulate YAP/TAZ activity. PMID:27173018

  11. Exposure of pink salmon embryos to dissolved polynuclear aromatic hydrocarbons delays development, prolonging vulnerability to mechanical damage.

    PubMed

    Carls, Mark G; Thedinga, John F

    2010-06-01

    Exposure to dissolved polynuclear aromatic hydrocarbons (PAHs) from crude oil delays pink salmon (Oncorhynchus gorbuscha) embryo development, thus prolonging their susceptibility to mechanical damage (shock). Exposure also caused mortality, edema, and anemia consistent with previous studies. Hatching and yolk consumption were delayed, indicating the rate of embryonic development was slowed by PAH exposure. The net result was that exposed embryos were more susceptible to shock than normal, unexposed embryos. Susceptibility to shock was protracted by 4-6d for more than a month in embryos exposed to exponentially declining, dissolved PAH concentrations in water passed through oiled rock; the initial total PAH concentration was 22.4microgL(-1) and the geometric mean concentration was 4.5microgL(-1) over the first 20d. Protracted susceptibility to shock caused by exposure to PAHs dissolved from oil could potentially increase the reported incidence of mortality in oiled stream systems, such as those in Prince William Sound after the Exxon Valdez oil spill, if observers fail to discriminate between direct mortality and shock-induced mortality. PMID:20089299

  12. Exposure of pink salmon embryos to dissolved polynuclear aromatic hydrocarbons delays development, prolonging vulnerability to mechanical damage.

    PubMed

    Carls, Mark G; Thedinga, John F

    2010-06-01

    Exposure to dissolved polynuclear aromatic hydrocarbons (PAHs) from crude oil delays pink salmon (Oncorhynchus gorbuscha) embryo development, thus prolonging their susceptibility to mechanical damage (shock). Exposure also caused mortality, edema, and anemia consistent with previous studies. Hatching and yolk consumption were delayed, indicating the rate of embryonic development was slowed by PAH exposure. The net result was that exposed embryos were more susceptible to shock than normal, unexposed embryos. Susceptibility to shock was protracted by 4-6d for more than a month in embryos exposed to exponentially declining, dissolved PAH concentrations in water passed through oiled rock; the initial total PAH concentration was 22.4microgL(-1) and the geometric mean concentration was 4.5microgL(-1) over the first 20d. Protracted susceptibility to shock caused by exposure to PAHs dissolved from oil could potentially increase the reported incidence of mortality in oiled stream systems, such as those in Prince William Sound after the Exxon Valdez oil spill, if observers fail to discriminate between direct mortality and shock-induced mortality.

  13. Molecular biosensing mechanisms in the spleen for the removal of aged and damaged red cells from the blood circulation.

    PubMed

    Sugawara, Yoshiaki; Hayashi, Yuko; Shigemasa, Yuki; Abe, Yoko; Ohgushi, Ikumi; Ueno, Eriko; Shimamoto, Fumio

    2010-01-01

    Heinz bodies are intraerythrocytic inclusions of hemichrome formed as a result of hemoglobin (Hb) oxidation. They typically develop in aged red cells. Based on the hypothesis that hemichrome formation is an innate characteristic of physiologically normal Hb molecules, we present an overview of our previous findings regarding the molecular instability of Hb and the formation of hemichrome, as well as recent findings on Heinz body formation within normal human erythrocytes. Human adult Hb (HbO(2) A) prepared from healthy donors showed a tendency to produce hemichrome, even at close to physiological temperature and pH. Recent studies found that the number of Heinz bodies formed in red cells increased with increasing temperature when freshly drawn venous blood from healthy donors was subjected to mild heating above 37 °C. These findings suggest that Hb molecules control the removal of non-functional erythrocytes from the circulation via hemichrome formation and subsequent Heinz body clustering. In this review, we discuss the molecular biosensing mechanisms in the spleen, where hemichrome formation and subsequent Heinz body clustering within erythrocytes play a key role in the removal of aged and damaged red cells from the blood circulation.

  14. Repeated exposures to roadside particulate matter extracts suppresses pulmonary defense mechanisms, resulting in lipid and protein oxidative damage.

    PubMed

    Pardo, Michal; Porat, Ziv; Rudich, Assaf; Schauer, James J; Rudich, Yinon

    2016-03-01

    Exposure to particulate matter (PM) pollution in cities and urban canyons can be harmful to the exposed population. However, the underlying mechanisms that lead to health effects are not yet elucidated. It is postulated that exposure to repeated, small, environmentally relevant concentrations can affect lung homeostasis. This study examines the impact of repeated exposures to urban PM on mouse lungs with focus on inflammatory and oxidative stress parameters. Aqueous extracts from collected urban PM were administered to mice by 5 repeated intra-tracheal instillations (IT). Multiple exposures, led to an increase in cytokine levels in both bronchoalveolar lavage fluid and in the blood serum, indicating a systemic reaction. Lung mRNA levels of antioxidant/phase II detoxifying enzymes decreased by exposure to the PM extract, but not when metals were removed by chelation. Finally, disruption of lung tissue oxidant-inflammatory/defense balance was evidenced by increased levels of lipid and protein oxidation. Unlike response to a single IT exposure to the same dose and source of extract, multiple exposures result in lung oxidative damage and a systemic inflammatory reaction. These could be attributed to compromised capacity to activate the protective Nrf2 tissue defense system. It is suggested that water-soluble metals present in urban PM, potentially from break and tire wear, may constitute major drivers of the pulmonary and systemic responses to multiple exposure to urban PM.

  15. Selective Cytotoxic Action and DNA Damage by Calcitriol-Cu(II) Interaction: Putative Mechanism of Cancer Prevention

    PubMed Central

    Rizvi, Asim; Hasan, S. Saif; Naseem, Imrana

    2013-01-01

    Background Vitamin D is known to play an important role in cancer-prevention. One of the features associated with the onset of malignancy is the elevation of Cu (II) levels. The mode of cancer-prevention mediated by calcitriol, the biologically active form of vitamin D, remain largely unknown. Methods Using exogenously added Cu (II) to stimulate a malignancy like condition in a novel cellular system of rabbit calcitriol overloaded lymphocytes, we assessed lipid peroxidation, protein carbonylation, DNA damage and consequent apoptosis. Free radical mediators were identified using free radical scavengers and the role of Cu (II) in the reaction was elucidated using chelators of redox active cellular metal ions. Results Lipid peroxidation and protein carbonylation (markers of oxidative stress), consequent DNA fragmentation and apoptosis were observed due to calcitriol-Cu (II) interaction. Hydroxyl radicals, hydrogen peroxide and superoxide anions mediate oxidative stress produced during this interaction. Amongst cellular redox active metals, copper was found to be responsible for this reaction. Conclusion This is the first report implicating Cu (II) and calcitriol interaction as the cause of selective cytotoxic action of calcitriol against malignant cells. We show that this interaction leads to the production of oxidative stress due to free radical production and consequent DNA fragmentation, which leads to apoptosis. A putative mechanism is presented to explain this biological effect. PMID:24086705

  16. Embedded damage sensor using triboluminescence as a transduction mechanism for detecting failure of a material under load

    NASA Astrophysics Data System (ADS)

    Lesho, Jeffery Carl

    Damage sensors are devices that monitor the state of health of structures or materials and that provide a signal indication when external forces or other conditions have caused the structure to fail. Continuous monitoring of structures is vital for safety reasons as well as for reduction of maintenance costs. The present study investigated the use of triboluminescent materials as a transduction mechanism for the detection of failure, combined with development of an electronic system to telemeter the optical pulses to a remote receiver for analysis and classification. The goal of the latter work was to create a low cost system that was small enough to be implanted into a smart material with a useful life of one year. The investigation had four main parts. First a search for an intense triboluminescent radiative material was undertaken. When an appropriate material was identified, a new improved method was developed that yielded a more efficient approach to processing. Research into the mechanism for the chosen material was conducted to determine if a new material could be engineered to yield larger signals. Second, a very low power opto-electronics system was developed that included an electronic circuit designed to monitor the sensor, and when a triboluminescent optical pulse is detected, it activates a transmitter that telemeters the optical decay signal to an external receiver. The receiver captures the optical decay as sampled digital data and correlates the signal with the known optical decay of the triboluminescent radiation. Third, a 'smart material' was fabricated with the triboluminescent sensor embedded in a block of epoxy. This material was tested to failure and the failure event was captured and the data was classified. Lastly, a correlation procedure for classifying the optical decays was written to actively look for failure events and filter out noise. Positive correlation results indicate that fracture has actually occurred.

  17. High order ADER schemes for a unified first order hyperbolic formulation of continuum mechanics: Viscous heat-conducting fluids and elastic solids

    NASA Astrophysics Data System (ADS)

    Dumbser, Michael; Peshkov, Ilya; Romenski, Evgeniy; Zanotti, Olindo

    2016-06-01

    This paper is concerned with the numerical solution of the unified first order hyperbolic formulation of continuum mechanics recently proposed by Peshkov and Romenski [110], further denoted as HPR model. In that framework, the viscous stresses are computed from the so-called distortion tensor A, which is one of the primary state variables in the proposed first order system. A very important key feature of the HPR model is its ability to describe at the same time the behavior of inviscid and viscous compressible Newtonian and non-Newtonian fluids with heat conduction, as well as the behavior of elastic and visco-plastic solids. Actually, the model treats viscous and inviscid fluids as generalized visco-plastic solids. This is achieved via a stiff source term that accounts for strain relaxation in the evolution equations of A. Also heat conduction is included via a first order hyperbolic system for the thermal impulse, from which the heat flux is computed. The governing PDE system is hyperbolic and fully consistent with the first and the second principle of thermodynamics. It is also fundamentally different from first order Maxwell-Cattaneo-type relaxation models based on extended irreversible thermodynamics. The HPR model represents therefore a novel and unified description of continuum mechanics, which applies at the same time to fluid mechanics and solid mechanics. In this paper, the direct connection between the HPR model and the classical hyperbolic-parabolic Navier-Stokes-Fourier theory is established for the first time via a formal asymptotic analysis in the stiff relaxation limit. From a numerical point of view, the governing partial differential equations are very challenging, since they form a large nonlinear hyperbolic PDE system that includes stiff source terms and non-conservative products. We apply the successful family of one-step ADER-WENO finite volume (FV) and ADER discontinuous Galerkin (DG) finite element schemes to the HPR model in the stiff

  18. [Micromorphology of leaf epidermis of some Venezuelan rice cultivars (Poaceae) associated with the mechanical damage of Sogata T. orizicolus (Homoptera: Delphacidae)].

    PubMed

    Velásquez-Salazar, Rosalia; Diamont, Diego

    2014-06-01

    Rice cultivars are affected directly and indirectly by the insect sogata. The mechanical damage or direct loss, is produced after feeding and ovoposition on the young leaves tissues, while the indirect damage is produced after the transmission of the Rice hoja blanca virus. We studied the morpho-anatomic structures associated with the resistance of the mechanical damage produced by the insect, in six rice cultivars, including controls for resistance and susceptibility (Makalioka and Bluebonnet 50), during August 2011, in Fundacion Danac, Venezuela. Samples were taken from leaf 3, where cuticle thickness, presence of macrohair, microhair and silica bodies in the second third of the leaf was evaluated. A significant difference to thickness of the cuticle, the presence of microhair in the leaves, and presence of silica bodies was observed among cultivars, determining a significant correlation among the number of macrohair and microhair in the adaxial leaf blade with the presence of silica bodies, and thickness of the cuticle and number of posed insects. Thickness of the cuticle and presence of silica bodies in the intercostals space of microhair and macrohair showed to be the variables most related to mechanical damage and resistance mechanism. PMID:25102661

  19. Mechanical damage of red blood cells by rotary blood pumps: selective destruction of aged red blood cells and subhemolytic trauma.

    PubMed

    Sakota, Daisuke; Sakamoto, Ryuki; Sobajima, Hideo; Yokoyama, Naoyuki; Waguri, Satoshi; Ohuchi, Katsuhiro; Takatani, Setsuo

    2008-10-01

    In this study, mean cell volume (MCV), mean cell hemoglobin concentration (MCHC), and mean cell hemoglobin (MCH) were measured to quantify RBC damage by rotary blood pumps. Six-hour hemolysis tests were conducted with a Bio-pump BPX-80, a Sarns 15200 roller pump, and a prototype mag-lev centrifugal pump (MedTech Heart) using fresh porcine blood circulated at 5 L/min against a 100 mm Hg head pressure. The temperature of the test and noncirculated control blood was maintained at 37 degrees C. The normalized index of hemolysis (NIH) of each pump was determined by measuring the plasma-free hemoglobin level. The MCV was measured with a Coulter counter, and MCHC was derived from total hemoglobin and hematocrit. MCH was derived from MCV and MCHC. A multivariance statistical analysis (ANOVA) revealed statistically significant differences (n = 15, P < 0.05) in MCV, MCHC, and MCH between the blood sheared by the rotary blood pumps and the nonsheared control blood. Normalized to the control blood, the Bio-pump BPX-80 showed an MCV of 1.04 +/- 0.03, an MCHC of 0.95 +/- 0.04, and an MCH of 0.98 +/- 0.02; the mag-lev MedTech Heart had an MCV of 1.02 +/- 0.02, an MCHC of 0.97 +/- 0.02, and an MCH of 0.99 +/- 0.01; and the roller pump exhibited an MCV of 1.03 +/- 0.03, an MCHC of 0.96 +/- 0.03, and an MCH of 0.99 +/- 0.01. Per 0.01 increase in NIH, the BPX-80 showed a normalized MCV change of +10.1% and a normalized MCHC change of -14.0%; the MedTech Heart demonstrated a +6.9% MCV and -9.5% MCHC change; and the roller pump had a +0.5% MCV and -0.6% MCHC change. Due to shear in the pump circuits, the RBC increased while the MCHC decreased. The likely mechanism is that older RBCs with smaller size and higher hemoglobin concentration were destroyed fast by the shear, leaving younger RBCs with larger size and lower hemoglobin concentration. Subhemolytic trauma caused the intracellular hemoglobin to decrease due to gradual hemoglobin leakage through the micropores formed in the thinned

  20. The role of microstructure on deformation and damage mechanisms in a Nickel-based superalloy at elevated temperatures

    NASA Astrophysics Data System (ADS)

    Maciejewski, Kimberly E.

    The overall objective of this research work is the development and implementation of a mechanistic based time-dependent crack growth model which considers the role of creep, fatigue and environment interactions on both the bulk and the grain boundary phase in ME3 disk material. The model is established by considering a moving crack tip along a grain boundary path in which damage events are described in terms of the grain boundary deformation and related accommodation processes. Modeling of these events was achieved by adapting a cohesive zone approach (an interface with internal singular surfaces) in which the grain boundary dislocation network is smeared into a Newtonian fluid element. The deformation behavior of this element is controlled by the continuum in both far field (internal state variable model) and near field (crystal plasticity model) and the intrinsic grain boundary viscosity which is characterized by microstructural parameters, including grain boundary precipitates and morphology, and is able to define the mobility of the element by scaling the motion of dislocations into a mesoscopic scale. Within the cohesive zone element, the motion of gliding dislocations in the tangential direction relates to the observed grain boundary sliding displacement, the rate of which is limited by the climb of dislocations over grain boundary obstacles. Effects of microstructural variation and orientation of the surrounding continuum are embedded in the tangential stress developing in the grain boundary. The mobility of the element in the tangential direction (i.e. by grain boundary sliding) characterizes the accumulation of irreversible displacement while the vertical movement (migration), although present, is assumed to alter stress by relaxation and, thus, is not considered a contributing factor in the damage process. This process is controlled by the rate at which the time-dependent sliding reaches a critical displacement and as such, a damage criterion is

  1. Repairing of N-mustard derivative BO-1055 induced DNA damage requires NER, HR, and MGMT-dependent DNA repair mechanisms.

    PubMed

    Kuo, Ching-Ying; Chou, Wen-Cheng; Wu, Chin-Chung; Wong, Teng-Song; Kakadiya, Rajesh; Lee, Te-Chang; Su, Tsann-Long; Wang, Hui-Chun

    2015-09-22

    Alkylating agents are frequently used as first-line chemotherapeutics for various newly diagnosed cancers. Disruption of genome integrity by such agents can lead to cell lethality if DNA lesions are not removed. Several DNA repair mechanisms participate in the recovery of mono- or bi-functional DNA alkylation. Thus, DNA repair capacity is correlated with the therapeutic response. Here, we assessed the function of novel water-soluble N-mustard BO-1055 (ureidomustin) in DNA damage response and repair mechanisms. As expected, BO-1055 induces ATM and ATR-mediated DNA damage response cascades, including downstream Chk1/Chk2 phosphorylation, S/G2 cell-cycle arrest, and cell death. Further investigation revealed that cell survival sensitivity to BO-1055 is comparable to that of mitomycin C. Both compounds require nucleotide excision repair and homologous recombination, but not non-homologous end-joining, to repair conventional cross-linking DNA damage. Interestingly and unlike mitomycin C and melphalan, MGMT activity was also observed in BO-1055 damage repair systems, which reflects the occurrence of O-alkyl DNA lesions. Combined treatment with ATM/ATR kinase inhibitors significantly increases BO-1055 sensitivity. Our study pinpoints that BO-1055 can be used for treating tumors that with deficient NER, HR, and MGMT DNA repair genes, or for synergistic therapy in tumors that DNA damage response have been suppressed. PMID:26208482

  2. Repairing of N-mustard derivative BO-1055 induced DNA damage requires NER, HR, and MGMT-dependent DNA repair mechanisms

    PubMed Central

    Wu, Chin-Chung; Wong, Teng-Song; Kakadiya, Rajesh; Lee, Te-Chang; Su, Tsann-Long; Wang, Hui-Chun

    2015-01-01

    Alkylating agents are frequently used as first-line chemotherapeutics for various newly diagnosed cancers. Disruption of genome integrity by such agents can lead to cell lethality if DNA lesions are not removed. Several DNA repair mechanisms participate in the recovery of mono- or bi-functional DNA alkylation. Thus, DNA repair capacity is correlated with the therapeutic response. Here, we assessed the function of novel water-soluble N-mustard BO-1055 (ureidomustin) in DNA damage response and repair mechanisms. As expected, BO-1055 induces ATM and ATR-mediated DNA damage response cascades, including downstream Chk1/Chk2 phosphorylation, S/G2 cell-cycle arrest, and cell death. Further investigation revealed that cell survival sensitivity to BO-1055 is comparable to that of mitomycin C. Both compounds require nucleotide excision repair and homologous recombination, but not non-homologous end-joining, to repair conventional cross-linking DNA damage. Interestingly and unlike mitomycin C and melphalan, MGMT activity was also observed in BO-1055 damage repair systems, which reflects the occurrence of O-alkyl DNA lesions. Combined treatment with ATM/ATR kinase inhibitors significantly increases BO-1055 sensitivity. Our study pinpoints that BO-1055 can be used for treating tumors that with deficient NER, HR, and MGMT DNA repair genes, or for synergistic therapy in tumors that DNA damage response have been suppressed. PMID:26208482

  3. Elucidation of the mechanisms of action of Bacteriophage K/nano-emulsion formulations against S. aureus via measurement of particle size and zeta potential.

    PubMed

    Esteban, Patricia Perez; Jenkins, A Toby A; Arnot, Tom C

    2016-03-01

    In earlier work we have demonstrated the effect that nano-emulsions have on bacterial growth, and most importantly the enhanced bacteriophage infectivity against Staphylococcus aureus in planktonic culture when phage are carried in nano-emulsions. However, the mechanisms of enhancement of the bacteriophage killing effect are not specifically understood. This work focuses on the investigation of the possible interactions between emulsion droplets and bacterial cells, between emulsion droplets and bacteriophages, and finally interactions between all three components: nano-emulsion droplets, bacteria, and bacteriophages. The first approach consists of simple calculations to determine the spatial distribution of the components, based on measurements of particle size. It was found that nano-emulsion droplets are much more numerous than bacteria or bacteriophage, and due to their size and surface area they must be covering the surface of both cells and bacteriophage particles. Stabilisation of bacteriophages due to electrostatic forces and interaction with nano-emulsion droplets is suspected, since bacteriophages may be protected against inactivation due to 'charge shielding'. Zeta potential was measured for the individual components in the system, and for all of them combined. It was concluded that the presence of nano-emulsions could be reducing electrostatic repulsion between bacterial cells and bacteriophage, both of which are very negatively 'charged'. Moreover, nano-emulsions lead to more favourable interaction between bacteriophages and bacteria, enhancing the anti-microbial or killing effect. These findings are relevant since the physicochemical properties of nano-emulsions (i.e. particle size distribution and zeta potential) are key in determining the efficacy of the formulation against infection in the context of responsive burn wound dressings-which is the main target for this work.

  4. Elucidation of the mechanisms of action of Bacteriophage K/nano-emulsion formulations against S. aureus via measurement of particle size and zeta potential.

    PubMed

    Esteban, Patricia Perez; Jenkins, A Toby A; Arnot, Tom C

    2016-03-01

    In earlier work we have demonstrated the effect that nano-emulsions have on bacterial growth, and most importantly the enhanced bacteriophage infectivity against Staphylococcus aureus in planktonic culture when phage are carried in nano-emulsions. However, the mechanisms of enhancement of the bacteriophage killing effect are not specifically understood. This work focuses on the investigation of the possible interactions between emulsion droplets and bacterial cells, between emulsion droplets and bacteriophages, and finally interactions between all three components: nano-emulsion droplets, bacteria, and bacteriophages. The first approach consists of simple calculations to determine the spatial distribution of the components, based on measurements of particle size. It was found that nano-emulsion droplets are much more numerous than bacteria or bacteriophage, and due to their size and surface area they must be covering the surface of both cells and bacteriophage particles. Stabilisation of bacteriophages due to electrostatic forces and interaction with nano-emulsion droplets is suspected, since bacteriophages may be protected against inactivation due to 'charge shielding'. Zeta potential was measured for the individual components in the system, and for all of them combined. It was concluded that the presence of nano-emulsions could be reducing electrostatic repulsion between bacterial cells and bacteriophage, both of which are very negatively 'charged'. Moreover, nano-emulsions lead to more favourable interaction between bacteriophages and bacteria, enhancing the anti-microbial or killing effect. These findings are relevant since the physicochemical properties of nano-emulsions (i.e. particle size distribution and zeta potential) are key in determining the efficacy of the formulation against infection in the context of responsive burn wound dressings-which is the main target for this work. PMID:26700237

  5. Gurson's Model: ALE Formulation and Strain Localization

    NASA Astrophysics Data System (ADS)

    da Cunda, Luiz A. B.; Creus, Guillermo J.

    2007-05-01

    This paper presents a brief review of Gurson's damage model, employed to describes the strength degradation in ductile metals submitted to large plastic deformations. The damage model is applied using finite elements and an Arbitrary Lagrangian-Eulerian formulation (ALE), to ensure a better quality to the finite elements mesh. The study of the combined application of ALE and Gurson approach to damage modeling and strain localization is the object of this paper.

  6. Gurson's Model: ALE Formulation and Strain Localization

    SciTech Connect

    Cunda, Luiz A. B. da; Creus, Guillermo J.

    2007-05-17

    This paper presents a brief review of Gurson's damage model, employed to describes the strength degradation in ductile metals submitted to large plastic deformations. The damage model is applied using finite elements and an Arbitrary Lagrangian-Eulerian formulation (ALE), to ensure a better quality to the finite elements mesh. The study of the combined application of ALE and Gurson approach to damage modeling and strain localization is the object of this paper.

  7. Soaking formulations that can soften and remove hardened bovine manure: part II, effects on quality of leather

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously developed soaking formulations were shown to soften adobe-type manure and facilitating its removal thus limiting its damaging effects on bovine hides. The mechanical stress due to the weight and pressure of hard to remove adobe-type manure on bovine hides can cause unwanted holes in the ...

  8. Mechanical Properties and Real-Time Damage Evaluations of Environmental Barrier Coated SiC/SiC CMCs Subjected to Tensile Loading Under Thermal Gradients

    NASA Technical Reports Server (NTRS)

    Appleby, Matthew; Zhu, Dongming; Morscher, Gregory

    2015-01-01

    SiC/SiC ceramic matrix composites (CMCs) require new state-of-the art environmental barrier coatings (EBCs) to withstand increased temperature requirements and high velocity combustion corrosive combustion gasses. The present work compares the response of coated and uncoated SiC/SiC CMC substrates subjected to simulated engine environments followed by high temperature mechanical testing to asses retained properties and damage mechanisms. Our focus is to explore the capabilities of electrical resistance (ER) measurements as an NDE technique for testing of retained properties under combined high heat-flux and mechanical loading conditions. Furthermore, Acoustic Emission (AE) measurements and Digital Image Correlation (DIC) were performed to determine material damage onset and accumulation.

  9. Damage Mechanisms and Controlled Crack Propagation in a Hot Pressed Silicon Nitride Ceramic. Ph.D. Thesis - Northwestern Univ., 1993

    NASA Technical Reports Server (NTRS)

    Calomino, Anthony Martin

    1994-01-01

    The subcritical growth of cracks from pre-existing flaws in ceramics can severely affect the structural reliability of a material. The ability to directly observe subcritical crack growth and rigorously analyze its influence on fracture behavior is important for an accurate assessment of material performance. A Mode I fracture specimen and loading method has been developed which permits the observation of stable, subcritical crack extension in monolithic and toughened ceramics. The test specimen and procedure has demonstrated its ability to generate and stably propagate sharp, through-thickness cracks in brittle high modulus materials. Crack growth for an aluminum oxide ceramic was observed to be continuously stable throughout testing. Conversely, the fracture behavior of a silicon nitride ceramic exhibited crack growth as a series of subcritical extensions which are interrupted by dynamic propagation. Dynamic initiation and arrest fracture resistance measurements for the silicon nitride averaged 67 and 48 J/sq m, respectively. The dynamic initiation event was observed to be sudden and explosive. Increments of subcritical crack growth contributed to a 40 percent increase in fracture resistance before dynamic initiation. Subcritical crack growth visibly marked the fracture surface with an increase in surface roughness. Increments of subcritical crack growth loosen ceramic material near the fracture surface and the fracture debris is easily removed by a replication technique. Fracture debris is viewed as evidence that both crack bridging and subsurface microcracking may be some of the mechanisms contributing to the increase in fracture resistance. A Statistical Fracture Mechanics model specifically developed to address subcritical crack growth and fracture reliability is used together with a damaged zone of material at the crack tip to model experimental results. A Monte Carlo simulation of the actual experiments was used to establish a set of modeling input

  10. The role of microstructure on deformation and damage mechanisms in a Nickel-based superalloy at elevated temperatures

    NASA Astrophysics Data System (ADS)

    Maciejewski, Kimberly E.

    The overall objective of this research work is the development and implementation of a mechanistic based time-dependent crack growth model which considers the role of creep, fatigue and environment interactions on both the bulk and the grain boundary phase in ME3 disk material. The model is established by considering a moving crack tip along a grain boundary path in which damage events are described in terms of the grain boundary deformation and related accommodation processes. Modeling of these events was achieved by adapting a cohesive zone approach (an interface with internal singular surfaces) in which the grain boundary dislocation network is smeared into a Newtonian fluid element. The deformation behavior of this element is controlled by the continuum in both far field (internal state variable model) and near field (crystal plasticity model) and the intrinsic grain boundary viscosity which is characterized by microstructural parameters, including grain boundary precipitates and morphology, and is able to define the mobility of the element by scaling the motion of dislocations into a mesoscopic scale. Within the cohesive zone element, the motion of gliding dislocations in the tangential direction relates to the observed grain boundary sliding displacement, the rate of which is limited by the climb of dislocations over grain boundary obstacles. Effects of microstructural variation and orientation of the surrounding continuum are embedded in the tangential stress developing in the grain boundary. The mobility of the element in the tangential direction (i.e. by grain boundary sliding) characterizes the accumulation of irreversible displacement while the vertical movement (migration), although present, is assumed to alter stress by relaxation and, thus, is not considered a contributing factor in the damage process. This process is controlled by the rate at which the time-dependent sliding reaches a critical displacement and as such, a damage criterion is

  11. Modeling Fatigue Damage in Long-Fiber Thermoplastics

    SciTech Connect

    Nguyen, Ba Nghiep; Kunc, Vlastimil; Bapanapalli, Satish K.

    2009-10-30

    This paper applies a fatigue damage model recently developed for injection-molded long-fiber thermoplastics (LFTs) to predict the modulus reduction and fatigue lifetime of glass/polyamide 6,6 (PA6,6) specimens. The fatigue model uses a multiscale mechanistic approach to describe fatigue damage accumulation in these materials subjected to cyclic loading. Micromechanical modeling using a modified Eshelby-Mori-Tanaka approach combined with averaging techniques for fiber length and orientation distributions is performed to establish the stiffness reduction relation for the composite as a function of the microcrack volume fraction. Next, continuum damage mechanics and a thermodynamic formulation are used to derive the constitutive relations and the damage evolution law. The fatigue damage model has been implemented in the ABAQUS finite element code and has been applied to analyze fatigue of the studied glass/PA6,6 specimens. The predictions agree well with the experimental results.

  12. Comparative Effects of Ions, Molecular Crowding, and Bulk DNA on the Damage Search Mechanisms of hOGG1 and hUNG.

    PubMed

    Cravens, Shannen L; Stivers, James T

    2016-09-20

    The energetic nature of the interactions of DNA base excision repair glycosylases with undamaged and damaged DNA and the nuclear environment are expected to significantly impact the time it takes for these enzymes to search for damaged DNA bases. In particular, the high concentration of monovalent ions, macromolecule crowding, and densely packed DNA chains in the cell nucleus could alter the search mechanisms of these enzymes as compared to findings in dilute buffers typically used in in vitro experiments. Here we utilize an in vitro system where the concerted effects of monovalent ions, macromolecular crowding, and high concentrations of bulk DNA chains on the activity of two paradigm human DNA glycosylases can be determined. We find that the energetic nature of the observed binding free energies of human 8-oxoguanine DNA glycosylase (hOGG1) and human uracil DNA glycosylase (hUNG) for undamaged DNA are derived from different sources. Although hOGG1 uses primarily nonelectrostatic binding interactions with nonspecific DNA, hUNG uses a salt-dependent electrostatic binding mode. Both enzymes turn to a nonelectrostatic mode in their specific complexes with damaged bases in DNA, which enhances damage site specificity at physiological ion concentrations. Neither enzyme was capable of efficiently locating and removing their respective damaged bases in the combined presence of physiological ions and a bulk DNA chain density approximating that found in the nucleus. However, the addition of an inert crowding agent to mimic macromolecular crowding in the nucleus largely restored their ability to track DNA chains and locate damaged sites. These findings suggest how the concerted action of monovalent ions and crowding could contribute to efficient DNA damage recognition in cells. PMID:27571472

  13. Comparative Effects of Ions, Molecular Crowding, and Bulk DNA on the Damage Search Mechanisms of hOGG1 and hUNG.

    PubMed

    Cravens, Shannen L; Stivers, James T

    2016-09-20

    The energetic nature of the interactions of DNA base excision repair glycosylases with undamaged and damaged DNA and the nuclear environment are expected to significantly impact the time it takes for these enzymes to search for damaged DNA bases. In particular, the high concentration of monovalent ions, macromolecule crowding, and densely packed DNA chains in the cell nucleus could alter the search mechanisms of these enzymes as compared to findings in dilute buffers typically used in in vitro experiments. Here we utilize an in vitro system where the concerted effects of monovalent ions, macromolecular crowding, and high concentrations of bulk DNA chains on the activity of two paradigm human DNA glycosylases can be determined. We find that the energetic nature of the observed binding free energies of human 8-oxoguanine DNA glycosylase (hOGG1) and human uracil DNA glycosylase (hUNG) for undamaged DNA are derived from different sources. Although hOGG1 uses primarily nonelectrostatic binding interactions with nonspecific DNA, hUNG uses a salt-dependent electrostatic binding mode. Both enzymes turn to a nonelectrostatic mode in their specific complexes with damaged bases in DNA, which enhances damage site specificity at physiological ion concentrations. Neither enzyme was capable of efficiently locating and removing their respective damaged bases in the combined presence of physiological ions and a bulk DNA chain density approximating that found in the nucleus. However, the addition of an inert crowding agent to mimic macromolecular crowding in the nucleus largely restored their ability to track DNA chains and locate damaged sites. These findings suggest how the concerted action of monovalent ions and crowding could contribute to efficient DNA damage recognition in cells.

  14. Damage-mitigating control of space propulsion systems for high performance and extended life

    NASA Technical Reports Server (NTRS)

    Ray, Asok; Wu, Min-Kuang; Dai, Xiaowen; Carpino, Marc; Lorenzo, Carl F.

    1993-01-01

    Calculations are presented showing that a substantial improvement in service life of a reusable rocket engine can be achieved by an insignificant reduction in the system dynamic performance. The paper introduces the concept of damage mitigation and formulates a continuous-time model of fatigue damage dynamics. For control of complex mechanical systems, damage prediction and damage mitigation are carried out based on the available sensory and operational information such that the plant can be inexpensively maintained and safely and efficiently steered under diverse operating conditions. The results of simulation experiments are presented for transient operations of a reusable rocket engine.

  15. Early stage fatigue damage occurs in bovine tendon fascicles in the absence of changes in mechanics at either the gross or micro-structural level.

    PubMed

    Shepherd, Jennifer H; Riley, Graham P; Screen, Hazel R C

    2014-10-01

    Many tendon injuries are believed to result from repetitive motion or overuse, leading to the accumulation of micro-damage over time. In vitro fatigue loading can be used to characterise damage during repeated use and investigate how this may relate to the aetiology of tendinopathy. This study considered the effect of fatigue loading on fascicles from two functionally distinct bovine tendons: the digital extensor and deep digital flexor. Micro-scale extension mechanisms were investigated in fascicles before or after a period of cyclic creep loading, comparing two different measurement techniques - the displacement of a photo-bleached grid and the use of nuclei as fiducial markers. Whilst visual damage was clearly identified after only 300 cycles of creep loading, these visual changes did not affect either gross fascicle mechanics or fascicle microstructural extension mechanisms over the 900 fatigue cycles investigated. However, significantly greater fibre sliding was measured when observing grid deformation rather than the analysis of nuclei movement. Measurement of microstructural extension with both techniques was localised and this may explain the absence of change in microstructural deformation in response to fatigue loading. Alternatively, the data may demonstrate that fascicles can withstand a degree of matrix disruption with no impact on mechanics. Whilst use of a photo-bleached grid to directly measure the collagen is the best indicator of matrix deformation, nuclei tracking may provide a better measure of the strain perceived directly by the cells. PMID:25001495

  16. Early stage fatigue damage occurs in bovine tendon fascicles in the absence of changes in mechanics at either the gross or micro-structural level

    PubMed Central

    Shepherd, Jennifer H.; Riley, Graham P.; Screen, Hazel R.C.

    2014-01-01

    Many tendon injuries are believed to result from repetitive motion or overuse, leading to the accumulation of micro-damage over time. In vitro fatigue loading can be used to characterise damage during repeated use and investigate how this may relate to the aetiology of tendinopathy. This study considered the effect of fatigue loading on fascicles from two functionally distinct bovine tendons: the digital extensor and deep digital flexor. Micro-scale extension mechanisms were investigated in fascicles before or after a period of cyclic creep loading, comparing two different measurement techniques – the displacement of a photo-bleached grid and the use of nuclei as fiducial markers. Whilst visual damage was clearly identified after only 300 cycles of creep loading, these visual changes did not affect either gross fascicle mechanics or fascicle microstructural extension mechanisms over the 900 fatigue cycles investigated. However, significantly greater fibre sliding was measured when observing grid deformation rather than the analysis of nuclei movement. Measurement of microstructural extension with both techniques was localised and this may explain the absence of change in microstructural deformation in response to fatigue loading. Alternatively, the data may demonstrate that fascicles can withstand a degree of matrix disruption with no impact on mechanics. Whilst use of a photo-bleached grid to directly measure the collagen is the best indicator of matrix deformation, nuclei tracking may provide a better measure of the strain perceived directly by the cells. PMID:25001495

  17. Damage analysis and mechanical response of as-received and heat-treated Nicalon/CAS-2 glass-ceramic matrix composites

    SciTech Connect

    Lee, S.S.

    1993-01-01

    Experimental results of damage development in and mechanical response of heat-treated Nicalon/CAS-2 laminates subjected to monotonic flexure and axial loading and to cyclic tensile loading are reported. The specimens were subjected to post-processing heat treatments at 900, 1000, and 1100 C in air for 100 hours. Changes at the fiber/matrix interface/interphase due to post-processing heat treatments were also characterized. The combined effect of fiber debonding and transverse matrix cracking in both 90 deg and 0 deg plies plays an important role in damage development in (0/90)(sub 4s), Nicalon/CAS-2 laminates, especially in developing the secondary damage modes such as longitudinal matrix cracking and delamination. Frictional wear effects found in cyclically loaded specimens may be responsible for the observed temperature profiles during the intermediate stage of fatigue life. It is also believed that frictional wear is critical to the failure of notch sensitive fibers. Different damage modes such as brittle' matrix crack propagation and quasi-brittle' matrix crack propagation were observed in heat-treated specimens. Results obtained from microanalysis using an analytical scanning transmission electron microscope equipped with an energy dispersive spectrometer, and microindentation indicated that the changes of damage and failure modes were directly related to the changes of characteristics at the fiber/matrix interface/interphase.

  18. Mean stress and the exhaustion of fatigue-damage resistance

    NASA Technical Reports Server (NTRS)

    Berkovits, Avraham

    1989-01-01

    Mean-stress effects on fatigue life are critical in isothermal and thermomechanically loaded materials and composites. Unfortunately, existing mean-stress life-prediction methods do not incorporate physical fatigue damage mechanisms. An objective is to examine the relation between mean-stress induced damage (as measured by acoustic emission) and existing life-prediction methods. Acoustic emission instrumentation has indicated that, as with static yielding, fatigue damage results from dislocation buildup and motion until dislocation saturation is reached, after which void formation and coalescence predominate. Correlation of damage processes with similar mechanisms under monotonic loading led to a reinterpretation of Goodman diagrams for 40 alloys and a modification of Morrow's formulation for life prediction under mean stresses. Further testing, using acoustic emission to monitor dislocation dynamics, can generate data for developing a more general model for fatigue under mean stress.

  19. Delivery of human mesenchymal adipose-derived stem cells restores multiple urological dysfunctions in a rat model mimicking radical prostatectomy damages through tissue-specific paracrine mechanisms.

    PubMed

    Yiou, René; Mahrouf-Yorgov, Meriem; Trébeau, Céline; Zanaty, Marc; Lecointe, Cécile; Souktani, Richard; Zadigue, Patricia; Figeac, Florence; Rodriguez, Anne-Marie

    2016-02-01

    Urinary incontinence (UI) and erectile dysfunction (ED) are the most common functional urological disorders and the main sequels of radical prostatectomy (RP) for prostate cancer. Mesenchymal stem cell (MSC) therapy holds promise for repairing tissue damage due to RP. Because animal studies accurately replicating post-RP clinical UI and ED are lacking, little is known about the mechanisms underlying the urological benefits of MSC in this setting. To determine whether and by which mechanisms MSC can repair damages to both striated urethral sphincter (SUS) and penis in the same animal, we delivered human multipotent adipose stem cells, used as MSC model, in an immunocompetent rat model replicating post-RP UI and ED. In this model, we demonstrated by using noninvasive methods in the same animal from day 7 to day 90 post-RP injury that MSC administration into both the SUS and the penis significantly improved urinary continence and erectile function. The regenerative effects of MSC therapy were not due to transdifferentiation and robust engraftment at injection sites. Rather, our results suggest that MSC benefits in both target organs may involve a paracrine process with not only soluble factor release by the MSC but also activation of the recipient's secretome. These two effects of MSC varied across target tissues and damaged-cell types. In conclusion, our work provides new insights into the regenerative properties of MSC and supports the ability of MSC from a single source to repair multiple types of damage, such as those seen after RP, in the same individual.

  20. Spironolactone promotes autophagy via inhibiting PI3K/AKT/mTOR signalling pathway and reduce adhesive capacity damage in podocytes under mechanical stress

    PubMed Central

    Li, Dong; Lu, Zhenyu; Xu, Zhongwei; Ji, Junya; Zheng, Zhenfeng; Lin, Shan; Yan, Tiekun

    2016-01-01

    Mechanical stress which would cause deleterious adhesive effects on podocytes is considered a major contributor to the early progress of diabetic nephropathy (DN). Our previous study has shown that spironolactone could ameliorate podocytic adhesive capacity in diabetic rats. Autophagy has been reported to have a protective role against renal injury. The present study investigated the underlying mechanisms by which spironolactone reduced adhesive capacity damage in podocytes under mechanical stress, focusing on the involvement of autophagy. Human conditional immortalized podocytes exposed to mechanical stress were treated with spironolactone, LY294002 or rapamycin for 48 h. The accumulation of LC3 puncta was detected by immunofluorescence staining. Podocyte expression of mineralocorticoid receptor (MR), integrin β1, LC3, Atg5, p85-PI3K, p-Akt, p-mTOR were detected by Western blotting. Podocyte adhesion to collagen type IV was also performed with spectrophotometry. Immunofluorescence staining showed that the normal level of autophagy was reduced in podocytes under mechanical stress. Decreased integrin β1, LC3, Atg5 and abnormal activation of the PI3K/Akt/mTOR pathway were also detected in podocytes under mechanical stress. Spironolactone up-regulated integrin β1, LC3, Atg5 expression, down-regulated p85-PI3K, p-Akt, p-mTOR expression and reduced podocytic adhesive capacity damage. Our data demonstrated that spironolactone inhibited mechanical-stress-induced podocytic adhesive capacity damage through blocking PI3K/Akt/mTOR pathway and restoring autophagy activity. PMID:27129295

  1. Damage Detection Based on Power Dissipation Measured with PZT Sensors through the Combination of Electro-Mechanical Impedances and Guided Waves

    PubMed Central

    Sevillano, Enrique; Sun, Rui; Perera, Ricardo

    2016-01-01

    The use of piezoelectric ceramic transducers (such as Lead-Zirconate-Titanate—PZT) has become more and more widespread for Structural Health Monitoring (SHM) applications. Among all the techniques that are based on this smart sensing solution, guided waves and electro-mechanical impedance techniques have found wider acceptance, and so more studies and experimental works can be found containing these applications. However, even though these two techniques can be considered as complementary to each other, little work can be found focused on the combination of them in order to define a new and integrated damage detection procedure. In this work, this combination of techniques has been studied by proposing a new integrated damage indicator based on Electro-Mechanical Power Dissipation (EMPD). The applicability of this proposed technique has been tested through different experimental tests, with both lab-scale and real-scale structures. PMID:27164104

  2. Damage Detection Based on Power Dissipation Measured with PZT Sensors through the Combination of Electro-Mechanical Impedances and Guided Waves.

    PubMed

    Sevillano, Enrique; Sun, Rui; Perera, Ricardo

    2016-01-01

    The use of piezoelectric ceramic transducers (such as Lead-Zirconate-Titanate-PZT) has become more and more widespread for Structural Health Monitoring (SHM) applications. Among all the techniques that are based on this smart sensing solution, guided waves and electro-mechanical impedance techniques have found wider acceptance, and so more studies and experimental works can be found containing these applications. However, even though these two techniques can be considered as complementary to each other, little work can be found focused on the combination of them in order to define a new and integrated damage detection procedure. In this work, this combination of techniques has been studied by proposing a new integrated damage indicator based on Electro-Mechanical Power Dissipation (EMPD). The applicability of this proposed technique has been tested through different experimental tests, with both lab-scale and real-scale structures. PMID:27164104

  3. Two important mechanisms damaging KH2PO4 crystal processed by ultraprecision fly cutting and their relationships with cutting parameters.

    PubMed

    Li, Mingquan; Chen, Mingjun; Cheng, Jian; Xiao, Yong; Jiang, Wei

    2013-05-20

    Mid-frequency waviness and subsurface crack are two fundamental factors that damage KH(2)PO(4) (KDP) crystal processed by ultraprecise fly cutting. In this paper, the motif theory and the Fourier model method are used to analyze the influence of the two factors on the laser-induced damage threshold (LIDT) of KDP. Research results indicate that the modulation degrees increase nearly linearly when the waviness amplitude and subsurface crack depth increase, and, meanwhile, the LIDT tends to decrease. The two factors have different effects during different stages of KDP failure. The mean amplitudes of waviness and subsurface damage depth have similar changing regulations with different feeds. From the machining perspective, we need not necessarily know which is more dangerous, because when one factor is controlled, the other one will also be restrained at the same time. In general, smaller feed and cutting depth are benefits for improving the LIDT of KDP.

  4. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension

    PubMed Central

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A.; Castillo, Andrés E.; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E.; Kalergis, Alexis M.

    2016-01-01

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage. PMID:27347925

  5. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension.

    PubMed

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A; Castillo, Andrés E; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E; Kalergis, Alexis M

    2016-06-23

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage.

  6. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension.

    PubMed

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A; Castillo, Andrés E; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E; Kalergis, Alexis M

    2016-01-01

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage. PMID:27347925

  7. Optimal antimicrobial formulation and physical-mechanical properties of edible films based on Açaí and Pectin for food preservation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This work aimed to develop edible films based on pectin and açaí. Films were incorporated with apple skin polyphenols (ASP) and thyme essential oil (TEO) according to the central composite design. Antimicrobial optimal formulation was determined using the response surface methodology and desirabilit...

  8. Prevention of iron- and copper-mediated DNA damage by catecholamine and amino acid neurotransmitters, L-DOPA, and curcumin: metal binding as a general antioxidant mechanism.

    PubMed

    García, Carla R; Angelé-Martínez, Carlos; Wilkes, Jenna A; Wang, Hsiao C; Battin, Erin E; Brumaghim, Julia L

    2012-06-01

    Concentrations of labile iron and copper are elevated in patients with neurological disorders, causing interest in metal-neurotransmitter interactions. Catecholamine (dopamine, epinephrine, and norepinephrine) and amino acid (glycine, glutamate, and 4-aminobutyrate) neurotransmitters are antioxidants also known to bind metal ions. To investigate the role of metal binding as an antioxidant mechanism for these neurotransmitters, L-dihydroxyphenylalanine (L-DOPA), and curcumin, their abilities to prevent iron- and copper-mediated DNA damage were quantified, cyclic voltammetry was used to determine the relationship between their redox potentials and DNA damage prevention, and UV-vis studies were conducted to determine iron and copper binding as well as iron oxidation rates. In contrast to amino acid neurotransmitters, catecholamine neurotransmitters, L-DOPA, and curcumin prevent significant iron-mediated DNA damage (IC(50) values of 3.2 to 18 μM) and are electrochemically active. However, glycine and glutamate are more effective at preventing copper-mediated DNA damage (IC(50) values of 35 and 12.9 μM, respectively) than L-DOPA, the only catecholamine to prevent this damage (IC(50) = 73 μM). This metal-mediated DNA damage prevention is directly related to the metal-binding behaviour of these compounds. When bound to iron or copper, the catecholamines, amino acids, and curcumin significantly shift iron oxidation potentials and stabilize Fe(3+) over Fe(2+) and Cu(2+) over Cu(+), a factor that may prevent metal redox cycling in vivo. These results highlight the disparate antioxidant activities of neurotransmitters, drugs, and supplements and highlight the importance of considering metal binding when identifying antioxidants to treat and prevent neurodegenerative disorders. PMID:22450660

  9. FY07 LDRD Final Report A Fracture Mechanics and Tribology Approach to Understanding Subsurface Damage on Fused Silica during Grinding and Polishing

    SciTech Connect

    Suratwala, T I; Miller, P E; Menapace, J A; Wong, L L; Steele, R A; Feit, M D; Davis, P J; Walmer, C D

    2008-02-05

    The objective of this work is to develop a solid scientific understanding of the creation and characteristics of surface fractures formed during the grinding and polishing of brittle materials, specifically glass. In this study, we have experimentally characterized the morphology, number density, and depth distribution of various surface cracks as a function of various grinding and polishing processes (blanchard, fixed abrasive grinding, loose abrasive, pitch polishing and pad polishing). Also, the effects of load, abrasive particle (size, distribution, foreign particles, geometry, velocity), and lap material (pitch, pad) were examined. The resulting data were evaluated in terms of indentation fracture mechanics and tribological interactions (science of interacting surfaces) leading to several models to explain crack distribution behavior of ground surfaces and to explain the characteristics of scratches formed during polishing. This project has greatly advanced the scientific knowledge of microscopic mechanical damage occurring during grinding and polishing and has been of general interest. This knowledge-base has also enabled the design and optimization of surface finishing processes to create optical surfaces with far superior laser damage resistance. There are five major areas of scientific progress as a result of this LDRD. They are listed in Figure 1 and described briefly in this summary below. The details of this work are summarized through a number of published manuscripts which are included this LDRD Final Report. In the first area of grinding, we developed a technique to quantitatively and statistically measure the depth distribution of surface fractures (i.e., subsurface damage) in fused silica as function of various grinding processes using mixtures of various abrasive particles size distributions. The observed crack distributions were explained using a model that extended known, single brittle indentation models to an ensemble of loaded, sliding

  10. Damage identification and health monitoring of structural and mechanical systems from changes in their vibration characteristics: A literature review

    SciTech Connect

    Doebling, S.W.; Farrar, C.R.; Prime, M.B.; Shevitz, D.W.

    1996-05-01

    This report contains a review of the technical literature concerning the detection, location, and characterization of structural damage via techniques that examine changes in measured structural vibration response. The report first categorizes the methods according to required measured data and analysis technique. The analysis categories include changes in modal frequencies, changes in measured mode shapes (and their derivatives), and changes in measured flexibility coefficients. Methods that use property (stiffness, mass, damping) matrix updating, detection of nonlinear response, and damage detection via neural networks are also summarized. The applications of the various methods to different types of engineering problems are categorized by type of structure and are summarized. The types of structures include beams, trusses, plates, shells, bridges, offshore platforms, other large civil structures, aerospace structures, and composite structures. The report describes the development of the damage-identification methods and applications and summarizes the current state-of-the-art of the technology. The critical issues for future research in the area of damage identification are also discussed.

  11. The Hsp90 inhibitor SNX-7081 is synergistic with fludarabine nucleoside via DNA damage and repair mechanisms in human, p53-negative chronic lymphocytic leukemia

    PubMed Central

    Alomari, Munther; Mirzaei, Mehdi; Best, O. Giles; Pascovici, Dana; Mactier, Swetlana; Mulligan, Stephen P.; Haynes, Paul A.; Christopherson, Richard I.

    2015-01-01

    Clinical trials of heat shock protein 90 (Hsp90) inhibitors have been limited by high toxicity. We previously showed that the Hsp90 inhibitor, SNX-7081, synergizes with and restores sensitivity to fludarabine nucleoside (2-FaraA) in human chronic lymphocytic leukemia (CLL) cells with lesions in the p53 pathway (Best OG, et al., Leukemia Lymphoma 53:1367-75, 2012). Here, we used label-free quantitative shotgun proteomics and comprehensive bioinformatic analysis to determine the mechanism of this synergy. We propose that 2-FaraA-induced DNA damage is compounded by SNX-7081-mediated inhibition of DNA repair, resulting in enhanced induction of apoptosis. DNA damage responses are impaired in part due to reductions in checkpoint regulators BRCA1 and cyclin D1, and cell death is triggered following reductions of MYC and nucleolin and an accumulation of apoptosis-inducing NFkB2 p100 subunit. Loss of nucleolin can activate Fas-mediated apoptosis, leading to the increase of pro-apoptotic proteins (BID, fas-associated factor-2) and subsequent apoptosis of p53-negative, 2-FaraA refractory CLL cells. A significant induction of DNA damage, indicated by increases in DNA damage marker ϕH2AX, was observed following the dual drug treatment of additional cell lines, indicating that a similar mechanism may operate in other p53-mutated human B-lymphoid cancers. These results provide valuable insight into the synergistic mechanism between SNX-7081 and 2-FaraA that may provide an alternative treatment for CLL patients with p53 mutations, for whom therapeutic options are currently limited. Moreover, this drug combination reduces the effective dose of the Hsp90 inhibitor and may therefore alleviate any toxicity encountered. PMID:26556860

  12. Tetanic contraction induces enhancement of fatigability and sarcomeric damage in atrophic skeletal muscle and its underlying molecular mechanisms.

    PubMed

    Yu, Zhi-Bin

    2013-11-01

    Muscle unloading due to long-term exposure of weightlessness or simulated weightlessness causes atrophy, loss of functional capacity, impaired locomotor coordination, and decreased resistance to fatigue in the antigravity muscles of the lower limbs. Besides reducing astronauts' mobility in space and on returning to a gravity environment, the molecular mechanisms for the adaptation of skeletal muscle to unloading also play an important medical role in conditions such as disuse and paralysis. The tail-suspended rat model was used to simulate the effects of weightlessness on skeletal muscles and to induce muscle unloading in the rat hindlimb. Our series studies have shown that the maximum of twitch tension and the twitch duration decreased significantly in the atrophic soleus muscles, the maximal tension of high-frequency tetanic contraction was significantly reduced in 2-week unloaded soleus muscles, however, the fatigability of high-frequency tetanic contraction increased after one week of unloading. The maximal isometric tension of intermittent tetanic contraction at optimal stimulating frequency did not alter in 1- and 2-week unloaded soleus, but significantly decreased in 4-week unloaded soleus. The 1-week unloaded soleus, but not extensor digitorum longus (EDL), was more susceptible to fatigue during intermittent tetanic contraction than the synchronous controls. The changes in K+ channel characteristics may increase the fatigability during high-frequency tetanic contraction in atrophic soleus muscles. High fatigability of intermittent tetanic contraction may be involved in enhanced activity of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and switching from slow to fast isoform of myosin heavy chain, tropomyosin, troponin I and T subunit in atrophic soleus muscles. Unloaded soleus muscle also showed a decreased protein level of neuronal nitric oxide synthase (nNOS), and the reduction in nNOS-derived NO increased frequency of calcium sparks and elevated

  13. 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.

  14. Possible Involvement of Nitric Oxide Modulatory Mechanisms in the Neuroprotective Effect of Centella asiatica Against Sleep Deprivation Induced Anxiety Like Behaviour, Oxidative Damage and Neuroinflammation.

    PubMed

    Chanana, Priyanka; Kumar, Anil

    2016-04-01

    Sleep deprivation (SD) is an experience of inadequate or poor quality of sleep that may produce significant alterations in multiple neural systems. Centella asiatica (CA) is a psychoactive medicinal herb with immense therapeutic potential. The present study was designed to explore the possible nitric oxide (NO) modulatory mechanism in the neuroprotective effect of CA against SD induced anxiety like behaviour, oxidative damage and neuroinflammation. Male laca mice were sleep deprived for 72 h, and CA (150 and 300 mg/kg) was administered alone and in combination with NO modulators for 8 days, starting five days before 72-h SD exposure. Various behavioural (locomotor activity, elevated plus maze) and biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels and superoxide dismutase activity), neuroinflammation marker (TNF-alpha) were assessed subsequently. CA (150 and 300 mg/kg) treatment for 8 days significantly improved locomotor activity, anti-anxiety like effect and attenuated oxidative damage and TNF α level as compared to sleep-deprived 72-h group. Also while the neuroprotective effect of CA was increased by NO antagonists, it was diminished by NO agonists. The present study suggests that NO modulatory mechanism could be involved in the protective effect of CA against SD-induced anxiety-like behaviour, oxidative damage and neuroinflammation in mice.

  15. Possible Involvement of Nitric Oxide Modulatory Mechanisms in the Neuroprotective Effect of Centella asiatica Against Sleep Deprivation Induced Anxiety Like Behaviour, Oxidative Damage and Neuroinflammation.

    PubMed

    Chanana, Priyanka; Kumar, Anil

    2016-04-01

    Sleep deprivation (SD) is an experience of inadequate or poor quality of sleep that may produce significant alterations in multiple neural systems. Centella asiatica (CA) is a psychoactive medicinal herb with immense therapeutic potential. The present study was designed to explore the possible nitric oxide (NO) modulatory mechanism in the neuroprotective effect of CA against SD induced anxiety like behaviour, oxidative damage and neuroinflammation. Male laca mice were sleep deprived for 72 h, and CA (150 and 300 mg/kg) was administered alone and in combination with NO modulators for 8 days, starting five days before 72-h SD exposure. Various behavioural (locomotor activity, elevated plus maze) and biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels and superoxide dismutase activity), neuroinflammation marker (TNF-alpha) were assessed subsequently. CA (150 and 300 mg/kg) treatment for 8 days significantly improved locomotor activity, anti-anxiety like effect and attenuated oxidative damage and TNF α level as compared to sleep-deprived 72-h group. Also while the neuroprotective effect of CA was increased by NO antagonists, it was diminished by NO agonists. The present study suggests that NO modulatory mechanism could be involved in the protective effect of CA against SD-induced anxiety-like behaviour, oxidative damage and neuroinflammation in mice. PMID:26848139

  16. Multiphoton absorption is probably not the primary threshold damage mechanism for femtosecond laser pulse exposures in the retinal pigment epithelium

    NASA Astrophysics Data System (ADS)

    Glickman, Randolph D.; Johnson, Thomas E.

    2004-07-01

    Laser induced breakdown has the lowest energy threshold in the femtosecond domain, and is responsible for production of threshold ocular lesions. It has been proposed that multiphoton absorption may also contribute to ultrashort-pulse tissue damage, based on the observation that 33 fs, 810 nm pulse laser exposures caused more DNA breakage in cultured, primary RPE cells, compared to CW laser exposures delivering the same average power. Subsequent studies, demonstrating two-photon excitation of fluorescence in isolated RPE melanosomes, appeared to support the role of multiphoton absorption, but mainly at suprathreshold irradiance. Additional experiments have not found a consistent difference in the DNA strand breakage produced by ultrashort and CW threshold exposures. DNA damage appears to be dependent on the amount of melanin pigmentation in the cells, rather than the pulsewidth of the laser; current studies have found that, at threshold, CW and ultrashort pulse laser exposures produce almost identical amounts of DNA breakage. A theoretical analysis suggest that the number of photons delivered to the RPE melanosome during a single 33-fsec pulse at the ED50 irradiance is insufficient to produce multiphoton excitation. This result appears to exclude the melanosome as a locus for two- or three-photon excitation; however, a structure with a larger effective absorption cross-section than the melanosome may interact with the laser pulses. One possibility is that the nuclear chromatin acts as a unit absorber of photons resulting in DNA damage, but this does not explain the near equivalence of ultrashort and CW exposures in the comet assay model. This equivalence indicated that multiphoton absorption is not a major contributor to the ultrashort pulse laser damage threshold in the near infrared.

  17. The development of ShortWatch, a novel overtemperature or mechanical damage sensing technology for wires or cables. Final report

    SciTech Connect

    Watkins, Ken; Morris, Jack; Wong, C.P.; Luo, Shijian

    2001-09-07

    'ShortWatch' is a patented technology which for the first time offers electrical wire/cable products providing real-time, 'in-situ' (1) condition monitoring that warns of insulation damage before an electrical fault occurs, (2) assessment of the ability to perform in a Design Basis event, (3) distributed sensor warning of overtemperature, and (4) insulation leakage measurement capability providing arc sensing and a reliable tool for wire age prediction.

  18. A Review of the Mechanism of Injury and Treatment Approaches for Illness Resulting from Exposure to Water-Damaged Buildings, Mold, and Mycotoxins

    PubMed Central

    2013-01-01

    Physicians are increasingly being asked to diagnose and treat people made ill by exposure to water-damaged environments, mold, and mycotoxins. In addition to avoidance of further exposure to these environments and to items contaminated by these environments, a number of approaches have been used to help persons affected by exposure to restore their health. Illness results from a combination of factors present in water-damaged indoor environments including, mold spores and hyphal fragments, mycotoxins, bacteria, bacterial endotoxins, and cell wall components as well as other factors. Mechanisms of illness include inflammation, oxidative stress, toxicity, infection, allergy, and irritant effects of exposure. This paper reviews the scientific literature as it relates to commonly used treatments such as glutathione, antioxidants, antifungals, and sequestering agents such as Cholestyramine, charcoal, clay and chlorella, antioxidants, probiotics, and induced sweating. PMID:23710148

  19. Vitamins as radioprotectors in vivo. I. Protection by vitamin C against internal radionuclides in mouse testes: Implications to the mechanism of damage caused by the Auger effect

    SciTech Connect

    Narra, V.R.; Harapanhalli, R.S.; Howell, R.W.; Rao, D.V. ); Sastry, K.S.R. )

    1994-03-01

    The potential of vitamin C, an antioxidant, to protect the radiosensitive spermatogonial cells in mouse testes against the effects of chronic irradiation by radionuclides incorporated into tissue was investigated. Interestingly, when injected intratesticularly, a small and nontoxic amount of vitamin C (1.5 [mu]g in 3 [mu]l saline) protected the spermatogonia against the damage associated with high-LET radiation caused by Auger electrons from similarly administered 5-([sup 125]I)-iodo-2[prime]-deoxyuridine ([sup 125]IdU). A dose modification factor (DMF) of 2.3 was obtained. In contrast, no protection was observed when [sup 210]Po, an [alpha]-particle emitter, was administered similarly. These findings suggest that the mechanism of action of the Auger effect is of an indirect nature, which is in contrast to the direct action generally believed to be responsible for biological damage caused by high-LET radiations. 31 refs., 4 figs., 1 tab.

  20. Observed physical processes in mechanical tests of PBX9501 and recomendations for experiments to explore a possible plasticity/damage threshold

    SciTech Connect

    Buechler, Miles A.

    2012-05-02

    This memo discusses observations that have been made in regards to a series of monotonic and cyclic uniaxial experiments performed on PBX9501 by Darla Thompson under Enhanced Surveilance Campaign support. These observations discussed in Section Cyclic compression observations strongly suggest the presence of viscoelastic, plastic, and damage phenomena in the mechanical response of the material. In Secton Uniaxial data analysis and observations methods are discussed for separating out the viscoelastic effects. A crude application of those methods suggests the possibility of a critical stress below which plasticity and damage may be negligible. The threshold should be explored because if it exists it will be an important feature of any constitutive model. Additionally, if the threshold exists then modifications of experimental methods may be feasible which could potentially simplify future experiments or provide higher quality data from those experiments. A set of experiments to explore the threshold stress are proposed in Section Exploratory tests program for identifying threshold stress.

  1. Distinct Mechanisms Mediating Methamphetamine-Induced Neuronal Apoptosis and Dopamine Terminal Damage Share the Neuropeptide Substance P in the Striatum of Mice

    PubMed Central

    ZHU, JUDY P.Q.; XU, WENJING; ANGULO, JESUS A.

    2010-01-01

    Methamphetamine (METH) is an addictive psychostimulant that induces damage to the dopamine terminals and the apoptosis of some neurons of the striatum. Our laboratory demonstrated using either a single bolus dose (30 mg/kg) or a binge (10 mg/kg 4× at 2-h intervals) of METH that pharmacological blockade of the substance P receptor (neurokinin-1) attenuates METH-induced damage to both the presynaptic dopamine terminals and the apoptosis of some neurons of the striatum. To determine the phenotype of striatal neuron ablated by METH, we combined TUNEL (Terminal Deoxyncleotidyl Transferase-Mediated dUTP Nick End Labeling) with immunofluorescence for selective markers of projection and interneurons. METH induces the loss of approximately 20% of the projection neurons. The cholinergic and γ-aminobutyric acid (GABA)-parvalbumin interneurons sustain losses of 30% and 50%, respectively. The somatostatin/neuropeptide Y (NPY)/nitric oxide synthase (NOS) interneurons are not impacted by METH. To investigate the mechanism by which substance P mediates METH-induced damage in this part of the brain, we ablated the striatal interneurons that express the neurokinin-1 receptor (NK-1R) with the selective neurotoxin substance P-SAP. Ablation of the NK-1R-expressing interneurons prevented METH-induced apoptosis in the striatum but was without effect on depletion of dopamine terminal markers. We propose that substance P mediates the apoptosis of some striatal neurons via the intrastriatal activation of nitric oxide synthesis. In contrast, substance P may mediate damage of the dopamine terminals via an extrastriatal mechanism involving the substantia nigra and cortical glutamate release. PMID:17105911

  2. Lung endothelial barrier protection by resveratrol involves inhibition of HMGB1 release and HMGB1-induced mitochondrial oxidative damage via an Nrf2-dependent mechanism.

    PubMed

    Dong, Wen-Wen; Liu, Yu-Jian; Lv, Zhou; Mao, Yan-Fei; Wang, Ying-Wei; Zhu, Xiao-Yan; Jiang, Lai

    2015-11-01

    High-mobility group box 1 (HMGB1) contributes to lung vascular hyperpermeability during ventilator-induced lung injury. We aimed to determine whether the natural antioxidant resveratrol protected against HMGB1-induced endothelial hyperpermeability both in vitro and in vivo. We found that HMGB1 decreased vascular endothelial (VE)-cadherin expression and increased endothelial permeability, leading to mitochondrial oxidative damage in primary cultured mouse lung vascular endothelial cells (MLVECs). Both the mitochondrial superoxide dismutase 2 mimetic MnTBAP and resveratrol blocked HMGB1-induced mitochondrial oxidative damage, VE-cadherin downregulation, and endothelial hyperpermeability. In in vivo studies, anesthetized male ICR mice were ventilated for 4h using low tidal volume (6 ml/kg) or high tidal volume (HVT; 30 ml/kg) ventilation. The mice were injected intraperitoneally with resveratrol immediately before the onset of ventilation. We found that resveratrol attenuated HVT-associated lung vascular hyperpermeability and HMGB1 production. HVT caused a significant increase in nuclear factor-erythroid 2-related factor 2 (Nrf2) nuclear translocation and Nrf2 target gene expression in lung tissues, which was further enhanced by resveratrol treatment. HMGB1 had no effect on Nrf2 activation, whereas resveratrol treatment activated the Nrf2 signaling pathway in HMGB1-treated MLVECs. Moreover, Nrf2 knockdown reversed the inhibitory effects of resveratrol on HMGB1-induced mitochondrial oxidative damage and endothelial hyperpermeability. The inhibitory effect of resveratrol on cyclic stretch-induced HMGB1 mRNA expression in primary cultured MLVECs was also abolished by Nrf2 knockdown. In summary, this study demonstrates that resveratrol protects against lung endothelial barrier dysfunction initiated by HVT. Lung endothelial barrier protection by resveratrol involves inhibition of mechanical stretch-induced HMGB1 release and HMGB1-induced mitochondrial oxidative damage

  3. Case Formulation in TADS CBT

    ERIC Educational Resources Information Center

    Rogers, Gregory M.; Reinecke, Mark A.; Curry, John F.

    2005-01-01

    For the Treatment for Adolescents With Depression Study (TADS), a cognitive-behavioral therapy (CBT) manual was developed with the aim of balancing standardization and flexibility. In this article, we describe the manual's case formulation procedures, which served as one major mechanism of flexibility in TADS CBT. We first describe the essential…

  4. Silymarin protects epidermal keratinocytes from ultraviolet radiation-induced apoptosis and DNA damage by nucleotide excision repair mechanism.

    PubMed

    Katiyar, Santosh K; Mantena, Sudheer K; Meeran, Syed M

    2011-01-01

    Solar ultraviolet (UV) radiation is a well recognized epidemiologic risk factor for melanoma and non-melanoma skin cancers. This observation has been linked to the accumulation of UVB radiation-induced DNA lesions in cells, and that finally lead to the development of skin cancers. Earlier, we have shown that topical treatment of skin with silymarin, a plant flavanoid from milk thistle (Silybum marianum), inhibits photocarcinogenesis in mice; however it is less understood whether chemopreventive effect of silymarin is mediated through the repair of DNA lesions in skin cells and that protect the cells from apoptosis. Here, we show that treatment of normal human epidermal keratinocytes (NHEK) with silymarin blocks UVB-induced apoptosis of NHEK in vitro. Silymarin reduces the amount of UVB radiation-induced DNA damage as demonstrated by reduced amounts of cyclobutane pyrimidine dimers (CPDs) and as measured by comet assay, and that ultimately may lead to reduced apoptosis of NHEK. The reduction of UV radiation-induced DNA damage by silymarin appears to be related with induction of nucleotide excision repair (NER) genes, because UV radiation-induced apoptosis was not blocked by silymarin in NER-deficient human fibroblasts. Cytostaining and dot-blot analysis revealed that silymarin repaired UV-induced CPDs in NER-proficient fibroblasts from a healthy individual but did not repair UV-induced CPD-positive cells in NER-deficient fibroblasts from patients suffering from xeroderma pigmentosum complementation-A disease. Similarly, immunohistochemical analysis revealed that silymarin did not reduce the number of UVB-induced sunburn/apoptotic cells in the skin of NER-deficient mice, but reduced the number of sunburn cells in their wild-type counterparts. Together, these results suggest that silymarin exert the capacity to reduce UV radiation-induced DNA damage and, thus, prevent the harmful effects of UV radiation on the genomic stability of epidermal cells.

  5. Dual mechanism of brain damage induced in vivo by the major metabolites accumulating in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome.

    PubMed

    Viegas, Carolina Maso; Busanello, Estela Natacha Brandt; Tonin, Anelise Miotti; de Moura, Alana Pimentel; Grings, Mateus; Ritter, Luciana; Schuck, Patrícia Fernanda; Ferreira, Gustavo da Costa; Sitta, Angela; Vargas, Carmen Regla; Wajner, Moacir

    2011-01-19

    Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is an autosomal recessive disorder caused by a defect in the mitochondrial ornithine transporter, leading to accumulation of ornithine (Orn), homocitrulline (Hcit) and ammonia. Progressive neurological regression whose pathogenesis is not well established is common in this disease. The present work investigated the in vivo effects of intracerebroventricular administration of Orn and Hcit on important parameters of oxidative stress and energy metabolism in cerebral cortex from young rats. Orn and Hcit significantly increased thiobarbituric acid-reactive substances values and carbonyl formation, indicators of lipid and protein oxidative damage, respectively. Furthermore, N-acetylcysteine and the combination of the free radical scavengers ascorbic acid plus α-tocopherol attenuated the lipid oxidation and totally prevented the protein oxidative damage provoked by Orn and Hcit, suggesting that reactive species were involved in these effects. Hcit, but not Orn administration, also decreased glutathione concentrations, as well as the activity of catalase and glutathione peroxidase, indicating that Hcit provokes a reduction of brain antioxidant defenses. As regards to the parameters of energy metabolism, we verified that Orn and Hcit significantly inhibited the citric acid cycle function (inhibition of CO(2) synthesis from [1-(14)C] acetate), the aerobic glycolytic pathway (reduced CO(2) production from [U-(14)C] glucose) and complex I-III activity of the respiratory chain. Hcit also inhibited the activity of aconitase, an enzyme very susceptible to free radical attack. Taken together, our data indicate that mitochondrial homeostasis is disturbed by Orn and especially by Hcit. It is presumed that the impairment of brain bioenergetics and the oxidative damage induced by these metabolites may possibly contribute to the brain deterioration and neurological symptoms affecting patients with HHH syndrome. PMID

  6. Computational simulation of the bone remodeling using the finite element method: an elastic-damage theory for small displacements

    PubMed Central

    2013-01-01

    Background The resistance of the bone against damage by repairing itself and adapting to environmental conditions is its most important property. These adaptive changes are regulated by physiological process commonly called the bone remodeling. Better understanding this process requires that we apply the theory of elastic-damage under the hypothesis of small displacements to a bone structure and see its mechanical behavior. Results The purpose of the present study is to simulate a two dimensional model of a proximal femur by taking into consideration elastic-damage and mechanical stimulus. Here, we present a mathematical model based on a system of nonlinear ordinary differential equations and we develop the variational formulation for the mechanical problem. Then, we implement our mathematical